Univariate Analysis Of Association Research Articles

Validation of genetic risk scores for coronary artery disease, developed on European population samples, in Russian population

Aim. To evaluate the information content of genetic risk scores (GRSs) for coronary artery disease (CAD), previously developed on European populations, in representatives of the Russian population.Material and methods. The work involved 1685 people from the ESSE-Ivanovo epidemiological study. CAD was verified in 3,1% of individuals. The coronary composite endpoint was assessed annually during 8-year follow-up. Next generation sequencing was performed using a targeted panel. Logistic regression analysis and area under the ROC curve (AUC) were used. Age, sex, and smoking status were taken into account in the multivariate model.Results. Of the 16 GRSs included in the analysis, only 2 GRSs demonstrated significance in the univariate analysis of association with CAD (highest AUC — 0,577). In a multivariate model, with an increase by 1 standard deviation (SD) for the 6 studied GRSs, a significant association with CAD was obtained — the odds ratio varied in the range of 1,31-1,47. The two GRSs demonstrated significant differences in the incidence of CAD between the groups corresponding to the upper and lower quintiles. Forty-five endpoints were registered. The risk ratio for the end point with an increase in GRS by 1 SD, taking into account cofactors, exceeded statistical significance for the 9 analyzed GRS and was in the range of 1,36-1,54.Conclusion. For the first time in Russia, 16 CAD GRSs, previously developed on European samples, was validated. The results were reproduced only for a few of the studied CAD SGRs.

The geno-geo-climate nexus: contributions of geographic and ecological factors in shaping the genomic divergence of two closely related threatened rainforest species of Fontainea Heckel (Euphorbiaceae)

ContextProcesses that shape genomic and ecological divergence can reveal important evolutionary dynamics to inform the conservation of threatened species. Fontainea is a genus of rainforest shrubs and small trees including critically endangered and threatened species restricted to narrow, but complex geographic and ecological regions. Several species of Fontainea are subject to spatially explicit conditions and experience limited intra-specific gene flow, likely generating genetic differentiation and local adaptation.ObjectivesHere, we explored the genetic and ecological mechanisms underlying patterns of diversification in two, closely related threatened Fontainea species. Our aim was to compare spatial patterns of genetic variation between the vulnerable Fontainea australis (Southern Fontainea) and critically endangered F. oraria (Coastal Fontainea), endemic to the heterogeneous subtropical region of central, eastern Australia, where large-scale clearing has severely reduced rainforest habitat to a fraction (< 1%) of its pre-European settlement extent.MethodsWe used a set of 10,000 reduced-representation markers to infer genetic relationships and the drivers of spatial genetic variation across the two species. In addition, we employed a combination of univariate and multivariate genome-environment association analysis using a set of topo-climatic variables to explore potential patterns of local adaptation as a factor impacting genomic divergence.ResultsOur study revealed that Coastal Fontainea have a close genetic relationship with Southern Fontainea. We showed that isolation by distance has played a key role in their genetic variation, indicating that vicariance can explain the spatial genetic distribution of the two species. Genotype-environment analyses showed a strong association with temperature and topographic features, suggesting adaptation to localised thermal environments. We used a multivariate redundancy analysis to identify a range of putatively adapted loci associated with local environmental conditions.ConclusionsDivergent selection at the local-habitat scale as a result of dispersal limitations and environmental heterogeneity (including physical barriers) are likely contributors to adaptive divergence between the two Fontainea species. Our findings have presented evidence to indicate that Southern and Coastal Fontainea were comprised of distinct genetic groups and ecotypes, that together may form a single species continuum, with further phenotype research suggested to confirm the current species boundaries. Proactive conservation actions, including assisted migration to enhance the resilience of populations lacking stress-tolerant single nucleotide polymorphisms (SNPs) may be required to secure the long-term future of both taxa. This is especially vital for the critically endangered Coastal Fontainea given projections of habitat decline for the species under future climate scenarios.

The Neurosurgeon's Dilemma—Do Antiplatelet/Anticoagulant Medications Increase the Risk of Catheter-Associated Hemorrhage in External Ventricular Drain Placement?

IntroductionExternal ventricular drain (EVD) placement is a common neurosurgical procedure that can be performed at bedside. A frequent complication following EVD placement is catheter-associated hemorrhage (CAH). The hemorrhage itself is rarely clinically significant but may be complicated in patients taking anticoagulant or antiplatelet (AC/AP) medications. MethodsA total of 757 patients were who underwent EVD placement at bedside were included as part of a retrospective study at a large academic medical center. Demographic factors, use of AC/AP therapies, and several other clinical variables were recorded and assessed in univariate and multivariate regression analysis for association with CAH and mortality. ResultsOne hundred (13.2%) patients experienced CAH within 24 hours of the procedure. After univariate analysis, in two tandem-run multivariate regression analyses after stepwise variable selection, use of two or more AC/AP agents (OR=2.362, p=0.020) and dual antiplatelet therapy with aspirin and clopidogrel (OR=3.72, p=0.009) were significantly associated with CAH. Use of non-coated catheters was a protective factor against CAH compared to use of antibiotic-coated catheters (OR=0.55, p=0.019). Multivariate analysis showed age, multi-agent therapy, and thrombocytopenia were significantly associated with increased mortality. ConclusionThere was increased risk of CAH after EVD placement in patients taking more than one AC/AP agent regardless of presenting pathology. In particular, use of aspirin and clopidogrel combined was associated with significantly higher odds of CAH, although it was not associated with higher mortality. In addition, there appears to be an association between use of antibiotic-coated catheters and CAH across univariate and multivariate analysis.

Financial Toxicity in the Spanish Speaking Population

Advances in therapy have significantly improved cancer survival outcomes but with a harmful patient consequence: financial toxicity. Financial toxicity consists of a patient's many economic burdens from cancer treatment, encompassing direct healthcare costs as well as additional devastating financial consequences, such as job loss and medical bankruptcy. With rising cancer treatment costs, financial toxicity has become a problem that is increasingly impactful in both cancer treatment and survivorship, amplifying disparities, negatively impacting quality of life, treatment adherence and survival. The long-term research goal that this study will contribute to is to develop culturally appropriate and effective patient navigation resources and psychosocial support resources for interventions to increase coping and resilience to financial toxicity in high-risk populations. This study will seek to generate the early data needed to help develop the content and method of delivering strategies, tailored for an underserved, Spanish-speaking Latino population. Eligibility Participant must be 18 years of age or older at the time of study participation, able to read and speak Spanish, have diagnosis of cancer within the past 2 years or be on active treatment for their cancer; all disease sites and all stages are eligible for enrollment. We will exclude patients unable to give consent. Methods This is a prospective observational study of cancer patients and survivors, with participants to be recruited from Scripps MD Anderson Cancer Center. Participating clinics will be screened in the electronic medical record for individuals who meet above eligibility criteria. At the time of clinic visits, eligible individuals will be approached. Individuals who express that they would like to participate in the survey study will receive the study packet with the consent statement and baseline survey questions. Study participants will also be invited to participate in the OPTIONAL patient navigation portion of the study. Participants who are not active on the MyScripps patient portal will be invited to join the patient navigation portion of the study. Those elect to participate will be provided a device if they do not have their own. Participants will be given a Greenphire Clincard on which they will receive a total of $75 in three installments. Research team members will enter the item responses into the REDCap database. They will undergo a follow-up survey during a range from 4 months to 9 months from the initial survey date. Those participating in the patient navigation portion of the study will be contacted by the navigator on a monthly basis through the electronic portal or telephone. Statistics We plan to enroll N= 80 Spanish-speaking patients in the survey study. For correlation testing, we hypothesize a moderate effect size (correlation = 0.32) for the association between the primary outcome measure, the baseline measure of self-efficacy (Hope State score) and the baseline financial toxicity score (Economic Strain and Resilience in Cancer). For feasibility testing of navigation participation, feasibility will be assessed through descriptive statistics. We hypothesize that it is feasible for 50% of invited patients to participate. When the sample size is 40, a two-sided 95% confidence interval for participant completion rate will extend 0.15 from the observed proportion for an expected proportion of 0.50. Analysis The primary outcome measure is financial toxicity, measured using the ENRICh instrument at baseline. The primary predictor is the baseline Hope State score. This modeled association is of primary interest in the analysis. We will conduct descriptive and univariate/multivariate analyses on this association of primary interest, including Chi-square test, t-test. Other univariate and multivariate analyses of associations between financial toxicity and other measures obtained from survey measures, as well as clinical, demographic, socioeconomic, and care delivery variables, considered descriptive and exploratory, will be performed. Accounting for multiple comparisons will be based on stepdown procedures and familywise error rate control; we plan to control this overall error rate using the Holm-Sidak adjustment, or procedure with equitable properties.

Variants in JAZF1 are associated with asthma, type 2 diabetes, and height in the United Kingdom biobank population.

Background: Asthma, type 2 diabetes (T2D), and anthropometric measures are correlated complex traits that all have a major genetic component. Objective: To investigate the overlap in genetic variants associated with these complex traits. Methods: Using United Kingdom Biobank data, we performed univariate association analysis, fine-mapping, and mediation analysis to identify and dissect shared genomic regions associated with asthma, T2D, height, weight, body mass index (BMI), and waist circumference (WC). Results: We found several genome-wide significant variants in and around the JAZF1 gene that are associated with asthma, T2D, or height with two of these variants shared by the three phenotypes. We also observed an association in this region with WC when adjusted for BMI. However, there was no association with WC when it was not adjusted for BMI or weight. Additionally, only suggestive associations between variants in this region and BMI were observed. Fine-mapping analyses suggested that within JAZF1 there are non-overlapping regions harboring causal susceptibility variants for asthma, T2D, and height. Mediation analyses supported the conclusion that these are independent associations. Conclusion: Our findings indicate that variants in the JAZF1 are associated with asthma, T2D, and height, but the associated causal variant(s) are different for each of the three phenotypes.

Investigating the impact of demographic disparities on clinical outcomes in cutaneous T-cell lymphoma (CTCL): A multicenter retrospective cohort analysis.

7573 Background: Black patients have been shown to have a higher incidence of cutaneous T-cell lymphomas (CTCL) and display unique clinicopathologic features at diagnosis, however, drivers of these disparities and the role of social determinants of health (SDoH) remain poorly understood. Methods: To further characterize the prognostic relevance of racial and demographic disparities in CTCL, we performed a retrospective review of 1,198 patients seen at 8 different academic treatment centers in the United States between 2000-2020. Clinical variables included demographics, disease characteristics, and survival. Race and ethnicity were stratified into 2 groups for this analysis: non-Hispanic Black (B) and Non-Black (NB). Distance to center was stratified into short, intermediate, or long commute ( &lt; 10, 10-50, &gt; 50 miles, respectively) based on home zip code. The primary endpoint was overall survival (OS). Univariate association and multivariable analyses were assessed using Cox proportional hazards models. Results: Among 1,198 total patients, 42.4% identified as B and 58.6% as NB. B patients presented younger, had a shorter commute, lower income, but no difference in insurance compared to NB patients. There was no difference in survival by race (Median OS 74 months (95% CI 65-84) compared to 65 (95% CI 58-75) for NB patients). Distance to center was strongly associated with survival and remained significant on multivariate analyses after controlling for age, race, and other SDoH. Longer commute was associated with worse OS compared to short commute for both B and NB counterparts (median 55 months [95% CI 49-66] vs. 79 [95% CI 69-90] and 75 [95% CI 63-86], respectively, p = 0.006). Conclusions: We characterized the impact of race and SDoH on overall survival (OS) in a diverse, multicenter cohort of patients with CTCL. We found that distance to cancer center was the most important factor contributing to disparities in OS in this study. This highlights the importance of improving access to care, particularly in rare and clinically heterogeneous diseases such as CTCL.

Clusters based on demography, disease phenotype, and autoantibody status predicts mortality in lupus: data from Indian lupus cohort (INSPIRE).

SLE is associated with significant mortality, and data from South Asia is limited. Thus, we analysed the causes and predictors of mortality and hierarchical cluster-based survival in the Indian SLE Inception cohort for Research (INSPIRE). Data for patients with SLE was extracted from the INSPIRE database. Univariate analyses of associations between mortality and a number of disease variables were conducted. Agglomerative unsupervised hierarchical cluster analysis was undertaken using 25 variables defining the SLE phenotype. Survival rates across clusters were assessed using non-adjusted and adjusted Cox proportional-hazards models. Among 2072 patients (with a median follow-up of 18 months), there were 170 deaths (49.2 deaths per 1000 patient-years) of which cause could be determined in 155 patients. 47.1% occurred in the first 6 months. Most of the mortality (n = 87) were due to SLE disease activity followed by coexisting disease activity and infection (n = 24), infections (n = 23), and 21 to other causes. Among the deaths in which infection played a role, 24 had pneumonia. Clustering identified four clusters, and the mean survival estimates were 39.26, 39.78, 37.69 and 35.86 months in clusters 1, 2, 3 and 4, respectively (P < 0.001). The adjusted hazard ratios (HRs) (95% CI) were significant for cluster 4 [2.19 (1.44, 3.31)], low socio-economic-status [1.69 (1.22, 2.35)], number of BILAG-A [1.5 (1.29, 1.73)] and BILAG-B [1.15 (1.01, 1.3)], and need for haemodialysis [4.63 (1.87,11.48)]. SLE in India has high early mortality, and the majority of deaths occur outside the health-care setting. Clustering using the clinically relevant variables at baseline may help identify individuals at high risk of mortality in SLE, even after adjusting for high disease activity.

Widespread Proprioceptive Acuity Impairment in Chronic Back Pain: A Cross-sectional Study

ObjectiveTo investigate whether proprioceptive accuracy measured with the Joint Position Sense (JPS) in patients with chronic neck and low back pain is impaired exclusively in affected areas or also in distant areas, not affected by pain. DesignCross-sectional study. SettingInterdisciplinary outpatient rehabilitation clinic for back and neck pain. ParticipantsPatients with chronic neck pain (n=30), patients with chronic low back pain (n=30), and age- and sex-matched asymptomatic control subjects (n=30; N=90). InterventionsNot applicable. Main Outcome MeasuresPatients and asymptomatic control subjects completed a test procedure for the JPS of the cervical spine, lumbar spine, and ankle in a randomized order. Between group differences were analyzed with the univariate analysis of variance and associations of the JPS with clinical features using the Pearson's correlation coefficient. ResultsBoth patients with chronic neck pain (P<.001) and patients with chronic low back pain (P<.01) differed significantly from asymptomatic controls in the JPS of the cervical spine, lumbar spine and ankle joint, regardless of the painful area. No difference was shown between patient groups (P>.05). An association of the JPS with clinical characteristics, however, could not be shown. ConclusionThese results suggest widespread impairment of proprioceptive accuracy in patients with chronic and low back pain and a role for central sensorimotor processes in musculoskeletal pain conditions.

Prevalence and Predictors of Carpal Tunnel Syndrome Symptoms Among Teachers in Riyadh: A Cross-Sectional Study.

Background Carpal tunnel syndrome (CTS) is a musculoskeletal disorder (MSD) afflicting the upper limbs with a prevalence of approximately14.4% in the general population. Previous studies have noted the increasing prevalence of MSDs among teachers but have not investigated in depth the prevalence and predictors of CTS symptoms in this population. The aim of this study was to help fill this gap in the literature by investigating teachers working in Riyadh, Saudi Arabia. Methods We conducted this cross-sectional study in Riyadh using an online survey. We distributed the Boston carpal tunnel questionnaire (BCTQ) to schoolteachers in the city through the social media applications Twitter, WhatsApp, and Telegram. We assessed the respondents' symptoms using Univariate association analyses with a Wilcoxon rank sum test for the continuous variables and Fisher's exact test and Pearson's chi-squared test for the categorical variables. We assessed the independent risk factors for CTS by constructing multivariate binary logistic regression models and expressed the results using the odds ratio (OR) and 95% confidence intervals (95% CIs), with p < 0.05 indicating statistical significance. Results The sample for this study included 490 teachers. Among them, the prevalence of moderate to severe CTS symptoms was 40.0%, and self-reported CTS was 9.1%. The teachers who were female, relatively old, left-handed, retired, and spent significant time using a pen, keyboard, and/or blackboard were more likely than those who were male, relatively young, right-handed, and did not spend significant time using a pen, keyboard, and/or blackboard to self-report CTS and exhibit moderate to severe symptoms. Conclusions We found a relatively high percentage (40.0%) of CTS symptoms among teachers working in Riyadh. This finding suggests that any sign of CTS symptoms should be checked to ensure early diagnosis and treatment, which contribute to positive outcomes, particularly given the recent increase in such risk factors for CTS as diabetes, hypothyroidism, and high BMI in populations worldwide.

The effects of non-andrological medications on erectile dysfunction: a large single-center retrospective study

PurposeTo evaluate the association among andrological diseases at the first outpatient visit and the medications taken by patients for other comorbidities, as well as the differential impact between specific medication and relative comorbidities.MethodsThis is a single-center retrospective study based on subjects who referred to the Andrology Unit with a well-defined andrological diagnosis.ResultsA total of 3752 subjects were studied (mean age ± DS 46.2 ± 16.5 years). A total of 19 categories of andrological diseases and 110 type of medications for other comorbidities were identified. ED was the most frequent andrological pathology at the first andrological examination (28.7%), followed by infertility (12.4%). The couple of variables that were statistically significant in the univariate association analysis (p < 0.001) were: ED and (a) antihypertensives; (b) antihyperglycemics; (c) lipids-lowering; (d) psychotropics. The univariate and multivariate regression analyses confirmed the association. All the related comorbidities were also significantly associated with the univariate analysis, and all remained significantly associated with multivariate analysis. A multivariate analysis was also conducted to analyze the association between ED and the following pairs of variables “DM-antihyperglycemics”, “dyslipidemia-lipids-lowering”, and “hypertension-antihypertensives”. In all cases, the pathology, but not the specific treatment, was significantly associated with ED.ConclusionED is significantly associated with antihypertensive, antihyperglycemic, lipid-lowering, psychotropic drugs’ intake. Anyway, ED appears to be more related to the diseases than to the specific therapies. The definitive cause/effect relationship should be established based on future prospective studies.

Diagnostic metabolomic profiling of Parkinson's disease biospecimens

BackgroundReliable and sensitive biomarkers are needed for enhancing and predicting Parkinson's disease (PD) diagnosis. ObjectiveTo investigate comprehensive metabolomic profiling of biochemicals in CSF and serum for determining diagnostic biomarkers of PD. MethodsFifty subjects, symptomatic with PD for ≥5 years, were matched to 50 healthy controls (HCs). We used ultrahigh-performance liquid chromatography linked to tandem mass spectrometry (UHPLC-MS/MS) for measuring relative concentrations of ≤1.5 kDalton biochemicals. A reference library created from authentic standards facilitated chemical identifications. Analytes underwent univariate analysis for PD association, with false discovery rate-adjusted p-value (≤0.05) determinations. Multivariate analysis (for identifying a panel of biochemicals discriminating PD from HCs) used several biostatistical methods, including logistic LASSO regression. ResultsComparing PD and HCs, strong differentiation was achieved from CSF but not serum specimens. With univariate analysis, 21 CSF compounds exhibited significant differential concentrations. Logistic LASSO regression led to selection of 23 biochemicals (11 shared with those determined by the univariate analysis). The selected compounds, as a group, distinguished PD from HCs, with Area-Under-the-Receiver-Operating-Characteristic (ROC) curve of 0.897. With optimal cutoff, logistic LASSO achieved 100% sensitivity and 96% specificity (and positive and negative predictive values of 96% and 100%). Ten-fold cross-validation gave 84% sensitivity and 82% specificity (and 82% positive and 84% negative predictive values). From the logistic LASSO-chosen regression model, 2 polyamine metabolites (N-acetylcadaverine and N-acetylputrescine) were chosen and had the highest fold-changes in comparing PD to HCs. Another chosen biochemical, acisoga (N-(3-acetamidopropyl)pyrrolidine-2-one), also is a polyamine metabolism derivative. ConclusionsUHPLC-MS/MS assays provided a metabolomic signature highly predictive of PD. These findings provide further evidence for involvement of polyamine pathways in the neurodegeneration of PD.

Somatic single nucleotide variations and copy number variation can be used to distinguish high grade serous ovarian cancer from benign fallopian tubes with high accuracy (219)

Somatic single nucleotide variations and copy number variation can be used to distinguish high grade serous ovarian cancer from benign fallopian tubes with high accuracy (219)

Potential Association of Hypernatremia With Mortality in Patients With Acute Kidney Injury and COVID-19.

BackgroundThe outcome of acute kidney injury (AKI) in patients with COVID-19 and the factors associated with its outcome, including mortality, are understudied among the Indian population.ObjectiveThe objective of this study is to determine the outcome of AKI in a cohort of patients with COVID-19 admitted to medical wards and associated intensive care unit (ICU) and the factors associated with its outcome, including mortality.MethodThis is a retrospective study of patients with COVID-19 and AKI admitted to a tertiary care hospital. A total of 1765 patients were admitted to a hospital with COVID-19 between March 23, 2021, and June 30, 2021, during the second wave of the pandemic chiefly attributed to SARS-Co-V-2 lineage B.1.617. Patients with AKI for whom a nephrology call was sought for management (N=60) were included. Measurements carried out were the stage of AKI, co-morbidities, ICU admission, mechanical ventilation, lab parameters, and mortality. We classified AKI by comparing the highest to lowest recorded serum creatinine in hospital and staged AKI based on the Kidney Disease: Improving Global Outcomes (KDIGO) system. We further developed stepwise logistic regression models to find independent factors associated with mortality. ResultsOut of the 1765 patients hospitalized with COVID-19, a total of 60 (3.4%) patients with AKI were referred to nephrology for management. The observed mortality in this cohort was 41/60 (68.3%). AKI stage 3 was observed to be the most common (78.3%). Based on a univariate analysis of association, age, chronic kidney disease, admission to ICU, the requirement for vasopressor and ventilation, lactate dehydrogenase (LDH) DH, liver function tests (LFT), hypernatremia, and leucocytosis were associated with the mortality of patients (p<0.05) with AKI and COVID-19 infection. Multivariate analysis using logistic regression led to the identification of hypernatremia (OR 5.24 {0.95-42.31}) and multiple co-morbidities (OR 2.59 {1.03-8.75}, p<0.07) as potential factors independently associated with mortality.ConclusionThe study indicates the potential association of hypernatremia with mortality in AKI, along with the simultaneous presence of multiple co-morbidities with COVID-19. As the statistical power of the association is weak, we are claiming the association as potential only. It needs to be confirmed in other larger studies.

Identification of novel genes influencing eosinophil-specific protein levels in asthma families

Eosinophils play a key role in the asthma allergic response by releasing cytotoxic molecules such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) that generate epithelium damages. We sought to identify genetic variants influencing ECP and EDN levels in asthma-ascertained families. We performed univariate and bivariate genome-wide association analyses of ECP and EDN levels in 1018 subjects from the EGEA study with follow-up in 153 subjects from the Saguenay-Lac-Saint-Jean study and combined the results of these 2 studies through meta-analysis. We then conducted Bayesian statistical fine mapping together with quantitative trait locus and functional annotation analyses to identify the most likely functional genetic variants and candidate genes. We identified 5 genome-wide significant loci (P&amp;lt; 5×10&lt;sup&gt;-8&lt;/sup&gt;) including 7 distinct signals associated with ECP and/or EDN levels. The genes targeted by our fine mapping and functional search include RNASE2 and RNASE3 (14q11), which encode EDN and ECP, respectively, and 4 other genes that regulate ECP and EDN levels. These 4 genes were JAK1 (1p31), a transcription factor that plays a key role in the immune response and acts as a potential therapeutic target for eosinophilic asthma; ARHGAP25 (2p13), which is involved in leukocyte recruitment to inflammatory sites; NDUFA4 (7p21), which encodes a component of the mitochondrial respiratory chain and is involved in cellular response to stress; and CTSL (9q22), which is involved in immune response, extracellular remodeling, and allergic inflammation. Analysis of specific phenotypes produced by eosinophils allows the identification of genes that play a major role in allergic response and inflammation, and offers potential therapeutic targets for asthma.

Safety and efficacy of currently used COVID‐19 vaccines: Results of a pilot survey

IntroductionAfter its emergence in China, the COVID‐19 pandemic has spread rapidly around the world, affecting all of our lives. Over the past few months, different vaccines have been issued to the public following FDA approval. Since their release, the number of COVID‐19 cases in the United States have gone down significantly. However, there is a long way to go until the eradication of the virus. There has also been a strong emergence of delta variants across the world, which (for the most part) can still be partially blocked by vaccines. This is why it is so important everyone gets a vaccine for COVID‐19.PurposeThe purpose of this project was to determine the public’s opinion of COVID‐19 and the COVID‐19 vaccines, while also determining correlation between different demographics and these opinions.HypothesisThere are many different factors within various demographics that cause a correlation to a certain belief regarding COVID‐19 and COVID‐19 vaccines.Materials and MethodsThis study was conducted in collaboration with Loyola University Chicago. Survey questions about COVID‐19 and COVID‐19 vaccinations have been sent electronically to the respondents. Initial results based on a pilot study where the answers from 250 respondents were compiled. Basic descriptive statistics were used to characterize the sample and study variables. Univariate analysis of associations between categorical variables and vaccination intent and acceptance were assessed by chi‐square statistics. Multivariate analysis performed by regression analysis to determine significant independent predictors. A p‐value of less than 0.05 was considered to indicate statistical significance; all tests were 2‐tailed.ResultsIn our study population vaccine willingness have been found as 94,4%, the rate of receiving at least one dose of vaccination have been found as 90,8%. In univariate analysis, gender, believing that vaccinations protect others and having enough information about safety and efficacy of vaccines have been found significant factors for vaccine willingness. For receiving at least one dose of vaccination, gender, previous COVID‐19 infection, believing that vaccinations protect others, having enough information about safety and efficacy of vaccines, the degree of COVID‐19 related effects on person’s life, knowledge that COVID‐19 can cause blood clots and the degree of concerns about delta variant have been found significant factors for vaccine willingness. In multivariate analysis only believing that vaccinations protect others have been found as an independent factor for vaccine willingness. For receiving at least one dose of vaccination, believing that vaccinations protect others, the degree of COVID‐19 related effects on person’s life and having enough information about safety and efficacy of vaccines have been found independent factors in multivariate analysis.ConclusionThere are several vaccines currently available in the United States. All of these vaccines provide immunity against COVID‐19 and its variants which have been identified in 2020 and 2021. The level of immunity and the reported adverse events vary with each of the vaccines. Despite minor issues the vaccination outweighs the benefits and provides a clear approach to control this pandemic.

African American and Caucasian patients with Sézary syndrome have no differences in outcomes at an ethnically diverse urban medical center

Sézary syndrome (SS) is an aggressive cutaneous T-cell lymphoma with poor survival. We performed a retrospective review of SS patients at Emory University from 1990 to 2020. We collected data on race, clinical characteristics, therapy, and social determinants of health. Clinical endpoints were overall survival (OS) and time to next treatment (TTNT). Univariate association and multivariable analyses were assessed by Cox proportional hazards models. Among 62 patients, 45.2% were AA. The median OS and TTNT were 3.1 years and 6.3 months, respectively, with no difference by race. AA patients had a higher median baseline LDH (360 vs. 232, p = 0.002) and a longer delay in initiation of systemic therapy compared to CC patients (3.17 vs. 2.14 months, p = 0.039), but a shorter commute (<10 miles) and no difference in insurance coverage (p = 0.260). AA patients at an academic center had unique clinical features and treatment patterns, but similar survival to CC SS patients.

PET/MR Imaging in Evaluating Treatment Failure of Head and Neck Malignancies: A Neck Imaging Reporting and Data System-Based Study.

PET/MR imaging is a relatively new hybrid technology that holds great promise for the evaluation of head and neck cancer. The aim of this study was to assess the performance of simultaneous PET/MR imaging versus MR imaging in the evaluation of posttreatment head and neck malignancies, as determined by its ability to predict locoregional recurrence or progression after imaging. The electronic medical records of patients who had posttreatment PET/MR imaging studies were reviewed, and after applying the exclusion criteria, we retrospectively included 46 studies. PET/MR imaging studies were independently reviewed by 2 neuroradiologists, who recorded scores based on the Neck Imaging Reporting and Data System (using CT/PET-CT criteria) for the diagnostic MR imaging sequences alone and the combined PET/MR imaging. Treatment failure was determined with either biopsy pathology or initiation of new treatment. Statistical analyses including univariate association, interobserver agreement, and receiver operating characteristic analysis were performed. There was substantial interreader agreement among PET/MR imaging scores (κ = 0.634; 95% CI, 0.605-0.663). PET/MR imaging scores showed a strong association with treatment failure by univariate association analysis, with P < .001 for the primary site, neck lymph nodes, and combined sites. Receiver operating characteristic curves of PET/MR imaging scores versus treatment failure indicated statistically significant diagnostic accuracy (area under curve range, 0.864-0.987; P < .001). Simultaneous PET/MR imaging has excellent discriminatory performance for treatment outcomes of head and neck malignancy when the Neck Imaging Reporting and Data System is applied. PET/MR imaging could play an important role in surveillance imaging for head and neck cancer.

Patterns of Hematologic Function and Cytokine Release Syndrome Severity in ALL Patients Receiving CAR-T and TCR-T Therapies Using Pooled Clinical Trial Data

Background:Despite the potential for durable disease remission seen with Chimeric Antigen Receptor (CAR-T) and T-Cell Receptor (TCR-T) therapies, their use is limited by the potential for acute toxicity from Cytokine-Release Syndrome (CRS).Across all grades, CRS has seen rates as high as 100% in some trials of patients receiving CAR-T, and up to 15% receiving TCR-T. Prior research indicates an association of hematologic abnormalities with CRS. Due to smaller average trial size and limited adoption, to date, of CAR and TCR therapies, there have been no large-scale studies to date exploring these associations with CRS severity in a wide range of patients across treatment types. This study sought to address these evidence gaps using retrospective analysis of pooled clinical trial data in Acute Lymphocytic Leukemia (ALL), using, to our knowledge, the single largest data repository of of CAR-T and TCR-T clinical patient data, with high resolution measurements across a spectrum of clinical domains.Methods:Eligible Phase I, II and III completed clinical trials in Acute Lymphocytic Leukemia (ALL), with patients receiving either CAR-T or TCR-T, were identified from the Medidata Enterprise Data Store, which comprises over 22,000 historical clinical trials, for de-identified retrospective aggregate analyses. Baseline characteristics, including demographics, medical history, prior treatment regimens were assessed and stratified by treatment type. Pre-trial history of hematologic conditions, such as neutropenia and anemia, were also assessed. Using Common Terminology Criteria for Adverse Events (CTCAE) 4.03, patients were assigned to categories of any CRS, mild CRS (grade 1) and moderate-to-severe CRS (2+). Hematologic function was assessed at baseline through first exposure to treatment, including counts of erythrocytes, neutrophils, eosinophils and basophils. Baseline marrow blast cell percentage was assessed as a marker of tumor burden. Univariate analyses of associations between pre-treatment baseline variables and CRS were conducted using Wilcoxon signed rank tests.Results:The pooled CT data contained 1,410 ALL patients, of whom over 60% were 18 year of age or greater. Baseline blood chemistries indicated 21% with anemia, 12% with thrombocytopenia, 6% neutropenic and 5.3% with elevated LDH. Although CAR-T patients accounted for 14.9% of the cohort, 47% of CRS events observed were associated with CAR-T treatment. In line with expectations from prior literature, factors associated with moderate-to-severe CRS included prior history of anemia, reduced platelet levels, low neutrophil counts, and delayed neutrophil recovery. Nearly all cases of moderate-to-severe CRS occurred in subjects exhibiting both low neutrophil and low platelet counts (Figure 1). Similar associations were seen in patients with pretreatment history of anemia (Figure 2). Consistent with literature on tumor burden and CRS, patients without CRS tended to have lower marrow blast percentages. Lymphocyte levels at baseline were far lower in patients receiving CAR-T therapy, with slower recovery than in patients receiving TCR-T. While consistent with CAR-T pre-treatment lymphodepletion, this finding was noteworthy given the association of neutropenia with CRS.Conclusions:Overall findings suggest patterns of routine hematologic function at baseline can potentially be used to assess risk of moderate-to-severe CRS in patients receiving CAR-T and TCR-T agents. The association with these markers could also suggest a mechanism of CRS as a function of tumor cell concentration, modified by the strength and presence of innate immunity mechanisms such as granulocytes, and potentially mediated by intermediates such as macrophages, in line with emerging literature., Further analysis may facilitate development of predictive algorithms to identify patients at greater risk for severe CRS prior to as well as shortly after treatment. This has implications for enhancing supportive care for patients receiving CAR- and TCR therapies. Additionally, a data-driven stratification of patients by risk of CRS will allow improved utilization and management of care resources. [Display omitted] DisclosuresAgarwal: Medidata Acorn AI, a Dassault Systèmes Company: Current Employment. Socolov: Medidata Acorn AI, a Dassault Systèmes Company: Current Employment. Buderi: Medidata Acorn AI, a Dassault Systèmes Company: Current Employment. Rusli: Medidata Acorn AI, a Dassault Systèmes Company: Current Employment. Bouzit: Medidata Acorn AI, a Dassault Systèmes Company: Current Employment. Talwai: Medidata Acorn AI, a Dassault Systèmes Company: Current Employment. Itzkovich: Medidata Acorn AI, a Dassault Systèmes Company: Current Employment. Galaznik: Medidata Acorn AI, a Dassault Systèmes Company: Current Employment, Current equity holder in publicly-traded company. Aptekar: Medidata Acorn AI, a Dassault Systèmes Company: Current Employment.

Total Laparoscopic Hysterectomy – Analysis of Learning Points & Complications over a Span of Two Decades.

Study Objective 1. Analysis of learning curve for Total laparoscopic hysterectomy (TLH); 2. Comparison of complication rates of 773 TLH between 1st & 2nd decade. Design Retrospective comparative analysis of prospectively collected data (Canadian Task force II – 2). Setting Centre for Endoscopic Surgery. Patients or Participants Total 773 patients posted for TLH over 20-years (2000-2019) for benign pathology excluding malignancy, anesthetic unfit and pelvic organ prolapse cases. Interventions Total Laparoscopic Hysterectomy with or without Bilateral Salpingo-oophorectomy. Measurements and Main Results All cases were divided into initial 10-years (group-I) of 386 cases and later 10-years (group-II) of 387 cases. No difference found in patient's demographic characteristic between first and second group. Analysis was done from prospectively collected data from outpatient and inpatient records elucidated in a structure pre-set protocol. Intra-operative variants were reviewed from real time video graphic records. Statistical method used, mean and standard deviation for operating time. P value for statistical significance. Chi-square test & Student t-test for continuous and categorical variables. Odd Ratio, univariate & multivariate logistic regression analysis for association. Significant reduction in mean operative-time was observed in first 125 to 250th case of TLH (p=0.001) which reflects the impact of learning. Comparison between group-I and group-II revealed significant reduction in major and minor complication rate from 3.35% to 1.03% (p=0.0277) and 1.81% to 0.25% (p = 0.033) respectively. The bladder complication in group-I and II were 8 & 2 respectively and only group-I had 4 ureteric and 1 bowel injury. Conversion rate was 7.3% throughout where endometriosis, 2 previous LSCS & bowel adhesions emerged as the strongest predictors of conversion with OR=6.72, 4.71 & 2.57 respectively. Conclusion Appropriate supervised training and increased experience after learning curve leads to marked reduction in operative time and complication rates of TLH. Conversion rate is independent of experience. 1. Analysis of learning curve for Total laparoscopic hysterectomy (TLH); 2. Comparison of complication rates of 773 TLH between 1st & 2nd decade. Retrospective comparative analysis of prospectively collected data (Canadian Task force II – 2). Centre for Endoscopic Surgery. Total 773 patients posted for TLH over 20-years (2000-2019) for benign pathology excluding malignancy, anesthetic unfit and pelvic organ prolapse cases. Total Laparoscopic Hysterectomy with or without Bilateral Salpingo-oophorectomy. All cases were divided into initial 10-years (group-I) of 386 cases and later 10-years (group-II) of 387 cases. No difference found in patient's demographic characteristic between first and second group. Analysis was done from prospectively collected data from outpatient and inpatient records elucidated in a structure pre-set protocol. Intra-operative variants were reviewed from real time video graphic records. Statistical method used, mean and standard deviation for operating time. P value for statistical significance. Chi-square test & Student t-test for continuous and categorical variables. Odd Ratio, univariate & multivariate logistic regression analysis for association. Significant reduction in mean operative-time was observed in first 125 to 250th case of TLH (p=0.001) which reflects the impact of learning. Comparison between group-I and group-II revealed significant reduction in major and minor complication rate from 3.35% to 1.03% (p=0.0277) and 1.81% to 0.25% (p = 0.033) respectively. The bladder complication in group-I and II were 8 & 2 respectively and only group-I had 4 ureteric and 1 bowel injury. Conversion rate was 7.3% throughout where endometriosis, 2 previous LSCS & bowel adhesions emerged as the strongest predictors of conversion with OR=6.72, 4.71 & 2.57 respectively. Appropriate supervised training and increased experience after learning curve leads to marked reduction in operative time and complication rates of TLH. Conversion rate is independent of experience.

Association Between PDL1 Genetic Variation and Efficacy of Apatinib Monotherapy in Patients with Previously Treated Advanced NSCLC: A Real-World Retrospective Study.

BackgroundThis study aimed to explore associations between PDL1 polymorphisms and efficacy of apatinib for patients with previously treated advanced non–small cell lung cancer (NSCLC) in a real-world setting.MethodsWe retrospectively recruited 148 patients with previously treated advanced NSCLC from January 2015 to December 2019 continuously. Clinical efficacy in patients receiving apatinib treatment was evaluated. Adverse reactions were documented during treatment. Biological specimens of peripheral blood and cancer tissue biopsies were obtained for the genotyping of genetic variations in PDL1 and corresponding gene-mRNA expression, respectively. Univariate association analysis between the status of PDL1 genetic variations and survival was performed with Kaplan–Meier survival analysis.ResultsThe objective response rate of the 148 patients was 17.6% and disease-control rate 68.9%. Prognostic data suggested that median progression-free survival (PFS) was 3.8 (95% CI 3.13–4.47) months and median overall survival (OS) 10.5 (95% CI 9.06–11.95) months. Regarding PDL1 genetic variation, only rs2297136 was of clinical significance. Prognosis analysis revealed that PFS and OS for the rs2297136 genotype were significantly different. Median PFS of patients with TC/CC and TT genotypes was 3 and 4.5 months, respectively (P=0.006). Median OS of the two genotypes was 9 and 11.6 months, respectively (P=0.04). Furthermore, the safety profile suggested that the most common adverse reactions were hypertension, dermal toxicity, fatigue, and oral toxicity. This study failed to find any significant association between adverse reactions and rs2297136. Interestingly, mRNA-expression analysis demonstrated that mRNA expression of PDL1 in biopsy cancer–tissue specimens was significantly different based on rs2297136-genotype status (P<0.001).ConclusionThe PDL1 polymorphism rs2297136 could be used as a potential biomarker for the prognosis of patients with NSCLC receiving apatinib monotherapy.