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Background The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients. Methods The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models. Result The series comprises 1376 patients; 238 treated with DPF and 1138 with PF between 2008 and 2019. DPF was associated with increased progression-free survival (PFS) and overall survival (OS) with time ratio (TR) 1.27 (95% credible interval [CrI], 1.15–1.40), and TR 1.19 (95% CrI, 1.09–1.27), respectively. Serious adverse events were more common with DPF, particularly hematological effects (32% vs 22%). Younger participants received greater DPF dose density without achieving greater disease control, while severe toxicity was likewise higher. DPF yielded superior OS in Lauren intestinal (TR 1.27, 95% CrI, 1.08–1.11) vs diffuse subtype (TR 1.17, 95% CrI, 1.09–1.24) and the probability of increasing OS > 15% was 90% vs 67% in each subtype, respectively. The effect dwindles over time, which can be attributed to pathological changes and clinical practice changes. Conclusion Our study confirms the effect of DPF is highly dependent on several clinical–pathological variables, with discreet and gradually declining benefit over platinum doublets in later years, at the expense of increased toxicity. These results may help to underpin the idea that external validity of AGC trials should be revised regularly.

Aims: To obtain real-world data on ramucirumab use and effectiveness for the treatment of advanced gastric cancer (AGC) or gastroesophageal junction adenocarcinoma (GEJ). Methods: Observational, retrospective study carried out in 20 Spanish hospitals, in patients who started ramucirumab treatment between December 2015 and December 2018. Descriptive analysis was conducted for patient characteristics, treatment patterns and effectiveness outcomes. Results: Three hundred seventeen patients were included (93.7% treated with ramucirumab-paclitaxel and 6.3% with ramucirumab); age 62.5 (11.3) years; 66.9% male. Median progression-free survival and overall survival were 3.9 months (95% CI: 3.4–4.3) and 7.4 (95% CI: 6.4–8.9) in combination regimen and 2.0 (1.1–2.8) and 4.3 (95% CI: 1.9–7.3) in monotherapy, respectively. Conclusion: The study findings were consistent with available real-world studies and randomized clinical trials.

OBJECTIVE: Advanced gastric cancer (AGC) is a common neoplasm in older adults. Nevertheless, there are few specific management data in the literature. The aim of this study was to assess non-inferiority of survival and efficacy-related outcomes of chemotherapy used in older vs non-older patients with AGC.MATERIALS AND METHODS: We recruited 1485 patients from the AGAMENON registry of AGC treated with polychemotherapy between 2008-2017. A statistical analysis was conducted to prove non-inferiority for overall survival (OS) associated with the use of chemotherapy schedules in individuals ≥70 vs.

Research into cancer-associated thrombosis (CAT) entails managing dynamic data that pose an analytical challenge. Thus, methods that assume proportional hazards to investigate prognosis entail a risk of misinterpreting or overlooking key traits or time-varying effects. We examined the AGAMENON registry, which collects data from 2,129 patients with advanced gastric cancer. An accelerated failure time (AFT) multistate model and flexible competing risks regression were used to scrutinize the time-varying effect of CAT, as well as to estimate how covariates dynamically predict cumulative incidence. The AFT model revealed that thrombosis shortened progression-free survival and overall survival with adjusted time ratios of 0.72 and 0.56, respectively. Nevertheless, its prognostic effect was nonproportional and disappeared over time if the subject managed to survive long enough. CAT that occurred later had a more pronounced prognostic effect. In the flexible competing risks model, multiple covariates were seen to have significant time-varying effects on the cumulative incidence of CAT (Khorana score, secondary thromboprophylaxis, high tumor burden, and cisplatin-containing regimen), whereas other predictors exerted a constant effect (signet ring cells and primary thromboprophylaxis). The model that assumes proportional hazards was incapable of capturing the effect of these covariates and predicted the cumulative incidence in a biased way. This study evinces that flexible and multistate models are a useful and innovative method to describe the dynamic effect of variables associated with CAT and should be more widely used.

Trastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC. This Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression. The rate of HER2 testing increased steadily over time, from 58.3 % in 2008 to 92.9 % in 2016. HER2 was positive in 194 tumors (21.3 %). In the stratified Cox PH regression, each 1 % increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3 % increase in the risk of death: hazard ratio, 1.0035 (CI 95 %, 1.001-1.005), P = 0.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2. Patients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner.

Objetivo Se investigo la sensibilidad de 190 estreptococos alfahemoliticos y 30 Gemella spp., en su mayoria comensales y resistentes a eritromicina, frente a 7 antibioticos betalactamicos, glucopepticos y aminoglucosidos. Material y metodos Para determinar la sensibilidad a los antimicrobianos se utilizaron las tecnicas de dilucion y difusion en agar, segun las normas del National Committee for Clinical Laboratory Standards/Clinical and Laboratory Standards Institute (NCCLS/CLSI). Resultados El 62,6% de los estreptococos alfahemoliticos y el 53,3% de Gemella spp. no fueron sensibles a penicilina (concentracion inhibitoria minima al 50% [CIM50]: 0,5 μg/ml). Cefuroxima fue la cefalosporina que presento menor actividad (CIM50: 1 μg/ml y 0,5 μg/ml, en estreptococos y Gemella spp.), mientras que cefotaxima, ceftriaxona (CIM50: 0,25 μg/ml) y cefepima (CIM50: 0,5 μg/ml) presentaron una actividad superior a penicilina. El 100% de los aislamientos fueron sensibles a vancomicina, teicoplanina y gentamicina. Cuatro cepas de estreptococos alfahemoliticos presentaron resistencia de alto nivel a estreptomicina y tres a kanamicina. No hubo diferencia significativa en el comportamiento de los antibioticos estudiados frente a las cepas con diferente fenotipo de resistencia a macrolidos. Tanto en los aislamientos con fenotipo M como en aquellos con fenotipo constitutivo (MLSBc) predomino la resistencia a penicilina y a otros antibioticos betalactamicos frente al patron de resistencia, que incluye solo penicilina o bien penicilina, otros antibioticos betalactamicos y aminoglucosidos. Conclusiones Las tasas de resistencia a penicilina en las cepas comensales resistentes a eritromicina son particularmente elevadas, hecho que tiene una importante implicacion clinica por el caracter endogeno de las infecciones causadas por estas bacterias. La menor actividad de cefuroxima podria sugerir que su utilizacion frente a otros patogenos preservaria en mayor grado a la microbiota orofaringea estudiada.

Pulsed-field gel electrophoresis (PFGE) of SmaI macrorestriction fragments of genomic DNA as well as staphylococcal cassette chromosome mec (SCCmec) typing for mecA-carrying isolates were used to study the distribution of clonal types among 177 Staphylococcus aureus clinical isolates recovered in a Spanish hospital between 2000 and 2003. Five major clonal types (P1 to P5) were identified by PFGE, with one of them (P1) comprising the majority of strains (47.5%). According to SCCmec typing, SCCmec type IVA was the most prevalent type, showing increasing prevalence in the hospital setting with respect to other pandemic clones. One SCCmec pattern was detected in different PFGE types, which demonstrates that the latter is a major discriminative typing method. Three novel SCCmec elements or variants were found, each in a different PFGE type. Oxacillin (methicillin)-resistant and -susceptible S. aureus (MRSA and MSSA, respectively) strains were detected showing identical PFGE patterns, suggesting horizontal transfer of mecA to MSSA and/or mecA deletion from MRSA. Persistence of several S. aureus clones throughout the years within the same hospital environment was also observed.

The epidemiologic relatedness of 29 erythromycin-resistant Gemella sp. strains from normal flora, characterized previously, were evaluated by pulsed-field gel electrophoresis (PFGE). Three isolates carried the tet (O) gene and the tet (M) gene. The msr (A) gene was found in two Gemella morbillorum strains in combination with the erm (B) or mef (E) gene. The sequences of the mef (A/E ) , erm (B), and msr (A) genes showed a high similarity to the corresponding sequences of other gram-positive cocci. All the strains harboring the mef (A/E) gene and the msr (D) gene possessed open reading frame 3 (ORF3)/ORF6. The 16 G. morbillorum isolates represented 15 distinct DNA profiles. Four clusters were identified (≥80% genetic relatedness). The 12 Gemella haemolysans strains belonged to different PFGE types. The clonal diversity found suggests that horizontal transfer may be the main route through which erythromycin resistance is acquired.

We assessed the mechanisms of resistance to macrolide-lincosamide-streptogramin B (MLS B ) antibiotics and related antibiotics in erythromycin-resistant viridans group streptococci ( n = 164) and Gemella spp. ( n = 28). The macrolide resistance phenotype was predominant (59.38%); all isolates with this phenotype carried the mef (A) or mef (E) gene, with mef (E) being predominant (95.36%). The erm (B) gene was always detected in strains with constitutive and inducible MLS B resistance and was combined with the mef (A/E) gene in 47.44% of isolates. None of the isolates carried the erm (A) subclass erm (TR), erm (A), or erm (C) genes. The mel gene was detected in all but four strains carrying the mef (A/E) gene. The tet (M) gene was found in 86.90% of tetracycline-resistant isolates and was strongly associated with the presence of the erm (B) gene. The cat pC194 gene was detected in seven chloramphenicol-resistant Streptococcus mitis isolates, and the aph ( 3′ )- III gene was detected in four viridans group streptococcal isolates with high-level kanamycin resistance. The intTn gene was found in all isolates with the erm (B), tet (M), aph ( 3′ ) -III , and cat pC194 gene. The mef (E) and mel genes were successfully transferred from both groups of bacteria to Streptococcus pneumoniae R6 by transformation. Viridans group streptococci and Gemella spp. seem to be important reservoirs of resistance genes.

Susceptibility to seven betalactam antibiotics, glycopeptides and aminoglycosides was investigated in 190 erythromycin-resistant alpha-hemolytic streptococci and 30 Gemella spp, mainly from normal flora.Antimicrobial susceptibility testing was performed by a standard agar diffusion test and a standard agar dilution method according to NCCLS/CLSI criteria.62.6% of alfahemolytic streptococci and 53.3% of Gemella spp. were not susceptible to penicillin (MIC50: 0,5 microg/mL). Cefuroxime was the least active cephalosporin (MIC50: 1 microg/mL and 0.5 microg/mL, in streptococci and Gemella spp., respectively), whereas cefotaxime, ceftriaxone (MIC50: 0.25 microg/mL) and cefepime (MIC50: 0.5 microg/mL) were more active than penicillin. All isolates were susceptible to vancomycin, teicoplanin and gentamicin. Four alfahemolytic streptococcal strains showed high-level resistance to streptomycin, and three strains to kanamycin. There were no significant differences in resistance rates to the antibiotics studied between strains with different macrolide resistance phenotypes. Resistance to penicillin and other betalactam antibiotics (73.8%) was prevalent in M phenotype strains and resistance to penicillin and other classes of antibiotics predominated in constitutive (cMLS(B)) strains (71.4%).Resistance to penicillin in erythromycin-resistant strains was notably high in this study. This fact has important clinical implications because of the endogenous character of alpha-hemolytic streptococcal and Gemella spp. infections. The lower cefuroxime activity suggests that use of this agent against other pathogens would be effective in preserving the oropharyngeal microflora analyzed.

Alterations in the erm(A) regulatory region of six clinical isolates of Staphylococcus epidermidis and one of Staphylococcus haemolyticus displaying a constitutive resistance phenotype were investigated. Anovel deletion of 10 bp with respect to the corresponding sequence of Tn554 was identified in the attenuator of a constitutively expressed erm(A) gene of one of the S. epidermidis isolates. Thus far, this is the smallest deletion conferring constitutive resistance in the translational attenuator of erm(A) in a naturally occurring S. epidermidis strain of human origin.

High-level aminoglycoside resistance was assessed in 190 commensal erythromycin-resistant alpha-hemolytic streptococcal strains. Of these, seven were also aminoglycoside-resistant: one Streptococcus mitis strain was resistant to high levels of kanamycin and carried the aph(3 ')-III gene, four S. mitis strains were resistant to high levels of streptomycin and lacked aminoglycoside-modifying enzymes, and two S. oralis strains that were resistant to high levels of kanamycin and streptomycin harbored both the aph(3 ')-III and the ant(6) genes. The two S. oralis strains also carried the ant(6)-sat4- aph(3 ' ')-III aminoglycoside-streptothricin resistance gene cluster, but it was not contained in a Tn5405-like structure. The presence of this resistance gene cluster in commensal streptococci suggests an exchange of resistance genes between these bacteria and enterococci or staphylococci.

Phoradendron liga (Gill. ex H. et A.) Eichl. is a Viscaceae widely distributed in Argentina. It has been commonly used in folk medicine as a substitute of the European mistletoe (Viscum album L.) to decrease high blood pressure due to their external similarity. In this study, the anatomical features as well as micromolecular and macromolecular analysis of this species are reported. Anatomical study has shown that Phoradendron liga presents as anatomic features: papillous cuticle, clusters in leaves and stems, and isodiametric stone cells only in stems. The analysis of flavonoids showed that this species produces C-glycosylflavones and 3-desoxyproanthocyanidins. Protein study showed a protein pattern with components ranging from 14 to 90 kDa and the presence of related epitopes between the species was demonstrated by cross recognition using anti-Phoradendron and anti-Viscum antisera of both species by Western blot assay. In addition, a galactose specific lectin (L-Phl) was isolated form Phoradendron liga extracts. These results are part of a comprehensive project on Argentine hemiparasite species destinated to be applied to quality control of commercial samples and disclosed their potential use as a potential source for immunomodulatory compounds.

A trypsin inhibitor (PDTI) was isolated from Peltophorum dubium seeds by affinity chromatography on a thyroglobulin-agarose or a trypsin-agarose column. In both cases, SDS-PAGE showed two bands of M(r) 20,000 and 22,000, which could not be resolved. Their amino-terminal sequences were identical and similar to that of Kunitz-type soybean trypsin inhibitor (SBTI). Mass spectrometry analysis of tryptic digests of both bands showed 16 coincident peaks, suggesting that they are closely related proteins. The K(i)s for trypsin and chymotrypsin inhibitory activity of PDTI were 1.6 x 10(-7) and 1.3 x 10(-5)M, respectively. Lectin-like activity of PDTI and SBTI, detected by hemagglutination of rabbit erythrocytes, was inhibited by sialic acid-containing compounds. PDTI and SBTI caused apoptosis of Nb2 rat lymphoma cells, demonstrated by decrease of viability, DNA hypodiploidy, DNA fragmentation, and caspase-3-like activity. They had no effect on normal mouse splenocytes or lymphocytes, whereas they caused apoptosis of concanavalin A-stimulated mouse lymphocytes.