- Short vs. long duration antimicrobial treatment for community-onset bacteremia: A propensity-score matching study. [Journal Article]
- IJInt J Antimicrob Agents 2019 May 17
- The efficacy and safety of short-course intravenous (IV) antimicrobial therapy for bloodstream infections is unknown. To compare the outcomes of patients receiving short-course (5-10 days) and long-c…
The efficacy and safety of short-course intravenous (IV) antimicrobial therapy for bloodstream infections is unknown. To compare the outcomes of patients receiving short-course (5-10 days) and long-course (11-16 days) IV antibiotic therapy for community-onset bacteremia, the retrospective 8-year cohort study included 1431 hospitalized adults was conducted. Of the 1,010 patients who received short-course therapy, 726 were matched with 363 patients in the long-course group through the propensity-score matching at a ratio of 1:2, based on independent predictors of 30-day mortality recognized using the multivariate regression model. After appropriate matching, similarities between the two groups in the proportion of baseline characteristics, in terms of age, sex, major comorbidities, comorbidity severity, bacteremia severity at onset, and major bacteremia sources, and the 30-day crude mortality rate after bacteremia onset were observed. Notably, clinical outcomes within 30 days after the end of IV therapy, in terms of proportions of post-treatment overall infections (2.2% vs. 6.1%, P = 0.001), infections caused by antimicrobial-resistant pathogens ([ARPs], 1.7% vs. 4.4%, P = 0.007), and thereby post-treatment crude mortality (1.4% vs. 3.6%, P = 0.009), were lower in the short-course group. Conclusively, for adults having community-onset uncomplicated bacteremia, short-course (5-10 days) of IV antibiotic treatment did not result in an increased risk of mortality but instead decreased their odds of overall and ARP infections after the treatment course.
- Diabetes Research & Clinical Practice Series : Implications of the recent CVOTs in Type 2 Diabetes: Impact on guidelines: the endocrinologist point of view. [Review]
- DRDiabetes Res Clin Pract 2019 May 17
- The management of type 2 diabetes mellitus (T2DM) essentially consists in controlling hyperglycaemia, together with other vascular risk factors, in order to reduce the incidence and severity of diabe…
The management of type 2 diabetes mellitus (T2DM) essentially consists in controlling hyperglycaemia, together with other vascular risk factors, in order to reduce the incidence and severity of diabetic complications. Whereas glucose control using classical glucose-lowering agents (except perhaps metformin) largely fails to reduce cardiovascular disease (CVD), two new pharmacological classes, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter type 2 inhibitors (SGLT2is), have proven their ability to reduce major cardiovascular events in patients with established CVD. Furthermore, SGLT2is reduced the risk of hospitalisation for heart failure and the progression of renal disease. According to the 2018 ADA-EASD consensus report, the choice of a second agent to be added to metformin should now be driven by the presence or not of atherosclerotic CVD, heart failure or renal disease, all conditions that should promote the use of a SGLT2i or a GLP-1 RA with proven efficacy. Thus endocrinologists have to face a new paradigm in the management of T2DM, with a shift from a primary objective of glucose control without inducing hypoglycaemia and weight gain to a goal of cardiovascular and renal protection, largely independent of glucose control. Of note, however, the latter remains crucial to reduce the risk of microangiopathy.
- Invasive Ductular Reaction Operates Hepatobiliary Junctions upon Hepatocellular Injury in Rodents and Humans. [Journal Article]
- AJAm J Pathol 2019 May 17
- Ductular reaction (DR) is observed in virtually all liver diseases both in humans and rodents. Depending on the injury, DR is confined within the periportal area or invades the parenchyma. Upon sever…
Ductular reaction (DR) is observed in virtually all liver diseases both in humans and rodents. Depending on the injury, DR is confined within the periportal area or invades the parenchyma. Upon severe hepatocellular injury, invasive DR has been proposed to arise for supplying the liver with new hepatocytes. However, experimental data evidenced that DR contribution to hepatocyte repopulation is at the most modest, unless replicative capacity of hepatocytes is abrogated. Here, we proposed that invasive DR could contribute to operating hepatobiliary junctions upon hepatocellular injury. We used the choline-deficient ethionine-supplemented (CDE) mouse model of hepatocellular injury and human liver samples to evaluate the hepatobiliary junctional role of the invasive form of DR. We showed that CDE-induced DR expanded as biliary epithelium into the lobule and established new junctions with the canaliculi. By contrast, no new ductular-canalicular junctions were observed in mouse models of biliary obstructive injury exhibiting non-invasive DR. Similarly, in humans, an increased number of hepatobiliary junctions were observed in hepatocellular diseases (viral, drug-induced or metabolic) in which DR invaded the lobule but not in biliary diseases (obstruction or cholangitis) in which DR was contained within the portal mesenchyme. In conclusion, our data in rodents and humans support that invasive DR plays a hepatobiliary junctional role to maintain structural continuity between hepatocytes and ducts in disorders affecting hepatocytes.
- Consumption of nuts and seeds and pancreatic ductal adenocarcinoma risk in the European Prospective Investigation into cancer and Nutrition. [Journal Article]
- IJInt J Cancer 2019 May 20
- Four epidemiologic studies have assessed the association between nut intake and pancreatic cancer risk with contradictory results. The present study aims to investigate the relation between nut intak…
Four epidemiologic studies have assessed the association between nut intake and pancreatic cancer risk with contradictory results. The present study aims to investigate the relation between nut intake (including seeds) and pancreatic ductal adenocarcinoma (PDAC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to estimate hazards ratio (HR) and 95% confidence intervals (95%CI) for nut intake and PDAC risk. Information on intake of nuts was obtained from the EPIC country-specific dietary questionnaires. After a mean follow-up of 14 years, 476160 participants were eligible for the present study and included 1283 PDAC cases. No association was observed between consumption of nuts and PDAC risk (highest intake vs non-consumers: HR:0.89, 95%CI:0.72-1.10, P-trend:0.70). Further, no evidence for effect-measure modification was observed when different subgroups were analyzed. Overall, in EPIC, the highest intake of nuts was not statistically significantly associated with PDAC risk. This article is protected by copyright. All rights reserved.
- Enteral vs. parenteral nutrition in septic shock: are they equivalent? [Journal Article]
- COCurr Opin Crit Care 2019 May 16
- CONCLUSIONS: The strong paradigm of favoring the enteral over the parenteral route in critically ill patients has been challenged. As a consequence, updated guidelines recommend withholding enteral nutrition in patients with uncontrolled shock. It is still unclear, however, whether parenteral nutrition is advantageous in patients with shock although benefits are conceivable in light of less gastrointestinal complications. Thus far, no guideline has addressed indications for parenteral nutrition in these patients. By considering recent scientific evidence, specific guideline recommendations, and expert opinions, we present a clinical algorithm that may facilitate decision-making when feeding critically ill patients with shock.
- Translating the European Society for Clinical Nutrition and Metabolism 2019 guidelines into practice. [Journal Article]
- COCurr Opin Crit Care 2019 May 16
- CONCLUSIONS: A pragmatic approach to incorporate the recent ESPEN guidelines into everyday clinical practice is provided.
- Pilot Study: Neurocognitive Disorders and Colonoscopy in Older Adults. [Journal Article]
- A&AAnesth Analg 2019 May 15
- In a preoperative anesthesia setting with integrated neuropsychology for individuals >64 years of age, we completed a pilot study examining the association between neurocognitive disorders with frequ…
In a preoperative anesthesia setting with integrated neuropsychology for individuals >64 years of age, we completed a pilot study examining the association between neurocognitive disorders with frequency of missed colonoscopies and quality of bowel preparation (prep). Gastroenterologists completed the Boston Bowel Preparation Scale (BBPS) for each patient. Of 47 older adults seen in our service, 68% met criteria for neurocognitive disorders. All individuals failing to attend the colonoscopy procedure had met criteria for major neurocognitive disorder. Poor bowel prep was also identified in 100% of individuals with major neurocognitive disorder and 28% of individuals with mild neurocognitive disorder. Our pilot data suggest that, in high-risk individuals, the presence of neurocognitive disorders is risk factors for missed appointments and inadequate bowel prep. These pilot data provide reference statistics for future intervention protocols.
- Functional analysis of new variants at the Low Density Lipoprotein Receptor associated with familial hypercholesterolemia. [Journal Article]
- HMHum Mutat 2019 May 20
- Familial hypercholesterolemia is an autosomal dominant disease of lipid metabolism caused by defects in the genes LDLR, APOB, PCSK9. The prevalence of heterozygous familial hypercholesterolemia (HeFH…
Familial hypercholesterolemia is an autosomal dominant disease of lipid metabolism caused by defects in the genes LDLR, APOB, PCSK9. The prevalence of heterozygous familial hypercholesterolemia (HeFH) is estimated between 1/200 and 1/250. Early detection of patients with FH allows initiation of treatment, thus reducing the risk of coronary heart disease. In this study we performed in vitro characterization of new LDLR variants found in our patients. Genetic analysis was performed by Next Generation Sequencing (NGS) using a customized panel of 198 genes in DNA samples of 516 subjects with a clinical diagnosis of probable or definitive FH. All new LDLR variants found in our patients were functionally validated in CHO-ldlA7 cells. LDLR activity was measured by flow cytometry and LDLR expression was detected by immunofluorescence. Seven new variants at LDLR were tested: c.518 G>C;p.(Cys173Ser), c.[684G>T;694G>T];p.[Glu228Asp;Ala232Ser], c.926C>A;p.(Pro309His), c.1261A>G;p.(Ser421Gly), c.1594T>A;p.(Tyr532Asn), and c.2138delC;p.(Thr713Lysfs*17). We classified all variants as pathogenic except p.(Ser421Gly) and p.(Ala232Ser). The functional in vitro characterization of rare variants at the LDLR is a useful tool to classify the new variants. This approach allows us to confirm the genetic diagnosis of FH, avoiding the classification as "uncertain significant variants", and therefore, carry out cascade family screening. This article is protected by copyright. All rights reserved.
- Nutritional Heterogeneity Among Aspergillus fumigatus Strains Has Consequences for Virulence in a Strain- and Host-Dependent Manner. [Journal Article]
- FMFront Microbiol 2019; 10:854
- Acquisition and subsequent metabolism of different carbon and nitrogen sources have been shown to play an important role in virulence attributes of the fungal pathogen Aspergillus fumigatus, such as …
Acquisition and subsequent metabolism of different carbon and nitrogen sources have been shown to play an important role in virulence attributes of the fungal pathogen Aspergillus fumigatus, such as the secretion of host tissue-damaging proteases and fungal cell wall integrity. We examined the relationship between the metabolic processes of carbon catabolite repression (CCR), nitrogen catabolite repression (NCR) and virulence in a variety of A. fumigatus clinical isolates. A considerable amount of heterogeneity with respect to the degree of CCR and NCR was observed and a positive correlation between NCR and virulence in a neutropenic mouse model of pulmonary aspergillosis (PA) was found. Isolate Afs35 was selected for further analysis and compared to the reference strain A1163, with both strains presenting the same degree of virulence in a neutropenic mouse model of PA. Afs35 metabolome analysis in physiological-relevant carbon sources indicated an accumulation of intracellular sugars that also serve as cell wall polysaccharide precursors. Genome analysis showed an accumulation of missense substitutions in the regulator of protease secretion and in genes encoding enzymes required for cell wall sugar metabolism. Based on these results, the virulence of strains Afs35 and A1163 was assessed in a triamcinolone murine model of PA and found to be significantly different, confirming the known importance of using different mouse models to assess strain-specific pathogenicity. These results highlight the importance of nitrogen metabolism for virulence and provide a detailed example of the heterogeneity that exists between A. fumigatus isolates with consequences for virulence in a strain-specific and host-dependent manner.
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- Differential Neuroplastic Changes in Fibromyalgia and Depression Indexed by Up-Regulation of Motor Cortex Inhibition and Disinhibition of the Descending Pain System: An Exploratory Study. [Journal Article]
- FHFront Hum Neurosci 2019; 13:138
- CONCLUSIONS: These findings support the hypothesis that in FM a deteriorated function of cortical inhibition, indexed by a higher SICI parameter, a lower function of the DPMS, together with a higher level of BDNF indicate that FM has different pathological substrates from depression. They suggest that an up-regulation phenomenon of intracortical inhibitory networks associated with a disruption of the DPMS function occurs in FM.