Estudio multicéntrico de nefritis intersticial aguda por fármacos: características clínicas e influencia del tratamiento esteroideo

La Nefritis Intersticial Aguda por Fármacos (NIAF) representa un elevado porcentaje de fracaso renal agudo (FRA) en la práctica clínica. Algunos estudios señalan que alrededor del 15-27 % de las biopsias realizadas por un FRA tienen como lesión responsable de la insuficiencia renal una NIAF. Probablemente esta lesión está infradiagnósticada ya que hay muchos casos de NIAF que no son biopsiados y el diagnóstico se establece por elementos clínicos y por el antecedente de la administración de un fármaco nuevo. Aunque numerosos medicamentos han sido involucrados como responsables de esta entidad, los antibióticos y los Antiinflamatorios No Esteroideos (AINE) siguen siendo los fármacos más frecuentemente implicados. La etiopatogenia de la lesión histológica es bien conocida y está producida por un mecanismo de hipersensibilidad al fármaco. Esta reacción alérgica puede dar lugar a una clínica sistémica (fiebre, rash cutáneo, eosinofilia) asociada a un FRA, aunque una proporción significativa de pacientes tiene una presentación oligosintomática y el diagnóstico se basa en el antecedente de la administración de un fármaco nuevo. En tanto que este concepto está bien asentado, todavía existe polémica acerca del papel de los esteroides en el tratamiento de la NIAF. Muchos estudios apuntan que el curso natural de la mayoría de las NIAF suele consistir en una mejoría inicial de la función renal tras la suspensión del fármaco implicado. Sin embargo, esta mejoría inicial frecuentemente se interrumpe y muchos pacientes quedan con cierto grado de insuficiencia renal crónica (IRC). Mientras que algunos estudios han sugerido una influencia positiva de los esteroides, mostrando una recuperación más rápida y completa de la función renal en los pacientes tratados, otros estudios no han confirmado estos efectos favorables de los esteroides. Por todo ello una información muy valiosa y de gran trascendencia seria el identificar aquellos factores que condicionan la evolución clínica de la NIAF e investigar si el momento de inicio del tratamiento es un dato clave que puede afectar a la respuesta de los esteroides..

Prevalence of submicroscopic malaria infection in immigrants living in Spain

BACKGROUND: The importance of submicroscopic malaria infections in high-transmission areas could contribute to maintain the parasite cycle. Regarding non-endemic areas, its importance remains barely understood because parasitaemia in these afebrile patients is usually below the detection limits for microscopy, hence molecular techniques are often needed for its diagnosis. In addition to this, the lack of standardized protocols for the screening of submicroscopic malaria in immigrants from endemic areas may underestimate the infection with Plasmodium spp. The aim of this study was to assess the prevalence of submicroscopic malaria in afebrile immigrants living in a non-endemic area. METHODS: A prospective, observational, multicentre study was conducted. Afebrile immigrants were included, microscopic observation of Giemsa-stained thin and thick blood smears, and two different molecular techniques detecting Plasmodium spp. were performed. Patients with submicroscopic malaria were defined as patients with negative blood smears and detection of DNA of Plasmodium spp. with one or both molecular techniques. Demographic, clinical, analytical and microbiological features were recorded and univariate analysis by subgroups was carried out with STATA v15. RESULTS: A total of 244 afebrile immigrants were included in the study. Of them, 14 had a submicroscopic malaria infection, yielding a prevalence of 5.7% (95% confidence interval 3.45-9.40). In 71.4% of the positive PCR/negative microscopy cases, Plasmodium falciparum alone was the main detected species (10 out of the 14 patients) and in 4 cases (28.6%) Plasmodium vivax or Plasmodium ovale were detected. One patient had a mixed infection including three different species. CONCLUSIONS: The prevalence of submicroscopic malaria in afebrile immigrants was similar to that previously described in Spain. Plasmodium vivax and P. ovale were detected in almost a third of the submicroscopic infections. Screening protocols for afebrile immigrants with molecular techniques could be useful for a proper management of these patients.This work was funded by projects PI14/01671, PI17/01791 and PI14CIII/00014, from the Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and cofounded by the European Regional Development Fund, and approved by the Ethics Committee of our Institution. There was no funding from the PCR manufacturers; they did not play any role in data analysis or in the reporting of the results.S

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Does expert opinion match the definition of lupus low disease activity state? Prospective analysis of 500 patients from a Spanish multicentre cohort.

To apply the lupus low disease activity state (LLDAS) definition within a large cohort of patients and to assess the agreement between the LLDAS and the physician's subjective evaluation of lupus activity. We conducted a cross-sectional analysis of a prospective multicentre study of SLE patients. We applied the LLDAS and assessed whether there was agreement with the clinical status according to the physician's opinion. A total of 508 patients [92% women; mean age 50.4 years (s.d. 3.7)] were recruited and 304 (62.7%) patients were in the LLDAS. According to physician assessment, 430 (86.1%) patients were classified as remission or low activity. Overall agreement between both evaluations was 71.4% (95% CI: 70.1, 70.5) with a Cohen's κ of 0.3 [interquartile range (IQR) 0.22-0.37]. Most cases (96.1%) in the LLDAS were classified as remission or low activity by the expert. Of the patients who did not fulfil the LLDAS, 126 (70.4%) were classified as having remission/low disease activity. The main reasons for these discrepancies were the presence of new manifestations compared with the previous visit and a SLEDAI 2K score >4, mainly based on serological activity. Almost two-thirds of SLE patients were in the LLDAS. There was a fair correlation between the LLDAS and the physician's evaluation. This agreement improves for patients fulfilling the LLDAS criteria. The discordance between both at defining lupus low activity, the demonstrated association of the LLDAS with better outcomes and the fact that the LLDAS is more stringent than the physician's opinion imply that we should use the LLDAS as a treat-to-target goal

Does expert opinion match the definition of Lupus Low Disease Activity State? prospective analysis of 500 patients from a Spanish multicentre cohort

Data de publicació electrònica: 12-08-2022Objectives: To apply Lupus Low Disease Activity State (LLDAS) definition within a large cohort of patients and to assess the agreement between the LLDAS and the physician's subjective evaluation of lupus activity. Methods: A cross-sectional analysis of a prospective multicentre study of Systemic Lupus Erythematosus (SLE) patients. We applied the LLDAS and assessed whether there was agreement with the clinical status according to the physiciańs opinion. Results: 508 patients (92% women; mean age (±SD): 50.4 years (± 13.7)). A total of 304 (62.7%) patients were in LLDAS. According to physician assessment, 430 patients (86,1%) were classified as remission or low activity. Overall agreement between both evaluations was 71.4% (95% CI: 70.1-70.5%) with a Coheńs kappa of 0.3 (0.22-0.37). Most cases (96.1%) in LLDAS were classified as remission or low activity by the expert. Of the patients that did not fulfill LLDAS, 126 (70.4%) were classified as having remission/low disease activity. The main reasons for these discrepancies were the presence of new manifestations compared with the previous visit and a SLEDAI 2-K > 4, mainly based on serological activity. Conclusions: Almost two thirds of SLE patients were in LLDAS. There was a fair correlation between LLDAS and the physician's evaluation. This agreement improves for patients fulfilling the LLDAS criteria. The discordance between both at defining lupus low activity, the demonstrated association of LLDAS with better outcomes and the fact that LLDAS is more stringent than physician's opinion imply that we should use the LLDAS as a treat to target goal

Does remission in systemic lupus erythematosus according to the 2021 DORIS definition match the treating rheumatologist's judgement?

Objectives: To assess agreement between the 2021 Definition Of Remission In SLE (DORIS) and physician-judged lupus activity. Methods: A cross-sectional analysis was conducted of data from a Spanish prospective multicentre study of SLE patients. We applied the 2021 DORIS criteria and assessed whether remission status based on this definition agreed with remission as per physician clinical judgement and reasons for disagreement between them. Results: Out of 508 patients [92% women; mean age (s.d.): 50.4 years (13.7)] studied, 267 (54.4%) met the criteria for 2021 DORIS remission. Based on physicians' judgement, 277 (55.9%) patients were classified as in remission or serologically active clinically quiescent (SACQ). The overall rate of agreement between these assessments was 81.2% (95% CI: 79.9, 82.9%) with a Cohen's kappa of 0.62 (0.55-0.69). Overall, 46 (9.1%) patients were classified as in remission/SACQ by rheumatologists but did not meet the 2021 DORIS criteria for remission. The main reasons for discrepancies were a clinical SLE Disease Activity Index (cSLEDAI) score >0 in 39 patients, a Physician Global Assessment score >0.5 in five patients, and prednisone >5 mg/day in another five patients. Conclusions: The 2021 DORIS remission is an achievable target in clinical practice. There is substantial agreement between the DORIS definition and physician-judged remission. The discordance was mainly due to physicians classifying some patients with ongoing mild disease activity as in remission. Thus, the standardized DORIS definition should be used to define the target in a treat-to-target strategy for the management of SLE

Respiratory and Gastrointestinal COVID-19 Phenotypes in Kidney Transplant Recipients.

Coronavirus infectious disease 2019 (COVID-19) pandemic has posed at risk the kidney transplant (KT) population. We describe clinical pictures, risk factors for death, and chances to recovery in a large cohort of KT recipients with COVID-19. Inclusion in a Spanish prospectively filled registry was allowed for KT cases with confirmed COVID-19. Outcomes were assessed as in-hospital mortality or recovery. The study population comprised of 414 patients. Fever, respiratory symptoms, and dyspnea were the most frequent COVID-19-related symptoms, and 81.4% of them had pneumonia. More than one-third of patients showed digestive symptoms at diagnosis, combinations of nausea, vomiting, and diarrhea. Most patients were hospitalized, 12.1% in intensive care units, and 17.6% needed ventilator support. Treatment for COVID-19 included frequently hydroxychloroquine, azithromycin, high-dose steroids, lopinavir/ritonavir, and tocilizumab. After a mean follow-up of 44 days, the fatality rate was 26.3%. Pneumonia without gastrointestinal symptoms was associated with a 36.3% mortality (respiratory phenotype), and gastrointestinal symptoms without pneumonia with a 5.3% mortality (gastrointestinal phenotype). The mixed pneumonia and gastrointestinal phenotype showed an intermediate mortality of 19.5% (mixed phenotype). Multivariate Cox regression analysis showed that age and pneumonia were independently associated with death, whereas the gastrointestinal phenotype was associated with recovery. COVID-19 is frequent among the KT population. Advanced age and pneumonia are the main clinical features associated with a high-mortality rate. Gastrointestinal disease is associated with a more benign course and lower mortality