Aims Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) methods to quantify total lurbinectedin, its plasma protein binding to derive the unbound fraction and its main ...metabolites 1′,3′-dihydroxy-lurbinectedin (M4) and N-desmethyl-lurbinectedin (M6) in human plasma, were developed and validated. Materials & methods For lurbinectedin, sample extraction was performed using supported liquid extraction. For metabolites, liquid-liquid extraction with stable isotope–labeled analogue internal standards was used. Plasma protein binding was evaluated using rapid equilibrium dialysis. In vitro investigations at different plasma protein concentrations were carried out to estimate dissociation rate constants to albumin and alpha-1-acid glycoprotein (AAG). Results Calibration curves displayed good linearity over 0.1 to 50 ng/mL for lurbinectedin and 0.5 to 20 ng/mL for the metabolites. Methods were validated in accordance with established guidance. The inter-day precision and accuracy ranged from 5.1% to 10.7%, and from -5% to 6% (lurbinectedin in plasma); from 3.1% to 6.6%, and from 4% to 6% (lurbinectedin in plasma:PBS); from 4.5% to 12.9%, and from 4% to 9% (M4); and from 7.5% to 10.5%, and from 6% to 12% (M6). All methods displayed good linearity (r2 >0.99). Recovery was evaluated for lurbinectedin in plasma:PBS (66.4% to 86.6%), M4 (7.82% to 13.4%) and M6 (22.2% to 34.3%). The method for lurbinectedin in plasma has been applied in most clinical studies, while the plasma:PBS and metabolites methods were used to evaluate the impact of special conditions on lurbinectedin PK. Lurbinectedin plasma protein binding was 99.6% and highly affected by AAG concentration. Conclusions These UPLC–MS/MS methods enable the rapid and sensitive quantification of lurbinectedin and its main metabolites in clinical samples.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Detection of the C-polysaccharide of Streptococcus pneumoniae in urine by an immune-chromatographic test is increasingly used to evaluate patients with community-acquired pneumonia.
We assessed the ...sensitivity and specificity of this test in the largest series of cases to date and used logistic regression models to determine predictors of positivity in patients hospitalized with community-acquired pneumonia.
We performed a multicenter, prospective, observational study of 4,374 patients hospitalized with community-acquired pneumonia.
The urinary antigen test was done in 3,874 cases. Pneumococcal infection was diagnosed in 916 cases (21%); 653 (71%) of these cases were diagnosed exclusively by the urinary antigen test. Sensitivity and specificity were 60 and 99.7%, respectively. Predictors of urinary antigen positivity were female sex; heart rate≥125 bpm, systolic blood pressure<90 mm Hg, and SaO2<90%; absence of antibiotic treatment; pleuritic chest pain; chills; pleural effusion; and blood urea nitrogen≥30 mg/dl. With at least six of all these predictors present, the probability of positivity was 52%. With only one factor present, the probability was only 12%.
The urinary antigen test is a method with good sensitivity and excellent specificity in diagnosing pneumococcal pneumonia, and its use greatly increased the recognition of community-acquired pneumonia due to S. pneumoniae. With a specificity of 99.7%, this test could be used to direct simplified antibiotic therapy, thereby avoiding excess costs and risk for bacterial resistance that result from broad-spectrum antibiotics. We also identified predictors of positivity that could increase suspicion for pneumococcal infection or avoid the unnecessary use of this test.
Background: Beta-trace protein (BTP) and cystatin C (CysC) are novel biomarkers of renal function. We assessed the ability of both to predict major bleeding (MB) in patients with non-ST-segment ...elevation acute coronary syndromes (NSTE-ACS), compared to other renal function parameters and clinical risk scores. Methods and Results: We included 273 patients. Blood samples were obtained within 24h of admission. The endpoint was MB. During a follow-up of 760 days (411–1,098 days), 25 patients (9.2%) had MB. Patients with MB had higher concentrations of BTP (0.98mg/L; 0.71–1.16mg/L vs. 0.72mg/L, 0.60–0.91mg/L, P=0.002), CysC (1.05mg/L; 0.91–1.30mg/L vs. 0.90mg/L, 0.75–1.08mg/L, P=0.003), higher CRUSADE score (39±16 points vs. 29±15 points, P=0.002) and lower estimated glomerular filtration rate (eGFR; 66±27 vs. 80±30ml·min–1·1.73m–2, P=0.02) than patients without MB; there was no difference in creatinine level between the groups (P=0.14). After multivariable adjustment, both were predictors of MB, while eGFR and creatinine did not achieve statistical significance. Among subjects with eGFR >60ml·min–1·1.73m–2, those with elevated concentrations of both biomarkers had a significantly higher risk for MB. Net reclassification indexes from the addition of BTP and CysC to CRUSADE risk score were 38% and 21% respectively, while the relative integrated discrimination indexes were 12.5% and 3.8%. Conclusions: Among NSTE-ACS patients, BTP and CysC were superior to conventional renal parameters for predicting MB, and improved clinical stratification for hemorrhagic risk. (Circ J 2013; 77: 2088–2096)
Available remains of the barbourofelin Albanosmilus jourdani from the Middle to Late Miocene of the Vallès-Penedès Basin (NE Iberian Peninsula) are described. In addition to the dentognathic remains ...described by previous authors, the new material includes a complete cranium, a calvarium and several mandibles from Abocador de Can Mata, Creu Conill 20 and Hostalets Superior. It is concluded that Albanosmilus, previously considered a subjective junior synonym of Sansanosmilus, must be resurrected as a polytypic genus including A. jourdani (= A. vallesiensis). The most plesiomorphic North American barbourofelin, previously included in Barbourofelis, is also transferred into Albanosmilus as A. whitfordi. An emended diagnosis of Albanosmilus is provided. The results of a cladistic analysis support the monophyly of the family Barbourofelidae and the tribe Barbourofelini, further indicating that amongst the latter, Sansanosmilus occupies the basalmost position. The two Albanosmilus species are more derived, although the analysis fails to resolve conclusively whether A. whitfordi is more closely related to A. jourdani or Barbourofelis s.s. From a palaeobiogeographical viewpoint, our results suggest that: (1) barbourofelins originated in Eurasia during the early Middle Miocene; (2) Barbourofelis originated in North America during the late Middle Miocene, following the dispersal of Eurasian Albanosmilus into that continent; and (3) the presence of Barbourofelis in Turkey during the Late Miocene may represent a later independent dispersal event from North America back into Eurasia.
Carbapenemase-Producing
(CP-Eco) isolates, though less prevalent than other CP-Enterobacterales, have the capacity to rapidly disseminate antibiotic resistance genes (ARGs) and cause serious ...difficult-to-treat infections. The aim of this study is phenotypically and genotypically characterizing CP-Eco isolates collected from Spain to better understand their resistance mechanisms and population structure.
Ninety representative isolates received from 2015 to 2020 from 25 provinces and 59 hospitals Spanish hospitals were included. Antibiotic susceptibility was determined according to EUCAST guidelines and whole-genome sequencing was performed. Antibiotic resistance and virulence-associated genes, phylogeny and population structure, and carbapenemase genes-carrying plasmids were analyzed.
The 90 CP-Eco isolates were highly polyclonal, where the most prevalent was ST131, detected in 14 (15.6%) of the isolates. The carbapenemase genes detected were
(45.6%),
(23.3%),
(7.8%),
(6.7%), and
(6.7%). Forty (44.4%) were resistant to 6 or more antibiotic groups and the most active antibiotics were colistin (98.9%), plazomicin (92.2%) and cefiderocol (92.2%). Four of the seven cefiderocol-resistant isolates belonged to ST167 and six harbored
. Five of the plazomicin-resistant isolates harbored
. IncL plasmids were the most frequent (45.7%) and eight of these harbored
.
was found in IncF plasmids in eight isolates. Metallo-β-lactamases were more frequent in isolates with resistance to six or more antibiotic groups, with their genes often present on the same plasmid/integron. ST131 isolates were associated with
and
virulence genes. This study highlights the genetic versatility of CP-Eco and its potential to disseminate ARGs and cause community and nosocomial infections.
En 2014 se publicó el Documento de Consenso desarrollado por SEIP-SERPE-SEOP para el diagnóstico y el tratamiento de las infecciones osteoarticulares (IOA). En 2015 se constituyó RIOPed como red ...nacional multidisciplinar para la investigación en IOA. El objetivo del estudio ha sido valorar el grado de adecuación a las recomendaciones establecidas en el consenso durante un año de seguimiento.
Estudio prospectivo multicéntrico nacional realizado entre septiembre de 2015 y septiembre de 2016 en 37 hospitales con inclusión de pacientes menores de16años diagnosticados de IOA, confirmada mediante aislamiento microbiológico, o probable: artritis séptica (AS) con >40.000 leucocitos en líquido sinovial u osteomielitis (OM)/osteoartritis (OA)/espondilodiscitis (ED) con prueba de imagen compatible. Los resultados se compararon con los obtenidos en el estudio retrospectivo realizado entre 2008 y 2012.
Se incluyeron 255 casos: 131 OM, 79 AS, 30 OA y 15 ED. Respecto a las pruebas complementarias que el consenso consideró de obligada realización, la radiografía se llevó a cabo en el 87,8% de los casos, el hemocultivo en el 91,6% y el cultivo de líquido sinovial en el 99% de AS. Se realizó RM en el 71% de las OM. La elección del tratamiento antibiótico intravenoso empírico se adecuó a las recomendaciones en el 65,1% de los casos, y en el 62,3% para el tratamiento oral. Se llevó a cabo cirugía en el 36,8% de las AS (85,7% artrotomía), con un descenso significativo respecto al estudio retrospectivo (p=0,014). Solo el 58,5% de casos se ajustaron a las recomendaciones de duración del tratamiento; sin embargo, se comprobó una menor duración del tratamiento intravenoso.
En general, el grado de adecuación a las recomendaciones que marcaron el grupo de expertos es bueno para las pruebas complementarias y aceptable respecto a la elección del tratamiento antibiótico, aun detectándose casi un 40% de inadecuación. Se ha conseguido un descenso de la estancia hospitalaria.
In 2014 the Consensus Document produced by the Spanish Paediatric Societies (SEIP-SERPE-SEOP) was published to help in the diagnosis and treatment of osteoarticular infections (OAI). In 2015 the RIOPed was considered as a multidisciplinary national network for the investigation into OAI. The aim of this study was to assess the level of adaption to the recommendations established in the Consensus during one year of follow-up.
A prospective, national multicentre study was carried out in 37 hospitals between September 2015 and September 2016. The study included patients >16years-old with a diagnosis of OAI, confirmed by microbiological isolation, or probable: septic arthritis (SA) with >40,000 white cells in synovial fluid, or osteomyelitis (OM)/spondylodiscitis (SD) with a compatible imaging test. The results were compared with those obtained in a retrospective study conducted between 2008 and 2012.
A total of 235 cases were included, of which 131 were OM, 79 SA, 30 OA, and 15 SD. As regards the complementary tests that the Consensus considered mandatory to perform, radiography was carried out on 87.8% of the cases, a blood culture on 91.6%, and culture of the synovial fluid in 99% of SA. A magnetic resonance (MR) was performed on 71% of the OM cases. The choice of intravenous empirical antibiotic treatment was adapted to the recommendations in 65.1% of cases, and in 62.3% for the oral treatment. Surgery was performed in 36.8% of SA cases (85.7% arthrotomy), with a significant decrease compared to the retrospective study (P=.014). Only 58.5% of cases followed the recommendations on the duration of the treatment; however, a lower duration of intravenous treatment was observed.
In general, the level of adaptation to the recommendations that were set by the Expert Group, is good for the complementary tests, and acceptable as regards the choice of antibiotic treatment, although inadequate in almost 40% of cases. A decrease in hospital stay was achieved.
In this study, a quick and easy analytical method was optimised to obtain the tocopherol (T) profile of almond oil samples in less than 18
min including the sample preparation process. As the ...tocopherol determination is being carried out on the almond oil, a previous optimisation step to analyse moisture and fat is simultaneously carried out. Additionally, the method was applied to the analysis of four almond cultivars (Marcona, Guara, Garrigues and Butte) cultivated in different locations during the 2004 and 2005 growing seasons. α-T mean values for the almond samples included in the study varied from 8.5 to 19.4
mg/100
g of dry almond. β+γ-T values ranged from 0.141 to 0.838
mg/100
g of dry almond. Meanwhile, δ-T was found in trace quantities in all almonds. After applying an ANOVA analysis to the data, Marcona samples were found to be significatively different to the other three cultivars included in the analysis on the basis of α-T and β+γ-T content. Moreover, a study of degradation of tocopherol homologues over time was done showing that after a year of storage, shelled and unshelled almonds maintained more than 80% of the initial tocopherol meanwhile, greater losses and variabilities in β+γ-T and δ-T were observed.
Introduction: In 2014 the Consensus Document produced by the Spanish Paediatric Societies (SEIP-SERPE-SEOP) was published to help in the diagnosis and treatment of osteoarticular infections (OAI). In ...2015 the RIOPed was considered as a multidisciplinary national network for the investigation into OAI. The aim of this study was to assess the level of adaption to the recommendations established in the Consensus during one year of follow-up. Material and methods: A prospective, national multicentre study was carried out in 37 hospitals between September 2015 and September 2016. The study included patients >16 years-old with a diagnosis of OAI, confirmed by microbiological isolation, or probable: septic arthritis (SA) with >40,000 white cells in synovial fluid, or osteomyelitis (OM)/spondylodiscitis (SD) with a compatible imaging test. The results were compared with those obtained in a retrospective study conducted between 2008 and 2012. Results: A total of 235 cases were included, of which 131 were OM, 79 SA, 30 OA, and 15 SD. As regards the complementary tests that the Consensus considered mandatory to perform, radiography was carried out on 87.8% of the cases, a blood culture on 91.6%, and culture of the synovial fluid in 99% of SA. A magnetic resonance (MR) was performed on 71% of the OM cases. The choice of intravenous empirical antibiotic treatment was adapted to the recommendations in 65.1% of cases, and in 62.3% for the oral treatment. Surgery was performed in 36.8% of SA cases (85.7% arthrotomy), with a significant decrease compared to the retrospective study (P = .014). Only 58.5% of cases followed the recommendations on the duration of the treatment; however, a lower duration of intravenous treatment was observed. Conclusions: In general, the level of adaptation to the recommendations that were set by the Expert Group, is good for the complementary tests, and acceptable as regards the choice of antibiotic treatment, although inadequate in almost 40% of cases. A decrease in hospital stay was achieved. Resumen: Introducción: En 2014 se publicó el Documento de Consenso desarrollado por SEIP-SERPE-SEOP para el diagnóstico y el tratamiento de las infecciones osteoarticulares (IOA). En 2015 se constituyó RIOPed como red nacional multidisciplinar para la investigación en IOA. El objetivo del estudio ha sido valorar el grado de adecuación a las recomendaciones establecidas en el consenso durante un año de seguimiento. Material y métodos: Estudio prospectivo multicéntrico nacional realizado entre septiembre de 2015 y septiembre de 2016 en 37 hospitales con inclusión de pacientes menores de 16 años diagnosticados de IOA, confirmada mediante aislamiento microbiológico, o probable: artritis séptica (AS) con >40.000 leucocitos en líquido sinovial u osteomielitis (OM)/osteoartritis (OA)/espondilodiscitis (ED) con prueba de imagen compatible. Los resultados se compararon con los obtenidos en el estudio retrospectivo realizado entre 2008 y 2012. Resultados: Se incluyeron 255 casos: 131 OM, 79 AS, 30 OA y 15 ED. Respecto a las pruebas complementarias que el consenso consideró de obligada realización, la radiografía se llevó a cabo en el 87,8% de los casos, el hemocultivo en el 91,6% y el cultivo de líquido sinovial en el 99% de AS. Se realizó RM en el 71% de las OM. La elección del tratamiento antibiótico intravenoso empírico se adecuó a las recomendaciones en el 65,1% de los casos, y en el 62,3% para el tratamiento oral. Se llevó a cabo cirugía en el 36,8% de las AS (85,7% artrotomía), con un descenso significativo respecto al estudio retrospectivo (P = ,014). Solo el 58,5% de casos se ajustaron a las recomendaciones de duración del tratamiento; sin embargo, se comprobó una menor duración del tratamiento intravenoso. Conclusiones: En general, el grado de adecuación a las recomendaciones que marcaron el grupo de expertos es bueno para las pruebas complementarias y aceptable respecto a la elección del tratamiento antibiótico, aun detectándose casi un 40% de inadecuación. Se ha conseguido un descenso de la estancia hospitalaria.
To assess the effect of the publication of the Women's Health Initiative (WHI) study on patients' and physicians' attitudes in relation to hormone therapy (HT).
A survey focused on the degree of ...knowledge and on the reactions to the WHI study was administered to 600 women allocated in two groups according to their socioeconomic status, high (HSES) or low (LSES). Additionally, 283 physicians were surveyed to determine their attitudes regarding HT after the publication of the WHI study. The rates of HT prescription before and after publication of the study were compared.
Among patients, HT use and knowledge of the WHI study were less common among women of lower socioeconomic status (LSES 16.7% v HSES 47.3%, and LSES 15.7% v HSES 67.3%; P < 0.0001). Of the women in the LSES group who were HT users and had knowledge on the subject of the WHI study (n = 30), 56.7% contacted their physicians and 6.6% abandoned HT. These rates were similar for women in the HSES group. Among physicians, 97.2% of physicians referred to being aware of the WHI study, and 64.7% modified their clinical approach. The main changes were that 21.5% applied more rigorous risk/benefit assessment, 20.1% lowered hormone dosage, 18.8% decreased continuous-combined therapy use, 12.1% shortened the duration of HT, 7.7% abandoned medroxyprogesterone or conjugated estrogen use, and 5.0% increased the use of transdermal estrogens, tibolone, or other alternatives. As for prescriptions, after the publication of the WHI study, there was an 8.6% drop in the rate of HT prescriptions. This decrease was more pronounced for prescriptions based on conjugated equine estrogen and medroxyprogesterone acetate. In contrast, prescription of transdermal estrogens and tibolone increased 5.2% and 16%, respectively.
There was a significant change in physicians' and patients' attitudes toward HT after publication of the WHI study.
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