Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Modulation of dendritic spine plasticity, neuroinflammation and neurogenesis in 3XTG-AD mice hippocampus through glucocorticoid receptors

AIMS: The Glucocorticoids hormones act, through mineralcorticoid and glucocorticoid receptors (GRs). GRs are activated by high concentrations of glucocorticoids that in brain induced alteration comparable to those produced by Alzheimer\u2019s Disease (AD). The aim is to assess the role of GRs in the pathogenesis of AD, related to synaptic plasticity, microglia activation and neurogenesis, in 3xTg-AD mouse model. METHOD: We administered agonist (dexamethasone) or antagonist (mifepristone) of GRs, to 3xTg male mice. Brains were processed for Golgi Cox staining to highlight dendritic spines and/or in combination with immunofluorescence using antibody of IBA1, for microglia. We also treated cultures of cortical and hippocampal neurons from E18 pups of 3xTg and C57BL/6 mice, and cultures of microglia from C57BL/6. RESULTS: Dexamethasone induced, on neurons, a 23% and 14% reduction of spine density in CA1 region of hippocampus, respectively at 6 and 10 months of age, whereas mifepristone resulted in a 14% and 10.5% significant increase. Related to microglia, dexamethasone induced in CA1 an increase of density (by 30%), IBA1 signal and hypertrophy. CD68 signal, a marker of phagocytosis, is increased in microglia cultures after dexamethasone treatment and reduced after mifepristone treatment. In neuron cultures, Tau and GR are clearly detectable and increased in 3xTg rather than C57BL/6. We are also treating them with glucocorticoids to underline spine changes, using PSD95, and the involvement of Rho GTPases, N-cadherin and BDNF pathways. Moreover, we are treating animals with BrdU to investigate hippocampal neurogenesis. CONCLUSION: There could be a synergy between the molecular pathways existing in AD and the molecular action of glucocorticoids. GR hyper-activation, in 3xTg mice, induces a degeneration of dendritic spines in CA1 region of hippocampus, through neuron intracellular mechanisms and microglia activation. So, blockade of GR could represent a therapeutic target to slow down the AD progression

Static compliance and driving pressure are associated with ICU mortality in intubated COVID-19 ARDS

Background: Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. Methods: Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th–April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. Results: A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values < 48 ml/cmH2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06–1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55–1.52). Multivariable analysis confirmed these findings. Conclusions: Crs < 48 ml/cmH2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death

Outcomes of COVID-19 patients intubated after failure of non-invasive ventilation: a multicenter observational study

The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the intensive care unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: (1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and (2) assessing whether the length of NIV application affects patient survival. This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February\u2013April 2020), who underwent endotracheal intubation after NIV failure. Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60\u201376] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06\u20134.98), p = 0.03) and age (OR 1.18 (95% CI 1.04\u20131.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality

Kidney dysfunction and related cardiovascular risk factors among patients with type 2 diabetes

Background. Kidney dysfunction is a strong predictor of end-stage renal disease and cardiovascular (CV) events. The main goal was to study the clinical correlates of diabetic kidney disease in a large cohort of patients with type 2 diabetes mellitus (T2DM) attending 236 Diabetes Clinics in Italy.Methods. Clinical data of 120 903 patients were extracted from electronic medical records by means of an ad hoc-developed software. Estimated glomerular filtration rate (GFR) and increased urinary albumin excretion were considered. Factors associated with the presence of albuminuria only, GFR &lt; 60 mL/min/1.73 m(2) only or both conditions were evaluated through multivariate analysis.Results. Mean age of the patients was 66.6 +/- 11.0 years, 58.1% were male and mean duration of diabetes was 11.1 +/- 9.4 years. The frequency of albuminuria, low GFR and both albuminuria and low GFR was 36.0, 23.5 and 12.2%, respectively. Glycaemic control was related to albuminuria more than to low GFR, while systolic and pulse pressure showed a trend towards higher values in patients with normal kidney function compared with those with both albuminuria and low GFR. Multivariate logistic analysis showed that age and duration of disease influenced both features of kidney dysfunction. Male gender was associated with an increased risk of albuminuria. Higher systolic blood pressure levels were associated with albuminuria, with a 4% increased risk of simultaneously having albuminuria and low GFR for each 5 mmHg increase.Conclusions. In this large cohort of patients with T2DM, reduced GFR and increased albuminuria showed, at least in part, different clinical correlates. A worse CV risk profile is associated with albuminuria more than with isolated low GFR

Mortality after surgery in Europe: a 7 day cohort study

Background: Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe.Methods: We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ² and Fisher’s exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p&lt;0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries.Findings: We included 46 539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9–3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0–3·0] for Iceland to 21·5% [16·9–26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19 1·05; p=0·06] for Finland to 6·92 [2·37–20·27; p=0·0004] for Poland).Interpretation: The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients.Funding: European Society of Intensive Care Medicine, European Society of Anaesthesiology