Diagnostic value of platelet parameters and megakaryocyte formula of bone marrow in idiopathic thrombocytopenic purpura

The parameters of the megakaryocyte formula and peripheral blood platelet indices were studied in 237 people with diagnoses of idiopathic thrombocytopenic purpura (ITP) and myelodysplastic syndrome (MDS). A correlation analysis was performed between megakaryocyte subpopulations and platelet counts. The threshold values for MPV, PCT and PDW were determined by ROC analysis with the construction of the ROC curve, the calculation of the area under the curve (AUC) and the cutoff threshold. The obtained values make it possible to make a differential diagnosis between ITP and MDS by platelet parameters of peripheral blood without examining the bone marrow.

Analysis of the impact of sex and age on the variation in the prevalence of antinuclear autoantibodies in Polish population: a nationwide observational, cross-sectional study

The detection of antinuclear autoantibody (ANA) is dependent on many factors and varies between the populations. The aim of the study was first to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cutoff threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA-staining patterns. We tested 1731 patient samples using commercially available IIFA using two cutoff thresholds of 1:100 and 1:160. We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cutoff level. For a cutoff threshold 1:100, the positive population was 19.5% and for the 1:160 cutoff threshold, it was 11.7%. The most prevalent ANA-staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA more common in women (72%); 64% of ANA-positive patients were over 50 years of age. ANA prevalence in the Polish population is at a level observed in other highly developed countries and is more prevalent in women and elderly individuals. To reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cutoff threshold.

Cutoff Threshold Decisions for Classification Algorithms with Risk Aversion

Classification algorithms predict the class membership of an unknown record. Methods such as logistic regression or the naïve Bayes algorithm produce a score related to the likelihood that a record belongs to a particular class. A cutoff threshold is then defined to delineate the prediction of one class over another. This paper derives analytic results for the selection of an optimal cutoff threshold for a classification algorithm that is used to inform a two-action decision in the cases of risk aversion and risk neutrality. The results provide insight to how the optimal cutoff thresholds relate to the associated costs and the sensitivity and specificity of the algorithm for both the risk neutral and risk averse decision makers. The optimal risk averse threshold is not reliably above or below the optimal risk neutral threshold, but the relation depends on the parameters of a particular application. The results further show the risk averse optimal threshold is insensitive to the size of the data set or the magnitude of the costs, but instead is sensitive to the proportion of positive records in the data and the ratio of costs. Numeric examples and sensitivity analysis derive further insight. Results show the percent value gap from a misspecified risk attitude increases as the specificity of the classification algorithm decreases.

Atrial high-rate episodes predict major adverse cardio/cerebrovascular events in patients with cardiac implantable electrical devices

Patients with atrial high-rate episodes (AHRE) have a high risk of neurologic events, although the causal role and optimal cutoff threshold of AHRE for major adverse cardio/cerebrovascular events (MACCE) are unknown. This study aimed to identify independent factors for AHRE and subsequent atrial fibrillation (AF) after documented AHRE. We enrolled 470 consecutive patients undergoing cardiac implantable electrical device (CIED) implantations. The primary endpoint was subsequent MACCE after AHRE ≥ 6 min, 6 h, and 24 h. AHRE was defined as > 175 beats per minute (bpm) (Medtronic®) or > 200 bpm (Biotronik®) lasting ≥ 30 s. Multivariate Cox regression analysis with time-dependent covariates was used to determine variables associated with independent risk of MACCE. The patients’ median age was 76 year, and 126 patients (26.8%) developed AHRE ≥ 6 min, 63 (13.4%) ≥ 6 h, and 39 (8.3%) ≥ 24 h. During follow-up (median: 29 months), 142 MACCE occurred in 123 patients. Optimal AHRE cutoff value was 6 min, with highest Youden index for MACCE. AHRE ≥ 6 min ~ 24 h was independently associated with MACCE and predicted subsequent AF. Male gender, lower body mass index, or BMI, and left atrial diameter were independently associated with AHRE ≥ 6 min ~ 24 h. Patients with CIEDs who develop AHRE ≥ 6 min have an independently increased risk of MACCE. Comprehensive assessment of patients with CIEDs is warranted.

Development of ACE2 autoantibodies after SARS-CoV-2 infection

Background Activation of the immune system is implicated in the Post-Acute Sequelae after SARS-CoV-2 infection (PASC) but the mechanisms remain unknown. Angiotensin-converting enzyme 2 (ACE2) cleaves angiotensin II (Ang II) resulting in decreased activation of the AT1 receptor and decreased immune system activation. We hypothesized that autoantibodies against ACE2 may develop after SARS-CoV-2 infection, as anti-idiotypic antibodies to anti-spike protein antibodies. Methods and findings We tested plasma or serum for ACE2 antibodies in 67 patients with known SARS-CoV-2 infection and 13 with no history of infection. None of the 13 patients without history of SARS-CoV-2 infection and 1 of the 20 outpatients that had a positive PCR test for SARS-CoV-2 had levels of ACE2 antibodies above the cutoff threshold. In contrast, 26/32 (81%) in the convalescent group and 14/15 (93%) of patients acutely hospitalized had detectable ACE2 antibodies. Plasma from patients with antibodies against ACE2 had less soluble ACE2 activity in plasma but similar amounts of ACE2 protein compared to patients without ACE2 antibodies. We measured the capacity of the samples to inhibit ACE2 enzyme activity. Addition of plasma from patients with ACE2 antibodies led to decreased activity of an exogenous preparation of ACE2 compared to patients that did not have antibodies. Conclusions Many patients with a history of SARS-CoV-2 infection have antibodies specific for ACE2. Patients with ACE2 antibodies have lower activity of soluble ACE2 in plasma. Plasma from these patients also inhibits exogenous ACE2 activity. These findings are consistent with the hypothesis that ACE2 antibodies develop after SARS-CoV-2 infection and decrease ACE2 activity. This could lead to an increase in the abundance of Ang II, which causes a proinflammatory state that triggers symptoms of PASC.

Can we predict failure in licensure exams from medical students’ undergraduate academic performance?

Background: In 2015, the Medical Council of Canada increased the minimum pass level for the Medical Council of Canada Qualifying Examination Part I, and students had a higher rate of failure than in previous years. The purpose of this study was to predict students at an increased odds of examination failure to allow for early, targeted interventions. Methods: We divided our dataset into a derivation cohort and two validation cohorts and used multiple logistic regression to predict licensing examination failure. We then performed receiver operating characteristics and a sensitivity analysis using different cutoffs for explanatory variables to identify the cutoff threshold with the best predictive value at identifying students at increased odds of failure. Results: After multivariate analysis, only pre-clerkship GPA was a significant independent predictor of failure (OR 0.76, 95% CI [0.66, 0.88], p < 0.001). The probability of failure increased steeply when the pre-clerkship GPA fell below 80% and 76% was found to be the most efficient cutoff for predicting failure (OR 9.37, 95% CI [3.08, 38.41]). Conclusions: Pre-clerkship performance can predict students at increased odds of licensing examination failure. Further studies are needed to explore whether early interventions for at-risk students alter their examination performance.

High Prevalence of Post-stroke Anxiety in Elderly Patients Following COVID-19 Outbreak

Objective: Post-stroke anxiety (PSA) is a common affective disorder in patients with ischemic stroke. The elderly are more susceptible to mental health issues, however, few studies have so far focused on PSA in elderly patients, especially in the context of the COVID-19, causing psychological issues in the general population. The aim of the present study was to assess the prevalence and risk factors of PSA in elderly patients following COVID-19 outbreak.Methods: We retrospectively analyzed 206 elderly inpatients with newly diagnosed acute ischemic stroke in the First Affiliated Hospital, Sun Yat-sen University, from January 2020 to December 2020. Patients were categorized into the PSA group and the non-PSA group based on Hamilton Anxiety Scale scores at admission (within 1 week after stroke onset). Demographic and clinical data, mental state by Mini-Mental State Examination, depression by Hamilton Depression Scales (HAMD), and stroke severity and outcome by National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale were compared between the two groups. Univariate analysis and binary logistic regression analysis were used to analyze risk factors associated with PSA. We determined the cutoff scores for significant predictors of PSA using the area under the curve (AUC) and receiver operating characteristic.Results: Of the 206 stroke patients, 62 (30.1%) developed anxiety. Binary logistic regression analysis showed that female gender [adjusted odds ratio (aOR): 2.288, 95% confidence interval (CI):1.021–5.128, P = 0.044], high NIHSS scores [aOR: 1.264, 95% CI: 1.074–1.486, P = 0.005] and HAMD scores [aOR: 1.345, 95% CI: 1.215–1.490, P &lt; 0.001] were independent risk factors for PSA. The cutoff threshold for the NIHSS scores was 3.5 points with an AUC of 0.64 and the cutoff threshold for HAMD scores was 5.5 points with an AUC of 0.89.Conclusion: Our results showed a high incidence of PSA in elderly patients after the COVID-19 outbreak. Female gender, high NIHSS and HAMD scores were the independent risk factors for PSA.

Umbilical Cord Drug Screening in Multiple Births: Experience from a Reference Laboratory and Academic Medical Center

The objective of this study was to review the results of umbilical cord drug screening in twins and triplets (multiples) to compare drug(s) and/or drug metabolite(s) detected. Results that did not agree between multiples were considered mismatched and were investigated. A retrospective analysis was conducted using de-identified data from a national reference laboratory, and results were compared with data from an academic medical center, where detailed medical chart review was performed. Umbilical cord was analyzed for stimulants, sedatives, opioids, and other drugs and metabolites. For the reference laboratory dataset, 23.3% (n=844) of 3,616 umbilical cords from twins (n=3,550) or triplets (n=66) were positive for one or more drugs and/or metabolites. Of these, mismatched results were identified for thirty-seven sets of twins (2.1%) and no sets of triplets. The most frequent mismatches were found in opioids (n=24), with morphine (n=5) being the most mismatched of any single analyte in the panel. Mismatches for the marijuana metabolite 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (9-COOH-THC) in the reference laboratory dataset occurred in six of 737 sets of twins (0.8%) and no triplets. For the academic medical center dataset, 21.9% (n=57) of 260 umbilical cords tested positive for one or more drugs and/or metabolite(s). Of these, 4 mismatches (3.2%) were identified, including 9-COOH-THC (n=2), phentermine (n=1), and oxycodone (n=1), all involving twins. All involved cases where the discrepant analyte was likely present in the negative twin but either slightly below reporting cutoff threshold, or failed analytical quality criteria. Mismatched results of umbilical cord drug screening occur in less than 4% of twins and most often occur when the analyte is slightly above the reporting cutoff in just one infant.

Manufacturer Signal-to-Cutoff Threshold Underestimates Cumulative Incidence of SARS-CoV-2 Infection: Evidence from the Los Angeles Firefighters Study

While SARS-CoV-2 serologic testing is used to measure cumulative incidence of COVID-19, appropriate signal-to-cut off (S/Co) thresholds remain unclear. We demonstrate S/Co thresholds based on known negative samples significantly increases seropositivity and more accurately estimates cumulative incidence of disease compared to manufacturer-based thresholds.

Distinct SARS-CoV-2 antibody reactivity patterns in coronavirus convalescent plasma revealed by a coronavirus antigen microarray

A coronavirus antigen microarray (COVAM) was constructed containing 11 SARS-CoV-2, 5 SARS-1, 5 MERS, and 12 seasonal coronavirus recombinant proteins. The array is designed to measure immunoglobulin isotype and subtype levels in serum or plasma samples against each of the individual antigens printed on the array. We probed the COVAM with COVID-19 convalescent plasma (CCP) collected from 99 donors who recovered from a PCR+ confirmed SARS-CoV-2 infection. The results were analyzed using two computational approaches, a generalized linear model (glm) and random forest (RF) prediction model, to classify individual specimens as either Reactive or non-reactive against the SARS-CoV-2 antigens. A training set of 88 pre-COVID-19 specimens (PreCoV) collected in August 2019 and102 positive specimens from SARS-CoV-2 PCR+ confirmed COVID-19 cases was used for these analyses. Results compared with an FDA emergency use authorized (EUA) SARS-CoV2 S1-based total Ig chemiluminescence immunoassay (Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 Total, CoV2T) and with a SARS-CoV-2 S1-S2 spike-based pseudovirus micro neutralization assay (SARS-CoV-2 reporter viral particle neutralization titration (RVPNT) showed high concordance between the three assays. Three CCP specimens that were negative by the VITROS CoV2T immunoassay were also negative by both COVAM and the RVPNT assay. Concordance between VITROS CoV2T and COVAM was 96%, VITROS CoV2T and RVPNT 93%, and RVPNT and COVAM 91%. The discordances were all weakly reactive samples near the cutoff threshold of the VITROS CoV2T immunoassay. The multiplex COVAM allows CCP to be grouped according to antibody reactivity patterns against 11 SARS-CoV-2 antigens. Unsupervised K-means analysis, via the gap statistics, as well as hierarchical clustering analysis revealed three main clusters with distinct reactivity intensities and patterns. These patterns were not recapitulated by adjusting the VITROS CoV2T or RVPNT assay thresholds. Plasma classified by COVAM reactivity patterns offers potential to improve CCP therapeutic efficacy CoV2T alone. The use of a SARS-CoV-2 antigen array can qualify CCP for administration as a treatment for acute COVID-19, and interrogate vaccine immunogenicity and performance in preclinical, clinical studies, and routine vaccination to identify antibody responses predictive of protection from infection and disease.