Achieving and maintaining a high-quality response is the treatment goal for patients with newly diagnosed multiple myeloma (NDMM). The phase 3 PETHEMA/GEM2012 study, in 458 patients aged ≤65 years ...with NDMM, is evaluating bortezomib (subcutaneous) + lenalidomide + dexamethasone (VRD) for 6 cycles followed by autologous stem cell transplant (ASCT) conditioned with IV busulfan + melphalan vs melphalan and posttransplant consolidation with 2 cycles of VRD. We present grouped response analysis of induction, transplant, and consolidation. Responses deepened over time; in patients who initiated cycle 6 of induction (n = 426), the rates of a very good partial response or better were 55.6% by cycle 3, 63.8% by cycle 4, 68.3% by cycle 5, and 70.4% after induction. The complete response rate of 33.4% after induction in the intent-to-treat (ITT) population, which was similar in the 92 patients with high-risk cytogenetics (34.8%), also deepened with further treatment (44.1% after ASCT and 50.2% after consolidation). Rates of undetectable minimal residual disease (median 3 × 10−6 sensitivity) in the ITT population also increased from induction (28.8%) to transplant (42.1%) and consolidation (45.2%). The most common grade ≥3 treatment-emergent adverse events during induction were neutropenia (12.9%) and infection (9.2%). Grade ≥2 peripheral neuropathy (grouped term) during induction was 17.0%, with a low frequency of grade 3 (3.7%) and grade 4 (0.2%) events. VRD is an effective and well-tolerated regimen for induction in NDMM with deepening response throughout induction and over the course of treatment. This trial was registered at www.clinicaltrials.gov as #NCT01916252 and EudraCT as #2012-005683-10.
•VRD was effective and well tolerated before ASCT; 33.4% complete response/28.8% minimal residual disease–negative after 6 induction cycles.•Responses deepened with VRD throughout induction and over the course of treatment with few discontinuations due to toxicity.
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The increasing resistance to carbapenems is an alarming threat in the fight against multiresistant bacteria. The dissemination properties of antimicrobial resistance genes are supported by their ...detection in a diverse population of bacteria, including strains isolated from the environment. The objective of this study was to investigate the presence of carbapenemase-producing Enterobacteriaceae (CPE) collected from a river ecosystem in the Barcelona metropolitan area (Spain). Identification of β-lactamases and other resistance determinants was determined as was the antimicrobial susceptibility profile. Moreover, screening of virulence factors, plasmid addiction systems, plasmid partition systems and replicon typing was performed. The results identified 8 isolates belonging to different species (Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Klebsiella oxytoca, Raoultella ornithinolytica). The most prevalent enzyme was KPC-2 (n = 6), followed by VIM-1 (n = 2) and IMI-2 (n = 1), whereas no OXA-48-type was detected. In addition, one strain was positive for both KPC-2 and VIM-1 enzymes. All the carbapenemase-encoding plasmids carried at least one plasmid addiction or partition system, being vagCD and parAB the most frequently detected, respectively. E. coli and K. pneumoniae isolates carried a low number of virulence-associated factors and none of the detected clones has previously been identified in the clinical setting. These findings support the high dissemination potential of the carbapanemase-encoding genes and reinforce the idea that the environment is another reservoir that may play an important role in the capture, selection and dissemination of carbapenem resistance genes.
(named in honor of the American bacteriologists Paul and Linda Baumann) is a Gram-negative, multidrug-resistant (MDR) pathogen that causes nosocomial infections, especially in intensive care units ...(ICUs) and immunocompromised patients with central venous catheters.
has developed a broad spectrum of antimicrobial resistance, associated with a higher mortality rate among infected patients compared with other non-
species. In terms of clinical impact, resistant strains are associated with increases in both in-hospital length of stay and mortality.
can cause a variety of infections; most involve the respiratory tract, especially ventilator-associated pneumonia, but bacteremia and skin wound infections have also been reported, the latter of which has been prominently observed in the context of war-related trauma. Cases of meningitis associated with
have been documented. The most common risk factor for the acquisition of MDR
is previous antibiotic use, following by mechanical ventilation, length of ICU/hospital stay, severity of illness, and use of medical devices. Current efforts focus on addressing all the antimicrobial resistance mechanisms described in
, with the objective of identifying the most promising therapeutic scheme. Bacteriophage- and artilysin-based therapeutic approaches have been described as effective, but further research into their clinical use is required.
Research exploring the development and outcome of COVID-19 infections has led to the need to find better diagnostic and prognostic biomarkers. This cross-sectional study used targeted metabolomics to ...identify potential COVID-19 biomarkers that predicted the course of the illness by assessing 110 endogenous plasma metabolites from individuals admitted to a local hospital for diagnosis/treatment. Patients were classified into four groups (≈ 40 each) according to standard polymerase chain reaction (PCR) COVID-19 testing and disease course: PCR-/controls (i.e., non-COVID controls), PCR+/not-hospitalized, PCR+/hospitalized, and PCR+/intubated. Blood samples were collected within 2 days of admission/PCR testing. Metabolite concentration data, demographic data and clinical data were used to propose biomarkers and develop optimal regression models for the diagnosis and prognosis of COVID-19. The area under the receiver operating characteristic curve (AUC; 95% CI) was used to assess each models' predictive value. A panel that included the kynurenine: tryptophan ratio, lysoPC a C26:0, and pyruvic acid discriminated non-COVID controls from PCR+/not-hospitalized (AUC = 0.947; 95% CI 0.931-0.962). A second panel consisting of C10:2, butyric acid, and pyruvic acid distinguished PCR+/not-hospitalized from PCR+/hospitalized and PCR+/intubated (AUC = 0.975; 95% CI 0.968-0.983). Only lysoPC a C28:0 differentiated PCR+/hospitalized from PCR+/intubated patients (AUC = 0.770; 95% CI 0.736-0.803). If additional studies with targeted metabolomics confirm the diagnostic value of these plasma biomarkers, such panels could eventually be of clinical use in medical practice.
This study compared the time course of recovery following two resistance exercise protocols differing in the number of repetitions per set with regard to the maximum possible (to failure) number. Ten ...men performed three sets of 6 versus 12 repetitions with their 70% 1RM (3 × 6 12 versus 3 × 12 12) in the bench press (BP) and squat (SQ) exercises. Mechanical CMJ height, velocity against the 1 m s
load (V
-load), biochemical testosterone, cortisol, growth hormone, prolactin, insulin-like growth factor-1, creatine kinase (CK) and heart rate variability (HRV) and complexity (HRC) were assessed pre-, postexercise (Post) and at 6, 24 and 48 h-Post. Compared with 3 × 6 12, the 3 × 12 12 protocol resulted in significantly: higher repetition velocity loss within each set (BP: 65% versus 26%; SQ: 44% versus 20%); reduced V
-load until 24 h-Post (BP) and 6 h-Post (SQ); decreased CMJ height up to 48 h-Post; greater increases in cortisol (Post), prolactin (Post, 48 h-Post) and CK (48 h-Post); and reductions in HRV and HRC at Post. This study shows that the mechanical, neuroendocrine and autonomic cardiovascular response is markedly different when manipulating the number of repetitions per set. Halving the number of repetitions in relation to the maximum number that can be completed serves to minimize fatigue and speed up recovery following resistance training.
Human presence in the Antarctic is increasing due to research activities and the rise in tourism. These activities contribute a number of potentially hazardous substances. The aim of this study is to ...conduct the first characterisation of the pharmaceuticals and recreational drugs present in the northern Antarctic Peninsula region, and to assess the potential environmental risk they pose to the environment. The study consisted of a single sampling of ten water samples from different sources, including streams, ponds, glacier drains, and a wastewater discharge into the sea. Twenty-five selected pharmaceuticals and 21 recreational drugs were analysed. The highest concentrations were found for the analgesics acetaminophen (48.74 μg L−1), diclofenac (15.09 μg L−1) and ibuprofen (10.05 μg L−1), and for the stimulant caffeine (71.33 μg L−1). All these substances were detected in waters that were discharged directly into the ocean without any prior purification processes. The hazard quotient (HQ) values for ibuprofen, diclofenac and acetaminophen were far in excess of 10 at several sampling points. The concentrations of each substance measured and used as measured environmental concentration values for the HQ calculations are based on a one-time sampling. The Toxic Unit values indicate that analgesics and anti-inflammatories are the therapeutic group responsible for the highest toxic burden.
This study is the first to analyse a wide range of substances and to determine the presence of pharmaceuticals and psychotropic drugs in the Antarctic Peninsula region. We believe it can serve as a starting point to focus attention on the need for continued environmental monitoring of these substances in the water cycle, especially in protected regions such as the Antarctic. This will determine whether pharmaceuticals and recreational drugs are hazardous to the environment and, if so, can be used as the basis for risk-assessment studies to prioritise the exposure to risk.
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•Sixteen pharmaceuticals and recreational drugs were found in concentrations of ngL−1 to μgL−1.•The highest concentrations were found for the analgesics acetaminophen, diclofenac and ibuprofen.•Caffeine was the most commonly found substance, followed by ephedrine.•Acetaminophen, diclofenac and ibuprofen presented the highest HQ values and therefore the highest environmental risk.•Analgesics and anti-inflammatories have been identified as the group posing the highest risk to the Antarctic ecosystem.
Sixteen emerging contaminants were found in the Antarctic Peninsula region. Analgesics and anti-inflammatories have been identified as the group posing the highest risk to the Antarctic ecosystem.
Defining the Asthma-COPD Overlap Syndrome in a COPD Cohort Cosio, Borja G., MD; Soriano, Joan B., MD; López-Campos, Jose Luis, MD ...
Chest,
2016, January 2016, 2016-Jan, 2016-01-00, 20160101, Letnik:
149, Številka:
1
Journal Article
Recenzirano
Background Asthma-COPD overlap syndrome (ACOS) has been recently described by international guidelines. A stepwise approach to diagnosis using usual features of both diseases is recommended although ...its clinical application is difficult. Methods To identify patients with ACOS, a cohort of well-characterized patients with COPD and up to 1 year of follow-up was analyzed. We evaluated the presence of specific characteristics associated with asthma in this COPD cohort, divided into major criteria (bronchodilator test > 400 mL and 15% and past medical history of asthma) and minor criteria (blood eosinophils > 5%, IgE > 100 IU/mL, or two separate bronchodilator tests > 200 mL and 12%). We defined ACOS by the presence of one major criterion or two minor criteria. Baseline characteristics, health status (COPD Assessment Test CAT), BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index, rate of exacerbations, and mortality up to 1 year of follow-up were compared between patients with and without criteria for ACOS. Results Of 831 patients with COPD included,125 (15%) fulfilled the criteria for ACOS, and 98.4% of them sustained these criteria after 1 year. Patients with ACOS were predominantly male (81.6%), with symptomatic mild to moderate disease (67%), who were receiving inhaled corticosteroids (63.2%). There were no significant differences in baseline characteristics, and only survival was worse in patients with non-ACOS COPD after 1 year of follow-up ( P < .05). Conclusions The proposed ACOS criteria are present in 15% of a cohort of patients with COPD and these patients show better 1-year prognosis than clinically similar patients with COPD with no ACOS criteria. Trial Registry ClinicalTrials.gov; No.: NCT01122758 ; URL: www.clinicaltrials.gov
Multidrug resistance against conventional antibiotics poses an important threat to human health. In this context, antimicrobial peptides (AMPs) have been extensively studied for their antibacterial ...activity and promising results have been shown so far. However, AMPs tend to be rather vulnerable to protease degradation, which offsets their therapeutic appeal. Here, we demonstrate how replacing functional residues in the antimicrobial region of human RNase 3also named eosinophil cationic proteinby non-natural amino acids increases stability in human serum. These changes were also shown to reduce the hemolytic effect of the peptides in general terms, whereas the antimicrobial activity was reasonably preserved. Digestion profiles enabled us to design new peptides with superior stability and lower toxicity that could become relevant candidates to reach clinical stages.
Serological tests are essential for the control and management of COVID-19 pandemic (diagnostics and surveillance, and epidemiological and immunity studies). We introduce a direct serological ...biosensor assay employing proprietary technology based on plasmonics, which offers rapid (<15 min) identification and quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in clinical samples, without signal amplification. The portable plasmonic device employs a custom-designed multiantigen (RBD peptide and N protein) sensor biochip and reaches detection limits in the low ng mL–1 range employing polyclonal antibodies. It has also been implemented employing the WHO-approved anti-SARS-CoV-2 immunoglobulin standard. A clinical validation with COVID-19 positive and negative samples (n = 120) demonstrates its excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor as an accurate and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the disease management and for the evaluation of immunological status during vaccination or treatment.
Avian pathogenic Escherichia coli (APEC) are the major cause of colibacillosis in poultry production. In this study, a total of 22 E. coli isolated from colibacillosis field cases and 10 avian faecal ...E. coli (AFEC) were analysed. All strains were characterised phenotypically by susceptibility testing and molecular typing methods such as pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). The presence of 29 virulence genes associated to APEC and human extraintestinal pathogenic E. coli (ExPEC) was also evaluated. For cephalosporin resistant isolates, cephalosporin resistance genes, plasmid location and replicon typing was assessed. Avian isolates belonged to 26 O:H serotypes and 24 sequence types. Out of 22 APEC isolates, 91% contained the virulence genes predictors of APEC; iutA, hlyF, iss, iroN and ompT. Of all strains, 34% were considered ExPEC. PFGE analysis demonstrated a high degree of genetic polymorphism. All strains were multi-resistant, including those isolated from healthy animals. Eleven strains were resistant to cephalosporins; six contained blaCTX-M-14, two blaSHV-12, two blaCMY-2 and one blaSHV-2. Two strains harboured qnrA, and two qnrA together with aac(6')-Ib-cr. Additionally, the emergent clone O25b:H4-B2-ST131 was isolated from a healthy animal which harboured blaCMY-2 and qnrS genes. Cephalosporin resistant genes were mainly associated to the presence of IncK replicons. This study demonstrates a very diverse population of multi-drug resistant E. coli containing a high number of virulent genes. The E. coli population among broilers is a reservoir of resistance and virulence-associated genes that could be transmitted into the community through the food chain. More epidemiological studies are necessary to identify clonal groups and resistance mechanisms with potential relevance to public health.
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