The optimal measurement method considering reliability and validity in the anterior knee laxity of anterior cruciate ligament tears.

INTRODUCTION: To seek an optimal measurement method with high reliability and high validity for evaluation of the anterior knee laxity on stress radiographs and comparing the translation values to those of KT-2000 arthrometer. METHODS: Anterior knee laxity in 77 patients was measured preoperatively using the TelosTM and the KT-2000 arthrometer. Side-to-side difference measurements were taken using three conventional measuring methods and one proposed method (Modified Lateral). The knee position on the stress radiograph was evaluated and scored based on the stress radiograph qualifying criteria depending on stress film correctiveness. Intraclass correlation coefficients were analyzed to evaluate the reliability of the measurement methods and were compared between high (Group H) and low (Group L) radiograph quality score groups for each method. Validity was assessed by comparing the KT-2000 and the TelosTM using Pearson correlation (r value). RESULTS: The Modified Lateral method showed the best Intraclass Correlation Coefficients (ICCs), followed by Center to Center, and Medial to Medial and Lateral to Lateral methods without considering the quality of Telos. In the comparison between groups based on Telos quality for intra-rater reliability, the Medial to Medial (MM) method demonstrated the best reliability in both groups (MM: ICCs, Group H = 0.942, Group L = 0.917, P = 0.693). As for inter-rater reliability, the Modified Lateral (ML) method exhibited the best reliability in both groups (ML: ICCs, Group H = 0.923, Group L = 0.882, P = 0.547). The value measured using the ML method in Telos showed the highest correlation coefficient with the KT-2000 measured value in both groups H and L. There were no statistically significant differences among the correlation coefficient values. CONCLUSION: The Modified Lateral method is recommended for its high reliability, taking into account the differences in bilateral knee positions and anatomical discriminability on stress radiographs when evaluating anterior knee translation with Telos. It also best reflected the KT-2000 arthrometer. LEVEL OF EVIDENCE: Case Series, Level IV.

The effect of plum extracts and antioxidants on reduction of ethyl carbamate in plum liqueur.

Stone-fruit liqueurs contain high contents of the carcinogen ethyl carbamate (EC). In this study, we investigated the effect of plum fruit extract and single antioxidants present in plum fruit extracts on the reduction in the EC content during the macerating process in a plum liqueur model system and authentic plum liqueur. 30% ethanol model plum liqueur treated with 0.2% plum extract showed the lowest EC content with 55% reduction rate after the macerating process compared to the content in the control. Interestingly, neither 0.1% ascorbic acid nor 0.1% p-coumaric acid lowered the EC contents in the model liqueur, while they decreased the EC contents in authentic plum liqueur. This was possibly attributed to the synergistic effect of the plum fruit phenolics with the ascorbic acid and p-coumaric acid antioxidants. Thus, plum extracts can be applied to plum liqueurs to reduce the rate of EC formation. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01585-1.

The Effects of National Insurance Coverage Expansion and Genetic Counseling's Role on BRCA1/2 Mutation Tests in Breast Cancer Patients.

PURPOSE: This study aims to evaluate the impact of South Korea's national insurance coverage (NIC) expansion and the addition of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. MATERIALS AND METHODS: A retrospective review was conducted at the Samsung Medical Center (SMC), dividing patients into three groups: pre-NIC expansion, post-NIC expansion, and post-extra genetic counselor involvement. The number of BRCA1/2 tests performed and the detection rates among newly diagnosed and follow-up patients, particularly focusing on triple-negative breast cancer (TNBC) cases, were analyzed. RESULTS: Post-NIC expansion, there was a significant increase in BRCA1/2 testing rates, with a gradual rise in detection rates while maintaining statistical significance. TNBC patients under 60 experienced substantial increases in testing rates. The number of follow-up patients recalled for testing also rose significantly after the extra genetic counselor involvement. Additionally, NIC expansion increased insurance coverage for TNBC patients, enhancing accessibility to testing. CONCLUSION: The study highlights the positive impact of NIC expansion and genetic counselor involvement on BRCA1/2 mutation testing rates and subsequent patient management. Addressing financial barriers to testing and incorporating genetic counseling significantly improve patient outcomes. This model provides a potential strategy for enhancing early detection and personalized treatment for breast cancer patients with BRCA1/2 mutations, contributing to global cancer management efforts.

Proximity Between Screw and Endplate of Upper Instrumented Vertebra Using a Cortical Bone Trajectory Screw can Increase Radiographic Adjacent Segment Degeneration Risks in Patients With Lumbar Spinal Stenosis.

STUDY DESIGN: Retrospective observational study. OBJECTIVE: To determine the proximity between screw and endplate of the upper instrumented vertebra (UIV) using a cortical bone trajectory (CBT) screw as a predictive factor for radiographic adjacent segment degeneration (ASD) in patients surgically treated with transforaminal lumbar interbody fusion (TLIF) with CBT screws (CBT-TLIF) with lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: The risk factors for radiographic ASD after CBT-TLIF remain unknown. METHODS: Among patients surgically treated with CBT-TLIF at a single institute, 239 consecutive patients (80 males and 159 females) were enrolled. ASD was defined by the presence of one or more of the following three radiologic criteria on the adjacent segment: >3 mm anteroposterior translation, >10° segmental kyphosis, or >50% loss of disc height comparing immediate postoperative and 1-year follow-up radiographs. Clinical and radiological features associated with the development of ASD were retrospectively measured. Univariate and multivariate analyses were performed to identify risk factors associated with radiographic ASD. RESULTS: Radiographic ASD was observed in 71 (29.7%) cases at 1-year postoperative follow-up. The preoperative Pfirrmann grade of the adjacent segment (>grade 2), multi-level fusion (>2 levels), and proximity between the tip of CBT screws and endplate on the UIV were significantly associated with radiographic ASD (OR = 3.98, 95% CI [1.06-15.05], P=0.042 versus OR = 3.03, 95% CI [1.00-9.14], P=0.049 versus OR = 0.53, 95% CI [0.40-0.72], P<0.001). The cut-off value of the distance between the tip of the screw and endplate on UIV for radiographic ASD was approximately 2.5 mm (right-sided CBT screw; cut-off value 2.48 mm/ left-sided CBT screw; cut-off value 2.465 mm). CONCLUSION: Radiographic adjacent segment degeneration progression can occur when the cortical trajectory bone screw is close to the endplate of the upper instrumented vertebrae in patients with lumbar spinal stenosis undergoing fusion surgery.

Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Human Epidermal Growth Factor 2-Positive/Triple-Negative Breast Cancer Patients With Excellent Response.

PURPOSE: The Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy (ASLAN) trial aims to demonstrate the oncologic safety of omitting axillary surgery in patients with excellent response after neoadjuvant chemotherapy (NACT) for early human epidermal growth factor 2 (HER2)-positive (+)/triple-negative breast cancer (TNBC) who have undergone breast-conserving surgery (BCS) and adjuvant radiotherapy. The ASLAN trial will provide crucial information that could change the procedure in highly selected patients undergoing axillary surgery after NACT. METHODS: ASLAN is a prospective, multicenter, and single-arm surgical trial. The recruitment will be conducted among five tertiary care hospitals in the Republic of Korea. The total number of patients to be recruited will be 178, and we plan to complete patient enrollment by December 2023. The enrollment is considered among patients with HER2+ breast cancer (BC) or TNBC at clinical stage T1-3N0-1M0 who are expected to achieve breast pathological complete response (BpCR) based on a combination of radiologic imaging and physical examination after NACT. BCS was performed on eligible patients. After BCS, patients who showed BpCR were enrolled with the omission of sentinel lymph node biopsy (SLNB). The primary study endpoint upon completion of this trial is 5-year recurrence-free survival, and the secondary endpoints include the 5-year ipsilateral breast tumor recurrence interval, 5-year ipsilateral axillary recurrence interval, 5-year distant metastasis-free survival, 5-year BC-specific survival, 5-year overall survival, 5-year contralateral BC-free survival, re-operation rate according to breast biopsy after NACT, adverse events within 5 years, and quality of life. DISCUSSION: Several clinical trials are currently underway to determine whether SLNB can be omitted after NACT in patients with HER2+ BC or TNBC that are expected to achieve pathologic complete response. The ASLAN trial is expected to provide valuable clues regarding the feasibility of omitting axillary surgery in highly selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04993625. Registered on August 6, 2021. Clinical Research Information Service Identifier: KCT0006371. Registered on July 22, 2021.

Oncologic Outcomes of Immediate Breast Reconstruction in the Setting of Neoadjuvant Chemotherapy: A Long-term Follow-up Study of a Matched Cohort.

PURPOSE: Despite the increasing use of immediate breast reconstruction (IBR), its oncologic safety in the setting of neoadjuvant chemotherapy (NACT) needs to be comprehensively clarified in breast cancer management. The objective of the present study was to analyze the oncologic safety of IBR following NACT. METHODS: In total, 587 patients with breast cancer who underwent a total mastectomy (TM) with IBR after NACT between 2008 and 2017 at a single institution were retrospectively reviewed. The reviewed patients with IBR following skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) were matched 1:3 to patients who underwent TM alone after NACT. Matching variables included age, clinical T and N stages before NACT, response to NACT, pathologic T and N stages, and molecular subtypes. RESULTS: After propensity score matching, 95 patients who underwent IBR following SSM/NSM after NACT (IBR group) and 228 patients who underwent TM alone after NACT (TM group) were selected. The median follow-up period was 73 (range, 5-181) months after matching. After matching, there were no significant differences between the two groups in 5-year locoregional recurrence-free survival (88.8% vs. 91.2%, p = 0.516), disease-free survival (67.3% vs. 76.6%, p = 0.099), distant metastasis-free survival (71.9% vs. 81.9%, p = 0.057), or overall survival (84.1% vs. 91.5, p = 0.061) rates. In multivariate analyses, conducting IBR was not associated with increased risks for locoregional recurrence, any recurrence, distant metastasis, or overall death. CONCLUSION: Our findings suggest that IBR following SSM/NSM elicits comparable long-term oncologic outcomes to those of TM alone in the setting of NACT.

Daphnetin Alleviates Bleomycin-Induced Pulmonary Fibrosis through Inhibition of Epithelial-to-Mesenchymal Transition and IL-17A.

Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there is no cure for IPF, the development of drugs with improved efficacy in the treatment of IPF is required. Daphnetin, a natural coumarin derivative, has immunosuppressive, anti-inflammatory, and antioxidant activities. However, its antifibrotic effects have not yet been elucidated. In this study, we investigated the antifibrotic effects of daphnetin on pulmonary fibrosis and the associated molecular mechanism. We examined the effects of daphnetin on splenocytes cultured in Th17 conditions, lung epithelial cells, and a mouse model of bleomycin (BLM)-induced pulmonary fibrosis. We identified that daphnetin inhibited IL-17A production in developing Th17 cells. We also found that daphnetin suppressed epithelial-to-mesenchymal transition (EMT) in TGF-ß-treated BEAS2B cells through the regulation of AKT phosphorylation. In BLM-treated mice, the oral administration of daphnetin attenuated lung histopathology and improved lung mechanical functions. Our findings clearly demonstrated that daphnetin inhibited IL-17A and EMT both in vitro and in vivo, thereby protecting against BLM-induced pulmonary fibrosis. Taken together, these results suggest that daphnetin has potent therapeutic effects on lung fibrosis by modulating both Th17 differentiation and the TGF-ß signaling pathway, and we thus expect daphnetin to be a drug candidate for the treatment of IPF.

Risk factors of breast cancer recurrence in pathologic complete response achieved by patients following neoadjuvant chemotherapy: a single-center retrospective study.

Objective: Pathologic complete response (pCR) of breast cancer after neoadjuvant chemotherapy (NAC) is highly related to molecular subtypes. Patients who achieved tumor pCR after NAC have a better prognosis. However, despite of better prognosis, pCR patients have a potential for recurrence. There is little evidence of risk factors of recurrence in patients with pCR. We aim to analyze factors associated with tumor recurrence in patients who achieved pCR. Methods: This study retrospectively reviewed the data of patients diagnosed with breast cancer who achieved pCR after receiving NAC between January 2009 and December 2018 in Samsung Medical Center. pCR was defined as no residual invasive cancer in the breast and axillary nodes even if there is residual ductal carcinoma in situ (ypT0 or ypTis with ypN0). Breast cancers are classified into 4 subtypes based on hormone receptors (HR) and human epithelial growth factor receptor 2 (HER2) status. Patients who had bilateral breast cancer, ipsilateral supraclavicular or internal mammary lymph node metastasis, inflammatory breast cancer, distant metastasis, unknown subtype, and histologically unique case were excluded from the study. Results: In total 483 patients were included in this study except for patients who corresponded to the exclusion criteria. The median follow-up duration was 59.0 months (range, 0.5-153.3 months). Breast cancer recurred in 4.1% of patients (20 of 483). There was a significant difference in clinical T (P = 0.004) and clinical N (P = 0.034) stage in the Kaplan-Meier curve for disease-free survival. Molecular subtypes (P = 0.573), Ki67 (P = 1.000), and breast surgery type (P = 0.574) were not associated with tumor recurrence in patients who achieved pCR after NAC. In the clinical T stage and clinical N stage, there was a significant difference between recurrence and no-recurrence groups (clinical T stage; P = 0.045, clinical N stage; P = 0.002). Univariable Cox regression revealed statistical significance in the clinical T stage (P = 0.049) and clinical N stage (P = 0.010), while multivariable Cox regression demonstrated non-significance in the clinical T stage (P = 0.320) and clinical N stage (P = 0.073). Conclusion: Results in this study showed that clinical T, clinical N stage, and molecular subtypes were not statistically significant predictors of recurrence in patients who achieved pCR after NAC. In spite of that, pCR after NAC may be more important than clinical staging and molecular subtype in early breast cancer. In addition, escalated treatments for patients with HER2 + or triple-negative tumors would be considered with a strict patient selection strategy to prevent over-treatment as well as achieve pCR.

Macrophage-reprogramming upconverting nanoparticles for enhanced TAM-mediated antitumor therapy of hypoxic breast cancer.

In an attempt to achieve antitumor effects by switching the phenotype of macrophages from the tumor-promoting M2 type to the tumor-suppressing M1 type, we fabricated mannose-decorated/macrophage membrane-coated, silica-layered NaErF4@NaLuF4 upconverting nanoparticles (UCNPs) co-doped with perfluorocarbon (PFC)/chlorin e6 (Ce6) and loaded with paclitaxel (PTX) (UCNP@mSiO2-PFC/Ce6@RAW-Man/PTX: ∼61 nm; -11.6 mV). These nanoparticles were designed to have two major functionalities, (i) efficient singlet oxygen generation aided by an oxygen supply and (ii) good targeting to tumor-associated macrophage (TAMs) (M2-type), to induce polarization to M1 type macrophages that release proinflammatory cytokines and suppress breast cancers. The primary UCNPs consisted of lanthanide elements (erbium and lutetium) in a core@shell structure, and they facilely emitted 660 nm light in response to a deep-penetrating 808 nm near-infrared laser. Moreover, the UCNPs@mSiO2-PFC/Ce6@RAW-Man/PTX were able to release O2 and generate 1O2 because of the co-doped PFC/Ce6 and upconversion. Our nanocarriers' excellent uptake to RAW 264.7 macrophage cells (M2 type) and efficient M1-type polarization activity were clearly demonstrated using qRT-PCR and immunofluorescence-based confocal laser scanning microscopy. Our nanocarriers displayed significant cytotoxicity to 4T1 cells in 2D culture and 3D co-culture systems of 4T1/RAW 264.7 cells. More importantly, UCNPs@mSiO2-PFC/Ce6@RAW-Man/PTX (+808 nm laser) noticeably suppressed tumor growth in 4T1-xenografted mice, compared with the other treatment groups (332.4 vs. 709.5-1185.5 mm3). We attribute this antitumor efficacy to the prominent M1-type macrophage polarization caused by our nanocarriers through efficient ROS/O2 generation and targeting of M2-type TAMs via mannose ligands on coated macrophage-membrane.

Progesterone Receptor Expression Level Predicts Prognosis of Estrogen Receptor-Positive/HER2-Negative Young Breast Cancer: A Single-Center Prospective Cohort Study.

BACKGROUND: Although estrogen receptor (ER) expression levels affect the prognosis of breast cancer, studies about progesterone receptor (PR) expression levels are insufficient, especially in young breast cancer (YBC). The purpose of this study was to compare clinical characteristics and prognosis according to PR expression levels in invasive breast cancer patients. METHODS: A prospective cohort study was conducted to identify YBC patients with invasive carcinoma diagnosed at an age of less than 40 years old between 2013 and 2018. Clinicopathologic features and prognosis of ER-positive and human epidermal growth factor receptor 2 (HER2)-negative patients were investigated. Patients were stratified into strong PR (PR-positive cell proportion > 10%), low PR (PR-positive cell proportion = 1~10%), and PR-negative (PR-positive cell proportion < 1%). RESULTS: Among 458 patients enrolled, 386 (84.3%), 26 (5.7%), and 46 (10.0%) were categorized into strong PR, low PR, and PR-negative groups, respectively. The median follow-up duration was 58.6 months. Compared with the strong PR group, low PR and PR-negative groups were more likely to have high Ki-67 and a high nuclear grade. Low R and PR-negative groups had significantly worse disease-free survival (DFS) and distant metastasis-free survival (DMFS) than the strong PR group (p = 0.0033, p = 0007). Low PR group had an even higher risk of distant metastasis than PR-negative patients. Low PR patients and PR-negative had significantly lower overall survival (OS) rates than strong PR. CONCLUSION: Low PR might be a prognostic factor of ER-positive/HER2-negative in YBC.

Oral intake of collagen peptide NS improves hydration, elasticity, desquamation, and wrinkling in human skin: a randomized, double-blinded, placebo-controlled study.

Collagen hydrolysate, which contains bioactive peptides, is used as a dietary supplement for the refinement of elasticity, hydration, desquamation, and wrinkling of aging human skin. Here, we conducted a double-blind, randomized, and placebo-controlled oral administration study on the effects of a collagen peptide (CPNS) containing dipeptides, including Gly-Pro and Pro-Hyp, on skin wrinkling, desquamation, elasticity, and hydration. Our results show that an intake of 1650 mg per day of CPNS for 12 weeks had beneficial effects on skin health in a cohort of women aged from 30 to 60 years (n = 100). Compared with the placebo group, skin desquamation, hydration, skin wrinkling, and elasticity were significantly improved after 4, 4, 12, and 12 weeks of administration, respectively. In a safety test of CPNS ingestion, none of the participants showed any side effects during the clinical study period. These results demonstrate that the low molecular weight bioactive peptides contained in CPNS, such as Gly-Pro and Pro-Hyp, exert positive effects on skin hydration, elasticity, desquamation, and wrinkling.

Theophylline Attenuates BLM-Induced Pulmonary Fibrosis by Inhibiting Th17 Differentiation.

Idiopathic pulmonary fibrosis (IPF) is a chronic and refractory interstitial lung disease. Although there are two approved drugs for IPF, they were not able to completely cure the disease. Therefore, the development of new drugs is required for the effective treatment of IPF. In this study, we investigated the effect of theophylline, which has long been used for the treatment of asthma, on pulmonary fibrosis. The administration of theophylline attenuated the fibrotic changes of lung tissues and improved mechanical pulmonary functions in bleomycin (BLM)-induced pulmonary fibrosis. Theophylline treatment suppressed IL-17 production through inhibiting cytokines controlling Th17 differentiation; TGF-ß, IL-6, IL-1ß, and IL-23. The inhibition of IL-6 and IL-1ß by theophylline is mediated by suppressing BLM-induced ROS production and NF-κB activation in epithelial cells. We further demonstrated that theophylline inhibited TGF-ß-induced epithelial-to-mesenchymal transition in epithelial cells through suppressing the phosphorylation of Smad2/3 and AKT. The inhibitory effects of theophylline on the phosphorylation of Smad2/3 and AKT were recapitulated in BLM-treated lung tissues. Taken together, these results demonstrated that theophylline prevents pulmonary fibrosis by inhibiting Th17 differentiation and TGF-ß signaling.

When Bigger Is Not Greener: Ensuring the Sustainability of Power-to-Gas Hydrogen on a National Scale.

As the prices of photovoltaics and wind turbines continue to decrease, more renewable electricity-generating capacity is installed globally. While this is considered an integral part of a sustainable energy future by many nations, it also poses a significant strain on current electricity grids due to the inherent output variability of renewable electricity. This work addresses the challenge of renewable electricity surplus (RES) utilization with target-scaling of centralized power-to-gas (PtG) hydrogen production. Using the Republic of Korea as a case study, due to its ambitious plan of 2030 green hydrogen production capacity of 0.97 million tons year-1, we combine predictions of future, season-averaged RES with a detailed conceptual process simulation for green H2 production via polymer electrolyte membrane (PEM) electrolysis combined with a desalination plant in six distinct scale cases (0.5-8.5 GW). It is demonstrated that at scales of 0.5 to 1.75 GW the RES is optimally utilized, and PtG hydrogen can therefore outperform conventional hydrogen production both environmentally (650-2210 Mton CO2 not emitted per year) and economically (16-30% levelized cost reduction). Beyond these scales, the PtG benefits sharply drop, and thus it is answered how much of the planned green hydrogen target can realistically be "green" if produced domestically on an industrial scale.

Comparison of Recurrence Rate Between Re-Excision With Radiotherapy and Radiotherapy-Only Groups in Surgical Margin Involvement of In Situ Carcinoma.

PURPOSE: Surgical margin status is a surrogate marker for residual tumors after breast-conserving surgery (BCS). A comparison of ipsilateral breast tumor recurrence (IBTR) rates between re-excision combined with radiotherapy (excision with RTx) and RTx alone, following the confirmation of ductal carcinoma in situ (DCIS) in the resection margin after BCS, has not been reported previously. Therefore, in the present study, the clinical characteristics of DCIS involvement in the surgical resection margin between excision with RTx and RTx alone were investigated, and the IBTR rate was compared. METHODS: We analyzed 8,473 patients treated with BCS followed by RTx between January 2013 and December 2019. Patients were divided into 2 groups based on surgical resection margin status in permanent pathology, and superficial and deep margins were excluded. Patients who underwent re-excision with DCIS confirmed in the resection margin were identified and the IBTR rate was examined. RESULTS: Among 8,473 patients treated with BCS, 494 (5.8%) had positive surgical resection margins. The median follow-up period was 47 months. Among the 494 patients with a positive resection margin, 368 (74.5%) had residual DCIS at the surgical resection margin in the final pathology. Among those with confirmed DCIS at the resection margin, 24 patients (6.5%) were re-excised, and 344 patients (93.5%) underwent RTx after observation. The IBTR rates were 4.2% and 1.2% in the re-excision and observation groups, respectively. IBTR-free survival analysis revealed no significant difference between the excision with RTx and RTx-only groups (p = 0.262). CONCLUSION: The IBTR rate did not differ between the excision with RTx and RTx-only groups when DCIS was confirmed at the resection margins. This suggests that RTx and close observation without re-excision could be an option, even in cases where minimal involvement of DCIS is confirmed on surgical resection.

Endoscopic findings of dental implant found in the infundibulum showing the mucociliary clearance of the maxillary sinus.

Significance statement: A 53-year-old man with left facial pain was referred to our hospital. Nasal endoscopy revealed a purulent discharge at the left middle meatus and bulging of the uncinate process. Computed tomography demonstrated that the dental implant was blocking the left maxillary ostium. Functional endoscopic sinus surgery was performed under general anesthesia. After removal of the uncinate process, a yellowish purulent discharge in the left maxillary sinus discharged from the maxillary sinus. The presence of the dental implant in the infundibulum shows the direction of mucociliary clearance from the nasal sinus. This case indicates how our sinus clears a foreign body, and the direction in which the foreign body is removed.

A case report of primary myxoid liposarcoma mimicking as a parotid cystic lesion.

RATIONALE: Myxoid liposarcoma (MLS) is an extremely rare tumor of the salivary gland and it arises from undifferentiated pluripotent mesenchymal cells. We report a rare case of a primary MLS in the parotid gland. PATIENT CONCERNS: The patient was a 49-year-old female who presented with a hard fixed mass in the left parotid region. DIAGNOSIS: On computed tomography and MR images, this tumor has a low attenuation center with a thick enhancing wall and ill-defined margins. The absence of high-signal-intensity foci on T1-weighted images makes a MLS indistinguishable from most other soft-tissue masses. Pathologically, the tumor was diagnosed as MLS. INTERVENTIONS: The patient received total parotidectomy with facial nerve preservation and selective neck dissection. OUTCOMES: Immediate facial nerve function was House Brackmann Grade III and recovered within 3 months after the surgery. Follow-up period is 57 months and there was no recurrence until now. LESSONS: In this report, we report a rare case of primary MLS mimicking a cystic lesion of the parotid gland.

A nodular type of mantle cell lymphoma in the nasopharynx.

Mantle cell lymphoma (MCL) is a subtype of B-cell lymphoma derived from CD5-positive antigen-naïve pre-germinal center B-cells within the mantle zone that surrounds normal germinal center follicles. MCL comprises approximately 5 to 10% of all lymphomas. Tonsil is the most common location of MCL in the head and neck region, followed by the nasopharynx. Primary MCL involving the nasopharynx is extremely rare. Its clinical course is very aggressive with frequent relapses after conventional chemotherapy. It always presents as a protruding mass on the mucosal lining of the pharyngeal cavity. Here, we report a new nodular type of MCL in the nasopharynx. Endoscopically, this case showed multiple nodular lesions of primary MCL on the nasopharyngeal mucosa. This unique finding has not been reported yet in the English literature. These lesions should be differentiated from simple pharyngeal infections or benign lymphoid hyperplasia in the nasopharynx.

Isomer-Specific Monitoring of Sialylated N-Glycans Reveals Association of α2,3-Linked Sialic Acid Epitope With Behcet's Disease.

Behcet's disease (BD) is an immune disease characterized by chronic and relapsing systemic vasculitis of unknown etiology, which can lead to blindness and even death. Despite continuous efforts to discover biomarkers for accurate and rapid diagnosis and optimal treatment of BD, there is still no signature marker with high sensitivity and high specificity. As the link between glycosylation and the immune system has been revealed, research on the immunological function of glycans is being actively conducted. In particular, sialic acids at the terminus of glycoconjugates are directly implicated in immune responses, cell-cell/pathogen interactions, and tumor progression. Therefore, changes in sialic acid epitope in the human body are spotlighted as a new indicator to monitor the onset and progression of immune diseases. Here, we performed global profiling of N-glycan compositions derived from the sera of 47 healthy donors and 47 BD patients using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to preferentially determine BD target glycans. Then, three sialylated biantennary N-glycans were further subjected to the separation of linkage isomers and quantification using porous graphitized carbon-liquid chromatography (PGC-LC)/multiple reaction monitoring (MRM)-MS. We were able to successfully identify 11 isomers with sialic acid epitopes from the three glycan compositions consisting of Hex5HexNAc4NeuAc1, Hex5HexNAc4Fuc1NeuAc1, and Hex5HexNAc4NeuAc2. Among them, three isomers almost completely distinguished BD from control with high sensitivity and specificity with an area under the curve (AUC) of 0.945, suggesting the potential as novel BD biomarkers. In particular, it was confirmed that α2,3-sialic acid at the terminus of biantennary N-glycan was the epitope associated with BD. In this study, we present a novel approach to elucidating the association between BD and glycosylation by tracing isomeric structures containing sialic acid epitopes. Isomer-specific glycan profiling is suitable for analysis of large clinical cohorts and may facilitate the introduction of diagnostic assays for other immune diseases.

Discovery of N-glycan Biomarkers for the Canine Osteoarthritis.

Protein glycosylation is a post-translational modification that impacts on protein activity, stability, and interactions. It was sensitively altered by the cellular state and, therefore, is now used for a diagnostic or prognostic indicator of various human diseases such as cancer. To evaluate the clinical feasibility in the veterinary area, the N-glycan biomarkers were discovered from canine serum for the diagnosis of osteoarthritis (OA), which is one of the most common diseases of dogs. N-glycome was obtained from 20 µL of canine serum by the enzymatic cleavage followed by the purification and enrichment using solid-phase extraction. Independent compositions of 163 and 463 N-glycans were found from healthy control (n = 41) and osteoarthritis patients (n = 92), respectively. Initially, 31 of the potential biomarkers were screened by the p-values below 1.0 × 10-10 from ANOVA. Then, the area under the curve (AUC) and the intensity ratio between OA patient and healthy control (P/C ratio) were calculated. Considering the diagnostic efficacy, the AUC bigger than 0.9 and the P/C ratio larger than 3.0 were used to discover 16 N-glycans as diagnostic biomarkers. Particularly, five of the diagnostic biomarkers were AUC above 0.99 and three of N-glycans had AUC 1.0. The results suggest a clear possibility for N-glycan biomarkers to be used as a clinical tool in the veterinary medical area enabling to provide objective and non-invasive diagnostic information.