222 research outputs found
Emergence of KPC-producing Klebsiella pneumoniae in Italy
<p>Abstract</p> <p>Background</p> <p>The emergence of KPC-producing <it>K. pneumoniae </it>has now become a global concern. KPC beta-lactamases are plasmid-borne and, like extended spectrum beta lactamases (ESBLs), can accumulate and transfer resistance determinants to other classes of antibiotics. Therefore, infection control guidelines on early identification and control of the spread of organisms carrying these resistant determinants are needed.</p> <p>Findings</p> <p><it>Klebsiella pneumoniae </it>carbapenemase (KPC) was detected in two isolates of carbapenem-resistant <it>K. pneumoniae </it>obtained from patients at an Italian teaching hospital. The first strain was isolated from a culture drawn from a central venous device (CVC) in a patient with Crohn's disease who was admitted to a gastroenterology ward. The second was isolated from a urine sample collected from an indwelling urinary catheter in an intensive care unit (ICU) patient with a subdural haematoma. The patients had not travelled abroad. Both isolates were resistant to all β-lactams and were susceptible to imipenem and meropenem but resistant to ertapenem. Isolates also showed resistance to other classes of non-β-lactam antibiotics, such as quinolones, aminoglycosides (with the exception for amikacin), trimethoprim-sulfamethoxazole (TMP-SMX) and nitrofurantoin. They were determined to contain the plasmid encoding the carbapenemase gene <it>bla-KPC </it>and were also positive in the Hodge test.</p> <p>Conclusions</p> <p>This is the second report of KPC-producing isolates in Italy, but the first concerning KPC type 2 gene, and it may have important implications for controlling the transmission of microorganisms resistant to antibiotics.</p
Longitudinal study on low-dose aspirin versus placebo administration in silent brain infarcts: the silence study
Background. We investigated low-dose aspirin (ASA) efficacy and safety in subjects with silent brain infarcts (SBIs) in preventing new cerebrovascular (CVD) events as well as cognitive impairment. Methods. We included subjects aged ≥45 years, with at least one SBI and no previous CVD. Subjects were followed up to 4 years assessing CVD and SBI incidence as primary endpoint and as secondary endpoints: (a) cardiovascular and adverse events and (b) cognitive impairment. Results. Thirty-six subjects received ASA while 47 were untreated. Primary endpoint occurred in 9 controls (19.1%) versus 2 (5.6%) in the ASA group (p=0.10). Secondary endpoints did not differ in the two groups. Only baseline leukoaraiosis predicts primary [OR 5.4 (95%CI 1.3-22.9, p=0.022)] and secondary endpoint-A [3.2 (95%CI 1.1-9.6, p=0.040)] occurrence. Conclusions. These data show an increase of new CVD events in the untreated group. Despite the study limitations, SBI seems to be a negative prognostic factor and ASA preventive treatment might improve SBI prognosis. EU Clinical trial is registered with EudraCT Number: 2005-000996-16; Sponsor Protocol Number: 694/30.06.04
PPARG dysregulation as a potential molecular target in adrenal Cushing's syndrome
BACKGROUND
We performed a transcriptomic analysis of adrenal signaling pathways in various forms of endogenous Cushing's syndrome (CS) to define areas of dysregulated and druggable targets.
METHODOLOGY
Next-generation sequencing was performed on adrenal samples of patients with primary bilateral macronodular adrenal hyperplasia (PBMAH, n=10) and control adrenal samples (n=8). The validation groups included cortisol-producing adenoma (CPA, n=9) and samples from patients undergoing bilateral adrenalectomy for Cushing's disease (BADX-CD, n=8). In vivo findings were further characterized using three adrenocortical cell-lines (NCI-H295R, CU-ACC2, MUC1).
RESULTS
Pathway mapping based on significant expression patterns identified PPARG (peroxisome proliferator-activated receptor gamma) pathway as the top hit. Quantitative PCR (QPCR) confirmed that PPARG (l2fc<-1.5) and related genes - FABP4 (l2fc<-5.5), PLIN1 (l2fc<-4.1) and ADIPOQ (l2fc<-3.3) - were significantly downregulated (p<0.005) in PBMAH. Significant downregulation of PPARG was also found in BADX-CD (l2fc<-1.9, p<0.0001) and CPA (l2fc<-1.4, p<0.0001). In vitro studies demonstrated that the PPARG activator rosiglitazone resulted in decreased cell viability in MUC1 and NCI-H295R (p<0.0001). There was also a significant reduction in the production of aldosterone, cortisol, and cortisone in NCI-H295R and in Dihydrotestosterone (DHT) in MUC1 (p<0.05), respectively.
OUTCOME
This therapeutic effect was independent of the actions of ACTH, postulating a promising application of PPARG activation in endogenous hypercortisolism
The RPC system for the CMS experiment at the LHC
The CMS detector at the LHC has a redundant muon system. Two independent muon systems are used in the L1 trigger. One of them is based on wire chambers, the other on RPC detectors. Properly combining the answers of the two systems results in a highly efficient L1 trigger with high flexibility from the point of view of rate control. Simulation results show, however, that the RPC system suffers from false triggers caused by coincidence of spurious hits. System improvements, which could avoid oiling the chambers, are possible. RPCs have also proved to be very useful for muon track reconstruction
Neutron irradiation of RPCs for the CMS experiment
All the CMS muon stations will be equipped with Resistive Plate Chambers (RPCs). They will be exposed to high neutron background environment during the LHC running. In order to verify the safe operation of these detectors, an irradiation test has been carried out with two RPCs at high neutron flux (about ), integrating values of dose and fluence equivalent to 10 LHC-years. Before and after the irradiation, the performance of the detectors was studied with cosmic muons, showing no relevant aging effects. Moreover, no indication of damage or chemical changes were observed on the electrode surfaces
What Is the Optimal Duration of Adjuvant Mitotane Therapy in Adrenocortical Carcinoma? An Unanswered Question
A relevant issue on the treatment of adrenocortical carcinoma (ACC) concerns the optimal duration of adjuvant mitotane treatment. We tried to address this question, assessing whether a correlation exists between the duration of adjuvant mitotane treatment and recurrence-free survival (RFS) of patients with ACC. We conducted a multicenter retrospective analysis on 154 ACC patients treated for ≥12 months with adjuvant mitotane after radical surgery and who were free of disease at the mitotane stop. During a median follow-up of 38 months, 19 patients (12.3%) experienced recurrence. We calculated the RFS after mitotane (RFSAM), from the landmark time-point of mitotane discontinuation, to overcome immortal time bias. We found a wide variability in the duration of adjuvant mitotane treatment among different centers and also among patients cared for at the same center, reflecting heterogeneous practice. We did not find any survival advantage in patients treated for longer than 24 months. Moreover, the relationship between treatment duration and the frequency of ACC recurrence was not linear after stratifying our patients in tertiles of length of adjuvant treatment. In conclusion, the present findings do not support the concept that extending adjuvant mitotane treatment over two years is beneficial for ACC patients with low to moderate risk of recurrence
Experimental results on RPC neutron sensitivity
Abstract RPC neutron sensitivity has been studied during two tests done with different neutrons energies. In the first test, neutrons from spontaneous fission events of 252 Cf were used (average energy 2 MeV ); while in the second test neutrons were produced using a 50 MeV deuteron beam on a 1 cm thick beryllium target (average energy 20 MeV ). Preliminary results show that the neutron sensitivity in double gap mode is (0.52±0.03)×10−3 at about 2 MeV and (5.3±0.5)×10−3 at about 20 MeV
Benralizumab in Patients With Severe Eosinophilic Asthma With and Without Chronic Rhinosinusitis With Nasal Polyps: An ANANKE Study post-hoc Analysis
Background: Severe eosinophilic asthma (SEA) in the presence of chronic rhinosinusitis with nasal polyps (CRSwNP) indicates the presence of a more extensive eosinophilic inflammation. Post-hoc analyses from a pivotal clinical trial have demonstrated the enhanced efficacy of benralizumab on asthma outcomes in patients with CRSwNP as a comorbidity. Methods: This is a post-hoc analysis from the Italian multi-center observational retrospective ANANKE study. Patients were divided into two groups based on self-reported CRSwNP. Baseline clinical and laboratory features in the 12 months prior to benralizumab prescription were collected. Data of change over time of blood eosinophils, annualized exacerbations rates (AER), asthma control, lung function, oral corticosteroids (OCS) use, and benralizumab discontinuation were collected during the observation period. Results: At baseline, the 110 patients with CRSwNP were less frequently female (50.9% vs 74.2%) and obese (9.1% vs. 22.6%) with higher eosinophils (605 vs. 500 cells/mm3) and OCS use when compared to patients without CRSwNP. Similar reductions of AER were seen (-95.8% vs. -91.5% for any exacerbation and -99.1% vs. -92.2% for severe exacerbations in patients with and without CRSwNP, respectively). During benralizumab treatment, comorbid SEA+CRSwNP was associated with a lower risk of any exacerbation (p = 0.0017) and severe exacerbations (p = 0.025). After a mean ± SD exposure of 10.3 ± 5.0 months, half of the SEA+CRSwNP patients eliminated OCS use. No discontinuation for safety reasons was recorded. Conclusions: This study helped to confirm the baseline clinical features that distinguish patients with and without CRSwNP being prescribed benralizumab. Numerically enhanced OCS reduction and lower exacerbation risk were observed in patients with SEA and comorbid CRSwNP treated with benralizumab
ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving Benralizumab in a real-life setting: the observational rEtrospective ANANKE study
Background: Data from phase 3 trials have demonstrated the efficacy and safety of benralizumab in patients with severe eosinophilic asthma (SEA). We conducted a real-world study examining the baseline characteristics of a large SEA population treated with benralizumab in clinical practice and assessed therapy effectiveness. Methods: ANANKE is an Italian multi-center, retrospective cohort study including consecutive SEA patients who had started benralizumab therapy ≥ 3 months before enrolment (between December 2019 and July 2020), in a real-world setting. Data collection covered (1) key patient features at baseline, including blood eosinophil count (BEC), number and severity of exacerbations and oral corticosteroid (OCS) use; (2) clinical outcomes during benralizumab therapy. We also conducted two post-hoc analyses in patients grouped by body mass index and allergic status. Analyses were descriptive only. Results: Of 218 patients with SEA enrolled in 21 Centers, 205 were evaluable (mean age, 55.8 ± 13.3 years, 61.5% females). At treatment start, the median BEC was 580 cells/mm3 (interquartile range [IQR]: 400-850); all patients were on high-dose inhaled controller therapy and 25.9% were on chronic OCS (median dose: 10 mg/die prednisone-equivalent [IQR: 5-25]); 92.9% experienced ≥ 1 exacerbation within the past 12 months (annualized exacerbation rate [AER] 4.03) and 40.3% reported ≥ 1 severe exacerbation (AER 1.10). During treatment (median duration: 9.8 months [IQR 6.1-13.9]; ≥ 12 months for 34.2% of patients), complete eosinophil depletion was observed; exacerbation-free patients increased to 81% and only 24.3% reported ≥ 1 severe event. AER decreased markedly to 0.27 for exacerbations of any severity (- 93.3%) and to 0.06 for severe exacerbations (- 94.5%). OCS therapy was interrupted in 43.2% of cases and the dose reduced by 56% (median: 4.4 mg/die prednisone-equivalent [IQR: 0.0-10.0]). Lung function and asthma control also improved. The effectiveness of benralizumab was independent of allergic status and body mass index. Conclusions: We described the set of characteristics of a large cohort of patients with uncontrolled SEA receiving benralizumab in clinical practice, with a dramatic reduction in exacerbations and significant sparing of OCS. These findings support benralizumab as a key phenotype-specific therapeutic strategy that could help physicians in decision-making when prescribing biologics in patients with SEA. Trial registration ClinicalTrials.gov Identifier: NCT04272463
Longitudinal Study on Low-Dose Aspirin versus Placebo Administration in Silent Brain Infarcts: The Silence Study
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