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Hospitalized patients with COVID-19 show increased serum concentrations of neurofilament light chain that correlate with worse clinical outcomes., Brain damage marker in COVID-19 SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), causes neurological manifestations in a substantial proportion of patients. Determining the extent of neuronal injury is essential to better understand disease pathophysiology and to evaluate potential therapies. Prudencio et al. analyzed serum from 142 patients hospitalized with COVID-19 and showed that the expression of the neurofilament light protein (NFL), a marker of neuroaxonal injury, was elevated compared to healthy controls. In addition, serum NFL expression correlated with disease severity and tended to be reduced in subjects treated with remdesivir. The results suggest that serum NFL analysis should be incorporated when evaluating therapeutic trials for 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.

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 endpoint was the incidence of DVT/PE and the odds of developing DVT/PE using a conditional logistic regression model. The secondary endpoint 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.

To the Editor: Serum free light-chain (FLC) assays have been incorporated into diagnostic criteria for multiple myeloma (1). However, these assays are subject to analytical issues such as lot-to-lot variation, antigen excess, and nonlinearity (2). A recent lot change for κ FLC (Lot 130718, The Binding Site) prompted physician phone calls questioning normal κ results in patients with a history of increased concentrations, triggering laboratory investigations. Further analysis revealed prozone (or hook) effect, which occurs when the antigen (FLC) is present in great excess and impairs immune-complex formation, leading to analyte underestimation. A protocol to mitigate κ FLC antigen excess is to manually reflex to higher dilutions whenever the FLC ratio is ≥2. Samples with antigen excess were identified by this practice or in response to physician inquiry. Sample selection was blinded to any additional characteristics. Samples exhibiting prozone effect are shown in 25 cases in Table 1. Testing was performed on a nephelometric Siemens BN II platform. The discrepancy between the concentrations obtained with the assay's initial 1:100 dilution and the final reported dilution had a median fold difference of 9.0 (range, 2.6–7505). The upper limit of the 1:100 lot-specific calibration curve is 19.6 mg/dL. Therefore, it is distressing that concentrations obtained from the initial dilution do not appear as “>19.6” …

An estimated 1 billion people worldwide have deficient or insufficient levels of vitamin D (VitD). Considerable evidence indicates that VitD deficiency is associated with an increased risk of autoimmune and cardiovascular disease (CVD), yet it remains unclear whether low VitD is simply a biomarker or has a true pathologic role. In this study we examined how sex differences in VitD influences various CVDs. We found that patients with CVD had significantly lower VitD than healthy controls (no ICD9/10 codes). In myocarditis patients low VitD correlated to poor ejection fraction (EF) in women with myocarditis (p=0.02), but high VitD correlated with low EF in men (p=0.04). In VDR knockout mice we found that VDR decreased myocarditis in females (p=2E-8) but increased inflammation in males (p=0.03) with an increase in total immune cells (p=0.02), CD3, CD4 and CD8 T cells (p=0.04), and the inflammasome in females. VDR altered Treg (p=0.04), mast cells (p=0.04) and cytokine profiles in males. Additionally, sera VitD levels were significantly higher in WT male mice with myocarditis compared to females. Our findings in VDR mice indicate that VitD/VDR reduces myocarditis in females, but increases disease in males. These data suggest that VitD sufficiency may increase inflammation in men, while VitD deficiency may make disease worse in women. These findings suggest that Vitamin D may have a role in the pathogenesis of inflammatory and cardiovascular disease.

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.

A 43-year-old African-American man with a history of hypertension, depression, and chronic alcohol abuse presented to the emergency service of an outside hospital complaining of chest pain. Laboratory testing indicated hepatocellular injury with aspartate aminotransferase (AST)1 of 14000 U/L (reference interval 5–41 U/L) and alanine aminotransferase (ALT) of 6400 U/L (reference interval 8–45 U/L). Because laboratory indicators of liver function worsened, the patient was reinterviewed and confessed to having attempted suicide 3 days prior by ingesting about one-half gallon (approximately 4 L) of vodka and one-half bottle of extra-strength acetaminophen. The patient was administered a bolus of N-acetylcysteine (NAC) at the outside hospital and referred to our institution because of concern for progression to fulminant hepatic failure. Laboratory tests were repeated and results were consistent with significant hepatocellular damage secondary to acetaminophen poisoning, including increased AST of 11 000 U/L (reference interval 8–48 U/L), ALT of 6510 U/L (reference interval 7–55 U/L), total bilirubin of 395 μmol/L (23.1 mg/dL) [reference interval 2–17 μmol/L (0.1–1.0 mg/dL)], and direct-bilirubin of 207 μmol/L (12.1 mg/dL) [reference interval

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA Introduction: A and T are associated with the development of cardiac dysfunction. The kinetics of cardiac biomarkers early after A or T treatment (Rx) is undefined. Methods: We studied hs-TnT (detection limit: 3 ng/ml, myocardial infarction threshold 14 ng/ml) and nt-proBNP (detection limit: 5 pg/ml) levels just prior to (baseline), and on days +1, +2, +3 and +7 during the first and second cycle in breast cancer pts treated with A (n = 11) or T (n = 11). Baseline and peak values for each cycle, baseline to baseline, peak to peak, time to peak, and baseline corrected area under the curve (AUC) were calculated. Study No. [NCT01771549][1] Results: Group (grp) A pts were younger, 51 ± 18 years, than T grp pts, 60 ± 13 years. Three pts in A grp and 4 pts in T grp used antihypertensives. Baseline ejection fraction (EF) was 52-68% (A grp) and 56-69% (T grp). Hs-TnT was undetectable in 5/11 A grp, and 2/11 T grp pts at baseline. By cycle 2 day +1, all A pts had a detectable level of hs-TnT (p = 0.03) compared to 7/11 T pts. Median time to peak level for hs-TnT was 1.5 days for the A grp and 1.2 days for the T grp (NS). In the A grp, significant transient increase in nt-proBNP were also seen (Table). In the T grp, a significant rise in nt-proBNP was not seen in cycle 1 but was seen on cycle 2 day +1 and cycle 2 peak. AUC values were positive for hs-TnT in A pts but not in T pts, and were positive for nt-proBTNP for both A and T. Only 1 pt in A grp had symptomatic EF decline (47%) three months from start of A. None of T grp pts had EF decline. Conclusion: A, but not T was associated with increase in pre-Rx (cycle 2 only), peak, and AUC hs-TnT levels for cycles 1 and 2 with peak values occurring 1.5 days post-Rx. This study evaluating serial kinetics of cardiac biomarker in pts receiving A or T therapy, suggests that assessment of pre- and day +2 post-Rx values could be a means of quantifying cumulative myocardial injury over the chemotherapy course. *Roche Diagnostics Corp, Indianapolis, IN provided assay reagent kits. | hs-TnT, ng/ml | A, cycle 1 | A, cycle 2 | P-val | T, cycle 1 | T, cycle 2 | P-val | | ------------------ | ---------- | ----------- | ------------------------------------------- | ---------- | ---------- | ----- | | Baseline | 4.6 | 9.3

Background Umbilical cord blood (UCB) is an important alternative source of stem cells for patients who lack matched adult donors, particularly in ethnic minorities. The infused total nucleated cell (TNC) and CD34+ cell dose are important prognostic factors on transplant outcomes. UCB units collected from African Americans (AA) have lower TNC and CD34+ cell counts and more likely to be disqualified for banking compared to other racial and ethnic groups. Furthermore, AA, including pregnant women, have increased prevalence of vitamin D deficiency. Vitamin D has an established role in hematopoiesis; therefore, we investigated the racial differences in UCB vitamin D content and its correlation with UCB cell composition and hematopoietic potential. Methods 119 UCB units that did not meet the TNC count banking criteria were analyzed. 51 UCB units were collected from AA mothers and 68 from Caucasian mothers. We analyzed UCB variables including volume, hematocrit (HCT), TNCs, mononucleated cells (MNC), CD34+ cells, plasma 25-Hydroxy vitamin D [25(OH)D] and in vitro progenitor cell hematopoietic potential measured by Colony-Forming Cell (CFC) assay. Results The median values of 25(OH)D in UCB units were significantly lower in AA compare to Caucasians (p= Univariate analysis of 25(OH)D effect on UCB variables revealed a correlation between 25(OH)D level and TNC (r= 0.193, 95% CI 0.013-0.36; p= .0353) and UCB HCT (r= 0.196, 95% CI 0.016-0.363; p= .0327). A significantly higher MNC count was noted when 25(OH)D concentration was ≥ 20ng/mL (4.5x 108, range (1.7-9.5) vs. 3.9x 108, range (0.8-9); p= .0329). This correlation between 25(OH)D level and TNC and MNC was not detected after adjustment for race (Figure 1). However, 25(OH)D concentration ≥ 20 ng/mL significantly correlated with CBU HCT in AA race (median 31.9% (24-42) vs. 27.8%, range (21.4 - 40); p= .0124). Conclusion 25(OH)D level, TNC and HCT are all significantly lower in UCB units from AA compare to Caucasians. Independent of race, 25(OH)D directly correlated with TNC and MNC. These data suggest vitamin D and other yet to be determined factors play an important role in the mechanism of low UCB cell and progenitor counts. Disclosures: No relevant conflicts of interest to declare.