Biomarkers of Fibrosis in Patients with COVID-19 One Year After Hospital Discharge: A Prospective Cohort Study.

Beyond the acute infection of coronavirus disease (COVID-19), concern has arisen about long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of our study was to analyze if there is any biomarker of fibrogenesis in patients with COVID-19 pneumonia capable of predicting post-COVID-19 pulmonary sequelae. We conducted a multicenter, prospective, observational cohort study of patients admitted to a hospital with bilateral COVID-19 pneumonia. We classified patients into two groups according to severity, and blood sampling to measure matrix metalloproteinase 1 (MMP-1), MMP-7, periostin, and VEGF and respiratory function tests and high-resolution computed tomography were performed at 2 and 12 months after hospital discharge. A total of 135 patients were evaluated at 12 months. Their median age was 61 (interquartile range, 19) years, and 58.5% were men. We found between-group differences in age, radiological involvement, length of hospital stay, and inflammatory laboratory parameters. Differences were found between 2 and 12 months in all functional tests, including improvements in predicted forced vital capacity (98.0% vs. 103.9%; P = 0.001) and DlCO <80% (60.9% vs. 39.7%; P = 0.001). At 12 months, 63% of patients had complete high-resolution computed tomography resolution, but fibrotic changes persisted in 29.4%. Biomarker analysis demonstrated differences at 2 months in periostin (0.8893 vs. 1.437 ng/ml; P < 0.001) and MMP-7 (8.7249 vs. 15.2181 ng/ml; P < 0.001). No differences were found at 12 months. In multivariable analysis, only 2-month periostin was associated with 12-month fibrotic changes (odds ratio, 1.0013; 95% confidence interval, 1.0006-1.00231; P = 0.003) and 12-month DlCO impairment (odds ratio, 1.0006; 95% confidence interval, 1.0000-1.0013; P = 0.047). Our data suggest that early periostin postdischarge could predict the presence of fibrotic pulmonary changes.

Lung Function, Radiological Findings and Biomarkers of Fibrogenesis in a Cohort of COVID-19 Patients Six Months After Hospital Discharge / Función pulmonar, hallazgos radiológicos y biomarcadores de la fibrogénesis en una cohorte de pacientes de COVID-19 seis meses después del alta

Introduction Impairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia. Methods COVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits. Results In total, 313, aged 61.12±12.26 years, out of 481 included patients were available. The proportion of patients with DLCO<80% was 54.6% and 47% at 60 and 180 days. Associated factors with diffusion impairment at 6 months were female sex (OR: 2.97, 95%CI 1.74–5.06, p=0.001), age (OR: 1.03, 95% CI: 1.01–1.05, p=0.005), and peak RALE score (OR: 1.22, 95% CI 1.06–1.40, p=0.005). Patients with altered lung diffusion showed higher levels of MMP-7 (11.54±8.96 vs 6.71±4.25, p=0.001), and periostin (1.11±0.07 vs 0.84±0.40, p=0.001). 226 patients underwent CT scan, of whom 149 (66%) had radiological sequelae of COVID-19. In severe patients, 68.35% had ground glass opacities and 38.46% had parenchymal bands. Early fibrotic changes were associated with higher levels of MMP7 (13.20±9.20 vs 7.92±6.32, p=0.001), MMP1 (10.40±8.21 vs 6.97±8.89, p=0.023), and periostin (1.36±0.93 vs 0.87±0.39, p=0.001). Conclusion Almost half of patients with moderate or severe COVID-19 pneumonia had impaired pulmonary diffusion six months after discharge. Severe patients showed fibrotic lesions in CT scan and elevated serum biomarkers involved in pulmonary fibrosis.

Introducción El deterioro de la función pulmonar en las pruebas correspondientes y las alteraciones radiológicas son las preocupaciones principales en los supervivientes de la COVID-19. Nuestro objetivo fue evaluar los parámetros de la función respiratoria, los cambios en la TC de tórax y la correlación con los biomarcadores en sangre periférica involucrados en la fibrosis pulmonar a los 2 y a los 6 meses tras la neumonía por SARS-CoV-2. Métodos El ensayo COVID-FIBROTIC (clinicaltrials.gov NCT04409275) es un estudio de cohortes multicéntrico, prospectivo y observacional cuyo objetivo fue evaluar los pacientes dados de alta. Se realizaron pruebas de función pulmonar, detección de biomarcadores en plasma circulante y radiografía y TC de tórax durante las visitas ambulatorias. Resultados En total 313 pacientes, de 61,12±12,26 años, de los 481 incluidos estuvieron disponibles. La proporción de pacientes con DLCO<80% fue del 54,6 y del 47% a los 60 y 180 días. Los factores que se sociaron a la alteración de la difusión a los 6 meses fueron el sexo femenino (OR: 2,97; IC del 95%: 1,74-5,06; p=0,001), la edad (OR: 1,03; IC del 95%: 1,01-1,05; p=0,005) y la puntuación RALE más alta (OR: 1,22; IC del 95%: 1,06-1,40; p=0,005). Los pacientes con alteración de la difusión pulmonar mostraron niveles más altos de MMP-7 (11,54±8,96 frente a 6,71±4,25; p=0,001) y periostina (1,11±0.07 frente a 0,84±0,40; p=0,001). Se le realizó una TC a 226 pacientes de los cuales 149 (66%) presentaban secuelas radiológicas de la COVID-19. En los pacientes graves, el 68,35% mostraban opacidades en vidrio esmerilado y el 38,46%, bandas parenquimatosas. Los cambios fibróticos tempranos se asociaron a niveles más altos de MMP7 (13,20±9,20 frente a 7,92±6,32; p=0,001), MMP1 (10,40±8,21 frente a 6,97±8,89; p=0,023), y periostina (1,36±0,93 frente a 0,87±0,39; p=0,001). Conclusión Casi la mitad de los pacientes con neumonía moderada o grave por COVID-19 presentaba alteración de la difusión pulmonar 6 meses después del alta. Los pacientes graves mostraban lesiones fibróticas en laTC y un aumento de los biomarcadores séricos relacionados con la fibrosis pulmonar

Circulating levels of calprotectin, a signature of neutrophil activation in prediction of severe respiratory failure in COVID-19 patients: a multicenter, prospective study (CalCov study).

OBJECTIVE: Severe COVID-19 is characterized by a dysregulated immune response in which neutrophils play a critical role. Calprotectin reflects neutrophil activation and is involved in the self-amplifying thrombo-inflammatory storm in severe COVID-19. We aimed to evaluate the role of calprotectin in early prediction of severity in COVID-19 patients. METHODS: This was a multicenter prospective observational study enrolling consecutive adult COVID-19 patients. On arrival to emergency department, blood samples were collected for laboratory tests, including serum calprotectin. The primary outcome was severe respiratory failure requiring invasive mechanical ventilation and the secondary outcome was need for Intensive Care Unit (ICU) admission. RESULTS: Study population included 395 patients, 57 (14.4%) required invasive mechanical ventilation and 100 (25.3%) were admitted to ICU. Median serum calprotectin levels were significantly higher in intubated (3.73 mg/L vs. 2.63 mg/L; p < 0.001) and ICU patients (3.48 mg/L vs. 2.60 mg/L; p = 0.001). Calprotectin showed a significant accuracy to predict the need for invasive mechanical ventilation (ROC AUC 0.723) and ICU admission (ROC AUC 0.650). In multivariate analysis, serum calprotectin was an independent predictor of invasive mechanical ventilation (OR 1.161) and ICU admission (OR 1.068). CONCLUSION: Serum calprotectin can be used as an early predictor of severity in COVID-19 patients.

Lung Function, Radiological Findings and Biomarkers of Fibrogenesis in a Cohort of COVID-19 Patients Six Months After Hospital Discharge.

INTRODUCTION: Impairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia. METHODS: COVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits. RESULTS: In total, 313, aged 61.12 ± 12.26 years, out of 481 included patients were available. The proportion of patients with DLCO < 80% was 54.6% and 47% at 60 and 180 days. Associated factors with diffusion impairment at 6 months were female sex (OR: 2.97, 95%CI 1.74-5.06, p = 0.001), age (OR: 1.03, 95% CI: 1.01-1.05, p = 0.005), and peak RALE score (OR: 1.22, 95% CI 1.06-1.40, p = 0.005). Patients with altered lung diffusion showed higher levels of MMP-7 (11.54 ± 8.96 vs 6.71 ± 4.25, p = 0.001), and periostin (1.11 ± 0.07 vs 0.84 ± 0.40, p = 0.001). 226 patients underwent CT scan, of whom 149 (66%) had radiological sequelae of COVID-19. In severe patients, 68.35% had ground glass opacities and 38.46% had parenchymal bands. Early fibrotic changes were associated with higher levels of MMP7 (13.20 ± 9.20 vs 7.92 ± 6.32, p = 0.001), MMP1 (10.40 ± 8.21 vs 6.97 ± 8.89, p = 0.023), and periostin (1.36 ± 0.93 vs 0.87 ± 0.39, p = 0.001). CONCLUSION: Almost half of patients with moderate or severe COVID-19 pneumonia had impaired pulmonary diffusion six months after discharge. Severe patients showed fibrotic lesions in CT scan and elevated serum biomarkers involved in pulmonary fibrosis.

INTRODUCCIÓN: El deterioro de la función pulmonar en las pruebas correspondientes y las alteraciones radiológicas son las preocupaciones principales en los supervivientes de la COVID-19. Nuestro objetivo fue evaluar los parámetros de la función respiratoria, los cambios en la TC de tórax y la correlación con los biomarcadores en sangre periférica involucrados en la fibrosis pulmonar a los 2 y a los 6 meses tras la neumonía por SARS-CoV-2. MÉTODOS: El ensayo COVID-FIBROTIC (clinicaltrials.gov NCT04409275) es un estudio de cohortes multicéntrico, prospectivo y observacional cuyo objetivo fue evaluar los pacientes dados de alta. Se realizaron pruebas de función pulmonar, detección de biomarcadores en plasma circulante y radiografía y TC de tórax durante las visitas ambulatorias. RESULTADOS: En total 313 pacientes, de 61,12 ± 12,26 años, de los 481 incluidos estuvieron disponibles.La proporción de pacientes con DLCO < 80% fue del 54,6 y del 47% a los 60 y 180 días.Los factores que se asociaron a la alteración de la difusión a los 6 meses fueron el sexo femenino (OR: 2,97; IC del 95%: 1,74-5,06; p = 0,001), la edad (OR: 1,03; IC del 95%: 1,01-1,05; p = 0,005) y la puntuación RALE más alta (OR: 1,22; IC del 95%: 1,06-1,40; p = 0,005). Los pacientes con alteración de la difusión pulmonar mostraron niveles más altos de MMP-7 (11,54 ± 8,96 frente a 6,71 ± 4,25; p = 0,001) y periostina (1,11 ± 0.07 frente a 0,84 ± 0,40; p = 0,001). Se le realizó una TC a 226 pacientes de los cuales 149 (66%) presentaban secuelas radiológicas de la COVID-19. En los pacientes graves, el 68,35% mostraban opacidades en vidrio esmerilado y el 38,46%, bandas parenquimatosas. Los cambios fibróticos tempranos se asociaron a niveles más altos de MMP7 (13,20 ± 9,20 frente a 7,92 ± 6,32; p = 0,001), MMP1 (10,40 ± 8,21 frente a 6,97 ± 8,89; p = 0,023), y periostina (1,36 ± 0,93 frente a 0,87 ± 0,39; p = 0,001). CONCLUSIÓN: Casi la mitad de los pacientes con neumonía moderada o grave por COVID-19 presentaba alteración de la difusión pulmonar 6 meses después del alta. Los pacientes graves mostraban lesiones fibróticas en laTC y un aumento de los biomarcadores séricos relacionados con la fibrosis pulmonar.

Discordant SOX-1 antibodies results in paraneoplastic Lambert-Eaton syndrome diagnosis by the clinical laboratory.

BACKGROUND: Anti-Sry-like high mobility group box 1 (anti SOX-1) proteins are rare onconeural antibodies associated with paraneoplastic Lambert-Eaton myasthenic syndrome (LEMS). Few patients with anti-SOX-1 antibodies and negative anti-glial nuclear antibody reactivity have been described to date. CASE SUBJECT AND METHODS: Our case involves a 72-year-old female patient with progressive girdle weakness, sensation of heaviness in the lower limbs, predominantly distal and associated with circulatory problems together with instability when walking, with a high suspicion of an autoimmune myopathic disorder. Immunoblot test for autoimmune myopathies antibodies detection were all negative. Onconeuronal antibodies were determined in serum by indirect immunofluorescence being negative as well. Given the high suspicion, we also checked for the presence of other antineuronal antibodies whose patterns are not visible by IIF. RESULTS: Onconeuronal antibodies by immunoblot for the following antibodies: Hu, Ri, Yo, Zic4, Tr, PCA-2, MA-TA, CV2, GAD65, Zic4, Titin, SOX1, Recoverin and Amp, revealed an unexpected clear band in SOX-1, which are highly suggestive of paraneoplastic LEMS. DISCUSSION: We hypothesize that discordant onconeuronal antibodies results were due to the fact that positivity in IIF is associated with other SOX-B group proteins (normally related to cases of non-paraneoplastic neuropathy), while negativity in IIF and subsequent confirmed presence of specific SOX1 antibody by immunoblot could indicate an underlying tumor.

Decision support system through automatic algorithms and electronic request in diagnosis of anaemia for primary care patients.

INTRODUCTION: An appropriate management of anaemia laboratory tests is crucial for a correct diagnosis and treatment. A non-sequential "shotgun" approach (where every anaemia related test is ordered) causes workload and cost increases and could be potentially harmful. We have implemented a Decision Support System through our laboratory information system (LIMS) based on reflexive algorithms and automatic generation of interpretative reports specifically in diagnosis of anaemia for primary care patients. MATERIALS AND METHODS: When a request contained an "Anaemia Suspicion Study" profile, more than twenty automatic reflexive rules were activated in our LIMS based upon laboratory results. These rules normally involved the addition of reflexive tests. A final report was automatically generated for each interpretation which was always reviewed for their validity by two staff pathologists. We measured the impact of this system in the ordering of most common anaemia related tests and if a proper treatment was established based on the interpretive report. RESULTS: From all the studies performed, only 12% were positive being "iron deficiency" and "anaemia of chronic disease" the most frequent causes, 62% and 17%, respectively. Proper treatment was established in 88% of these anaemic patients. Total iron, transferrin, ferritin, folate and vitamin B12 demand decreased substantially after implementation representing a cost reduction of 40% only for these five tests. CONCLUSIONS: Our system has easily improved patient outcomes, advising on individual clinical cases. We have also noticeably reduced the number of over-requested tests and laboratory costs.

Computer physician order entry (CPOE) as a strategy to estimate laboratory activity and costs associated with cancer clinical trials.

INTRODUCTION: Most of clinical laboratories are not properly reimbursed for their activity related to clinical trials (CTs) conducted in their institutions due to a lack of measurement strategies. We implemented a specific computer physician order entry (CPOE) environment for CTs in order to facilitate ordering to providers and estimate the associated costs to be compared with the standard of care (SOC). MATERIALS AND METHODS: Four specific electronic formularies, restricted to two new virtual CTs clinical services (onco - CT and haemo - CT), were implemented in January 2015. For each clinical trial displayed in the panels there were several box-cells that contained several profiles based on the different phase of the trials. Tests included in the profiles were the tests required by protocol. Laboratory costs (€) per patient were compared between the CTs services and their regular outpatients clinical services (onco - Out and haemo - Out, considered the SOC) for three years. RESULTS: Costs per patient were higher for CTs services and increased progressively each year (25%, 70% and 70% and 0.6%, 2.7% and 17% in 2015, 2016 and 2017 for Oncology and Haematology, respectively). Taking into account all these differences and the number of patients attending a total difference in expense of + 130,377.7 € for the period 2015-2017 was obtained between CTs and outpatients services. CONCLUSIONS: Strategies through CPOE systems based on restricted and specific profiles for CTs ordering are a promising tool that can improve laboratory associated costs estimation and provide robust evidence in reimbursement negotiation processes with CTs sponsors.

"Send & hold" clinical decision support rules improvement to reduce unnecessary testing of vitamins A, E, K, B1, B2, B3, B6 and C.

BACKGROUND: We assessed the impact of several "send & hold" clinical decision support rules (CDSRs) within the electronical request system for vitamins A, E, K, B1, B2, B3, B6 and C for all outpatients at a large health department. METHODS: When ordered through electronical request, providers (except for all our primary care physicians who worked as a non-intervention control group) were always asked to answer several compulsory questions regarding main indication, symptomatology, suspected diagnosis, vitamin active treatments, etc., for each vitamin test using a drop-down list format. After samples arrival, tests were later put on hold internally by our laboratory information system (LIS) until review for their appropriateness was made by two staff pathologists according to the provided answers and LIS records (i.e. "send & hold"). The number of tests for each analyte was compared between the 10-month period before and after CDSRs implementation in both groups. RESULTS: After implementation, vitamins test volumes decreased by 40% for vitamin A, 29% for vitamin E, 42% for vitamin K, 37% for vitamin B1, 85% for vitamin B2, 68% for vitamin B3, 65% for vitamin B6 and 59% for vitamin C (all p values 0.03 or lower except for vitamin B3), whereas in control group, the majority increased or remained stable. In patients with rejected vitamins, no new requests and/or adverse clinical outcome comments due to this fact were identified. CONCLUSIONS: "Send & hold" CDSRs are a promising informatics tool that can support in utilization management and enhance the pathologist's leadership role as tests specialist.

Impact of an oral appliance on obstructive sleep apnea severity, quality of life, and biomarkers.

OBJECTIVE/HYPOTHESIS: To investigate outcomes including efficacy, quality of life, and levels of inflammatory markers of a mandibular advancement device (MAD) for moderate-to-severe obstructive sleep apnea (OSA). STUDY DESIGN: Case-control study. METHODS: Patients with apnea-hypopnea index (AHI) ≥ 15/hr who only accepted MAD therapy (study group) or who refused any treatment (control group) were recruited. At baseline and at 6 months, polysomnography, Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), C-reactive protein (CRP), interleukin 1ß, interleukin 6, and tumor necrosis factor α (TNF-α) were assessed in both groups. RESULTS: At baseline, the study group (n = 30) showed a higher percentage of rapid eye movement sleep and higher CRP levels (P < .05) than the control group (n = 10). At 6 months, the MAD significantly improved AHI and lowest oxygen saturation (P < .01), non-rapid eye movement (N)1 and N3 sleep stages (P < .05), ESS score (P < .05), FOSQ total score (P < .01), interleukin 1ß (P < .05), and TNF-α (P < .01) compared with the untreated group. In the overall, moderate, and severe OSA groups, 63.3%, 75%, and 50%, respectively, achieved at least good response. CONCLUSIONS: Use of a MAD significantly improved polysomnographic parameters, quality of life, and some inflammatory markers (CRP, IL-ß, and TNF-α) in a significant proportion of patients with moderate OSA and in some patients with severe OSA. Hence, a MAD may be a viable alternative therapy in patients with moderate-to-severe OSA who refuse continuous positive airway pressure. LEVEL OF EVIDENCE: 3b. Laryngoscope, 128:1720-1726, 2018.

PAI-1 levels are related to insulin resistance and carotid atherosclerosis in subjects with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCH) is a primary atherogenic dyslipidemia with insulin resistance and increased cardiovascular risk. Plasminogen activator inhibitor type 1 (PAI-1) and myeloperoxidase (MPO) activity are associated with proinflammatory and atherothrombotic risk. Our aim was to study the role played by PAI-1 and MPO activity in the carotid atherosclerosis prevalence in FCH subjects. 36 FCH unrelated subjects (17 women) were matched by age and body weight with 36 healthy normolipidemic subjects (19 female). Blood lipids, glucose, insulin, insulin resistance (homeostasis model assessment (HOMA)), MPO, and PAI-1 were determined in both groups. Carotid intima media thickness (IMT) was measured by the same investigator by standardized protocol. No differences in age, body mass index (BMI) or waist circumference were observed between the two groups. HOMA and PAI-1 values were higher in the FCH group, reaching statistical significance in those subjects with insulin resistance. In addition, PAI-1 values correlated significantly with metabolic syndrome components and carotid IMT. It is known that the elevated cardiovascular risk that characterizes FCH is frequently associated with insulin resistance. We have detected that two known proinflammatory and proatherothrombotic factors (MPO and PAI-1) are significantly elevated in FCH subjects with insulin resistance. These results could partly explain the high cardiovascular risk present in FCH subjects.

Utility of routine laboratory preoperative tests based on previous results: Time to give up.

INTRODUCTION: The usefulness and cost-effectiveness of routine laboratory preoperative tests (POTs) have been challenged recently. In fact, the American Society of Anesthesiologists (ASA) Task Force has stated that test results obtained from the medical record within 6 months of surgery generally are mostly acceptable. The aim of our study was to evaluate the degree of utility of POTs and their clinical benefit based on this recommendation. MATERIAL AND METHODS: We studied retrospectively every routine POT request from 8 randomly selected weeks in 2016. Every POT contained glucose, creatinine, haemoglobin and coagulation tests (PT-INR). Each pathological result for these tests was registered and classified as "expected" (if previous pathological result within 6 months existed for that test) or "unexpected" (if previous pathological result within 6 months did not exist for that test). Results of ASA physical status classification (a system for assessing the fitness of patients before surgery) and changes in patient management after POTs were retrieved from medical history as well. RESULTS: A total of 4516 tests (from 1129 patients) were analysed and 498 results were found pathological (11%). Of these, 403 were expected (8.9%) and 95 unexpected (2.1%). There was not any change in anaesthetic management for any patient due to these findings. CONCLUSIONS: Routine POTs are an inefficient and low-value service. POTs have to be always ordered selectively after a previous consideration of specific information obtained from several sources (medical records, interviews, examinations, type of surgery) and only if the information obtained will result in changes in the management of the patient.

Failure to review STAT clinical laboratory requests and its economical impact.

BACKGROUND: Failure to follow-up laboratory test results has been described as one of the major processes contributing to unsafe patient care. Currently, most of the laboratories do not know with certainty not only their rate of missed (or unreviewed) requests but the economical cost and impact that this issue implies. The aim of our study was to measure that rate and calculate the resulting costs. MATERIAL AND METHODS: In January 2015, we checked in our Laboratory Information Management System (LIMS) for every emergency request from 1(st) July 2011 to 30(th) June 2014, if they had been reviewed by any allowed user or not. 319,064 requests were ordered during that period of time. Results were expressed as "ordered requests", "missed requests" and its percentage. Additionally, total cost of missed requests was calculated in euros (€). "Non-productive days" were theorised (as the days producing requests that were not reviewed) based on these results. RESULTS: 7924 requests (2.5%) were never reviewed by clinicians. This represented a total cost of 203,039 € and 27 "non-productive" days in three years. Significant differences between inpatients, outpatients and emergency department as well as different emergencies units were found after application of statistical analysis. CONCLUSIONS: In terms of resources, never reviewed or missed requests appear to be a not negligible problem for the clinical laboratory management. Electronic result delivery, with electronic endorsement to indicate follow-up of requests along with better systems of electronic requesting should be investigated as a way of improving patient outcomes and save unnecessary expenses.

Usefulness of Clinical Data and Biomarkers for the Identification of Frailty After Acute Coronary Syndromes.

BACKGROUND: Frailty predicts mortality after acute coronary syndrome (ACS). The standard frailty scales, such as the Fried score, consist of a variety of questionnaires and physical tests. Our aim was to investigate easily available clinical data and blood markers to predict frailty at discharge, in elderly patients after ACS. METHODS: A total of 342 patients older than 65 years, survivors after ACS, were included. A high number of clinical variables were collected. In addition, blood markers potentially linked to frailty and related to the processes of inflammation, coagulation, hormonal dysregulation, nutrition, renal dysfunction, and heart dysfunction were determined. Frailty was evaluated using the Fried score at discharge. The main outcome was frailty defined by a Fried score ≥ 3 points. Secondary endpoints were mortality and myocardial infarction at 30-month median follow-up. RESULTS: A total of 116 patients were frail. Seven clinical variables or biomarkers predicted frailty: age ≥ 75 years, female, prior ischemic heart disease, admission heart failure, haemoglobin ≤ 12.5 g/dL, vitamin D ≤ 9 ng/mL, and cystatin-C ≥ 1.2 mg/L. This model based on clinical data and biomarkers showed an excellent discrimination accuracy for frailty (C-statistic = 0.818). During the follow-up, 105 patients died and 137 died or suffered myocardial infarction. The clinical data and biomarker model (C-statistics = 0.730 and 0.691) performed better than the Fried score (C-statistics = 0.676 and 0.650) for death and death or myocardial infarction, respectively. CONCLUSIONS: Easy available clinical data and biomarkers can identify frail patients at discharge after ACS and predict outcomes better than the standard Fried's frailty scale.

Frailty and other geriatric conditions for risk stratification of older patients with acute coronary syndrome.

BACKGROUND: Geriatric conditions may predict outcomes beyond age and standard risk factors. Our aim was to investigate a wide spectrum of geriatric conditions in survivors after an acute coronary syndrome. METHODS: A total of 342 patients older than 65 years were included. At hospital discharge, 5 geriatric conditions were evaluated: frailty (Fried and Green scores), physical disability (Barthel index), instrumental disability (Lawton-Brody scale), cognitive impairment (Pfeiffer questionnaire), and comorbidity (Charlson and simple comorbidity indexes). The outcomes were postdischarge mortality and the composite of death/myocardial infarction during a 30-month median follow-up. RESULTS: Seventy-four (22%) patients died and 105 (31%) suffered from the composite end point. Through univariable analysis, all individual geriatric indexes were associated with outcomes, mainly mortality. Of all of them, frailty using the Green score had the strongest discriminative accuracy (area under the receiver operating characteristic curve 0.76 for mortality). After full adjustment including clinical and geriatric data, the Green score was the only independent predictive geriatric condition (per point; mortality: hazard ratio 1.25, 95% CI 1.15-1.36, P = .0001; composite end point: hazard ratio 1.16, 95% CI 1.09-1.24, P = .0001). A Green score ≥ 5 points was the strongest mortality predictor. The addition of the Green score to the clinical model improved discrimination (area under the receiver operating characteristic curve 0.823 vs 0.846) and significantly reclassified mortality risk (net reclassification improvement 26.3, 95% CI 1.4-43.5; integrated discrimination improvement 4.0, 95% CI 0.8-9.0). The incremental predictive information was even greater over the GRACE score. CONCLUSIONS: Frailty captures most of the prognostic information provided by geriatric conditions after acute coronary syndromes. The Green score performed better than the other geriatric indexes.

Enquiry time as part of turnaround time: when do our clinicians really consult our results?

BACKGROUND: Traditionally, laboratories' turnaround times (TAT) have been calculated by only considering analytical or intralaboratory steps. The measure of the postanalytical impact in TAT has barely been studied and, more specifically, the running time from when finalised results are available to when clinicians make their first enquiry with an electronic medical record. METHODS: During May-June of 2013, two 'Times' were collected from our laboratory information system for all the priority requests coming from our day hospitals: 'Validation time' (TV), as the request report time with full verified results and 'Enquiry time' (TQ), as the time when the first consult was made via electronic medical record. We classified requests in groups depending on time results, and TQ-TV (percentiles) were calculated for each group. RESULTS: 654 (69%) requests were consulted by clinicians before 15 : 00 on the same day with available results. 191 (20%) were consulted after 15 : 00 and had complete results as well (p50 (TQ-TV): 5 days) while 61 (7%) were never consulted (up to 31/12/2013). 39 (4%) requests were finally consulted before 15 : 00 h with no available results, but the average time difference between validation and enquiry was 31 min. CONCLUSIONS: The results obtained lead us to reconsider the TAT established with our day hospitals in order to know if priority has to be reviewed or if there are failures in follow-up results. 'Enquiry time' appears to be a powerful tool in detecting these issues and shows that TATs are no longer just a 'laboratory problem'.

Análisis Multiplex de citoquinas intratecales en pacientes con deterioro cognitivo leve / Multiplex analysis of intrathecal cytokines in patients with mild cognitive impairment

Introducción. El estudio del papel de las citoquinas en los procesos neuroinmunológicos se ha intensificado en la última década, si bien los resultados han sido contradictorios debido al empleo de tecnologías poco sensibles. La implementación de la tecnología Multiplex en los inmunoensayos puede ser beneficiosa en la evaluación de pacientes con daño cognitivo leve (DCL) que evolucionan a enfermedad de Alzheimer (EA). Materiales y métodos. Treinta y siete pacientes con DCL y 24 sujetos control fueron estudiados mediante análisis Multiplex de citoquinas intratecales y en suero. Las variables del estudio fueron las citoquinas IL1β, IL2, IL5, IL6, IL7, IL8, IL10, IL12p70, IL13, factor necrosis tumoral alfa (TNFα), interferón gamma (IFNγ) y factor de crecimiento de granulocito-macrófago (GM-CSF) y los cocientes pro/antiinflamatorios IL6/IL10, IL6/IL5, IL8/IL10, IL8/IL5, TNFα/IL10 y TNFα/IL5. Se estudió la evolución a EA en los pacientes DCL y en los sujetos control en el período de un año. Resultados. Se encontraron diferencias significativas (p<0,05) para el cociente IL6/IL10 entre el grupo DCL y el grupo control (mediana [rango intercuartílico]): (1,39 [1,18-1,80] vs. 1,91 [2,68-1,18] pg/ml). De 37 pacientes con DCL, 14 evolucionaron a EA (DCL-EA) en el período de un año. De nuevo se encontraron diferencias significativas (p<0,05) en el cociente IL6/IL10 entre el grupo DCL-EA y DCL- S (o estable): (1,29 [0,84-1,56] vs. 1,42 [1,27-2,07] pg/ml). Ninguno de los sujetos control evolucionó a EA. Conclusiones. El descenso en el cociente IL6/IL10 en LCR puede ser un prometedor marcador diagnóstico de DCL y predictor/pronóstico de EA en DCL (AU)

Introduction. There has been an increase in the number of studies on the role of cytokines in neuro-immunological processes, over the last ten years, but some of these results have been contradictory due to a lack of sensitivity in the technology. The new Multiplex immunoassays can be beneficial for monitoring Mild Cognitive Impairment (MCI) patients who progress to Alzheimer Disease (AD). Methods. A study was conducted on 37 MCI patients and 24 control subjects by means of multiplex analysis of CSF cytokines. The variables measured were the following cytokines: IL1β, IL2, IL5, IL6, IL7, IL8, IL10, IL12p70, IL13, tumour necrosis factor alpha (TNFα), interferon gamma (IFNγ) and granulocyte – macrophage growth colony stimulating factor (GM-CSF), as well as the following pro/anti-inflammatory ratios: IL6/IL10, IL6/IL5, IL8/IL10, IL8/IL5, TNFα/IL10 and TNFα/IL5. Progress to AD in MCI patients was studied over a period of one year. Results. Significant differences were found (P<.05) for IL6/IL10 ratio between MCI patients and Control group (median [IR]): (1.39 [1.18-1.80] vs. 1.91 [2.68-1.18] pg/mL). Of the 37 MCI patients, 14 progressed to AD (DCL-EA group) within a year. Significant differences were also found (P<.05) for IL6/IL10 ratio between the DCL-EA group and the rest of MCI patients that did not progress (DCL-S or stable): (1.29 [0.84-1.56] vs. 1.42 [1.27-2.07] pg/mL). None of the control subjects progressed to AD. Conclusions. A decrease in CSF IL6/IL10 ratio could be a promising diagnostic biomarker in MCI and a prognostic biomarker of AD in MCI (AU)

Regional variations in test requiring patterns of general practitioners in Spain.

OBJECTIVE: To analyze the requesting patterns for a range of laboratory tests ordered in 2009 from eight laboratories providing services to eight health areas, using appropriate indicators. DESIGN: Indicators measured every test request per 1,000 inhabitants, and indicators that measured the number of tests per related test requested by general practitioners were calculated. The savings generated, if each Health Care Department achieved the appropriate indicator standard, were also calculated. Laboratory Information System registers were collected, and indicators were calculated automatically in each laboratory using a data warehouse application. RESULTS: There was a large difference in demand for tests by health areas. The ratio of related tests also showed a great variability. The savings generated if each Health Care Department had achieved the appropriate indicator standard were €172,116 for free thyroxine, €18,289 for aspartate aminotransferase, and €62,678 for urea. CONCLUSIONS: Considerable variability exists in general practitioners' demand for laboratory tests.