Safety of belimumab in association with denosumab in a patient affected by Lupus Erythematosus: a case report

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by multisystemic involvement. Owing to multifactorial etiologies, low bone mineral density (BMD) osteoporosis (OP) and fragility fractures (FFx) have been very frequently documented in these patients. Appropriate treatments to minimize underlying immunologic disease activity remain mandatory, and the development of strategies to prevent and treat important complications as osteoporosis is needed.We present the clinical case of a female SLE patient treated simultaneously with belimumab (anti-BLyS) for the underlying disease, and denosumab (anti-RANKL) for concomitant severe osteoporosis. As these monoclonal antibodies have been recently introduced into the market, their combination has not been reported in literature yet. In this case, the combined administration proved a viable option for a SLE patient with osteoporosis and bisphosphonates contraindications

Análisis Geológico y Metalogenético del Sector Norte de la Cordillera del Viento, Provincia del Neuquén

Fil: Zappettini, Eduardo O. Servicio Geológico Minero Argentino; Argentina.Fil: Cozzi, Guillermo. Servicio Geológico Minero Argentino; Argentina.Fil: Dalponte, Marcelo. Servicio Geológico Minero Argentino; Argentina.Fil: Godeas, Marta C. Servicio Geológico Minero Argentino; Argentina.Fil: Korzeniewski, Lidia I. Servicio Geológico Minero Argentino; Argentina.Fil: Peroni, Javier. Servicio Geológico Minero Argentino; Argentina.Fil: Segal, Susana. Servicio Geológico Minero Argentino; Argentina.Fil: Castro Godoy, Silvia. Servicio Geológico Minero Argentino; Argentina.El distrito Varvarco, ubicado en el sector norte de la Cordillera del Viento, provincia del Neuquén, comprende mineralizaciones polimetálicas auríferas (mina Santos y manifestaciones Gregorio (Radales 1), Radales 2, Lomas del Trapiche, La Pirita, El Indio y Arroyo Norte), manifestaciones cupro-argentíferas (vetas Silverio 1 y 2), y de hierro (El Fierrillo) y áreas de alteración hidrotermal (Auque Cap, Auque Breccia y Guaraco Norte). Se describen las mineralizaciones en un contexto metalogenético regional, se analiza la mineralogía, las inclusiones fluidas y las condiciones físico-químicas de formación de las asociaciones de alteración hidrotermal. Se destaca la presencia de alteración argílica avanzada caracterizada por la asociación pirofilita-diásporo-corindón. El relevamiento magnetométrico ha permitido analizar la continuidad y geometría de los cuerpos mineralizados. El conjunto de mineralizaciones se vincula con rocas plutónicas y subvolcánicas asignadas al Cretácico superior-Paleógeno (Granodiorita Varvarco, Granito Radales y diques subvolcánicos asociados) del que se brinda información geocronológica, geoquímica y petrológica que confirma su asignación a un magmatismo de arco de margen continental activo, sin señal adakítica. Se presenta un modelo metalogenético local y su vinculación con el marco regional. Los diversos tipos de asociaciones minerales identificadas y las características de las inclusiones fluidas analizadas en las vetas analizadas, sugieren que el conjunto podría vincularse con un sistema tipo pórfiro, si bien la alteración argílica avanzada de baja sulfuración y la presencia de mineralización de hierro (magnetita-hematita) permite plantear la hipótesis de un modelo de exploración del tipo IOCG, más afín con la escasez de azufre del sistema

Psychopathological Impact in Patients with History of Rheumatic Fever with or without Sydenham's Chorea: A Multicenter Prospective Study

Sydenham's chorea (SC) is a post-streptococcal autoimmune disorder of the central nervous system, and it is a major criterium for the diagnosis of acute rheumatic fever (ARF). SC typically improves in 12-15 weeks, but patients can be affected for years by persistence and recurrencies of both neurological and neuropsychiatric symptoms. We enrolled 48 patients with a previous diagnosis of ARF, with or without SC, in a national multicenter prospective study, to evaluate the presence of neuropsychiatric symptoms several years after SC's onset. Our population was divided in a SC group (n = 21), consisting of patients who had SC, and a nSC group (n = 27), consisting of patients who had ARF without SC. Both groups were evaluated by the administration of 8 different neuropsychiatric tests. The Work and Social Adjustment Scale (WSAS) showed significantly (p = 0.021) higher alterations in the SC group than in the nSC group. Furthermore, 60.4% (n = 29) of the overall population experienced neuropsychiatric symptoms other than choreic movements at diagnosis and this finding was significantly more common (p = 0.00) in SC patients (95.2%) than in nSC patients (33.3%). The other neuropsychiatric tests also produced significant results, indicating that SC can exert a strong psychopathological impact on patients even years after its onset

Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature.Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 +/- 26.9 yrs.; mean disease duration 8.9 +/- 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas.Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches.Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity