Assessment of causal association between thyroid function and lipid metabolism: a Mendelian randomization study

Background:Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR).Methods:The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.Results:The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.Conclusion:Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.     

Spicy food consumption is associated with cognition and cerebrospinal fluid biomarkers of Alzheimer disease

Background:Recent studies suggest that a healthy diet helps to prevent the development of Alzheimer disease (AD). This study aimed to investigate whether spicy food consumption is associated with cognition and cerebrospinal fluid (CSF) biomarkers of AD in the Chinese population.Methods:We enrolled 55 AD patients and 55 age- and gender-matched cognitively normal (CN) subjects in a case-control study, as well as a cohort of 131 participants without subjective cognitive decline (non-AD) in a cross-sectional study. Spicy food consumption was assessed using the Food Frequency Questionnaire (FFQ). Associations of FFQ scores with cognition and CSF biomarkers of AD were analyzed.Results:In the case-control study, spicy food consumption was lower in AD patients than that in CNs (4.0 [4.0–8.0] vs. 8.0 [4.5–10.0], P < 0.001); FFQ scores were positively associated with Mini-Mental Status Examination scores in the total sample (r = 0.218, P = 0.014). In the cross-sectional study, the association between spicy food consumption and cognition levels was verified in non-AD subjects (r = 0.264, P = 0.0023). Moreover, higher FFQ scores were significantly associated with higher β-Amyloid (1–42) (Aβ₄₂₎ levels and lower phospho-tau/Aβ₄₂ and total tau/Aβ₄₂ ratios in the CSF of non-AD subjects (P < 0.05).Conclusion:Spicy food consumption is closely related to higher cognition levels and reversed AD biomarkers in the CSF, suggesting that a capsaicin-rich diet might have the potential to modify the cognitive status and cerebral pathologies associated with AD.     

Association between serum bilirubin concentration and Parkinson's disease: a meta-analysis

Background:The antioxidant effects of bilirubin in Parkinson''s disease (PD) have recently gained much attention from the research community. However, results from these studies have been conflicting. This meta-analysis is conducted to assess the relationship between the serum bilirubin concentration and the risk of PD.Methods:Two reviewers performed a systematic literature search across five databases (MEDLINE, PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials). The case-control studies regarding bilirubin levels in PD patients published up to April 2020 were included. These studies were subjected to rigorous scrutiny and data extraction to determine the standard mean difference (SMD) and the 95% confidence interval (CI), which were analyzed using the Stata V.12.0 statistical software.Results:A total of eight studies which included 1463 PD cases and 1490 controls were incorporated into our meta-analysis. SMD analysis showed that there was a higher total bilirubin (TBIL) and direct bilirubin (DBIL) levels in PD patients compared with controls (for TBIL, SMD: 0.300, 95% CI: 0.050–0.549, P = 0.018; for DBIL, SMD: 0.395, 95% CI: 0.102–0.688, P = 0.008). However, no significant relationship was found between the serum indirect bilirubin and PD patients (SMD: −0.223, 95% CI: −0.952–0.505, P = 0.548). A subgroup analysis based on ethnicity indicated that the serum TBIL was higher in PD patients of Caucasian descent in contrast to matched healthy controls (SMD: 0.511, 95% CI: 0.324–0.698, P = 0.000, I² = 58.0%).Conclusion:Higher serum bilirubin levels in PD patients suggest that bilirubin might play a role in the pathogenesis of PD and have the potential to be utilized as a biochemical marker for PD diagnosis and treatment.     

Nomogram to predict pregnancy outcomes of emergency oocyte freeze-thaw cycles

Background:Existing clinical prediction models for in vitro fertilization are based on the fresh oocyte cycle, and there is no prediction model to evaluate the probability of successful thawing of cryopreserved mature oocytes. This research aims to identify and study the characteristics of pre-oocyte-retrieval patients that can affect the pregnancy outcomes of emergency oocyte freeze-thaw cycles.Methods:Data were collected from the Reproductive Center, Peking University Third Hospital of China. Multivariable logistic regression model was used to derive the nomogram. Nomogram model performance was assessed by examining the discrimination and calibration in the development and validation cohorts. Discriminatory ability was assessed using the area under the receiver operating characteristic curve (AUC), and calibration was assessed using the Hosmer–Lemeshow goodness-of-fit test and calibration plots.Results:The predictors in the model of “no transferable embryo cycles” are female age (odds ratio [OR] = 1.099, 95% confidence interval [CI] = 1.003–1.205, P = 0.0440), duration of infertility (OR = 1.140, 95% CI = 1.018–1.276, P = 0.0240), basal follicle-stimulating hormone (FSH) level (OR = 1.205, 95% CI = 1.051–1.382, P = 0.0084), basal estradiol (E2) level (OR = 1.006, 95% CI = 1.001–1.010, P = 0.0120), and sperm from microdissection testicular sperm extraction (MESA) (OR = 7.741, 95% CI = 2.905–20.632, P < 0.0010). Upon assessing predictive ability, the AUC for the “no transferable embryo cycles” model was 0.799 (95% CI: 0.722–0.875, P < 0.0010). The Hosmer–Lemeshow test (P = 0.7210) and calibration curve showed good calibration for the prediction of no transferable embryo cycles. The predictors in the cumulative live birth were the number of follicles on the day of human chorionic gonadotropin (hCG) administration (OR = 1.088, 95% CI = 1.030–1.149, P = 0.0020) and endometriosis (OR = 0.172, 95% CI = 0.035–0.853, P = 0.0310). The AUC for the “cumulative live birth” model was 0.724 (95% CI: 0.647–0.801, P < 0.0010). The Hosmer–Lemeshow test (P = 0.5620) and calibration curve showed good calibration for the prediction of cumulative live birth.Conclusions:The predictors in the final multivariate logistic regression models found to be significantly associated with poor pregnancy outcomes were increasing female age, duration of infertility, high basal FSH and E2 level, endometriosis, sperm from MESA, and low number of follicles with a diameter >10 mm on the day of hCG administration.     

Risk factors for gastric cancer: a large-scale,population-based case-control study

Background:Early detection of gastric cancer (GC) has been the topic of major efforts in China. This study aimed to explore the risk factors associated with GC and to provide evidence for the selection of a high-risk population of GC.Methods:Based on the cancer screening cohort of the National Cancer Screening Program in Urban China, GC patients diagnosed by endoscopy and pathological examinations constituted the case group, and controls were 1:3 matched by sex and age (±5 years) individually. The variables were selected by univariable analysis of factors such as body mass index (BMI), dietary habits, lifestyle, stomach disease history, and family history of GC; and multivariable logistic regression was used to analyze the influencing factors of GC and to calculate the odds ratio (OR) of related factors and its 95% confidence interval (CI).Results:A total of 215 GC cases and 645 matched healthy controls were included in the final analysis, with a median age of 61 years for the case and control groups. Overall analysis showed that high educational level (above primary school) (OR = 0.362, 95% CI = 0.219–0.599, P < 0.001), overweight/obesity (BMI ≥24 kg/m²; OR = 0.489, 95% CI = 0.329–0.726, P < 0.001), cigarette smoking (OR = 3.069, 95% CI = 1.700–5.540, P < 0.001), alcohol consumption (OR = 1.661, 95% CI = 1.028–2.683, P = 0.038), history of stomach disease (OR = 6.917, 95% CI = 4.594–10.416, P < 0.001), and family history of GC in first-degree relatives (OR = 4.291, 95% CI = 1.661–11.084, P = 0.003) were significantly correlated with the occurrence of GC. Subgroup analyses by age and gender indicated that GC risk was still increased in the presence of a history of stomach disease. A history of chronic gastritis, gastric ulcer, or gastric polyposis was positively associated with GC, with adjusted ORs of 4.155 (95% CI = 2.711–6.368), 1.839 (95% CI = 1.028–3.288), and 2.752 (95% CI = 1.197–6.326).Conclusions:Subjects who smoke, drink, with history of stomach disease and family history of GC in first-degree relatives are the high-risk populations for GC. Therefore, attention should be paid to these subjects for GC screening.     

Long-term outcomes of percutaneous coronary intervention for in-stent chronic total occlusion

BackgroundThe development of the technique has improved the success rate of percutaneous coronary intervention (PCI) for in-stent chronic total occlusion (IS-CTO). However, long-term outcomes remain unclear. The present study sought to investigate long-term outcomes of PCI for IS-CTO.MethodsA total of 474 IS-CTO patients were enrolled at two cardiac centers from 2015 to 2018 retrospectively. These patients were allocated into either successful or failed IS-CTO PCI groups. The primary endpoint (major adverse cardiac events [MACE]) consisted of recurrent angina pectoris (RAP), target-vessel myocardial infarction (MI), heart failure, cardiac death, or ischemia-driven target-vessel revascularization (TVR) at follow-up. Multivariable Cox regression analysis was used to investigate the association between treatment appropriateness and clinical outcomes.ResultsA total of 367 patients were successfully treated with IS-CTO PCI while 107 patients had failed recanalization. After a median follow-up of 30 months (interquartile range: 17–42 months), no significant difference was observed between the two groups for the following parameters: cardiac death (successful PCI vs. failed PCI: 0.9% vs. 2.7%; adjusted hazard ratio [HR]: 1.442; 95% confidence interval [CI]: 0.21–9.887; P = 0.709), RAP (successful PCI vs. failed PCI: 40.8% vs. 40.0%; adjusted HR: 1.025; 95% CI: 0.683–1.538; P = 0.905), heart failure (successful PCI vs. failed PCI: 6.1% vs. 2.7%; adjusted HR: 0.281; 95% CI: 0.065–1.206; P = 0.088), target-vessel related MI (successful PCI vs. failed PCI: 1.5% vs. 2.7%; adjusted HR: 1.150; 95% CI: 0.221–5.995; P = 0.868), MACE (successful PCI vs. failed PCI: 44.2% vs. 45.3%; adjusted HR: 1.052; 95% CI: 0.717–1.543; P = 0.797). More patients were free of angina in the successful IS-CTO PCI group compared with failed PCI in the first (80.4% vs. 60%, P < 0.01) and second years (73.3% vs. 60.0%, P = 0.02) following up. Successful IS-CTO PCI had a lower incidence of MACE in the first and second years (20.2% vs. 40.0%, P < 0.01; 27.9% vs. 41.3%, P = 0.023) compared with failed PCI. After a median follow-up of 30 months, the reocclusion rate was 28.5% and TVR was 26.1% in the successful IS-CTO PCI group. Receiving >18 months of dual antiplatelet therapy (DAPT) was an independent predictor of decreased risk of TVR (HR: 2.682; 95% CI: 1.295–5.578; P = 0.008) or MACE (without TVR) (HR: 1.898; 95% CI: 1.036–3.479; P = 0.038) in successful IS-CTO PCI.ConclusionsAfter a median follow-up of 30 months, the successful IS-CTO PCI group had MACE similar to that of the failed PCI group. However, the successful IS-CTO PCI group had improved angina symptoms and were free from requiring coronary artery bypass grafting in the first or second years. To decrease MACE, DAPT was found to be essential and recommended for at least 18 months for IS-CTO PCI.     

Increased early activation of CD56dimCD16dim/- natural killer cells in immunological non-responders correlates with CD4+ T-cell recovery

BackgroundNatural killer (NK) cells play a critical role in suppressing human immunodeficiency virus-1 (HIV-1) infection, but knowledge on whether and how NK cells affect immune reconstitution in HIV-1-infected individuals who receive antiretroviral therapy (ART) is limited.MethodsWe performed a case-control study with 35 healthy individuals and 66 HIV-1-infected patients including 32 immunological non-responders (INRs) with poor CD4⁺ T-cell recovery (<500 cells/μL after 4 years of ART) and 34 immunological responders (IRs) with improved CD4⁺ T-cell recovery (>500 cells/μL after 4 years of ART). NK cell phenotype, receptor repertoire, and early activation in INRs and IRs were investigated by flow cytometry.ResultsA significantly higher proportion of CD56^dimCD16^dim/- NK cells was observed in INRs than IRs before ART and after 4 years of ART. The number of CD56^dimCD16^dim/- NK cells was inversely correlated with CD4⁺ T-cell counts in INRs before ART (r = –0.344, P = 0.050). The more CD69-expressing NK cells there were, the lower the CD4⁺ T-cell counts and ΔCD4, and these correlations were observed in INRs after ART (r = –0.416, P = 0.019; r = –0.509, P = 0.003, respectively). Additionally, CD69-expressing CD56^dimCD16^dim/- NK cells were more abundant in INRs than those in IRs (P = 0.018) after ART, both of which had an inverse association trend towards significance with CD4⁺ T-cell counts. The expression of the activating receptors NKG2C, NKG2D, and NKp46 on CD56^dimCD16^dim/- NK cell subsets were higher in IRs than that in INRs after 4 years of ART (all P < 0.01). Strong inverse correlations were observed between CD69 expression and NKG2C, NKG2A^-NKG2C⁺, NKG2D, and NKp46 expression on CD56^dimCD16^dim/- NK cells in INRs after ART (NKG2C: r = –0.491, P = 0.004; NKG2A^-NKG2C⁺: r = –0.434, P = 0.013; NKG2D: r = –0.405, P = 0.021; NKp46: r = –0.457, P = 0.008, respectively).ConclusionsINRs had a larger number of CD56^dimCD16^dim/- NK cells characterized by higher activation levels than did IRs after ART. The increase in the CD56^dimCD16^dim/- NK cell subset may play an adverse role in immune reconstitution. Further functional studies of CD56^dimCD16^dim/- NK cells in INRs are urgently needed to inform targeted interventions to optimize immune recovery.     

Comparable efficacy of 100 mg aspirin twice daily and rivaroxaban for venous thromboembolism prophylaxis following primary total hip arthroplasty: a randomized controlled trial

Background:Aspirin has demonstrated safety and efficacy for venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA); however, inconsistent dose regimens have been reported in the literature. This study aimed to evaluate and compare the safety and efficacy of 100 mg aspirin twice daily with rivaroxaban in VTE prophylaxis following THA.Methods:Patients undergoing elective unilateral primary THA between January 2019 and January 2020 were prospectively enrolled in the study and randomly allocated to receive 5 weeks of VTE prophylaxis with either oral enteric-coated aspirin (100 mg twice daily) or rivaroxaban (10 mg once daily). Medication safety and efficacy were comprehensively evaluated through symptomatic VTE incidence, deep vein thrombosis (DVT) on Doppler ultrasonography, total blood loss (TBL), laboratory bloodwork, Harris hip score (HHS), post-operative recovery, and the incidence of other complications.Results:We included 70 patients in this study; 34 and 36 were allocated to receive aspirin and rivaroxaban prophylaxis, respectively. No cases of symptomatic VTE occurred in this study. The DVT rate on Doppler ultrasonography in the aspirin group was not significantly different from that in the rivaroxaban group (8.8% vs. 8.3%, χ² = 0.01, P = 0.91), confirming the non-inferiority of aspirin for DVT prophylaxis (χ² = 2.29, P = 0.01). The calculated TBL in the aspirin group (944.9 mL [658.5–1137.8 mL]) was similar to that in the rivaroxaban group (978.3 mL [747.4–1740.6mL]) (χ² = 1.55, P = 0.12). However, there were no significant inter-group differences in HHS at post-operative day (POD) 30 (Aspirin: 81.0 [78.8–83.0], Rivaroxaban: 81.0 [79.3–83.0], χ² = 0.43, P = 0.67) and POD 90 (Aspirin: 90.0 [89.0–92.0], Rivaroxaban: 91.5 [88.3–92.8], χ² = 0.77, P = 0.44), the incidence of bleeding events (2.9% vs. 8.3%, χ² = 0.96, P = 0.33), or gastrointestinal complications (2.9% vs. 5.6%, χ² = 1.13, P = 0.29).Conclusion:In terms of safety and efficacy, the prophylactic use of 100 mg aspirin twice daily was not statistically different from that of rivaroxaban in preventing VTE and reducing the risk of blood loss following elective primary THA. This supports the use of aspirin chemoprophylaxis following THA as a less expensive and more widely available option for future THAs.Trial Registration:Chictr.org, ChiCTR18000202894; http://www.chictr.org.cn/showproj.aspx?proj=33284     

Analysis of potential factors contributing to refusal of invasive strategy after ST-segment elevation myocardial infarction in China

Background:Reduced application of percutaneous coronary intervention (PCI) is associated with higher mortality rates after ST-segment elevation myocardial infarction (STEMI). We aimed to evaluate potential factors contributing to the refusal of PCI in STEMI patients in China.Methods:We studied 957 patients diagnosed with STEMI in the emergency departments (EDs) of six public hospitals in China. The differences in baseline characteristics and 30-day outcome were investigated between patients who refused PCI and those who underwent PCI. Multivariable logistic regression was used to evaluate the potential factors associated with refusing PCI.Results:The potential factors contributing to refusing PCI were older than 65 years (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.56–4.52, P < 0.001), low body mass index (BMI) (OR 0.91, 95% CI 0.84–0.98, P = 0.013), not being married (OR 0.29, 95% CI 0.17–0.49, P < 0.001), history of myocardial infarction (MI) (OR 2.59, 95% CI 1.33–5.04, P = 0.005), higher heart rate (HR) (OR 1.02, 95% CI 1.01–1.03, P = 0.002), cardiac shock in the ED (OR 5.03, 95% CI 1.48–17.08, P = 0.010), pre-hospital delay (>12 h) (OR 3.31, 95% CI 1.83–6.02, P < 0.001) and not being hospitalized in a tertiary hospital (OR 0.45, 95% CI 0.27–0.75, P = 0.002). Compared to men, women were older, were less often married, had a lower BMI and were less often hospitalized in tertiary hospitals.Conclusions:Patients who were older, had lower economic or social status, and had poorer health status were more likely to refuse PCI after STEMI. There was a sex difference in the potential predictors of refusing PCI. Targeted efforts should be made to improve the acceptance of PCI among patients with STEMI in China.     

Association between follistatin-related protein 1 and the functional status of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Background:Follistatin-like 1 (FSTL1) plays both pro-inflammatory and anti-inflammatory roles in the inflammatory processes. We investigated whether serum FSTL1 could predict the current anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV)-specific indices.Methods:We randomly selected 74 patients with AAV from a prospective and observational cohort of Korean patients with AAV. Clinical and laboratory data and AAV-specific indices were recorded. FSTL1 concentration was determined using the stored sera. The lowest tertile of the short-form 36-item health survey (SF-36) was defined as the current low SF-36. The cutoffs of serum FSTL1 for the current low SF-36 physical component summary (PCS) and SF-36 mental component summary (MCS) were extrapolated by the receiver operator characteristic curve.Results:The median age was 62.5 years (55.4% were women). Serum FSTL1 was significantly correlated with SF-36 PCS (r =  − 0.374), SF-36 MCS (r = −0.377), and C-reactive protein (CRP) (r = 0.307), but not with Birmingham vasculitis activity score (BVAS). In the multivariable linear regression analyses, BVAS, CRP, and serum FSTL1 were independently associated with the current SF-36 PCS (β = −0.255, β = −0.430, and β = −0.266, respectively) and the current SF-36 MCS (β = −0.234, β =−0.229, and β = −0.296, respectively). Patients with serum FSTL1 ≥779.8 pg/mL and those with serum FSTL1 ≥841.6 pg/mL exhibited a significantly higher risk of having the current low SF-36 PCS and SF-36 MCS than those without (relative risk 7.583 and 6.200, respectively).Conclusion:Serum FSTL1 could predict the current functional status in AAV patients.     

Risk factors associated with osteoporosis and fracture in psoriatic arthritis

Background:Although there are few studies mentioned there may be some relationship between psoriatic arthritis (PsA) and osteoporosis, clinical data in real world still need to be clarified in China. The aim of this study was to assess the areal and volumetric bone mineral density (BMD), frequency of fracture, and risk factors in patients with PsA.Methods:A total of one hundred PsA patients who visited Peking University First Hospital and one hundred age- and sex-matched healthy controls with DXA data were enrolled in the study. Patients with clinical fractures confirmed by X-ray during follow-up were also recorded. Clinical characteristics of the patients were recorded and compared between the abnormal BMD group and the normal BMD group, as well as between the fracture and non-fracture groups. Risk factors for fracture and low BMD were analyzed.Results:Mean BMD at the total hip and femoral neck was significantly lower in PsA patients than that in healthy controls (0.809 ± 0.193 vs. 0.901 ± 0.152 g/cm², P = 0.041; 0.780 ± 0.146 vs. 0.865 ± 0.166 g/cm², P = 0.037, respectively). Moreover, lumbar spine BMD was negatively correlated with psoriasis duration, swollen joint count and DAS28-CRP (r = –0.503, –0.580, –0.438; P < 0.05). Total hip BMD and femoral neck BMD were negatively correlated with HAQ (r = –0.521, –0.335; P < 0.05). Fractures occurred in 29 patients during the follow-up period. Logistic regression analysis showed that older age (OR 1.132 [95%CI: 1.026–1.248), P < 0.05], higher HAQ score (OR 1.493, 95%CI: 1.214–1.836, P < 0.01), higher disease activity index for psoriatic arthritis (OR 1.033, 95% CI: 1.002–1.679, P < 0.05) and hip joint involvement (OR 6.401, 95% CI: 4.012–44.180, P < 0.05) were risk factors for fracture in the multivariate model.Conclusions:Increased risks of osteoporosis and fracture were found in PsA patients compared to healthy controls. Besides age, high disease activity and hip joint involvement were risk factors for decreased BMD and fracture.     

Calcium channel blockers improve prognosis of patients with coronavirus disease 2019 and hypertension

Background:Hypertension is considered an important risk factor for the coronavirus disease 2019 (COVID-19). The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system (RAAS) inhibitors, calcium channel blockers (CCBs), and beta-blockers. The association between commonly used anti-hypertensive medications and the clinical outcome of COVID-19 patients with hypertension has not been well studied.Methods:We conducted a retrospective cohort study that included all patients admitted with COVID-19 to Huo Shen Shan Hospital and Guanggu District of the Maternal and Child Health Hospital of Hubei Province, Wuhan, China. Clinical and laboratory characteristics were extracted from electronic medical records. Hypertension and anti-hypertensive treatment were confirmed by medical history and clinical records. The primary clinical endpoint was all-cause mortality. Secondary endpoints included the rates of patients in common wards transferred to the intensive care unit and hospital stay duration. Logistic regression was used to explore the risk factors associated with mortality and prognosis. Propensity score matching was used to balance the confounders between different anti-hypertensive treatments. Kaplan-Meier curves were used to compare the cumulative recovery rate. Log-rank tests were performed to test for differences in Kaplan-Meier curves between different groups.Results:Among 4569 hospitalized patients with COVID-19, 31.7% (1449/4569) had a history of hypertension. There were significant differences in mortality rates between hypertensive patients with CCBs (7/359) and those without (21/359) (1.95% vs. 5.85%, risk ratio [RR]: 0.32, 95% confidence interval [CI]: 0.13–0.76, χ² = 7.61, P = 0.0058). After matching for confounders, the mortality rates were similar between the RAAS inhibitor (4/236) and non-RAAS inhibitor (9/236) cohorts (1.69% vs. 3.81%, RR: 0.43, 95% CI: 0.13–1.43, χ² = 1.98, P = 0.1596). Hypertensive patients with beta-blockers (13/340) showed no statistical difference in mortality compared with those without (11/340) (3.82% vs. 3.24%, RR: 1.19, 95% CI: 0.53–2.69, χ² = 0.17, P = 0.6777).Conclusions:In our study, we did not find any positive or negative effects of RAAS inhibitors or beta-blockers in COVID-19 patients with hypertension, while CCBs could improve prognosis.     

In vitro fertilization-embryo transfer in patients with unexplained recurrent pregnancy loss

Background:Empiric therapy for patients with unexplained recurrent pregnancy loss (URPL) is not precise. Some patients will ask for assisted reproductive technology due to secondary infertility or advanced maternal age. The clinical outcomes of URPL patients who have undergone in vitro fertilization-embryo transfer (IVF-ET) require elucidation. The IVF outcome and influencing factors of URPL patients need further study.Methods:A retrospective cohort study was designed, and 312 infertile patients with URPL who had been treated during January 2012 to December 2015 in the Reproduction Center of Peking University Third Hospital were included. By comparing clinical outcomes between these patients and those with tubal factor infertility (TFI), the factors affecting the clinical outcomes of URPL patients were analyzed.Results:The clinical pregnancy rate (35.18% vs. 34.52% in fresh ET cycles, P = 0.877; 34.48% vs. 40.27% in frozen-thawed ET cycles, P = 0.283) and live birth rate (LBR) in fresh ET cycles (27.67% vs. 26.59%, P = 0.785) were not significantly different between URPL group and TFI group. URPL group had lower LBR in frozen-thawed ET cycles than that of TFI group (23.56% vs. 33.56%, P = 0.047), but the cumulative LBRs (34.69% vs. 38.26%, P = 0.368) were not significantly different between the two groups. The increased endometrial thickness (EMT) on the human chorionic gonadotropin day (odds ratio [OR]: 0.848, 95% confidence interval [CI]: 0.748–0.962, P = 0.010) and the increased number of eggs retrieved (OR: 0.928, 95% CI: 0.887–0.970, P = 0.001) were protective factors for clinical pregnancy in stimulated cycles. The increased number of eggs retrieved (OR: 0.875, 95% CI: 0.846–0.906, P < 0.001), the increased two-pronucleus rate (OR: 0.151, 95% CI: 0.052–0.437, P < 0.001), and increased EMT (OR: 0.876, 95% CI: 0.770–0.997, P = 0.045) in ET day were protective factors for the cumulative live birth outcome.Conclusion:After matching ages, no significant differences in clinical outcomes were found between the patients with URPL and the patients with TFI. A thicker endometrium and more retrieved oocytes increase the probability of pregnancy in fresh transfer cycles, but a better normal fertilization potential will increase the possibility of a live birth.     

D2 lymphadenectomy with complete mesogastrium excision vs. conventional D2 gastrectomy for advanced gastric cancer

Background:The complete mesogastrium excision (CME) based on D2 radical gastrectomy is believed to significantly reduce the local-regional recurrence compared with D2 radical gastrectomy in advanced gastric cancer, and it is widely used in China. This study aimed to explore whether D2 + CME is superior to D2 on surgical outcomes during gastrectomy from Chinese data.Methods:Feasible studies comparing the D2 + CME (D2 + CME group) and D2 (D2 group) published up to March 2020 are searched from electronic databases. The data showing surgical and complication outcomes are extracted to be pooled and analyzed.Results:Fourteen records including 1352 patients were included. The D2 + CME group had a shorter mean operative time (weighted mean difference [WMD] = —16.72 min, 95% confidence interval [CI]: −26.56 to −6.87 min, P < 0.001), lower mean blood loss (WMD = −39.08 mL, 95% CI: −49.94 to −28.21 mL, P < 0.001), higher mean number of retrieved lymph nodes (WMD = 2.13, 95% CI: 0.58–3.67, P = 0.007), shorter time to first flatus (WMD = −0.31 d, 95% CI: −0.53 to − 0.10 d, P = 0.005), and postoperative hospital days (WMD = −1.09, 95% CI: −1.92 to −0.25, P = 0.010) than the D2 group. Subgroup analysis suggested that the advantages from the D2 + CME group were obvious in traditional open radical gastrectomy, proximal gastrectomy, and distal gastrectomy compared with D2 group. The evaluations of post-operative complications showed that the patients who underwent D2 + CME had a lower incidence of post-operative complications than the patients who underwent D2 surgery alone (relative risk [RR] = 0.65, 95% CI: 0.45–0.87, P = 0.003). The D2 radical gastrectomy plus CME improved 3-year overall survival (OS) (RR = 1.16, 95% CI: 1.02–1.32, P = 0.020) and lowered the local recurrence rate (RR = 0.51, 95% CI: 0.28–0.94, P = 0.030). The patients undergoing laparoscopic surgery or total gastrectomy had more significant advantages compared between D2 + CME and D2 groups in 3-year OS.Conclusion:The data from China show that D2 radical gastrectomy plus CME are reliable procedures and safety compared to D2 radical gastrectomy with faster recovery, lower risk, and better prognosis.     

Long-term results of extensive aortoiliac occlusive disease (EAIOD) treated by endovascular therapy and risk factors for loss of primary patency

Background:Although endovascular therapy has been widely used for focal aortoiliac occlusive disease (AIOD), its performance for extensive AIOD (EAIOD) is not fully evaluated. We aimed to demonstrate the long-term results of EAIOD treated by endovascular therapy and to identify the potential risk factors for the loss of primary patency.Methods:Between January 2008 and June 2018, patients with a clinical diagnosis of the 2007 TransAtlantic Inter-Society Consensus II (TASC II) C and D AIOD lesions who underwent endovascular treatment in our institution were enrolled. Demographic, diagnosis, procedure characteristics, and follow-up information were reviewed. Univariate analysis was used to identify the correlation between the variables and the primary patency. A multivariate logistic regression model was used to identify the independent risk factors associated with primary patency. Five- and 10-year primary and secondary patency, as well as survival rates, were calculated by Kaplan-Meier analysis.Results:A total of 148 patients underwent endovascular treatment in our center. Of these, 39.2% were classified as having TASC II C lesions and 60.8% as having TASC II D lesions. The technical success rate was 88.5%. The mean follow-up time was 79.2 ± 29.2 months. Primary and secondary patency was 82.1% and 89.4% at 5 years, and 74.8% and 83.1% at 10 years, respectively. The 5-year survival rate was 84.2%. Compared with patients without loss of primary patency, patients with this condition showed significant differences in age, TASC II classification, infrainguinal lesions, critical limb ischemia (CLI), and smoking. Multivariate logistic regression analysis showed age <61 years (adjusted odds ratio [aOR]: 6.47; 95% CI: 1.47–28.36; P = 0.01), CLI (aOR: 7.81; 95% CI: 1.92–31.89; P = 0.04), and smoking (aOR: 10.15; 95% CI: 2.79–36.90; P < 0.01) were independent risk factors for the loss of primary patency.Conclusion:Endovascular therapy was an effective treatment for EAIOD with encouraging patency and survival rate. Age <61 years, CLI, and smoking were independent risk factors for the loss of primary patency.     

Iron deficiency and early childhood caries: a systematic review and meta-analysis

Backgrounds:Previous surveys have found that children with iron deficiency (ID) were likely to suffer from early childhood caries (ECC). We aimed to assess the scientific evidence about whether ID is intrinsically related to ECC.Methods:The medical subject headings (MeSH) terms and free words were searched on PubMed, Web of Science, Cochrane, China National Knowledge Infrastructure, Wanfang, and the Database for Chinese Technical Periodicals from March 2020 to September 2020. Two researchers independently screened the articles. Data extraction and cross-checking were performed for the studies that met the inclusion criteria. Meta-analysis was performed using the Cochrane Collaboration''s Review Manager 5.3 software.Results:After excluding duplication and irrelevant literature, 12 case-control studies were included in the study. The meta-analysis demonstrated that children with ECC were more likely to have ID (odds ratio [OR] = 2.63, 95% confidence interval [CI]: [1.85, 3.73], P < 0.001). There was no statistically significant association found between the level of serum ferritin and ECC (weighted mean difference (WMD) = −5.80, 95% CI: [−11.97, 0.37], P = 0.07). Children with ECC were more likely to have iron-deficiency anemia (OR = 2.74, 95% CI: [2.41,3.11], P < 0.001). The hemoglobin (HGB) levels in the ECC group were significantly lower compared with that in the ECC-free group (WMD = −9.96, 95% CI: [−15.45, −4.46], P = 0.0004). The mean corpuscular volume (MCV) levels in the ECC group were significantly lower compared with that in the ECC-free group (WMD = −3.72, 95% CI: [−6.65, −0.79], P = 0.01).Conclusions:ID was more prevalent in children with ECC, and the markers of iron status in the ECC group, such as serum ferritin, HGB, and MCV, were relatively lower than the ECC-free group.     

Comparative effectiveness and safety of 32 pharmacological interventions recommended by guidelines for coronavirus disease 2019: a systematic review and network meta-analysis combining 66 trials

Background:The global pandemic coronavirus disease 2019 (COVID-19) has become a major public health problem and presents an unprecedented challenge. However, no specific drugs were currently proven. This study aimed to evaluate the comparative efficacy and safety of pharmacological interventions in patients with COVID-19.Methods:Medline, Embase, the Cochrane Library, and clinicaltrials.gov were searched for randomized controlled trials (RCTs) in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/SARS-CoV. Random-effects network meta-analysis within the Bayesian framework was performed, followed by the Grading of Recommendations Assessment, Development, and Evaluation system assessing the quality of evidence. The primary outcome of interest includes mortality, cure, viral negative conversion, and overall adverse events (OAEs). Odds ratio (OR) with 95% confidence interval (CI) was calculated as the measure of effect size.Results:Sixty-six RCTs with 19,095 patients were included, involving standard of care (SOC), eight different antiviral agents, six different antibiotics, high and low dose chloroquine (CQ_HD, CQ_LD), traditional Chinese medicine (TCM), corticosteroids (COR), and other treatments. Compared with SOC, a significant reduction of mortality was observed for TCM (OR = 0.34, 95% CI: 0.20–0.56, moderate quality) and COR (OR = 0.84, 95% CI: 0.75–0.96, low quality) with improved cure rate (OR = 2.16, 95% CI: 1.60–2.91, low quality for TCM; OR = 1.17, 95% CI: 1.05–1.30, low quality for COR). However, an increased risk of mortality was found for CQ_HD vs. SOC (OR = 3.20, 95% CI: 1.18–8.73, low quality). TCM was associated with decreased risk of OAE (OR = 0.52, 95% CI: 0.38–0.70, very low quality) but CQ_HD (OR = 2.51, 95% CI: 1.20–5.24) and interferons (IFN) (OR = 2.69, 95% CI: 1.02–7.08) vs. SOC with very low quality were associated with an increased risk.Conclusions:COR and TCM may reduce mortality and increase cure rate with no increased risk of OAEs compared with standard care. CQ_HD might increase the risk of mortality. CQ, IFN, and other antiviral agents could increase the risk of OAEs. The current evidence is generally uncertain with low-quality and further high-quality trials are needed.