The value of repeat biopsy in lupus nephritis flares

Whether a repeat renal biopsy is helpful during lupus nephritis (LN) flares remains debatable. In order to analyze the clinical utility of repeat renal biopsy in this complex situation, we retrospectively reviewed our series of 54 LN patients who had one or more repeat biopsies performed only on clinical indications. Additionally, we reviewed 686 well-documented similar cases previously reported (PubMed 1990-2015). The analysis of all patients reviewed showed that histological transformations are common during a LN flare, ranging from 40% to 76% of cases. However, the prevalence of transformations and the clinical value of repeat biopsy vary when they are analyzed according to proliferative or nonproliferative lesions. The great majority of patients with class II (78% in our series and 77.5% in the literature review) progressed to a higher grade of nephritis (classes III, IV, or V), resulting in worse renal prognosis. The frequency of pathological conversion in class V is lower (33% and 43%, respectively) but equally clinically relevant, since almost all cases switched to a proliferative class. Therefore, repeat biopsy is highly advisable in patients with nonproliferative LN at baseline biopsy, because these patients have a reasonable likelihood of switch to a proliferative LN that may require more aggressive immunosuppression. In contrast, the majority of patients (82% and 73%) with proliferative classes in the reference biopsy (III, IV or mixed III/IV + V), remained into proliferative classes on repeat biopsy. Although rebiopsy in this group does not seem as necessary, it is still advisable since it will allow us to identify the 18% to 20% of patients that switch to a nonproliferative class. In addition, consistent with the reported clinical experience, repeat biopsy might also be helpful to identify selected cases with clear progression of proliferative lesions despite the initial treatment, for whom it is advisable to intensify inmunosuppression. Thus, our experience and the literature data support that repeat biopsy also brings more advantges than threats in this group. The results of the repeat biopsy led to a change in the immunosuppresive treatment in more than half of the patients on average, intensifying it in the majority of the cases, but also reducing it in 5% to 30%

Shrinking lung syndrome in systemic lupus erythematosus: A case series and review of the literature

Shrinking lung syndrome (SLS) is a rare and less known complication mainly associated with systemic lupus erythematosus (SLE). In this study, we analyze the clinical features, investigation findings, approaches to management, and outcome in a case series of 9 adult patients with SLE and SLS diagnosed during a 35-year period in 3 referral tertiary care hospitals in Spain. Additionally, we reviewed 80 additional cases previously reported (PubMed 1965-2015). These 80 cases, together with our 9 patients, form the basis of the present analysis. The overall SLS prevalence in our SLE population was 1.1% (9/829). SLS may complicate SLE at any time over its course, and it usually occurs in patients without previous or concomitant major organ involvement. More than half of the patients had inactive lupus according to SELENA-systemic lupus erythematosus disease activity index (SLEDAI) scores. Typically, it presents with progressive exertional dyspnea of variable severity, accompanied by pleuritic chest pain in 76% of the cases. An important diagnostic delay is common. The diagnostic tools that showed better yield for SLS detection are the imaging techniques (chest x-ray and high-resolution computed tomography) along with pulmonary and diaphragmatic function tests. Evaluation of diaphragm dome motion by M-mode ultrasonography and phrenic nerve conduction studies are less useful. There are no standardized guidelines for the treatment of SLS in SLE. The majority of patients were treated with medium or high doses of glucocorticoids. Several immunosuppressive agents have been used in conjunction with steroids either if the patient fails to improve or since the beginning of the treatment. Theophylline and beta-agonists, alone or in combination with glucocorticoids, have been suggested with the intent to increase diaphragmatic strength. The overall long-term prognosis was good. The great majority of patients had significant clinical improvement and stabilization, or mild to moderate improvement on pulmonary function tests. The mortality rate was very low

Registros de cirugía cardíaca: revisión internacional

Registres; Cirurgia cardíaca; Nivell internacionalRegistros; Cirugía cardíaca; Nivel internacionalRecords; Heart surgery; International levelObjective: to assess, in the currently available continuous registries of cardiac surgicalprocedures, features regarding authorship, outcome variables, quality control, their consequences for the quality of care, and bibliometric impact. Methods: 1) A systematic review of the information published on the medical literature or reported in the Internet, and 2) A structured survey addressed to persons identifi ed as representative of the recovered registries. Results: twenty-eight registries fulfi lling the inclusion criteria were identifi ed. Using the survey and the review of web pages additional data were obtained of 9 more registries. Most registries were based on national or regional initiatives or from scientifi c societies and their principal aim was quality of care improvement. Their authors were predominantly cardiac surgeons. Most registries only recorded in-hospital events, and from most of them internal documents that were returned to participants for feedback were generated. Although in most registries some quality control measures were undertaken, these were not comprehensive. Several registries generated articles in high impact journals. Greater impact corresponded to those registries that were associated with intensive and widespread campaigns for quality improvement or with collateral Studies derived from the registry.Objetivo: evaluar, en los registros continuos de cirugía cardíaca actualmente existentes a nivel internacional, sus características de autoría, variables de resultado, control de calidad, infl uencia en la calidad asistencial e impacto bibliométrico. Métodos: 1) Revisión sistemática de la información publicada en la literatura médica y en Internet. 2) Realización de una encuesta estructurada a los responsables de los registros identificados. Resultados: se identifi caron 28 registros que cumplían los criterios de inclusión. Mediante encuesta y revisión de página web se obtuvieron datos adicionales de 9 de ellos. La gran mayoría correspondían a iniciativas nacionales, regionales o de sociedades científicas para mejoría de la calidad asistencial. Los autores predominantes eran cirujanos cardíacos. La mayoría de registros contemplaban sólo resultados intrahospitalarios, y en la mayoría se generaban documentos internos que retornaban la información correspondiente a los participantes. A pesar de que en la mayoría se realizaban actividades de control de calidad, éstas no eran exhaustivas. Varios de los registros generaron publicaciones científi cas de impacto. El mayor de éstos correspondió a registros asociados a campañas intensas y ampliamente difundidas de mejoría de la calidad o a estudios colaterales derivados del propio registro.Objectiu: avaluar, en els registres continus de cirurgia cardíaca actualment existents a nivell internacional, les seves característiques d'autoria, variables de resultat, control de qualitat, influència en la qualitat assistencial i impacte bibliomètric. Mètodes: 1) Revisió sistemàtica de la informació publicada a la literatura mèdica ia Internet. 2) Realització d'una enquesta estructurada als responsables dels registres identificats. Resultats: es identificació car 28 registres que complien els criteris d'inclusió. mitjançant enquesta i revisió de pàgina web es van obtenir dades addicionals de 9 d'ells. La gran majoria corresponien a iniciatives nacionals, regionals o de societats científiques per a millora de la qualitat assistencial. Els autors predominants eren cirurgians cardíacs. La majoria de registres contemplaven només resultats intrahospitalaris, i en la majoria es generaven documents interns que retornaven la informació corresponent als participants. Tot i que en la majoria es realitzaven activitats de control de qualitat, aquestes no eren exhaustives. Diversos dels  registres van generar publicacions científiques ques d'impacte. El major d'aquests va correspondre a registres associats a campanyes intenses i àmpliament difoses de millora de la qualitat o a estudis col·laterals derivats del propi registre

Involvement of the parenchyma of the central nervous system in Behçet disease

Introducción: la enfermedad de Behçet es una vasculitis sistémica que presenta clínica neurológica con una frecuencia que varía entre el 16 y el 40%. Se ha relacionado la afectación parenquimatosa con un peor pronóstico en los pacientes con neurobehçet (NB). Objetivo: revisar la clínica y evolución de los pacientes con NB y afectación parenquimatosa del sistema nervioso central (SNC). Casos clínicos. Siete pacientes con enfermedad de Behçet y focalidad neurológica fueron atendidos en nuestro centro entre 1989 y 1996. El diagnóstico inicial fue de ictus isquémico en cinco de los siete pacientes. Tanto los estudios de neuroimagen como los del líquido cefalorraquídeo resultaron siempre patológicos. Los estudios vasculares (arteriografía y eco-Doppler de troncos supraórticos) fueron normales. Un enfermo fue éxitus letalis. Cuatro pacientes presentaron secuelas tras el tratamiento. Conclusión: el NB ha de formar parte del diagnóstico diferencial del ictus. La afectación parenquimatosa del SNC se acompaña de meningitis linfocitaria y puede, además, condicionar un peor pronóstico funcional

Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the presence of autoantibodies against factor VIII (FVIII). As with other autoimmune diseases, its etiology is complex and its genetic basis is unknown. The aim of this study was to identify the immunogenetic background that predisposes individuals to AHA. HLA and KIR gene clusters, as well as KLRK1, were sequenced using next-generation sequencing in 49 AHA patients. Associations between candidate genes involved in innate and adaptive immune responses and AHA were addressed by comparing the alleles, genotypes, haplotypes, and gene frequencies in the AHA cohort with those in the donors' samples or Spanish population cohort. Two genes of the HLA cluster, as well as rs1049174 in KLRK1, which tags the natural killer (NK) cytotoxic activity haplotype, were found to be linked to AHA. Specifically, A*03:01 (p = 0.024; odds ratio (OR) = 0.26[0.06-0.85]) and DRB1*13:03 (p = 6.8 x 103, OR = 7.56[1.64-51.40]), as well as rs1049174 (p = 0.012), were significantly associated with AHA. In addition, two AHA patients were found to carry one copy each of the low-frequency allele DQB1*03:09 (nallele = 2, 2.04%), which was completely absent in the donors. To the best of our knowledge, this is the first time that the involvement of these specific alleles in the predisposition to AHA has been proposed. Further molecular and functional studies will be needed to unravel their specific contributions. We believe our findings expand the current knowledge on the genetic factors involved in susceptibility to AHA, which will contribute to improving the diagnosis and prognosis of AHA patients

Pragmatic, open-label, single-center, randomized, phase II clinical trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus in patients with severe pneumonia secondary to COVID-19: the TACROVID trial protocol

Introduction: Some COVID-19 patients evolve to severe lung injury and systemic hyperinflammatory syndrome triggered by both the coronavirus infection and the subsequent host-immune response. Accordingly, the use of immunomodulatory agents has been suggested but still remains controversial. Our working hypothesis is that methylprednisolone pulses and tacrolimus may be an effective and safety drug combination for treating severe COVID-19 patients. Methods: and analysis: TACROVID is a randomized, open-label, single-center, phase II trial to evaluate the ef- ficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) versus SoC alone, in patients at advanced stage of COVID-19 disease with lung injury and systemic hyperinflammatory response. Patients are randomly assigned (1:1) to one of two arms (42 patients in each group). The primary aim is to assess the time to clinical stability after initiating randomization. Clinical stability is defined as body temperature≤37.5 ◦C, and PaO2/FiO2 > 400 and/or SatO2/FiO2 > 300, and respiratory rate ≤24 rpm; for 48 consecutive hours. Discussion: Methylprednisolone and tacrolimus might be beneficial to treat those COVID-19 patients progressing into severe pulmonary failure and systemic hyperinflammatory syndrome. The rationale for its use is the fast effect of methylprednisolone pulses and the ability of tacrolimus to inhibit both the CoV-2 replication and the secondary cytokine storm. Interestingly, both drugs are low-cost and can be manufactured on a large scale; thus, if effective and safe, a large number of patients could be treated in developed and developing countries

Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial

Introduction: Severe lung injury is triggered by both the SARS-CoV-2 infection and the subsequent host-immune response in some COVID-19 patients. Methods: We conducted a randomized, single-center, open-label, phase II trial with the aim to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus plus standard of care (SoC) vs. SoC alone, in hospitalized patients with severe COVID-19. The primary outcome was time to clinical stability within 56 days after randomization. Results: From April 1 to May 2, 2020, 55 patients were prospectively included for subsequent randomization; 27 were assigned to the experimental group and 28 to the control group. The experimental treatment was not associated with a difference in time to clinical stability (hazard ratio 0.73 [95% CI 0.39-1.37]) nor most secondary outcomes. Median methylprednisolone cumulative doses were significantly lower (360 mg [IQR 360-842] vs. 870 mg [IQR 364-1451]; p = 0.007), and administered for a shorter time (median of 4.00 days [3.00-17.5] vs. 18.5 days [3.00-53.2]; p = 0.011) in the experimental group than in the control group. Although not statistically significant, those receiving the experimental therapy showed a numerically lower all-cause mortality than those receiving SoC, especially at day 10 [2 (7.41%) vs. 5 (17.9%); OR 0.39 (95% CI 0.05-2.1); p = 0.282]. The total number of non-serious adverse events was 42 in each the two groups. Those receiving experimental treatment had a numerically higher rate of non-serious infectious adverse events [16 (38%) vs. 10 (24%)] and serious infectious adverse events [7 (35%) vs. 3 (23%)] than those receiving SoC. Conclusions: The combined use of methylprednisolone pulses plus tacrolimus, in addition to the SoC, did not significantly improve the time to clinical stability or other secondary outcomes compared with the SoC alone in severe COVID-19. Although not statistically significant, patients receiving the experimental therapy had numerically lower all-cause mortality than those receiving SoC, supporting recent non-randomized studies with calcineurin inhibitors. It is noteworthy that the present trial had a limited sample size and several other limitations. Therefore, further RCTs should be done to assess the efficacy and safety of tacrolimus to tackle the inflammatory stages of COVID-19

Simulación interprofesional en estudiantes de ciencias de la salud

Resumen: Antecedentes y objetivo: la educación interprofesional permite mejorar la comunicación y adquirir las competencias interprofesionales para un mejor cuidado del paciente. El objetivo del presente estudio fue analizar dichos cambios en el grupo clase, y antes-después de participar en una asignatura de grado basada en la simulación interprofesional (SIP). Metodología: estudio descriptivo transversal en estudiantes de primer curso del grado de Enfermería y segundo del grado de Medicina antes de participar en la asignatura optativa de SIP en el curso académico posterior. Se realizó un estudio prospectivo antes y después con 12 estudiantes del grado de Enfermería y 12 de Medicina que recibieron dicha formación. Se usó la Escala de Socialización Interprofesional y Valores para valorar actitudes y creencias hacia la educación colaborativa y la socialización en el grupo profesional. Se analizaron diferencias entre grados con el Test U de Mann-Whitney y entre las 2 fases con la prueba de Friedman parar datos apareados. Resultados: globalmente, el alumnado de Enfermería mostraba, previo a la simulación, un mejor conocimiento del rol, que el alumnado de Medicina. En el corte presimulación, los alumnos de la asignatura de Simulación Interprofesional, puntuaron bajo en los ítems de la escala ISVS relacionados con el uso de un lenguaje común, conocimiento del rol y toma de decisiones compartidas. En el corte postsimulación puntuaron de forma significativamente más alta en todos los ítems de la escala (p < 0,001). Conclusiones: La educación basada en SIP es óptima para desarrollar la socialización interprofesional entre estudiantes de Enfermería y Medicina en el contexto de una asignatura optativa con estudiantes de ambos grados. Posibilita el entrenamiento del propio rol y el conocimiento del rol de los otros miembros, mejorando la comunicación y el trabajo en equipo. Abstract: Background and objective: Interprofessional education allows improving communication and acquiring interprofessional competencies for better patient care. The aim of the present study was to analyze such changes in the class group, and before-after participating in an undergraduate subject based on interprofessional simulation. Methodology: Descriptive cross-sectional study in first year students of the nursing degree and second year students of the medical degree before participating in the interprofessional simulation elective subject in the subsequent academic year. A prospective before and after study was conducted with 12 students of the nursing degree and 12 medical students who received such training. The Interprofessional Socialization and Values Scale was used to assess attitudes and beliefs toward collaborative education and socialization in the professional group. Differences between grades were analyzed with the Mann-Whitney U test and between the two phases with the Friedman test for paired data. Results: Overall, nursing students showed better pre-simulation role knowledge than medical students. In the pre-simulation cut-off, interprofessional simulation students scored low on the ISVS scale items related to the use of common language, role knowledge and shared decision making. In the post-simulation cut-off they scored significantly higher on all items of the scale (p < 0.001). Conclusions: Interprofessional simulation-based education is optimal for developing interprofessional socialization between nursing and medical students in the context of an elective subject with students from both grades. It enables training of one's own role and knowledge of the role of the other members, improving communication and teamwork

Loss of bone mineral density in premenopausal women with systemic lupus erythematosus

OBJECTIVE--To evaluate bone mineral density (BMD) in premenopausal patients with systemic lupus erythematosus (SLE). METHODS--We measured BMD by dual energy x ray absorptiometry at lumbar vertebrae L2-4 and at the right femoral neck in 74 premenopausal white patients (mean age 30.8 years) with SLE who were receiving glucocorticoid therapy, and in a control group. RESULTS--The mean cumulative dose of prednisone was 32.5 (SD 28) g. The mean dose at the time of absorptiometry was 13.7 (6.9) mg. BMD was significantly reduced at the spine and at the femoral neck in SLE patients when compared with the control group: L2-4 = 0.943 (0.1) g/cm2 v 1.038 (0.1) g/cm2 (p < 0.001); femoral neck = 0.766 (0.09) g/cm2 v 0.864 (0.1) g/cm2 (p < 0.001). Nine patients (12.1%), but none of the control group, had a BMD less than the reference range. CONCLUSION--BMD in premenopausal patients with SLE was less than that in a control group and less than the reference range of values defining the presence of osteoporosis in 12.1%. We did not find a relationship between BMD and either cumulative or baseline dose of corticosteroid therapy

Involvement of the parenchyma of the central nervous system in Behçet disease

Introducción: la enfermedad de Behçet es una vasculitis sistémica que presenta clínica neurológica con una frecuencia que varía entre el 16 y el 40%. Se ha relacionado la afectación parenquimatosa con un peor pronóstico en los pacientes con neurobehçet (NB). Objetivo: revisar la clínica y evolución de los pacientes con NB y afectación parenquimatosa del sistema nervioso central (SNC). Casos clínicos. Siete pacientes con enfermedad de Behçet y focalidad neurológica fueron atendidos en nuestro centro entre 1989 y 1996. El diagnóstico inicial fue de ictus isquémico en cinco de los siete pacientes. Tanto los estudios de neuroimagen como los del líquido cefalorraquídeo resultaron siempre patológicos. Los estudios vasculares (arteriografía y eco-Doppler de troncos supraórticos) fueron normales. Un enfermo fue éxitus letalis. Cuatro pacientes presentaron secuelas tras el tratamiento. Conclusión: el NB ha de formar parte del diagnóstico diferencial del ictus. La afectación parenquimatosa del SNC se acompaña de meningitis linfocitaria y puede, además, condicionar un peor pronóstico funcional