scholarly journals MtDNA variations at C5178a and A249d decrease the risk of severe COVID-19 in a Han Chinese population from Central China

Author(s):  
Yi Wu ◽  
Xianhui Wang ◽  
Xihua Li ◽  
Liyuan Song ◽  
Shilong Yu ◽  
...  

Abstract Background: Mitochondria have been shown to play vital roles during SARS-CoV-2 infection and COVID-19 development. Currently, whether mitochondrial DNA (mtDNA) variations, which define mtDNA haplogroups and determine OXPHOS performance and ROS production, are associated with COVID-19 risk is unclear. Methods: A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography (CT) scanning. The exclusion criteria for the healthy controls were any history of diseases in the one-month preceding study assessment. MtDNA variations defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based upon mtDNA phylogenetic analysis using Mitomap Phylogeny. Student’s t-test was used for continuous variables, and Pearson’s chi-squared test or Fisher’s exact test was used for categorical variables. To assess the independent effect of each mtDNA variation defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for the possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) determined through clinical and radiographic examinations. Results: Multivariate logistic regression analyses revealed that mtDNA variations at C5178a and A249d were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI = 0.428-0.814, p = 0.001; and OR = 0.654, 95% CI = 0.457-0.936, p = 0.020, respectively), while A4833G, A4715G, T3394C and G5417A/C16257a/C16261T were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI = 1.179-4.608, p = 0.015; OR = 2.033, 95% CI = 1.242-3.322, p = 0.005; OR = 3.040, 95% CI = 1.522-6.061, p = 0.002; and OR = 2.890, 95% CI = 1.199-6.993, p = 0.018, respectively). Conclusion: mtDNA variations C5178a and A249d might contribute to an individual’s resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual’s risk of developing severe COVID-19. Trial registration: no.

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Yi Wu ◽  
Xian-Hui Wang ◽  
Xi-Hua Li ◽  
Li-Yuan Song ◽  
Shi-Long Yu ◽  
...  

Abstract Background Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk. Methods A population-based case–control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student’s t-test was used for continuous variables, and Pearson’s chi-squared test or Fisher’s exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations. Results Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI 0.428–0.814, P = 0.001; and OR = 0.654, 95% CI 0.457–0.936, P = 0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI 1.179–4.608, P = 0.015; OR = 2.033, 95% CI 1.242–3.322, P = 0.005; OR = 3.040, 95% CI 1.522–6.061, P = 0.002; and OR = 2.890, 95% CI 1.199–6.993, P = 0.018, respectively). Conclusions This is the first study to explore the association of mtDNA variants with individual’s risk of developing severe COVID-19. Based on the case–control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual’s resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual’s risk of developing severe COVID-19.


2020 ◽  
Author(s):  
Qun Lao ◽  
Ning Han ◽  
Yu-Zhu Jia ◽  
Yi-Dong Wu ◽  
Shi-Yong Zhao ◽  
...  

Abstract Background: This study aimed to explore the clinical manifestations of adenovirus infections and the epidemiologic factors for subsequent co-infection in children from Hangzhou, China.Methods: In this retrospective study, the characteristics of children with adenovirus infections presenting at Hangzhou Children’s Hospital and Zhejiang Xiaoshan Hospital from January to December in 2019 were collected. The epidemiologic factors for co-infection were assessed by the multivariate logistic regression analyses. Results: A total of 5,989 children presented with adenovirus infections, of which 559 children were hospitalized for adenovirus respiratory infections. The severity of adenovirus respiratory infection was divided as follows: mild (bronchiolitis, 73.6%), moderate (bronchopneumonia, 17.6%), or severe (pneumonia, 8.8%). Of the 559 children who were hospitalized, 267 presented with co-infection, while the remaining 292 only had adenovirus infections. Multivariate logistic regression analyses indicated that a longer duration of hospitalization was associated with an increased risk of co-infection (Odds ratio [OR]: 1.048; 95% confidence interval [CI]: 1.011-1.087; P = 0.0107). However, increased procalcitonin was associated with a reduced risk of co-infection (OR: 0.677; 95% CI: 0.462-0.992; P = 0.0456). Conclusions: The study indicated that most children with adenovirus respiratory infections showed mild manifestations, and the risk of co-infection was significantly correlated with the duration of hospitalization and procalcitonin level.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4255-4255
Author(s):  
Natasha Catherine Edwin ◽  
Suchitra Sundaram ◽  
Keith R. McCrae ◽  
Heesun J. Rogers ◽  
Bernard J. Silver

Abstract Background: The presence of the lupus anticoagulant (LA) is an established risk factor for thrombosis especially in the post operative setting. The risk of thrombosis among patients testing indeterminate for lupus anticoagulant is unknown. In our study we aim to estimate the incidence of postoperative thrombosis in this population and determine risk factors. Methods: We studied adult patients undergoing LA testing within 3 months of major surgery at the Cleveland Clinic between 2008 and 2013. The International Society for Thrombosis and Hemostasis (ISTH) defines the following criteria for a positive lupus anticoagulant: 1) a prolonged phospholipid dependent screening test, 2) an inhibitor demonstrated on a mixing study with normal plasma, 3) evidence that the inhibitor is phospholipid dependent, and 4) absence of a coexisting factor inhibitor, direct thrombin inhibitor or heparin. Patients fulfilling some but not all of the ISTH criteria were considered to be LA indeterminate. Patients with previous venous thromboembolism (VTE) and hypercoagulable states were excluded. We collected data on patient demographics, surgery and VTE in the first 30 postoperative days. Patients were divided into different groups based upon the presence of concomitant malignant or rheumatological disease, types of surgery and the utilization of thromboprophylaxis. Associations between categorical variables were determined using Fisher’s exact test. Multivariate logistic regression was performed; variables included age, type of surgery and utilization of pharmacologic thromboprophylaxis. Results: Of 791patients undergoing perioperative lupus anticoagulant testing, 176 were diagnosed LA indeterminate. The median age was 55 years with males comprising 52.3% of the population. Twenty six (14.7%) patients had a concomitant malignancy. Eighteen patients (10.2%) were diagnosed with a rheumatological illness. Seventy four (42.1%) patients underwent cardiac and vascular surgical procedures. General surgery including gastrointestinal surgery accounted for 53 (30.1%) patients. Neurosurgical patients (20) comprised 11.4% of the population studied. Fifteen (8.5%) patients underwent orthopedic surgery and fourteen (8%) patients had urologic procedures. Thirty eight (21.6%,CI 16.1-28.3%) patients developed VTE in the first 30 postoperative days. Of the patients with VTE, 16 (42.1%) had isolated deep vein thrombosis (DVT). Six patients had DVT associated with internal jugular vein (IJV) thrombosis (15.8%). Five patients (13.2%) patients had DVT associated with PE. Two patients (5.2%)had IJV DVT and PE in combination. Thrombosis was also reported at the sites of arteriovenous grafts, portal vein and in the central retinal vein. Twelve (31.5%) clots were related to the presence of indwelling central venous catheters. No significant association between presence of cancer or rheumatological disease and incident thrombosis was identified. Of those tested for beta 2 glycoprotein antibodies and anticardiolipin antibodies, no significant association was observed between presence of post-operative thrombosis and the presence of antibodies. While only 70 patients (39.8%) received any form of pharmacological prophylaxis against VTE, there was significant reduction in the incidence of VTE in patients that received prophylaxis as compared to those that did not. A statistically significant increased odds of thrombosis was observed in the neurosurgical population as compared to the patients undergoing other surgical procedures. On multivariate logistic regression analysis, neurosurgical patients had 3.4 fold increased risk of post operative thrombosis (CI 1.3-9.3) when compared to the rest of the surgical population studied, irrespective of the utilization of thromboprophylaxis. Conclusion: The incidence of thrombosis for patients with an incidental finding of LA indeterminate is 21.6%, comparable to that seen in the general population of patients undergoing similar procedures. This implies that standard guidelines should be used in choosing appropriate post-operative thromboprophylaxis in patients with this laboratory finding. More aggressive anticoagulant regimens do not appear to be necessary, although this remains to be confirmed in a controlled randomized study. Disclosures No relevant conflicts of interest to declare.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhiling Wang ◽  
Shuo Zhang ◽  
Yifei Ma ◽  
Wenhui Li ◽  
Jiguang Tian ◽  
...  

Abstract Background This study aimed to explore the risk factors for lymph node metastasis (LNM) in patients with endometrial cancer (EC) and develop a clinically useful nomogram based on clinicopathological parameters to predict it. Methods Clinical information of patients who underwent staging surgery for EC was abstracted from Qilu Hospital of Shandong University from January 1st, 2005 to June 31st, 2019. Parameters including patient-related, tumor-related, and preoperative hematologic examination-related were analyzed by univariate and multivariate logistic regression to determine the correlation with LNM. A nomogram based on the multivariate results was constructed and underwent internal and external validation to predict the probability of LNM. Results The overall data from the 1517 patients who met the inclusion criteria were analyzed. 105(6.29%) patients had LNM. According the univariate analysis and multivariate logistic regression analysis, LVSI is the most predictive factor for LNM, patients with positive LVSI had 13.156-fold increased risk for LNM (95%CI:6.834–25.324; P < 0.001). The nomogram was constructed and incorporated valuable parameters including histological type, histological grade, depth of myometrial invasion, LVSI, cervical involvement, parametrial involvement, and HGB levels from training set. The nomogram was cross-validated internally by the 1000 bootstrap sample and showed good discrimination accuracy. The c-index for internal and external validation of the nomogram are 0.916(95%CI:0.849–0.982) and 0.873(95%CI:0.776–0.970), respectively. Conclusions We developed and validated a 7-variable nomogram with a high concordance probability to predict the risk of LNM in patients with EC.


Author(s):  
Hung-Chih Chen ◽  
Hung-Yu Lin ◽  
Michael Chia-Yen Chou ◽  
Yu-Hsun Wang ◽  
Pui-Ying Leong ◽  
...  

The purpose of this study is to evaluate the relationship between hydroxychloroquine (HCQ) and diabetic retinopathy (DR) via the national health insurance research database (NHIRD) of Taiwan. All patients with newly diagnosed type 2 diabetes (n = 47,353) in the NHIRD (2000–2012) were enrolled in the study. The case group consists of participants with diabetic ophthalmic complications; 1:1 matching by age (±1 year old), sex, and diagnosis year of diabetes was used to provide an index date for the control group that corresponded to the case group (n = 5550). Chi-square test for categorical variables and Student’s t-test for continuous variables were used. Conditional logistic regression was performed to estimate the adjusted odds ratio (aOR) of DR. The total number of HCQ user was 99 patients (1.8%) in the case group and 93 patients (1.7%) in the control group. Patients with hypertension (aOR = 1.21, 95% CI = 1.11–1.31) and hyperlipidemia (aOR = 1.65, 95% CI = 1.52–1.79) significantly increased the risk of diabetic ophthalmic complications (p < 0.001). Conversely, the use of HCQ and the presence of rheumatoid diseases did not show any significance in increased risk of DR. HCQ prescription can improve systemic glycemic profile, but it does not decrease the risk of diabetic ophthalmic complications.


2021 ◽  
pp. 1-6
Author(s):  
Ken Iijima ◽  
Hajime Yokota ◽  
Toshio Yamaguchi ◽  
Masayuki Nakano ◽  
Takahiro Ouchi ◽  
...  

OBJECTIVE Sufficient thermal increase capable of generating thermocoagulation is indispensable for an effective clinical outcome in patients undergoing magnetic resonance–guided focused ultrasound (MRgFUS). The skull density ratio (SDR) is one of the most dominant predictors of thermal increase prior to treatment. However, users currently rely only on the average SDR value (SDRmean) as a screening criterion, although some patients with low SDRmean values can achieve sufficient thermal increase. The present study aimed to examine the numerical distribution of SDR values across 1024 elements to identify more precise predictors of thermal increase during MRgFUS. METHODS The authors retrospectively analyzed the correlations between the skull parameters and the maximum temperature achieved during unilateral ventral intermediate nucleus thalamotomy with MRgFUS in a cohort of 55 patients. In addition, the numerical distribution of SDR values was quantified across 1024 elements by using the skewness, kurtosis, entropy, and uniformity of the SDR histogram. Next, the authors evaluated the correlation between the aforementioned indices and a peak temperature > 55°C by using univariate and multivariate logistic regression analyses. Receiver operating characteristic curve analysis was performed to compare the predictive ability of the indices. The diagnostic performance of significant factors was also assessed. RESULTS The SDR skewness (SDRskewness) was identified as a significant predictor of thermal increase in the univariate and multivariate logistic regression analyses (p < 0.001, p = 0.013). Moreover, the receiver operating characteristic curve analysis indicated that the SDRskewness exhibited a better predictive ability than the SDRmean, with area under the curve values of 0.847 and 0.784, respectively. CONCLUSIONS The SDRskewness is a more accurate predictor of thermal increase than the conventional SDRmean. The authors suggest setting the SDRskewness cutoff value to 0.68. SDRskewness may allow for the inclusion of treatable patients with essential tremor who would have been screened out based on the SDRmean exclusion criterion.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tia C Kohs ◽  
Vikram Raghunathan ◽  
Patricia Liu ◽  
Ramin Amirsoltani ◽  
Michael Oakes ◽  
...  

Introduction: Extracorporeal membrane oxygenation (ECMO) is used to provide circulatory support and facilitate gas exchange via cardiopulmonary bypass. The relationship between ECMO and the incidence of severe thrombocytopenia (platelet count <50 x 10 9 /L) and subsequent clinical consequences are ill defined. We aimed to identify the risk factors for the development of thrombocytopenia and its clinical implications. Methods: This is a single-center retrospective cohort study of adults who received venoarterial (VA) ECMO. We examined consecutive platelet counts while on ECMO. Univariate logistic regression was used to determine if mean platelet count, platelet count range, or severe thrombocytopenia were predictors of overall survival, hemorrhage and thrombosis. A multivariate logistic regression model was used to identify factors that contribute to the development of the aforementioned patient outcomes. Results: In our cohort, 33 patients were included with a mean age of 55 years and duration of ECMO of 5.9 days. All patients received heparin, 33.3% received antiplatelet therapy and 45.5% developed severe thrombocytopenia. In univariate, analysis the development of severe thrombocytopenia increased the odds of major bleeding by 450% (OR 5.500, 95% CI 1.219 - 24.813, P -value 0.027), and the odds of surviving hospitalization decreased 84.1% (OR 0.159, 95% CI 0.033 - 0.773, P -value 0.023). Multivariate logistic regression controlling for additional clinical variables found no significant association between the development of severe thrombocytopenia and rates of thrombosis, hemorrhage, or overall survival. Platelet count decreased over time while on ECMO. Conclusions: Nearly half of the patients requiring VA-ECMO developed severe thrombocytopenia, which was associated with an increased risk of hemorrhage and in-hospital mortality. Additional studies are required to clarify the clinical implications of severe thrombocytopenia in ECMO patients.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Molly Bates ◽  
Kyle Darpel ◽  
Nneka Amadife ◽  
Adam Dugan ◽  
Jessica D Lee

Introduction: Several theories exist regarding the pathogenesis of posterior reversible encephalopathy syndrome (PRES). One theory suggests that PRES occurs when systemic blood pressure exceeds the upper limit of cerebral autoregulation. Endothelial dysfunction has been proposed as an alternative pathogenesis to account for PRES outside the setting of acute hypertension. This mechanism has been implicated in other conditions associated with PRES including autoimmune diseases, cytotoxic medications, sepsis, and eclampsia. The purpose of this study was to determine if COPD, a disease known to cause endothelial dysfunction, has a causative association with the development of PRES. Methods: A single center retrospective, age-matched, case-control study was performed from January 2013 to June 2019 comparing patients discharged with a primary diagnosis of PRES to a control group with acute ischemic stroke. Demographics, medical comorbidities, initial blood pressure, and clinical outcomes were compared between the two groups. For categorical variables, p-values were calculated using χ2 and Fisher’s exact tests. For continuous variables, p-values were calculated using two-sample t-tests. The effect of COPD and acute hypoxic respiratory failure on PRES status was investigated using multivariate logistic regression. Results: A total of 94 PRES subjects and 109 control subjects were included for analysis. Mean age did not differ between the two groups; however, the PRES group was more likely to be female (78.7% vs. 49.5%, p<0.001). COPD was present in 26.6% (n=25) of cases and 11% (n= 12) of controls (odds ratio 4.12, p=0.003). Occurrence of hypertension did not differ significantly between the two groups (78.0% vs 86.2%). Among patients with PRES in the setting of COPD (n=25), 60% (n=16) did not meet criteria for hypertensive emergency. Controlling for hypertensive emergency status in a multivariate logistic regression analysis, patients with COPD were 3.21 times more likely to develop PRES (p= 0.004). Conclusions: To our knowledge, very few reports of PRES in the setting of COPD have been described in the literature and no association of PRES and COPD has been defined to date. Our data support the role of COPD as a risk factor in the development of PRES.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Thomas M Hemmen ◽  
Rema Raman ◽  
Karin Ernstrom ◽  
Debra Paulson ◽  
Valerie Lake ◽  
...  

Background: Dysphagia is common after stroke and is associated with an increased risk for pulmonary complications and mortality. Current standards mandate screening for dysphagia before oral intake in all acute stroke patients. We aimed to show if this early screening affects long-term outcomes after stroke. Methods: We included all UCSD Medical Center discharges with diagnosis AIS, ICH and SAH between July 1 2008 and June 30 2011; and evaluated baseline demographics, admission diagnosis (AIS, ICH, SAH), admission source (ED or transfer) length of hospital stay (LOS), ICU-LOS, aspiration pneumonia, in-hospital, 30-day and 6-month mortality by public death records for all patients. Patients were grouped as: 1) no dysphagia screening performed, 2) Nil per os (NPO) until discharge, 3) dysphagia screening performed. Adjustments for stroke severity and CMI were not possible. Statistical comparisons were done with the Kruskal-Wallis test (continuous variables) or Fisher-Freeman-Halton test (categorical variables). For pairwise comparisons we used the Wilcoxon tests (continuous variables) or Fisher’s Exact test (categorical variables), with Holm’s adjusted p-values. Results: A total of 476 patients were included, Group 1: 47, Group 2: 119, Group 3: 310. There was no significant difference in age, gender, race/ethnicity, and diagnosis of HTN, DM, afib, prior stroke and admission source. More patients with SAH and ICH were in Group 2. Overall, LOS and ICU LOS, aspiration pneumonia, in-hospital, 30-day and 6-month mortality were found to be different among groups (p<0.0001). Pair-wise comparisons showed that all outcomes were significantly higher in Group 2, but similar between Groups 1 and 3 (NS). Conclusion: We found no difference in outcomes between patients who received dysphagia screening versus not (Group 1 vs 3). Excluding patients who were left NPO and are more likely to suffer from ICH, SAH with increased morbidity and mortality, it remains uncertain if a targeted early dysphagia screening can reduce morbidity and mortality after stroke. Further studies are needed to find the appropriate population that most benefits from dysphagia screening.


2020 ◽  
Author(s):  
Sufen Zhou ◽  
Hongyan Guo ◽  
Heng Liu ◽  
Mingqun Li

Abstract Background: This study aimed to investigate potential predictors, including cerebroplacental ratio (CPR), middle cerebral artery (MCA)/uterine artery pulsatility index (PI) ratio, for adverse perinatal outcome in pregnancies at term.Methods: This was an observational, prospective study of recruited pregnancies at term. An adverse perinatal outcome was set as the primary observational endpoint. The receiver operating characteristic (ROC) curve was plotted to investigate the predictive and cut-off values of risk factors for adverse perinatal outcome. Independent risk factors (maternal, neonatal, prenatal ultrasound and Doppler variables) for adverse perinatal outcome were evaluated by the univariate and multivariate logistic regression analyses.Results: A total of 392 pregnancies at term were included and 19.4% of them had suffered adverse perinatal outcome. CPR (OR: 0.42, 95%CI: 0.20-0.93, P=0.032) and MCA/uterine artery PI ratio (OR: 0.25, 95%CI: 0.16-0.42, P=0.032) were two independent risk factors for adverse perinatal outcome by univariate and multivariate logistic regression analyses.Conclusions: MCA/uterine artery PI ratio is a good predictor of adverse perinatal outcome in pregnancies at term.


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