Serum sample containing endogenous antibodies interfering with multiple hormone immunoassays. Laboratory strategies to detect interference

Objectives: Endogenous antibodies (EA) may interfere with immunoassays, causing erroneous results for hormone analyses. As (in most cases) this interference arises from the assay format and most immunoassays, even from different manufacturers, are constructed in a similar way, it is possible for a single type of EA to interfere with different immunoassays. Here we describe the case of a patient whose serum sample contains EA that interfere several hormones tests. We also discuss the strategies deployed to detect interference. Subjects and methods: Over a period of four years, a 30-year-old man was subjected to a plethora of laboratory and imaging diagnostic procedures as a consequence of elevated hormone results, mainly of pituitary origin, which did not correlate with the overall clinical picture. Results: Once analytical interference was suspected, the best laboratory approaches to investigate it were sample reanalysis on an alternative platform and sample incubation with antibody blocking tubes. Construction of an in-house ''nonsense'' sandwich assay was also a valuable strategy to confirm interference. In contrast, serial sample dilutions were of no value in our case, while polyethylene glycol (PEG) precipitation gave inconclusive results, probably due to the use of inappropriate PEG concentrations for several of the tests assayed. Conclusions: Clinicians and laboratorians must be aware of the drawbacks of immunometric assays, and alert to the possibility of EA interference when results do not fit the clinical pattern

Screening dyslexia for English using HCI measures and machine learning

More than 10% of the population has dyslexia, and most are diagnosed only after they fail in school. This work seeks to change this through early detection via machine learning models that predict dyslexia by observing how people interact with a linguistic computer-based game. We designed items of the game taking into account (i) the empirical linguistic analysis of the errors that people with dyslexia make, and (ii) specific cognitive skills related to dyslexia: Language Skills, Working Memory, Executive Functions, and Perceptual Processes. . Using measures derived from the game, we conducted an experiment with 267 children and adults in order to train a statistical model that predicts readers with and without dyslexia using measures derived from the game. The model was trained and evaluated in a 10-fold cross experiment, reaching 84.62% accuracy using the most informative features.Peer ReviewedPostprint (author's final draft

Transverse orange nail lesions following SARS-CoV-2 infection

We report the case of an 89-year-old woman in a nursing home who amid an outbreak of coronavirus disease 2019 (COVID-19) presented cough and asthenia

Optimal opportunistic screening of atrial fibrillation using pulse palpation in cardiology outpatient clinics: Who and how

Atrial fibrillation (AF) remain a prevalent undiagnosed condition frequently encountered in primary care.We aimed to find the parameters that optimize the diagnostic accuracy of pulse palpation to detect AF. We also aimed to create a simple algorithm for selecting which individuals would benefit from pulse palpation and, if positive, receive an ECG to detect AF.Nurses from four Cardiology outpatient clinics palpated 7,844 pulses according to a randomized list of arterial territories and durations of measure and immediately followed by a 12-lead ECG, which we used as the reference standard. We calculated the sensitivity and specificity of the palpation parameters. We also assessed whether diagnostic accuracy depended on the nurse's experience or on a list of clinical factors of the patients. With this information, we estimated the positive predictive values and false omission rates according to very few clinical factors readily available in primary care (age, sex, and diagnosis of heart failure) and used them to create the algorithm.The parameters associated with the highest diagnostic accuracy were palpation of the radial artery and classifying as irregular those palpations in which the nurse was uncertain about pulse regularity or unable to palpate pulse (sensitivity = 79%; specificity = 86%). Specificity decreased with age. Neither the nurse's experience nor any investigated clinical factor influenced diagnostic accuracy. We provide the algorithm to select the ≥40 years old individuals that would benefit from a pulse palpation screening: a) do nothing in <60 years old individuals without heart failure; b) do ECG in ≥70 years old individuals with heart failure; c) do radial pulse palpation in the remaining individuals and do ECG if the pulse is irregular or you are uncertain about its regularity or unable to palpate it.Opportunistic screening for AF using optimal pulse palpation in candidate individuals according to a simple algorithm may have high effectiveness in detecting AF in primary care

MRI Investigation of the Differential Impact of Left Ventricular Ejection Fraction After Myocardial Infarction in Elderly vs. Nonelderly Patients to Predict Readmission for Heart Failure

Acute heart failure; Acute myocardial infarction; ElderlyInsuficiència cardíaca aguda; Infart agut de miocardi; Gent granInsuficiencia cardíaca aguda; Infarto agudo de miocardio; AncianoBackground Patients with ST-segment elevation myocardial infarction (STEMI), especially elderly individuals, have an increased risk of readmission for acute heart failure (AHF). Purpose To study the impact of left ventricular ejection fraction (LVEF) by MRI to predict AHF in elderly (>70 years) and nonelderly patients after STEMI. Study Type Prospective. Population Multicenter registry of 759 reperfused STEMI patients (23.3% elderly). Field Strength/Sequence 1.5-T. Balanced steady-state free precession (cine imaging) and segmented inversion recovery steady-state free precession (late gadolinium enhancement) sequences. Assessment One-week MRI-derived LVEF (%) was quantified. Sequential MRI data were recorded in 579 patients. Patients were categorized according to their MRI-derived LVEF as preserved (p-LVEF, ≥50%), mildly reduced (mr-LVEF, 41%–49%), or reduced (r-LVEF, ≤40%). Median follow-up was 5 [2.33–7.54] years. Statistical Tests Univariable (Student's t, Mann–Whitney U, chi-square, and Fisher's exact tests) and multivariable (Cox proportional hazard regression) comparisons and continuous-time multistate Markov model to analyze transitions between LVEF categories and to AHF. Hazard ratios (HR) with 95% confidence intervals (CIs) were computed. P < 0.05 was considered statistically significant. Results Over the follow-up period, 79 (10.4%) patients presented AHF. MRI-LVEF was the most robust predictor in nonelderly (HR 0.94 [0.91–0.98]) and elderly patients (HR 0.94 [0.91–0.97]). Elderly patients had an increased AHF risk across the LVEF spectrum. An excess of risk (compared to p-LVEF) was noted in patients with r-LVEF both in nonelderly (HR 11.25 [5.67–22.32]) and elderly patients (HR 7.55 [3.29–17.34]). However, the mr-LVEF category was associated with increased AHF risk only in elderly patients (HR 3.66 [1.54–8.68]). Less transitions to higher LVEF states (n = 19, 30.2% vs. n = 98, 53%) and more transitions to AHF state (n = 34, 53.9% vs. n = 45, 24.3%) were observed in elderly than nonelderly patients. Data Conclusion MRI-derived p-LVEF confers a favorable prognosis and r-LVEF identifies individuals at the highest risk of AHF in both elderly and nonelderly patients. Nevertheless, an excess of risk was also found in the mr-LVEF category in the elderly group. Evidence Level 2. Technical Efficacy Stage 2.Grant sponsor: This work was supported by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (grant numbers PI20/00637, PI15/00531, and CIBERCV16/11/00486, CIBERCV16/11/00420, CIBERCV16/11/00479, and CM21/00175 to V.M.-G.), Fundació La Marató TV3 (grant 20153030-31-32), La Caixa Banking Foundation (HR17-00527) and by Conselleria de Educación – Generalitat Valenciana (PROMETEO/2021/008). J.G. acknowledges financial support from the “Agencia Estatal de Investigación” (grant FJC2020-043981-I/AEI/10.13039/501100011033)

Improved selectivity and cytotoxic effects of irinotecan via liposomal delivery: A comparative study on Hs68 and HeLa cells

Irinotecan (CPT-11) is an effective chemotherapeutic agent widely used to treat different cancers. Otherwise, the liposomal delivery of anti-tumor agents has been shown to be a promising strategy. The aim of this study has been to analyze the effect of liposomal CPT-11 (CPT-11lip) on two human cell lines (Hs68 and HeLa) to establish the suitability of this CPT-11 nanocarrier. We have demonstrated the highest uptake of CPT-11lip in comparison with that of CPT-11sol, in lactate buffer, and that CPT-11lip was internalized in the cells through an endocytic process whereas CPT-11sol does so by passive diffusion. CPT-11lip was not cytotoxic to normal fibroblast Hs68 cells, but induced a massive apoptosis accompanied by cell senescence in HeLa cells. CPT-11lip treatment modified the morphology of HeLa cells, induced different cell cycle alterations and accumulated into lysosomes in both cell lines. In particular, CPT-11lip treatment showed that surviving HeLa cells remained in a state of senescence whereas only a temporal growth arrest was induced in Hs68 cells. Results of RT-PCR indicated that the different responses in Hs68 (survival) and HeLa cells (apoptotic death), seemed to be induced by a p53- and p53- independent mechanism, respectively. An analysis of DNA damage also determined that released CPT-11 from liposomes was able to reach the nucleus and exert a genotoxic effect in both cell lines, which was repaired in Hs68 but not in HeLa cells. All results indicate that phospholipid-cholesterol liposomes possess optimum properties for CPT-11 delivery, being biocompatible and selectively cytotoxic against HeLa tumorigenic cells.