Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Tintinnids from Todos Santos Bay, B.C., Mexico (1980-1985). I. Taxonomy

Tintinnids from Todos Santos Bay, Baja California (Mexico), were collected from 1980 to 1985 by means of 83 horizontal surface tows with a standard No. 20 net (75 µm mesh size). Based on lorica morphology, 66 species and 30 genera were identified. Ten species are considered as permanent due to their presence in plankton during at least four years. Other records include: two cold-water, five tropical and two cosmopolitan species. Such an assembly suggests that the bay is subject to changing conditions. A key to the genera is presented with 70 light microscope photographs, 41 SEM pictures and seven line drawings. Remarks on synonymy, specific taxonomic characters and polymorphism are included. Ultrastructure observations proved to be of great aid in these forementioned aspects. The high diversity suggests that Todos Santos Bay harbors several different microhabitats

Cysts of lingulodinium polyedrum, red tide producing organism in the todos santos bay (winter-spring, 2000)

Dinoflagellate cysts with dinosporin walls were identified for the first time in samples collected at Todos Santos Bay, Baja California, Mexico, during winter-spring 2000. Eighteen neritic species characteristic of temperate to temperate-cool neritic regions were identified, mainly from the Gonyaulacaceae and Congruentidiaceae families. The cysts were concentrated in the coastal zone, at depths shallower than 25 m, associated with surface fine sediments. Lingulodinium polyedrum (Stein) Dodge was the dominant species in both the sediments and in the water column, producing spring and summer red tides in the area

Diffraction pattern applicability in the identification of Ceratium species

At present, a subject of great interest for the scientific community is to obtain automatic systems for counting and identifying organisms responsible for red tides. Nevertheless, there are key problems that affect the results in the correct identification and quantification, such as image background (detritus, lighting variation in the microscope), variation in cell sedimentation in the observation field, natural morphological variation of the species in a sample, intra- and interspecific problems, and organism fragmentation. These problems are quantified by means of digital analysis of the phytoplankton organisms' image diffraction patterns. Quantification was accomplished by analyzing the results of the image diffraction pattern correlations and the image correlations. The results showed that the use of diffraction patterns in the identification of six Ceratium species overcomes the numerous noise problems mentioned above

Toxic and harmful marine phytoplankton and microalgae (HABs) in Mexican Coasts

Harmful Algal Blooms (HABs) are becoming an increasing problem to human health and environment (including effects on natural and cultured resources, tourism and ecosystems) all over the world. In Mexico a number of human fatalities and important economic losses have occurred in the last 30 years because of these events. There are about 70 species of planktonic and non-planktonic microalgae considered harmful in Mexican coasts. The most important toxin-producing species are the dinoflagellates Gymnodinium catenatuni and Pyrodinium bahamense var. compressum, in the Mexican Pacific, and Karenia brevis in the Gulf of Mexico, and consequently the poisonings documented in Mexico are Paralytic Shellfish Poisoning (PSP) and Neurotoxic Shellfish Poisoning (NSP). Although there is evidence that Amnesic Shellfish Poisoning (ASP), Diarrhetic Shellfish Poisoning (DSP) and Ciguatera Fish Poisoning (CFP) also occur in Mexico, these problems are reported less frequently. The type of phytoplankton and epiphytic microalgae, their toxins and harmful effects as well as current methodology used to study these phenomena are presented in this paper. As an experienced group of workers, we include descriptions of monitoring and mitigation programs, our proposals for collaborative projects and perspectives on future research