Comparison of Sampson and extended Martin/Hopkins methods of low-density lipoprotein cholesterol calculations with direct measurement in pediatric patients with hypertriglyceridemia.

OBJECTIVE: The Friedewald equation is the commonly used method of low-density lipoprotein cholesterol (LDL-C) calculation, requiring reflex to direct LDL-C measurement when triglycerides (TG) ≥ 400 mg/dL. Recently formulated Sampson and extended Martin/Hopkins methods have been validated with TG up to 800 mg/dL and thus have the potential to replace direct LDL-C measurement. Given the growing prevalence of childhood dyslipidemia, the objective of this study was to compare Sampson and extended Martin/Hopkins methods of LDL-C calculation with the direct measurement in a pediatric cohort with 400 ≤ TG ≤ 799 mg/dL. METHODS: This study retrieved standard lipid panels and corresponding direct LDL-C measurements of 131 patients with 400 ≤ TG ≤ 799 mg/dL from a pediatric population. Following the application of Sampson and extended Martin/Hopkins calculations, calculated values were compared with direct LDL-C measurements using ordinary least squares linear regression analysis and bias plotting. RESULTS: Both Sampson and extended Martin/Hopkins LDL-C calculations exhibited a strong correlation with the direct measurements (Pearson r = 0.89) in patients with 400 ≤ TG ≤ 800 mg/dL. Average percentages of bias of 45% and 21% were found between the direct LDL-C measurements and Sampson or extended Martin/Hopkins calculations, respectively. CONCLUSION: Both Sampson and extended Martin/Hopkins calculations are applicable as clinical alternatives of direct LDL-C measurement in pediatric patients given 400 ≤ TG ≤ 799 mg/dL.

Post-acute sequelae of COVID-19 and longitudinal antibody levels in a community-based cohort.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection invokes variable immune responses and poses a risk of post-acute sequelae SARS-CoV-2 infection (PASC) symptoms; however, most data on natural history are derived from patients with severe infection. Further data are needed among patients with mild infection, who comprise most cases. METHODS: The Dallas Fort-Worth (DFW) COVID-19 Prevalence Study included 21,597 community-dwelling adults (ages 18-89) who underwent COVID-19 PCR and anti-nucleocapsid antibody testing between July 2020 and March 2021. We invited participants with positive COVID-19 results (cases) and a subset with negative results (controls), matched on age, sex, race/ethnicity, and ZIP code, to complete a follow-up questionnaire for PASC symptoms and repeat anti-nucleocapsid testing, and anti-spike antibody testing between July and December 2021. RESULTS: Of 3,917 adults invited to participate, 2260 (57.7%) completed the questionnaire- 1150 cases and 1110 controls. Persistent symptoms were reported in 21.1% of cases, with the most common being shortness of breath, fatigue, and loss of taste or smell. Among 292 cases with asymptomatic infection, >15% reported new fatigue and 8-10% reported new loss of taste/smell, myalgias, or headache. Median anti-nucleocapsid levels in cases decreased from 3.5U to 0.7U over a median follow-up of 8.6 months. Anti-spike antibody levels at 6-7 months post-vaccination in cases were similar to that of controls. CONCLUSIONS: More than 1 in 5 patients with COVID-19 infection, including those with mild infection, reported persistent symptoms during follow-up. Both nucleocapsid and spike protein antibody levels decreased within six months following a COVID-19 infection and vaccination.

Population-based correlates of COVID-19 infection: An analysis from the DFW COVID-19 prevalence study.

BACKGROUND: COVID-19 has resulted in over 1 million deaths in the U.S. as of June 2022, with continued surges after vaccine availability. Information on related attitudes and behaviors are needed to inform public health strategies. We aimed to estimate the prevalence of COVID-19, risk factors of infection, and related attitudes and behaviors in a racially, ethnically, and socioeconomically diverse urban population. METHODS: The DFW COVID-19 Prevalence Study Protocol 1 was conducted from July 2020 to March 2021 on a randomly selected sample of adults aged 18-89 years, living in Dallas or Tarrant Counties, Texas. Participants were asked to complete a 15-minute questionnaire and COVID-19 PCR and antibody testing. COVID-19 prevalence estimates were calculated with survey-weighted data. RESULTS: Of 2969 adults who completed the questionnaire (7.4% weighted response), 1772 (53.9% weighted) completed COVID-19 testing. Overall, 11.5% of adults had evidence of COVID-19 infection, with a higher prevalence among Hispanic and non-Hispanic Black persons, essential workers, those in low-income neighborhoods, and those with lower education attainment compared to their counterparts. We observed differences in attitudes and behaviors by race and ethnicity, with non-Hispanic White persons being less likely to believe in the importance of mask wearing, and racial and ethnic minorities more likely to attend social gatherings. CONCLUSION: Over 10% of an urban population was infected with COVID-19 early during the pandemic. Differences in attitudes and behaviors likely contribute to sociodemographic disparities in COVID-19 prevalence.

SARS-CoV-2 infection enhances mitochondrial PTP complex activity to perturb cardiac energetics.

SARS-CoV-2 is a newly identified coronavirus that causes the respiratory disease called coronavirus disease 2019 (COVID-19). With an urgent need for therapeutics, we lack a full understanding of the molecular basis of SARS-CoV-2-induced cellular damage and disease progression. Here, we conducted transcriptomic analysis of human PBMCs, identified significant changes in mitochondrial, ion channel, and protein quality-control gene products. SARS-CoV-2 proteins selectively target cellular organelle compartments, including the endoplasmic reticulum and mitochondria. M-protein, NSP6, ORF3A, ORF9C, and ORF10 bind to mitochondrial PTP complex components cyclophilin D, SPG-7, ANT, ATP synthase, and a previously undescribed CCDC58 (coiled-coil domain containing protein 58). Knockdown of CCDC58 or mPTP blocker cyclosporin A pretreatment enhances mitochondrial Ca2+ retention capacity and bioenergetics. SARS-CoV-2 infection exacerbates cardiomyocyte autophagy and promotes cell death that was suppressed by cyclosporin A treatment. Our findings reveal that SARS-CoV-2 viral proteins suppress cardiomyocyte mitochondrial function that disrupts cardiomyocyte Ca2+ cycling and cell viability.

Methods of Low-Density Lipoprotein-Cholesterol Measurement: Analytical and Clinical Applications.

Among the five major classes of lipoprotein particles, low-density lipoprotein-cholesterol (LDL-C) is the primary lipoprotein risk factor for the development of cardiovascular diseases (CVD) through the promotion of atherosclerotic pathogenesis. Therefore, it is of paramount importance to accurately measure the plasma concentration of LDL-C using an appropriate method to examine the risk of CVD and determine the efficacy of therapeutic interventions to reduce the cholesterol level and examine the risk assessment strategy. At present, there is a wide variety of methods available for LDL-C measurement. In this review, we have outlined the commonly used methods of LDL-C measurement. These methods have been classified into non-automated analytical methods, calculation methods, and automated direct measurement of LDL-C. We have also described some recently proposed promising calculation methods which are being considered for clinical adoption. This current review could assist the clinicians to have a better understanding regarding the measurement techniques and comparative utilities of different methods of LDL-C measurement and guide them to select an appropriate method based on accuracy, turnaround time, and cost of test.

Variability and Lability of Ammonia Levels in Healthy Volunteers and Patients With Cirrhosis: Implications for Trial Design and Clinical Practice.

INTRODUCTION: Ammonia levels are used to assess hepatic encephalopathy, but their levels are highly variable in clinical practice. METHODS: We studied factors associated with variation in ammonia values in cirrhotic patients without previous hepatic encephalopathy and healthy volunteers (HVs). RESULTS: Ammonia increased by 12% and 18% at 1 and 2 hour, respectively, after a protein meal in 64 cirrhotic patients (P < 0.001). In 237 HVs, ammonia levels varied significantly between sites (P < 0.0001). New site-specific ammonia upper limits based on HV levels using a strict analysis protocol differed from routinely used values. Correlation between paired fresh samples was high (r = 0.83) but modest between fresh and frozen samples (r = 0.62). DISCUSSION: Sample handling, processing, and protein intake impact ammonia levels across sites.

Unusual case of Epstein-Barr virus DNA tissue positive: blood negative in a patient with post-transplant lymphoproliferative disorder.

Detection of PTLD uses PCR to detect circulating EBV DNA in the blood or in situ hybridization to identify EBV DNA in tissue biopsies. EBV DNA was detected in the tissue section using both real-time PCR and in situ hybridization. We report an unusual presentation of PTLD with no detectable EBV DNA in the blood using EBER-1 and EBNA-1 PCR assays. This report suggests that the use of EBV-PCR for the early detection of PTLD in blood samples may not be 100% effective in detecting disease.

Virally induced CD4+ T cell depletion is not sufficient to induce AIDS in a natural host.

Peripheral blood CD4+ T cell counts are a key measure for assessing disease progression and need for antiretroviral therapy in HIV-infected patients. More recently, studies have demonstrated a dramatic depletion of mucosal CD4+ T cells during acute infection that is maintained during chronic pathogenic HIV as well as SIV infection. A different clinical disease course is observed during the infection of natural hosts of SIV infection, such as sooty mangabeys (Cercocebus atys), which typically do not progress to AIDS. Previous studies have determined that SIV+ mangabeys generally maintain healthy levels of CD4+ T cells despite having viral replication comparable to HIV-infected patients. In this study, we identify the emergence of a multitropic (R5/X4/R8-using) SIV infection after 43 or 71 wk postinfection in two mangabeys that is associated with an extreme, persistent (>5.5 years), and generalized loss of CD4+ T cells (5-80 cells/microl of blood) in the absence of clinical signs of AIDS. This study demonstrates that generalized CD4+ T cell depletion from the blood and mucosal tissues is not sufficient to induce AIDS in this natural host species. Rather, AIDS pathogenesis appears to be the cumulative result of multiple aberrant immunologic parameters that include CD4+ T cell depletion, generalized immune activation, and depletion/dysfunction of non-CD4+ T cells. Therefore, these data provide a rationale for investigating multifaceted therapeutic strategies to prevent progression to AIDS, even following dramatic CD4 depletion, such that HIV+ humans can survive normal life spans analogous to what occurs naturally in SIV+ mangabeys.