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1.
Curr Microbiol ; 80(6): 211, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37191823

RESUMO

Bacterial strain Marseille-P3954 was isolated from a stool sample of a 35-year-old male patient living in France. It was a gram-positive, rod-shaped anaerobic, non-motile, and non-spore-forming bacterium. C16:0 and C18:1n9 were the major fatty acid, while its genome measured 2,422,126 bp with 60.8 mol% of G+C content. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain Marseille-P3954 had 85.51% of similarity with Christensenella minuta, its closest related species with standing in nomenclature. As this value is very low compared to the recommended threshold, it suggested that the Marseille-P3954 strain belongs to a new bacterial genus, classified in a new family. On the basis of these genomic, phenotypic, and phylogenetic evidences, we propose that strain Marseille-P3954 should be classified as a new genus and species, Maliibacterium massiliense gen. nov., sp. nov. The type strain of M. massiliense sp. nov. is Marseille-P3954 (CSUR P3954 = CECT 9568).


Assuntos
Ácidos Graxos , Genômica , Masculino , Humanos , Adulto , Filogenia , RNA Ribossômico 16S/genética , Fezes/microbiologia , DNA Bacteriano/genética , Análise de Sequência de DNA , Técnicas de Tipagem Bacteriana
2.
Future Oncol ; 18(16): 2007-2028, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35187947

RESUMO

Aim: To evaluate the comparative efficacy and safety of identified first-line therapies for patients with EGFR mutation-positive (EGFRm+) advanced non-small-cell lung cancer (NSCLC), with a focus on ramucirumab + erlotinib. Methods: In the absence of head-to-head studies, a Bayesian network meta-analysis was conducted using randomized clinical trial data to evaluate first-line systemic therapies with erlotinib/gefitinib as the reference treatment. Results: For progression-free survival, ramucirumab + erlotinib was comparable to osimertinib and dacomitinib in the primary analysis. Conclusion: The analysis showed ramucirumab + erlotinib efficacy to be comparable to best-in-class treatment options for previously untreated patients with EGFRm+ advanced NSCLC. Registration information: PROSPERO ID: CRD42020136247.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Teorema de Bayes , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Cloridrato de Erlotinib/efeitos adversos , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Metanálise em Rede , Inibidores de Proteínas Quinases/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Curr Microbiol ; 79(2): 47, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982255

RESUMO

Using microbial culturomics, we were able to isolate strain Marseille-P3078 from a stool sample of a healthy 50-year-old Saudi Arabian woman. To this end, we used taxonogenomics that combines phenotypic, biochemical and genomic analyses, to describe this bacterium. Cells from strain Marseille-P3078 are anaerobic and Gram-negative rods that are motile and unable to sporulate. Its genome size is 3,377,914-bp-long with a 66.33 mol% G + C content. Based on its phenotypic and genomic features, including a 94.6% 16S rRNA similarity with Paraeggerthella hongkongensis strain JCM 14552, its closest phylogenetic neighbor withstanding in nomenclature, we propose that strain Marseille-P3078T (= CSUR P3078 = DSM 104007) is the representative strain of a new genus for which we propose the name Arabiibacter massiliensis gen. nov., sp. nov.


Assuntos
RNA Ribossômico 16S , Anaerobiose , Composição de Bases , DNA Bacteriano/genética , Fezes , Feminino , Humanos , Pessoa de Meia-Idade , Filogenia , RNA Ribossômico 16S/genética , Arábia Saudita , Análise de Sequência de DNA
4.
Artigo em Inglês | MEDLINE | ID: mdl-34047688

RESUMO

Five novel bacterial strains, Marseille-P1476T (=CSURP1476T=DSM 100642T), Marseille-P3256T (=CSURP3256T=CECT 9977T), Marseille-P2936T (=CSURP2936T=DSM 103159T), Marseille-P2912T (=CSURP2912T=DSM 103345T) and Marseille-P3197T (=CSURP3197T=CCUG 71847T), were isolated from various human specimens. These five strains were not identified at the species level by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Following 16S rRNA gene sequence comparisons with the GenBank database, the highest nucleotide sequence similarities of all studied strains were obtained to members of the paraphyletic genus Olsenella. A polyphasic taxono-genomic strategy (16S rRNA gene-based and core genome-based phylogeny, genomic comparison, phenotypic and biochemical characteristics) enabled us to better classify these strains and reclassify Olsenella species. Among the studied strains, Marseille-P1476T, Marseille-P2936T and Marseille-P3197T belonged to new species of the genus Olsenella for which we propose the names Olsenella massiliensis sp. nov., Olsenella phocaeensis sp. nov. and Olsenella urininfantis sp. nov., respectively. Strains Marseille-P2912T and Marseille-P3256T belonged to a new genus for which the names Thermophilibacter provencensis gen. nov., sp. nov. and Thermophilibacter mediterraneus gen. nov., sp. nov. are proposed, respectively. We also propose the creation of the genera Parafannyhessea gen. nov., Tractidigestivibacter gen. nov. and Paratractidigestivibacter gen. nov. and the reclassification of Olsenella umbonata as Parafannyhessea umbonata comb. nov., Olsenella scatoligenes as Tractidigestivibacter scatoligenes comb. nov., and Olsenella faecalis as Paratractidigestivibacter faecalis comb. nov.


Assuntos
Actinobacteria/classificação , Filogenia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Genômica , Humanos , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
5.
Curr Microbiol ; 78(7): 2481-2487, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34043027

RESUMO

Strain Marseille-P2012T was described to represent a new bacterial genus belonging to the phylum Firmicutes using the taxonogenomics concept. It was isolated from stool samples of a healthy 2-year-old Senegalese boy in a study of the human gut microbiota. This strain is a Gram-positive, anaerobic, non-motile and coccus-shaped bacterium. The 16S rRNA gene sequence of strain Marseille-P2012 exhibited 90.5% similarity with Finegoldia magna strain ATCC 29,328, the phylogenetically closest species with standing in nomenclature. The genome of strain Marseille-P2012T is 1,832,315 bp-long with 32.46 mol% of G + C content. With regard to its phenotypic, biochemical and genomic characteristics, this bacterium was classified as a new bacterial genus and species, Lagierella massiliensis gen. nov., sp. nov., with strain Marseille-P2012T (= CSUR P2012 = DSM100854) as type strain.


Assuntos
RNA Ribossômico 16S , Pré-Escolar , DNA Bacteriano/genética , Fezes , Firmicutes , Humanos , Masculino , Filogenia , RNA Ribossômico 16S/genética
6.
Antonie Van Leeuwenhoek ; 112(6): 905-918, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30689151

RESUMO

Using the culturomics approach, we isolated two strains, Marseille-P2963 and Marseille-P3753, from the intestinal microbiota of a 19-year-old healthy Saudi Arabian Bedouin male and from a 32-year-old healthy Senegalese male faecal transplant donor. Here, we studied their phenotypic, phylogenetic and genomic characteristics. Both strains were phylogenetically related, but different from Ruminococcus species. Bacterial cells were anaerobic, rod-shaped, non-spore-forming and not motile, with neither catalase nor oxidase activities. Their growth temperatures ranged from 28 to 45 °C, with an optimal growth at 37 °C. The genomes are 2,842,720 bp- and 2,707,061 bp-long respectively. The G + C contents are 47.18% and 46.90%, respectively. Based on these characteristics, we propose the creation of a new genus within the family Ruminococcaceae named Massiliimalia gen. nov., that contains the new species Massiliimalia massiliensis gen. nov., sp. nov., and Massiliimalia timonensis gen. nov., sp. nov. Strains Marseille-P2963T (= CSUR P2963 = DSM 106837) and Marseille-P3753T (= CSUR P3753 = CCUG 71632) are their type strains, respectively.


Assuntos
Clostridiales/isolamento & purificação , Fezes/microbiologia , Genoma Bacteriano , Composição de Bases , Clostridiales/classificação , Clostridiales/genética , DNA Bacteriano/genética , Microbioma Gastrointestinal , Tamanho do Genoma , Genômica , Humanos , Masculino , Filogenia , RNA Ribossômico 16S/genética , Arábia Saudita , Adulto Jovem
8.
Anaerobe ; 43: 47-55, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27923606

RESUMO

The strain GD9T is the type strain of the newly proposed species Blautia massiliensis sp. nov., belonging to the family Lachnospiraceae. It was isolated from a fresh stool sample collected from a healthy human using the culturomics strategy. Cells are Gram-negative rods, oxygen intolerant, non-motile and non-spore forming. The 16S rRNA gene sequencing showed that strain GD9T was closely related to Blautia luti, with a 97.8% sequence similarity. Major fatty acids were C14:0 (19.8%) and C16:0 (53.2%). Strain GD9T exhibits a genome of 3,717,339 bp that contains 3,346 protein-coding genes and 81 RNAs genes including 63 tRNAs. The features of this organism are described here, with its complete genome sequence and annotation. Compared with other Blautia species which are Gram positive, the strain was Gram negative justifying an emended description of the genus Blautia.


Assuntos
Clostridiales/classificação , Microbioma Gastrointestinal , Genoma Bacteriano/genética , Adulto , Clostridiales/genética , Clostridiales/isolamento & purificação , DNA Bacteriano/química , DNA Bacteriano/genética , Ácidos Graxos/análise , Fezes/microbiologia , Humanos , Masculino , Metagenoma , Anotação de Sequência Molecular , Filogenia , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
9.
J Med Econ ; 26(1): 1479-1488, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38035666

RESUMO

AIM: Increasing trend for progression-free survival (PFS)-based primary endpoint in oncology has led to lack of mature overall survival (OS) data at the time of approval. To address this evidence gap in economic evaluations, we used a joint Bayesian approach to predict survival outcomes using immature OS data from the RELAY trial. METHODS: Patient data from RELAY and systematic literature review (SLR) of phase 3 randomized clinical trials with hazard ratio (HR) estimates of mature PFS and immature OS were considered. OS and PFS were analyzed individually using a univariate model; bivariate analysis was performed using a joint model based on modified Bayesian normal induced copula estimation model. First, a Bayesian univariate model incorporated informative priors based on predicted HR and acceleration factor for OS and PFS. Second, a Bayesian-based joint model of RELAY PFS and OS data was based on the correlation between PFS and OS established in trials of similar populations. Marginal distribution of PFS was used to estimate the same for OS. RESULTS: Publications (N = 122) of first-line treatments in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer were identified in the SLR, of which 36 trials were linked to RELAY. Twenty-six trials with HR data were used. The univariate model could predict OS with reduced uncertainty compared with the frequentist approach. In the joint model, the marginal OS distribution borrowed strength from the marginal PFS distribution through the established correlation coefficient. LIMITATIONS: Bayesian approach was successfully used in RELAY analysis but may not be universally applied to oncology trials due to the different associations of OS and PFS and different trial patient populations. CONCLUSIONS: We demonstrated that both the univariate and joint Bayesian models reduced uncertainty in predicting OS compared to frequentist method. The methodology introduced here will have potential applications in clinical decision-making for other oncology trials.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Teorema de Bayes , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Análise Custo-Benefício , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Ramucirumab , Ensaios Clínicos Fase III como Assunto
10.
Artigo em Inglês | MEDLINE | ID: mdl-37811343

RESUMO

Background: Abemaciclib was recently approved by the European Medicines Agency in combination with adjuvant endocrine therapy (ET) for adult patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive early breast cancer (EBC) at high risk of recurrence. Objective: To evaluate the cost-effectiveness of abemaciclib plus ET vs. ET alone in patients with HR+, HER2-, node-positive EBC at high risk of disease recurrence, from the Italian healthcare system perspective. Methods: A cohort state transition model was developed with five states: invasive disease-free survival (IDFS), nonmetastatic recurrence, remission, metastatic recurrence, and death. The analysis had a time horizon of 30 years. Individual patient-level data from the monarchE trial (NCT03155997) were used to generate IDFS estimates. Resource use included drug acquisition/administration, best supportive care, terminal care, adverse events, hospitalization, post-progression therapy, and associated resource use in the metastatic disease health state. Health state utilities were derived from monarchE patient-level data and other sources, applying Italian tariffs where feasible. Results: The estimated total discounted costs (€39,249 vs. €16,806; difference: €22,443) and quality-adjusted life years (QALYs) (11.49 vs. 10.50; difference: 0.99) were higher for abemaciclib plus ET compared with ET alone. The incremental cost-effectiveness ratio was €22,651 per QALY gained. The likelihood of abemaciclib plus ET being cost-effective vs. ET alone was 99% at a willingness-to-pay threshold of €30,000 per QALY gained. Conclusion: Abemaciclib plus ET is a cost-effective treatment option vs. ET alone for those with HR+, HER2- node-positive EBC at high risk of recurrence in Italy.

11.
Int J Urol ; 19(7): 626-32, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22458762

RESUMO

OBJECTIVES: To evaluate the overall survival postnephrectomy for renal cancer for patients aged over 80 years, and to identify preoperative prognostic factors that might influence therapeutic strategies. METHODS: In a retrospective study in five French departments of urology, 179 patients aged over 80 years with renal cell carcinoma underwent radical nephrectomy between 1990 and 2011. The following data were collected: age, sex, body mass index, Charlson Comorbidity Index, American Society of Anesthesiology class, Eastern Cooperative Oncology Group Performance Status, type of surgery, period of follow-up, survival, death etiology, symptoms, Fuhrman grade and tumor-nodes-metastasis stage. RESULTS: After a 29.6-month follow up, 89 patients (49.7%) died. Death etiologies were: cancer for 46 (52%) patients, immediate or distant perioperative complications for five patients (6%) and three patients (3%) respectively, cardiovascular disease for 16 patients (18%), other cancers for three patients (3%) and unknown for 16 patients (18%). In a multivariate analysis, T-stage, M-stage and Charlson Comorbidity Index were identified as independent prognostic factors. Patients were divided into three groups (good, intermediate and bad prognosis) with significantly different survivals of 91, 36 and 22 months (P < 0.0001), respectively. CONCLUSIONS: Preoperative data, including T-stage, M-stage and Charlson Comorbidity Index represent significant independent prognostic factors for survival for patients aged over 80 years. These data might help the clinician in selecting the most suitable candidates for radical nephrectomy among elderly patients with renal cancer.


Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Nefrectomia , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Comorbidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Metástase Linfática , Masculino , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos
12.
Microbes Infect ; 23(8): 104842, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34020025

RESUMO

Strain Marseille-P1302 was isolated from the stool of a 2-year-old Nigerian boy suffering from Kwashiorkor, a form of severe acute malnutrition. The strain grows in aerobic atmosphere and bacterial cells are Gram-positive cocci ranging in diameter from 0.8 to 1 µm. Among species with standing in nomenclature, strain Marseille-P1302 exhibited a highest 16S rRNA sequence similarity of 94.97% with Brevilactibacter flavus strain VG341T, but was phylogenetically-closest to Brevilactibacter sinopodophylli strains KCTC 33808T. The draft genome of strain Marseille-P1302 was 2,934,258-bp-long with a 70.38% G + C content, and contained 2704 protein-coding genes and 55 RNAs that included 9 rRNA genes. On the basis of these data, we propose the creation of the new genus Nigeribacterium gen. nov., with strain Marseille-P1302T (= CSUR P1302 = DSM 29084) being the type strain of the new species Nigeribacterium. massiliense gen. nov., sp. nov.


Assuntos
Genômica , Composição de Bases , Pré-Escolar , DNA Bacteriano/genética , Humanos , Masculino , Filogenia , RNA Ribossômico 16S/genética
13.
Pan Afr Med J ; 37: 318, 2020.
Artigo em Francês | MEDLINE | ID: mdl-33654537

RESUMO

Arteria lusoria or retroesophageal right subclavian artery is the most common aortic arch malformation, accounting for 0.5-2.5% of cases. It can be detected in patients with symptoms including airway and/or esophageal compression such as dyspnea or dysphagia or even recurrent respiratory infections; but it is mostly asymptomatic, as reported by several authors. We here report the case of a 44-year-old female patient treated in our emergency room due to respiratory distress syndrome associated with arteria lusoria. This is a rare cause of dyspnea which should be suspected in patients with dyspnea not responding to medical treatment. Asymptomatic patients undergo medical treatment associated with simple surveillance. Surgery is necessary when it becomes symptomatic or when it is associated with Kommerell diverticulum (KD).


Assuntos
Anormalidades Cardiovasculares/diagnóstico , Dispneia/etiologia , Artéria Subclávia/anormalidades , Adulto , Anormalidades Cardiovasculares/complicações , Feminino , Humanos , Síndrome do Desconforto Respiratório/etiologia
14.
Curr Med Res Opin ; 35(7): 1241-1256, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30649973

RESUMO

Objective: To describe the cost-effectiveness of pembrolizumab plus chemotherapy (carboplatin and paclitaxel or nab-paclitaxel; P + C) in metastatic, squamous, non-small-cell lung cancer (NSCLC) patients in the US. Methods: A model comparing P + C versus C alone is developed utilizing partitioned survival analysis. Primary clinical efficacy, treatment utilization, health utility and safety data are derived from the KEYNOTE-407 trial and projected over 20 years. Costs for drugs and non-drug disease management are also incorporated. Additionally, the cost-effectiveness of P + C vs. pembrolizumab monotherapy (P) is evaluated via an indirect treatment comparison, for patient subgroups with PD-L1 Tumor Proportion Score (TPS) ≥ 50% and 1-49%. Results: Overall, P + C is projected to increase life expectancy by 1.95 years vs. C (3.86 versus 1.91). The resultant ICER is $86,293/QALY. In patients with PD-L1 ≥ 50%, 1-49% and <1 the corresponding incremental cost-effectiveness ratios (ICERs) are $99,777/QALY, $85,986/QALY and $87,507/QALY, respectively. Versus P, in the PD-L1 ≥ 50% subgroup, P + C appears cost saving; however, this result should be interpreted with caution as there is considerable uncertainty in the relative efficacy of these comparators. Conclusions: Across all eligible patients, the addition of pembrolizumab to chemotherapy is projected to approximately double life expectancy, yielding an extension to a point not previously seen in metastatic squamous NSCLC. Overall, and within all relevant PD-L1 subgroups, use of P + C yields an ICER below $100,000/QALY, and can be a cost-effective first-line treatment for eligible metastatic squamous NSCLC patients for whom chemotherapy is currently administered. In the PD-L1 ≥ 50% subgroup, additional follow-up within trials of pembrolizumab plus chemotherapy and pembrolizumab monotherapy are needed to better define cost-effectiveness between these comparators.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Albuminas/administração & dosagem , Antígeno B7-H1/metabolismo , Carboplatina/administração & dosagem , Análise Custo-Benefício , Humanos , Paclitaxel/administração & dosagem , Anos de Vida Ajustados por Qualidade de Vida , Análise de Sobrevida
15.
Microbiologyopen ; 8(6): e00758, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30701700

RESUMO

As part of the culturomics project aiming at describing the human microbiota, we report in this study the description of the new bacterial genus Raoultibacter gen. nov. that includes two new species, that is, R. massiliensis sp. nov. and R. timonensis sp. nov. The R. massiliensis type strain Marseille-P2849T was isolated from the fecal specimen of a healthy 19-year-old Saudi Bedouin, while R. timonensis type strain Marseille-P3277T was isolated from the feces of an 11-year-old pygmy female living in Congo. Strain Marseille-P2849T exhibited 91.4% 16S rRNA sequence similarity with Gordonibacter urolithinfaciens, its phylogenetic closest neighbor with standing in nomenclature. As well, strain Marseille-P3277T exhibited 97.96% 16S rRNA similarity with strain Marseille-P2849T . Both strains were Gram-positive, motile, nonspore-forming rod and form transparent microcolonies on blood agar in both anaerobic and microaerophilic atmospheres. The genome sizes of strain Marseille-P2849T and strain Marseille-P3277T were 3,657,161 bp and 4,000,215 bp, respectively. Using a taxono-genomic approach combining the phenotypic, biochemical, and genomic characteristics, we propose the genus Raoultibacter gen. nov., which contains strains Marseille-P2849T (= CSUR P2849T , = DSM 103407T ) and Marseille-P3277T (=CCUG 70680T , =CSUR P3277T ) as type strains of the species R. massiliensis sp. nov., and R. timonensis sp. nov., respectively.


Assuntos
Actinobacteria/isolamento & purificação , Microbioma Gastrointestinal , Actinobacteria/classificação , Actinobacteria/genética , DNA Bacteriano/genética , Fezes/microbiologia , Genoma Bacteriano , Genômica , Humanos , Masculino , Filogenia , RNA Ribossômico 16S/genética , Adulto Jovem
16.
Pan Afr Med J ; 32: 70, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31223361

RESUMO

Ophidian envenomations are a public health problem in Africa, causing 20.000 annual deaths. This mortality reflects the difficulties in the management of these complications, in particular of bleeding complications. We report the case of Mr SL, aged 35 years, farmer, victim of snake bite causing haemorrhagic syndrome followed by a progressive onset of acute abdomen. Ultrasound objectified high abundant effusion. Effusion puncture was performed which showed unclotting blood. Given the re-establishment of the hemoperitoneum after three doses of antivenin serum as well as the coagulation of the samples collected using drying tube, exploratory laparotomy was performed on day 9. It showed retroperitoneal hematoma, with bulging appearance, in the mesocolon which flowed in the peritoneal cavity. Aspiration of 1500ml of blood and rinsing with physiological serum were performed. The postoperative course was uneventful. The patient was transferred to the department of surgery three days after surgery and was discharged on day 19.


Assuntos
Antivenenos/administração & dosagem , Hematoma/etiologia , Mordeduras de Serpentes/complicações , Abdome Agudo/etiologia , Abdome Agudo/terapia , Adulto , Hematoma/cirurgia , Hemoperitônio/etiologia , Hemoperitônio/terapia , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Masculino , Recidiva , Espaço Retroperitoneal
17.
Clin Cancer Res ; 13(21): 6359-68, 2007 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17975148

RESUMO

PURPOSE: Oxaliplatin displays a frequent dose-limiting neurotoxicity due to its interference with neuron voltage-gated sodium channels through one of its metabolites, oxalate, a calcium chelator. Different clinical approaches failed in neurotoxicity prevention, except calcium-magnesium infusions. We characterized oxalate outcome following oxaliplatin administration and its interference with cations and amino acids. We then looked for genetic predictive factors of oxaliplatin-induced neurotoxicity. EXPERIMENTAL DESIGN: We first tested patients for cations and oxalate levels and did amino acid chromatograms in urine following oxaliplatin infusion. In the second stage, before treatment with FOLFOX regimen, we prospectively looked for variants in genes coding for the enzymes involved (a) in the oxalate metabolism, especially glyoxylate aminotransferase (AGXT), and (b) in the detoxification glutathione cycle, glutathione S-transferase pi, and for genes coding for membrane efflux proteins (ABCC2). RESULTS: In the first 10 patients, urinary excretions of oxalate and cations increased significantly within hours following oxaliplatin infusion, accompanied by increased excretions of four amino acids (glycine, alanine, serine, and taurine) linked to oxalate metabolism. In a further 135 patients, a minor haplotype of AGXT was found significantly predictive of both acute and chronic neurotoxicity. Neither glutathione S-transferase pi nor ABCC2 single nucleotide polymorphisms we looked for were linked to neurotoxicity. CONCLUSION: These data confirm the involvement of oxalate in oxaliplatin neurotoxicity and support the future use of AGXT genotyping as a pretherapeutic screening test to predict individual susceptibility to neurotoxicity.


Assuntos
Neoplasias/tratamento farmacológico , Neoplasias/genética , Neurotoxinas/química , Compostos Organoplatínicos/química , Compostos Organoplatínicos/metabolismo , Oxalatos/metabolismo , Idoso , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Cálcio/metabolismo , Genótipo , Glutationa Transferase/metabolismo , Humanos , Magnésio/metabolismo , Pessoa de Meia-Idade , Modelos Biológicos , Proteína 2 Associada à Farmacorresistência Múltipla , Compostos Organoplatínicos/toxicidade , Oxalatos/química , Oxaliplatina , Valor Preditivo dos Testes , Análise de Sequência de DNA , Canais de Sódio/química
18.
J Med Econ ; 21(12): 1191-1205, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30188231

RESUMO

AIMS: To describe cost-effectiveness of pembrolizumab plus platinum and pemetrexed chemotherapy in metastatic, non-squamous, NSCLC patients in the US. MATERIALS AND METHODS: A model is developed utilizing partitioned survival analysis to estimate the cost-effectiveness of KEYNOTE-189 trial comparators pembrolizumab + chemotherapy (carboplatin/cisplatin + pemetrexed) vs chemotherapy alone. Clinical efficacy, treatment utilization, health utility, and safety data are derived from the trial and projected over 20 years. For extrapolating survival beyond the trial, a novel SEER population-data approach is applied (primary analysis), with separate estimation via traditional parametric extrapolation methods. Costs for drugs and non-drug disease management are also incorporated. Based on an indirect treatment comparison, cost-effectiveness of pembrolizumab + chemotherapy vs pembrolizumab monotherapy is evaluated for patients with programmed death-ligand 1 (PD-L1) ≥ 50%. RESULTS: In the full non-squamous population, pembrolizumab + chemotherapy is projected to increase life expectancy by 2.04 years vs chemotherapy (3.96 vs 1.92), for an approximate doubling of life years. Resultant incremental cost-effectiveness ratios (ICERs) are $104,823/QALY and $87,242/life year. In patients with PD-L1 ≥ 50% and 1-49%, life expectancy is more than doubled (4.53 vs 1.88 years) and (4.87 vs 2.01 years), with a 32% (2.60 vs 1.97 years) increase in PD-L1 < 1% patients. Corresponding incremental costs/quality-adjusted life year (QALY) are $103,402, $66,837, and $183,529 for PD-L1 ≥ 50%, 1-49%, and <1% groups, respectively. Versus pembrolizumab monotherapy in PD-L1 ≥ 50% patients, representing current standard of care, pembrolizumab + chemotherapy increases life expectancy by 65% (4.53 vs 2.74 years) at an ICER of $147,365/QALY. LIMITATIONS AND CONCLUSIONS: The addition of pembrolizumab to chemotherapy is projected to extend life expectancy to a point not previously seen in previously untreated metastatic non-squamous NSCLC. Although ICERs vary by sub-group and comparator, results suggest pembrolizumab + chemotherapy yields ICERs near, or in most cases, well below a 3-times US per capita GDP threshold of $180,000/QALY, and may be a cost-effective first-line treatment for metastatic non-squamous NSCLC patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/economia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Análise Custo-Benefício , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Gastos em Saúde/estatística & dados numéricos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Modelos Econométricos , Metástase Neoplásica , Pemetrexede/economia , Pemetrexede/uso terapêutico , Compostos de Platina/economia , Compostos de Platina/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Análise de Sobrevida
19.
Stand Genomic Sci ; 13: 8, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29682169

RESUMO

We report the properties of a draft genome sequence of the bacterium Fermentimonas caenicola strain SIT8 (= CSUR P1560). This strain, whose genome is described here, was isolated from the fecal flora of a healthy 28-month-old Senegalese boy. Strain SIT8 is a facultatively anaerobic Gram-negative bacillus. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 2,824,451-bp long (1 chromosome but no plasmid) contains 2354 protein-coding and 46 RNA genes, including four rRNA genes.

20.
Microbiologyopen ; 7(1)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29076642

RESUMO

Strain SIT6T was isolated from the fecal flora of a severely malnourished child as part of a broad "culturomics" study aiming to maximize the culture conditions for the in-depth exploration of the human microbiota. An analysis of the 16S rRNA gene sequence showed that strain SIT6T shared 94.1% 16S rRNA gene sequence similarity with Bacillus thermoamylovorans DKPT (NR_029151), the phylogenetically closest type species. Colonies are creamy white, circular, 4-5 mm in diameter after cultivation at 37°C for 24 hr on 5% sheep blood-enriched Colombia agar. Growth occurs at temperatures in the range of 25-56°C (optimally at 37°C). Strain SIT6T is a gram-positive, facultative anaerobic rod and motile by means of peritrichous flagella and sporulating; it is catalase and oxidase positive. The 2,784,637-bp-long genome, composed of 16 contigs, has a G+C content of 35.19%. Of the 2,646 predicted genes, 2,572 were protein-coding genes and 74 were RNAs. The major fatty acids are saturated species (15:0 iso, 16:0 and 17:0 anteiso). Of the 14 detected fatty acids, 11 are saturated, either linear or branched (iso and anteiso). Digital DNA-DNA hybridization (dDDH) estimation and average genomic identity of orthologous gene sequences (AGIOS) of the strain SIT6T against genomes of the type strains of related species ranged between 18.6% and 38.3% and between 54.77% and 65.50%, respectively. According to our taxonogenomics results, we propose the creation of Bacillus kwashiorkori sp. nov. that contains the type strain SIT6T (=CSUR P2452T , =DSM 29059T ).


Assuntos
Bacillus/classificação , Bacillus/isolamento & purificação , Fezes/microbiologia , Desnutrição , Aerobiose , Bacillus/genética , Bacillus/fisiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , Análise por Conglomerados , Citosol/química , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Ácidos Graxos/análise , Genoma Bacteriano , Humanos , Lactente , Locomoção , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Temperatura
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