Acute and long-term immune responses to SARS-CoV-2 infection in unvaccinated children and young adults with inborn errors of immunity

PurposeTo describe SARS-CoV-2 infection outcome in unvaccinated children and young adults with inborn errors of immunity (IEI) and to compare their specific acute and long-term immune responses with a sex-, age-, and severity-matched healthy population (HC).MethodsUnvaccinated IEI patients up to 22 years old infected with SARS-CoV-2 were recruited along with a cohort of HC. SARS-CoV-2 serology and ELISpot were performed in the acute phase of infection (up to 6 weeks) and at 3, 6, 9, and 12 months.ResultsTwenty-five IEI patients (median age 14.3 years, min.-max. range 4.5-22.8; 15/25 males; syndromic combined immunodeficiencies: 48.0%, antibody deficiencies: 16.0%) and 17 HC (median age 15.3 years, min.-max. range 5.4-20.0; 6/17 males, 35.3%) were included. Pneumonia occurred in 4/25 IEI patients. In the acute phase SARS-CoV-2 specific immunoglobulins were positive in all HC but in only half of IEI in whom it could be measured (n=17/25): IgG+ 58.8% (10/17) (p=0.009); IgM+ 41.2% (7/17)(p<0.001); IgA+ 52.9% (9/17)(p=0.003). Quantitative response (index) was also lower compared with HC: IgG IEI (3.1 ± 4.4) vs. HC (3.5 ± 1.5)(p=0.06); IgM IEI (1.9 ± 2.4) vs. HC (3.9 ± 2.4)(p=0.007); IgA IEI (3.3 ± 4.7) vs. HC (4.6 ± 2.5)(p=0.04). ELISpots positivity was qualitatively lower in IEI vs. HC (S-ELISpot IEI: 3/11, 27.3% vs. HC: 10/11, 90.9%; p=0.008; N-ELISpot IEI: 3/9, 33.3% vs. HC: 11/11, 100%; p=0.002) and also quantitatively lower (S-ELISpot IEI: mean index 3.2 ± 5.0 vs. HC 21.2 ± 17.0; p=0.001; N-ELISpot IEI: mean index 9.3 ± 16.6 vs. HC: 39.1 ± 23.7; p=0.004). As for long term response, SARS-CoV-2-IgM+ at 6 months was qualitatively lower in IEI(3/8, 37.5% vs. 9/10 HC: 90.0%; p=0.043), and quantitatively lower in all serologies IgG, M, and A (IEI n=9, 1.1 ± 0.9 vs. HC n=10, 2.1 ± 0.9, p=0.03; IEI n=9, 1.3 ± 1.5 vs. HC n=10, 2.9 ± 2.8, p=0.02; and IEI n=9, 0.6 ± 0.5 vs. HC n=10, 1.7 ± 0.8, p=0.002 –respectively) but there were no differences at remaining time points.ConclusionsOur IEI pediatric cohort had a higher COVID-19 pneumonia rate than the general age-range population, with lower humoral and cellular responses in the acute phase (even lower compared to the reported IEI serological response after SARS-CoV-2 vaccination), and weaker humoral responses at 6 months after infection compared with HC

Systemic pro-inflammatory response identifies patients with cancer with adverse outcomes from SARS-CoV-2 infection: the OnCovid Inflammatory Score

Background: Patients with cancer are particularly susceptible to SARS-CoV-2 infection. The systemic inflammatory response is a pathogenic mechanism shared by cancer progression and COVID-19. We investigated systemic inflammation as a driver of severity and mortality from COVID-19, evaluating the prognostic role of commonly used inflammatory indices in SARS-CoV-2-infected patients with cancer accrued to the OnCovid study. Methods: In a multicenter cohort of SARS-CoV-2-infected patients with cancer in Europe, we evaluated dynamic changes in neutrophil:lymphocyte ratio (NLR); platelet:lymphocyte ratio (PLR); Prognostic Nutritional Index (PNI), renamed the OnCovid Inflammatory Score (OIS); modified Glasgow Prognostic Score (mGPS); and Prognostic Index (PI) in relation to oncological and COVID-19 infection features, testing their prognostic potential in independent training (n=529) and validation (n=542) sets. Results: We evaluated 1071 eligible patients, of which 625 (58.3%) were men, and 420 were patients with malignancy in advanced stage (39.2%), most commonly genitourinary (n=216, 20.2%). 844 (78.8%) had ≥1 comorbidity and 754 (70.4%) had ≥1 COVID-19 complication. NLR, OIS, and mGPS worsened at COVID-19 diagnosis compared with pre-COVID-19 measurement (p<0.01), recovering in survivors to pre-COVID-19 levels. Patients in poorer risk categories for each index except the PLR exhibited higher mortality rates (p<0.001) and shorter median overall survival in the training and validation sets (p<0.01). Multivariable analyses revealed the OIS to be most independently predictive of survival (validation set HR 2.48, 95% CI 1.47 to 4.20, p=0.001; adjusted concordance index score 0.611). Conclusions: Systemic inflammation is a validated prognostic domain in SARS-CoV-2-infected patients with cancer and can be used as a bedside predictor of adverse outcome. Lymphocytopenia and hypoalbuminemia as computed by the OIS are independently predictive of severe COVID-19, supporting their use for risk stratification. Reversal of the COVID-19-induced proinflammatory state is a putative therapeutic strategy in patients with cancer

Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease

Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10- (95% CI 3.3 × 10--1.1 × 10-)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD

Association of candidate gene polymorphisms with chronic kidney disease : Results of a case-control analysis in the NEFRONA cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2,445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionization-time of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

TFG 2013/2014

Amb aquesta publicació, EINA, Centre universitari de Disseny i Art adscrit a la Universitat Autònoma de Barcelona, dóna a conèixer el recull dels Treballs de Fi de Grau presentats durant el curs 2013-2014. Voldríem que un recull com aquest donés una idea més precisa de la tasca que es realitza a EINA per tal de formar nous dissenyadors amb capacitat de respondre professionalment i intel·lectualment a les necessitats i exigències de la nostra societat. El treball formatiu s’orienta a oferir resultats que responguin tant a paràmetres de rigor acadèmic i capacitat d’anàlisi del context com a l’experimentació i la creació de nous llenguatges, tot fomentant el potencial innovador del disseny.Con esta publicación, EINA, Centro universitario de diseño y arte adscrito a la Universidad Autónoma de Barcelona, da a conocer la recopilación de los Trabajos de Fin de Grado presentados durante el curso 2013-2014. Querríamos que una recopilación como ésta diera una idea más precisa del trabajo que se realiza en EINA para formar nuevos diseñadores con capacidad de responder profesional e intelectualmente a las necesidades y exigencias de nuestra sociedad. El trabajo formativo se orienta a ofrecer resultados que respondan tanto a parámetros de rigor académico y capacidad de análisis, como a la experimentación y la creación de nuevos lenguajes, al tiempo que se fomenta el potencial innovador del diseño.With this publication, EINA, University School of Design and Art, affiliated to the Autonomous University of Barcelona, brings to the public eye the Final Degree Projects presented during the 2013-2014 academic year. Our hope is that this volume might offer a more precise idea of the task performed by EINA in training new designers, able to speak both professionally and intellectually to the needs and demands of our society. The educational task is oriented towards results that might respond to the parameters of academic rigour and the capacity for contextual analysis, as well as to considerations of experimentation and the creation of new languages, all the while reinforcing design’s innovative potential

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

Utilitat del QuantiFERON®-TB Gold Plus en el diagnòstic de la infecció tuberculosa latent i la malaltia tuberculosa en població pediàtrica

Programa de Doctorat en Medicina i Recerca Translacional / Tesi realitzada a l'Hospital Sant Joan de Déu[cat] INTRODUCCIÓ: Els nens infectats per Mycobacterium tuberculosis tenen un major risc d’emmalaltir de tuberculosi i de fer-ho presentant-ne formes greus. La detecció de la infecció latent a través de tests d'immunodiagnòstic és essencial per poder indicar la quimioprofilaxi i disminuir la possibilitat de progressió a malaltia. A més, la positivitat dels tests reforça la sospita de tuberculosi activa, fet important atès que la confirmació microbiològica sovint no és possible en pacients pediàtrics. El test QuantiFeron-Plus (QFT-Plus) es basa en la detecció d’interferó gamma (IFNγ) secretat per limfòcits sensibilitzats. En comparació als seus predecessors, el QFT-Plus té la particularitat de presentar un segon tub reactiu (TB2). Es planteja que el TB2 serviria per avaluar la resposta dels limfòcits CD8, fet que podria ser important en pacients joves i en aquells amb una alta càrrega bacil·lar. El test s’ha avaluat escassament en pacients pediàtrics. Així, la realització d’aquest treball es justifica per la idiosincràsia de la tuberculosi pediàtrica així com per l’escassa evidència prèvia sobre l’ús del QFT-Plus en pediatria. MÈTODES I OBJECTIUS: Els pacients que conformen els quatre treballs de la tesi han estat reclutats transversal i multicèntricament en el si de la pTBred. S’hi van incloure 1751 pacients menors de 18 anys a qui es va fer el test QFT-Plus. El primer estudi tenia com a objectiu estudiar la sensibilitat del QFT- Plus per diagnosticar la malaltia tuberculosa; el segon, avaluar-ne l’especificitat en pacients sotmesos al QFT-Plus per sospita clínica de malaltia però amb un diagnòstic alternatiu al de tuberculosi; el tercer, estudiar la sensibilitat per a tuberculosi i també el rendiment del test en casos d’infecció latent, així com determinar els factors independentment associats que el test presenti un resultat indeterminat; i el quart, avaluar el paper específic del TB2 i determinar com varia en el temps la concentració d’IFNγ en pacients un cop han rebut tractament antituberculós. RESULTATS: La sensibilitat del QFT-Plus per a tuberculosi va resultar del 83%, similar a la del QuantiFeron Gold-in-tube (QFT-GIT), predecessor del QFT-Plus. La sensibilitat va ser major en pacients amb malaltia confirmada. La sensibilitat del PPD va ser similar a la del QFT-Plus. Per contra, la concordança entre ambdós tests va ser moderada. L’especificitat va resultar del 91,5%, similar a la d’estudis que avaluaven l’especificitat del QFT-GIT seguint la mateixa metodologia. D’entre els infants amb infecció latent, la taxa de positivitat del QFT-Plus va ser del 68,2%, essent la concordança entre QFT-Plus i PPD en aquests pacients del 54,7%. Mitjançant una regressió logística, es van identificar com a factors de risc independents de presentar un resultat indeterminat per al test: 1) edat menor de 5 anys; 2) recompte baix de limfòcits; i 3) nivells elevats de proteïna C reactiva. Al quart estudi s’hi van reclutar 295 pacients amb un QFT-Plus positiu. Es va avaluar la diferència de concentració d’IFNγ entre ambdós tubs reactius (DCI) com a marcador subrogat de la resposta dels limfòcits CD8. Ni en el global dels pacients ni en aquells en qui caldria esperar una resposta CD8 més marcada no es va veure una DCI significativa. Estudis citomètrics previs mostraven detecció de resposta CD8 al TB2 però també, i sovint de manera més marcada, al TB1; de manera que el QFT-Plus podria no estar correctament dissenyat per a la detecció de resposta específica CD8. Es va repetir el test a 65 pacients amb un resultat positiu, un cop van finalitzar el tractament antituberculós. Només la meitat dels infants van presentar una disminució marcada dels nivells d’IFNγ, sense que resultés possible la identificació d’un perfil concret de pacient en qui la concentració disminuís més marcadament. Així, no sembla que el test sigui útil per a la monitorització de la resposta al tractament.[eng] INTRODUCTION: Young children infected with Mycobacterium tuberculosis are at increased risk of developing active tuberculosis. Thus, identifying latent tuberculosis infection through immunodiagnostic tests is essential to reduce the risk of disease progression. QuantiFeron-Plus test (QFT-Plus) is based on the detection of released interferon gamma (IFNγ). Distinctively, it has a second reactive tube (TB2), which is meant to be able to evaluate the response of CD8 lymphocytes. However, there is a lack of previous studies evaluating this test in pediatric patients. OBJECTIVES AND METHODS: This thesis includes four articles. Patients were recruited within the pTBred network. Up to 1751 children younger than 18 years tested with QFT-Plus were finally included. The objectives of these articles were: a) to evaluate both the sensitivity and specificity of QFT- Plus; b) to analyze its performance in patients with latent infection; c) to determine independent risk factors to present an indeterminate result; d) to describe the specific role of the TB2; and e) to identify released IFNγ concentration changes after completing tuberculosis treatment. RESULTS: The sensitivity of QFT-Plus was 83% and its specificity was 91.5%, similarly to previously reported results for its predecessor QuantiFeron Gold-in-tube. TST sensitivity was similar to that of QFT- Plus, whereas the concordance between both tests was moderate. Among children with latent infection, the QFT-Plus positivity rate was 68.2%, while the concordance between QFT-Plus and TST in these patients was 54.7%. Using logistic regression, the following independent risk factors for presenting an indeterminate result were identified: 1) age under 5 years; 2) low lymphocyte account; and 3) elevated C- reactive protein levels. In the fourth study, we included 295 patients with a positive QFT-Plus result. The difference in IFNγ concentration (DIC) between both reagent tubes was used as a surrogate marker of CD8 response. We did not observe a significant DIC, nor in the overall of patients neither in those in whom an increased CD8 response would be expected. Sixty-five patients with an initial positive result had the test repeated after completing the treatment. Only half of them presented a significant decrease in IFNγ levels. Thus, QFT-Plus does not appear to be useful for monitoring treatment response

Utilitat del QuantiFERON®-TB Gold Plus en el diagnòstic de la infecció tuberculosa latent i la malaltia tuberculosa en població pediàtrica

[cat] INTRODUCCIÓ: Els nens infectats per Mycobacterium tuberculosis tenen un major risc d’emmalaltir de tuberculosi i de fer-ho presentant-ne formes greus. La detecció de la infecció latent a través de tests d'immunodiagnòstic és essencial per poder indicar la quimioprofilaxi i disminuir la possibilitat de progressió a malaltia. A més, la positivitat dels tests reforça la sospita de tuberculosi activa, fet important atès que la confirmació microbiològica sovint no és possible en pacients pediàtrics. El test QuantiFeron-Plus (QFT-Plus) es basa en la detecció d’interferó gamma (IFNγ) secretat per limfòcits sensibilitzats. En comparació als seus predecessors, el QFT-Plus té la particularitat de presentar un segon tub reactiu (TB2). Es planteja que el TB2 serviria per avaluar la resposta dels limfòcits CD8, fet que podria ser important en pacients joves i en aquells amb una alta càrrega bacil·lar. El test s’ha avaluat escassament en pacients pediàtrics. Així, la realització d’aquest treball es justifica per la idiosincràsia de la tuberculosi pediàtrica així com per l’escassa evidència prèvia sobre l’ús del QFT-Plus en pediatria. MÈTODES I OBJECTIUS: Els pacients que conformen els quatre treballs de la tesi han estat reclutats transversal i multicèntricament en el si de la pTBred. S’hi van incloure 1751 pacients menors de 18 anys a qui es va fer el test QFT-Plus. El primer estudi tenia com a objectiu estudiar la sensibilitat del QFT- Plus per diagnosticar la malaltia tuberculosa; el segon, avaluar-ne l’especificitat en pacients sotmesos al QFT-Plus per sospita clínica de malaltia però amb un diagnòstic alternatiu al de tuberculosi; el tercer, estudiar la sensibilitat per a tuberculosi i també el rendiment del test en casos d’infecció latent, així com determinar els factors independentment associats que el test presenti un resultat indeterminat; i el quart, avaluar el paper específic del TB2 i determinar com varia en el temps la concentració d’IFNγ en pacients un cop han rebut tractament antituberculós. RESULTATS: La sensibilitat del QFT-Plus per a tuberculosi va resultar del 83%, similar a la del QuantiFeron Gold-in-tube (QFT-GIT), predecessor del QFT-Plus. La sensibilitat va ser major en pacients amb malaltia confirmada. La sensibilitat del PPD va ser similar a la del QFT-Plus. Per contra, la concordança entre ambdós tests va ser moderada. L’especificitat va resultar del 91,5%, similar a la d’estudis que avaluaven l’especificitat del QFT-GIT seguint la mateixa metodologia. D’entre els infants amb infecció latent, la taxa de positivitat del QFT-Plus va ser del 68,2%, essent la concordança entre QFT-Plus i PPD en aquests pacients del 54,7%. Mitjançant una regressió logística, es van identificar com a factors de risc independents de presentar un resultat indeterminat per al test: 1) edat menor de 5 anys; 2) recompte baix de limfòcits; i 3) nivells elevats de proteïna C reactiva. Al quart estudi s’hi van reclutar 295 pacients amb un QFT-Plus positiu. Es va avaluar la diferència de concentració d’IFNγ entre ambdós tubs reactius (DCI) com a marcador subrogat de la resposta dels limfòcits CD8. Ni en el global dels pacients ni en aquells en qui caldria esperar una resposta CD8 més marcada no es va veure una DCI significativa. Estudis citomètrics previs mostraven detecció de resposta CD8 al TB2 però també, i sovint de manera més marcada, al TB1; de manera que el QFT-Plus podria no estar correctament dissenyat per a la detecció de resposta específica CD8. Es va repetir el test a 65 pacients amb un resultat positiu, un cop van finalitzar el tractament antituberculós. Només la meitat dels infants van presentar una disminució marcada dels nivells d’IFNγ, sense que resultés possible la identificació d’un perfil concret de pacient en qui la concentració disminuís més marcadament. Així, no sembla que el test sigui útil per a la monitorització de la resposta al tractament.[eng] INTRODUCTION: Young children infected with Mycobacterium tuberculosis are at increased risk of developing active tuberculosis. Thus, identifying latent tuberculosis infection through immunodiagnostic tests is essential to reduce the risk of disease progression. QuantiFeron-Plus test (QFT-Plus) is based on the detection of released interferon gamma (IFNγ). Distinctively, it has a second reactive tube (TB2), which is meant to be able to evaluate the response of CD8 lymphocytes. However, there is a lack of previous studies evaluating this test in pediatric patients. OBJECTIVES AND METHODS: This thesis includes four articles. Patients were recruited within the pTBred network. Up to 1751 children younger than 18 years tested with QFT-Plus were finally included. The objectives of these articles were: a) to evaluate both the sensitivity and specificity of QFT- Plus; b) to analyze its performance in patients with latent infection; c) to determine independent risk factors to present an indeterminate result; d) to describe the specific role of the TB2; and e) to identify released IFNγ concentration changes after completing tuberculosis treatment. RESULTS: The sensitivity of QFT-Plus was 83% and its specificity was 91.5%, similarly to previously reported results for its predecessor QuantiFeron Gold-in-tube. TST sensitivity was similar to that of QFT- Plus, whereas the concordance between both tests was moderate. Among children with latent infection, the QFT-Plus positivity rate was 68.2%, while the concordance between QFT-Plus and TST in these patients was 54.7%. Using logistic regression, the following independent risk factors for presenting an indeterminate result were identified: 1) age under 5 years; 2) low lymphocyte account; and 3) elevated C- reactive protein levels. In the fourth study, we included 295 patients with a positive QFT-Plus result. The difference in IFNγ concentration (DIC) between both reagent tubes was used as a surrogate marker of CD8 response. We did not observe a significant DIC, nor in the overall of patients neither in those in whom an increased CD8 response would be expected. Sixty-five patients with an initial positive result had the test repeated after completing the treatment. Only half of them presented a significant decrease in IFNγ levels. Thus, QFT-Plus does not appear to be useful for monitoring treatment response

Proximal tibiofibular dislocation in a closing-wedge high tibial osteotomy causes lateral radiological gapping of the knee: a prospective randomized study

Background: To determine whether a proximal tibiofibular joint dislocation (TFJD) increases lateral compartment gapping more than a fibular head osteotomy (FHO) during a closing-wedge high tibial osteotomy (CWHTO). The second objective was to determine whether lateral compartment gapping affects clinical outcomes. Methods: A prospective randomized clinical study was carried out that included 18 patients in Group 1 (FHO) and 18 in Group 2 (TFJD). Varus-stress radiographs of all the patients with both knees at full extension and at 30 ° of flexion were studied pre-operatively and 12 months post-operatively. Lateral compartment gapping was measured in millimeters. The Knee Society Score (KSS) was used to assess clinical stability. Results: The difference between the pre- and post-operative measurements relative to gapping in the lateral knee compartment at 0 ° of knee flexion was 1.3 mm (SD 1.8) in Group 1 and 4.5 mm (SD 2.4) in Group 2 (p = 0.006). At 30 ° of knee flexion, this difference was 1.9 mm (SD 1.2) in Group 1 and 5.2 mm (SD 3.1) in Group 2 (p = 0.01). No differences were observed in the pre- and post-operative period relative to gapping in healthy knees. Pre-operatively, both groups presented similar KSS knee values: Group 1 with 54.7 (SD 11.7), Group 2 with 54.8 (SD 11.1) (n.s.). Post-operatively, these values were also similar: Group 1 with 93.2 (SD 7.4), Group 2 with 93.5 (SD 5.5) (n.s.). Conclusions: In patients who have undergone a CWHTO, TFJ dislocation increases knee lateral compartment gapping when compared to an FHO at 0 ° and 30 ° of knee flexion. However, this fact seems to have no repercussion on the functional status of the knees as measured with the KSS at the one-year follow-up

QuantiFERON-TB Gold Plus Assay Specificity in Children and Adolescents With Suspected Tuberculosis-A Multicenter Cross-sectional Study in Spain

In this cross-sectional study of 284 children and adolescents with clinically or radiologically suspected tuberculosis in a low-endemic country, the QuantiFERON-TB Gold Plus assay specificity, sensitivity, positive predictive value and negative predictive value were 91.5%, 87.3%, 86.4%, and 91.2%, respectively. The specificity was higher than that observed in tuberculin skin tests performed simultaneously, but similar to previous-generation interferon-gamma release assays.Sin financiación3.806 JCR (2021) Q1, 31/130 Pediatrics1.104 SJR (2021) Q1, 29/320 Pediatrics, Perinatology and Child HealthNo data IDR 2020UE