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Background/Purpose The intergenic SNP rs10865331 at 2p15 was identified as a major risk factor for ankylosing spondylitis (AS) susceptibility in genome-wide association studies (GWAS). B3GNT2 gene regulates polylactosamine synthesis is potentially functionally relevant to AS disease development. We investigated whether SNP rs10865331 and two B3GNT2 SNPs (rs11900673 and rs1136151) are associated with AS susceptibility and disease severity in Taiwanese. Methods Distributions of genotypes, alleles, and haplotypes of three SNPs were compared between 1,472 AS patients and 2,117 healthy blood donors and among AS patients stratified by clinical characteristics. Results The intergenic SNP rs10865331 was significantly associated with AS (PFDR = 1.02E-05) in Taiwanese. In AS patients stratified by positivity of HLA-B27 and syndesmophyte formation, all three B3GNT2 locus SNPs (rs11900673, rs1136151, and rs10865331) were significantly associated with syndesmophyte formation among HLA-B27 positive AS patients. Haplotype analyses revealed that the “CTA” (rs11900673C/rs1136151T/rs10865331A) haplotype was significantly associated with AS susceptibility (Padj = 0.0177) and syndesmophyte formation (Padj = 0.016) in HLA-B27 positive patients. In contrast, “TCG” (rs11900673T/rs1136151C/rs10865331G) haplotype showed protection against AS development (Padj = 0.0005 for HLA-B27 positive and Padj = 0.004 for HLA-B27 negative, respectively) and syndesmophyte formation (Padj = 0.0017) in HLA-B27 positive patients. Furthermore, B3GNT2 mRNA expressions were negatively associated with erythrocyte sedimentation rate (ESR, P = 0.0103), C-reactive protein (CRP, P = 0.0353), Bath ankylosing spondylitis functional index (BASFI, P = 0.0171), and syndesmophyte formation (P = 0.0148). Conclusion Our data suggest that B3GNT2 gene may contribute to AS development and affect AS severity by interacting with HLA-B27 in Taiwanese.

To evaluate the correlation between structural parameters and visual acuity (VA) in advanced glaucoma.Prospective, cross-sectional study.A total of 238 eyes from 238 patients (82 were men and mean ± SD age was 59.9 ± 13.8 years) from a tertiary center were divided into an advanced (mean deviation of 24-2 visual field tests from -12.01 to -20.0 dB) and severe (-20 dB) glaucoma group. Structural parameters were obtained by RTVue (Optovue Inc) optical coherence tomography and angiography. Pearson correlation, partial correlation adjusted for age and axial length, and receiver operating characteristic curves to detect decreased VA (20/25) were performed.In the advanced glaucoma group (133 eyes), superficial (Pearson correlation coefficient, r = -0.46, P.001; partial correlation coefficient, r' = -0.30, P.001) and deep macular vessel densities (VDs) (r = -0.47, P.001; r' = -0.30, P.001) showed highest correlation with VA. The area under the receiver operating characteristic curves of the superficial parafoveal/macular VDs were 0.816 (95% CI, 0.735-0.897) and 0.808 (95% CI, 0.725-0.891), respectively. In the severe glaucoma group (105 eyes), deep nasal grid VD (r = -0.31, P = 0.002; r' = -0.35, P.001) showed highest correlation with VA. Deep macular VD showed better correlation with VA than other structural parameters. The area under the receiver operating characteristic curves of deep macular VD and deep nasal grid VD were 0.740 (95% CI, 0.632-0.849) and 0.748 (95% CI, 0.640-0.857), respectively.Macular VD showed better correlation with VA in advanced glaucoma. Deep macular VD, especially nasal grid, may be a promising structural parameter in severe glaucoma.

B-cell maturation antigen-targeted chimeric antigen receptor T-cell therapy (BCMA CAR-T) is an effective treatment of relapsed refractory multiple myeloma (MM). However, the pattern of infectious complications is not well elucidated. We performed a single-center retrospective analysis of infection outcomes up to 1 year after BCMA CAR-T for MM from 2018 to 2020. Fifty-five patients with MM were treated with BCMA CAR-T. Before lymphodepletion (LD), 35% of patients had severe hypogammaglobulinemia and 18% had severe lymphopenia. Most patients (68%) received bridging chemotherapy (BC) before LD. In the first month after CAR-T, 98% patients had grade 3 to 4 neutropenia. At 1 year after infusion, 76% patients had hypogammaglobulinemia. With a median follow-up of 6.0 months (95% confidence interval, 4.7-7.4), there were a total of 47 infection events in 29 (53%) patients: 40% bacterial, 53% viral, and 6% fungal. Most (92%) were mild-moderate and of the lower/upper respiratory tract system (68%). Half of the infections (53%) occurred in the first 100 days after CAR-T infusion. Although no statistically significant risk factors for infection were identified, prior lines of therapy, use of BC, recent infections, and post–CAR-T lymphopenia were identified as possible risk factors that need to be further explored. This is the largest study to date to assess infectious complications after BCMA CAR-T. Despite multiple risk factors for severe immunosuppression in this cohort, relatively few life-threatening or severe infections occurred. Further larger studies are needed to better characterize the risk factors for and occurrence of infections after BCMA CAR-T.

Purpose : The association between visual impairment (VI) and the risk of dementia has been poorly understood. We sought to investigate the VI-dementia relationship in the UK Biobank Study. Design : Prospective cohort study Methods : A total of 117,187 volunteers (aged 40-69 years) deemed free of dementia at baseline were included. Habitual distance visual acuity worse than 0.3 logMAR units in the better-seeing eye was used to define VI. The incident dementia was based on electronically linked hospital inpatient and death records. Results : During a median follow up of 5.96 years, the presence of VI was significantly associated with incident dementia (HR=1.78, 95% CI: 1.18-2.68, P=0.006). There was a clear trend between the severity of VI and the risk of dementia (P for trend=0.002). Conclusions : We found VI was associated with increased risk of dementia, with a progressively greater risk among those with worse visual acuity. Our findings suggested that visual impairment might be a modifiable risk factor for dementia and highlighted the potential value of VI elimination to delay the manifestation of dementia.

Background Age‐related muscle dysfunctions are common disorders resulting in poor quality of life in the elderly. Probiotic supplementation is a potential strategy for preventing age‐related sarcopenia as evidence suggests that probiotics can enhance muscle function via the gut–muscle axis. However, the effects and mechanisms of probiotics in age‐related sarcopenia are currently unknown. In this study, we examined the effects of Lactobacillus casei Shirota (LcS), a probiotic previously reported to improve muscle function in young adult mice. Methods We administered LcS (1 × 108 or 1 × 109 CFU/mouse/day) by oral gavage to senescence‐accelerated mouse prone‐8 mice for 12 weeks (16‐ to 28‐week‐old). Sixteen‐week‐old and 28‐week‐old SMAP8 mice were included as non‐aged and aged controls, respectively. Muscle condition was evaluated using dual‐energy X‐ray absorptiometry for muscle mass, holding impulse and grip strength tests for muscle strength, and oxygen consumption rate, gene expressions of mitochondrial biogenesis, and mitochondrial number assays for mitochondria function. Inflammatory cytokines were determined using enzyme‐linked immunosorbent assay. Gas chromatography–mass spectrometry was utilized to measure the short‐chain fatty acid levels. The gut microbiota was analysed based on the data of 16S rRNA gene sequencing of mouse stool. Results The LcS supplementation reduced age‐related declines in muscle mass (>94.6%, P 66% in holding impulse and >96.3% in grip strength, P 65.9% in the mice given high dose of LcS, P 89.4%, P 2.0] were positively correlated with healthy muscle and physiological condition (P 2.0) were negatively associated with healthy muscle and physiological condition (P

Background/purpose: Three first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely available to treat advanced lung adenocarcinoma harboring EGFR mutation. However, studies comparing efficacy or effectiveness of these EGFR TKIs came out with inconclusive results. Methods: In this real-world data analysis with a nationwide retrospective cohort design, adult patients with newly diagnosed advanced lung adenocarcinoma with EGFR mutation between 2011 and 2016, who received a first-line EGFR TKI, were included. Overall survival (OS) and time to next treatment (TTNT) were compared between patients receiving different EGFR TKIs after overlap weighting. Results: We enrolled 10,431 patients, including 6,230, 2,359, and 1842 in gefitinib, erlotinib, and afatinib groups, respectively. The median (95% confidence interval [CI]) OS were 24.2 (22.9–26.2), 25.7 (24.0–27.9), and 29.1 (25.8–32.1) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p = 0.001). The hazard ratios (95% CI) for the afatinib group were 0.85 (0.74–0.98) and 0.91 (0.79–1.05) comparing with the gefitinib and erlotinib groups, respectively. The median (95% CI) TTNT were 10.9 (10.4–11.2), 11.7 (11.3–12.1), 13.4 (12.5–14.3) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p

Study objective Necrotizing fasciitis (NF) is an uncommon life-threatening necrotizing skin and soft tissue infection. Bullae are special skin manifestations of NF. This study was conducted to analyze the differences between different types of bullae of limbs with NF for providing the information to emergency treatment. Methods From April 2015 to August 2018, patients were initially enrolled based on surgical confirmation of limbs with NF. According to the presence of different bullae types, patients were divided into no bullae group (Group N), serous-filled bullae group (Group S), and hemorrhagic bullae group (Group H). Data such as demographics, clinical outcomes, microbiological results, presenting symptoms/signs, and laboratory findings were compared among these groups. Results In total, 187 patients were collected, with 111 (59.4%) patients in Group N, 35 (18.7%) in Group S, and 41 (21.9%) in Group H. Group H had the highest incidence of amputation, required intensive care unit care, and most patients infected with Vibrio species. In Group N, more patients were infected with Staphylococcus spp. than Group H. In Group S, more patients were infected with β-hemolytic Streptococcus than Group H. Patients with bacteremia, shock, skin necrosis, anemia, and longer prothrombin time constituted higher proportions in Group H and S than in Group N. Conclusions In southern Taiwan, patients with NF accompanied by hemorrhagic bullae appear to have more bacteremia, Vibrio infection, septic shock, and risk for amputation. If the physicians at the emergency department can detect for the early signs of NF as soon as possible, and more patient’s life and limbs may be saved.

Introduction Chimeric antigen receptor (CAR) T-cells can induce a rapid disease response but are frequently associated with immunologic toxicities. In addition to cytokine release syndrome (CRS), macrophage activation syndrome-like manifestations (MAS-L), characterized by uncontrolled immune activation, have been described (Shah et al, 2020). Traditional MAS definitions are challenging to apply in patients receiving CAR T cells, due to overlapping signs and symptoms with lymphodepletion and CRS. Therefore, we sought to develop novel criteria to characterize MAS-L following CAR T cells and used these criteria to identify risk factors for developing MAS-L. Methods We conducted a retrospective review of 55 patients who received B cell maturation antigen-directed CAR T cells for multiple myeloma from 11/1/17 - 5/1/20. Based on the labs readily available in our patient population, we defined MAS-L using the following criteria: 1) rate of ferritin rise ³ 100 mg/L/hour within a 24 hour period and 2) minimum fibrinogen 2 times the upper limit of normal. In developing these simplified criteria, we considered multiple laboratory markers of inflammation (ferritin, LDH, soluble interleukin receptor-2, natural killer cell activity) and end organ damage. Infection was defined as any culture positivity, febrile neutropenia, or clinical suspicion such that a new antimicrobial was started in the 30 days prior to CAR T cells. Wilcoxon rank-sums and Fisher’s exact test were used to compare continuous and categorical variables, respectively. Overall (OS) and progression-free survival (PFS) were compared using log-rank tests. Results Of the 55 patients, 12 (21.8%) met the above criteria for MAS-L with similar disease trajectories. Following CAR T cells, all 12 patients first developed CRS, characterized by an elevated C-reactive protein (CRP) and administration of tocilizumab, and subsequently developed MAS-L, characterized by decrease in fibrinogen and rapid rise of ferritin and LDH (Figure 1). Compared to the 45 patients who did not develop MAS-L, patients with MAS-L had similar baseline patient and disease characteristics (Table 1); however, a significantly higher proportion of patients with MAS-L had an infection prior to receiving CAR T cells (75% vs 9.3%, p Compared to patients who did not develop MAS-L, a similar proportion of MAS-L patients developed any CRS (100% vs 84%, p = 0.33) and ³ grade 2 CRS (50% vs 50%, p = 1). Neurotoxicity was more common in patients with MAS-L (42% vs 14%, p = 0.05). A greater proportion of patients with MAS-L received tocilizumab (100% vs 70%, p = 0.05), systemic steroids (92% vs 27%, p Following CAR T cell therapy, patients with MAS-L had longer hospitalizations (21 vs 19 days, p = 0.009) and a greater proportion required ICU-level care (27% vs 2%, p = 0.02). OS and PFS between the two groups were similar (p = 0.15 and 0.63, respectively), with a 1-year OS of 65.2% vs 90.6% and PFS of 35.4% vs 54.7% for patients with vs without MAS-L, respectively. In univariate logistic regression of baseline patient factors, disease characteristics, and ferritin, CRP, and D-dimer prior to receiving CAR T cells, only a history of documented infection in the 30 days prior to CAR T cells predicted MAS-L development (Hazard Ratio 29.2, 95% CI 5.54 - 154, p Conclusions In this analysis, we developed novel criteria for defining MAS-L following CAR T cell therapy and used these criteria to define the unique laboratory profile and clinical trajectory of patients with MAS-L. We also identify pre-existing infection as a strong risk factor for MAS-L development. Although patients with MAS-L frequently require prolonged monitoring, this immunologic toxicity can be mitigated with steroids, anakinra, and supportive care, and patients ultimately have similar survival compared to patients without MAS-L. Larger studies are needed to prospectively validate these novel criteria. Download : Download high-res image (447KB) Download : Download full-size image Disclosures Wolf: Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Martin: Sanofi, Amgen, Seattle Genetics, JNJ - Janssen: Research Funding; Legend Biotech: Consultancy. Shah: BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy. Wong: Bristol Myers Squibb: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Janssen: Research Funding; Roche: Research Funding; Fortis: Research Funding; GSK: Research Funding.

Background From the perspective of information processing, an integrated understanding of the structural and functional connectomes in depression patients is important, a multimodal meta-analysis is required to detect the robust alterations in graph metrics across studies. Methods Following a systematic search, 952 depression patients and 1447 controls in nine diffusion magnetic resonance imaging (dMRI) and twelve rest state functional MRI (rs-fMRI) studies with high methodological quality met the inclusion criteria and were included in the meta-analysis. Results Regarding the dMRI results, no significant differences of meta-analytic metrics were found; regarding the rs-fMRI results, the modularity and local efficiency were found to be significantly lower in the depression group than in the controls (Hedge's g = -0.330 and -0.349, respectively). Conclusion Our findings suggested a lower modularity and network efficiency in the rs-fMRI network in depression patients, indicating that the pathological imbalances in brain connectomes needs further exploration. Limitations: Included number of trials was low and heterogeneity should be noted.

Purpose: To investigate the influence of benzalkonium chloride (BAK) on ocular surface disease (OSD) in glaucoma patients receiving ocular-hypotensive agent. Methods: Patients were randomized to re...

Objectives/hypothesis To examine the pathogenic bacterial spectra and prognosis of deep neck infection (DNI) in end-stage renal disease (ESRD) patients. Study design Retrospective study. Methods Patients diagnosed with DNI between 2004 and 2015 in Chang Gung Memorial Hospital were enrolled and divided into three groups, namely ESRD-DNI, chronic kidney disease (CKD)-DNI, and non-CKD-DNI. Differences in pathogenic bacteria, treatment, and prognosis were compared across the three groups. Results The bacterial spectra differed among the three groups. The main three facultative anaerobic or aerobic bacteria causing ESRD-DNIs were methicillin-resistant Staphylococcus aureus (MRSA; 25.4%), methicillin-susceptible S. aureus (MSSA; 14.1%), and Klebsiella pneumoniae (KP; 12.7%). For CKD-DNIs, they were KP (23.5%), Viridans streptococci (VS; 23.5%), and MSSA (14.7%). For non-CKD-DNIs, they were VS (31.7%), KP (17.2%), and coagulase-negative staphylococci (8.0%). Compared with the other groups, the ESRD-DNI group had higher white blood cell and C-reactive protein levels, longer hospital stays, more frequent admissions to the intensive care unit, more mediastinal complications, and a significantly higher mortality rate. Conclusions The ESRD-DNI group exhibited more severe disease activity and higher mortality compared with those of the CKD-DNI and non-CKD-DNI groups. MRSA was the leading pathogen for patients with ESRD-DNI. Physicians must implement strategies for the early detection of MRSA to accurately prescribe antibiotics and prevent nosocomial transmission. Level of evidence 4 Laryngoscope, 2021.

Objective To analyze the duration of gonadotropin hyperstimulation's impacts on oocyte quality and clinical outcomes in aged in vitro fertilization (IVF) patients. Materials and methods This retrospective study was carried out using IVF records of the Chang Gung Memorial Hospital IVF center from January 2017 to December 2019. A total of 308 IVF cycles with patients aged 40–44 years were included. Clinical characteristics of patients who received a short controlled ovarian hyperstimulation (COH) (i.e., 6–7 days; s-COH group) or a long COH treatment (i.e., 9–10 days; l-COH group) were compared. In addition, analysis was conducted using data within two age subgroups: 40–42 years and 42–44 years subgroups. Results The s-COH group received significantly lower total doses of gonadotropin and had smaller leading follicles at the time of ovulation trigger when compared to the l-COH group. The s-COH group also produced a significantly lower number of oocytes, mature metaphase II (MII) oocytes, and 2 PN zygotes compared to the l-COH group. However, there was no significant difference in the number of transferable and good-quality embryos between the two treatment groups. Likewise, the pregnancy rate and live birth rate were comparable in the s-COH and l-COH groups. Similar results were obtained when the analysis was limited to select age subgroups (i.e., 40–42 and 42–44 years subgroups). Conclusion While a long COH generates more oocytes per cycle, a 6–7 days COH treatment, which is at the lower end of the recommended window of stimulation, could achieve a pregnancy outcome comparable to that applied 9–10 days of COH in aged patients.

BACKGROUND Hepatic tuberculosis (TB) is uncommon clinically. Because of a lack of specific signs, characteristic symptoms and clinical manifestations and because pathological samples are difficult to obtain, hepatic TB is easily missed or misdiagnosed. CASE SUMMARY A 62-year-old Chinese man presented with jaundice for 1 wk and no abnormal laboratory tests other than elevated bilirubin, aminotransferases and C-reactive protein. Computed tomography (CT) of the abdomen showed a mass in the left lobe of the liver and hepatic hilum with striped calcified foci. Mild enhancement was visible at the edges, along with extensive intrahepatic biliary ductal dilatation in the right lobe of the liver. In the arterial phase of both CT and magnetic resonance imaging, the main trunk and right branch of the portal artery were partially visualized. Magnetic resonance cholangiopancreatography (MRCP) indicated that the left lobe of the liver and most of the bile ducts in the hilum were not visible. Pathological examination revealed coagulative necrosis, and granulomatous nodules were seen around areas of necrosis; therefore, TB was considered. CONCLUSION Hepatic tuberculosis is easily misdiagnosed or missed on imaging. Percutaneous puncture biopsy is the most useful tool for definitive diagnosis.

Chronic kidney disease (CKD) increases the risk of arrhythmia. The right ventricular outflow tract (RVOT) is a crucial site of ventricular tachycardia (VT) origination. We hypothesize that CKD increases RVOT arrhythmogenesis through its effects on calcium dysregulation. We analysed measurements obtained using conventional microelectrodes, patch clamp, confocal microscopy, western blotting, immunohistochemical examination and lipid peroxidation for both control and CKD (induced by 150 mg/kg neomycin and 500 mg/kg cefazolin daily) rabbit RVOT tissues or cardiomyocytes. The RVOT of CKD rabbits exhibited a short action potential duration, high incidence of tachypacing (20 Hz)‐induced sustained VT, and long duration of isoproterenol and tachypacing‐induced sustained and non‐sustained VT. Tachypacing‐induced sustained and non‐sustained VT in isoproterenol‐treated CKD RVOT tissues were attenuated by KB‐R7943 and partially inhibited by KN93 and H89. The CKD RVOT myocytes had high levels of phosphorylated CaMKII and PKA, and an increased expression of tyrosine hydroxylase‐positive neural density. The CKD RVOT myocytes exhibited large levels of I to, I Kr, NCX and L‐type calcium currents, calcium leak and malondialdehyde but low sodium current, SERCA2a activity and SR calcium content. The RVOT in CKD with oxidative stress and autonomic neuron hyperactivity exhibited calcium handling abnormalities, which contributed to the induction of VT.

OBJECTIVE To examine whether serum procalcitonin (PCT) is useful for differentiating acute pyelonephritis (APN) from asymptomatic bacteriuria and acute cystitis during pregnancy. METHODS A multicenter prospective observational study was conducted to compare serum white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and PCT level among pregnant women with asymptomatic bacteriuria, acute cystitis, and APN and healthy pregnant women (controls). Utility of WBC count, ESR, CRP, and PCT biomarkers for the prediction of APN during pregnancy were measured. RESULTS Area under the curve (AUC) values of PCT, CRP, ESR, and WBC count for predicting asymptomatic bacteriuria were 0.576, 0.628, 0.542, and 0.532, respectively; those for predicting acute cystitis were 0.766, 0.735, 0.681, and 0.597, respectively; and those for predicting acute pyelonephritis 0.859, 0.763, 0.711, and 0.732, respectively. Compared with the other inflammatory markers used to predict APN, PCT exhibited the highest AUC (0.859 [95% confidence interval (CI) 0.711-0.935]). A cutoff value of >0.25 ng/ml had a sensitivity of 87% and a specificity of 79%. CONCLUSION Serum PCT can be a valuable addition to existing methods of differentiating asymptomatic bacteriuria, acute cystitis, and APN during pregnancy and can facilitate the early identification of APN during pregnancy.

Objective To assess whether lifelong higher circulating 25-hydroxyvitamin D [25(OH)D] levels increase serum calcium levels and kidney stone disease (KSD) risk. Methods Summary data for KSD were obtained from the UK biobank genome-wide association study (6536 cases and 388 508 controls). We acquired summary data for 25(OH)D from 120 618 Europeans and another large-scale analysis (443 734 Europeans) for primary and secondary analysis. Random-effect inverse-variance weighted (IVW) and 7 additional sensitivity analyses were applied. Next, multivariable Mendelian randomization (MVMR) was performed by introducing data for serum calcium levels. Results Genetic predisposition for a 1-SD higher 25(OH)D level was associated with increased serum calcium levels (IVW; beta, 0.014; 95% CI, 0.010-0.018; P = 7.64E-10). Genetically predicted higher circulating 25(OH)D levels were associated with increased the risk of KSD, with per 1-SD odds ratios (ORs) of 1.47 (95% CI, 1.22-1.77; P = 5.49E-05) and 1.36 (95% CI, 1.03-1.80; P = 0.029) using the IVW and MVMR-Egger methods, respectively. In secondary analysis, similar results were found: 25(OH)D was associated with an increased risk of KSD in univariate Mendelian randomization (IVW; OR 1.71; 95% CI, 1.26-2.32; P = 0.001) and MVMR (OR 1.43; 95% CI, 1.16-1.76; P < 0.001) analyses. Most sensitivity analyses were consistent with the primary results, both for the primary and secondary analyses. Conclusions Our study supports that higher genetically predicted lifelong circulating 25(OH)D levels are associated with higher calcium levels and KSD risk. The effects of 25(OH)D on KSD were partially attenuated—but still significant—in MVMR.

Background The accuracy of estimating microvascular invasion (MVI) preoperatively in hepatocellular carcinoma (HCC) by clinical observers is low. Most recent studies constructed MVI predictive models utilizing radiological and/or radiomics features extracted from computed tomography (CT) images. These methods, however, rely heavily on human experiences and require manual tumor contouring. We developed a deep learning-based framework for preoperative MVI prediction by using CT images of arterial phase (AP) with simple tumor labeling and without the need of manual feature extraction. The model was further validated on CT images that were originally scanned at multiple different hospitals. Methods CT images of AP were acquired for 309 patients from China Medical University Hospital (CMUH). Images of 164 patients, who took their CT scanning at 54 different hospitals but were referred to CMUH, were also collected. Deep learning (ResNet-18) and machine learning (support vector machine) models were constructed with AP images and/or patients’ clinical factors (CFs), and their performance was compared systematically. All models were independently evaluated on two patient cohorts: validation set (within CMUH) and external set (other hospitals). Subsequently, explainability of the best model was visualized using gradient-weighted class activation map (Grad-CAM). Results The ResNet-18 model built with AP images and patients’ clinical factors was superior than other models achieving a highest AUC of 0.845. When evaluating on the external set, the model produced an AUC of 0.777, approaching its performance on the validation set. Model interpretation with Grad-CAM revealed that MVI relevant imaging features on CT images were captured and learned by the ResNet-18 model. Conclusions This framework provide evidence showing the generalizability and robustness of ResNet-18 in predicting MVI using CT images of AP scanned at multiple different hospitals. Attention heatmaps obtained from model explainability further confirmed that ResNet-18 focused on imaging features on CT overlapping with the conditions used by radiologists to estimate MVI clinically.

Purpose To evaluate the contralateral lymph node recurrence rate (clLNRR) of stage IVA to IVB well-lateralized oral cavity cancer. To evaluate the risk factors of clLNRR. Materials and methods Pathologic stage IVA-B squamous cell carcinoma of oral cavity, originating from buccal mucosa, gingiva, or retromolar trigone were retrospectively recruited. Those who did not receive definitive surgery, with previous cancer history, or with contralateral nodal metastasis at diagnosis were excluded. Results From 2010 to 2017, 120 cases were enrolled, including 103 pT4 and 38 pN2. Thirty-one patients underwent contralateral neck dissection, and 18 had contralateral elective nodal irradiation. After median follow up of 35.1 months, the 3-year clLNRR was 15.7% (95% CI: 8.8 - 22.6%) as first event and was 17.1% (95% CI: 9.8 - 24.4%) for overall recurrences. The 3-year disease-free survival and overall survival were 52.8% and 63.1%, respectively. In multivariate analysis, positive nodal metastasis, gingival origin, and perineural invasion were associated with significantly higher clLNRR. Nodal metastasis was the strongest prognostic factor for clLNRR (pN1, HR: 17.1, p = 0.010; pN2, HR: 16.7, p = 0.004, comparing to pN0). The 3-year clLNRR were 2.9% for pN0 (n = 71, 95% CI: 0 - 6.8%), 37.7% for pN1 (n = 11, 95% CI: 8.3 - 67.1%), and 38.4% for pN2 (n = 38, 95% CI: 19.2 - 57.6%). Advanced T classification, elective contralateral neck dissection, and contralateral nodal irradiation did not have significant impact on clLNRR. Conclusions Positive homolateral nodal metastasis, gingival origin, and perineural invasion were risk factors correlated with significantly higher clLNRR. For patient without nodal metastasis, the clLNRR was low and elective contralateral neck management might be safely omitted. For patients with homolateral nodal disease, the contralateral nodal recurrence was not unusual. The optimal treatment for these high risk patients warrant further research.

Our gut microbiome is constituted by trillions of microorganisms including bacteria, archaea and eukaryotic microbes. Nowadays, gut microbiome has been gradually recognized as a new organ system that systemically and biochemically interact with the host. Accumulating evidence suggests that the imbalanced gut microbiome contributes to the dysregulation of immune system and the disruption of cardiovascular homeostasis. Specific microbiome profiles and altered intestinal permeability are often observed in the pathophysiology of cardiovascular diseases. Gut-derived metabolites, toxins, peptides and immune cell-derived cytokines play pivotal roles in the induction of inflammation and the pathogenesis of dysfunction of heart and vasculature. Impaired crosstalk between gut microbiome and multiple organ systems, such as gut-vascular, heart-gut, gut-liver and brain-gut axes, are associated with higher cardiovascular risks. Medications and strategies that restore healthy gut microbiome might therefore represent novel therapeutic options to lower the incidence of cardiovascular and metabolic disorders.

Introduction Androgen deprivation therapy (ADT) is a key treatment modality in the management of prostate cancer (PCa), especially for patients with metastatic disease. Increasing evidences suggest that patients who received ADT have increased incidence of diabetes, myocardial infarction, stroke, and even mortality. It is important to understand the pathophysiological mechanisms on how ADT increases cardiovascular risk and induces cardiovascular events, which would provide important information for potential implementation of preventive measures. Methods Twenty-six 12-week-old male SD rats were divided into four groups for different types of ADTs including: the bilateral orchidectomy group (Orx), LHRH agonist group (leuprolide), LHRH antagonist group (degarelix), and control group. After treated with drug or adjuvant injection every 3 weeks for 24 weeks, all rats were sacrificed and total blood were collected. Aorta, renal arteries, and kidney were preserved for functional assay, immunohistochemistry, western blot, and quantitative reverse-transcription polymerase chain reaction. Results In vascular reactivity assays, aorta, intrarenal, and coronary arteries of all three ADT groups showed endothelial dysfunction. AT1R and related molecules at protein and messenger RNA (mRNA) level were tested, and AT1R pathway was shown to be activated and played a role in endothelial dysfunction. Both ACE and AT1R mRNA levels were doubled in the aorta in the leuprolide group while Orx and degarelix groups showed upregulation of AT1R in the kidney tissues. By immunohistochemistry, our result showed higher expression of AT1R in the intrarenal arteries of leuprolide and degarelix groups. The role of reactive oxygen species in endothelial dysfunction was confirmed by DHE fluorescence, nitrotyrosine overexpression, and upregulation of NOX2 in the different ADT treatment groups. Conclusion ADT causes endothelial dysfunction in male rats. GnRH receptor agonist compared to GnRH receptor antagonist, showed more impairment of endothelial function in the aorta and intrarenal arteries. Such change might be associated with upregulation and activation of AngII-AT1R-NOX2 induced oxidative stress in the vasculature. These results help to explain the different cardiovascular risks and outcomes related to different modalities of ADT treatment.

AimsTo examine independent and interactive associations of ophthalmic and systemic conditions with incident dementia.MethodsOur analysis included 12 364 adults aged 55–73 years from the UK Biobank cohort. Participants were assessed between 2006 and 2010 at baseline and were followed up until the early of 2021. Incident dementia was ascertained using hospital inpatient, death records and self-reported data.ResultsOver 1 263 513 person-years of follow-up, 2304 cases of incident dementia were documented. The multivariable-adjusted HRs (95% CI) for dementia associated with age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED) and glaucoma at baseline were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00) and (1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were all associated with an increased risk of dementia. Of the combination of AMD and a systemic condition, AMD-diabetes was associated with the highest risk for incident dementia (HR (95% CI): 2.73 (1.79 to 4.17)). Individuals with cataract and a systemic condition were 1.19–2.29 times more likely to develop dementia compared with those without cataract and systemic conditions. The corresponding number for DRED and a systemic condition was 1.50–3.24. Diabetes, hypertension, heart disease, depression and stroke newly identified during follow-up mediated the association between cataract and incident dementia as well as the association between DRED and incident dementia.ConclusionsAMD, cataract and DRED but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.

Papillary thyroid microcarcinoma (PTMC) frequently presents a favorable clinical outcome, while aggressive invasiveness can also be found in some of this population. Identifying the risk clinical factors of high-volume (> 5) central lymph node metastasis (CLNM) in PTMC patients could help oncologists make a better-individualized clinical decision. We retrospectively reviewed the clinical characteristics of adult patients with PTC in the Surveillance, Epidemiology, and End Results (SEER) database between Jan 2010 and Dec 2015 and in one medical center affiliated to Chongqing Medical University between Jan 2018 and Oct 2020. Univariate and multivariate logistic regression analyses were used to determine the risk factors for high volume of CLNM in PTMC patients. The male gender (OR = 2.02, 95% CI 1.46–2.81), larger tumor size (> 5 mm, OR = 1.64, 95% CI 1.13–2.38), multifocality (OR = 1.87, 95% CI 1.40–2.51), and extrathyroidal invasion (OR = 3.67; 95% CI 2.64–5.10) were independent risk factors in promoting high-volume of CLNM in PTMC patients. By contrast, elderly age (≥ 55 years) at diagnosis (OR = 0.57, 95% CI 0.40–0.81) and PTMC-follicular variate (OR = 0.60, 95% CI 0.42–0.87) were determined as the protective factors. Based on these indicators, a nomogram was further constructed with a good concordance index (C-index) of 0.702, supported by an external validating cohort with a promising C-index of 0.811. A nomogram was successfully established and validated with six clinical indicators. This model could help surgeons to make a better-individualized clinical decision on the management of PTMC patients, especially in terms of whether prophylactic central lymph node dissection and postoperative radiotherapy should be warranted.

It’s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86–19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82–20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06–15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Neighborhood socioeconomic deprivation is associated with adverse outcomes after pediatric liver transplant. We sought to determine if this relationship varies by transplant center. Using SRTR, we included patients

Whether selective serotonin reuptake inhibitors (SSRIs) can improve cognitive function in depressed patients remains unclear. We aimed to explore the effect of SSRIs on cognitive function and the influencing factors in patients with major depressive disorder (MDD) with impaired cognitive function. We used a neurocognitive test battery to assess five cognitive domains, namely, attention/vigilance, learning, memory, processing speed and executive functioning, and calculated the Global Deficit Score (GDS). A GDS≥0.5 indicated overall cognitive impairment. The changes in the cognitive domains and overall cognitive function were analyzed in MDD patients with a baseline GDS≥0.5 who completed 8 weeks of SSRI treatment. We divided the patients into the cognitive remission and nonremission groups to explore the associated factors. In total, 160 patients (mean age 37.6 ± 10.8 years, 30.6% male) were included in the final analysis. The median (quartiles) of baseline GDS and HRSD17 were 1.4 (0.8, 1.9) and 19.5 (17.0, 23.0), respectively. All five cognitive domains improved after the treatment, while only 41 (25.6%) patients achieved cognitive remission. Recurrence and a higher baseline GDS were risk factors for cognitive nonremission. More aggressive interventions may be needed to promote cognitive remission in clinical practice, especially for patients with severe cognitive impairment and recurrent episodes.

Background Patients with sickle cell disease (SCD) have vaso-occlusive crises (VOCs). Infusion centers (ICs) are alternatives to emergency department (ED) care and may improve patient outcomes. Objective To assess whether care in ICs or EDs leads to better outcomes for the treatment of uncomplicated VOCs. Design Prospective cohort. (ClinicalTrials.gov: NCT02411396). Setting 4 U.S. sites, with recruitment between April 2015 and December 2016. Participants Adults with SCD living within 60 miles of a study site. Measurements Participants were followed for 18 months after enrollment. Outcomes of interest were time to first dose of parenteral pain medication, whether pain reassessment was completed within 30 minutes after the first dose, and patient disposition on discharge from the acute care visit. Treatment effects for ICs versus EDs were estimated using a time-varying propensity score adjustment. Results Researchers enrolled 483 participants; the 269 who had acute care visits on weekdays are included in this report. With inverse probability of treatment-weighted adjustment, the mean time to first dose was 62 minutes in ICs and 132 minutes in EDs; the difference was 70 minutes (95% CI, 54 to 98 minutes; E-value, 2.8). The probability of pain reassessment within 30 minutes of the first dose of parenteral pain medication was 3.8 times greater (CI, 2.63 to 5.64 times greater; E-value, 4.7) in the IC than the ED. The probability that a participant's visit would end in admission to the hospital was smaller by a factor of 4 (0.25 [CI, 0.18 to 0.33]) with treatment in an IC versus an ED. Limitation The study was restricted to participants with uncomplicated VOCs. Conclusion In adults with SCD having a VOC, treatment in an IC is associated with substantially better outcomes than treatment in an ED. Primary funding source Patient-Centered Outcomes Research Institute.

Aim: Cell invasion leading to metastasis is a major cause of treatment failure in head–neck cancers (HNCs). Identifying prognostic molecules associated with invasiveness is imperative for clinical applications. Materials & methods: A systemic approach was used to globally survey invasion-related genes, including transcriptomic profiling, pathway analysis, data mining and prognostic assessment using TCGA-HNSC dataset. Results: Six functional pathways and six hub molecules (LAMA3, LAMC2, THBS1, IGF1R, PDGFB and TGFβ1) were identified that significantly contributed to cell invasion, leading to poor survival in HNC patients. Combinations of multiple biomarkers substantially increased the probability of accurately predicting prognosis. Conclusion: Our six defined invasion-related molecules may be used as a panel signature in precision medicine for prognostic indicators or molecular therapeutic targets for HNC.

Many studies have investigated subjective responses to noise, but few concerned about the influence of age on the annoyance (discomfort) caused by noise. It is difficult to get a quantitative model featuring the relationship between noise-induced annoyance and age from one or several laboratory studies due to relatively small samples and limited age groups. This paper investigated recent studies (published after the year 2000) on noise-induced annoyance by the literature review method. We classified the studies according to their employed noise types and summarized the quantified subjective values and the ranges of age. The quantitative values of annoyance obtained from variable rating scales were transferred to a uniform scale and normalized. A probability density function then figured out the corresponding annoyance of a certain age under the small sample -distribution assumption. A predicting model of noise-induced annoyance from the age of 7-55 was proposed, which fitted previous data well.

Introduction: Foreign body ingestion is the most common reason for otolaryngology specialist consultations in emergency departments. Among the different types of foreign bodies, fish bones are the most common, particularly in Asian populations. In Taiwan, upper aerodigestive tract foreign bodies (UADT-FBs) are mostly managed by residents in the otorhinolaryngology (ORL) department. Considering the learning curve required for all procedures, different management types between residents, and possible resulting safety issues, this study explored the outcomes of UADT-FB management by residents in different years of ORL training. Materials and Methods: The medical records of 2,283 patients who visited Kaohsiung Veterans General Hospital’s Emergency Department for UADT-FB during June 2013–August 2019 were retrospectively reviewed. The reviewed data included the demographic data of enrolled patients, outcomes of foreign body management, and follow-up chart records of the patients. Results: Among the 2,283 patients, 1,324 (58%) were found to be negative for foreign bodies, and foreign bodies in 951 (41.7%) were removed immediately. In the negative finding (NF) group, 2 (4.9%) patients were later found to be positive for foreign bodies during follow-up in the outpatient department. One (2.4%) patient developed a deep neck infection and esophageal perforation. The percentage of NFs decreased from 62.58% in residents in the first half of their first year (R1a) to 54% for third-year residents (R3). Comparing R1a with R3, the number needed to harm for retained UADT-FBs after patients visited the emergency department was 12.2. Discussion/Conclusion: This study provides data from 1 referral center regarding the management of UADT-FBs. With increasing resident training, the percentage of NFs declined from 62.58 to 54%. Young residents, especially those in the first 6 months of their training, should have senior residents perform a second examination if UADT-FBs are not found in suspected cases.

This study investigated the knowledge, thoughts, and attitudes of oncology nurses in China regarding fertility preservation for male cancer patients of childbearing age, and for offering counseling or oncofertility services for the men in their care. Data was collected from 18 oncology nurses in Southwest China through voluntary self-report and in-depth interviews. The qualitative interview data were analyzed using a descriptive phenomenology method based on the lived experience of the nurses. The interviewees commonly reported 6 main concerns regarding fertility preservation (FP): their insufficient knowledge and inadequate nursing education; the importance of offering such services to cancer patients; legal vulnerability if FP information is withheld from patients; the role of the nurse in counseling; and barriers to discussing FP in practice. Nurses had a positive attitude toward FP, but most had no practical role in routinely informing male patients of their options, and the nurses believed that discussion of FP was outside their scope of practice. This study offers insight into the perceptions of oncology nurses in a developing country regarding the provision of FP services for adult male cancer patients. These results lead us to recommend that local fertility nurses should be given new training regarding FP. Furthermore, nurse-led clinics are desirable. Future research should focus on the effectiveness of nurse participation in FP counseling and referral, and how to improve the professional confidence of oncology nurses for addressing FP issues.

Chia-Yu Huang,1– 3 Ming-Cheng Huang,3,4 Mao-Feng Sun,3,4 Cheng-Li Lin,5,6 Mei-Yao Wu,4,7 Wu-Chou Lin,3,8,&ast; Hung-Rong Yen3,4,9,10,&ast; 1Department of Family Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, 427, Taiwan; 2School of Medicine, Tzu Chi University, Hualien, 970, Taiwan; 3Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404, Taiwan; 4Department of Chinese Medicine, China Medical University Hospital, Taichung, 404, Taiwan; 5Management Office for Health Data, China Medical University Hospital, Taichung, 404, Taiwan; 6College of Medicine, China Medical University, Taichung, 404, Taiwan; 7School of Post-baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 404, Taiwan; 8Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, 404, Taiwan; 9Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, 404, Taiwan; 10Chinese Medicine Research Center, China Medical University, Taichung, 404, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hung-Rong Yen Tel +886-4-22053366 ext. 3313Email hungrongyen@mail.cmu.edu.twWu-Chou Lin Tel +886-4-22052121Email d0562@mail.cmuh.org.twBackground: Major depressive disorder is a significant public health concern, which often leads to loss of productivity, functional decline, and various complications. The aim of this study was to investigate the effectiveness of acupuncture in the risk reduction of coronary heart disease (CHD) in patients with depression.Methods: We enrolled patients diagnosed with depression between January 1, 1997, and December 31, 2010, through the Taiwanese National Health Insurance Research Database (NHIRD). Propensity score was used to match equal numbers (n=14,647) of acupuncture cohort and no-acupuncture cohort based on characteristics including sex, age, baseline comorbidity and medication. Patients were followed up until December 31, 2013, or withdrawn from the NHIRD. The Cox regression model was used to compare the hazard ratios (HRs) of CHD in the two cohorts.Results: The basic characteristics of the two groups were similar. A lower cumulative incidence of CHD was noted in the acupuncture cohort (Log rank test, p < 0.001). Over time, 1626 patients in the acupuncture cohort (21.05 per 1000 person-years) and 2412 patients in the no-acupuncture cohort (39.84 per 1000 person-years) developed CHD (adjusted HR=0.50, 95% CI 0.47– 0.53). The decreased CHD incidence was independent of age, sex, comorbidities, and medications used. The cumulative incidence of CHD was significantly lower in the acupuncture cohort than in the no-acupuncture cohort (Log rank test, p< 0.001).Conclusion: The results provided a real-world evidence that acupuncture may have beneficial effect on CHD risk reduction in patients with depression.Keywords: acupuncture, depression, coronary heart disease, National Health Insurance Research Database, real-world evidence

Objective To evaluate the value of using both HMG and recombinant FSH (r-FSH) in the GnRH antagonist protocol for women with high AMH. Materials and methods This retrospective, single-center cohort study was conducted from January 2013 to December 2018. Of 277 GnRH antagonist IVF/ICSI cycles in women with anti-Mullerian hormone (AMH) ≥5 μg/L, 170 cycles receiving the combination of r-FSH and HMG (77 with HMG added at the beginning of the GnRH antagonist cycle and 93 with HMG added after GnRH antagonist administration) and 107 cycles receiving r-FSH alone were analyzed. The dynamic hormone profiles and embryonic and clinical outcomes of the patients were evaluated. Results We observed significantly lower serum LH levels in the r-FSH + HMG groups during ovarian stimulation. The serum estradiol and progesterone levels were lower in the r-FSH + HMG groups on the trigger day. Nevertheless, there were no significant differences with respect to the number of oocytes retrieved, maturation, fertilization, blastocyst formation rate or ovarian hyperstimulation syndrome (OHSS). The implantation and live birth rates were increased in the r-FSH + HMG groups compared with the r-FSH alone group, with no statistical significance. Conclusions HMG for LH supplementation in the GnRH antagonist protocol for patients with high AMH is not significantly superior to r-FSH alone in terms of ovarian response and pregnancy outcome. Nevertheless, HMG supplementation might be appropriate for women with an initially inadequate response to r-FSH or intracycle LH deficiency.

Backgrounds To date, there is still no consensus about the clinical efficacy of non-surgical periodontal therapy in rheumatoid arthritis (RA) patients with periodontitis. Therefore, the aim of this study was to summarize clinical data regarding the efficacy of scaling and root planing (SRP) in patients with RA and periodontitis compared to non-RA periodontitis patients. Methods We selected randomized controlled trials (RCTs) that compared periodontal clinical data in RA as compared to non-RA periodontitis patients by searching Embase, PubMed and Cochrane Central Register of Controlled Trials and by manually retrieving from the earliest records to March 8, 2021. The overall effect size of plaque index (PI), gingival index (GI), attachment loss (AL), probing depth (PD) and bleeding on probing (BOP) were calculated by either a fixed or random-effect model, and subgroup analyses were conducted according to the different time points of follow-up. Two investigators extracted the data and assess the accuracy of the obtained results with 95% of Confidence Intervals (CI). Cochrane Collaboration's tool was responsible for the evaluation of the literature quality and the inter-study heterogeneity was evaluated by Q test and I2 statistic. Sensitivity analyses were applied for results with heterogeneity. Publication bias was determined by Begg's test, Egger's test and the trim-and-fill method. Results Seven RCTs including 212 patients eventually met the inclusion criteria for the study. As the primary results, the change of PD was not statistically significant and in the secondary results changes of PI, GI, AL and BOP were also not statistically significant in RA patients with periodontitis compared to non-RA periodontitis patients. In subgroup analysis, a larger BOP reduction at 3 months, PI and AL reduction at 6 months were observed in patients with RA and periodontitis group. The results of sensitivity analyses had no significant effect. No evidence of potential publication bias was tested. There were some limitations due to the small number of eligible RCTs. Conclusions SRP is equally effective in RA as compared to non-RA periodontitis patients. It suggests RA does not affect the clinical efficacy of non-surgical periodontal therapy. These results could serve evidence-based practice.

ObjectivePatients with diabetes have an increased risk of dementia. Improved prediction of dementia is an important goal in developing future prevention strategies. Diabetic retinopathy screening (DRS) photographs may be a convenient source of imaging biomarkers of brain health. We therefore investigated the association of retinal vascular measures (RVMs) from DRS photographs in patients with type 2 diabetes with dementia risk.Research Design and MethodsRVMs were obtained from 6,111 patients in the GoDARTS bioresource using VAMPIRE software. Their association, independent of Apo E4 genotype and clinical parameters, was determined for incident all cause dementia (ACD) and separately Alzheimer’s dementia (AD) and vascular dementia (VD). We used Cox’s proportional hazards with competing risk of death without dementia. The potential value of RVMs to increase the accuracy of risk prediction was evaluated.ResultsIncreased retinal arteriolar fractal dimension associated with increased risk of ACD (csHR 1.17; 1.08-1.26) and AD (HR 1.33; 1.16-1.52), whereas increased venular fractal dimension (FDV) was associated with reduced risk of AD (csHR 0.85; 0.74-0.96). Conversely, FDV was associated with increased risk of VD (csHR 1.22; 1.07-1.40). Wider arteriolar calibre was associated with a reduced risk of ACD (csHR 0.9; 0.83-0.98) and wider venular calibre was associated with a reduced risk of AD (csHR 0.87; 0.78-0.97). Accounting for competing risk did not substantially alter these findings. RVMs significantly increased the accuracy of prediction.ConclusionsConventional DRS photographs could enhance stratifying patients with diabetes at increased risk of dementia facilitating the development of future prevention strategies.

Performing subtrochanteric osteotomy with cemented components in patients with Crowe IV developmental dysplasia of the hip (DDH) is technically challenging and not widely reported. This study aimed to evaluate the mid-term outcomes of cemented stem total hip arthroplasty (THA) with subtrochanteric femoral shortening and transverse derotational osteotomy in patients with Crowe IV DDH.Data collected from patients with Crowe IV DDH who underwent cemented stem THA with subtrochanteric femoral shortening and transverse derotational osteotomy between 2010 and 2018 were retrospectively evaluated. The cemented Lubinus SP II femoral component and the cementless CombiCup acetabular component were used together in all cases. These data, including Harris hip scores, limb length discrepancy (LLD), severity of limp, Trendelenburg test, bone union, length of the resected femur, limb lengthening, level of the osteotomy site, and length bridging the osteotomy site, as well as complications, were analyzed. A paired Student t-test was used to analyze continuous variables, categorical data were compared using Fisher's exact probability test, and correlation analysis was performed using Spearman's rank correlation coefficient.Among 14 included patients (10 females and four males), the mean age was 60.4 years (range, 47-73). The mean follow-up period was 49.1 months, and no patient was lost to follow-up. The mean Harris hip score improved from 40.7 to 87.7. The mean LLD decreased from 52 to 12.7 mm. The mean length of the excised femoral segment was 38.4 mm, and the mean length of limb lengthening was 27.1 mm. The mean distance between the osteotomy site and the lesser trochanter was 21.1 mm after surgery. The mean length of the femoral stem bridging the osteotomy site was 97.6 mm. Finally, the mean osteotomy union time was 10.6 months. No statistically significant correlation was found between the osteotomy union time and these factors. No neurological deficits were noted. Delayed union was observed in one patient, and postoperative dislocation was observed in two patients. Cement leakage into the osteotomy gap was observed in one patient, however, no revisions were required, and no signs of loosening or migration were observed.Cemented stem THA combined with subtrochanteric femoral shortening and transverse derotational osteotomy is safe and effective in treating patients with Crowe IV DDH. Rather than leading to nonunion, cement leakage may negatively affect bone healing.

OBJECTIVE Salvage endoscopic nasopharyngectomy (ENPG) is a reasonable choice for resectable recurrent nasopharyngeal carcinoma (rNPC). However, in past decades, complete removal of the tumor was not feasible when the recurrent lesion was adjacent to the internal carotid artery (ICA). The present article introduces innovative strategies to ensure sufficient surgical margins while avoiding accidental injury to the ICA. STUDY DESIGN Retrospective study. SETTING Tertiary care center. METHODS We retrospectively reviewed rT2-3 rNPC patients with tumor lesions adjacent to the ICA (

Aims New-generation breakpoint cluster region-Abelson tyrosine kinase inhibitors (TKIs) have a higher incidence of cardiovascular events than imatinib in patients with chronic myeloid leukaemia (CML). However, this knowledge is insufficiently proven. Hence, this study aimed to explore the association between cardiovascular events and TKIs in patients with CML. Methods and results This retrospective population-based cohort study enrolled first-time users of imatinib, dasatinib, and nilotinib between 1 January 2007 and 31 December 2016. Arterial thromboembolic events (ATEs) were the primary outcome, while other cardiovascular-related events were the secondary outcomes. The event rates were estimated using Kaplan–Meier estimates, and the hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. Additionally, the competing risk was adjusted using the Fine and Gray competing risk model. We included 1207 patients. Nilotinib had a significantly higher ATE risk (subdistribution HR = 4.92, 95% CI = 1.68–14.36) than imatinib. Conversely, no difference was found for other cardiovascular-related events. Risks of ATE and other cardiovascular-related events were similar between dasatinib and imatinib and between nilotinib and dasatinib. The risk of ATE hospitalization consistently increased throughout the main analyses and sensitivity analyses. Conclusion Nilotinib-treated patients had a significantly higher risk of developing ATE than imatinib-treated patients. However, the risks of ATE and other cardiovascular-related events were not significantly different between dasatinib and imatinib.

Background Attention-deficit/hyperactivity disorder (ADHD) has been linked to pediatric asthma patients treated with montelukast. This study is the first to use a nationwide health insurance research database (NHIRD) to study whether asthmatic children using montelukast are at an increased risk of ADHD. Methods We used data from the Taiwan NHIRD, which is a longitudinal database of one million randomly selected subjects. The enrolled patients were followed up until 2013. Patients younger than and equal to 12 years old with new-onset asthma (ICD-9 CM code 493.X) diagnosed between 1997 and 2013 were enrolled. A multivariate Cox regression analysis was conducted to evaluate the association between montelukast treatment and the risk of ADHD (ICD-9-CM code 314.X). Results We enrolled a total of 54,487 asthmatic children younger than and equal to 12 years old who had at least one claim of inpatient admission or at least three claims of an ambulatory visit. Montelukast users and match controls were identified by matching age, gender, residence, the comorbidities including allergic rhinitis and atopic dermatitis, admission or emergency department visits due to asthma attack, and index date of starting montelukast in a 1:1 ratio, with 12,806 in the montelukast group and 12,806 in the non-montelukast group. The montelukast group had a similar risk of ADHD (n = 632, 4.94%) as the non-montelukast group (n = 610, 4.76%) [adjusted hazard ratio 1.04; 95% confidence interval, 0.93 to 1.17]. In children treated with montelukast, high cumulative days of montelukast use did not increase the risk of ADHD. Conclusion This nationwide population-based cohort study reveals that asthma children treated with montelukast were not at an increased risk of developing ADHD. Nevertheless, validation of our retrospective survey requires further prospective study.

Yu-Chiang Hung,1,* Pao-Yen Lin,2,* Hsienhsueh Elley Chiu,1 Po-Yu Huang,1 Wen-Long Hu1,3,4 1Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3Fooyin University College of Nursing, Kaohsiung, Taiwan; 4Kaohsiung Medical University College of Medicine, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Wen-Long HuDepartment of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Road, Niaosong District, Kaohsiung City, 833, TaiwanEmail oolonghu@gmail.comObjective: To evaluate the treatment effectiveness of laser acupuncture (LA) in patients with musculoskeletal pain.Methods: Major electronic databases, including Medline, PubMed, Embase, Cochrane Library, CINAHL, and Scopus were searched to identify double-blind, randomized controlled trials of LA in musculoskeletal disorders. The primary outcome was the treatment efficacy for pain. The secondary outcomes included the comparison of disability, functional impairment, and dropout rate between LA and sham treatment, as well as the effect of sham treatment for pain. The results from included studies were synthesized with the random effects model.Results: In total, 20 articles comprising 568 patients receiving LA and 534 patients receiving sham treatment were included in the current study. Our analysis showed LA significantly reduced pain (g=0.88, 95% confidence interval [CI]=0.35 to 1.42, p=0.001), disability (g=0.68, 95% CI=0.29 to 1.08, p< 0.001), and functional impairment (g=0.67, 95% CI=0.32 to 1.03, p< 0.001). Through meta-regression analysis, we found these effects were not moderated by mean age, the percentage of females, or treatment duration. Additionally, there was no significant difference between the two groups in dropout rate (risk ratio=0.73, p=0.08), and the sham treatment significantly reduced only pain intensity (g=0.54, 95% CI=0.32 to 0.77, p< 0.001).Conclusion: Our findings supported that LA significantly reduced pain, disability, and functional impairment in patients with musculoskeletal disorders. Further researches are required to determine the optimal therapeutic parameters and the suitable patients for receiving LA.Protocol Registration: CRD42020190919.Keywords: laser acupuncture, meta-analysis, pain, randomized controlled trial, traditional Chinese medicine

The mechanism of estrogen deficiency-induced cognitive impairment is still not fully elucidated. In this study, we assessed the effect of microRNA (miRNA) on the memory of long-term estrogen-deficient mice after ovariectomy (OVX) and normal aging. We observed that 5-month OVX and 22-month-old normal aging female mice showed significantly impaired spatial and object recognition memory, declined hippocampal long-term potentiation (LTP), and decreased hippocampal protein kinase C α (PKCα) protein. Quantitative real-time PCR analysis showed upregulated miRNA-23a-3p (miR-23a-3p) in the hippocampus of 5-month OVX and 22-month-old female mice. In vitro, overexpression of miR-23a-3p downregulated PKCα by binding the 3¢ UTRs of Prkca mRNAs, which was prevented by its antisense oligonucleotide AMO-23a. In vivo, adeno-associated virus-mediated overexpression of miR-23a-3p (AAV-pre-miR-23a-3p) suppressed hippocampal PKCα and impaired the memory of mice. Chromatin immunoprecipitation analysis showed that aryl hydrocarbon receptor (AhR) binds the promoter region of miR-23a-3p. The AhR-dependent downregulation of PKCα could be prevented by AMO-23a as well. Furthermore, knockdown of miR-23a-3p using AAV-AMO-23a rescued the cognitive and electrophysiological impairments of OVX and normal aging female mice. We conclude that long-term estrogen deficiency impairs cognition and hippocampal LTP by activating the AhR/miR-23a-3p/PKCα axis. The knockdown of miR-23a-3p may be a potentially valuable therapeutic strategy for estrogen deficiency-induced memory deficits., Graphical Abstract, Ovariectomy- or normal aging-induced long-term estrogen deficiency impairs the cognition of female mice through activating the hippocampal AhR/miR-23-3p/PKCα axis. Hippocampal miR-23-3p loss of function rescues the expression of PKCα and the cognitive function of ovariectomized and aging female mice.

To evaluate the relationship between obstructive sleep apnea (OSA) and diabetic macular edema (DME) and the effect of OSA on refractory DME in patients with type 2 diabetes (T2DM).Retrospective clinical cohort study.A population-based study was conducted at Chang Gung Memorial Hospital from March 1, 2009, to March 1, 2020. Among 14,152 patients who had undergone polysomnography (PSG) and whose data were registered on the sleep center's PSG database, 121 patients (242 eyes) with T2DM were enrolled according to the International Classification of Diseases, Ninth Revision (ICD-9) code 3620 for diabetic retinopathy (DR). Patients with a secondary cause of macular edema and those lacking medical records were excluded. All patients with T2DM enrolled in our study received both optical coherence tomography (OCT) and PSG. The prevalence of severe (apnea-hypopnea index [AHI] ≥30) and nonsevere (AHI30) OSA was compared between patients with and without DME and refractory DME.In total, 102 eyes (54 patients) were divided into groups of 40 eyes with DME or 62 eyes without DME. Severe OSA (odds ratio, 7.36; 95% confidence interval [CI]: 1.32-40.96; P = .023) was significantly associated with DME. Refractory DME was significantly more frequent in patients with severe OSA (27%) than in those with nonsevere OSA (0%; P = .009). Cox proportional hazards regression analysis revealed that OSA (hazard ratio, 2.97; CI, 1.08-8.16; P = .034) independently increased the DME risk after adjustment for age, sex, glycohemoglobin level, hypertension, and hypercholesterolemia.Severe OSA is a risk factor for DME and is associated with having refractory DME.

Objective To evaluated the clinical outcomes of periprosthetic joint infection (PJI) patients with destination joint spacer compared with that of two‐stage revision. Methods From January 2006 to December 2017, data of PJI patients who underwent implantation with antibiotic‐impregnated cement spacers in our center due to chronic PJI were collected retrospectively. The diagnosis of PJI was based on the American Society for Musculoskeletal Infection (MSIS) criteria for PJI. One of the following must be met for diagnosis of PJI: a sinus tract communicating with the prosthesis; a pathogenis isolated by culture from two separate tissue or fluid samples obtained from the affected prosthetic joint; four of the following six criteria exist: (i) elevated ESR and CRP; (ii) elevate dsynovial fluid white blood cell (WBC) count; (iii) elevated synovial fluid neutrophil percentage (PMN%); (iv) presence of purulence in the affected joint; (v) isolation of a microorganism in one periprosthetic tissue or fluid culture; (vi) more than five neutrophilsper high‐power fields in five high‐power fields observed from histological analysis of periprosthetic tissue at ×400 magnification. Age, sex, body mass index (BMI), and laboratory test results were recorded. All patients were followed up regularly after surgery, the infection‐relief rates were recorded, Harris hip score (HHS) and knee society score (KSS) were used for functional evaluation, a Doppler ultrasonography of the lower limb veins was performed for complication evaluation. The infection‐relief rates and complications were compared between destination joint spacer group and two‐stage revision group. Results A total of 62 patients who were diagnosed with chronic PJI were enrolled, with an age of 65.13 ± 9.94 (39–88) years. There were 21 cases in the destination joint spacer group and 41 cases in the temporary spacer group, namely, two‐stage revision group (reimplantation of prosthesis after infection relief). The Charlson comorbidity index (CCI) in the destination joint spacer group was higher than that in the temporary spacer group, and this might be the primary reason for joint spacer retainment. As for infection‐relief rate, there were three cases of recurrent infection (14.29%) in the destination joint spacer group and four cases of recurrent infection (9.76%) in the two‐stage revision group, there were no significant differences with regard to infection‐relief rate. Moreover, there two patients who suffered from spacer fractures, three cases of dislocation, one case of a periarticular fracture, and three cases of deep venous thrombosis in destination joint spacer group, while there was only one case of periprosthetic hip joint fracture, one case of dislocation, and one patient suffered from deep venous thrombosis of the lower extremity in two‐stage revision. The incidence of complications in the destination joint spacer group was higher than that of two‐stage revision. Conclusions In summary, the present work showed that a destination joint spacer might be provided as a last resort for certain PJI patients due to similar infection‐relief rate compared with two‐stage revision., Diagram of destination joint spacer.

BackgroundFor unknown reasons, Hispanic patients with cystic fibrosis (CF) have more severe pulmonary disease than non-Hispanic white patients. In CF, the pulmonary pathogen Pseudomonas aeruginosa is associated with worse outcomes. We sought to determine if Hispanic patients with CF are at an increased risk of acquiring P. aeruginosa or acquire it earlier than non-Hispanic white patients.MethodsThis is a longitudinal study comparing the timing and risk of acquisition of different forms of P. aeruginosa between Hispanic and non-Hispanic white patients aged 0-21 years old with CF in the CF Foundation Patient Registry (CFFPR) in 2008-2013. The age at the initial acquisition of P. aeruginosa (initial acquisition, mucoid, chronic, multidrug-resistant) was summarized using Kaplan-Meier survival curves and analyzed using Cox proportional hazards regression models.ResultsOf 10,464 patients, 788 (7.5%) were Hispanic and 9,676 (92.5%) were non-Hispanic white. Hispanic patients acquired all forms of P. aeruginosa at a younger age than non-Hispanic white patients. Hispanic patients had a higher risk of acquiring P. aeruginosa than non-Hispanic white patients: the hazard ratio (HR) was 1.26 (95% CI 1.16-1.38, p

Endoscopic sinus surgery offers a minimally invasive approach to reach the deep located nasopharynx, but the application of endoscopic nasopharyngectomy (ENPG) for locally recurrent nasopharyngeal carcinoma (NPC) has been limited by difficulties related to operating in the narrow nasal and nasopharyngeal cavities, achieving en bloc resection, protecting the internal carotid artery and reconstructing the defect. A series of innovations, such as the “third-hand technique,” “cube-like resection,” “dumpling-making technique,” and “pedicle nasal mucoperiosteal flap,” have been explored and applied to address these difficulties. Currently, ENPG accompanied with a nasal flap has been the most widely used modality for locally recurrent NPC with tumor limited in “resettable area,” and has led to better survival outcomes, better quality of life and lower treatment-related complication rates than salvage radiotherapy and traditional open surgery. Furthermore, ENPG has been extended to treat primary stage I NPC and postradiation nasopharyngeal necrosis, showing promising results in improving quality of life and survival.

The aim of this study was to construct and validate a DNA repair-related gene signature for evaluating the overall survival (OS) of patients with gastric cancer (GC). Differentially expressed DNA repair genes between GC and normal gastric tissue samples obtained from the TCGA database were identified. Univariate Cox analysis was used to screen survival-related genes and multivariate Cox analysis was applied to construct a DNA repair-related gene signature. An integrated bioinformatics approach was performed to evaluate its diagnostic and prognostic value. The prognostic model and the expression levels of signature genes were validated using an independent external validation cohort. Two genes (CHAF1A, RMI1) were identified to establish the prognostic signature and patients ware stratified into high- and low-risk groups. Patients in high-risk group presented significant shorter survival time than patients in the low-risk group in both cohorts, which were verified by the ROC curves. Multivariate analysis showed that the prognostic signature was an independent predictor for patients with GC after adjustment for other known clinical parameters. A nomogram incorporating the signature and known clinical factors yielded better performance and net benefits in calibration plot and decision curve analyses. Further, the logistic regression classifier based on the two genes presented an excellent diagnostic power in differentiating early HCC and normal tissues with AUCs higher than 0.9. Moreover, Gene Set Enrichment Analysis revealed that diverse cancer-related pathways significantly clustered in the high-risk and low-risk groups. Immune cell infiltration analysis revealed that CHAF1A and RMI1 were correlated with several types of immune cell subtypes. A prognostic signature using CHAF1A and RMI1 was developed that effectively predicted different OS rates among patients with GC. This risk model provides new clinical evidence for the diagnostic accuracy and survival prediction of GC.

To investigate the expression of bone morphogenetic protein 10 (BMP-10) in patients with endometrial carcinoma (EC) and its clinical significance. Totally 143 cancer tissue specimens were sampled from patients with EC and retrospectively analyzed. The immunohistochemical method was adopted for quantifying BMP-10 in EC tissues. Then the patients were assigned to high and low BMP-10 expression groups. The Kaplan–Meier method and log-rank test were adopted to compare the difference of tumor-free survival (TFS) rate and overall survival (OS) rate between the two groups. The COX proportional hazard model was used to analyze independent risk factors affecting the TFS rate and OS rate of patients with EC. There were 80 patients (55.94%) with low BMP-10 expression and 63 patients with high BMP-10 expression (54.06%). BMP-10 expression was significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.001), myometrial invasion depth (P

Objective First trimester screening is essential to preeclampsia (PE) prevention. Fetal Medicine Foundation (FMF) model combined maternal characteristics with mean arterial pressure (MAP), uterine artery pulsatility index (UtAPI) and placental growth factor (PlGF) to estimate risk. High detection rate (DR) was observed in Asia. The study aims to evaluate performance of screening in Taiwan. Materials and methods This was a prospective and non-interventional study between January, 2017 and June, 2018. Data was collected from 700 pregnant women at 11+0–13+6 gestational week. Maternal characteristics were recorded. MAP, UtAPI and PlGF were measured and converted into Multiple of the Median (MoM). Patient-specific risks were calculated with FMF model. Performance of screening was examined by ROC curve and DR. Results 25 women (3.57%) contracted PE, including 8 with preterm PE (1.14%). In preterm PE, mean MoM of MAP and UtAPI were higher (1.096 vs 1.000; 1.084 vs 1.035). Mean MoM of PlGF was lower (0.927 vs 1.031). DR in preterm PE achieved 12.5%, 50.0%, 50.0% and 62.5% at false-positive rate (FPR) of 5%, 10%, 15% and 20%. Conclusion FMF model showed high DR for PE in Taiwan. Integration of PE and Down screening could set up a one-step workflow.

Background Cataract surgery in combination with or after trabeculectomy is often required for improving vision in glaucoma patients. Intraocular pressure (IOP) changes may influence refractive outcomes after cataract surgery. We compared refractive outcomes of the combined and sequential approaches in managing glaucoma and cataract. Methods This retrospective case–control study included 52 patients (57 eyes) who underwent phacotrabeculectomy (combined group) and 39 patients (42 eyes) who underwent phacoemulsification at least three months post-trabeculectomy (sequential group). The IOP and refraction prediction error were compared at three months after cataract surgery. Univariate regression analyses were used to assess risk factors for the postoperative refraction prediction error. Results Anti-glaucomatous medications were not administered to either group. The mean postoperative IOP (12.96 vs. 13.80 mmHg; P = .392), refraction prediction error (−0.32 ± 1.53 vs. −0.47 ± 1.14 D, P = .594), mean absolute error (1.02 ± 1.18 vs. 0.8 ± 0.93 D, P = .320), and surgically induced astigmatism (1.85 ± 1.40 vs. 2.16 ± 1.16 D, P = .161) did not differ significantly between the combined and sequential groups. In the sequential group, the refraction prediction error correlated to the IOP change, with a 1-mm Hg rise resulting in a −0.07-diopter shift between the expected and observed refraction (r = −0.380, R2 = 0.144, P = .013); no such correlation was observed in the combined group. Conclusion Both approaches resulted in similar effective IOP control and accurate intraocular lens predictability. The IOP change affected the postoperative refraction prediction error only in the sequential approach.

Background: Portal vein embolization (PVE) is performed before major liver resection to increase liver volume remnant, controversy remains on the adverse effect of PVE on liver tumor patients. The current study highlighted the effect of PVE on the degree of hypertrophy of future liver remnant (FLR) and summarized PVE-related complications, aiming to provide a guideline for surgeons. Methods: A search of current published studies on PVE was performed. Meta-analysis was conducted to assess the effect of PVE on hypertrophy of FLR and summarized PVE-related complications. Results: 26 studies including 2335 patients were enrolled in the meta-analysis. All enrolled studies reported data regarding FLR hypertrophy rate, pooled effect size (ES) for FLR hypertrophy rate using a fixed-effect model was 0.105 (95%CI: 0.094-0.117, p=0.000), indicating PVE is favored in inducing FLR hypertrophy. Metatrim method indicated no obvious evidence of publication bias in the present meta-analysis. 247 (10.6%) patients exhibited PVE-related complications, receiving expectant treatment without affecting planned liver resection. Total 1782 patients (76%) underwent a subsequent liver resection after PVE, which is an encouraging result comparing with traditional resection rate in liver tumor patients. Conclusions: PVE is a safe and effective procedure with a low occurrence of related complications for inducing sufficient hypertrophy of FLR in liver tumor patients, which could elevate the resection rate of liver tumor patients. Careful patient cohort selection is crucial to avoid overuse of PVE in technically resectable patients. Further multiple central clinical trials are conducive to select optimal patient cohorts and provide a guideline for surgeons.

Objective: The aim of this study was to investigate sclerostin (SOST) expression in a rat model of experimental tympanosclerosis (TS) and its possible role in the formation of TS. Materials and Methods: Thirty-four SD rats were randomly divided into 2 groups: experimental group (n = 17) and normal group (n = 17). The left tympanic cavities in the experimental group were inoculated with methicillin-resistant Staphylococcus aureus. The changes of tympanic membranes were examined and recorded under otoendoscope. Haematoxylin-eosin staining was adopted to detect the morphological changes in the tympanic membrane and middle ear mucosa. Immunohistochemistry and Western blot analysis were used to observe the expression of SOST, Wnt3a, β-catenin, and P-ERK1/2. Results: In the experimental group, sclerotic lesions were observed in 54.5% ears in the end of 6 weeks. Morphological changes such as mucosa incrassation, inflammatory cells infiltration, fibrous tissue proliferation, and interstitial tissue incrassation prominently appeared in the tympanic membrane and middle ear mucosa. SOST protein was mainly distributed in the cytoplasm of epithelial cells and gland cells, the expression of which increased significantly in the calcified experimental ears. In addition, expression levels of Wnt3a, β-catenin, and P-ERK1/2 increased significantly in the calcified group too. Conclusion: The upregulated expression level of SOST may be involved in the formation of TS, first, through the pro-phosphorylation of ERK1/2 in the inflammatory stage, and then through the enhancement of Wnt3a in the osteogenic stage.