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Background: The lysis of platelets during in vitro coagulation leads to increased potassium concentrations.We aimed to establish the cut-off value for platelet count interfering serum potassium and to estimate the percentage of cases of pseudohyperkalemia and pseudonormokalemia in our hospital., Materials and Methods: Individuals diagnosed with essential thrombocytosis (2010-2019) based on the WHO criteria for the classification of myeloid neoplasms and acute leukemia were considered.The cut-off value for the interference of platelet count on serum potassium results was calculated using the reference change value. Sensitivity and specificity were calculated using a ROC-curve, and the size of the effect by the Cohen's d.The clinical impact of both phenomena was assessed by reviewing the medical records of individuals classified as such, and also looking for potential cases in 2019 on the laboratory information system., Results: Fifty-four individuals with essential thrombocytosis were included. Potassium concentration correlated with platelet count (P-value<0.001; Spearman's ρ =0.394) in serum. The cut-off value of platelet count interfering potassium was 598x10 3 /μL [CI95%: 533-662x10 3 /μL], with an associated sensitivity and specificity of 0.67 [CI95%:0.52-0.80] and 0.58 [CI95%:0.42-0.72] respectively.The medical records of patients classified as pseudohyperkalemia or pseudonormokalemia did not include any medical action for the modification of potassium levels. In 2019, up to 0.14% of the total serum potassium determinations were susceptible to be pseudohyperkalemia or pseudonormokalemia., Conclusion: This study provides a cut-off value for platelet count interfering serum potassium concentrations, and brings to light not only pseudohyperkalemia-related issues, but also the pseudonormokalemia phenomenon, which usually goes unnoticed., Competing Interests: Declaration of competing interests All authors declare no conflicts of interest., (Copyright © 2022 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All rights reserved.)

Objective: To analyse determinants of mortality at 15 years in a population over 60 years of age and physically active., Methods: This is a prospective longitudinal study. After 15 years of participating in an active ageing programme, participants were contacted by telephone to verify their state of health and to determine whether in that time they had had any fractures., Results: 561 individuals over 60 years of age were included, 82% of whom were women. Only differences in densitometric data, FRAX values and history of previous fracture at baseline characteristics were found between the group that died at 15 years and the group that remained alive. The only variables that were related to mortality risk were the basal data of the densitometric t-score (OR = .50, P < .001) and history of fracture in any location (OR = 2.44, P < .033)., Conclusions: The value of bone mineral density could be considered as a useful biomarker to calculate the risk of mortality in people over 60 years old with a physically active lifestyle., (Copyright © 2021 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Background: Providing evidence-based interpretative comments (IC) is an integral task of clinical laboratory professionals. It may be of special relevance for coagulation testing, where pathological first-line tests could trigger more specialized tests. Our aim was to evaluate the quality of ICs provided to the physician in two samples with activated partial thromboplastin time (APTT) prolongation., Material and Methods: Two lyophilized plasma samples and their respective fictional clinical cases (case 1: heparin contamination and case 2: factor VIII deficiency) were sent to European laboratories for APTT and APTT mixing test measurement, and elaboration of ICs based on their results. The quality of ICs was evaluated in terms of analytical classification, laboratory interpretation, advice to physician, clarity, length and whether the clinical question was answered., Results: A total of 214 laboratories were included. Classification of the analytical result was stated in 57 % of comments. Laboratory interpretation was found in 91 % of comments for case 1 and 83.3 % for case 2, among which 9.3 % and 6.5 % were considered wrong, respectively. Advice for the requesting physician was provided in 65.8 % of comments for case 1 and 61.2 % for case 2, among which 36 % and 4.7 % were considered wrong, respectively. More than 70 % of comments for both cases were evaluated as clear and of an adequate length., Conclusion: A significant number of laboratories provide clear interpretations and helpful advice for the management of altered coagulation results. Nevertheless, the finding of several confusing and misleading comments highlights the need for recommendations on elaboration of interpretative comments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Unexpected prolongation of first-line coagulation tests, including activated partial thromboplastin time (APTT), should trigger further work-up by performing mixing tests to elucidate the underlying cause, direct further specific testing and clarify their possible clinical impact. The aim of our study was to assess whether methodological diversity has any impact on the APTT mixing test results and their interpretation., Material and Methods: Two lyophilized plasma samples (case 1: heparin contamination [0.5 IU/mL]; case 2: factor VIII deficiency [0.13 IU/mL]) and their respective fictional clinical cases were sent to European laboratories for APTT measurement and performance of mixing tests. Participants were surveyed about the methodology (reagents, analytical platform, reference ranges), APTT results, mixing test conditions, their classification (normal, equivocal, prolonged) and categorization of the sample (factor deficiency, presence of inhibitor, anticoagulant, unknown)., Results: A total of 269 responses were included. For case 1, all participants reported a prolonged APTT, and 91% obtained no correction in the mixing test, without differences among reagents or analytical platforms. Only 15% of them selected the presence of an anticoagulant as the single cause for the prolongation. For case 2, 99% of participants reported a prolonged APTT, while some heterogeneity in the mixing test results was found. Eighty-six percent of participants selected factor deficiency as the cause for APTT prolongation., Conclusions: Most European laboratories obtained valid results for APTT and the subsequent mixing tests, despite using different methodologies. However, their classification could be improved. Therefore, more training and periodic evaluations are recommended to harmonize protocols and ensure proper result classification and categorization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Staphylococcus infection-associated glomerulonephritis (SAGN), is an autoimmune sequela of infection affecting a subset of infected patients without specific predictive factors, frequently presenting with acute nephritic syndrome and propensity for chronic kidney disease. We performed a comparative genotypic and phenotypic analysis of S. aureus isolates from patients that did and those that did not develop SAGN., Methods: We had 22 culture-proven cases of SAGN from Ohio State University Wexner Medical Center (OSUWMC) from 2004 to 2016, 9 of 22 being blood cultures, with archived isolates. These, along with blood culture isolates from 12 patients with no clinical evidence of SAGN (between ages 40 to 80 years) over the same period were used for genotyping. For host demographic comparison, we used all available SAGN cases ( n  = 85, including those with positive cultures other than blood; and patients with kidney biopsies received from referring hospitals) and all OSUWMC patients with positive Staphylococcus cultures without glomerulonephritis (GN) ( n  = 23,496)., Results: Multiple sequence types (STs) suggesting strain diversity was seen in the GN isolates with mainly clonal complexes (CC) 5 and 59. Mutations in the agr operon were identified in significantly higher number of the GN isolates (83%) than non-GN isolates (16%). Significant differences in β-hemolysis and biofilm formation was also observed between the groups., Conclusion: The functionality of these agr mutants remains to be seen, but the presently known effects of reduced agr function, namely increased surface adhesins, biofilm formation, and persistent bacteremia could be important microbial factors predisposing to SAGN and testing for them early during infection could help to predict its development., (© 2022 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Rationale: Abnormal values of hypercoagulability biomarkers, such as D-dimer, have been described in Coronavirus Disease 2019 (COVID-19), which has also been associated with disease severity and in-hospital mortality. COVID-19 patients with pneumonia are at greater risk of pulmonary embolism (PE). However, the real incidence of PE is not yet clear, since studies have been limited in size, mostly retrospective, and PE diagnostic procedures were only performed when PE was clinically suspected., Objectives: (1) To determine the incidence, clinical, radiological, and biological characteristics, and clinical outcomes of PE among patients hospitalized for COVID-19 pneumonia with D-dimer > 1,000 ng/mL. (2) To develop a prognostic model to predict PE in these patients., Methods: Single-center prospective cohort study. Consecutive confirmed cases of COVID-19 pneumonia with D-dimer > 1,000 ng/mL underwent computed tomography pulmonary angiography (CTPA). Demographic and laboratory data, comorbidities, CTPA scores, treatments administered, and clinical outcomes were analyzed and compared between patients with and without PE. A risk score was constructed from all these variables., Results: Between 6 April 2020 and 2 February 2021, 179 consecutive patients were included. The overall incidence of PE was 39.7% (71 patients) (CI 95%, 32-47%). In patients with PE, emboli were located mainly in segmental/subsegmental arteries (67%). Patients with PE did not differ from the non-PE group in sex, age, or risk factors for thromboembolic disease. Higher urea, D-Dimer, D-dimer-to-ferritin and D-dimer-to-lactate dehydrogenase (LDH) ratios, platelet distribution width (PDW), and neutrophil-to-lymphocyte ratio (NLR) values were found in patients with PE when compared to patients with non-PE. Besides, lymphocyte counts turned out to be lower in patients with PE. A score for PE prediction was constructed with excellent overall performance [area under the ROC curve-receiver operating characteristic (AUC-ROC) 0.81 (95% CI: 0.73-0.89)]. The PATCOM score stands for Pulmonary Artery Thrombosis in COVID-19 Mallorca and includes platelet count, PDW, urea concentration, and D-dimer-to-ferritin ratio., Conclusion: COVID-19 patients with pneumonia and D-dimer values > 1,000 ng/mL were presented with a very high incidence of PE, regardless of clinical suspicion. Significant differences in urea, D-dimer, PDW, NLR, and lymphocyte count were found between patients with PE and non-PE. The PATCOM score is presented in this study as a promising PE prediction rule, although validation in further studies is required., Competing Interests: AA-F reports personal fees from Astrazeneca, GSK, Chiesi, and Menarini, from outside the submitted work. JS reports personal fees, as a speaker, from Roche and Boehringer-Ingelheim, with no relationship with the submitted work. ES-L reports personal fees from Astrazeneca, GSK, and Boehringer-Ingelheim, personal and advisory board fees from MSD, and grants, personal, and advisory board fees from Actelion and Janssen, from outside the submitted work. BN reports personal fees from Roche, Brystol, and Boehringer-Ingelheim, with no relationship with the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Suarez Castillejo, Toledo-Pons, Calvo, Ramon-Clar, Martínez, Hermoso de Mendoza, Morell-García, Bauça, Berga, Núñez, Preda, Sauleda, Argente Castillo, Ballesteros, Martín, Sala-Llinas and Alonso-Fernández.)

Aluminum enters the body primarily through diet or occupational exposure, and is cleared through urine. However, this trace element may accumulate and cause toxicity in subjects with renal insufficiency, and even in dialysis patients. The mechanism of aluminum toxicity is related to increased oxidative and inflammatory stress, iron and calcium dyshomeostasis, or cholinergic dysregulation, among other. A review was conducted on the specimens and analytical methods used to determine aluminum in biological specimens and dialysis water. This paper describes the most relevant aspects related to quality assurance. This is a practical guideline for the development and implementation of a reliable method for determination of aluminum in the clinical laboratory. Serum aluminum is the main biomarker of toxicity. For cases of chronic exposure, urine testing is recommended. At present, inductively coupled plasma mass spectrometry (ICP-MS) is the gold-standard determination method, since it has been proven to have the best quantification limits, selectivity and robustness. Clear recommendations are provided in relation to the specimens used for aluminum determination. Relevant pre-analytical, analytical, and post-analytical considerations are also presented., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2022 Sonia Pérez San Martín et al., published by De Gruyter, Berlin/Boston.)

Objectives: Most errors in laboratory medicine occur in the pre- and post-analytical phases of the total testing process (TTP). In 2014, the Spanish Society of Laboratory Medicine (SEQC ML ) started the current Preanalytical Phase EQA Programme, with the objective of providing a tool for the improvement of the preanalytical phase. The aim of this study was to review the evolution of quality indicators (QI) and the comparability of established performance specifications (PS) with other EQA programmes., Methods: In the SEQC ML programme, participants were asked to register rejections of the main specimens and the causes for rejections. Data collected from 2014 to 2017, and then reviewed biennially (2018-2019), was used to calculate the percentiles; p25, p50, p75, and p90 for every round, and their means were set as PS. These PS were compared with the results of other programmes., Results: The evolution of QI results for 2018-2019 period showed general maintenance or improvement, e.g., a significant decrease in the number of serum samples with a haemolytic index ≥0.5 g/L, except for EDTA and citrate samples handle, maybe for an improvement in detection. The comparison with PS for the QI of the IFCC Working Group "Laboratory Errors and Patient Safety" and the Key Incident Management and Monitoring System (KIMMS) programme of the RCPA showed comparable results, supporting the validity of the established specifications., Conclusions: The PS obtained are a helpful tool for benchmarking and to identify processes of the preanalytical phase whose improvement should be set as a priority., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2022 Andrea Caballero et al., published by De Gruyter, Berlin/Boston.)

Antimicrobial resistance is a global public health threat, and gram-negative bacteria, such as Enterobacterales and Pseudomonas aeruginosa, are particularly problematic with difficult-to-treat resistance phenotypes. To reduce morbidity and mortality, a reduction in the time to effective antimicrobial therapy (TTET) is needed, especially among critically ill patients. The antibiogram is an effective clinical tool that can provide accurate antimicrobial susceptibility information and facilitate early antimicrobial optimization, decrease TTET, and improve outcomes such as mortality, hospital length of stay, and costs. Guidance is lacking on how to validate the susceptibility to new antibacterial agents. Commonly used traditional and combination antibiograms may not adequately assist clinicians in making treatment decisions. Challenges with the current susceptibility testing of new β-lactam/β-lactamase inhibitor combinations persist, impacting the appropriate antibacterial choice and patient outcomes. Novel antibiograms such as syndromic antibiograms that incorporate resistant gram-negative phenotypes and/or minimum inhibitory concentration distributions may assist in determining the need for earlier susceptibility testing or help define an earlier optimal use of the new β-lactam/β-lactamase inhibitors. The purpose of this review is to emphasize novel antibiogram approaches that are capable of improving the time to susceptibility testing and administration for new β-lactam/β-lactamase inhibitors so that they are earlier in a patient's treatment course.

Wilson's disease (WD) is an inherited disorder of copper metabolism caused by mutations in the ATP7B gene. This condition is characterized by the accumulation of copper in the liver and other organs and tissues causing hepatic and neuropsychiatric manifestations. This paper reviews the diagnostic performance and limitations of the biochemical tests commonly used to detect this underdiagnosed disease. It also provides some recommendations and suggests a set of standardized laboratory comments. At present, a rapid, simple, reliable biochemical test that confirms diagnosis of WD is not available. However, diagnosis can be established based on serum ceruloplasmin and urinary copper excretion. Total serum copper should be employed with caution, since it has a low negative predictive value. The use of estimated non-ceruloplasmin-bound copper is not recommended. Nevertheless, measured relative exchangeable copper has very high sensitivity and specificity and emerges as a potential gold standard for the biochemical diagnosis of WD. The development of novel assays for WD detection makes this disorder a potential candidate to be included in newborn screening programs., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2022 Eduardo Martínez-Morillo and Josep Miquel Bauça, published by De Gruyter, Berlin/Boston.)

Purpose: Treatment options for advanced cholangiocarcinoma are limited and prognosis is poor. Cholangiocarcinomas are highly heterogeneous at the molecular level, with divergent patterns between intrahepatic and extrahepatic forms, intrahepatic being particularly rich in actionable alterations. We compared survival in patients with advanced cholangiocarcinoma harboring alterations matched to targeted drugs, with patients harboring nonactionable alterations., Experimental Design: Patients with cholangiocarcinoma treated between 2011 and 2020 at one institution, with available molecular analyses, were retrospectively reviewed. Genomic alteration actionability was classified according to the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) and correlated with efficacy endpoints., Results: Of 327 patients included, 78.9% had intrahepatic cholangiocarcinoma, 97.9% had received chemotherapy for metastatic disease. Actionable molecular alterations per ESCAT were identified in 184 patients (56.3%), including IDH1 mutations and FGFR2 fusions (23.1% and 8.0% of patients with intrahepatic cholangiocarcinoma, respectively). Median overall survival in 50 patients with ESCAT I-IV alterations who received matched therapy (48 with intrahepatic cholangiocarcinoma) was 22.6 months [95% confidence interval (CI), 20.1-32.8], compared with 14.3 months (95% CI 11.9-18.1) in 130 patients without actionable ESCAT alterations (HR, 0.58; 95% CI, 0.40-0.85; P = 0.005). Among patients receiving matched targeted therapy, median progression-free survival was longer for patients with alterations classified as ESCAT I-II compared with ESCAT III-IV (5.0 vs. 1.9 months; HR, 0.36; 95% CI, 0.15-0.87; P = 0.02)., Conclusions: ESCAT represents a tool to guide clinicians in fine-tuning use of molecular profiling data to choose matched targeted therapies. Our data demonstrate that targeted treatment administered per alteration actionability according to ESCAT is associated with improved survival in cholangiocarcinoma, particularly in ESCAT I-II intrahepatic cholangiocarcinoma., (©2022 American Association for Cancer Research.)

Background: The first years of university can be very challenging for students. Previous research has focused on the study of the prevalence of burnout and of psychological distress in medical students. The aim of this study was to investigate the prevalence of psychological symptoms and burnout reported by first-year students, the relationship between these variables and their academic performance, and the differences between health and non-health sciences students., Methods: An observational study with a cross-sectional design was performed. Students of health sciences (medicine, nursing, physiotherapy, psychology), and non-health sciences (biology, social sciences, business management, and engineering) undergraduate programs completed the Brief Symptom Inventory (BSI-18) and the Maslach Burnout Inventory-Student Survey (MBI-SS). Students' grades for the first semester were collected., Results: A sample of 506 students participated. Prevalence of psychological distress was 27.1% and burnout was 7.3%. Academic performance was unaffected in relation to either psychological distress or burnout. Non-health sciences students showed a greater risk of depression., Conclusions: This study provides evidence of the high prevalence of psychological distress in the first year of college. Even when burnout prevalence was low, the results suggest the need to introduce prevention programs to improve the psychological wellbeing of these students.

Background: A description of individuals with SARS-CoV-2 infection comparing the first and second waves could help adapt health services to manage this highly transmissible infection., Objective: We aimed to describe the epidemiology of individuals with suspected SARS-CoV-2 infection, and the characteristics of patients with a positive test comparing the first and second waves in Catalonia, Spain., Methods: This study had 2 stages. First, we analyzed daily updated data on SARS-CoV-2 infection in individuals from Girona (Catalonia). Second, we compared 2 retrospective cohorts of patients with a positive reverse-transcription polymerase chain reaction or rapid antigen test for SARS-CoV-2. The severity of patients with a positive test was defined by their admission to hospital, admission to intermediate respiratory care, admission to the intensive care unit, or death. The first wave was from March 1, 2020, to June 24, 2020, and the second wave was from June 25, 2020, to December 8, 2020., Results: The numbers of tests and cases were lower in the first wave than in the second wave (26,096 tests and 3140 cases in the first wave versus 140,332 tests and 11,800 cases in the second wave), but the percentage of positive results was higher in the first wave than in the second wave (12.0% versus 8.4%). Among individuals with a positive diagnostic test, 818 needed hospitalization in the first wave and 680 in the second; however, the percentage of hospitalized individuals was higher in the first wave than in the second wave (26.1% versus 5.8%). The group that was not admitted to hospital included older people and those with a higher percentage of comorbidities in the first wave, whereas the characteristics of the groups admitted to hospital were more alike., Conclusions: Screening systems for SARS-CoV-2 infection were scarce during the first wave, but were more adequate during the second wave, reflecting the usefulness of surveillance systems to detect a high number of asymptomatic infected individuals and their contacts, to help control this pandemic. The characteristics of individuals with SARS-CoV-2 infection in the first and second waves differed substantially; individuals in the first wave were older and had a worse health condition., (©Lia Alves-Cabratosa, Marc Comas-Cufí, Jordi Blanch, Ruth Martí-Lluch, Anna Ponjoan, Antoni Castro-Guardiola, Abelardo Hurtado-Ganoza, Ana Pérez-Jaén, Maria Rexach-Fumaña, Delfi Faixedas-Brunsoms, Maria Angels Gispert-Ametller, Anna Guell-Cargol, Maria Rodriguez-Batista, Ferran Santaularia-Font, Ramon Orriols, Marc Bonnin-Vilaplana, Juan Carlos Calderón López, Gladis Sabater-Talaverano, Francesc Xavier Queralt Moles, Sara Rodriguez-Requejo, Esteve Avellana-Revuelta, Elisabet Balló, Ester Fages-Masmiquel, Josep-Maria Sirvent, Carol Lorencio, Josep Miquel Morales-Pedrosa, Patricia Ortiz-Ballujera, Rafel Ramos. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 06.01.2022.)

In the last decades, different non-thermal and thermal technologies have been developed for food processing. However, in many cases, it is not clear which experimental parameters must be reported to guarantee the experiments' reproducibility and provide the food industry a straightforward way to scale-up these technologies. Since reproducibility is one of the most important science features, the current work aims to improve the reproducibility of studies on emerging technologies for food processing by providing guidelines on reporting treatment conditions of thermal and non-thermal technologies. Infrared heating, microwave heating, ohmic heating and radiofrequency heating are addressed as advanced thermal technologies and isostatic high pressure, ultra-high-pressure homogenization sterilization, high-pressure homogenization, microfluidization, irradiation, plasma technologies, power ultrasound, pressure change technology, pulsed electric fields, pulsed light and supercritical CO 2 are approached as non-thermal technologies. Finally, growing points and perspectives are highlighted.

Objective: To describe the maternal, neonatal and pregnancy characteristics related to inhibition of lactation (IL) with cabergoline., Method: We assessed 20,965 occasions of breastfeeding initiation, according to data collected from obstetric records at the Hospital Clinic of Barcelona (Spain) between January 2011 and December 2017., Results: IL decreased over the study period from 8.78% to 6.18% (odds ratio [OR]: 0.93 per year; 95% confidence interval [95%CI]: 0.90-0.95). Women with a lower educational level (OR: 2.5; 95%CI: 2.0-3.0), mothers living in more depressed areas (OR: 1.08 per 10 extra points over 100; 95%CI: 1.04-1.12), smokers (OR: 2.2; 95%CI: 1.9-2.6), and those with more children (OR: 1.2 for each sibling; 95%CI: 1.1-1.3), preterm birth (OR: 1.8; 95%CI: 1.4-2.3), multiple births (OR: 1.6; 95%CI: 1.2-2.1) and a higher risk pregnancy (OR: 1.3 per risk point; 95%CI: 1.2-1.4) showed a higher prevalence of IL. Compared to women born in Spain, IL was less likely in all other women with the exception of Chinese women (OR: 7.0; 95%CI: 5.7-8.6). These disparities remained during the study period., Conclusions: Factors related to lower socioeconomic status and poor health were more likely to be associated with IL. The overall use of cabergoline decreased during the study period while inequalities persisted. Taking these inequalities into account is the first step to addressing them., (Copyright © 2021 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: Pancreatic cancer (PC) is one of the deadliest malignancies. The aim of this study was to determine the usefulness of the carbohydrate antigen 19.9 (CA19.9)/ carcinoembryonic antigen (CEA) ratio as a diagnostic tool., Methods: This was a retrospective observational study (2015-2019), including laboratory requests with increased CA19.9 and CEA but no previous neoplasia. Receiver operating characteristic (ROC) curve analyses were performed for the CA19.9/CEA ratio and for CA19.9 and CEA alone for the detection of PC, and cutoff values for all strategies were selected separately and in combination., Results: A total of 373 individuals were included. The area under the curve (AUC) for CA19.9/CEA was 0.872, whereas the AUC for CA19.9 was 0.847 and for CEA was 0.554. Cutoff values with the greatest diagnostic power were CA19.9/CEA >40, CA19.9 >1130 U/mL, and CEA > 14.5 U/mL. The combination of CA19.9/CEA > 40 with CA19.9 > 550 U/mL maximized the diagnostic accuracy for PC., Conclusion: Our results highlight the relevance of the measurement of serum CA19.9 and CEA in the detection of PC., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Tumour heterogeneity impacts the efficacy of metastatic cancer treatment even if actionable mutations are identified. Clinicians need to understand if assessing one lesion provides reliable information to drive a therapeutic decision in non-small-cell lung cancer (NSCLC) patients., Methods: We analysed inter-tumour heterogeneity from five autopsied individuals with NSCLC-harbouring mutations in the epidermal growth factor receptor (EGFR), treated with EGFR tyrosine kinase inhibitors (TKIs). Through a comprehensive next-generation sequencing (NGS) oncopanel, and an EGFR panel for digital droplet PCR (ddPCR), we compared metastases within individuals, longitudinal biopsies from the same lesions and, whenever possible, the primary naive tumour., Results: Analysis of 22 necropsies from five patients revealed homogeneity in pathogenic mutations and TKI-resistance mechanisms within each patient in four of them. In-depth analysis by whole-exome sequencing from patient 1 confirmed homogeneity in clonal mutations, but heterogeneity in passenger subclonal alterations. Different resistance mechanisms were detected depending on the patient and line of treatment. Three patients treated with a c-MET inhibitor in combination with TKI lost MET amplification upon progression., Conclusion: At a given point and under selective TKI pressure, a single metastasis biopsy in disseminated tumours from EGFR-mutated NSCLC patients could provide a reasonable assessment of actionable alterations useful for therapeutic decisions., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: Serum indices included in clinical chemistry instruments are widely used by laboratories to assess the quality of samples. Instruments that report quantitative results allow an evaluation of their diagnostic performance in a similar way to other biochemical tests. The Spanish Society of Laboratory Medicine (SEQC-ML) launched a monthly External Quality program of serum indices in 2018 using three lyophilized materials of simultaneous annual distribution. We present the results of the first three years of the program., Methods: The use of four different quality control materials with different concentrations in three alternate months allows an annual evaluation of the participant's accuracy. Assigned values are established by consensus among homogeneous groups, considering necessary at least 10 participants for a comparison at instrument level. The average percentage difference results per instrument allow the assessment of bias among groups., Results: The imprecision of the three indices ranges between 3 and 9%, with no major differences among instruments. Significant differences were observed in all indices among instruments with more than 10 participants (Roche Cobas, Abbott Architect, Abbott Alinity and Siemens Advia). The 90th percentile of the distribution of percentage differences was used as the analytical performance specification (APS). An improvement in performance was observed in the first three years of the program, probably due to the learning curve effect. In 2020, APS of 7.8, 12.2 and 9.7% were proposed for hemolytic, icteric and lipemic indices, respectively., Conclusions: Serum indices have a great impact on the quality and the reliability of laboratory test results. Participation in proficiency testing programs for serum indices is helpful to encourage harmonization among providers and laboratories., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: To analyse determinants of mortality at 15years in a population over 60years of age and physically active., Methods: This is a prospective longitudinal study. After 15years of participating in an active aging programme, participants were contacted by telephone to verify their state of health and to determine whether in that time they had had any fractures., Results: A total of 561 individuals over 60years of age were included, 82% of whom were women. Only differences in densitometric data, FRAX values and history of previous fracture at baseline characteristics were found between the group that died at 15years and the group that remained alive. The only variables that were related to mortality risk were the basal data of the densitometric T-score (OR=.50, P<.001) and history of fracture in any location (OR=2.44, P<.033)., Conclusions: The value of bone mineral density could be considered as a useful biomarker to calculate the risk of mortality in people over 60years old with a physically active lifestyle., (Copyright © 2021 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objectives: Anti-IL6R tocilizumab (TCZ) therapy has proved to be useful in the treatment of refractory ocular and/or neurological involvement of Behçet's disease (BD). However, TCZ efficacy in other BD manifestations remains unclear. In this study we aimed to assess the efficacy of TCZ in the different clinical phenotypes of BD., Methods: This is a multicentre study of BD patients treated with TCZ, due to refractivity to standard systemic treatment., Results: We studied 16 patients (10 men/6 women); mean age 36.5±18.2 years. The main clinical manifestations at TCZ onset were ocular, oral and/or genital ulcers, arthritis, folliculitis and/or neurological involvement. Before TCZ, they had received several conventional and/or biological immunosuppressants, such as methotrexate, cyclosporine, adalimumab or infliximab. TCZ was used in monotherapy or combined with conventional immunosuppressive drugs. The main indications for TCZ prescription were refractory uveitis (n=14) and refractory neurobehçet (n=2). After a median [IQR] follow-up of 20 [9-45] months using TCZ, neurological and ocular domains improved in most cases with complete remission in most patients with uveitis. Articular and peripheral venous manifestations also experienced a favourable evolution. However, oral/genital ulcers, skin lesions and intestinal manifestations followed a torpid course., Conclusions: TCZ is effective in BD with major clinical involvement. However, it does not seem to be effective in oral/genital ulcers or skin lesions.

Plant viruses can evolve towards new pathogenic entities that may eventually cause outbreaks and become epidemics or even pandemics. Seven years ago, tomato brown rugose fruit virus (ToBRFV) emerged, overcoming the genetic resistance that had been employed for more than sixty years against tobamoviruses in tomato. Since then, ToBRFV has spread worldwide, producing significant losses in tomato crops. While new resistances are deployed, the only means of control is the implementation of effective prevention and eradication strategies. For this purpose, in this work, we have designed, assessed, and compared an array of tests for the specific and sensitive detection of the ToBRFV in leaf samples. First, two monoclonal antibodies were generated against a singular peptide of the ToBRFV coat protein; antibodies were utilized to devise a double-antibody-sandwich enzyme-linked immunosorbent assay (DAS-ELISA) test that sensitively detects this virus and has no cross-reactivity with other related tobamoviruses. Second, a real-time quantitative PCR (RT-qPCR) test targeting the RNA-dependent replicase open reading frame (ORF) was designed, and its performance and specificity validated in comparison with the CaTa28 and CSP1325 tests recommended by plant protection authorities in Europe. Third, in line with the tendency to use field-deployable diagnostic techniques, we developed and tested two sets of loop-mediated isothermal amplification (LAMP) primers to double-check the detection of the movement protein ORF of ToBRFV, and one set that works as an internal control. Finally, we compared all of these methods by employing a collection of samples with different ToBRFV loads to evaluate the overall performance of each test.

In laboratory medicine, much effort has been put into analytical quality in the past decades, making this medical profession one of the most standardized with the lowest rates of error. However, even the best analytical quality cannot compensate for errors or low quality in the pre or postanalytical phase of the total testing process. Guidelines for data reporting focus solely on defined data elements, which have to be provided alongside the analytical test results. No guidelines on how to format laboratory reports exist. The habit of reporting as much diagnostic data as possible, including supplemental information, may lead to an information overload. Considering the multiple tasks physicians have to do simultaneously, unfiltered data presentation may contribute to patient risk, as important information may be overlooked, or juxtaposition errors may occur. As laboratories should aim to answer clinical questions, rather than providing sole analytical results, optimizing formatting options may help improve the effectiveness and efficiency of medical decision-making. In this narrative review, we focus on the underappreciated topic of laboratory result reporting. We present published literature, focusing on the impact of laboratory result report formatting on medical decisions as well as approaches, potential benefits, and limitations for alternative report formats. We discuss influencing variables such as, for example, the type of patient (e.g. acute versus chronic), the medical specialty of the recipient of the report, the display of reference intervals, the medium or platform on which the laboratory report is presented (printed paper, within electronic health record systems, on handheld devices, etc.), the context in which the report is viewed in, and difficulties in formatting single versus cumulative reports. Evidence on this topic, especially experimental studies, is scarce. When considering the medical impact, it is of utmost importance that laboratories focus not only on the analytical aspects but on the total testing process. The achievement of high analytical quality may be of minor value if essential results get lost in overload or scattering of information by using a non-formatted tabular design. More experimental studies to define guidelines and to standardize effective and efficient reporting are most definitely needed.

The present study draws from data collected with informal recyclers in the autonomous region of Catalonia in northeastern Spain. The purpose of the investigation is to determine the relationship between the formal and informal recycling sectors in Catalonia and determine how each of their activities impacts the other. From the case study in the city of Granollers, it was determined that from the spring of 2018 to the fall of 2019, the informal recyclers had the potential to collect roughly 44% of the cardboard in their geographical area, helping to meet the environmental goals of the region, but receiving no recognition for their work nor acknowledgement regarding their role in the waste management system. This investigation also analyzed the economic relationship between the formal and informal systems, and the effects that international events, such as China's National Sword policy, had on that relationship. It was determined that the embeddedness of waste systems and global waste markets affect not only the formal system, but their relationship with the informal system as well., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Recent growth and institutionalization in the field of mixed methods research has provided fertile ground for a wide range of thoughtful criticism of how this research approach has been developed and conceptualized by some members of the mixed methods community. This criticism reflects the increasing maturity of the field as well as the different theoretical perspectives and methodological practices of researchers in different disciplines. While debates addressing these criticisms are likely to lead to valuable insights, no empirical studies have been carried out to date that have investigated researchers' critical views on the development and conceptualization of mixed methods research. This study examines the criticisms of the mixed methods field raised by a cross-national sample of researchers in education, nursing, psychology, and sociology. We carried out a secondary analysis of semi-structured interviews with 42 researchers and identified 11 different criticisms, which we classified in four domains: essence of mixed methods, philosophy, procedures, and politics. The criticisms related to the procedures domain were equally distributed among the four disciplines, while those related to the essence, philosophy and politics domains were more common among sociologists. Based on our findings, we argue that the divergence of views on foundational issues in this field reflects researchers' affiliation to different communities of practice, each having its own principles, values, and interests. We suggest that a greater awareness of this divergence of perspectives could help researchers establish effective collaboration and anticipate potential challenges when working with researchers having different methodological approaches., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Quality control of ultrasonography markers is necessary to ensure greater efficacy of prenatal aneuploidy screening. The aim of this study was to assess the quality of the crown-rump length (CRL) and nuchal translucence (NT) measurement accuracy by the laboratory according to quality indicators., Methods: Retrospective observational study on 4,908 single-foetus pregnant women who underwent prenatal aneuploidy screening in the first trimester of pregnancy. Euploid foetuses with CRL between 45 and 84 mm were included, while those with NT≥3.5 mm were excluded. CRL measurement was considered to be accurate if the median multiples of the median (MoM) for pregnancy-associated plasma protein A (PAPP-A) was between 0.90 and 1.10. Fifteen sonographers participated in the study, six of whom comprised the control group. Systematic error for a sonographer was considered when CRL measurement was greater than ±2 mm with respect to the control group. Quality for NT was assured by means of the WHIRI method and each sonographer cumulative sum control chart (CUSUM)., Results: For CRL accuracy, five sonographers underestimated the measurements, while another four overestimated them, with no statistical differences. For smaller sized foetuses, all sonographers met the established specifications. Regarding NT control, three sonographers did not meet the quality criteria for the median MoM. All sonographers met the specifications for the logarithmic standard deviation of the NT MoM levels. Thirteen sonographers met the CUSUM specifications., Conclusions: Evaluation of a quality control of ultrasonography parameters by laboratory professionals is necessary to avoid under- or overestimation tendencies for CRL and NT measurements. CUSUM is a useful tool for the immediate correction of errors in NT measurements., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Myocardial injury is a common finding in COVID-19 strongly associated with severity. We analysed the prevalence and prognostic utility of myocardial injury, characterized by elevated cardiac troponin, in a large population of COVID-19 patients, and further evaluated separately the role of troponin T and I., Methods: This is a multicentre, retrospective observational study enrolling patients with laboratory-confirmed COVID-19 who were hospitalized in 32 Spanish hospitals. Elevated troponin levels were defined as values above the sex-specific 99th percentile upper reference limit, as recommended by international guidelines. Thirty-day mortality was defined as endpoint., Results: A total of 1280 COVID-19 patients were included in this study, of whom 187 (14.6%) died during the hospitalization. Using a nonspecific sex cut-off, elevated troponin levels were found in 344 patients (26.9%), increasing to 384 (30.0%) when a sex-specific cut-off was used. This prevalence was significantly higher (42.9% vs 21.9%; P < .001) in patients in whom troponin T was measured in comparison with troponin I. Sex-specific elevated troponin levels were significantly associated with 30-day mortality, with adjusted odds ratios (ORs) of 3.00 for total population, 3.20 for cardiac troponin T and 3.69 for cardiac troponin I., Conclusion: In this multicentre study, myocardial injury was a common finding in COVID-19 patients. Its prevalence increased when a sex-specific cut-off and cardiac troponin T were used. Elevated troponin was an independent predictor of 30-day mortality, irrespective of cardiac troponin assay and cut-offs to detect myocardial injury. Hence, the early measurement of cardiac troponin may be useful for risk stratification in COVID-19., (© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background and Objectives: Available evidence suggests a familial basis for OSA. The aim of the present study was to assess the potential influences of parental OSA in predicting the diagnosis and severity of OSA in snoring children., Methods: Observational study, we prospectively enrolled 84 children and their parents. A complete nocturnal polysomnography was performed. Children were categorized into 3 severity groups according to the apnea-hypopnea index (AHI<1h -1 , AHI≥1h -1 to AHI<5h -1 , and AHI≥5h -1 ). Adults were grouped according two criteria (AHI≥5h -1 and ≥10h -1 )., Results: There were no significant differences in age, gender, BMI and BMI z-score among groups. Among the children, 54.7% had an AHI≥1h -1 and 21.4% had an AHI≥5h -1 . Overall, we observed that 60.7% of fathers and 23.8% of mothers of our population had OSA (AHI≥5h -1 ). The prevalence of fathers with OSA increases with the children's severity (83% in the group of children with moderate-severe OSA, p=0.035). The odds of having moderate-severe pediatric OSA (AHI≥5h -1 ) were more than 4 times higher among children with a father with AHI≥5h -1 (OR: 4.92, 95% CI: 1.27-19.06; p=0.021). There was no evidence of any maternal influence on OSA severity among the children studied., Conclusions: Our findings suggest a high prevalence of OSA among the family members studied with an increased association of childhood OSA with paternal OSA. Prediction of OSA risk among children can be significantly improved by adding data on paternal OSA status., (Copyright © 2020 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Identification of predictors for severe disease progression is key for risk stratification in COVID-19 patients. We aimed to describe the main characteristics and identify the early predictors for severe outcomes among hospitalized patients with COVID-19 in Spain. This was an observational, retrospective cohort study (BIOCOVID-Spain study) including COVID-19 patients admitted to 32 Spanish hospitals. Demographics, comorbidities and laboratory tests were collected. Outcome was in-hospital mortality. For analysis, laboratory tests values were previously adjusted to assure the comparability of results among participants. Cox regression was performed to identify predictors. Study population included 2873 hospitalized COVID-19 patients. Nine variables were independent predictors for in-hospital mortality, including creatinine (Hazard ratio [HR]:1.327; 95% Confidence Interval [CI]: 1.040-1.695, p  = .023), troponin (HR: 2.150; 95% CI: 1.155-4.001; p  = .016), platelet count (HR: 0.994; 95% CI: 0.989-0.998; p  = .004) and C-reactive protein (HR: 1.037; 95% CI: 1.006-1.068; p  = .019). This is the first multicenter study in which an effort was carried out to adjust the results of laboratory tests measured with different methodologies to guarantee their comparability. We reported a comprehensive information about characteristics in a large cohort of hospitalized COVID-19 patients, focusing on the analytical features. Our findings may help to identify patients early at a higher risk for an adverse outcome.

Sparkling wines elaborated with a traditional method need to age in the bottle in contact with wine lees because yeast autolysis enriches the wines in colloids and improves their effervescence, foam and aromatic complexity. It is generally considered that lees protect the wine against oxidation because they consume small amounts of oxygen that can permeate the crown cap. However, to our knowledge there is no specific study on this subject using lees from real sparkling wine. Therefore, the oxygen consumption rate (OCR) of the lees of sparkling wines from the first to the ninth year of aging time was measured using a noninvasive fluorescence measurement method. The results indicate that lees really consume oxygen and that their OCR tended to decrease with the wine aging time. These data suggest that the lees' capacity to protect against oxidation decreases over time, which could affect the ability of sparkling wines to age properly., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Proper specimen collection is central to improving patient care by ensuring optimal yield of diagnostic tests, guiding appropriate management, and targeting treatment. The purpose of this article is to describe the development and implementation of a training-of-trainers educational program designed to improve clinical culture specimen collection among healthcare personnel (HCP) in Ethiopia., Methods: A Clinical Specimen Collection training package was created consisting of a Trainer's Manual, Reference Manual, Assessment Tools, Step-by-Step Instruction Guides (i.e., job aides), and Core Module PowerPoint Slides., Results: A two-day course was used in training 16 master trainers and 47 facility-based trainers responsible for cascading trainings on clinical specimen collection to HCP at the pre-service, in-service, or national-levels. The Clinical Specimen Collection Package is offered online via The Ohio State University's CANVAS online platform., Conclusions: The training-of-trainers approach may be an effective model for development of enhanced specimen collection practices in low-resource countries.

Background: In other healthcare professions, there has been extensive research into students' motivation, but studies aiming to determine what leads individuals to choose a degree in physiotherapy are scarce. This research study had three main objectives: to obtain a sociodemographic profile of first-year physiotherapy students in Catalonia; to determine the factors that lead individuals to choose a degree in physiotherapy; and to determine potential differences, according to gender and country of origin., Methods: This is an observational, cross-sectional, multicentre study. Data were collected by means of a self-administered, ad-hoc questionnaire, consisting of 15 Likert scale questions, options ranging from "not influencing at all -1-" to "extremely influencing -5-". Ten out of the twelve universities in Catalonia (Spain) that offer a degree in physiotherapy participated in this study. The sample consisted of 941 first-year physiotherapy students (55.2% men; mean age 20.1, SD: 3.4)., Results: The most determinant factors leading individuals to pursue a degree in physiotherapy were: helping others (95.6%); the relationship between physiotherapy and sports (79%); physiotherapy involving manual work (76.4%); and it being perceived as providing multiple job opportunities (75.9%). Male and French students were attracted due to its relation to sports (MD = 0.369, p  < 0.001 and MD = 0.130, p  < 0.027), perception of it being an easy degree (MD = 0.148, p  < 0.001 and MD = 0.091, p  < 0.037), admiration for a known physiotherapist (MD = 0.223, p  = 0.006 and MD = 0.265, p  = 0.001), employability (MD = 0.297, p  < 0.001 and MD = 0.706, p  < 0.001), good income (MD = 0.190, p  = 0.002 and MD = 0.609, p  < 0.001) and social recognition (MD = 0.164, p  = 0.011 and MD = 0.286, p  < 0.001). Helping others (MD = -0.149, p  < 0.001) and interest in the sciences (MD = -0.164, p  = 0.030) were more determinant for female students. Male students were more guided by recommendation (MD = 0.234, p  = 0.001) and to complement previous studies (MD = 0.237, p  = 0.016). French students tended to present more interest in the selection of physiotherapy as a wish since childhood (MD = 0.595, p  < 0.001), due to its multiple job opportunities (MD = 0.427, p  < 0.001) and because of manual work, and did not choose it to complement previous studies (MD = -1.122, p  < 0.001)., Conclusions: The desire to help and care for others, the relation to sports, and involving manual work are the predominant factors that lead students to pursue a degree in physiotherapy. Female students favour helping others and science, whereas male students favour its relation to sports, complementing studies, social factors (admiration, recommendation, friendship) and socioeconomic determinants such as employability, good income or social recognition. When compared to Spanish students, French students were more motivated by its connection to sports, social and socioeconomic factors and some vocational determinants such as being a wish since childhood and interest in a manual profession., Competing Interests: The authors declare there are no competing interests., (©2021 Fuente-Vidal et al.)

Background-Aim: Diabetes mellitus is one of the most prevalent diseases worldwide. According to the ADA 2020 guidelines, individuals with unstable glycemic control should be monitored every three months by measuring glycated hemoglobin (HbA1c). The aim of this study was to evaluate the demand adequacy for HbA1c in the monitoring of patients with diabetes mellitus with a highly unstable glycemic control., Methods: Retrospective observational study (2016-2019). All HbA1c tests from individuals ≥18 years requested by hospital physicians were considered.Highly unstable glycemic control was defined as HbA1c≥10.0%, and their monitoring was classified as: optimal, out of recommendations (if>3months) and lack of monitoring if no further HbA1c measurement was performed by the laboratory.For individuals classified as lack of monitoring , medical records were reviewed and further re-classified as: [1] due to patient's responsibility, [2] attributable to the requesting physician, [3] monitored by POCT, [4] unfeasibility of monitoring or [5] referral outside our area for follow-up., Results: During the assessed period, 1,156 patients had an HbA1c value≥10.0%. 67.5% of them were monitored either in the clinical laboratory or as POCT (33.7% optimal monitoring), whereas 21.0% patients were not monitored due to preventable situations., Conclusion: Lack of monitoring due to physician's reasons or patient's responsibility highlights the urgent need for an improvement., Competing Interests: Conflicts of interest All authors declare no conflicts of interest., (Copyright © 2021 International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). All rights reserved.)

Newborn Screening Programs (NSP) in Spain were born in the city of Granada in 1968. Till the 1980s, they were developed around the so-called "National Plan for Preventing Subnormality", covering up to 30% of the Spanish newborns. From 1982, when the health system management was transferred to the different autonomous regions, the NSP began to expand, and the bases to transform them into an organized and multidisciplinary activity, integrated and coordinated from the National Health System were settled. Despite this expansion, it is not until the 1990s when their coverage reaches almost 100% newborns in Spain. NSP grew up asymmetrically across the different autonomous regions. In 2005 and 2006 the scientific societies SEQC (Spanish Society of Clinical Chemistry) and AECNE (Spanish Society of Newborn Screening), coordinated by the Health Promotion Area of the General Directorate of Public Health, gathered together the necessary information to elaborate a report on the NSP in Spain addressed to the Interterritorial Council of the National Health System. In July 2013, that Council approved the seven diseases that should be part of each region newborn screening panel, being the first step towards the NSP harmonization in Spain. Currently, the NSP include between 8 and 29 diseases in their panels, thus more still more efforts are needed in order to achieve a higher uniformity.

Objective: To investigate whether early response to tocilizumab (TCZ) and sarilumab (SAR) therapy in patients with active rheumatoid arthritis (RA) is influenced by previous use of biologic agents., Methods: We performed a systematic literature review and a meta-analysis of original studies that analyzed the effectiveness of TCZ or SRL in subgroups of RA patients, including biologic-naïve patients versus those with inadequate response to at least one biologic DMARD (bDMARD), and patients with failure to 1 versus≥2 bDMARDs., Results: The study selection process finally included 17 articles corresponding to 14 studies, including 7 randomized controlled trials (RCTs). Although the existing literature that compared the response in biologic-naïve patients versus those with inadequate response to at least one bDMARD showed conflicting results, meta-analysis of 6 published studies revealed a significantly higher likelihood of remission (RR=1.3; 95% CI: 1.2-1.5) and low activity disease (RR=1.3; 95% CI: 1.2-1.4) in the biologic-naïve group at week 24. However, differences between groups were not clinically meaningful in all studies and not always maintained after 6 to 12months of treatment. In addition, data from RCT RADIATE and TARGET suggest that the response to IL-6 pathway inhibitors seems to be similar, regardless of the number of tumor necrosis factor inhibitors (TNFis) previously tested., Conclusion: Disease activity was more rapidly reduced in the early stages of treatment in biologic-naïve patients. However, near similar efficacy can be expected in patients who experienced a failure of at least one bDMARD (mainly TNFis) beyond the first 6 to 12months of treatment, suggesting that the response occurs independently of the number of prior TNFis., (Copyright © 2020 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Background-Aim: Different protocols exist for newborn screening of congenital hypothyroidism (CH) worldwide, with different thyrotropin cut-off values for repetition and confirmation tests. This study aimed to assess local protocol in terms of specificity and improve our screening process by optimizing thyrotropin cut-off values. Subsequently, the cut-off values obtained were retrospectively applied to evaluate the number of tests avoided., Methods: Retrospective observational study between 2013 and 2019. All newborn children with a confirmation test for CH were considered for the study. ROC curve analysis was performed for thyrotropin cut-off value optimization in DBS which triggers a confirmatory test, and odds ratios were calculated. For individuals affected by the cut-off value modification, serum thyrotropin and free thyroxine in the confirmation test were analyzed for consideration of clinical outcomes., Results: A total of 72,133 newborn children were screened for CH, and 208 individuals were included in the study. Incidence in our population was 1:2,000 live births. The area under the ROC curve was 0.819 (CI 95%: 0.748-0.897). While the current cut-off value (thyrotropin ≥ 10mIU/L) had a specificity of 31.8% [ORs: 3.5 (CI 95%: 1.4-8.8)], the optimal cut-off value (thyrotropin ≥ 15mIU/L) yielded a specificity of 92.4% for the detection of CH and transient hypothyroidism [ORs: 15.9 (CI 95%: 7.1-35.8)], with no loss of sensitivity., Discussion: While keeping a maximum sensitivity, optimization of cut-off values may be of great use not only in management, but also in reducing family stress, which is of special relevance for the newborn., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The use of UHPH sterilization in the absence of SO 2 has been used to eliminate wild microorganisms and inactivate oxidative enzymes. A white must of the Muscat of Alexandria grape variety was continuously processed by UHPH at 300 MPa (inlet temperature: 23-25 °C). The initial microbial load of the settled must was 4-log CFU/mL for both yeast and moulds, and slightly lower for bacteria. After UHPH processing, no microorganisms were detected in 1 mL. UHPH musts remain without fermentative activity for more than 60 days. Concentrations of the thermal markers indicated the absence of thermal damage in the UHPH-treated musts, since 5-hydroxymethylfurfural was not detected. In addition, the must treated by UHPH keeps terpene concentrations similar to those of the untreated controls. A strong inactivation of the oxidative enzymes was observed, with no browning at room temperature for more than 3 days. The antioxidant value of the UHPH-treated must was 156% higher than the control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Improved point-of-care diagnostic tests for tuberculosis (TB) in severe immune suppressed people living with HIV (PLWH) are needed to decrease morbidity and mortality outcomes. The aim of the study is to evaluate the performance of the lipoarabinomannan antigen test (LAM-test) with and without α-mannosidase pre-treated urine in a cohort of PLWH in primary care clinics in Guatemala. We further determined TB incidence, and mortality rates and its risk factors in PLWH with TB symptoms., Methods: Prospective longitudinal study of PLWH with TB symptoms. Urine samples were collected at 2 HIV sites to test the sensitivity of the LAM-test in urine with and without α-mannosidase pre-treatment. A composite reference standard of either a positive Mycobacterium tuberculosis complex culture and/or GeneXpert ® MTB/RIF (Xpert, Cepheid, Sunnyvale, CA, USA) results was used in the LAM-test diagnostic accuracy studies. Cox proportional hazards regression was used to study mortality predictors., Results: The overall sensitivity of the LAM-test was of 56.1% with 95% CI of (43.3-68.3). There were no differences in the LAM-test sensitivity neither by hospital nor by CD4 T cell values. LAM-test sensitivity in PLWH with < 200 CD4 T cells/µl was of 62.2% (95% CI 46.5-76.2). There were no significant differences in sensitivity when comparing LAM-test results obtained from untreated vs. α-mannosidase treated urine [55.2% (95% CI 42.6-67.4) vs. 56.9% (95% CI 44-69.2), respectively]. TB incidence in our cohort was of 21.4/100 person years (PYs) (95% CI 16.6-27.6), and mortality rate was of 11.1/100 PYs (95% CI 8.2-15.0). Importantly, PLWH with a positive LAM-test result had an adjusted hazard ratio (aHR) of death of 1.98 (1.0-3.8) with a significant p value of 0.044 when compared to PLWH with a negative LAM-test result., Conclusions: In this study, α-mannosidase treatment of urine did not significantly increase the LAM-test performance, however; this needs to be further evaluated in a large-scale study due to our study limitations. Importantly, high rates of TB incidence and mortality were found, and a positive LAM-test result predicted mortality in PLWH with TB clinical symptoms.

Introduction: Red cell distribution width (RDW) is a parameter included in the complete blood count which informs about the size of the circulating red blood cell population and its distribution. In adults, an increase in RDW was shown to be associated both with obstructive sleep apnoea (OSA) and with an increase in cardiovascular mortality. The aim of this study was to determine whether RDW is a potential biomarker for screening children with moderate-severe OSA., Methods: An observational study in snoring patients was performed. All patients underwent a sleep study and were classified either as simple snorers (apnoea-hypopnoea index (AHI) <1 event·h -1 ) or as patients with OSA (mild AHI ≥1 to <5 events·h -1 ; moderate-severe AHI ≥5 events·h -1 ). Blood analyses (complete blood count and C-reactive protein) were performed for every individual., Results: A total of 175 individuals were recruited. The mean age was 8.3±3.6 years. Correlation studies between RDW and several sleep-related parameters showed negative significant associations with minimum oxygen saturation, and positive significant associations with oxygen desaturation index (≥3% and ≥4%), AHI and the arousal index. A predictive model for paediatric severe OSA (AHI ≥5 events·h -1 ) was found based on mean corpuscular haemoglobin concentration (MCHC) <34.9 g·dL -1 and RDW >13.1% values, adjusting for body mass index z-score and age (area under the curve 0.657; p=0.004). In addition, differences were found in eosinophil count and C-reactive protein concentrations among the three subgroups., Conclusions: In children, RDW stands out as a biomarker associated with the severity of OSA. The use of RDW and MCHC could be a simple but useful tool for the severity prediction of paediatric OSA in snoring patients., Competing Interests: Conflict of interest: D. Morell-Garcia received a grant from Fondo de Investigación Sanitaria during the conduct of the study. Conflict of interest: N. Toledo-Pons received a grant from Fondo de Investigación Sanitaria during the conduct of the study. Conflict of interest: P. Sanchis received a grant from Fondo de Investigación Sanitaria during the conduct of the study. Conflict of interest: J.M. Bauça received a grant from Fondo de Investigación Sanitaria during the conduct of the study. Conflict of interest: J.M. Sánchez received a grant from Fondo de Investigación Sanitaria during the conduct of the study. Conflict of interest: J. Peña-Zarza received a grant from Fondo de Investigación Sanitaria during the conduct of the study. Conflict of interest: P. Giménez received a grant from Fondo de Investigación Sanitaria during the conduct of the study. Conflict of interest: J. Pierola received a grant from Fondo de Investigación Sanitaria during the conduct of the study. Conflict of interest: M. de la Peña-Bravo received a grant from Fondo de Investigación Sanitaria during the conduct of the study. Conflict of interest: A. Alonso-Fernández received a grant from Fondo de Investigación Sanitaria during the conduct of the study. Conflict of interest: A. Barceló received a grant from Fondo de Investigación Sanitaria during the conduct of the study., (Copyright ©ERS 2020.)

Background-Aim: Appropriately defined reference values are of vital importance for the correct interpretation of laboratory results. However, the implementation of in-house reference intervals by traditional methods is rare due to difficulties in the selection of reference individuals, so indirect methods are often alternatively used. Parathyroid hormone (PTH) is a crucial hormone for the metabolism of calcium and phosphorus whose result can lead to erroneous diagnoses and medical actions if adequate reference intervals are not readily available. Our goal was to obtain reference values ​​for adult population for PTH by using data mining. Based on possible new reference intervals, we also aimed to perform a retrospective evaluation of the individuals mistakenly classified., Methods: Retrospective observational study between 2014 and 2019. All requests from individuals aged ≥ 18 years were considered if PTH was requested together with serum creatinine, 25-hydroxyvitamin D, calcium, albumin and phosphate (within their respective reference intervals). PTH was measured on the Cobas e411 platform (Roche). Requests were grouped by age and sex. Differences among partitions were assessed by the Harris-Boyd's test and reference intervals were determined by the non-parametrical calculation of percentiles 2.5 and 97.5., Results: A total of 2279 laboratory requests were included. Reference intervals for PTH were seen to be sex-independent, but age-dependent reference intervals were needed: 18-39, 40-59 and >60 years. Based on the reference intervals obtained, up to 20.1% of individuals were misclassified., Conclusions: Appropriateness of PTH reference intervals would lead to a reduction in the number of additional tests and avoid wrong medical actions, thus improving not only patient safety, but also the healthcare system as a whole., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Coronavirus disease 2019 (COVID-19) pneumonia is associated to systemic hyper-inflammation and abnormal coagulation profile. D-dimer elevation is particularly frequent, and values higher than 1μg/mL have been associated with disease severity and in-hospital mortality. Previous retrospective studies found a high pulmonary embolism (PE) prevalence, however, it should be highlighted that diagnoses were only completed when PE was clinically suspected., Material and Methods: Single-center prospective cohort study. Between April 6th and April 17th 2020, consecutive confirmed cases of COVID-19 pneumonia with D-dimer >1 μg/mL underwent computed tomography pulmonary angiography (CTPA) to investigate the presence and magnitude of PE. Demographic and laboratory data, comorbidities, CTPA scores, administered treatments, and, clinical outcomes were analysed and compared between patients with and without PE., Results: Thirty consecutive patients (11 women) were included. PE was diagnosed in 15 patients (50%). In patients with PE, emboli were located mainly in segmental arteries (86%) and bilaterally (60%). Patients with PE were significantly older (median age 67.0 (IQR 63.0-73.0) vs. 57.0 (IQR 48.0-69.0) years, p = .048) and did not differ in sex or risk factors for thromboembolic disease from the non-PE group. D-dimer, platelet count, and, C reactive protein values were significantly higher among PE patients. D-dimer values correlated with the radiologic magnitude of PE (p<0.001)., Conclusions: Patients with COVID-19 pneumonia and D-dimer values higher than 1 μg/mL presented a high prevalence of PE, regardless of clinical suspicion. We consider that these findings could contribute to improve the prognosis of patients with COVID-19 pneumonia, by initiating anticoagulant therapy when a PE is found., Competing Interests: The authors have declared that no competing interests exist.

Competing Interests: Competing interests: Authors state no conflict of interest.

Background: Promising results have been reported with immune checkpoint inhibitors (ICI) in a small proportion of MPM patients. MMR deficiency (dMMR) has been well described in several malignancies and was approved as a biomarker for anti-PD-1 inhibitors. Next generation sequencing (NGS) data demonstrated that 2% of MPM harbor microsatellite instability. The aim of this study is to characterize MMR by immunohistochemistry (IHC) in a series of MPM including a subset of patients treated with immunotherapy., Methods: Tumors of 159 MPM p diagnosed between 2002 and 2017 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained for MLH1, MSH2, MSH6 and PMS2 and tumors were classified as dMMR (MMR protein expression negative) and MMR intact (all MMR proteins positively expressed). We retrospectively collected clinical outcomes under standard chemotherapy and experimental immunotherapy in the entire cohort., Results: MMR protein expression was analyzed in 158 samples with enough tissue and was positive in all of the cases. Twenty two patients received ICI with anti-CTLA4 or anti-PD-1 blockade in clinical trials, 58% had a response or stable disease for more than 6 m, with median progression-free survival (PFS) of 5.7 m (2.1-26.1 m). The median overall survival (mOS) in all population was 15 months (m) (13.5-18.8 m). In a multivariable model factors associated to improved mOS were PS 0, neutrophil-lymphocyte ratio (NLR) < 5 and epithelioid histology (p < 0.001)., Conclusions: In our series we were unable to identify any MPM patient with dMMR by IHC. Further studies are needed to elucidate potential predictive biomarkers of ICI benefit in MPM.

Objectives: Young laboratory medicine professionals (YLMPs) are the future of clinical laboratories. Although everyday practice shows significant differences among countries, especially during residency training, most of them face the same challenges. Besides promoting scientific, professional and clinical aspects of laboratory medicine in Europe, the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) should take into consideration YLMPs' concerns and interests to help them achieve excellence. The aim of this survey was to assess the opinion and expectations of YLMPs about their involvement in the activities of EFLM., Methods: An online survey was distributed to YLMPs in Europe through different channels. The questionnaire consisted of 21 items grouped into five sections: demographic questions, opinion about the current status of YLMPs within EFLM, YLMPs network, suggestions and opportunities, and scientific training and exchange. Where appropriate, responses from residents and specialists were compared., Results: A total of 329 valid responses were obtained from 53 different countries. Countries with the highest number of participants were Spain, Turkey, Croatia and Romania. A significant percentage would like to know more about EFLM and their activities (86%) and wish EFLM promoted networking and scientific exchanges (95%), for instance by means of a European YLMPs network (93%). EFLMLabX project was widely unknown (75%)., Conclusions: YLMPs demand better connection to share concerns about daily healthcare duties, to keep updated and to advance professionally. EFLM needs to improve their advertising through national societies to increase YLMPs' participation. In addition to international meetings and congresses, respondents have emphasized that workshops and other small group activities would significantly help promote laboratory medicine practice in Europe.

On March 12, 2020, with more than 20,000 confirmed cases and almost 1000 deaths in the European Region, the World Health Organization classified the COVID-19 outbreak as a pandemic. As of August 15, 2020, there are 21.5 million confirmed cases of COVID-19 and over 766,000 deaths from the virus, worldwide. Most governments have imposed quarantine measures of varied degrees of strictness on their populations in attempts to stall the spread of the infection in their communities. However, the isolation may have inflicted long-term psychological injury to the general population and, in particular, to at-risk groups such as the elderly, the mentally ill, children, and frontline healthcare staff. In this article, we offer the most up-to-date review of the effects of COVID-19 confinement on all the disorders listed in the Diagnostic and Statistical Manual of Mental Disorders. We make data-driven predictions of the impact of COVID-19 confinement on mental health outcomes and discuss the potential role of telemedicine and virtual reality in mental health screening, diagnosis, treatment, and monitoring, thus improving the above outcomes in such a difficult time., Competing Interests: Psious and IKONA are privately owned digital health companies., (Copyright: © 2020 DIGITAL MEDICINE.)

Enzymatic parameters (K M and V max ), residual activity, effect of bentonite and electrophoresis characterization of laccase in the presence of different oenological tannins (OT) were investigated in relation to B. cinerea negative effects in grapes and musts. Five OT were tested (gallotannin, ellagitannin, quebracho, grape-skin and grape-seed) in comparison with ascorbic acid (AA), sulfur dioxide (SO 2 ) and bentonite. We added OT, AA, SO 2 and bentonite to botrytized must obtained by inoculation of grapes with B. cinerea strain 213. Laccase activity was measured by the syringaldazine method at different concentrations of substrate. Enzymatic parameters were determined using Michaelis-Menten and Lineweaver-Burk plots. The B. cinerea strain was also grown in a liquid medium for laccase production. Molecular weight of laccases and effect of OT upon these laccases were studied by SDS-PAGE. Results confirm that bentonite, contrary to OT, did not permit to reduce laccase activity. Regardless the tannin considered, V max , K M and laccase activity were reduced and gallotannin, grape-skin and grape-seed tannin presented the greatest ability. Efficiency of grape-seed tannin addition in order to reduce the laccase activity, was comparable to that of AA or SO 2 at the typical doses employed in oenology for each one. Oenological tannins appear to be excellent processing aids to prevent laccase effects and contribute to reduce the use of SO 2 in grapes and musts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)