Lupus eritematoso sistémico: datos sociodemográficos y su correlación clínico-analítica en un hospital universitario

Objetivos: analizar las características sociodemográficas y clínicas de los pacientes con Lupus Eritematoso Sistémico (LES) del Servicio de Reumatología de un Hospital Universitario de Córdoba

Estratificación de riesgo cardiovascular en enfermedades autoinmunes en un hospital universitario

Introducción: Las enfermedades autoinmunes (EAI) han sido consideradas como no fatales; sin embargo, la mayoría de éstas tienen una historia natural de mortalidad prematura. Algunas como el lupus eritematoso sistémico (LES), artritis reumatoidea (AR), esclerosis sistémica (ES), polimiositis, vasculitis y otras, están asociadas a una mortalidad temprana comparable a las enfermedades cardiovasculares y neoplásicas. Objetivos: 1- Identificar las EAI con mayor riesgo cardiovascular previamente diagnosticadas en pacientes que sean atendidos en un servicio de Reumatología de un hospital universitario. 2- Comparar el riesgo cardiovascular calculado según la escala de Framingham y el modelo SCORE en pacientes con diagnóstico previo de enfermedad autoinmune. Material y métodos: Estudio analítico de corte transversal, en un servicio de Reumatología de un hospital universitario donde se reclutaron 129 historias clínicas de pacientes que acudieron espontáneamente entre el 1 de noviembre de 2010 y el 31 de mayo de 2011. Se elaboraron tablas de cruces de variables y su posterior cálculo con Chi Cuadrado y coeficiente de Pearson. Resultados: Las EAI con mayor riesgo cardiovascular fueron AR, vasculitis y EASN. La escala de Framingham mostró solo un paciente con AR que tenía RCV muy elevado. La vasculitis encabezó el RCV elevado con el 16,7%, pero esto corresponde solo a un paciente. El segundo lugar estaba representado por AR (10,7%), luego EASN (10%) y LES (4,5%). El modelo SCORE demostró que el 3,1% de las enfermedades tenía muy elevado RCV, porcentaje que estaba comprendido por 3 pacientes con AR y 1 con vasculitis. El RCV elevado estuvo representado sólo por AR en un 13,3%. Al comparar ambas escalas de riesgo cardiovascular, el 70,5% de 129 pacientes presentaron bajo RCV. Sólo un paciente (0,8%) con bajo RCV en la escala de Framingham tenía muy elevado RCV en el SCORE. De acuerdo al coeficiente de correlación R de Pearson existe un nivel de asociación de casi el 50%, por lo tanto, se demostró que existe muy buena correspondencia entre estas variables. Conclusión: Se encontró una correlación positiva entre las dos escalas, y las enfermedades con mayor riesgo cardiovascular fueron la AR, vasculitis y EASN, destacando el bajo número de casos de las últimas dos comparadas con la AR. Notoriamente el nivel de evidencia es mayor en AR y en LES que en cualquier otra patología autoinmune. Esto no descarta que el resto de ellas posea alto RCV. Futuros trabajos multicéntricos deberían plantearse para el desarrollo de guías destinadas al resto de las enfermedades autoinmunes o para la aplicación de las ya existentes

Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients

Background: Receptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG. Materials and Methods: We examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival. Results: Microarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that "RANK-negative" and "RANK-positive" patients had a SDFS of 105.7 months (95% CI: 73.9-124.4) and 58.9 months (95% CI: 34.7-68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029). Conclusions: This is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients

Los niveles séricos de Interleucina 22 e Interleucina 6 disminuyen luego del tratamiento en pacientes con artritis reumatoidea

Introducción: la artritis reumatoidea se caracteriza por inflamación de la membrana sinovial debido al infiltrado de células inmunitarias que secretan citocinas relacionadas a perfil Th17 como IL-22 e IL-6. La dinámica de estas citocinas durante el tratamiento permanece incomprendida. El objetivo fue evaluar los niveles séricos y en líquido sinovial (LS) de IL-22 e IL-6, correlacionarlos con diferentes parámetros bioquímicos y clínicos y medir sus cambios post-tratamiento. Material y métodos: se estudiaron 77 pacientes con AR y 30 controles. A 30 pacientes se los evaluó nuevamente luego de 3 meses de tratamiento y a 12 se les extrajo LS. Se midió VSG, PCR, FR, anti-CCPhs, IL-22 e IL-6. Se evaluó la actividad con DAS28 y respuesta al tratamiento con criterios EULAR

Ethical Criteria for the Admission and Management of Patients in the ICU Under Conditions of Limited Medical Resources: A Shared International Proposal in View of the COVID-19 Pandemic

Introduction The present pandemic has exposed us to unprecedented challenges that need to be addressed not just for the current state, but also for possible future similar occurrences. It is worth pointing out that discussions on the allocation of medical resources may not necessarily refer to an exception, but, unfortunately, to a regular condition for a large part of humanity (1). The criteria for admission to an Intensive Care Unit (ICU) setting generally take into account multiple factors. There must be a diagnostic and prognostic basis for the decisions made, considering both biological factors and patient values and wishes. Furthermore, the decision-making process should, whenever possible, respect the patient's advance directives as well as the relationship with the patient's family or attorney. Therapeutic neglect should be avoided. Having applied standard clinical evaluation criteria for the appropriate treatment of patients with COVID-19, including consideration of prognosis, if a hospital then finds itself unable to provide optimal treatment (e.g., due to a disproportion between the number of patients and the availability of beds, healthcare providers, ventilators, and drugs in the ICU), it becomes necessary to evaluate, case by case, how to achieve justice and the best possible good for the greatest number of patients. It is therefore mandatory to explore alternative solutions; these include increasing available beds and healthcare providers, implementing alternative, though suboptimal, approaches (where appropriate), transferring patients to other clinical units, etc. Making these decisions properly also involves the recovery of the political role of medicine and science (2). If the imbalance between needs and resources reaches a critical level, an emergency triage protocol, following the operational and ethical indications of “disaster medicine,” should be activated. These have been deployed in major and serious natural (earthquakes or tsunamis for example) and technological (factory explosions, public transport accidents for example) disasters, as well as following terrorist attacks (3, 4). The question of the feasibility of developing a clinical evaluation algorithm to support the decision-making of the triage team remains open, though many such protocols have been written. According to the above, we propose the following five ethical criteria for the triage of patients in conditions of limited resources, such as the COVID pandemic. They are the result of an interdisciplinary and intercultural dialogue between specialists from different disciplines. Several of the authors are working in the main epicenters of the crisis and currently are playing a central role in the bioethical, clinical, social and legal aspects of the management of the COVID-19 pandemic

Dynamics of circulating follicular helper T cell subsets and follicular regulatory T cells in rheumatoid arthritis patients according to HLA-DRB1 locus

B cells, follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are part of a circuit that may play a role in the development or progression of rheumatoid arthritis (RA). With the aim of providing further insight into this topic, here we evaluated the frequency of different subsets of Tfh and Tfr in untreated and long-term treated RA patients from a cohort of Argentina, and their potential association with particular human leukocyte antigen (HLA) class-II variants and disease activity. We observed that the frequency of total Tfh cells as well as of particular Tfh subsets and Tfr cells were increased in seropositive untreated RA patients. Interestingly, when analyzing paired samples, the frequency of Tfh cells was reduced in synovial fluid compared to peripheral blood, while Tfr cells levels were similar in both biological fluids. After treatment, a decrease in the CCR7loPD1hi Tfh subset and an increase in the frequency of Tfr cells was observed in blood. In comparison to healthy donors, seropositive patients with moderate and high disease activity exhibited higher frequency of Tfh cells while seropositive patients with low disease activity presented higher Tfr cell frequency. Finally, we observed that HLA-DRB1*09 presence correlated with higher frequency of Tfh and Tfr cells, while HLA-DRB1*04 was associated with increased Tfr cell frequency. Together, our results increase our knowledge about the dynamics of Tfh and Tfr cell subsets in RA, showing that this is altered after treatment

Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): A randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX

Background: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. Patients and methods: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progressionfree survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. Results: Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056]. Conclusions: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials

Cyclosporine A treatment in patients with Alport syndrome: a single-center experience

Limited and discordant data are available on cyclosporine A (CsA) treatment for proteinuria in Alport syndrome (AS). To address this lack of consistent data, we have studied 15 AS patients (14 males; mean age 15.3 +/- 6.0 years) treated with CsA. Patient selection criteria included a urinary protein/creatinine ratio a parts per thousand yen1 mg/mg and a creatinine clearance > 40 ml/min/1.73 m(2). CsA treatment was started at an initial dose of 5 mg/kg/day and subsequently adjusted to reach target C2 levels of 500 ng/ml. Renal function, proteinuria, and blood pressure were monitored. Blood pressure was treated to avoid the administration of angiotensin converting enzyme or angiotensin receptor blockers for the first 2 years of therapy. The average follow-up was 3.5 years. Five patients had chronic renal failure at the beginning of treatment, of whom three and one reached end-stage renal failure within 1 and 3 years, respectively. In the remaining 11 patients, the glomerular filtration rate declined by 11 +/- 6% within 6 months, but remained stable thereafter. Proteinuria decreased by 63 +/- 21% from baseline, but returned nearly to baseline after 2.5 years of follow-up. Based on these results, we suggest that CsA is effective in reducing proteinuria in patients with Alport syndrome but that this effect is temporary. Our data do not support the use of CsA therapy for proteinuric patients with AS, particularly if they have chronic renal failure