High-Sensitivity Troponin T and NT-proBNP Kinetics in Breast Cancer Chemotherapy.

BACKGROUND/AIMS: Doxorubicin (DOX) and trastuzumab (TRA) are associated with cardiac dysfunction. METHOD: High-sensitivity troponin T (hs-TnT) and brain natriuretic peptide attached to the amino acid N-terminal fragment in the prohormone (NT-proBNP) were measured before and on days +1, +2, +3, and +7 during cycles 1 and 2 of therapy with DOX or TRA in breast cancer patients. RESULTS: Five of eleven DOX-treated women, compared with 2/11 TRA-treated women, had undetectable baseline hs-TnT. By day +1 of cycle 2, all the DOX-treated women (p = 0.03) but only 7/11 TRA-treated women (p = ns) had detectible hs-TnT. Time to peak was 1-2 days for both groups. In the DOX-treated women, hs-TnT showed significant peaks from precycle baseline, increases in precycle 1 to precycle 2 levels, and a cycle 1 to cycle 2 peak and area under the curve (AUC). hs-TnT increased from precycle (1, 4.6 ± 6.3 pg/mL) to a cycle 2 peak of 16.1 ± 15.0 pg/mL (p < 0.002). No increases were seen with the TRA treatment. Transient posttreatment increases in NT-proBNP were seen after both therapies. CONCLUSION: DOX was associated with increased pretreatment baseline, peak, and AUC hs-TnT levels. Both DOX and TRA acutely perturb NT-proBNP. Assessment of pre- and posttreatment hs-TnT could be a means of quantifying cumulative myocardial injury in the course of chemotherapy.

Vitamin D effect on umbilical cord blood characteristics: a comparison between African Americans and Caucasians.

BACKGROUND: Umbilical cord blood (UCB) units collected from African Americans (AAs) have lower total nucleated cell (TNC) and CD34+ cell counts and are more likely to disqualify for banking compared to other ethnic groups. Furthermore, AAs have higher prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency. Given the importance of 25(OH)D in hematopoiesis, we examined the racial differences in UCB unit 25(OH)D content and its correlation with UCB cellular characteristics. STUDY DESIGN AND METHODS: A total of 119 UCB units that did not meet the TNC count banking criteria were analyzed. Fifty-one UCB units were collected from AA mothers and 68 from Caucasian mothers. We analyzed UCB volume, hematocrit (Hct), TNCs, mononuclear cells (MNCs), CD34+ cells, plasma 25(OH)D concentration, and progenitor clonogenic capacity measured by colony-forming cell (CFC) assay. RESULTS: Compared to Caucasians, AAs had significantly lower UCB 25(OH)D levels (p<0.0001), TNCs (p=0.002), MNCs (p=0.026), and CD34+ cells (p=0.026). Severe deficiency (25(OH)D<10 ng/mL) was only detected in AAs. No difference in median CFC count/10,000 MNCs was detected between AAs and Caucasians. Independent of race, a significant association was detected between 25(OH)D level and TNCs (r=0.193 p=0.035) and Hct (r=0.196 p=0.033). CONCLUSION: These results indicate the importance of 25(OH)D level as a racially independent predictor of UCB cellular characteristics and support further investigation of bioactive vitamin D and other predictors of hematopoiesis on cord blood quality.

Erratum: Neurofilament light chain and vaccination status associate with clinical outcomes in severe COVID-19.

[This corrects the article DOI: 10.1016/j.isci.2022.105272.].

Neurofilament light chain and vaccination status associate with clinical outcomes in severe COVID-19.

Blood neurofilament light chain (NFL) is proposed to serve as an estimate of disease severity in hospitalized patients with coronavirus disease 2019 (COVID-19). We show that NFL concentrations in plasma collected from 880 patients with COVID-19 within 5 days of hospital admission were elevated compared to controls. Higher plasma NFL associated with worse clinical outcomes including the need for mechanical ventilation, intensive care, prolonged hospitalization, and greater functional disability at discharge. No difference in the studied clinical outcomes between black/African American and white patients was found. Finally, vaccination associated with less disability at time of hospital discharge. In aggregate, our findings support the utility of measuring NFL shortly after hospital admission to estimate disease severity and show that race does not influence clinical outcomes caused by COVID-19 assuming equivalent access to care, and that vaccination may lessen the degree of COVID-19-caused disability.

Serum neurofilament light protein correlates with unfavorable clinical outcomes in hospitalized patients with COVID-19.

Brain imaging studies of patients with COVID-19 show evidence of macro- and microhemorrhagic lesions, multifocal white matter hyperintensities, and lesions consistent with posterior reversible leukoencephalopathy. Imaging studies, however, are subject to selection bias, and prospective studies are challenging to scale. Here, we evaluated whether serum neurofilament light chain (NFL), a neuroaxonal injury marker, could predict the extent of neuronal damage in a cohort of 142 hospitalized patients with COVID-19. NFL was elevated in the serum of patients with COVID-19 compared to healthy controls, including those without overt neurological manifestations. Higher NFL serum concentrations were associated with worse clinical outcomes. In 100 hospitalized patients with COVID-19 treated with remdesivir, a trend toward lower NFL serum concentrations was observed. These data suggest that patients with COVID-19 may experience neuroaxonal injury and may be at risk for long-term neurological sequelae. Neuroaxonal injury should be considered as an outcome in acute pharmacotherapeutic trials for COVID-19.

Deep vein thrombosis and pulmonary embolism among hospitalized coronavirus disease 2019-positive patients predicted for higher mortality and prolonged intensive care unit and hospital stays in a multisite healthcare system.

OBJECTIVE: We assessed the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients with coronavirus disease 2019 (COVID-19) compared with that in a matched cohort with similar cardiovascular risk factors and the effects of DVT and PE on the hospital course. METHODS: We performed a retrospective review of prospectively collected data from COVID-19 patients who had been hospitalized from March 11, 2020 to September 4, 2020. The patients were randomly matched in a 1:1 ratio by age, sex, hospital of admission, smoking history, diabetes mellitus, and coronary artery disease with a cohort of patients without COVID-19. The primary end point was the incidence of DVT/PE and the odds of developing DVT/PE using a conditional logistic regression model. The secondary end point was the hospitalization outcomes for COVID-19 patients with and without DVT/PE, including mortality, intensive care unit (ICU) admission, ICU stay, and length of hospitalization (LOH). Multivariable regression analysis was performed to identify the variables associated with mortality, ICU admission, discharge disposition, ICU duration, and LOH. RESULTS: A total of 13,310 patients had tested positive for COVID-19, 915 of whom (6.9%) had been hospitalized across our multisite health care system. The mean age of the hospitalized patients was 60.8 ± 17.0 years, and 396 (43.3%) were women. Of the 915 patients, 82 (9.0%) had had a diagnosis of DVT/PE confirmed by ultrasound examination of the extremities and/or computed tomography angiography of the chest. The odds of presenting with DVT/PE in the setting of COVID-19 infection was greater than that without COVID-19 infection (0.6% [5 of 915] vs 9.0% [82 of 915]; odds ratio [OR], 18; 95% confidence interval [CI], 8.0-51.2; P < .001). The vascular risk factors were not different between the COVID-19 patients with and without DVT/PE. Mortality (P = .02), the need for ICU stay (P < .001), duration of ICU stay (P < .001), and LOH (P < .001) were greater in the DVT/PE cohort than in the cohort without DVT/PE. On multivariable logistic regression analysis, the hemoglobin (OR, 0.71; 95% CI, 0.46-0.95; P = .04) and D-dimer (OR, 1.0; 95% CI, 0.33-1.56; P = .03) levels were associated with higher mortality. Higher activated partial thromboplastin times (OR, 1.1; 95% CI, 1.00-1.12; P = .03) and higher interleukin-6 (IL-6) levels (OR, 1.0; 95% CI, 1.01-1.07; P = .05) were associated with a greater risk of ICU admission. IL-6 (OR, 1.0; 95% CI, 1.00-1.02; P = .05) was associated with a greater risk of rehabilitation placement after discharge. On multivariable gamma regression analysis, hemoglobin (coefficient, -3.0; 95% CI, 0.03-0.08; P = .005) was associated with a prolonged ICU stay, and the activated partial thromboplastin time (coefficient, 2.0; 95% CI, 0.003-0.006; P = .05), international normalized ratio (coefficient, -3.2; 95% CI, 0.06-0.19; P = .002) and IL-6 (coefficient, 2.4; 95% CI, 0.0011-0.0027; P = .02) were associated with a prolonged LOH. CONCLUSIONS: A significantly greater incidence of DVT/PE occurred in hospitalized COVID-19-positive patients compared with a non-COVID-19 cohort matched for cardiovascular risk factors. Patients affected by DVT/PE were more likely to experience greater mortality, to require ICU admission, and experience prolonged ICU stays and LOH compared with COVID-19-positive patients without DVT/PE. Advancements in DVT/PE prevention are needed for patients hospitalized for COVID-19 infection.

Hurricanes: Are You Prepared?

Severe weather events such as hurricanes have the potential to cause significant disruption of laboratory operations. Comprehensive planning is essential to mitigate the impact of such events. The essential elements of a Hurricane Plan, based on our personal experiences, are detailed in this article.

Early Absent Pupillary Light Reflexes After Cardiac Arrest in Patients Treated with Therapeutic Hypothermia.

Loss of pupillary light reactivity is one recognized indicator of poor prognosis after cardiopulmonary resuscitation (CPR). However, drug overdose, low cardiac output, and/or resuscitation drugs can lead to impaired pupillary light reflex. To investigate pupillary light reflex status before therapeutic hypothermia (TH) in relation to neurological outcome, we retrospectively reviewed the data of a prospectively implemented TH protocol in patients with cardiac arrest (CA) at Mayo Clinic in Jacksonville, Florida (January 2006-January 2012), and Mayo Clinic in Scottsdale, Arizona (August 2010-March 2014). During this period, all CA patients who underwent hypothermia were included. These patients were selected from an institutional database and hypothermia data set. The Cerebral Performance Category (CPC) at time of discharge was our primary outcome measure. A CPC of 1 to 2 was defined as good outcome and a CPC from 3 to 5 was defined as poor outcome. We identified 99 patients who had CA treated with TH. Twenty-nine patients (29%) had pupils that were nonreactive to light on admission examination before TH, eight of whom later had return of pupil reactivity by day 3. Two of these 29 patients (6.9%) had good outcome, compared to 24 of 70 patients (34.3%) with pupils that were reactive to light (p = 0.005). Both of these patients had CA after illicit drug overdose. Early nonreactive pupils occurred in almost a third of patients after CPR and before TH in our patient population. Recovery of pupillary light reactivity is possible, and in a small minority of those cases (particularly when CA is preceded by the use of illicit drugs), a good outcome can be achieved.

Accuracy of calculated free testosterone differs between equations and depends on gender and SHBG concentration.

Serum free testosterone (fT) concentrations are often calculated, however different equations often yield discrepant results. This study explores the sources of this variability. We compared three established and two new equations that differed only by their testosterone association constants with isotope dilution equilibrium dialysis in two patient groups with different gender distributions. Equation components were examined to determine how they impacted correlation with isotope dilution equilibrium dialysis. Association constants derived for each patient group correlated best with isotope dilution equilibrium dialysis for that group and not the other set. Samples with the poorest correlation between isotope dilution equilibrium dialysis and calculated fT results had significantly higher SHBG concentrations. Regardless of equation, ≥ 25% of samples showed unacceptable deviation from isotope dilution equilibrium dialysis. Association constants and gender makeup and SHBG concentration of the patient groups used to establish an equation all significantly impact correlation with isotope dilution equilibrium dialysis. Application of many fT equations to wider populations will therefore frequently yield results that differ substantially from isotope dilution equilibrium dialysis.