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OBJECTIVE: The triglyceride-glucose index (TyG) has been proposed as a marker of insulin resistance (IR) and has shown associations with cardiovascular diseases. This study aimed to investigate the relationship between the TyG and the coronary slow flow phenomenon (CSFP) and explore the index's potential as a predictor of this condition. PATIENTS AND METHODS: A total of 187 patients who underwent coronary angiography were included; of these, 91 patients were diagnosed with CSFP, and 96 patients with normal coronary flow served as a control group. The TyG was calculated using fasting triglyceride and glucose levels. RESULTS: The results showed that the TyG was significantly higher in the CSFP group compared with the control group (p < 0.001). Additionally, the TyG exhibited a moderate positive correlation with the thrombolysis-in-myocardial-infarction frame count in coronary arteries (p < 0.001). A multivariate logistic regression analysis revealed that the TyG, along with gender, ejection fraction, and uric acid, remained significant predictors of CSFP (p < 0.05). CONCLUSIONS: This study's findings suggest that the TyG may serve as a useful marker for identifying individuals at risk of CSFP and provide insights into the potential role of IR in its pathophysiology.
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Biomarcadores , Glucemia , Angiografía Coronaria , Fenómeno de no Reflujo , Triglicéridos , Humanos , Triglicéridos/sangre , Masculino , Femenino , Glucemia/análisis , Glucemia/metabolismo , Persona de Mediana Edad , Biomarcadores/sangre , Fenómeno de no Reflujo/sangre , Fenómeno de no Reflujo/diagnóstico , Fenómeno de no Reflujo/diagnóstico por imagen , Resistencia a la Insulina , Circulación Coronaria , AncianoRESUMEN
BACKGROUND: Fibroblast growth factor receptor 3 (FGFR3) alterations are oncogenic drivers of urothelial carcinoma (UC). Pemigatinib is a selective, oral inhibitor of FGFR1-3 with antitumor activity. We report the efficacy and safety of pemigatinib in the open-label, single-arm, phase II study of previously treated, unresectable or metastatic UC with FGFR3 alterations (FIGHT-201; NCT02872714). PATIENTS AND METHODS: Patients ≥18 years old with FGFR3 mutations or fusions/rearrangements (cohort A) and other FGF/FGFR alterations (cohort B) were included. Patients received pemigatinib 13.5 mg once daily continuously (CD) or intermittently (ID) until disease progression or unacceptable toxicity. The primary endpoint was centrally confirmed objective response rate (ORR) as per RECIST v1.1 in cohort A-CD. Secondary endpoints included ORR in cohorts A-ID and B, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Overall, 260 patients were enrolled and treated (A-CD, n = 101; A-ID, n = 103; B, n = 44; unconfirmed FGF/FGFR status, n = 12). All discontinued treatment, most commonly due to progressive disease (68.5%). ORR [95% confidence interval (CI)] in cohorts A-CD and A-ID was 17.8% (10.9% to 26.7%) and 23.3% (15.5% to 32.7%), respectively. Among patients with the most common FGFR3 mutation (S249C; n = 107), ORR was similar between cohorts (A-CD, 23.9%; A-ID, 24.6%). In cohorts A-CD/A-ID, median (95% CI) DOR was 6.2 (4.1-8.3)/6.2 (4.6-8.0) months, PFS was 4.0 (3.5-4.2)/4.3 (3.9-6.1) months, and OS was 6.8 (5.3-9.1)/8.9 (7.5-15.2) months. Pemigatinib had limited clinical activity among patients in cohort B. Of 36 patients with samples available at progression, 6 patients had 8 acquired FGFR3 secondary resistance mutations (V555M/L, n = 3; V553M, n = 1; N540K/S, n = 2; M528I, n = 2). The most common treatment-emergent adverse events overall were diarrhea (44.6%) and alopecia, stomatitis, and hyperphosphatemia (42.7% each). CONCLUSIONS: Pemigatinib was generally well tolerated and demonstrated clinical activity in previously treated, unresectable or metastatic UC with FGFR3 mutations or fusions/rearrangements.
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Antineoplásicos , Carcinoma de Células Transicionales , Morfolinas , Pirimidinas , Pirroles , Neoplasias de la Vejiga Urinaria , Humanos , Adolescente , Carcinoma de Células Transicionales/tratamiento farmacológico , Antineoplásicos/efectos adversos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , GenómicaRESUMEN
BACKGROUND: Among patients with advanced renal cell carcinoma (RCC), those with sarcomatoid histology (sRCC) have the poorest prognosis. This analysis assessed the efficacy of avelumab plus axitinib versus sunitinib in patients with treatment-naive advanced sRCC. METHODS: The randomized, open-label, multicenter, phase III JAVELIN Renal 101 trial (NCT02684006) enrolled patients with treatment-naive advanced RCC. Patients were randomized 1 : 1 to receive either avelumab plus axitinib or sunitinib following standard doses and schedules. Assessments in this post hoc analysis of patients with sRCC included efficacy (including progression-free survival) and biomarker analyses. RESULTS: A total of 108 patients had sarcomatoid histology and were included in this post hoc analysis; 47 patients in the avelumab plus axitinib arm and 61 in the sunitinib arm. Patients in the avelumab plus axitinib arm had improved progression-free survival [stratified hazard ratio, 0.57 (95% confidence interval, 0.325-1.003)] and a higher objective response rate (46.8% versus 21.3%; complete response in 4.3% versus 0%) versus those in the sunitinib arm. Correlative gene expression analyses of patients with sRCC showed enrichment of gene pathway scores for cancer-associated fibroblasts and regulatory T cells, CD274 and CD8A expression, and tumors with The Cancer Genome Atlas m3 classification. CONCLUSIONS: In this subgroup analysis of JAVELIN Renal 101, patients with sRCC in the avelumab plus axitinib arm had improved efficacy outcomes versus those in the sunitinib arm. Correlative analyses provide insight into this subtype of RCC and suggest that avelumab plus axitinib may increase the chance of overcoming the aggressive features of sRCC.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Axitinib , Carcinoma de Células Renales , Neoplasias Renales , Sunitinib , Protocolos de Quimioterapia Combinada Antineoplásica , Axitinib/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Sunitinib/uso terapéuticoRESUMEN
BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.
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COVID-19 , Neoplasias , Anciano , Prueba de COVID-19 , Femenino , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Pandemias , SARS-CoV-2RESUMEN
Anaerosphaera massiliensis strain Marseille-P4592T (= CSURP4592T; = CCUG72452T) is a new species isolated from the stool of a 39-year-old male Pygmy from the Democratic Republic of Congo.
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An obligate aerobic, Gram-positive, non-sporulating, rod-shaped bacterium designated Marseille P3888T was isolated from the stool sample of a healthy male pygmy. We described its main characteristics, and sequenced and annotated its genome. The 16S rRNA analysis revealed 98.10% sequence similarity with Corynebacterium terpenotabidum, the phylogenetically closest species with standing in nomenclature. The genome had a size of 3142051 bp with a guanine + cytosine content of 66.83%. We proposed the creation of the new Corynebacterium neomassiliense sp. nov. strain Marseille-P3888T.
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The interest in studying gut microbiota has been rekindled with the advent of molecular techniques, in particular, metagenomics. Culturomics (high throughput microbial culture with identification of the colonies by Maldi-TOF) has demonstrated its complementarity with metagenomics for comprehensive study of the microbiota. The main metagenomic studies have revealed an increase in biodiversity, with in particular an increase of Spirochaetes and Prevotella in subjects of African origin compared with Western subjects. Studies on malnutrition have shown a reduction of all bacteria and in particular of anaerobic bacteria and methanogenic archaea. Of the 1,162 bacteria isolated by culturomics studies, 476 were isolated only from non-African samples, 445 were isolated in African and non-African groups, and 241 bacteria were isolated from samples of African origin including 68 new species. Further studies of African microbiota by culturomics and metagenomics will make it possible to assess whether some bacteria have particular specificities and if these might play a role in certain pathologies such as malnutrition.
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Microbioma Gastrointestinal , Metagenómica/métodos , África , HumanosRESUMEN
Enterococcus mediterraneensis strain Marseille-P4358T (= CSURP4358T) is a new species isolated from the stool of a 39-year-old male Pygmy from the Democratic Republic of Congo.
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[This corrects the article DOI: 10.1016/j.nmni.2017.04.003.].
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Enterococcus timonensis sp. nov., strain Marseille-P2817T, is a facultatively anaerobic, motile and non-spore-forming Gram-positive coccus which was isolated from the sputum of a healthy adult man in Marseilles. We present herein its phenotypic description together with MALDI-TOF (matrix-assisted laser-desorption/ionization time-of-flight) mass spectrometry analysis and genome sequencing and comparison. The genome of Enterococcus timonensis is 2 123 933 bp long with 38.46 mol% of G+C content, and it contains 1983 protein-coding genes and 65 RNA genes (including nine rRNA genes).
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BACKGROUND: Microphthalmia Transcription Factor (MITF)family translocation renal cell carcinoma (tRCC) is a rare RCC subtype harboring TFE3/TFEB translocations. The prognosis in the metastatic (m) setting is poor. Programmed death ligand-1 expression was reported in 90% of cases, prompting us to analyze the benefit of immune checkpoint inhibitors (ICI) in this population. PATIENTS AND METHODS: This multicenter retrospective study identified patients with MITF family mtRCC who had received an ICI in any of 12 referral centers in France or the USA. Response rate according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed. Genomic alterations associated with response were determined for 8 patients. RESULTS: Overall, 24 patients with metastatic disease who received an ICI as second or later line of treatment were identified. Nineteen (82.6%) of these patients had received a VEGFR inhibitor as first-line treatment, with a median PFS of 3 months (range, 1-22 months). The median PFS for patients during first ICI treatment was 2.5 months (range, 1-40 months); 4 patients experienced partial response (16,7%) and 3 (12,5%) had stable disease. Of the patients whose genomic alterations were analyzed, two patients with mutations in bromodomain-containing genes (PBRM1 and BRD8) had a clinical benefit. Resistant clones in a patient with exceptional response to ipilimumab showed loss of BRD8 mutations and increased mutational load driven by parallel evolution affecting 17 genes (median mutations per gene, 3), which were enriched mainly for O-glycan processing (29.4%, FDR = 9.7 × 10- 6). CONCLUSIONS: MITF family tRCC is an aggressive disease with similar responses to ICIs as clear-cell RCC. Mutations in bromodomain-containing genes might be associated with clinical benefit. The unexpected observation about parallel evolution of genes involved in O-glycosylation as a mechanism of resistance to ICI warrants exploration.
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Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Células Renales/genética , Inmunomodulación/efectos de los fármacos , Neoplasias Renales/genética , Factor de Transcripción Asociado a Microftalmía/genética , Familia de Multigenes , Translocación Genética , Adolescente , Adulto , Anciano , Antineoplásicos Inmunológicos/farmacología , Biomarcadores de Tumor , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Niño , Preescolar , Femenino , Genómica/métodos , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Factor de Transcripción Asociado a Microftalmía/antagonistas & inhibidores , Persona de Mediana Edad , Estadificación de Neoplasias , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
The number of isolated new microorganisms has dramatically increased after the readaption of culture using the culturomics approach. Each of these microorganisms is deposited in an international strain collection institute, with its name being attributed and published by the scientist who isolated it. The attributed name is of Latin or Latinized origin and chosen on the basis of the geographical location of the sample collection, the institute or geographical region where the project was being performed, the name of a concerned scientist, and characteristics of the sample or the microorganism. Our institution has played an important role in the isolation of new microorganisms, with the first effort reporting 468 new bacterial species (3% of the bacterial species isolated at least once worldwide) and 327 species isolated for the first time from human beings, which in turn resulted in an increase of 30% of the total number of microorganisms isolated. Additionally, more than 100 giant viruses, including seven new species, have been isolated at our institute. In the present work, after recalling the rules of nomenclature, we detail the naming of the new microorganisms chosen at our laboratory. The most common species name was massiliensis, attributed 161 times. We consider it imperative for the cultivators, who have frequently made considerable efforts in the field of microbial culture, to be the ones who name the newly isolated microorganisms, taking into consideration the Latinized nomenclature standards.
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Culturomics is a concept developing different culture conditions in order to enlarge our knowledge of the human microbiota through the discovery of previously uncultured bacteria. This enabled us to isolate six new species of the Bacteroides genus: Bacteroides mediterraneensis strain Marseille-P2644, Bacteroides ihuae strain Marseille-P2824, Bacteroides togonis strain Marseille-P3166, Bacteroides ndongoniae strain Marseille-P3108, Bacteroides ilei strain Marseille-P3208 and Bacteroides congonensis strain Marseille-P3132. Those bacteria are Gram-negative anaerobic bacilli. We describe here their phenotypic features, together with phylogenetic analysis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry spectrum, fatty acid composition, and genome sequencing and annotation.
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The taxonogenomic approach, including the culturomics techniques, is now currently used to isolate and characterize new bacteria. These approaches notably allowed us to discover six new species of the Actinomyces genus: Actinomyces ihuae strain SD1, Actinomyces bouchesdurhonensis strain Marseille-P2825, Actinomyces urinae strain Marseille-P2225, Actinomyces marseillensis strain Marseille-P2818, Actinomyces mediterranea strain Marseille-P3257 and Actinomyces oralis strain Marseille-P3109. Each is the type strain of the corresponding bacterial species. 16S ribosomal RNA gene sequence comparison was used to classify these strains among the Actinomyces genus. These strains are all Gram positive, rod shaped and facultative aerobic. We describe the main characteristics of each bacterium and present their complete genome sequence and annotation.
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We present the description of Sanguibacter massiliensis sp. nov., Actinomyces minihominis sp. nov., Clostridium minihomine sp. nov., Neobittarella massiliensis gen. nov. and Miniphocibacter massiliensis gen. nov., new bacterial species isolated by culturomics from human stool samples.
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We report the main characteristics of 'Enterococcus timonensis' strain Marseille-P2817T (CSUR P2817), 'Leptotrichia massiliensis' sp. nov., strain Marseille-P3007T (CSUR P3007), 'Actinomyces marseillensis' sp. nov., strain Marseille-P2818T (CSUR P2818), 'Actinomyces pacaensis' sp. nov., strain Marseille-P2985T (CSUR P2985), 'Actinomyces oralis' sp. nov., strain Marseille-P3109T (CSUR P3109), 'Actinomyces culturomici' sp. nov., strain Marseille-P3561T (CSUR P3561) and 'Gemella massiliensis' sp. nov., strain Marseille-P3249T (CSUR P3249) which were isolated from human sputum samples.
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We report the isolation of a new bacterium species, 'Lactobacillus raoultii' strain Marseille P4006 (CSUR P4006), isolated from a vaginal sample of a 45-year-old woman with bacterial vaginosis.
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Strain Marseille-P3237 was isolated from a stool sample of a healthy 35-year-old Congolese pygmy female. This anaerobic, Gram-negative, non-spore-forming and non-motile coccus-shaped bacterium is a member of the order Coriobacteriales. It exhibits a 2 009 306-bp genome with a 65.46 mol% G+C content and is closely related to, but distinct from, members of the Olsenella genus. We propose the creation of the new genus Libanicoccus gen. nov. and of the new species Libanicoccus massiliensis sp. nov.