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 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 m 2), 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

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Elliptic flow of identified hadrons in Pb-Pb collisions at 1asNN = 2.76 TeV

The elliptic flow coefficient (v2) of identified particles in Pb-Pb collisions at 1asNN = 2.76 TeV was measured with the ALICE detector at the Large Hadron Collider (LHC). The results were obtained with the Scalar Product method, a two-particle corre- lation technique, using a pseudo-rapidity gap of | 06\u3b7| > 0.9 between the identified hadron under study and the reference particles. The v2 is reported for \u3c0\ub1, K\ub1, K0S, p+p, \u3c6, \u39b+\u39b, \u39e 12+\u39e+ and \u3a9 12+\u3a9+ in several collision centralities. In the low transverse momentum (pT) region, pT 3 GeV/c

A Synthesis of Levetiracetam based on (S)-N-Phenylpantolactam as chiral auxiliary

Risoluzione di composti di interesse farmaceutic

Antibacterial activity of some medicinal Eupatorium species against antibiotic resistant pathogenic bacteria

Thirty six samples arising from hexane, dichloromethane, and methanol extracts from four medicinal Eupatorium species were screened against Gram positive and Gram negative resistant bacteria associated with nosocomial infections by disk diffusion method. The best antibacterial extracts were selected by correspondence analysis. The hexane extracts showed high inhibition against clinical isolated bacteria. The qualitative chemical analysis was realized in the best antibacterial hexane extracts. The main components identified were triterpenes and benzopyran compounds which of extensively had been reported their antibacterial activities. Our results showing that medicinal Eupatorium species studied in this work have metabolites secondary antibacterial particularly against antibiotic resistant strains, Klebsiella pneumoniae and Staphylococcus aureus and validate their uses in traditional medicine.Treinta y seis extractos hexánicos, diclorometanólicos y metanólicos de cuatro especies medicinales de Eupatorium fueron ensayados contra bacterias resistentes Gram positivas y Gram negativas asociadas con infecciones nosocomiales por el método de difusión en disco. Los mejores extractos antibacterianos fueron seleccionados por un análisis de correspondencia. Los extractos hexánicos mostraron mejor inhibición de los aislados clínicos. El análisis químico cualitativo fue realizado a los extractos con mejor actividad antibacteriana. Los principales componentes identificados fueron triterpenos y benzopiranos los cuales han sido extensamente reportados por sus actividades antibacterianas. Nuestros resultados muestran que las especies medicinales de Eupatorium estudiadas en este trabajo tienen metabolitos secundarios antibacterianos contra bacterias resistentes a antibióticos tales como, Klebsiella pneumoniae y Staphylococcus aureus, y se validan sus usos en la medicina tradicional

NOVAC – Network for Observation of Volcanic and Atmospheric Change, recent developments and present status

The NOVAC project, funded by European Union, was started in October 2005 with the aim to establish a global network of stations for the quantitative measurement of volcanic gas emissions. The network is based on a novel type of instrument, the Scanning Dual-beam mini-DOAS. Primarily theinstruments will be used to provide new parameters in the toolbox of observatories for gas emission estimates, geophysical research and hazard assessment. In addition, data are exploited for other scientific purposes, e.g. global estimates of volcanic gas emissions, regional to global statistical analysis, and studies of atmospheric chemistry. In particular large scale validation of satellite measurements of volcanic gas emissions will be possible, bringing space-borne observation of volcanoes a significant step forward.The Scanning Dual-beam Mini-DOAS instrument is capable of real-time automatic, unattended measurement of the total emission fluxes of SO2 and BrO from a volcano with better then 5 minutes time resolution during daylight. The high time-resolution of the data enables correlations with othergeophysical data, e.g. seismicity, thus significantly extending the information available for real-time hazard assessment and research. By comparing high time resolution gas emission data with emissions from neighboring volcanoes on different geographical scales, or with other geophysical events (earthquakes, tidal waves) mechanisms of volcanic forcing may be revealed.The network today encompasses 58 instruments installed on 24 volcanoes, including some of the most active and strongest degassing volcanoes in the world.In addition a mobile version of the instrument has been developed intended for rapid deployment at a volcano in relation to a volcanic crisis.The project and its present status will be presented

NOVAC – Network for Observation of Volcanic and Atmospheric Change, recent developments and present status

The NOVAC project, funded by European Union, was started in October 2005 with the aim to establish a global network of stations for the quantitative measurement of volcanic gas emissions. The network is based on a novel type of instrument, the Scanning Dual-beam mini-DOAS. Primarily theinstruments will be used to provide new parameters in the toolbox of observatories for gas emission estimates, geophysical research and hazard assessment. In addition, data are exploited for other scientific purposes, e.g. global estimates of volcanic gas emissions, regional to global statistical analysis, and studies of atmospheric chemistry. In particular large scale validation of satellite measurements of volcanic gas emissions will be possible, bringing space-borne observation of volcanoes a significant step forward.The Scanning Dual-beam Mini-DOAS instrument is capable of real-time automatic, unattended measurement of the total emission fluxes of SO2 and BrO from a volcano with better then 5 minutes time resolution during daylight. The high time-resolution of the data enables correlations with othergeophysical data, e.g. seismicity, thus significantly extending the information available for real-time hazard assessment and research. By comparing high time resolution gas emission data with emissions from neighboring volcanoes on different geographical scales, or with other geophysical events (earthquakes, tidal waves) mechanisms of volcanic forcing may be revealed.The network today encompasses 58 instruments installed on 24 volcanoes, including some of the most active and strongest degassing volcanoes in the world.In addition a mobile version of the instrument has been developed intended for rapid deployment at a volcano in relation to a volcanic crisis.The project and its present status will be presented

CD30 expression by bone marrow mast cells from different diagnostic variants of systemic mastocytosis

AimsCD30 expression by bone marrow (BM) mast cells (MC) has been reported recently in systemic mastocytosis (SM) patients. The aim of this study was to investigate the potential diagnostic and prognostic value of CD30 expression in SM as assessed by multiparameter flow cytometry. Methods and resultsA total of 163 consecutive BM samples corresponding to 142 SM patients and 21 non-mastocytosis cases were studied. CD30 was positive in most SM patients (80\%), but in only one non-mastocytosis case (4.8\%). When combined with CD25, CD30 contributed to an improved accuracy over that of CD25 alone (98\% versus 93\%) mainly because most (eight of nine) of the well-differentiated SM (WDSM), who lacked CD25, were CD30(+). Similar levels of expression of CD30 were observed among all different subgroups of SM except mast cell leukaemia; among indolent SM (ISM) patients, no significant association was observed between the levels of CD30 expression and other clinical and biological features of the disease. ConclusionsThe increased expression of CD30 associated with absence of CD25 contributes to the diagnosis of WDSM and its distinction from other subtypes of SM. By contrast, CD30 expression did not contribute either to prognostic stratification of ISM or to the differential diagnosis between ISM and aggressive SM cases