Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Aproximación al esquema sintaxonómico de la vegetaciónde la región del Caribe y América del Sur

In this work, we present a preliminary phytosociological synthesis of the vegetation of the Caribbean region and South America to the alliance level. As result, we can recognize 95 phytosociological classes. For the moment, as novelties, 6 new classes (Alnetea acuminatae Calamagrostio effusae-Espeletietea grandifl orae, Chiliotrichetea diffusi, Gaultherio-Aristotelietea, Palauo dissecti-Nolanetea gayanae and Pruno rigidae-Oreopanecetea fl oribundae), 2 orders Andropogono multinervosi- Eragrostietalia cubensis and Cortaderietalia jubatae) and 3 alliances (Najo guadalupensis-Ruppion maritimae, Polylepidion incano-pautae and Pruno tucumanensis-Alnion acuminatae) are described.En este trabajo presentamos una síntesis fi tosociológica preliminar sobre la vegetación de la región del Caribe y América del Sur hasta el nivel de alianza. Como resultado, podemos reconocer 95 clases fi tosociológicas. Por el momento, como novedades, describimos 6 nuevas clases (Alnetea acuminatae, Calamagrostio effusae-Espeletietea grandifl orae, Chiliotrichetea diffusi, Gaultherio-Aristotelietea, Palauo dissecti-Nolanetea gayanae y Pruno rigidae- reopanecetea fl oribundae), 2 órdenes (Andropogono multinervosi-Eragrostietalia cubensis y Cortaderietalia jubatae) y 3 alianzas (Najo guadalupensis-Ruppion maritimae, Polylepidion incano-pautae y Pruno tucumanensis-Alnion acuminatae)

A phytosociological analysis and synopsis of the dry woodlands and succulent vegetation of the Peruvian Andes

ABSTRACT A phytosociological approach to dry forest and cactus communities on the occidental slopes of the Peruvian Andes is presented in base of 164 plots carried out following the Braun-Blanquet method. From them, 52 have been made recently, and the other 112 were taken from the literature. After a multivariate analysis, using a hierarchical clustering and a detendred correspondence analysis, the Acacio-Prosopidetea class (dry forest and cactus communities, developed on soils with some edaphic humidity or precipitations derived from El Niño Current), the Opuntietea sphaericae class (cactus communities of central and southern Peru, on few stabilized rocky or sandy soils) and the Carico-Caesalpinietea class (dry forests of the Peruvian coastal desert, influenced by the maritime humidity of the cold Humboldt Current), are differentiated. Within the Acacio-Prosopidetea class, two alliances are commented: the Bursero-Prosopidion pallidae (with two new associations Loxopterygio huasanginis-Neoraimondietum arequipensis and Crotono ruiziani-Acacietum macracanthae), and the new alliance Baccharido-Jacarandion acutifoliae (with the new associations Armatocereo balsasensis-Cercidietum praecocis and Diplopterydo leiocarpae-Acacietum macracanthae). For the Opuntietea sphaericae class, the association Haageocereo versicoloris-Armatocereetum proceri (Espostoo-Neoraimondion) is described on the basis of plots from hyperarid localities of central Peru. Finally, a typological classification of the studied plant communities is given