Efficacy and safety of fexuprazan in patients with symptoms and signs of laryngopharyngeal reflux disease: a randomized clinical trial.

PURPOSE: Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD. METHODS: This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events. RESULTS: A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p = .036 and .045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough. CONCLUSION: Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI. TRIAL REGISTRATION: KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100 .

Radiographic rotational profiles of the proximal and distal humerus: analysis of 46 computed tomography scans with 3-dimensional simulation.

BACKGROUND: To date, no study has investigated the radiographic rotational profiles (RRPs) of the proximal and distal humerus. However, malrotation after minimally invasive surgery for humeral fracture has been an unsolved problem. Therefore, we aimed to investigate the RRPs of the proximal and distal humerus that linearly correlate with rotational status and show significant differences as the rotational status changes. METHODS: Forty-six computed tomography scans of the humerus were 3-dimensionally reconstructed, and 5 rotational statuses (20° and 10° of internal rotation; neutral; and 10° and 20° of external rotation) were simulated. Seven candidate RRPs of the proximal humerus and 4 candidates of the distal humerus were measured for each rotational status. The overall differences and trends in the RRPs as the rotational status changed were evaluated, and multiple comparisons were performed between the RRPs for each of the 5 rotational statuses. Moreover, the correlations between the RRPs and rotational status with adjustment of retroversion were analyzed. Finally, interobserver and intraobserver reliabilities were evaluated. RESULTS: The following proximal and distal RRPs were linearly correlated with rotational status, differed significantly between the rotational statuses, and showed a relatively low prediction error and excellent interobserver and intraobserver reliabilities: the distance from the tip of the lesser tuberosity to the lateral margin of the proximal humerus (PL1) and the medial margin of the head (PL2), as well as the PL1 to PL2 ratio (PRL), in the proximal humerus; and the distance from the medial margin of the olecranon process to the medial epicondyle (DOP), the widest width of the overlapped olecranon fossa (DOF), and the distance from the lateral margin of the capitellum to the lateral epicondyle (DC) in the distal humerus. CONCLUSION: Our findings suggest that PL1, PL2, and PRL in the proximal humerus and DOP, DOF, and DC in the distal humerus are potentially useful and reproducible RRPs for restoring the intrinsic rotational alignment in humeral fractures.

Femoral matched tibia component rotation has little effect on the tibial torsion after total knee arthroplasty.

PURPOSE: Tibiofemoral synchronization technique matches the rotational alignment of the tibial component to the femoral component during the total knee arthroplasty (TKA). The rotational axis of the proximal tibia can be changed by this technique, which affects tibial torsion postoperatively. The purpose of this study was to investigate whether the tibiofemoral synchronization technique affect the tibial torsion, and the lower limb rotation after primary TKA. It was hypothesised that the tibial torsion would change after primary TKA. METHODS: Ninety-three posterior stabilised TKAs from 89 patients were included from January 2017 to December 2018. Mechanical hip-knee-ankle axis (mHKA), in plain radiographs, femoral anteversion, tibial torsion, femoral neck-malleolar angle (FNMA), and rotational alignment of the femoral and the tibial components in pre- and postoperative CT scans were measured by two blinded observers. The primary outcome was a postoperative change in femoral anteversion, tibial torsion and FNMA. Clinical outcomes were evaluated using the American Knee Society Knee Score (AKSKS)/Function Score (AKSFS), and Oxford Knee Score (OKS) preoperatively and at 1 year after TKA. Patients' perception of changes in the foot progression angle after TKA was investigated. Statistical significance was set at p < 0.05. RESULTS: The mean rotational mismatch between the femoral and the tibial component was 0.6 ± 3.2°. There was a significant decrease in femoral anteversion (9.5 ± 6.7° vs. 5.2 ± 6.6°, p < 0.001), and a significant increase in the FNMA (17.6 ± 9.7° vs. 21.8 ± 10.5°, p = 0.005) after TKA, while no significant change in tibia torsion was observed (25.4 ± 8.8° vs. 24.9 ± 9.3°, p = 0.739). AKSS (37.8 ± 15.1 vs. 92.8 ± 8.8, p < 0.001), AKSFS (53.9 ± 18.1 vs. 89.9 ± 5.3, p < 0.001), and OKS (18.0 ± 7.3 vs. 39.9 ± 4.8, p < 0.001) were significantly improved at 1 year after TKA. Ten knees (11%) had changes in tibial torsion greater than ± 10° postoperatively. Four of five patients who had changes in FNMA greater than 15° perceived the external rotation of the foot progression angle after TKA. All four patients had an increase in tibial torsion larger than 10°. CONCLUSION: Our study shows that the tibiofemoral synchronization technique less likely affects the tibial torsion after primary TKA.

Fucoidan attenuates radioiodine-induced salivary gland dysfunction in mice.

BACKGROUND: Radioiodine (RI) treatments can destroy the cellular components of salivary glands (SG) and disrupt their function. This study investigated whether fucoidan could attenuate radioiodine-induced SG dysfunction in a mouse model. METHODS: Female C57BL/6 mice (n = 36) were classified into three groups; i) a normal (control) group, ii) an RI-treated group (0.2 mCi/20 g mouse, administered orally), and iii) a fucoidan and RI-treated group. Mice in each group were classified into three subgroups and sacrificed at 2, 4, and 12 weeks after RI treatment. The measurements of salivary flow rates and lag times and histomorphologic examinations were performed, and apoptotic assays were conducted. Changes in salivary 99mTechnetium (Tc)-pertechnetate parameters using single-photon emission computed tomography were followed. RESULTS: Salivary flow rates and lag times in the fucoidan group were improved compared to the RI-treated group. Histologic examinations of SGs in the fucoidan group showed mucin-rich parenchymal areas and reduced periductal fibrosis as compared to the RI-treated group. Moreover, compared with the RI-treated group, fucoidan-treated groups showed evidence of cytoprotection, with a greater number of salivary epithelial cells and myoepithelial cells being observed. Fewer apoptotic cells were observed in the fucoidan group as compared to the RI group. The extent of 99mTc pertechnetate excretion in the fucoidan group was similar to that of the control group. CONCLUSION: Our results demonstrate that fucoidan administration before RI treatment could attenuate RI-induced SG damage and provides a possible candidate for preventing SG damage induced by RI.

Montreal cognitive assessment reflects cognitive reserve.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is known to have discriminative power for patients with Mild Cognitive Impairment (MCI). Recently Cognitive Reserve (CR) has been introduced as a factor that compensates cognitive decline. We aimed to assess whether the MoCA reflects CR. Furthermore, we assessed whether there were any differences in the efficacy between the MoCA and the Mini-Mental State Examination (MMSE) in reflecting CR. METHODS: MoCA, MMSE, and the Cognitive Reserve Index questionnaire (CRIq) were administered to 221 healthy participants. Normative data and associated factors of the MoCA were identified. Correlation and regression analyses of the MoCA, MMSE and CRIq scores were performed, and the MoCA score was compared with the MMSE score to evaluate the degree to which the MoCA reflected CR. RESULTS: The MoCA reflected total CRIq score (CRI; B = 0.076, P < 0.001), CRI-Education (B = 0.066, P <  0.001), and CRI-Working activity (B = 0.025, P = 0.042), while MMSE reflected total CRI (B = 0.044, P <  0.001) and CRI-Education (B = 0.049, P <  0.001) only. The MoCA differed from the MMSE in the reflection of total CRI (Z = 2.30). CONCLUSION: In this study, we show that the MoCA score reflects CR more sensitively than the MMSE score. Therefore, we suggest that MoCA can be used to assess CR and early cognitive decline.

Usefulness of Magnetic Resonance Sialography for the Evaluation of Radioactive Iodine-Induced Sialadenitis.

PURPOSE: Radioactive iodine (RAI) ablation therapy after thyroidectomy commonly leads to obstructive sialadenitis. Magnetic resonance (MR) sialography is an emerging imaging modality that enables morphological and functional changes to be evaluated. This study was conducted to investigate the usefulness of MR sialography for the evaluation of RAI sialadenitis. In addition, the authors evaluated the correlation of MR sialographic grading with symptom severity using a symptom questionnaire (SQ), and salivary gland (SG) functions as determined by salivary flow rates (SFRs) and salivary scintigraphy (SSG) parameters. METHODS: Eighteen patients with RAI sialadenitis who underwent MR sialography imaging were retrospectively enrolled. Subjective symptom scores were assessed and objective SG functions were evaluated. MR sialographic characteristics were analyzed and correlations between MR sialographic findings and clinicopathologic data, SQ, SFRs, and SSG parameters were investigated. RESULTS: MR sialography demonstrated diagnostic findings of ductal stenosis and sialectasis, non-visualized ducts, and glandular atrophy mainly involving parotid glands. A significant correlation was found between obstructive symptom scores and ductal stenosis and sialectasis grades (both p < 0.05). Degrees of ductal stenosis and sialectasis were significantly correlated with SSG excretory variables [time from stimulation to minimum count (t min) and maximum secretion; all p < 0.05]. Significant linear correlations were found between duct nonvisualization and uptake variables [uptake ratio (UR) and maximum accumulation (MA); both p < 0.05]. Glandular volumes were also significantly correlated with UR and MA (both p < 0.05). CONCLUSIONS: MR sialography images are useful for evaluating RAI sialadenitis, and its findings are in accordance with disease severity. An MR sialographic grading system is suggested to describe the severity of obstructive sialadenitis and SG dysfunction.

The Analysis of Neutrophil to Lymphocyte Ratio (NLR), Lymphocyte to Monocyte Ratio (LMR), and Platelet to Lymphocyte Ratio (PLR) in Patients with Adenoidectomy and Tonsillectomy.

Background/Objectives: Adenoidectomy and tonsillectomy are among the most commonly performed procedures in ENT practice. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) are recognized inflammatory markers. This study aims to evaluate the changes in NLR, PLR, and LMR in patients undergoing adenoidectomy and tonsillectomy. Methods: The study group consisted of 980 patients who underwent adenoidectomy and/or tonsillectomy. Preoperative and postoperative inflammatory markers were measured in all patients. The NLR, LMR, and PLR values were then calculated and analyzed. Results: In patients undergoing adenoidectomy and/or tonsillectomy, the postoperative NLR was significantly lower than the preoperative NLR. Similarly, the postoperative LMR was significantly higher, and the postoperative PLR was significantly lower compared to their preoperative values. Conclusions: The significant changes in NLR, LMR, and PLR following adenoidectomy and/or tonsillectomy suggest a reduction in systemic inflammation post-surgery. These findings indicate that these procedures may contribute to the improvement of inflammatory status in patients, highlighting the potential role of these markers in monitoring surgical outcomes.

Dynamics of Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte Ratio (LMR), and Platelet-to-Lymphocyte Ratio (PLR) in Patients with Deep Neck Infection.

Background: Inflammatory biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), have been utilized as prognostic factors in various diseases. This study aims to evaluate changes in the NLR, PLR, and LMR in patients diagnosed with a deep neck infections (DNI) to identify useful prognostic markers. Methods: This single-center, retrospective cohort study utilized data from the electronic medical records of patients admitted to the ENT department of a tertiary university hospital between January 2000 and August 2024. Patients diagnosed with a DNI during the study period were enrolled. Preoperative and postoperative inflammatory markers were measured in all patients, and NLR, LMR, and PLR values were calculated and analyzed. Results: The post-treatment NLR was significantly lower than the pre-treatment NLR. Similarly, the post-treatment LMR was significantly higher and the post-treatment PLR was significantly lower compared to pre-treatment values. Patients admitted to the ICU had higher inflammatory markers than those in general wards. Additionally, patients with elevated inflammatory markers had longer hospital stays. Inflammatory markers were also higher in older patients and those who underwent surgical treatment. Conclusions: Significant changes in the NLR, LMR, and PLR in patients diagnosed with a DNI can serve as useful prognostic markers. These findings suggest that monitoring these markers may help to assess and improve the inflammatory status of patients, highlighting their potential role in guiding treatment.

Efficacy and safety of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with autologous bone for the treatment of long bone nonunion: A report of a prospective case series.

INTRODUCTION: Recombinant human Bone morphogenetic proteins have been used for the treatment of nonunions with promising results. We have been investigating both experimentally and clinically the efficacy of the rhBMP-2 with the macro / micro-porous hydroxyapatite carrier granules on the potency on the reconstruction of long bone defect. The purpose of this study was to prospectively evaluate the efficacy and safety of this specific rhBMP-2 with HA carrier granules mixed with autologous cancellous bone in patients with nonunion and bone defect resulted from the fracture related infection. MATERIALS AND METHODS: This was a retrospective review of a prospective cohort at a university hospital. Patients diagnosed with nonunion under the definition of the United States Food and Drug Administration with bone defect after long bone fractures were enrolled from January 2020 to February 2021. We included patients with atrophic and oligotrophic nonunion, and hypertrophic nonunion with malalignment that needed to be corrected. The other patient group was consisted of segmental bone defect resulted from FRI. The maximum amount of rhBMP-2 allowed in this clinical study was 6 mg and was added to autologous bone at a 1:1 ratio. Autologous bone was added to the mixture if the volume of mixed graft was insufficient to fill the bone defect. Patients were followed 3, 6, and 12 months post-operatively. Each visit, a radiograph was taken for assessment. Visual analog scale (VAS), questionnaire for quality of life (SF-12 physical component summary [PCS], mental component summary [MCS]), and weight-bearing status were collected for functional outcome assessment. Drug safety was assessed by examining BMP-2 antibodies. RESULTS: Of the 24 enrolled patients (mean age: 57 years), 15 (62.5 %), 2 (8.33 %), and 7 (29.17 %) presented atrophic nonunion, hypertrophic nonunion with deformity, and bone defect after fracture related infection, respectively. Thirteen patients had nonunion in the femur, 9 in the tibia, and 1 in the humerus and radius. The average amount of harvested autologous bone was 9.25 g and 4.96 mg of rhBMP-2. All 24 patients achieved union after 1-year follow up. The union rate was 95.83 % and 100 % at 6 and 12 months postoperatively, respectively. Preoperative SF-12 PCS (mean: 34.71) improved at 6 and 12 months postoperatively, respectively. Preoperative SF-12 MCS (mean: 42.89) improved 12 months postoperatively (49.13, p = 0.0338). Change of VAS was statistically significant 3 months postoperatively (p = 0.0012). No adverse effects or development of BMP-2 antibodies were observed. CONCLUSION: BMP-2 combined with autogenous bone resulted in excellent radiographical and functional outcomes in a relatively small prospective series of patients with nonunion and bone defect, without adverse effects. Further investigations are necessary to support our finding and optimize treatment strategies in nonunion patients.

Deep learning-radiomics integrated noninvasive detection of epidermal growth factor receptor mutations in non-small cell lung cancer patients.

This study focused on a novel strategy that combines deep learning and radiomics to predict epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC) using computed tomography (CT). A total of 1280 patients with NSCLC who underwent contrast-enhanced CT scans and EGFR mutation testing before treatment were selected for the final study. Regions of interest were segmented from the CT images to extract radiomics features and obtain tumor images. These tumor images were input into a convolutional neural network model to extract 512 image features, which were combined with radiographic features and clinical data to predict the EGFR mutation. The generalization performance of the model was evaluated using external institutional data. The internal and external datasets contained 324 and 130 EGFR mutants, respectively. Sex, height, weight, smoking history, and clinical stage were significantly different between the EGFR-mutant patient groups. The EGFR mutations were predicted by combining the radiomics and clinical features, and an external validation dataset yielded an area under the curve (AUC) value of 0.7038. The model utilized 1280 tumor images, radiomics features, and clinical characteristics as input data and exhibited an AUC of approximately 0.81 and 0.78 during the primary cohort and external validation, respectively. These results indicate the feasibility of integrating radiomics analysis with deep learning for predicting EGFR mutations. CT-image-based genetic testing is a simple EGFR mutation prediction method, which can improve the prognosis of NSCLC patients and help establish personalized treatment strategies.

Deep learning-based analysis of EGFR mutation prevalence in lung adenocarcinoma H&E whole slide images.

EGFR mutations are a major prognostic factor in lung adenocarcinoma. However, current detection methods require sufficient samples and are costly. Deep learning is promising for mutation prediction in histopathological image analysis but has limitations in that it does not sufficiently reflect tumor heterogeneity and lacks interpretability. In this study, we developed a deep learning model to predict the presence of EGFR mutations by analyzing histopathological patterns in whole slide images (WSIs). We also introduced the EGFR mutation prevalence (EMP) score, which quantifies EGFR prevalence in WSIs based on patch-level predictions, and evaluated its interpretability and utility. Our model estimates the probability of EGFR prevalence in each patch by partitioning the WSI based on multiple-instance learning and predicts the presence of EGFR mutations at the slide level. We utilized a patch-masking scheduler training strategy to enable the model to learn various histopathological patterns of EGFR. This study included 868 WSI samples from lung adenocarcinoma patients collected from three medical institutions: Hallym University Medical Center, Inha University Hospital, and Chungnam National University Hospital. For the test dataset, 197 WSIs were collected from Ajou University Medical Center to evaluate the presence of EGFR mutations. Our model demonstrated prediction performance with an area under the receiver operating characteristic curve of 0.7680 (0.7607-0.7720) and an area under the precision-recall curve of 0.8391 (0.8326-0.8430). The EMP score showed Spearman correlation coefficients of 0.4705 (p = 0.0087) for p.L858R and 0.5918 (p = 0.0037) for exon 19 deletions in 64 samples subjected to next-generation sequencing analysis. Additionally, high EMP scores were associated with papillary and acinar patterns (p = 0.0038 and p = 0.0255, respectively), whereas low EMP scores were associated with solid patterns (p = 0.0001). These results validate the reliability of our model and suggest that it can provide crucial information for rapid screening and treatment plans.

Development of a multi-modal learning-based lymph node metastasis prediction model for lung cancer.

PURPOSE: This study proposed a three-dimensional (3D) multi-modal learning-based model for the automated prediction and classification of lymph node metastasis in patients with non-small cell lung cancer (NSCLC) using computed tomography (CT) images and clinical information. METHODS: We utilized clinical information and CT image data from 4239 patients with NSCLC across multiple institutions. Four deep learning algorithm-based multi-modal models were constructed and evaluated for lymph node classification. To further enhance classification performance, a soft-voting ensemble technique was applied to integrate the outcomes of multiple multi-modal models. RESULTS: A comparison of the classification performance revealed that the multi-modal model, which integrated CT images and clinical information, outperformed the single-modal models. Among the four multi-modal models, the Xception model demonstrated the highest classification performance, with an area under the curve (AUC) of 0.756 for the internal test dataset and 0.736 for the external validation dataset. The ensemble model (SEResNet50_DenseNet121_Xception) exhibited even better performance, with an AUC of 0.762 for the internal test dataset and 0.751 for the external validation dataset, surpassing the multi-modal model's performance. CONCLUSIONS: Integrating CT images and clinical information improved the performance of the lymph node metastasis prediction models in patients with NSCLC. The proposed 3D multi-modal lymph node prediction model can serve as an auxiliary tool for evaluating lymph node metastasis in patients with non-pretreated NSCLC, aiding in patient screening and treatment planning.

Bone marrow-derived clonal mesenchymal stem cells as a source of cell therapy for promoting vocal fold wound healing.

OBJECTIVES: We investigated whether mouse bone marrow-derived clonal mesenchymal stem cells (BM-cMSCs) could promote vocal fold (VF) wound healing by using a xenograft animal model. METHODS: Homogeneous BM-cMSCs isolated by a subfractionation culturing method from the bone marrow aspirates of green fluorescent protein transgenic mice were injected into the VFs of rabbits immediately after direct mechanical injury. Macroscopic, biomechanical (rheometric), histologic, immunohistochemical, and transcriptional evaluations were performed on the scarred VFs 1 to 3 months after injury. Engraftment of the implanted BM-cMSCs was determined by detection of green fluorescent protein cells in the recipient VF by confocal microscopy. RESULTS: The BM-cMSC-treated VFs showed improved morphological properties and viscoelasticity as compared to control VFs injected with phosphate-buffered saline solution. Histologic and immunohistochemical evaluations showed less excessive collagen deposition and increased density of glycosaminoglycans in the BM-cMSC-treated VFs as compared to the control VFs at 3 months after injury (p = 0.003 and p = 0.037, respectively). BM-cMSC transplantation led to a significant attenuation of fibronectin (p = 0.036) and transforming growth factor beta1 (p = 0.042) messenger RNA expression at 1 month after injury. Green fluorescent protein-expressing BM-cMSCs engrafted in recipient VFs were found at 1 month after implantation. CONCLUSIONS: BM-cMSCs appeared to survive in the injured xenogeneic VFs after transplantation for up to 1 month and favorably enhanced the wound healing of VFs after injury. We conclude that BM-cMSCs are a possible source of cell therapy for vocal fold regeneration.

Treatment of obstructive sleep apnea syndrome using radiofrequency-assisted uvulopalatoplasty with tonsillectomy.

Radiofrequency surgery was introduced to minimize thermal damage to the tissue. A radiofrequency electrode can be used to make cuts in the free edge of the soft palate like those done in laser-assisted uvulopalatoplasty [radiofrequency-assisted uvulopalatoplasty (RAUP)]. Tonsillectomy can enlarge the lateral diameter of the pharynx. The aim of our study was to evaluate the efficacy of RAUP with tonsillectomy in treatment of obstructive sleep apnea syndrome (OSAS). Ninety-two patients with obstructive sleep apnea were included in this study. Patients were categorized according to disease severity and Friedman's staging system. Patients were assessed with the preoperative visual analog scale (VAS) for snoring, Epworth Sleepiness Scale (ESS) and apnea-hypopnea index (AHI) at baseline and repeated at 6 months postoperatively. The intensity of postoperative pain, speech deficits and dysphagia were also recorded. There was a significant improvement in the VAS score for snoring, ESS and AHI before and after surgery. Overall, the results of the present study indicated a surgery success rate (a 50 % decrease in AHI and AHI <20) of 66 % (61 of 92 patients). Postoperative pain, speech deficits and dysphagia were reduced at 2 weeks after surgery. The results of this study suggest that RAUP with tonsillectomy is an effective treatment for patients with OSAS.

Adiponectin is associated with inflammaging and age-related salivary gland lipid accumulation.

Dry mouth is frequently observed in the elderly, and enhanced lipid accumulation plays a critical role in cellular senescence in the salivary gland (SG). We investigated the mechanisms that mediate lipogenesis-associated SG senescence. Adult (28.6 ± 6.6 y.o. and 43.3 ± 1.5 y.o.) and aged (82.0 ± 4.3 y.o. and 88.0 ± 4.3 y.o.) human parotid and submandibular glands were compared with respect to histologic findings, 8-OHdG (8-hydroxy 2 deoxyguanosine) expression patterns, TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) and SA-ß-gal (senescence-associated ß-galactosidase) assay results. Also, microarray analysis was performed on RNA extracted from adult and aged SG to identify DEGs (differentially expressed genes). The effects of silencing ADIPOQ (Adiponectin) were evaluated by quantifying cell proliferation, immunohistochemical staining for cellular senescence and inflammation-associated proteins, SA-ß-gal assays, RT-PCR, and western blot. Histological findings demonstrated the presence of more lipocytes, chronic inflammation, fibrosis, and lymphocytic infiltration in old SG. In addition, old tissues demonstrated higher expressions of SA-ß-gal, more apoptotic cells in TUNEL assays, and higher oxidative stress by 8-OHdG immunostaining. Microarray analysis showed lipogenesis was significantly upregulated in old tissues. Silencing of ADIPOQ (a lipogenesis-related gene) reduced inflammation and SA-ß-gal levels and increased cell proliferation and the expressions of amylase and aquaporin 5 in human SG epithelial cells. The study shows ADIPOQ is a potential target molecule for the modulation of lipogenesis associated with SG senescence.

Clinical outcome of rim-plate-augmented separate vertical wiring with supplementary fixation for the treatment of patellar fracture associated comminuted inferior pole.

Despite the variety of treatment methods, comminuted inferior pole fractures of the patella remain difficult and technically demanding to achieve stable internal fixation. The purpose of this study is to evaluate the clinical outcomes of rim plate-augmented separate vertical wiring with supplementary fixation in the management of comminuted inferior pole fractures, AO/OTA 34-A1, C2, and C3, which has the secondary horizontal fracture line on lower articular boundary. From our study, bony union was achieved in all patients at an average of 3.1 ± 1.4 months after surgery. There was no patient with loss of reduction, fixation failure, or infection during follow-up. The average final range of motion was 131.6° ± 7.2°. Lysholm knee scores gradually increased over 3, 6, 9, and 12 months postoperatively by 58.7, 74.0, 82.9, and 89.4, respectively. Isokinetic peak torque deficit of the knee extensor muscles in 3, 6, 9, and 12 months postoperatively was 59.9%, 49.7%, 35.7%, and 28.1%, respectively. The rim plate-augmented separate vertical wiring with supplementary fixation for the treatment of patellar fracture associated comminuted inferior pole is effective and can be safely applied AO/OTA 34-C2 or C3 with favorable outcomes.

Supernatant of activated platelet-rich plasma rejuvenated aging-induced hyposalivation in mouse.

Hyposalivation is a common complaint among the elderly, but no established treatment prevents age-induced hyposalivation. Platelet derivatives such as platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and plasma rich in growth factor (PRGF), are used widely in different areas of regenerative medicine to enhance the wound healing processes. This study examined whether the local injection of the supernatant of activated PRP (saPRP) into the salivary gland (SG) could help prevent aging-induced SG dysfunction and explored the mechanisms responsible for the protective effects on the SG hypofunction. The platelets were separated from the blood of male SD rats (220 ± 20 g). saPRP was manufactured by removing the fibrin clot after activating platelet with calcium ionophore 10 µM (A23187). The total protein and TGF-ß1 levels were significantly higher in saPRP than in PRP. Human salivary gland epithelial cell(hSGEC) was treated with saPRP or PRP after senescence through irradiation. The significant proliferation of hSGEC was observed in saPRP treated group compared to irradiation only group and irradiation + PRP group. Cellular senescence, apoptosis, and inflammation significantly reduced in saPRP group. The SG function and structural tissue remodeling by the saPRP were investigated with naturally aged mice. The mice were divided into three groups: 3 months old (3 M), 22 months old (22 M), and 22 months old treated with saPRP (22 M + saPRP). Salivary flow rate and lag time were significantly improved in 22 M + saPRP group compared to 22 M group. The histologic examinations showed the significant proliferation of acinar cell in 22 M + saPRP group. The decrease of senescence, apoptosis, and inflammation observed by western blot in 22 M + saPRP group. The saPRP induced the proliferation of hSGECs, leading to a significant decrease in cellular senescence via decrease inflammation and apoptosis, in vitro. Moreover, the acini cells of the salivary gland were regenerated, and the salivary function increased in aged mice. These results showed that saPRP could be a treatment agent against aging-induced SG dysfunction.

Efficacy of crizotinib retreatment after crizotinib-related interstitial lung disease in a patient with ROS1-rearranged advanced lung adenocarcinoma: A case report and potential crizotinib retreatment strategy.

Crizotinib is an oral selective small-molecular tyrosine kinase inhibitor (TKI) that suppress the activity of anaplastic lymphoma kinase (ALK) and ROS1 kinases, as well as mesenchymal-epithelial transition. The cumulative clinical trials in patients with advanced ALK- or ROS1-rearrangement NSCLC indicate that crizotinib has significant antitumor activity and a tolerable safety profile, with mild or moderate adverse events of visual disorders, diarrhea, nausea, and vomiting. As with other TKIs, however, the occurrence of crizotinib-related interstitial lung disease (crizotinib-ILD) remains a major clinical dilemma that can lead to the permanent discontinuation of TKI during cancer treatment. When there is no suitable alternative therapy for patients who develop crizotinib-ILD, some clinicians have reported successful crizotinib retreatment in cases of ALK-rearrangement NSCLC. Unfortunately, there are no specific guidelines for the treatment or retreatment of TKI-related ILD. We herein report the first successful crizotinib retreatment after crizotinib-ILD in a patient with ROS1-rearranged NSCLC, and suggest a retreatment strategy after crizotinib-ILD based on a literature review.

Cell-derived vesicles from adipose-derived mesenchymal stem cells ameliorate irradiation-induced salivary gland cell damage.

Introduction: Salivary gland (SG) damage is commonly caused by aging, irradiation, and some medications, and currently, no damage modifying agent is available. However, cell therapy based on mesenchymal stem cells (MSCs) has been proposed as a therapeutic modality for irradiated SGs. Therefore, we administered cell-derived vesicles (CDVs) of adipose-derived mesenchymal stem cells (ADMSCs) to irradiated SG cells to investigate their radioprotective effects in vitro. Methods: The artificial CDVs were obtained from ADMSC by tangential flow filtration (TFF) purification and ultracentrifugation. Cultured human SG epithelial cells were exposed to 2, 5 or 15 Gy of 4 MV X-rays produced by a linear accelerator. The effects of ADMSC-CDVs on SG epithelial cells damaged by irradiation were tested by proliferation activity, transepithelial electrical resistance (TEER), and amylase activity. Results: Exposure to penetrating radiation inhibited the proliferation of SG epithelial cells, but the radiation intensity required to reduce the proliferation of human submandibular gland epithelial cells (hSMGECs) was greater than required for other SG cells. ADMSC-CDVs restored the proliferative ability of SG epithelial cells reduced by irradiation, and the proliferation capacities of irradiated human parotid gland epithelial cells (hPGECs) and human sublingual gland epithelial cells (hSLGECs) were increased by administering ADMSC-CDVs to non-irradiated SG epithelial cells. Furthermore, amylase activity in irradiated hPGECs, hSMGECs, and hSLGECs was lower than in non-irradiated controls. However, amylase ability was restored in all by ADMSC-CDV treatment. Also, TEER was diminished by irradiation in hPGECs, hSMGECs, and hSLGECs and restored by ADMSC-CDV administration. Conclusion: Overall, our findings demonstrate that ADMSC-CDVs have potent radioprotective effects on irradiated SG cells.

Influence of carpal-ulnar translation on clinical outcome after scaphocapitate arthrodesis for the treatment of late-stage Kienböck disease.

BACKGROUND: This study sought to compare postoperative outcomes after scaphocapitate arthrodesis (SCA) for the treatment of late-stage Kienböck disease according to the amount of ulnar translation of the carpus and to identify surgical factors associated with carpal-ulnar translation. METHODS: Thirty-nine patients diagnosed with Kienböck disease (Lichtman stages III-IV) and treated with SCA were retrospectively reviewed. They were divided into the translated group (n=28) and untranslated group (n=11) according to the presence of carpal-ulnar translation. The following surgical factors in the patients were assessed: excision of the lunate, postoperative carpal height ratio, and radioscaphoid angle (RSA). Pain Visual Analog scale (VAS) score, wrist range of motion, grip strength, modified Mayo wrist score (MMWS), the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, and progression of radioscaphoid osteoarthritis were also assessed. RESULTS: All patients showed functional improvement after a mean postoperative follow-up period of 40 months (VAS: 4.1 vs. 1.1, p <0.001; grip strength, 42.3 vs. 51.2 lb., p = 0.002; MMWS, 52.6 vs. 69.5, p <0.001; QuickDASH, 33.7 vs. 21.5, p <0.001). No statistically significant differences were found between the two groups in terms of outcome measures. Among the assessed surgical factors, the mean postoperative RSA was significantly smaller in the translated group than in the untranslated group (34.8° vs. 46.8°, p = 0.008). The proportion of patients with postoperative RSA <30° was significantly higher in the translated group than in the untranslated group (54.5% vs. 0%, p<0.001). CONCLUSION: These results suggest that sufficient pain relief and functional improvement can be achieved after SCA for the treatment of late-stage Kienböck disease disregarding the occurrence of carpal-ulnar translation. In this study, overcorrection to RSA <30° induced more frequent carpal-ulnar translation after SCA.