Plasma Concentration of 36 (Poly)phenols and Prospective Body Weight Change in Participants from the EPIC Cohort.

INTRODUCTION: Dietary intake of (poly)phenols has been linked to reduced adiposity and body weight (BW) in several epidemiological studies. However, epidemiological evidence on (poly)phenol biomarkers, particularly plasma concentrations, is scarce. We aimed to investigate the associations between plasma (poly)phenols and prospective BW change in participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: This study included 761 participants with data on BW at baseline and after 5 years of follow-up. Plasma concentrations of 36 (poly)phenols were measured at baseline using liquid chromatography-tandem mass spectrometry. Associations were assessed through general linear mixed models and multinomial logistic regression models, using change in BW as a continuous or as a categorical variable (BW loss, maintenance, gain), respectively. Plasma (poly)phenols were assessed as log2-transformed continuous variables. The false discovery rate (FDR) was used to control for multiple comparisons. RESULTS: Doubling plasma (poly)phenol concentrations showed a borderline trend towards a positive association with BW loss. Plasma vanillic acid showed the strongest association (-0.53 kg/5 years; 95% confidence interval [CI]: -0.99, -0.07). Similar results were observed for plasma naringenin comparing BW loss versus BW maintenance (odds ratio: 1.1; 95% CI: 1.0, 1.2). These results did not remain significant after FDR correction. CONCLUSION: Higher concentrations of plasma (poly)phenols suggested a tendency towards 5-year BW maintenance or loss. While certain associations seemed promising, they did not withstand FDR correction, indicating the need for caution in interpreting these results. Further studies using (poly)phenol biomarkers are needed to confirm these suggestive protective trends.

Hospitalization and Mortality among Black Patients and White Patients with Covid-19.

BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19-positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19-positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.

Impact of presenting stroke severity and thrombolysis on outcomes following urgent carotid interventions.

BACKGROUND: Carotid interventions are increasingly performed in select patients following acute stroke. We aimed to determine the effects of presenting stroke severity (National Institutes of Health Stroke Scale [NIHSS]) and use of systemic thrombolysis (tissue plasminogen activator [tPA]) on discharge neurological outcomes (modified Rankin scale [mRS]) after urgent carotid endarterectomy (uCEA) and urgent carotid artery stenting (uCAS). METHODS: Patients undergoing uCEA/uCAS at a tertiary Comprehensive Stroke Center (January 2015 to May 2022) were divided into two cohorts: (1) no thrombolysis (uCEA/uCAS only) and (2) use of thrombolysis before the carotid intervention (tPA + uCEA/uCAS). Outcomes were discharge mRS and 30-day complications. Regression models were used to determine an association between tPA use and presenting stroke severity (NIHSS) and discharge neurological outcomes (mRS). RESULTS: Two hundred thirty-eight patients underwent uCEA/uCAS (uCEA/uCAS only, n = 186; tPA + uCEA/uCAS, n = 52) over 7 years. In the thrombolysis cohort compared with the uCEA/uCAS only cohort, the mean presenting stroke severity was higher (NIHSS = 7.6 vs 3.8; P = .001), and more patients presented with moderate to severe strokes (57.7% vs 30.2% with NIHSS >4). The 30-day stroke, death, and myocardial infarction rates in the uCEA/uCAS only vs tPA + uCEA/uCAS were 8.1% vs 11.5% (P = .416), 0% vs 9.6% (P < .001), and 0.5% vs 1.9% (P = .39), respectively. The 30-day stroke/hemorrhagic conversion and myocardial infarction rates did not differ with tPA use; however, the difference in deaths was significantly higher in the tPA + uCEA/uCAS cohort (P < .001). There was no difference in neurological functional outcome with or without thrombolysis use (mean mRS, 2.1 vs 1.7; P = .061). For both minor strokes (NIHSS ≤4 vs NIHSS >4: relative risk, 1.58 vs 1.58, tPA vs no tPA, respectively, P = .997) and moderate strokes (NIHSS ≤10 vs NIHSS >10: relative risk, 1.94 vs 2.08, tPA vs no tPA, respectively; P = .891), the likelihood of discharge functional independence (mRS score of ≤2) was not influenced by tPA. CONCLUSIONS: Patients with a higher presenting stroke severity (NIHSS) had worse neurological functional outcomes (mRS). Patients presenting with minor and moderate strokes were more likely to have discharge neurological functional independence (mRS of ≤2), regardless of whether they received tPA or not. Overall, presenting NIHSS is predictive of discharge neurological functional autonomy and is not influenced by the use of thrombolysis.

Telehealth and Medicare Type 2 Diabetes Care Outcomes: Evidence From Louisiana.

BACKGROUND: At the onset of the COVID-19 pandemic, the Centers for Medicare and Medicaid Services broadened access to telehealth. This provided an opportunity to test whether diabetes, a risk factor for COVID-19 severity, can be managed with telehealth services. OBJECTIVE: The objective of this study was to examine the impacts of telehealth on diabetes control. RESEARCH DESIGN: A doubly robust estimator combined a propensity score-weighting strategy with regression controls for baseline characteristics using electronic medical records data to compare outcomes in patients with and without telehealth care. Matching on preperiod trajectories in outpatient visits and weighting by odds were used to ensure comparability between comparators. SUBJECTS: Medicare patients with type 2 diabetes in Louisiana between March 2018 and February 2021 (9530 patients with a COVID-19 era telehealth visit and 20,666 patients without one). MEASURES: Primary outcomes were glycemic levels and control [ie, hemoglobin A1c (HbA1c) under 7%]. Secondary outcomes included alternative HbA1c measures, emergency department visits, and inpatient admissions. RESULTS: Telehealth was associated with lower pandemic era mean A1c values [estimate=-0.080%, 95% confidence interval (CI): -0.111% to -0.048%], which translated to an increased likelihood of having HbA1c in control (estimate=0.013; 95% CI: 0.002-0.024; P<0.023). Hispanic telehealth users had relatively higher COVID-19 era HbA1c levels (estimate=0.125; 95% CI: 0.044-0.205; P<0.003). Telehealth was not associated with differences in the likelihood of having an emergency department visits (estimate=-0.003; 95% CI: -0.011 to 0.004; P<0.351) but was associated with more the likelihood of having an inpatient admission (estimate=0.024; 95% CI: 0.018-0.031; P<0.001). CONCLUSION: Telehealth use among Medicare patients with type 2 diabetes in Louisiana stemming from the COVID-19 pandemic was associated with relatively improved glycemic control.

The Impact of Reimbursement for Non-Face-to-Face Chronic Care Management on Comprehensive Metabolic Biomarkers Among Multimorbid Patients With Type 2 Diabetes.

AIMS: We evaluated the impact of reimbursement for non-face-to-face chronic care management (NFFCCM) on comprehensive metabolic risk factors among multimorbid Medicare beneficiaries with type 2 diabetes in Louisiana. MATERIALS AND METHODS: We implemented a propensity score method to obtain comparable treatment (n=1501 with NFFCCM) and control (n=17,524 without NFFCCM) groups. Patients with type 2 diabetes were extracted from the electronic health records stored in REACHnet. The study period was from 2013 to February 2020. The comprehensive metabolic risk factors included the primary outcome of glycated hemoglobin (HbA1c) (as the primary outcome) and the secondary outcomes of body mass index (BMI), systolic blood pressure (BP), and low-density lipoprotein cholesterol. RESULTS: Receiving any NFFCCM was associated with improvement in all outcomes measures: a reduction in HbA1c of 0.063% (95% CI: 0.031%-0.094%; P <0.001), a reduction in BMI of 0.155 kg/m 2 (95% CI: 0.029-0.282 kg/m 2 ; P =0.016), a reduction in systolic BP of 0.816 mm Hg (95% CI: 0.469-1.163 mm Hg; P <0.001), and a reduction in low-density lipoprotein cholesterol of 1.779 mg/dL (95% CI: 0.988 2.570 mg/dL; P <0.001). Compared with the control group, the treatment group had 1.6% more patients with HbA1c <7% (95% CI: 0.3%-2.9%; P =0.013). CONCLUSIONS: Patients with diabetes in Louisiana receiving NFFCCM experienced better control of HbA1c, BMI, BP, and low-density lipoprotein outcomes.

COVID-19 bacteremic co-infection is a major risk factor for mortality, ICU admission, and mechanical ventilation.

BACKGROUND: Recent single-center reports have suggested that community-acquired bacteremic co-infection in the context of Coronavirus disease 2019 (COVID-19) may be an important driver of mortality; however, these reports have not been validated with a multicenter, demographically diverse, cohort study with data spanning the pandemic. METHODS: In this multicenter, retrospective cohort study, inpatient encounters were assessed for COVID-19 with community-acquired bacteremic co-infection using 48-h post-admission blood cultures and grouped by: (1) confirmed co-infection [recovery of bacterial pathogen], (2) suspected co-infection [negative culture with ≥ 2 antimicrobials administered], and (3) no evidence of co-infection [no culture]. The primary outcomes were in-hospital mortality, ICU admission, and mechanical ventilation. COVID-19 bacterial co-infection risk factors and impact on primary outcomes were determined using multivariate logistic regressions and expressed as adjusted odds ratios with 95% confidence intervals (Cohort, OR 95% CI, Wald test p value). RESULTS: The studied cohorts included 13,781 COVID-19 inpatient encounters from 2020 to 2022 in the University of Alabama at Birmingham (UAB, n = 4075) and Ochsner Louisiana State University Health-Shreveport (OLHS, n = 9706) cohorts with confirmed (2.5%), suspected (46%), or no community-acquired bacterial co-infection (51.5%) and a comparison cohort consisting of 99,170 inpatient encounters from 2010 to 2019 (UAB pre-COVID-19 pandemic cohort). Significantly increased likelihood of COVID-19 bacterial co-infection was observed in patients with elevated ≥ 15 neutrophil-to-lymphocyte ratio (UAB: 1.95 [1.21-3.07]; OLHS: 3.65 [2.66-5.05], p < 0.001 for both) within 48-h of hospital admission. Bacterial co-infection was found to confer the greatest increased risk for in-hospital mortality (UAB: 3.07 [2.42-5.46]; OLHS: 4.05 [2.29-6.97], p < 0.001 for both), ICU admission (UAB: 4.47 [2.87-7.09], OLHS: 2.65 [2.00-3.48], p < 0.001 for both), and mechanical ventilation (UAB: 3.84 [2.21-6.12]; OLHS: 2.75 [1.87-3.92], p < 0.001 for both) across both cohorts, as compared to other risk factors for severe disease. Observed mortality in COVID-19 bacterial co-infection (24%) dramatically exceeds the mortality rate associated with community-acquired bacteremia in pre-COVID-19 pandemic inpatients (5.9%) and was consistent across alpha, delta, and omicron SARS-CoV-2 variants. CONCLUSIONS: Elevated neutrophil-to-lymphocyte ratio is a prognostic indicator of COVID-19 bacterial co-infection within 48-h of admission. Community-acquired bacterial co-infection, as defined by blood culture-positive results, confers greater increased risk of in-hospital mortality, ICU admission, and mechanical ventilation than previously described risk factors (advanced age, select comorbidities, male sex) for COVID-19 mortality, and is independent of SARS-CoV-2 variant.

Clopidogrel resistance is common in patients undergoing vascular and coronary interventions.

OBJECTIVES: "Clopidogrel resistance," also defined as heightened platelet reactivity (HPR) while on clopidogrel therapy, may lead to a sub-optimal antiplatelet effect and a potential thrombotic event. There is limited literature addressing the prevalence of HPR in a large cohort of patients receiving either coronary or endovascular interventions. METHODS: In a large integrated healthcare system, patients with a P2Y12 reaction units (PRU) test were identified. HPR was defined as a PRU ≥ 200 during clopidogrel therapy. Vascular and coronary interventions were identified utilizing CPT codes, HPR prevalence was calculated, and Fischer's exact test was used to determine significance. RESULTS: From an initial cohort of 2,405,957 patients (October 2014 to January 2020), we identified 3301 patients with PRU tests administered. Of these, 1789 tests had a PRU ≥ 200 (HPR overall prevalence, 54%). We then identified 1195 patients who underwent either an endovascular or coronary procedure and had a PRU measurement. This corresponded to 935 coronary and 260 endovascular interventions. In the coronary cohort, the HPR prevalence was 54% (503/935). In the vascular cohort, the HPR prevalence was 53% (137/260); there was no difference between cohorts in HPR prevalence (p = 0.78). CONCLUSION: "Clopidogrel resistance" or HPR was found to be present in nearly half of patients with cardiovascular disease undergoing intervention. Our data suggest HPR is more common in the cardiovascular patient population than previously appreciated. Evaluating patients for HPR is both inexpensive ($25) and rapid (< 10 min). Future randomized studies are warranted to determine whether HPR has a clinically detectable effect on revascularization outcomes.

Unexpected Term Neonatal Intensive Care Unit Admissions and a Potential Role for Centralized Remote Fetal Monitoring.

OBJECTIVE: Centralized remote fetal monitoring (CRFM) has been proposed as a method to improve the performance of intrapartum fetal heart rate (FHR) monitoring and perinatal outcomes. The purpose of this study is to determine whether CRFM was associated with a reduction in unexpected term neonatal intensive care unit (NICU) admissions. STUDY DESIGN: A pre-post design was used to examine the effectiveness of CRFM which was implemented in stages across five hospitals. The exposure group was all women who underwent intrapartum monitoring via CRFM. The unexposed group was of women who delivered at the same hospitals prior to implementation of CRFM. Pregnancies with expected NICU admissions, gestational age <37 weeks, birth weight <2,500 g, or major fetal anomalies detected prenatally were excluded. The primary outcome was unexpected term NICU admission; secondary outcomes were cesarean and operative vaginal delivery (OVD), and 5-minute Apgar's score of <7 rates. Maternal and delivery characteristics were examined with Student's t, Wilcoxon's, Chi-square, and Fisher's exact tests. Multivariable logistic regression was performed to control for potential confounders. RESULTS: There were 19,392 live births included in this analysis. In the univariable analysis, the odds of unexpected term NICU admission was lower among the CRFM exposed group compared with the unexposed group (odds ratio [OR] = 0.86, 95% confidence interval [CI]: 0.75-0.99; p = 0.038). In multivariable analysis, this did not reach statistical significance (OR = 0.92, 95% CI: 0.79-1.06; p = 0.24). Cesarean and OVD were less likely in the exposed group (OR = 0.91, 95% CI: 0.85-0.97; p = 0.008) and (OR = 0.70, 95% CI: 0.59-0.83, p < 0.001), respectively, in univariable analysis. When adjusted for potential confounders, the effect remained statistically significant for cesarean delivery (OR = 0.92, 95% CI: 0.85-0.98; p = 0.012). When adjusted for hospital, OVD rate was lower at the highest volume and highest acuity site (OR = 0.48, 95% CI: 0.36-0.65, p < 0.001). CONCLUSION: In some practice settings, utilization of a CRFM system may decrease the risk of unexpected term NICU admission, cesarean, and OVD rate. KEY POINTS: · CRFM may decrease unexpected term NICU admissions in some clinical settings.. · CRFM may decrease cesarean delivery rates in some clinical settings.. · CRFM may decrease OVD rates in some clinical settings..

PD-1 expression in hepatocellular carcinoma predicts liver-directed therapy response and bridge-to-transplant survival.

BACKGROUND: Hepatocellular carcinoma (HCC) patients undergo liver-directed therapy (LDT) to control tumor burden while awaiting liver transplantation with response impacting waitlist survival. In this study, we investigate the link between absolute lymphocyte count (ALC) and PD-1 expression with response to LDT and bridge-to-transplant survival. METHODS: Treatment-naïve HCC patients (n = 86) undergoing LDT were enrolled at a single center from August 2016-March 2020. Response to LDT was determined using mRECIST. Blood samples were collected on the day of LDT and at follow-up. Cells were analyzed for phenotype by flow cytometry. Outcomes were liver transplantation or tumor progression. RESULTS: Incomplete response to initial LDT was associated with tumor progression precluding liver transplantation (OR: 7.6, 1.7 - 33.3, P < 0.001). Univariate analysis of baseline T cell phenotypes revealed ALC (OR: 0.44, 0.24-0.85, P = 0.009) as well as intermediate expression of PD-1 on CD4 (OR: 3.3, 1.03-10.3, P = 0.034) and CD8 T cells (OR: 3.0, 0.99-8.8 P = 0.043) associated with incomplete response to LDT. Elevations in PD-1 expression were associated with increased risk of bridge-to-transplant tumor progression (HR: 3.2, 1.2-9.4). In patients successfully bridged to liver transplantation, pre-treatment peripheral PD-1 profile was associated with advanced tumor staging (P < 0.005) with 2/4 of patients with elevations in PD-1 having T3-T4 TNM staging compared to 0 with low PD-1 expression. CONCLUSION: Low lymphocyte count or elevated expression of the PD-1 checkpoint inhibitor is associated with incomplete response to LDT and increased risk of bridge-to-transplant tumor progression. Patients with impaired T cell homeostasis may benefit from PD-1 immunotherapy to improve response to LDT and improve bridge-to-transplant outcomes.

Neurologic outcomes of carotid and other emergent interventions for ischemic stroke over 6 years with dataset enhanced by machine learning.

BACKGROUND: The current mainstays of ischemic stroke treatment include the use of thrombolysis (tissue plasminogen activator [tPA]), urgent carotid endarterectomy (uCEA) or urgent carotid artery stenting (uCAS), and mechanical endovascular reperfusion/thrombectomy (MER). Scarce data describe the presenting stroke severity and neurologic outcomes for these acute ischemic stroke interventions, alone or in combination. The authors hypothesize that patients undergoing carotid interventions experience better functional neurologic outcomes than other stroke interventions. METHODS: A comprehensive stroke center dataset was combined with data for stroke-related procedures, comorbidities, complications, and physician documentation collected from electronic medical record data. A total of 10,975 patient encounter records from January 1, 2015, through July 31, 2021, were retrieved. The presenting stroke severity was determined by vascular/stroke neurologists using the National Institutes of Health Stroke Scale (NIHSS). Functional neurologic outcomes were reported using the modified Rankin scale (mRS) score, which quantifies the degree of neurologic disability. Because mRS values were only available for 3627 encounters in the original dataset, the authors developed a machine learning algorithm to analyze physician documentation and assign an mRS value. After the exclusion and machine learning analysis, a total of 5170 patient encounters were included for statistical analysis. Statistical analyses included the χ2 test, one-way analysis of variance and logistic regression on 30-day complications, stroke severity, and neurologic outcomes. RESULTS: Patients were divided into five cohorts: (1) uCEA or uCAS (n = 189), (2) tPA alone (n = 1053), (3) MER alone (n = 418), (4) tPA + MER (n = 199), and (5) no intervention (n = 3311). Patients undergoing uCEA/uCAS were significantly more likely to be male, smokers, and have a history of peripheral arterial disease compared with other stroke cohorts. The length of stay was shortest for patients who only received tPA or no intervention (6 days), followed by uCEA/uCAS (7.2 days), MER (10.2 days), and tPA + MER (8.8 days) cohorts (P < .001). The 30-day mortality was highest in the MER cohort (12.2%) and lowest in the uCEA/uCAS cohort (2.6%). The uCEA/uCAS cohort compared with other cohorts had the lowest presenting stroke severity (NIHSS 4.9 vs NIHSS 6.9-16.0), and best neurologic outcomes (mRS 1.7 vs mRS 1.8-2.6). CONCLUSIONS: After an ischemic stroke, patients undergoing urgent carotid interventions had the lowest presenting stroke severity (NIHSS) and highest rate of independent neurologic outcomes (mRS) compared with other stroke interventions. Incoming stroke severity correlates with functional neurologic outcomes, and patients who present with an NIHSS of 10 or less who undergo uCEA/uCAS have a high likelihood of independent neurologic functional outcome (mRS of ≤2).

Racial and Workplace Disparities in Seroprevalence of SARS-CoV-2, Baton Rouge, Louisiana, USA.

By using paired molecular and antibody testing for severe acute respiratory syndrome coronavirus 2 infection, we determined point prevalence and seroprevalence in Louisiana, USA, during the second phase of reopening. Infections were highly variable by race and ethnicity, work environment, and ZIP code. Census-weighted seroprevalence was 3.6%, and point prevalence was 3.0%.

Rapid progression of carotid stenosis was rare in a large integrated healthcare system during an eight-year period.

OBJECTIVE: Few studies have evaluated the rapid progression of carotid stenosis on a large scale. We created a custom software algorithm to analyze an electronic medical record database to examine the natural progression of carotid stenosis, identify a subset of patients with rapid progression, and evaluate the specific patient risk factors associated with this rapid progression. METHODS: Patients in a large integrated healthcare system who had undergone two or more carotid ultrasound scans from August 2010 to August 2018 were identified. We did not distinguish between those with an established carotid stenosis diagnosis and those with a screening ultrasound scan. We used our novel algorithm to extract data from their carotid ultrasound reports. The degrees of carotid stenosis were categorized as follows: level 1, 0% to 39%; level 2, 40% to 59%; level 3, 60% to 79%; level 4, 80% to 99%; and level 5, complete occlusion. The primary endpoint was rapid vs slow progression of carotid stenosis, with rapid progression defined as an increase of two or more levels within any 18-month period of the study, regardless of the date of the initial ultrasound scan. The association of the demographic and clinical characteristics with rapid progression was assessed by univariable and multivariable logistic regression. RESULTS: From a cohort of 4.4 million patients, we identified 4982 patients with two or more carotid ultrasound scans and a median follow-up period of 13.1 months (range, 0.1-93.7 months). Of the 4982 patients, 879 (17.6%) had shown progression of carotid stenosis. Only 116 patients (2.3%) had had progression to level 4 (80%-99% stenosis) from any starting level during a median of 11.5 months. A total of 180 patients (3.6%) were identified as experiencing rapid progression during a median follow-up of 9.9 months. The final multivariable analysis showed that younger age (P < .01), white race (P = .02), lower body mass index (P = .01), a diagnosis of peripheral arterial disease (P = .03), and a diagnosis of transient ischemic attack (P < .01) were associated with rapid progression. CONCLUSIONS: Using a novel algorithm to extract data from >4 million patient records, we found that rapid progression of carotid stenosis appears to be rare. Although 17.6% of patients showed any degree of progression, only 3.6% had experienced rapid progression. Among those with any disease progression, 20.5% had experienced rapid progression. Although the overall incidence of rapid progression was low, patients with any progression might warrant close follow-up, especially if they have the associated risk factors for rapid progression. The custom software algorithm might be a powerful tool for creating and evaluating large datasets.

The Association Between Neighborhood Social Vulnerability and COVID-19 Testing, Positivity, and Incidence in Alabama and Louisiana.

Racial/ethnic and socioeconomic disparities in COVID-19 burden have been widely reported. Using data from the state health departments of Alabama and Louisiana aggregated to residential Census tracts, we assessed the relationship between social vulnerability and COVID-19 testing rates, test positivity, and incidence. Data were cumulative for the period of February 27, 2020 to October 7, 2020. We estimated the association of the 2018 Social Vulnerability Index (SVI) overall score and theme scores with COVID-19 tests, test positivity, and cases using multivariable negative binomial regressions. We adjusted for rurality with 2010 Rural-Urban Commuting Area codes. Regional effects were modeled as fixed effects of counties/parishes and state health department regions. The analytical sample included 1160 Alabama and 1105 Louisiana Census tracts. In both states, overall social vulnerability and vulnerability themes were significantly associated with increased COVID-19 case rates (RR 1.57, 95% CI 1.45-1.70 for Alabama; RR 1.36, 95% CI 1.26-1.46 for Louisiana). There was increased COVID-19 testing with higher overall vulnerability in Louisiana (RR 1.26, 95% CI 1.14-1.38), but not in Alabama (RR 0.95, 95% CI 0.89-1.02). Consequently, test positivity in Alabama was significantly associated with social vulnerability (RR 1.66, 95% CI 1.57-1.75), whereas no such relationship was observed in Louisiana (RR 1.05, 95% CI 0.98-1.12). Social vulnerability is a risk factor for COVID-19 infection, particularly among racial/ethnic minorities and those in disadvantaged housing conditions without transportation. Increased testing targeted to vulnerable communities may contribute to reduction in test positivity and overall COVID-19 disparities.

Seroprevalence of SARS-CoV-2 and Infection Fatality Ratio, Orleans and Jefferson Parishes, Louisiana, USA, May 2020.

Using a novel recruitment method and paired molecular and antibody testing for severe acute respiratory syndrome coronavirus 2 infection, we determined seroprevalence in a racially diverse municipality in Louisiana, USA. Infections were highly variable by ZIP code and differed by race/ethnicity. Overall census-weighted seroprevalence was 6.9%, and the calculated infection fatality ratio was 1.63%.

Validity of Cardiovascular Data From Electronic Sources: The Multi-Ethnic Study of Atherosclerosis and HealthLNK.

BACKGROUND: Understanding the validity of data from electronic data research networks is critical to national research initiatives and learning healthcare systems for cardiovascular care. Our goal was to evaluate the degree of agreement of electronic data research networks in comparison with data collected by standardized research approaches in a cohort study. METHODS: We linked individual-level data from MESA (Multi-Ethnic Study of Atherosclerosis), a community-based cohort, with HealthLNK, a 2006 to 2012 database of electronic health records from 6 Chicago health systems. To evaluate the correlation and agreement of blood pressure in HealthLNK in comparison with in-person MESA examinations, and body mass index in HealthLNK in comparison with MESA, we used Pearson correlation coefficients and Bland-Altman plots. Using diagnoses in MESA as the criterion standard, we calculated the performance of HealthLNK for hypertension, obesity, and diabetes mellitus diagnosis by using International Classification of Diseases, Ninth Revision codes and clinical data. We also identified potential myocardial infarctions, strokes, and heart failure events in HealthLNK and compared them with adjudicated events in MESA. RESULTS: Of the 1164 MESA participants enrolled at the Chicago Field Center, 802 (68.9%) participants had data in HealthLNK. The correlation was low for systolic blood pressure (0.39; P<0.0001). In comparison with MESA, HealthLNK overestimated systolic blood pressure by 6.5 mm Hg (95% confidence interval, 4.2-7.8). There was a high correlation between body mass index in MESA and HealthLNK (0.94; P<0.0001). HealthLNK underestimated body mass index by 0.3 kg/m2 (95% confidence interval, -0.4 to -0.1). With the use of International Classification of Diseases, Ninth Revision codes and clinical data, the sensitivity and specificity of HealthLNK queries for hypertension were 82.4% and 59.4%, for obesity were 73.0% and 89.8%, and for diabetes mellitus were 79.8% and 93.3%. In comparison with adjudicated cardiovascular events in MESA, the concordance rates for myocardial infarction, stroke, and heart failure were, respectively, 41.7% (5/12), 61.5% (8/13), and 62.5% (10/16). CONCLUSIONS: These findings illustrate the limitations and strengths of electronic data repositories in comparison with information collected by traditional standardized epidemiological approaches for the ascertainment of cardiovascular risk factors and events.

Lineage-specific regulation of PD-1 expression in early-stage hepatocellular carcinoma following 90yttrium transarterial radioembolization - Implications in treatment outcomes.

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths in the world. Liver-directed therapies, including 90Yttrium (90Y) radioembolization, play an integral role in the management of HCC with excellent response rates. This has led to clinical trials of immunotherapy in combination with 90Y. Elevated PD-1 expression and lymphopenia were recently shown as risk factors for disease progression in early-stage HCC treated with liver-directed therapies. The aim of this study was to investigate PD-1 expression dynamics in bridge/downstage to transplant in HCC patients receiving first-cycle 90Y and evaluate the impact of these changes on response rates and time-to-progression (TTP). METHODS: Patients with HCC receiving first-cycle 90Y as a bridge to liver transplantation (n = 99) were prospectively enrolled. Blood specimens were collected before 90Y and again during routine imagining follow-up to analyze PD-1 expression via flow cytometry. Complete and objective response rates (CR and ORR) were determined using mRECIST. RESULTS: In 84/88 patients with available follow-up imaging, 83% had a localized ORR with 63% having localized CR. For overall response, 71% and 54% experienced ORR and CR, respectively. Post-90Y PD-1 upregulation in CD8 + associated with HCC progression and decreased TTP. Treatment with 90Y was associated with an anticipated significant post-treatment drop in lymphocytes (P < 0.001) that was independent of PD-1 expression for either CD4+ or CD8+ T cells (P = 0.751 and P = 0.375) and not associated with TTP risk. The change in lymphocytes was not correlated with PD-1 expression following treatment nor TTP. CONCLUSIONS: Elevated PD-1 expression on peripheral T cells is associated with increased risk of HCC progression and shorter time to progression in bridging/downstaging to transplant HCC patients undergoing first-cycle 90Y. Treatment-induced lymphopenia was not associated with treatment response, or increased progression risk, suggesting this anticipated adverse event does not impact short-term HCC outcomes.

Imaging Delay Following Liver-Directed Therapy Increases Progression Risk in Early- to Intermediate-Stage Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths in the world. Patients with early-stage HCC are treated with liver-directed therapies to bridge or downstage for liver transplantation (LT). In this study, the impact of HCC care delay on HCC progression among early-stage patients was investigated. Early-stage HCC patients undergoing their first cycle of liver-directed therapy (LDT) for bridge/downstaging to LT between 04/2016 and 04/2022 were retrospectively analyzed. Baseline variables were analyzed for risk of disease progression and time to progression (TTP). HCC care delay was determined by the number of rescheduled appointments related to HCC care. The study cohort consisted of 316 patients who received first-cycle LDT. The HCC care no-show rate was associated with TTP (p = 0.004), while the overall no-show rate was not (p = 0.242). The HCC care no-show rate and HCC care delay were further expanded as no-show rates and rescheduled appointments for imaging, laboratory, and office visits, respectively. More than 60% of patients experienced HCC care delay for imaging and laboratory appointments compared to just 8% for office visits. Multivariate analysis revealed that HCC-specific no-show rates and HCC care delay for imaging (p < 0.001) were both independently associated with TTP, highlighting the importance of minimizing delays in early-stage HCC imaging surveillance to reduce disease progression risk.

A bioinformatic analysis of T-cell epitope diversity in SARS-CoV-2 variants: association with COVID-19 clinical severity in the United States population.

Long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the identification of T-cell epitopes affecting host immunogenicity. In this computational study, we explored the CD8+ epitope diversity estimated in 27 of the most common HLA-A and HLA-B alleles, representing most of the United States population. Analysis of 16 SARS-CoV-2 variants [B.1, Alpha (B.1.1.7), five Delta (AY.100, AY.25, AY.3, AY.3.1, AY.44), and nine Omicron (BA.1, BA.1.1, BA.2, BA.4, BA.5, BQ.1, BQ.1.1, XBB.1, XBB.1.5)] in analyzed MHC class I alleles revealed that SARS-CoV-2 CD8+ epitope conservation was estimated at 87.6%-96.5% in spike (S), 92.5%-99.6% in membrane (M), and 94.6%-99% in nucleocapsid (N). As the virus mutated, an increasing proportion of S epitopes experienced reduced predicted binding affinity: 70% of Omicron BQ.1-XBB.1.5 S epitopes experienced decreased predicted binding, as compared with ~3% and ~15% in the earlier strains Delta AY.100-AY.44 and Omicron BA.1-BA.5, respectively. Additionally, we identified several novel candidate HLA alleles that may be more susceptible to severe disease, notably HLA-A*32:01, HLA-A*26:01, and HLA-B*53:01, and relatively protected from disease, such as HLA-A*31:01, HLA-B*40:01, HLA-B*44:03, and HLA-B*57:01. Our findings support the hypothesis that viral genetic variation affecting CD8 T-cell epitope immunogenicity contributes to determining the clinical severity of acute COVID-19. Achieving long-term COVID-19 immunity will require an understanding of the relationship between T cells, SARS-CoV-2 variants, and host MHC class I genetics. This project is one of the first to explore the SARS-CoV-2 CD8+ epitope diversity that putatively impacts much of the United States population.

Pediatric Gastrointestinal Outcomes During the Post-Acute Phase of COVID-19.

Background: The impact of COVID-19 on gastrointestinal (GI) outcomes in children during the post-acute and chronic phases of the disease is not well understood. Methods: We conducted a retrospective cohort study across twenty-nine healthcare institutions from March 2020 to September 2023, including 413,455 pediatric patients with confirmed SARS-CoV-2 infection and 1,163,478 controls without infection. Infection was confirmed via polymerase chain reaction (PCR), serology, antigen tests, or clinical diagnosis of COVID-19 and related conditions. We examined the incidence of predefined GI symptoms and disorders during the post-acute (28 to 179 days post-infection) and chronic (180 to 729 days post-infection) phases. The adjusted risk ratios (aRRs) were calculated using stratified Poisson regression, with stratification based on propensity scores. Results: Our cohort comprised 1,576,933 patients, with females representing 48.0% of the sample. The analysis revealed that children with SARS-CoV-2 infection had an increased risk of developing at least one GI symptom or disorder in both the post-acute (8.64% vs. 6.85%; aRR 1.25, 95% CI 1.24-1.27) and chronic phases (12.60% vs. 9.47%; aRR 1.28, 95% CI 1.26-1.30) compared to uninfected peers. Specifically, the risk of abdominal pain was higher in COVID-19 positive patients during the post-acute phase (2.54% vs. 2.06%; aRR 1.14, 95% CI 1.11-1.17) and chronic phase (4.57% vs. 3.40%; aRR 1.24, 95% CI 1.22-1.27). Interpretation: Children with a history of SARS-CoV-2 infection are at an increased risk of GI symptoms and disorders during the post-acute and chronic phases of COVID-19. This highlights the need for ongoing monitoring and management of GI outcomes in this population.