89 research outputs found
Evidence of illegitimate recombination between two pasteurellaceae plasmids resulting in a novel multi-resistance replicon, pM3362MDR, in Actinobacillus pleuropneumoniae
Evidence of plasmids carrying the tetracycline resistance gene, tet(B), was found in the previously reported whole genome sequences of 14 United Kingdom, and 4 Brazilian, isolates of Actinobacillus pleuropneumoniae. Isolation and sequencing
of selected plasmids, combined with comparative sequence analysis, indicated that the four Brazilian isolates all harbor plasmids that are nearly identical to pB1001, a plasmid previously found in Pasteurella multocida isolates from Spain. Of the United Kingdom isolates, 13/14 harbor plasmids that are (almost) identical to pTetHS016 from Haemophilus parasuis. The remaining United Kingdom isolate, MIDG3362, harbors a 12666 bp plasmid that shares extensive regions of similarity with pOV from P. multocida (which carries bla ROBâ1 , sul2, and strAB genes), as well as with pTetHS016. The newly identified multi-resistance plasmid, pM3362MDR, appears to have arisen
through illegitimate recombination of pTetHS016 into the stop codon of the truncated strB gene in a pOV-like plasmid. All of the tet(B)-carrying plasmids studied were capable of replicating in Escherichia coli, and predicted origins of replication were
identified. A putative origin of transfer (oriT) sequence with similar secondary structure and a nic-site almost identical to that of RP4 was also identified in these plasmids, however, attempts to mobilize them from an RP4-encoding E. coli donor strain were not successful, indicating that specific conjugation machinery may be required
Screening of medicinal plants for antibacterial activities on Staphylococcus aureus strains isolated from bovine mastitis
A multicenter randomized phase 4 trial comparing sodium picosulphate plus magnesium citrate vs. polyethylene glycol plus ascorbic acid for bowel preparation before colonoscopy. The PRECOL trial
Background: Adequate bowel preparation before colonoscopy is crucial.
Unfortunately, 25% of colonoscopies have inadequate bowel cleansing. From
a patient perspective, bowel preparation is the main obstacle to colonoscopy.
Several low-volume bowel preparations have been formulated to provide
more tolerable purgative solutions without loss of efficacy.
Objectives: Investigate efficacy, safety, and tolerability of Sodium
Picosulphate plus Magnesium Citrate (SPMC) vs. Polyethylene Glycol
plus Ascorbic Acid (PEG-ASC) solutions in patients undergoing
diagnostic colonoscopy.
Materials and methods: In this phase 4, randomized, multicenter, twoarm trial, adult outpatients received either SPMC or PEG-ASC for bowel
preparation before colonoscopy. The primary aims were quality of bowel
cleansing (primary endpoint scored according to Boston Bowel Preparation
Scale) and patient acceptance (measured with six visual analogue scales). The
study was open for treatment assignment and blinded for primary endpoint
assessment. This was done independently with videotaped colonoscopies
reviewed by two endoscopists unaware of study arms. A sample size of 525
patients was calculated to recognize a difference of 10% in the proportion of
successes between the arms with a two-sided alpha error of 0.05 and 90%
statistical power.
Results: Overall 550 subjects (279 assigned to PEG-ASC and 271 assigned
to SPMC) represented the analysis population. There was no statistically
significant difference in success rate according to BBPS: 94.4% with
PEG-ASC and 95.7% with SPMC (P = 0.49). Acceptance and willing to
repeat colonoscopy were significantly better for SPMC with all the scales.
Compliance was less than full in 6.6 and 9.9% of cases with PEG-ASC and
SPMC, respectively (P = 0.17). Nausea and meteorism were significantly more
bothersome with PEG-ASC than SPMC. There were no serious adverse events
in either group.
Conclusion: SPMC and PEG-ASC are not different in terms of efficacy, but
SPMC is better tolerated than PEG-ASC. SPMC could be an alternative to lowvolume PEG based purgative solutions for bowel preparation
A new schedule of fotemustine in temozolomide-pretreated patients with relapsing glioblastoma
In the present study we investigated the feasibility and effectiveness of a new biweekly schedule of fotemustine (FTM) in patients with recurrent glioblastoma, after at least one previous treatment. The primary endpoint was progression-free survival at 6 months; secondary objectives were clinical response, overall survival, disease-free survival, and toxicity. Forty patients (median age 52.8 years; median Karnofsky Performance Status at progression 90) underwent second-line chemotherapy with FTM. Selected patients were previously treated with a standard radiotherapy course with concomitant temozolomide (TMZ). After tumor relapse or progression proven by magnetic resonance imaging (MRI), all patients underwent chemotherapy with FTM, given intravenously at dose of 80 mg/m2 every 2 weeks for five consecutive administrations (induction phase), and then every 3 weeks at 100 mg/m2 as maintenance. A total of 329 infusions were administered; the median number of cycles administered was 8. All patients completed the induction phase, and 29 patients received at least one maintenance infusion. Response to treatment was assessed using MacDonald criteria. One complete response [2.5%, 95% confidence interval (CI): 0â10%], 9 partial responses (22.5%, 95% CI: 15â37%), and 16 stable diseases (40%, 95% CI: 32â51%) were observed. Median time to progression was 6.7 months (95% CI: 3.9â9.1 months). Progression-free survival at 6 months was 61%. Median survival from beginning of FTM chemotherapy was 11.1 months. The schedule was generally well tolerated; the main toxicities were hematologic (grade 3 thrombocytopenia in two cases). To the best of our knowledge, this is the first report specifically dealing with the use of a biweekly induction schedule of FTM. The study demonstrates that FTM has therapeutic efficacy as single-drug second-line chemotherapy with a favorable safety profile
Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial
<p>Abstract</p> <p>Background</p> <p>To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer.</p> <p>Methods</p> <p>Patients with locally advanced or metastatic breast cancer, aged †70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed.</p> <p>Results</p> <p>From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03); patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p < 0.001). Neutropenia and stomatitis were worse in the 3-weekly arm, where two toxic deaths were observed. Overall response rate was 39.1% and 33.3% in 3-weekly and weekly arms; hazard ratio of progression was 1.29 (95% CI: 0.84-1.97) and hazard ratio of death was 1.38 (95% CI: 0.82-2.30) in the weekly arm.</p> <p>Conclusions</p> <p>In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00540800">NCT00540800</a>.</p
Quantitative histological analysis of the mandibular branch of the facial nerve in rats
Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both
Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPDâ+âHF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPDâ+âHF. Patients with COPDâ+âHF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPDâ+âHF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPDâ+âHF for all causes (pâ=â0.010), respiratory causes (pâ=â0.006), cardiovascular causes (pâ=â0.046) and respiratory plus cardiovascular causes (pâ=â0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population
Complement lectin pathway activation is associated with COVID-19 disease severity, independent of MBL2 genotype subgroups
IntroductionWhile complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.MethodsWe therefore investigated activation of the lectin pathway in two independent cohorts of SARS-CoV-2 infected patients, while also analysing MBL protein levels and potential effects of the six major single nucleotide polymorphisms (SNPs) found in the MBL2 gene on COVID-19 severity and outcome.ResultsWe show that the lectin pathway is activated in acute COVID-19, indicated by the correlation between complement activation product levels of the MASP-1/C1-INH complex (p=0.0011) and C4d (p<0.0001) and COVID-19 severity. Despite this, genetic variations in MBL2 are not associated with susceptibility to SARS-CoV-2 infection or disease outcomes such as mortality and the development of Long COVID.ConclusionIn conclusion, activation of the MBL-LP only plays a minor role in COVID-19 pathogenesis, since no clinically meaningful, consistent associations with disease outcomes were noted
Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTICâHF: baseline characteristics and comparison with contemporary clinical trials
Aims:
The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTICâHF) trial. Here we describe the baseline characteristics of participants in GALACTICâHF and how these compare with other contemporary trials.
Methods and Results:
Adults with established HFrEF, New York Heart Association functional class (NYHA)ââ„âII, EF â€35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokineticâguided dosing: 25, 37.5 or 50âmg bid). 8256 patients [male (79%), nonâwhite (22%), mean age 65âyears] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NTâproBNP 1971âpg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTICâHF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressureâ<â100âmmHg (n = 1127), estimated glomerular filtration rate <â30âmL/min/1.73 m2 (n = 528), and treated with sacubitrilâvalsartan at baseline (n = 1594).
Conclusions:
GALACTICâHF enrolled a wellâtreated, highârisk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
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