scholarly journals Elevation of Neurodegenerative Serum Biomarkers among Hospitalized COVID-19 Patients

2021 ◽  
Author(s):  
Jennifer A. Frontera ◽  
Allal Boutajangout ◽  
Arjun V. Masurkar ◽  
Rebecca A. Betensky ◽  
Yulin Ge ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Neurological Complications ◽  
Cox Proportional Hazards ◽  
Serum Biomarkers ◽  
Hospital Death ◽  
Regression Analyses ◽  
Total Tau ◽  
Proportional Hazards Regression ◽  
Age Related ◽  
History Of

ABSTRACTINTRODUCTIONOlder adults hospitalized with COVID-19 are susceptible to neurological complications, particularly encephalopathy, which may reflect age-related neurodegenerative processes.METHODSSerum total tau, ptau-181, GFAP, NFL, UCHL1, and amyloid-beta(Aβ-40,42) were measured in hospitalized COVID-19 patients without a history of dementia, and compared among patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions using multivariable Cox proportional hazards regression analyses.RESULTSAmong 251 patients, admission serum ptau-181 and UCHL1 were significantly elevated in patients with encephalopathy (both P<0.05) and total tau, GFAP, and NFL were significantly lower in those discharged home(all P<0.05). These markers correlated significantly with severity of COVID illness. NFL, GFAP and UCH-L1 were significantly higher in hospitalized COVID patients than in non-COVID controls with mild cognitive impairment or Alzheimer’s disease(AD).DISCUSSIONAge-related neurodegenerative biomarkers were elevated to levels observed in AD and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.

scholarly journals Identification of Arp2/3 Complex Subunits as Prognostic Biomarkers for Hepatocellular Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Shenglan Huang ◽  
Dan Li ◽  
LingLing Zhuang ◽  
Liying Sun ◽  
Jianbing Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Expression ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Biomarkers ◽  
Migration And Invasion ◽  
Regression Analyses ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression

The actin-related protein 2/3 complex (Arp2/3) is a major actin nucleator that has been widely reported and plays an important role in promoting the migration and invasion of various cancers. However, the expression patterns and prognostic values of Arp2/3 subunits in hepatocellular carcinoma (HCC) remain unclear. In this study, The Cancer Genome Atlas (TCGA) and UCSC Xena databases were used to obtain mRNA expression and the corresponding clinical information, respectively. The differential expression and Arp2/3 subunits in HCC were analyzed using the “limma” package of R 4.0.4 software. The prognostic value of each subunit was evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression analyses. The results revealed that mRNA expression of Arp2/3 members (ACTR2, ACTR3, ARPC1A, APRC1B, ARPC2, ARPC3, ARPC4, ARPC5, and ARPC5L) was upregulated in HCC. Higher expression of Arp2/3 members was significantly correlated with worse overall survival (OS) and shorter progression-free survival (PFS) in HCC patients. Cox proportional hazards regression analyses demonstrated that ACTR3, ARPC2, and ARPC5 were independent prognostic biomarkers of survival in patients with HCC. The relation between tumor immunocyte infiltration and the prognostic subunits was determined using the TIMER 2.0 platform and the GEPIA database. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms of prognostic subunits in the carcinogenesis of HCC. The results revealed that ACTR3, ARPC2, and ARPC5 were significantly positively correlated with the infiltration of immune cells in HCC. The GSEA results indicated that ACTR3, ARPC2, and ARPC5 are involved in multiple cancer-related pathways that promote the development of HCC. In brief, various analyses indicated that Arp2/3 complex subunits were significantly upregulated and predicted worse survival in HCC, and they found that ACTR3, ARPC2, and ARPC5 could be used as independent predictors of survival and might be applied as promising molecular targets for diagnosis and therapy of HCC in the future.

Active monitoring of 12760 clozapine recipients in the UK and Ireland

1999 ◽  
Vol 175 (6) ◽  
pp. 576-580 ◽  
Author(s):  
Janet Munro ◽  
Desmond O'Sullivan ◽  
Christopher Andrews ◽  
Alejandro Arana ◽  
Ann Mortimer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Treatment Resistant ◽  
Active Monitoring ◽  
Case Register ◽  
Proportional Hazards Regression ◽  
Age Related ◽  
The Uk ◽  
To Receive

BackgroundPeople prescribed clozapine for treatment-resistant schizophrenia have mandatory haematological monitoring through a case register for identifying reversible neutropenia.AimsTo quantify risk factors for agranulocytosis in subjects receiving clozapine.MethodData from 12 760 subjects registered to receive clozapine from January 1990 to April 1997 were analysed. Risk factors for agranulocytosis were quantified using a Cox proportional-hazards regression analysis.ResultsThe risk for agranulocytosis in Asian subjects was 2.4 times that in Caucasians (P=0.03). There was an age-related increase in risk of 53% per decade (P=0.0001).ConclusionsThe case register yielded valuable information for guiding research into the causes of the haematological reactions.

scholarly journals Pain in Patients With Type 2 Diabetes-Related Polyneuropathy Is Associated With Vascular Events and Mortality

2020 ◽  
Vol 105 (9) ◽  
pp. 3005-3014
Author(s):  
Brittany R Lapin ◽  
Kevin M Pantalone ◽  
Alex Milinovich ◽  
Shannon Morrison ◽  
Andrew Schuster ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Proportional Hazards ◽  
Negative Binomial ◽  
Cox Proportional Hazards ◽  
Vascular Events ◽  
Proportional Hazards Regression ◽  
Increased Risk ◽  
History Of ◽  
Mortality Hazard Ratio

Abstract Purpose Type 2 diabetes–related polyneuropathy (DPN) is associated with increased vascular events and mortality, but determinants and outcomes of pain in DPN are poorly understood. We sought to examine the effect of neuropathic pain on vascular events and mortality in patients without DPN, DPN with pain (DPN + P), and DPN without pain (DPN-P). Methods A retrospective cohort study was conducted within a large health system of adult patients with type 2 diabetes from January 1, 2009 through December 31, 2016. Using an electronic algorithm, patients were classified as no DPN, DPN + P, or DPN-P. Primary outcomes included number of vascular events and time to mortality. Independent associations with DPN + P were evaluated using multivariable negative binomial and Cox proportional hazards regression models, adjusting for demographics, socioeconomic characteristics, and comorbidities. Results Of 43 945 patients with type 2 diabetes (age 64.6 ± 14.0 years; 52.1% female), 13 910 (31.7%) had DPN: 9104 DPN + P (65.4%) vs 4806 DPN-P (34.6%). Vascular events occurred in 4538 (15.1%) of no DPN patients, 2401 (26.4%) DPN + P, and 1006 (20.9%) DPN-P. After adjustment, DPN + P remained a significant predictor of number of vascular events (incidence rate ratio [IRR] = 1.55, 95% CI, 1.29-1.85), whereas no DPN was protective (IRR = 0.70, 95% CI, 0.60-0.82), as compared to DPN-P. Compared to DPN-P, DPN + P was also a significant predictor of mortality (hazard ratio = 1.42, 95% CI, 1.25-1.61). Conclusions Our study found a significant association between pain in DPN and an increased risk of vascular events and mortality. This observation warrants longitudinal study of the risk factors and natural history of pain in DPN.

scholarly journals Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study

2020 ◽  
Author(s):  
Qiao Shi ◽  
Xiaoyi Zhang ◽  
Fang Jiang ◽  
Xuanzhe Zhang ◽  
Chibu Bimu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Retrospective Study ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Laboratory Data ◽  
Cox Proportional Hazards ◽  
Hospital Death ◽  
Regression Analyses ◽  
Patients With Diabetes

<div><b>OBJECTIVE: </b>Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics, outcomes and analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes.</div><div><b><br></b></div><div><b>RESEARCH DESIGN AND METHODS: </b>This two-center, retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N=153) who were discharged or died from January 1, 2020, to March 8, 2020, were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients.</div><div><br></div><div><b>RESULTS:</b> Of 1561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (IQR, 56.0-72.0) years. A higher proportion of ICU admission (17.6% vs 7.8%, P=0.01) and more fatal cases (20.3% vs 10.5%, P=0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazards ratio [HR] 2.50, 95% CI 1.30-4.78), cardiovascular disease (HR 2.24, 95% CI 1.19-4.23) and chronic pulmonary disease (HR 2.51, 95% CI 1.07-5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84-2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs 63.0 years), most were male (71.0% vs 29.0%), and were more likely to have underlying hypertension (83.9% vs 50.0%) and cardiovascular disease (45.2% vs 14.8%) (all P-values<0.05). Age ≥70 years (HR 2.39, 95% CI 1.03-5.56) and hypertension (HR 3.10, 95% CI 1.14-8.44) were independent risk factors for in-hospital death of patients with diabetes.</div><div><br></div><div><b>CONCLUSIONS: </b>COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.</div>

scholarly journals The impact of preoperative use of calcium channel blockers on outcomes of patients undergoing esophagectomy: a propensity score-matched cohort study

2020 ◽  
Author(s):  
Qihua Lin ◽  
Tianhua Zhang ◽  
Zhijie Wu ◽  
Huiting Li ◽  
Junjie Yu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Propensity Scores ◽  
Proportional Hazards ◽  
Perioperative Complications ◽  
Cox Proportional Hazards ◽  
Perioperative Outcomes ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Proportional Hazards Regression ◽  
History Of

Abstract BACKGROUND In this study, we compared the effects of using preoperative CCBs on perioperative outcomes, cancer recurrence and overall survival in patients undergoing esophagectomy. METHODS A retrospective cohort study was performed on patients who underwent esophagectomy at the Sun Yat-Sen University Cancer Center (n=2415, 2009-2013). Univariate and multivariate logistic regression analyses were performed to assess the perioperative outcomes, while recurrence-free survival and overall survival were assessed using Kaplan-Meier survival estimates and compared using a multivariate Cox proportional hazards regression, adjusted with propensity scores. RESULTS There were 162 patients in the CCB group and 1110 patients in the non-CCB group and the total incidence of perioperative complications was 45.7% in the CCB group and 42.5% in the non-CCB group. The differences in total perioperative complications and other perioperative outcomes were not significantly different between the two groups (P>0.05). The mortality rate was not significantly different between the two groups after matching (38.1% vs 31.6%, P=0.233). The difference in recurrence rate between the two groups was not statistically significant after matching (43.2% vs 32.9%, P = 0.061). Overall survival was shorter in patients with preoperative CCB use than in patients without CCB use (hazards ratio: 1.517, 95% confidence intervals (CI): 1.036-2.220, P=0.030). The multivariate Cox proportional hazards regression adjusted with propensity scores found that a history of smoking cigarettes, clinical stage III at diagnosis, preoperative CCB use, preoperative diuretics use, operation type and postoperative chemotherapy affected the overall survival of patients after esophagectomy. Recurrence-free survival was similar between the CCB and non-CCB groups (HR: 1.425, 95%CI: 0.989-2.053, P=0.054). A history of chronic lung disease, hypertension, and preoperative use of beta-blockers affected the recurrence-free survival of patients after esophagectomy. CONCLUSION Preoperative CCBs use was associated with shorter overall survival but did not affect recurrence-free survival or the postoperative complications for patients undergoing esophagectomy.

scholarly journals Short Communication: Vitamin D and COVID-19 infection and mortality in UK Biobank

2020 ◽  
Author(s):  
Claire E Hastie ◽  
Jill P Pell ◽  
Naveed Sattar
Keyword(s):  
Vitamin D ◽  
Proportional Hazards ◽  
Vitamin D Supplementation ◽  
Cox Proportional Hazards ◽  
Regression Analyses ◽  
Uk Biobank ◽  
Hydroxyvitamin D ◽  
Proportional Hazards Regression ◽  
Potential Link ◽  
25 Hydroxyvitamin D

AbstractPurposeVitamin D has been proposed as a potential causal factor in COVID-19 risk. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 mortality, and inpatient confirmed COVID-19 infection, in UK Biobank participants.MethodsUK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration, were linked to COVID-19 mortality. Univariable and multivariable Cox proportional hazards regression analyses were performed for the association between 25(OH)D and COVID-19 death, and poisson regression analyses for the association between 25(OH)D and severe COVID-19 infection.ResultsComplete data were available for 341,484 UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection. Vitamin D was associated with severe COVID-19 infection and mortality univariably (mortality HR=0.99; 95% CI 0.98-0.998; p=0.016), but not after adjustment for confounders (mortality HR=0.998; 95% CI=0.99-1.01; p=0.696).ConclusionsOur findings do not support a potential link between vitamin D concentrations and risk of severe COVID-19 infection and mortality. Recommendations for vitamin D supplementation to lessen COVID-19 risks may provide false reassurance.

Risk of non-infectious uveitis or myasthenia gravis in patients on checkpoint inhibitors in a large healthcare claims database

2020 ◽  
pp. bjophthalmol-2020-317060 ◽  
Author(s):  
Tian Xia ◽  
Alexander J Brucker ◽  
Brendan McGeehan ◽  
Brian L VanderBeek
Keyword(s):  
Multivariate Analysis ◽  
Myasthenia Gravis ◽  
Index Date ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Cox Proportional Hazards ◽  
Proportional Hazards Regression ◽  
Increased Risk ◽  
History Of ◽  
Infectious Uveitis

AimTo determine if checkpoint inhibitors (CPIs) confer an increased risk of non-infectious uveitis or myasthenia gravis (MG) compared to patients on non-checkpoint inhibitor (N-CPI) chemotherapy.MethodsA retrospective cohort study was performed comparing patients in a large commercial and Medicare advantage database exposed to CPI compared to N-CPI. All patients who initiated a CPI (ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, cemiplimab and durvalumab) were eligible. Date of earliest CPI in the exposure group and N-CPI chemotherapy in the comparator group was considered the index date. Exclusion occurred in both cohorts for any history of uveitis or MG diagnosis and having <1 year in the insurance plan prior to the index date, and <6 months in plan following the index date. Every exposed patient was matched up to 1:10 based on demographics and index year to patients on N-CPI chemotherapy. Multivariate Cox proportional hazards regression modelling was performed.ResultsFor evaluation of incidence of non-infectious uveitis, 26 (0.3%) of 8678 patients on CPI and 123 (0.2%) of 76 153 N-CPI comparators were found to have non-infectious uveitis. After multivariate analysis, CPIs showed an increased hazard for uveitis compared to N-CPI (HR=2.09; 95% CI 1.36 to 3.22, p=0.001). For the MG analysis, 11 (0.1%) of 9210 patients developed MG in the CPI group and 36 (0.04%) of 80 620 comparators. The CPI cohort had a higher hazard of developing MG (HR=2.60; 95% CI 1.34 to 5.07, p=0.005) compared to controls in multivariate analysis.ConclusionsExposure to CPI confers a higher risk for non-infectious uveitis and MG compared to N-CPI chemotherapy.

scholarly journals A novel long non-coding RNA, AC012456.4, as a valuable and independent prognostic biomarker of survival in oral squamous cell carcinoma

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5307 ◽  
Author(s):  
Xuegang Hu ◽  
Zailing Qiu ◽  
Jianchai Zeng ◽  
Tingting Xiao ◽  
Zhihong Ke ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Survival Analysis ◽  
Oral Squamous Cell Carcinoma ◽  
Proportional Hazards ◽  
Prognostic Biomarker ◽  
Cox Proportional Hazards ◽  
Regression Analyses ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Kaplan Meier

Oral squamous cell carcinoma (OSCC) is a major malignant cancer of the head and neck. Long non-coding RNAs (lncRNAs) have emerged as critical regulators during the development and progression of cancers. This study aimed to identify a lncRNA-related signature with prognostic value for evaluating survival outcomes and to explore the underlying molecular mechanisms of OSCC. Associations between overall survival (OS), disease-free survival (DFS) and candidate lncRNAs were evaluated by Kaplan–Meier survival analysis and univariate and multivariate Cox proportional hazards regression analyses. The robustness of the prognostic significance was shown via the Gene Expression Omnibus (GEO) database. A total of 2,493 lncRNAs were differentially expressed between OSCC and control samples (fold change >2, p < 0.05). We used Kaplan–Meier survival analysis to identify 21 lncRNAs for which the expression levels were associated with OS and DFS of OSCC patients (p < 0.05) and found that down-expression of lncRNA AC012456.4 especially contributed to poor DFS (p = 0.00828) and OS (p = 0.00987). Furthermore, decreased expression of AC012456.4 was identified as an independent prognostic risk factor through multivariate Cox proportional hazards regression analyses (DFS: p = 0.004, hazard ratio (HR) = 0.600, 95% confidence interval(CI) [0.423–0.851]; OS: p = 0.002, HR = 0.672, 95% CI [0.523–0.863). Gene Set Enrichment Analysis (GSEA) indicated that lncRNA AC012456.4 were significantly enriched in critical biological functions and pathways and was correlated with tumorigenesis, such as regulation of cell activation, and the JAK-STAT and MAPK signal pathway. Overall, these findings were the first to evidence that AC012456.4 may be an important novel molecular target with great clinical value as a diagnostic, therapeutic and prognostic biomarker for OSCC patients.

scholarly journals Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center, Retrospective Study

2020 ◽  
Author(s):  
Qiao Shi ◽  
Xiaoyi Zhang ◽  
Fang Jiang ◽  
Xuanzhe Zhang ◽  
Chibu Bimu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Retrospective Study ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Laboratory Data ◽  
Cox Proportional Hazards ◽  
Hospital Death ◽  
Regression Analyses ◽  
Patients With Diabetes

<div><b>OBJECTIVE: </b>Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics, outcomes and analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes.</div><div><b><br></b></div><div><b>RESEARCH DESIGN AND METHODS: </b>This two-center, retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N=153) who were discharged or died from January 1, 2020, to March 8, 2020, were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients.</div><div><br></div><div><b>RESULTS:</b> Of 1561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (IQR, 56.0-72.0) years. A higher proportion of ICU admission (17.6% vs 7.8%, P=0.01) and more fatal cases (20.3% vs 10.5%, P=0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazards ratio [HR] 2.50, 95% CI 1.30-4.78), cardiovascular disease (HR 2.24, 95% CI 1.19-4.23) and chronic pulmonary disease (HR 2.51, 95% CI 1.07-5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84-2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs 63.0 years), most were male (71.0% vs 29.0%), and were more likely to have underlying hypertension (83.9% vs 50.0%) and cardiovascular disease (45.2% vs 14.8%) (all P-values<0.05). Age ≥70 years (HR 2.39, 95% CI 1.03-5.56) and hypertension (HR 3.10, 95% CI 1.14-8.44) were independent risk factors for in-hospital death of patients with diabetes.</div><div><br></div><div><b>CONCLUSIONS: </b>COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.</div>

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