Could pre-diabetes be considered a clinical condition? opinions from an endocrinologist and a cardiologist

The prevalence of pre-diabetes is increasing worldwide and may start 7 to 10 years before the clinical diagnosis of diabetes. In this stage the presence and accumulation of risk factors is common and already implies an increase in cardiovascular risk. Likewise, the onset of cardiovascular diseases (CVD), mainly coronary artery disease (CAD), peripheral vascular disease and cerebrovascular disease can also take place, all of which account for high rates of morbidity and mortality worldwide. Considering pre-diabetes as a clinical entity, non-pharmacological and pharmacological treatments are indicated with drugs which have shown clinical benefits related to reduction in morbidity and mortality. However, there is still need for new long-term studies to assess the real benefits of several new therapeutical approaches, as well as its cost-effectiveness

Neural networks for fatigue crack propagation predictions in real-time under uncertainty

Crack propagation analyses are fundamental for all mechanical structures for which safety must be guaranteed, e. g. as for the aviation and aerospace fields. The estimation of life for structures in presence of defects is a process inevitably affected by numerous and unavoidable uncertainty and variability sources, whose effects need to be quantified to avoid unexpected failures or excessive conservativism. In this work, residual fatigue life prediction models have been created through neural networks for the purpose of performing probabilistic life predictions of damaged structures in real-time and under stochastically varying input parameters. In detail, five different neural network architectures have been compared in terms of accuracy, computational runtimes and minimum number of samples needed for training, so to determine the ideal architecture with the strongest generalization power. The networks have been trained, validated and tested by using the fatigue life predictions computed by means of simulations developed with FEM and Monte Carlo methods. A real-world case study has been presented to show how the proposed approach can deliver accurate life predictions even when input data are uncertain and highly variable. Results demonstrated that the “H1-L1” neural network has been the best model, achieving an accuracy (Mean Square Error) of 4.8e-7 on the test dataset, and the best and the most stable results when decreasing the amount of data. Additionally, since requiring only very few parameters, its potential applicability for Structural Health Monitoring purposes in small cost-effective GPU devices resulted to be attractive

A descriptive pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime-avibactam for treating DTR gram-negative infections in a case series of critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF)

Purpose: To explore pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) ceftazidime-avibactam for treating difficult-to-treat resistant Gram-negative (DTR-GN) infections in critical patients undergoing continuous venovenous haemodiafiltration (CVVHDF). Materials and methods: Patients treated with CI ceftazidime-avibactam for DTR-GN infections during CVVHDF were retrospectively assessed. Ceftazidime and avibactam concentrations were measured at steady-state and the free fraction (fCss) was calculated. Total clearance (CLtot) of both agents were calculated and the impact of CVVHDF intensity was assessed by linear regression. The joint PK/PD target of ceftazidime-avibactam was defined as optimal when both fCss/MIC≥4 for ceftazidime and fCss/CT > 1 for avibactam were achieved. Relationship between ceftazidime-avibactam PK/PD targets and microbiological outcome was assessed. Results: Eight patients with DTR-GN infections were retrieved. Median fCss were 84.5 (73.7–87.7 mg/L) for ceftazidime and 24.8 mg/L (20.7–25.8 mg/L) for avibactam. Median CLtot was 2.39 L/h (2.05–2.96 L/h) for ceftazidime and 2.56 L/h (2.12–2.98 L/h) for avibactam. Median CVVHDF dose was 38.6 mL/h/kg (35.9–40.0 mL/kg/h). CLtot were linearly correlated with CVVHDF dose (r = 0.53;p = 0.03, and r = 0.64;p = 0.006, respectively). The joint PK/PD targets were optimal granting microbiological eradication in all the assessable cases. Conclusion: CI administration of 1.25–2.5 g q8h ceftazidime-avibactam may allow prompt attainment and maintenance of optimal joint PK/PD targets during high-intensity CVVHDF

Breakthrough invasive fungal infections in liver transplant recipients exposed to prophylaxis with echinocandins vs other antifungal agents: A systematic review and meta-analysis

Introduction: Although echinocandins are recommended as first-line prophylaxis for high-risk orthotopic liver transplant (OLT) recipients, occurrence of breakthrough-invasive fungal infections (IFIs) remains a serious concern. We aim to assess the risk of breakthrough IFIs among OLT recipients exposed to prophylaxis with echinocandins compared to other antifungals. Materials and methods: Two authors independently searched PubMed-MEDLINE, Embase, study registries and reference lists from inception to March 2021, to retrieve randomised controlled trials (RCTs) or observational studies comparing efficacy and safety of echinocandins vs other antifungals for prophylaxis in OLT recipients. Data were independently extracted from two authors, and the quality of included studies was independently assessed according to ROB 2.0 tool for RCTs and ROBINS-I tool for observational studies. The primary outcome was occurrence of breakthrough IFI at the end of prophylaxis (EOP). Results: 698 articles were screened, and ten studies (3 RCTs and 7 observational) were included. No difference between echinocandins and other antifungals in terms of breakthrough IFIs at the EOP emerged both from RCTs (odds ratio [OR] 0.85, 95% CI 0.24–2.99) and observational studies (OR 1.43, 95% CI 0.28–7.40). No difference emerged also for secondary outcomes. In the subgroup comparison between echinocandins and polyenes, a trend for higher risk of breakthrough IFI at the EOP (OR 4.82, 95% CI 0.97–24.03) was noted. Conclusions: Echinocandins do not seem to be associated with increased risk of breakthrough IFIs in OLT recipients. However, the large diversity in the comparator group hinders a definitive interpretation. Further studies exploring the relationship between echinocandin use and breakthrough IFIs according to specific comparators are warranted

In-Network Outlier Detection in Wireless Sensor Networks

To address the problem of unsupervised outlier detection in wireless sensor networks, we develop an approach that (1) is flexible with respect to the outlier definition, (2) computes the result in-network to reduce both bandwidth and energy usage,(3) only uses single hop communication thus permitting very simple node failure detection and message reliability assurance mechanisms (e.g., carrier-sense), and (4) seamlessly accommodates dynamic updates to data. We examine performance using simulation with real sensor data streams. Our results demonstrate that our approach is accurate and imposes a reasonable communication load and level of power consumption.Comment: Extended version of a paper appearing in the Int'l Conference on Distributed Computing Systems 200

Baixos níveis de glicemia e outras complicações durante suplementação de hormônio do crescimento na sepse

O perfil glicêmico esperado em pacientes pós-operatórios sépticos recebendo nutrição enteral de elevado teor calórico é de valores sanguíneos no limite superior do normal ou mesmo hiperglicemia moderada.A adição de hormônio do crescimento (GH) como agente anabólico deveria reforçar ainda mais esta tendência.Num paciente com câncer submetido a gastrectomia parcial e linfadenectomia, que se complicou no pós operatório com abscesso subfrênico e sepse prolongada, administrou-se conjuntamente dieta de sonda (38,3 kcal/kg/dia) e GH (0,17 UI/kg/dia).Antes da introdução de GH as taxas glicêmicas situavam-se nos limites inferiores do normal, e esta tendência persistiu durante a maior parte do período terapêutico.Duas complicações adicionais, nominalmente parada cardíaca e edema periférico, foram documentadas nesta mesma etapa.Conclui-se que a sepse é o mais provável mecanismo de redução da glicemia neste caso, e que o emprego de dieta enteral e de GH não conseguiu prevenir tal efeito.É questionável se a parada cardíaca foi devida ao suplemento hormonal, mas o edema periférico é um secundarismo bem conhecido deste agente em estudos clínicos.Blood glucose levels in the high normal range or even moderate hyperglycemia is the expected profile in septic postoperative patients receiving high-calorie enteral alimentation. The addition of growth hormone as an anabolic agent should additionally reinforce this tendency. In a cancer patient undergoing partial gastrectomy with lymphadenectomy and suffering from postoperative subphrenic abscess and prolonged sepsis, tube feeding (38.3 kcal/kg/day) and growth hormone (0.17 IU/kg/day) were simultaneously administered for 25 days. Blood glucose levels were in the lower limits of the normal range before growth hormone introduction, and continued with a similar tendency during most of the therapeutic period. Two additional complications, namely heart arrest and peripheral edema, were documented during the same period. It is concluded that sepsis was the most likely mechanism for low glucose values, and that high-calorie enteral diet and growth hormone supplementation did not prevent that result. It is uncertain whether heart arrest was due to the drug, but its association with peripheral edema is well documented in clinical series