Which Is the Best Biologic for Nasal Polyps: Dupilumab, Omalizumab, or Mepolizumab? A Network Meta-Analysis.

INTRODUCTION: Compared with the placebo, biologics are beneficial in reducing nasal polyp mass and safe in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, there lacks a head-to-head randomized trial comparing biologics. We aimed to determine the best biologic for CRSwNP. METHODS: We performed a systematic review and network meta-analysis (NMA), which was registered with PROSPERO (No. CRD42021226766). A comprehensive search was performed in PubMed, Embase, Web of Science, and the Cochrane Library on December 29, 2020. Only randomized controlled trials (RCTs) assessing biologics in adult patients for CRSwNP were included. RESULTS: Nine RCTs with 1,190 patients comparing 3 different biologics (dupilumab, omalizumab, and mepolizumab) and the placebo were included. Dupilumab had the best efficacy in terms of nasal polyp score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22) score, University of Pennsylvania Smell Identification Test (UPSIT) score, and nasal congestion score (NCS) for surface under the cumulative ranking curve (SUCRA) values of 0.900, 0.916, 1.000, and 0.807, respectively. Omalizumab ranked second in efficacy in terms of SNOT-22, UPSIT, and NCS for SUCRA values of 0.606, 0.500, and 0.693, respectively. Mepolizumab ranked second in efficacy in terms of NPS for SUCRA values of 0.563 and had the highest risk of adverse events (AEs) for SUCRA values of 0.746. CONCLUSION: This is the first NMA that compared different biologics in patients with CRSwNP. Based on the efficacy (NPS) and safety (AEs), dupilumab is the best choice and omalizumab is the second best option for CRSwNP. Although mepolizumab ranked second in efficacy, it had the highest risk of AEs.

Comparison of anatomical thermal ablation and routine thermal ablation for hepatocellular carcinoma≤50 mm: A propensity score matching.

AIM: The present study was to evaluated the clinical value of anatomical thermal ablation to treat hepatocellular carcinoma compared with routine thermal ablation. METHODS: Hepatocellular carcinoma patients with tumor diameter ≤50 mm treated by thermal ablation at our center were retrospectively enrolled from October 2015 to December 2018. Enrolled patients were grouped into the anatomical ablation group and routine ablation group, respectively. To minimize the effects of potential confounders from selection bias, a propensity score matching was carried out. Technical efficacy, recurrence and survivals rates were compared. RESULTS: Altogether 101 patients (119 lesions) were grouped into the anatomical ablation group and 101 patients (131 lesions) into the routine ablation group. The ablation zone volume of the anatomical ablation group was 36.8 (2.5-176.9) ml, significantly larger than that of the routine ablation group (28.5 [28.5 (2.8-184.3) ml] (p = 0.005)). Adjusted with propensity score matching, The 1-, 2-, and 3-year local recurrence rates were 0.0%, 0.0%, and 0.0% for the anatomical ablation group and 6.9%, 10.1%, and 10.1% for the routine ablation group, respectively (p = 0.013). The cumulative 1-, 2-, and 3-year progression-free survival rates were 93.4%, 82.7%, and 79.0% for the anatomical ablation group, 74.2%, 56.9%, and 51.6% for the routine ablation group (p = 0.001). CONCLUSIONS: Anatomical ablation could be a favorable ablation strategy to improve therapeutic effect of thermal ablation for HCC with visible feeding vessels and reserved liver function.

Correction of the Estimated Hearing Level of NB Chirp ABR in Normal Hearing Population.

INTRODUCTION: The narrowband chirp (NB Chirp), a frequency-specific sound stimulus signal obtained by limiting the frequency bandwidth based on chirp, is applied to the frequency specified auditory brainstem response (fsABR) increasingly. Although some studies demonstrated that NB Chirp-evoked auditory brainstem response (NB Chirp ABR) causes a better neural response than tone burst-evoked auditory brainstem response and is preferred for fsABR, there is little known about how to better estimate an individual's hearing level through the threshold of NB Chirp ABR. The present study intended to compare the accuracy and deviation of NB Chirp ABR corrected by different approaches in estimating the hearing level of people with normal hearing. METHODS: A total of 66 volunteers with normal hearing were randomly divided into a model group (n = 26), test group 1 (n = 20), and test group 2 (n = 20). The model group was used to calculate the threshold difference between NB Chirp ABR and pure-tone audiometry at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz, as well as the regression equation, providing a reference for the correction of estimated hearing level of NB Chirp ABR. Test group 1 was used to observe the accuracy and deviation of the "noncorrection (N)," "threshold difference (A1)," and "regression equation (A2)" methods in correcting the estimated hearing level of NB Chirp ABR. Test group 2 was used to replicate the analysis of test group 1 to verify the repeatability of the experimental results. All data were analyzed using SPSS 24.0. RESULTS: Test group 1 and test group 2 had similar results. First, the accuracy of the estimated hearing level of N was significantly higher than that of A1 or A2. Second, compared with "0," the deviation of the estimated hearing level of N was bigger than that of A1 or A2 at 500 Hz and 1,000 Hz, while similar at 2,000 Hz and 4,000 Hz. Finally, there was no significant difference in the deviation of the estimated hearing level between A1 and A2 at 500 Hz and 1,000 Hz. CONCLUSION: Among people with normal hearing, it was necessary to correct NB Chirp ABR at 500 Hz and 1,000 Hz for lower deviation of the estimated hearing level. Both correction approaches based on threshold difference and regression equation can be used.

Impact of Examined Lymph Node Count for Esophageal Squamous Cell Carcinoma in Patients who Underwent Right Transthoracic Esophagectomy.

BACKGROUND: The impact of the number of examined lymph nodes (ELNs) on stage correction and prognostication in patients with esophageal squamous cell carcinoma (ESCC) who underwent right transthoracic esophagectomy is still unclear. METHODS: Patients with ESCC who underwent right transthoracic esophagectomy at Sun Yat-sen University Cancer Center between January 1997 and December 2013 were retrospectively enrolled. The Cox proportional hazards regression model was used to determine the effect of ELN count on overall survival. The impact of ELN count on stage correction was evaluated using the hypergeometric distribution and Bayes theorem and ß-binomial distribution estimation, respectively. The threshold of ELNs was determined using the LOWESS smoother and piecewise linear regression. RESULTS: Among the 875 included patients, greater ELNs were associated with a higher rate of nodal metastasis. Significant association between staging bias and the number of ELNs is only observed through the Bayes method. The ELN count did not impact 90-day mortality but significantly impacted long-term survival (adjusted hazard ratio [aHR] 0.986), especially in those patients with node-negative disease (aHR 0.972). In patients with node-negative disease, cut-point analysis showed a threshold ELN count of 21. CONCLUSIONS: A greater number of ELNs is associated with more accurate node staging and better long-term survival in resected ESCC patients. We recommended harvesting at least 21 LNs to acquire accurate staging and long-term survival information for patients with declared node-negative disease using the right thoracic approach.

Social Support and Tinnitus Distress: The Importance of Developing Positive Psychological Qualities in Patients with Chronic Tinnitus.

INTRODUCTION: The role of social support in the relief of tinnitus distress and related mechanisms remains unclear. This study aimed to confirm a hypothesis that the influence of social support on tinnitus distress is mediated by resilience and self-esteem. METHODS: The Social Support Rating Scale, Connor-Davidson Resilience Scale, Positive Version of Rosenberg Self-Esteem Scale, and Tinnitus Handicap Inventory were used to assess 296 patients who experience chronic subjective tinnitus. The collected data were subjected to correlational analysis, mediating effect testing, and structural equation model analysis using R 3.3.1 with the mediate and lavaan packages. RESULTS: The result showed that social support had significant positive correlations with resilience and self-esteem, while resilience and self-esteem had significant negative correlations with tinnitus distress. Furthermore, social support indirectly affected tinnitus distress through the full mediating effects of resilience and self-esteem and could indirectly affect resilience through the partial mediating effects of self-esteem. CONCLUSION: These results suggested that the key to social support for alleviating tinnitus distress lies in the development of patients' resilience and self-esteem. Promoting the development of positive psychological quality of tinnitus patients and improving their perception of social support may become the new approaches of clinical management of tinnitus.

A Tool for Early Prediction of Severe Coronavirus Disease 2019 (COVID-19): A Multicenter Study Using the Risk Nomogram in Wuhan and Guangdong, China.

BACKGROUND: Because there is no reliable risk stratification tool for severe coronavirus disease 2019 (COVID-19) patients at admission, we aimed to construct an effective model for early identification of cases at high risk of progression to severe COVID-19. METHODS: In this retrospective multicenter study, 372 hospitalized patients with nonsevere COVID-19 were followed for > 15 days after admission. Patients who deteriorated to severe or critical COVID-19 and those who maintained a nonsevere state were assigned to the severe and nonsevere groups, respectively. Based on baseline data of the 2 groups, we constructed a risk prediction nomogram for severe COVID-19 and evaluated its performance. RESULTS: The training cohort consisted of 189 patients, and the 2 independent validation cohorts consisted of 165 and 18 patients. Among all cases, 72 (19.4%) patients developed severe COVID-19. Older age; higher serum lactate dehydrogenase, C-reactive protein, coefficient of variation of red blood cell distribution width, blood urea nitrogen, and direct bilirubin; and lower albumin were associated with severe COVID-19. We generated the nomogram for early identifying severe COVID-19 in the training cohort (area under the curve [AUC], 0.912 [95% confidence interval {CI}, .846-.978]; sensitivity 85.7%, specificity 87.6%) and the validation cohort (AUC, 0.853 [95% CI, .790-.916]; sensitivity 77.5%, specificity 78.4%). The calibration curve for probability of severe COVID-19 showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analyses indicated that nomogram conferred high clinical net benefit. CONCLUSIONS: Our nomogram could help clinicians with early identification of patients who will progress to severe COVID-19, which will enable better centralized management and early treatment of severe disease.

The lncRNA SOX2OT rs9839776 C>T Polymorphism Indicates Recurrent Miscarriage Susceptibility in a Southern Chinese Population.

Genetic susceptibility may be involved in the onset of recurrent miscarriage. Previous studies have shown that some genetic polymorphisms that regulate cell migration are associated with susceptibility to recurrent miscarriage. The SOX2 overlapping transcript (SOX2OT) may regulate the migration and invasion of multiple tumor cells and is related to susceptibility to various diseases. However, whether lncRNA SOX2OT polymorphisms are related to recurrent miscarriage susceptibility is unclear. Therefore, we investigated the relationship between the lncRNA SOX2OT rs9839776 C>T polymorphism and recurrent miscarriage susceptibility. We recruited 570 subjects with recurrent miscarriage and 578 healthy control subjects from a population in southern China and used the TaqMan method for genotyping. We found a significant association between the rs9839776 CT genotype in the SOX2OT gene and an increased risk for recurrent miscarriage (CT vs CC: adjusted OR = 1.357, 95%CI = 1.065 - 1.728, P = 0.0134). However, we did not observe any significant associations between the recurrent miscarriage risk and the number of miscarriages in different age groups. In conclusion, our study indicated that the rs9839776 CT genotype may contribute to an increased risk of recurrent miscarriage in the southern Chinese population and that rs9839776 may act as a prognostic biomarker in recurrent miscarriage patients. However, an experiment-based study with a larger sample size should be performed to confirm these results.

Anatomical thermal ablation as an alternative to surgical resection for subcapsular hepatocellular carcinoma.

PURPOSE: To simulate the advantages of anatomical resection, a new strategy of anatomical thermal ablation was proposed. The objective of this study was to evaluate the clinical value of anatomical thermal ablation (ATA) to treat subcapsular hepatocellular carcinoma by comparing it with anatomical resection (AR) and non-anatomical resection (NAR). METHODS: This retrospective cohort study enrolled hepatocellular carcinoma patients with subcapsular tumor diameter ≤ 50 mm treated by ATA or surgical resection at our center from October 2015 to December 2018. ATA features ablation of the Glisson capsule, ablation of the liver parenchyma between the tumor and hepatic veins or inferior vena cava and then puncture from the surrounding part to the central part of the tumor. Outcome parameters were compared. RESULTS: Seventy-six patients were grouped into ATA group, 95 patients into AR group and 41 patients into NAR group. The 1-, 2-, and 3-year local recurrence rates were 0.0%, 0.0%, 0.0% for ATA group, 0.0%, 1.4%, 1.4% for the AR group and 0.0%, 0.0%, and 0.0% for the NAR group, respectively (P = 0.449). The 1-, 2-, and 3-year progression-free survival rates were 90.6%, 80.9%, and 74.6% for ATA group, 91.5%, 80.2%, and 80.2% for the AR group and 82.9%, 73.8%, and 73.8% for the NAR group, respectively (P = 0.608). The 1-, 2-, and 3-year overall survival rates were 100.0%, 95.2%, and 95.2% for the ATA group, 96.8%, 95.6%, and 95.6% for the AR group and 97.6%, 95.0%, and 95.0% for the NAR group, respectively (P = 0.970). No difference was found in major complication rate among these groups (P = 0.091). CONCLUSION: For subcapsular hepatocellular carcinoma, ATA could be an alternative to surgical resection with its comparable treatment effect and safety.

The Chinese version of the Pediatric Quality Of Life Inventory™ (PedsQL™) healthcare satisfaction generic module (version 3.0): psychometric evaluation.

BACKGROUND: Healthcare satisfaction is an important indicator in quality of healthcare evaluations. Instruments with psychometric evaluation for pediatric healthcare satisfaction in China have been rarely studied. The PedsQL™ 3.0 Healthcare Satisfaction Generic Module was a widely used instrument designed to measure parents' satisfaction of the healthcare for their children with chronic diseases. This study aimed to evaluate the psychometric properties of the Chinese version of the PedsQL™ 3.0 Healthcare Satisfaction Generic Module. METHODS: We used the standard procedure of cross-culture adaptation to develop the Chinese version of the PedsQL™ 3.0 Healthcare Satisfaction Generic Module. We administered the scale to 354 parents with children experiencing chronic diseases from 5 third-grade class-A hospitals in Guangzhou by the convenience sampling method. The psychometric properties of the scale were evaluated. RESULTS: The response rate was 94.4%. All the subscales reached the minimum reliability standard of 0.70 for Cronbach's alpha coefficient and the recommended test-retest reliability standard of 0.80 for intra-class correlation coefficients (ICCs). There were higher correlation coefficients between items and their hypothesized subscales than those with other subscales. Confirmatory factor analysis showed that the scale had adequate construct validity with the main indexes of goodness of fit CFI and RMSEA as 0.99 and 0.078, respectively. CONCLUSIONS: The results demonstrate that the Chinese version of the PedsQL™ 3.0 Healthcare Satisfaction Generic Module is a feasible instrument with adequate psychometric properties.

Thermal ablation as an alternative to liver transplantation for hepatocellular carcinoma with clinically significant portal hypertension: propensity score matching study.

Purpose: The objectives were to investigate the safety and efficacy of thermal ablation as an alternative to liver transplantation for hepatocellular carcinoma patients with clinically significant portal hypertension (CSPH). Materials and Methods: From July 2016 to September 2019, hepatocellular carcinoma patients with CSPH treated by liver transplantation (N=37) or thermal ablation (N=114) were enrolled. Cumulative intrahepatic recurrence, overall survival and major complications were compared by propensity score matching. Results: In the two matched groups, the 1-, 2-, and 3-year intrahepatic recurrence rates for the ablation group (22.3%, 50.0%, and 50.0%, respectively) were significantly higher than those for the transplantation group (4.5%, 4.5%, and 4.5%, respectively) (P=0.016). The 1-, 2-, and 3-year overall survival rates were comparable between the two groups [96.1%, 88.7%, and 88.7%, respectively (ablation group) vs. 84.6%, 76.2%, and 76.2%, respectively (transplantation group)] (P=0.07). The major complication rate for the ablation group [4.8% (3/62)] was significantly lower than that for the transplantation group [36.0% (9/25)] (P<0.001). Conclusions: Thermal ablation is a safe and effective alternative for hepatocellular carcinoma patients with CSPH.

Personality Traits and Tinnitus Distress: Results Based on Patients with Tinnitus in China.

Background: Due to the socio-cultural differences between China and other countries, which may affect the development of an individual's personality and behavior, it is necessary to explore the relationship between personality traits and tinnitus distress in the context of China's socio-cultural background. Methods: The Tinnitus Handicap Inventory and the Eysenck Personality Questionnaire Short Scale Chinese version were used to explore the influence of personality traits on tinnitus distress in Chinese patients with tinnitus. Results: The results were not entirely consistent with previous studies from other countries. First, extroversion was significantly higher in patients with bothersome tinnitus, both in acute and chronic conditions. Second, the personality traits that affected the patients with bothersome tinnitus were different in different conditions. Finally, the tridimensional personality structure, high psychoticism / normal extroversion / normal neuroticism, was significantly higher in people with bothersome tinnitus. Furthermore, the difference became more obvious with a prolonged disease course. Conclusions: This study suggested that the relationship between personality traits and tinnitus distress in Chinese patients with tinnitus was not the same as in other countries. "High psychoticism / normal extroversion / normal neuroticism" may be a risk factor for chronic bothersome tinnitus in China.

Alirocumab effect on preventing periprocedural ischaemic events in coronary heart disease patients undergoing coronary stenting (APPEASE trial): study protocol of a multicentre, open-label, randomised controlled trial.

INTRODUCTION: Percutaneous coronary intervention (PCI)-related myocardial infarction (type 4a MI) and major periprocedural myocardial injury have been demonstrated leading to poor prognosis of patients with coronary heart disease (CHD) undergoing elective PCI and still remain high occurrence even after the therapy of dual antiplatelet agents and statins. Proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has been shown to be effectively in reducing the risk of acute MI (AMI). However, the effect of alirocumab on preventing PCI-related MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI remains uncertain. METHODS AND ANALYSIS: Alirocumab effect on Preventing Periprocedural ischaemic Events in coronary heart diseAse patients undergoing coronary StEnting trial is a multicentre, open-label, randomised controlled trial aiming to determine whether alirocumab could reduce the incidence of type 4a MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI. In total, 422 non-AMI CHD patients planned to undergo elective PCI will be randomly assigned to receive standard pharmacotherapy of CHD (control group) or additional use of subcutaneous alirocumab 75 mg 1 day before procedure (alirocumab group). The primary outcome is type 4a MI or major periprocedural myocardial injury defined as high-sensitivity cardiac troponin elevating above 5×99 th percentile upper reference limit in 48 hours after PCI. Patients will continue receiving standard pharmacotherapy or additional biweekly subcutaneous alirocumab 75 mg for 3 months according to the initial randomisation group. We will follow up for 3 months and record all the major adverse cardiovascular events (MACEs). Incidence of PCI-related MI or major periprocedural myocardial injury, and MACE in 3 months after PCI will be compared between control group and alirocumab group. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University with approval number: (2022)02-140-01. The results of this study will be reported through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200063191.

Non-Invasive Prediction Models for Esophageal Varices and Red Signs in Patients With Hepatitis B Virus-Related Liver Cirrhosis.

Background: Red signs are closely related to esophageal variceal bleeding, and, despite improvements in therapy, the mortality rate remains high. We aimed to identify non-invasive predictors of esophageal varices and red signs in patients with hepatitis B virus-related liver cirrhosis. Methods: This retrospective study included 356 patients with hepatitis B virus-related liver cirrhosis after applying inclusion and exclusion criteria among 661 patients. All patients underwent endoscopy, ultrasonography, laboratory examinations, and computed tomography/magnetic resonance imaging. Univariate and multivariate logistic regression analysis were performed, and prediction models for esophageal varices and red signs were constructed. Results: Multivariate analysis revealed that spleen diameter, splenic vein diameter, and lymphocyte ratio were independent risk factors for esophageal varices and red signs. On this basis, we proposed two models: i) a spleen diameter-splenic vein diameter-lymphocyte ratio-esophageal varices prediction model (SSL-EV model); and ii) a spleen diameter-splenic vein diameter-lymphocyte ratio-red sign prediction model (SSL-RS model). The areas under the receiver operating characteristic curve for the two prediction models were 0.843 and 0.783, respectively. With a cutoff value of 1.55, the first prediction model had 81.3% sensitivity and 76.1% specificity for esophageal varices prediction. With a cutoff value of -0.20, the second prediction model had 72.1% sensitivity and 70.7% specificity for the prediction of red signs. Conclusions: We proposed a new statistical model, the spleen diameter-splenic vein diameter-lymphocyte ratio-red sign prediction model (SSL-RS model), to predict the presence of red signs non-invasively. Combined with the spleen diameter-splenic vein diameter-lymphocyte ratio-esophageal varices prediction model (SSL-EV model), these non-invasive prediction models will be helpful in guiding clinical decision-making and preventing the occurrence of esophageal variceal bleeding.

LASSO Regression-Based Diagnosis of Acute ST-Segment Elevation Myocardial Infarction (STEMI) on Electrocardiogram (ECG).

Electrocardiogram (ECG) is an important tool for the detection of acute ST-segment elevation myocardial infarction (STEMI). However, machine learning (ML) for the diagnosis of STEMI complicated with arrhythmia and infarct-related arteries is still underdeveloped based on real-world data. Therefore, we aimed to develop an ML model using the Least Absolute Shrinkage and Selection Operator (LASSO) to automatically diagnose acute STEMI based on ECG features. A total of 318 patients with STEMI and 502 control subjects were enrolled from Jan 2017 to Jun 2019. Coronary angiography was performed. A total of 180 automatic ECG features of 12-lead ECG were input into the model. The LASSO regression model was trained and validated by the internal training dataset and tested by the internal and external testing datasets. A comparative test was performed between the LASSO regression model and different levels of doctors. To identify the STEMI and non-STEMI, the LASSO model retained 14 variables with AUCs of 0.94 and 0.93 in the internal and external testing datasets, respectively. The performance of LASSO regression was similar to that of experienced cardiologists (AUC: 0.92) but superior (p < 0.05) to internal medicine residents, medical interns, and emergency physicians. Furthermore, in terms of identifying left anterior descending (LAD) or non-LAD, LASSO regression achieved AUCs of 0.92 and 0.98 in the internal and external testing datasets, respectively. This LASSO regression model can achieve high accuracy in diagnosing STEMI and LAD vessel disease, thus providing an assisting diagnostic tool based on ECG, which may improve the early diagnosis of STEMI.

Effects of Psychosomatic Mutual Aid Treatment on Anxiety and Depression in Turner Syndrome.

Background: Turner syndrome (TS) affects approximately one out of 2,500 females. Previous research indicates that girls with TS experience psychosocial impairment in addition to their physical health issues. However, there is no current data demonstrating whether reducing the clinical symptoms of girls or women with TS through hormone replacement therapy (HRT) combined with psychological interventions, referred to as psychosomatic mutual aid treatment (PMAT), improves physical and psychological self-identification, so that psychological problems such as anxiety, depression, low self-esteem, social loneliness, and psychological resilience are improved. Therefore, the objective of this research was to assess the efficacy of PMAT on anxiety and depression in girls and women with TS. Methods: Twenty-six girls and women with TS aged 11-29 years (17.5 ± 4.2 years) were recruited. Anxiety and depression were assessed using Hamilton Anxiety Rating Scale (HAMA) and Zung Self-Rating Depression Scale (SDS) questionnaires, respectively. The 26 TS patients were surveyed for anxiety and depression before the beginning of PMAT and again in January 2020. In addition, 20 healthy volunteer women aged 16-39 years (23.1 ± 5.7 years) were selected as the control group and filled in the questionnaire. Results: Pre-therapy (pre-HRT and Pre-PMAT) there were significant differences between the TS patients (n = 26) and healthy controls (n = 20). In particular, the TS patients had higher anxiety status (P = 0.04) and severity (P = 0.03) (HAMA score), as well as depression status (P = 0.002) and severity (P < 0.001) (SDS score). Post-therapy there was no longer any difference in depression scores, but TS patients still had higher levels of anxiety post-therapy compared with healthy control women (psychic symptoms score, P = 0.03; anxiety status score, P = 0.04; anxiety severity score, P = 0.04). In the TS patients, there was an improvement in depression scores (SDS score P < 0.001; depression severity score, P = 0.005) after therapy but no change in levels of anxiety. Conclusions: PMAT significantly improves depression status, but not anxiety, in girls and women with TS. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=124736, identifier: ChiCTR2100045230.

Comparative Efficacy and Safety of PD-1/PD-L1 Inhibitors for Patients with Solid Tumors: A Systematic Review and Bayesian Network Meta-analysis.

Purpose: The clinical use of immunotherapies targeting programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) is rapid expanding, but the equivalency of these inhibitors remains unclear. We aimed to comprehensively compare the efficacy and safety of PD-1/PD-L1 inhibitors with a systematic review and Bayesian network meta-analysis Methods: We searched PubMed, Web of Knowledge, related reviews and abstracts for randomized controlled trials of five PD-1/PD-L1 inhibitors for patients with solid tumors before November 30th, 2018. We estimated summary hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for grade 3-5 treatment-related adverse events (TrAEs) using pairwise and network meta-analysis with random-effects. This study was registered with PROSPERO (#CRD42018116624). Results: Totally, 43 reports of 35 trials comprising 21261 patients were eligible for the analysis. Nivolumab, pembrolizumab, atezolizumab and durvalumab were more effective than control treatment, and no significant differences were identified in OS and PFS between any two inhibitors. Avelumab was associated with significantly inferior OS to nivolumab (HR 1.37, 95%CrI 1.05-1.78) and pembrolizumab (HR 1.33, 95%CrI 1.02-1.73), and with inferior PFS to nivolumab (HR 1.60, 95%CrI 1.03-2.51). Compared with placebo, nivolumab had increased risk of grade 3-5 TrAEs (OR 2.35, 95%CrI 1.35-4.17). Compared with standard-of-care, nivolumab (OR 0.39, 95%CrI 0.28-0.54), pembrolizumab (OR 0.43, 95%CrI 0.30-0.60), atezolizumab (OR 0.37, 95%CrI 0.21-0.64) and avelumab (OR 0.24, 95%CrI 0.12-0.48) significantly reduced grade 3-5 TrAEs. There were not significant differences in grade 3-5 TrAEs between any two inhibitors. Conclusion: This Bayesian network meta-analysis revealed that nivolumab, pembrolizumab, atezolizumab and durvalumab yielded equivalent survival, while avelumab was associated with unfavorable survival. PD-1/PD-L1 inhibitors were comparable in the risk of TrAEs, and safer than conventional therapies.

Efficacy and safety of omalizumab in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To assess the efficacy and safety of omalizumab for chronic rhinosinusitis with nasal polyps (CRSwNP) and to identify evidence gaps that will guide future research on omalizumab for CRSwNP. DESIGN: Systematic review and meta-analysis. DATA SOURCES: A comprehensive search was performed in PubMed, Embase, Web of Science and the Cochrane Library on 13 October 2020. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) comparing omalizumab with placebo, given for at least 16 weeks in adult patients with CRSwNP. DATA EXTRACTION AND SYNTHESIS: Two independent authors screened search results, extracted data and assessed studies using the Cochrane risk of bias tool. Data were pooled using the inverse-variance method and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the χ2 test and the I2 statistic. RESULTS: A total of four RCTs involving 303 participants were identified. When comparing omalizumab to placebo, there was a significant difference in Nasal Polyps Score (MD=-1.20; 95% CI -1.48 to -0.92), Nasal Congestion Score (MD=-0.67; 95% CI -0.86 to -0.48), Sino-Nasal Outcome Test-22 (MD=-15.62; 95% CI -19.79 to -11.45), Total Nasal Symptom Score (MD=-1.84; 95% CI -2.43 to -1.25) and reduced need for surgery (risk ratio (RR)=5.61; 95% CI 1.99 to 15.81). Furthermore, there was no difference in the risk of serious adverse events ((RR=1.40; 95% CI 0.29 to 6.80), adverse events (RR=0.83; 95% CI 0.60 to 1.15) and rescue systemic corticosteroid (RR=0.52; 95% CI 0.17 to 1.61). CONCLUSIONS: This was the first meta-analysis that identified omalizumab significantly improved endoscopic, clinical and patient-reported outcomes in adults with moderate to severe CRSwNP and it was safe and well tolerated. PROSPERO REGISTRATION NUMBER: CRD42020207639.

Reference values and the effect of clinical parameters on thyroid hormone levels during early pregnancy.

OBJECTIVE: Thyroid dysfunction is a common endocrine problem during pregnancy; correct diagnosis and appropriate treatments are essential to avoid adverse pregnancy outcomes. Besides, it is vital to identify and quantify the major risk factors for gestational thyroid dysfunction, including thyroid autoimmunity, human chorionic gonadotropin (HCG) concentration, body mass index (BMI) and parity. The study objective was to establish reference ranges during early pregnancy and to explore the relationship between risk factors and thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyroxine (FT3). DESIGN, PATIENTS AND MEASUREMENTS: To establish the reference ranges of thyroid hormone during early pregnancy in China and to identify the risk factors for thyroid dysfunction, woman in the first trimester of pregnancy (4-12 weeks gestation) were recruited. After excluding thyroid peroxidase antibody (TPO-Ab) positive and/or thyroglobulin antibody (TG-Ab) positive women, previous thyroid disease, a lack of iodine intake, reference values were calculated by 2.5th to 97.5th percentiles. RESULTS: After exclusion of TPO-Ab and/or TG-Ab positive women, reference values were as follows: TSH, 0.11-3.67 mIU/l; FT3, 3.19-5.91 pmol/l; FT4 10.95-16.79 pmol/l. Higher BMI was associated with lower FT4 concentrations (P=0.005). In multiple regression analysis, TSH was significantly and positively associated with TG (P=0.03). Maternal parity and maternal age may be risk factors for the abnormal thyroidal response to hCG concentrations. CONCLUSIONS: Our study defined first trimester-specific reference ranges for serum TSH, FT4, FT3 in a Chinese population, and demonstrated that BMI ≥23kg/m2, maternal parity ≥3 and maternal age ≥30 years may increase the risk of thyroid dysfunction.

Analysis of Studies in Tinnitus-Related Gene Research.

OBJECTIVE: Summarize and analyze the current research results of tinnitus-related genes, explore the potential links between the results of each study, and provide reference for subsequent studies. METHODS: Collect and sort out the research literature related to tinnitus genes included in PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang Data Knowledge Service Platform before December 31, 2019. Then the relevant contents of the literature were sorted out and summarized. RESULTS: Fifty-one articles were finally selected for analysis: 31 articles (60.8%) were classified as researches on animal models of tinnitus, and 20 (39.2%) as researches on tinnitus patients. Existing studies have shown that genes related to oxidative stress, inflammatory response, nerve excitation/inhibition, and nerve growth are differentially expressed in tinnitus patients or animal models, and have presented the potential links between genes or proteins in the occurrence and development of tinnitus. CONCLUSION: The research on tinnitus-related genes is still in the exploratory stage, and further high-quality research evidence is needed.