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Standard first-line chemotherapy results in disease progression and death within one year in most patients with human epidermal growth factor receptor 2 (HER2)-negative gastro-oesophageal adenocarcinoma1-4. Nivolumab plus chemotherapy demonstrated superior overall survival versus chemotherapy at 12-month follow-up in gastric, gastro-oesophageal junction or oesophageal adenocarcinoma in the randomized, global CheckMate 649 phase 3 trial5 (programmed death ligand-1 (PD-L1) combined positive score ≥5 and all randomized patients). On the basis of these results, nivolumab plus chemotherapy is now approved as a first-line treatment for these patients in many countries6. Nivolumab and the cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor ipilimumab have distinct but complementary mechanisms of action that contribute to the restoration of anti-tumour T-cell function and induction of de novo anti-tumour T-cell responses, respectively7-11. Treatment combining 1 mg kg-1 nivolumab with 3 mg kg-1 ipilimumab demonstrated clinically meaningful anti-tumour activity with a manageable safety profile in heavily pre-treated patients with advanced gastro-oesophageal cancer12. Here we report both long-term follow-up results comparing nivolumab plus chemotherapy versus chemotherapy alone and the first results comparing nivolumab plus ipilimumab versus chemotherapy alone from CheckMate 649. After the 24.0-month minimum follow-up, nivolumab plus chemotherapy continued to demonstrate improvement in overall survival versus chemotherapy alone in patients with PD-L1 combined positive score ≥5 (hazard ratio 0.70; 95% confidence interval 0.61, 0.81) and all randomized patients (hazard ratio 0.79; 95% confidence interval 0.71, 0.88). Overall survival in patients with PD-L1 combined positive score ≥ 5 for nivolumab plus ipilimumab versus chemotherapy alone did not meet the prespecified boundary for significance. No new safety signals were identified. Our results support the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastro-oesophageal adenocarcinoma.
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Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Neoplasias Gástricas , Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1 , Neoplasias Esofágicas/tratamiento farmacológico , Unión Esofagogástrica , Estudios de Seguimiento , Humanos , Ipilimumab/efectos adversos , Ipilimumab/uso terapéutico , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
BACKGROUND: In an interim analysis of this phase 3 trial, the addition of pembrolizumab to chemotherapy resulted in longer progression-free survival than chemotherapy alone among patients with advanced triple-negative breast cancer whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS; the number of PD-L1-staining tumor cells, lymphocytes, and macrophages, divided by the total number of viable tumor cells, multiplied by 100) of 10 or more. The results of the final analysis of overall survival have not been reported. METHODS: We randomly assigned patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer in a 2:1 ratio to receive pembrolizumab (200 mg) every 3 weeks plus the investigator's choice of chemotherapy (nanoparticle albumin-bound paclitaxel, paclitaxel, or gemcitabine-carboplatin) or placebo plus chemotherapy. The primary end points were progression-free survival (reported previously) and overall survival among patients whose tumors expressed PD-L1 with a CPS of 10 or more (the CPS-10 subgroup), among patients whose tumors expressed PD-L1 with a CPS of 1 or more (the CPS-1 subgroup), and in the intention-to-treat population. Safety was also assessed. RESULTS: A total of 847 patients underwent randomization: 566 were assigned to the pembrolizumab-chemotherapy group, and 281 to the placebo-chemotherapy group. The median follow-up was 44.1 months. In the CPS-10 subgroup, the median overall survival was 23.0 months in the pembrolizumab-chemotherapy group and 16.1 months in the placebo-chemotherapy group (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.55 to 0.95; two-sided P = 0.0185 [criterion for significance met]); in the CPS-1 subgroup, the median overall survival was 17.6 and 16.0 months in the two groups, respectively (hazard ratio, 0.86; 95% CI, 0.72 to 1.04; two-sided P = 0.1125 [not significant]); and in the intention-to-treat population, the median overall survival was 17.2 and 15.5 months, respectively (hazard ratio, 0.89; 95% CI, 0.76 to 1.05 [significance not tested]). Adverse events of grade 3, 4, or 5 that were related to the trial regimen occurred in 68.1% of the patients in the pembrolizumab-chemotherapy group and in 66.9% in the placebo-chemotherapy group, including death in 0.4% of the patients in the pembrolizumab-chemotherapy group and in no patients in the placebo-chemotherapy group. CONCLUSIONS: Among patients with advanced triple-negative breast cancer whose tumors expressed PD-L1 with a CPS of 10 or more, the addition of pembrolizumab to chemotherapy resulted in significantly longer overall survival than chemotherapy alone. (Funded by Merck Sharp and Dohme; KEYNOTE-355 ClinicalTrials.gov number, NCT02819518.).
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Anticuerpos Monoclonales Humanizados , Inhibidores de Puntos de Control Inmunológico , Neoplasias de la Mama Triple Negativas , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/biosíntesis , Antígeno B7-H1/genética , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
Objective: Determine the association between periodontal disease (PD) and obesity through an umbrella review. Materials and Methods: A search for information until March 2024 was carried out in the following electronic databases: PubMed, Cochrane library, Scopus, SciELO, Web of Science, Google Scholar, Proquest Dissertations and Theses, and OpenGrey. We included studies that were systematic reviews (SR) with or without meta-analysis, without time or language restrictions, that evaluated primary studies that associated PD with obesity. Literary or narrative reviews, rapid reviews, intervention studies, observational studies, preclinical and basic research, summaries, comments, case reports, protocols, personal opinions, letters, and posters were excluded. The AMSTAR-2 tool was used to determine the quality and overall confidence of the included studies. Results: The preliminary search yielded a total of 419 articles, discarding those that did not meet the selection criteria, leaving only 14 articles. All studies reported that PD was associated with obesity, with an OR and RR ranging from 1.1 to 1.46 and 1.64 to 2.21, respectively. Conclusions: Based on the results and conclusions of the SR with a high overall confidence level, PD is associated with obesity.
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Obesidad , Enfermedades Periodontales , Humanos , Enfermedades Periodontales/complicaciones , Enfermedades Periodontales/epidemiología , Obesidad/complicacionesRESUMEN
Beta-2 Human papillomaviruses 38b, 107, and 122 have been frequently found in cervical cancer samples in western Mexico. Because their E6/E7 genes functions are not fully elucidated, we deepen into their transformation capabilities. To achieve this goal, primary human fibroblasts (FB) were transduced with E6/E7 genotype-specific viral particles. Additionally, E6/E7 from HPVs 16 and 18 were included as controls. All E6/E7-cell models increased their lifespan; however, it is important to highlight that FB-E6/E7-122 showed growth as accelerated as FB-E6/E7-16 and 18. Furthermore, both FB-E6/E7-38b and 122 exhibited abilities to migrate, and FB-E6/E7-122 presented high invasive capacity. On the other hand, ΔNp73 expression was found in all cell models, except for FB-pLVX (empty-vector). Finally, RNAseq found differentially expressed genes enriched in signaling pathways related to cell cycle, epithelial-mesenchymal transition, and cancer, among others. This study shows for the first time, the great transformative potential that genotypes of the Beta-2 also possess, especially HPV122. These Beta-2 HPVs can modulate some of the genes that are well known to be regulated by Alpha-HPVs, however, they also possess alternative strategies to modulate diverse signaling pathways. These data support the idea that Beta-2 HPVs should play an important role in co-infections with Alpha-HPV during carcinogenesis.
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Proteínas Oncogénicas Virales , Neoplasias del Cuello Uterino , Femenino , Fibroblastos/metabolismo , Humanos , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Proteínas Represoras/metabolismo , Neoplasias del Cuello Uterino/genéticaRESUMEN
BACKGROUND: Evidence suggests the incidence of non-affective psychotic disorders (NAPDs) varies across persons and places, but data from the Global South is scarce. We aimed to estimate the treated incidence of NAPD in Chile, and variance by person, place and time. METHODS: We used national register data from Chile including all people, 10-65 years, with the first episode of NAPD (International Classification of Diseases, Tenth Revision: F20-F29) between 1 January 2005 and 29 August 2018. Denominators were estimated from Chilean National Census data. Our main outcome was treated incidence of NAPD and age group, sex, calendar year and regional-level population density, multidimensional poverty and latitude were exposures of interest. RESULTS: We identified 32 358 NAPD cases [12 136 (39.5%) women; median age-at-first-contact: 24 years (interquartile range 18-39 years)] during 171.1 million person-years [crude incidence: 18.9 per 100 000 person-years; 95% confidence interval (CI) 18.7-19.1]. Multilevel Poisson regression identified a strong age-sex interaction in incidence, with rates peaking in men (57.6 per 100 000 person-years; 95% CI 56.0-59.2) and women (29.5 per 100 000 person-years; 95% CI 28.4-30.7) between 15 and 19 years old. Rates also decreased (non-linearly) over time for women, but not men. We observed a non-linear association with multidimensional poverty and latitude, with the highest rates in the poorest regions and those immediately south of Santiago; no association with regional population density was observed. CONCLUSION: Our findings inform the aetiology of NAPDs, replicating typical associations with age, sex and multidimensional poverty in a Global South context. The absence of association with population density suggests this risk may be context-dependent.
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Trastornos Psicóticos , Adolescente , Adulto , Trastornos Psicóticos Afectivos , Chile/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pobreza , Trastornos Psicóticos/psicología , Adulto JovenRESUMEN
BACKGROUND: Pembrolizumab monotherapy showed durable antitumour activity and manageable safety in patients with metastatic triple-negative breast cancer. We aimed to examine whether the addition of pembrolizumab would enhance the antitumour activity of chemotherapy in patients with metastatic triple-negative breast cancer. METHODS: In this randomised, placebo-controlled, double-blind, phase 3 trial, done in 209 sites in 29 countries, we randomly assigned patients 2:1 with untreated locally recurrent inoperable or metastatic triple-negative breast cancer using a block method (block size of six) and an interactive voice-response system with integrated web-response to pembrolizumab (200 mg) every 3 weeks plus chemotherapy (nab-paclitaxel; paclitaxel; or gemcitabine plus carboplatin) or placebo plus chemotherapy. Randomisation was stratified by type of on-study chemotherapy (taxane or gemcitabine-carboplatin), PD-L1 expression at baseline (combined positive score [CPS] ≥1 or <1), and previous treatment with the same class of chemotherapy in the neoadjuvant or adjuvant setting (yes or no). Eligibility criteria included age at least 18 years, centrally confirmed triple-negative breast cancer; at least one measurable lesion; provision of a newly obtained tumour sample for determination of triple-negative breast cancer status and PD-L1 status by immunohistochemistry at a central laboratory; an Eastern Cooperative Oncology Group performance status score 0 or 1; and adequate organ function. The sponsor, investigators, other study site staff (except for the unmasked pharmacist), and patients were masked to pembrolizumab versus saline placebo administration. In addition, the sponsor, the investigators, other study site staff, and patients were masked to patient-level tumour PD-L1 biomarker results. Dual primary efficacy endpoints were progression-free survival and overall survival assessed in the PD-L1 CPS of 10 or more, CPS of 1 or more, and intention-to-treat populations. The definitive assessment of progression-free survival was done at this interim analysis; follow-up to assess overall survival is continuing. For progression-free survival, a hierarchical testing strategy was used, such that testing was done first in patients with CPS of 10 or more (prespecified statistical criterion was α=0·00411 at this interim analysis), then in patients with CPS of 1 or more (α=0·00111 at this interim analysis, with partial alpha from progression-free survival in patients with CPS of 10 or more passed over), and finally in the intention-to-treat population (α=0·00111 at this interim analysis). This study is registered with ClinicalTrials.gov, NCT02819518, and is ongoing. FINDINGS: Between Jan 9, 2017, and June 12, 2018, of 1372 patients screened, 847 were randomly assigned to treatment, with 566 patients in the pembrolizumab-chemotherapy group and 281 patients in the placebo-chemotherapy group. At the second interim analysis (data cutoff, Dec 11, 2019), median follow-up was 25·9 months (IQR 22·8-29·9) in the pembrolizumab-chemotherapy group and 26·3 months (22·7-29·7) in the placebo-chemotherapy group. Among patients with CPS of 10 or more, median progression-free survival was 9·7 months with pembrolizumab-chemotherapy and 5·6 months with placebo-chemotherapy (hazard ratio [HR] for progression or death, 0·65, 95% CI 0·49-0·86; one-sided p=0·0012 [primary objective met]). Median progression-free survival was 7·6 and 5·6 months (HR, 0·74, 0·61-0·90; one-sided p=0·0014 [not significant]) among patients with CPS of 1 or more and 7·5 and 5·6 months (HR, 0·82, 0·69-0·97 [not tested]) among the intention-to-treat population. The pembrolizumab treatment effect increased with PD-L1 enrichment. Grade 3-5 treatment-related adverse event rates were 68% in the pembrolizumab-chemotherapy group and 67% in the placebo-chemotherapy group, including death in <1% in the pembrolizumab-chemotherapy group and 0% in the placebo-chemotherapy group. INTERPRETATION: Pembrolizumab-chemotherapy showed a significant and clinically meaningful improvement in progression-free survival versus placebo-chemotherapy among patients with metastatic triple-negative breast cancer with CPS of 10 or more. These findings suggest a role for the addition of pembrolizumab to standard chemotherapy for the first-line treatment of metastatic triple-negative breast cancer. FUNDING: Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1/efectos de los fármacos , Antígeno B7-H1/metabolismo , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Evaluación de Resultado en la Atención de Salud , Placebos/administración & dosificación , Supervivencia sin Progresión , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/secundarioRESUMEN
Background: Among other negative effects, herbicides induce oxidative stress, leading to lipid peroxidation and protein oxidation. Therefore, there is a growing need to identify natural compounds with sufficient antioxidant capacity and mitigate the negative effects of herbicides without side effects.Objective: Our study aimed to examine the protective effect of the phenolic extract of wild garlic (WG) leaves on terbuthylazine-treated erythrocytes.Material and methods: In human erythrocytes treated with the herbicide terbuthylazine (4.5 mg/L) alone and a combination of terbuthylazine and WG extract, we measured malondialdehyde (MDA) and haemoglobin (Hb) concentrations and the antioxidant activities of CuZn superoxide dismutase (SOD1; EC 1.15.1.1) and catalase (CAT; EC 1.11.1.6) in vitro.Results: In comparison with terbuthylazine, WG extract reduced the concentrations of MDA and Hb from 59.69 to 43.45 nmol/gHb (27%, p < 0.001) and 165.08 to 128.64 g/L (22%, p < 0.05), respectively. Catalase activity was induced for samples treated with both WG extract and terbuthylazine compared with terbuthylazine alone (p < 0.05).Conclusions: The results demonstrated that WG may reduce the toxicity of terbuthylazine, and the erythrocyte membrane may be the primary site of phenolic action. Therefore, the lipid peroxidation intensity could be a biomarker of oxidative damage caused by terbuthylazine and the protective effect of WG.
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Eritrocitos/efectos de los fármacos , Ajo/química , Peroxidación de Lípido/efectos de los fármacos , Extractos Vegetales/farmacología , Triazinas/toxicidad , Catalasa/sangre , Eritrocitos/enzimología , Eritrocitos/metabolismo , Hemoglobinas/metabolismo , Humanos , Malondialdehído/sangre , Superóxido Dismutasa/sangreRESUMEN
STATEMENT OF PROBLEM: As Candida albicans biofilm formation is associated with severe local and systemic infections in denture-wearing patients, its prevention or reduction becomes an essential factor in the health of this population. PURPOSE: The purpose of this in vitro study was to investigate whether 2 photopolymerized coatings of poly(acrylic acid) (PAA) and poly(itaconic acid) (PIA) can effectively reduce the adhesion of C albicans on denture base acrylic resin surfaces. MATERIAL AND METHODS: The surface of the polymethyl methacrylate (PMMA) denture base was modified through photopolymerization of a thin film of PAA or PIA. The polymeric coatings were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), contact angle goniometry (CA), and surface roughness measurement (Ra). For biological evaluation, the coated PMMA surfaces were tested in a C albicans biofilm dynamic formation model, observed by confocal laser scanning microscopy (CLSM), and quantified by the number of colony-forming units (CFUs). The cytotoxicity of the polymeric coatings was also evaluated by using a lactic dehydrogenase-based (LDH) test. For statistical analysis, ANOVA and the nonparametric Kruskal-Wallis test were used (α=.05). RESULTS: The PMMA resin base surfaces coated with PAA and PIA had an inhibitory effect on C albicans growth, the wettability of the coated surface, and the average roughness. The PAA and PIA coatings had no statistically significant cytotoxic effect on periodontal ligament fibroblasts. CONCLUSIONS: PMMA acrylic resin base material was superficially modified through the incorporation of carboxylic acid groups by using PAA and PIA coatings that reduced the adherence of C albicans biofilm by 90%.
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Candida albicans , Polimetil Metacrilato , Biopelículas , Bases para Dentadura , Humanos , Ensayo de Materiales , Propiedades de SuperficieRESUMEN
BACKGROUND: Cannabis use among young people in Chile has increased significantly in the last years. There is a consistent link between cannabis and psychosis. AIM: To compare cannabis use in patients with a first episode of psychosis and healthy controls. MATERIAL AND METHODS: We included 74 patients aged 20 ± 3 years (78% males) admitted to hospital with a first episode of psychosis and a group of 60 healthy controls aged 23 ± 4 years (63% males). Cannabis consumption was assessed, including age of first time use and length of regular use. RESULTS: Patients with psychosis reported a non-significantly higher frequency of life-time cannabis use. Patients had longer periods of regular cannabis use compared with healthy subjects (Odds ratio [OR] 2.4; 95% confi-dence intervals [CI] 1.14-5.05). Patients also used cannabis for the first time at an earlier age (16 compared with 17 years, p < 0.0). The population attributable fraction for regular cannabis use associated with hospital admissions due to psychosis was 17.7% (95% CI 1.2-45.5%). CONCLUSIONS: Cannabis use is related to psychosis in this Chilean group of patients. This relationship is stronger in patients with early exposure to the drug and longer the regular use. One of every five admissions due to psychosis is associated with cannabis consumption. These data should influence cannabis legisla-tion and the public policies currently being discussed in Chile.
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Cannabis , Trastornos Psicóticos , Adolescente , Adulto , Estudios de Casos y Controles , Chile/epidemiología , Femenino , Humanos , Masculino , Trastornos Psicóticos/epidemiología , Factores de Riesgo , Adulto JovenRESUMEN
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report 3-year efficacy and safety results from the phase III CheckMate 649 trial. Patients with previously untreated advanced or metastatic gastroesophageal adenocarcinoma were randomly assigned to nivolumab plus chemotherapy or chemotherapy. Primary end points were overall survival (OS) and progression-free survival (PFS) by blinded independent central review (BICR) in patients whose tumors expressed PD-L1 combined positive score (CPS) ≥5. With 36.2-month minimum follow-up, for patients with PD-L1 CPS ≥5, the OS hazard ratio (HR) for nivolumab plus chemotherapy versus chemotherapy was 0.70 (95% CI, 0.61 to 0.81); 21% versus 10% of patients were alive at 36 months, respectively; the PFS HR was 0.70 (95% CI, 0.60 to 0.81); 36-month PFS rates were 13% versus 8%, respectively. The objective response rate (ORR) per BICR was 60% (95% CI, 55 to 65) with nivolumab plus chemotherapy versus 45% (95% CI, 40 to 50) with chemotherapy; median duration of response was 9.6 months (95% CI, 8.2 to 12.4) versus 7.0 months (95% CI, 5.6 to 7.9), respectively. Nivolumab plus chemotherapy also continued to show improvement in OS, PFS, and ORR versus chemotherapy in the overall population. Adding nivolumab to chemotherapy maintained clinically meaningful long-term survival benefit versus chemotherapy alone, with an acceptable safety profile, supporting the continued use of nivolumab plus chemotherapy as standard first-line treatment for advanced gastroesophageal adenocarcinoma.
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Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas , Unión Esofagogástrica , Nivolumab , Neoplasias Gástricas , Humanos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Nivolumab/uso terapéutico , Nivolumab/efectos adversos , Nivolumab/administración & dosificación , Unión Esofagogástrica/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Masculino , Estudios de Seguimiento , Femenino , Anciano , Persona de Mediana Edad , Supervivencia sin Progresión , AdultoRESUMEN
BACKGROUND: To compare the clinical effectiveness of ion-releasing restorations (IRR) vs. composite resin (CR) in dental restorations. METHODS: A systematic search was carried out from articles published until January 2024, in the biomedical databases: PubMed, Cochrane Library, Scielo, Scopus, Web of Science and Google Scholar. Randomized clinical trials were included, with a follow-up time greater than or equal to 1 year, without time and language limits and which reported the clinical effect of IRR compared to CR in dental restorations. The RoB 2.0 tool was used to assess the risk of bias of the included studies and the GRADEPro GDT tool was used to assess the quality of evidence and the strength of recommendation of the results. RESULTS: The search yielded a total of 1109 articles. After excluding those that did not meet the selection criteria, 29 articles remained for the quantitative synthesis. The analysis found no statistically significant difference when comparing the dental restorations with IRRs or CRs. CONCLUSION: The literature reviewed suggests that there are no differences between the IRRs and CRs in dental restorations.
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BACKGROUND: In KEYNOTE-355 (NCT02819518), addition of pembrolizumab to chemotherapy led to statistically significant improvements in progression-free survival and overall survival in patients with advanced triple-negative breast cancer (TNBC) with tumor PD-L1 combined positive score (CPS) ≥10. We report patient-reported outcomes (PROs) from KEYNOTE-355. METHODS: Patients were randomized 2:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus investigator's choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin). QLQ-C30, QLQ-BR23, and EQ-5D visual analogue scale (VAS) were prespecified. PROs were analyzed for patients who received ≥1 dose of study treatment and completed ≥1 PRO assessment. Change in PRO scores from baseline were assessed at week 15 (latest time point at which completion/compliance rates were ≥60%/≥80%). Time to deterioration (TTD) in PROs was defined as time to first onset of ≥ 10-point worsening in score from baseline. RESULTS: PRO analyses included 317 patients with tumor PD-L1 CPS ≥10 (pembrolizumab plus chemotherapy; n = 217; placebo plus chemotherapy, n = 100). There were no between-group differences in change from baseline to week 15 in QLQ-C30 global health status/quality of life (GHS/QoL; least-squares mean difference, -1.81 [95% CI, -6.92 to 3.30]), emotional functioning (-1.43 [-7.03 to 4.16]), physical functioning (-1.05 [-6.59 to 4.50]), or EQ-5D VAS (0.18 [-5.04 to 5.39]), and no between-group difference in TTD in QLQ-C30 GHS/QoL, emotional functioning, or physical functioning. CONCLUSIONS: Together with the efficacy and safety findings, PRO results from KEYNOTE-355 support pembrolizumab plus chemotherapy as a standard of care for patients with advanced TNBC with tumor PD-L1 (CPS ≥10).
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Creatinine is an amino acid derived from creatine catabolism at different steps of the body's organs, and its detection is significant because levels out of normal values are linked to some diseases like kidney failure. Normal concentration levels of creatinine in blood are from 45 to 110 µM, while in urine, typical concentrations range between 3.3 to 27 mM, and in saliva from 8.8 and 26.5 µM. Nowadays, the creatinine detection is carried through different spectroscopic-colorimetric methods; however, the resulting values present errors due to high interferences, delayed analysis, and poor stability. Electrochemical sensors have been an alternative to creatinine detection, and the electrochemical methods have been adapted to detect in enzymatic and non-enzymatic sensors, the latter being more relevant in recent years. Nanomaterials have made creatinine sensors more stable, sensitive, and selective. This review presents recent advances in creatinine electrochemical sensors for advances in point-of-care (POC) sensing devices, comprising both a materials point of view and prototypes for advanced sensing. The effect of the metal, particle size, shape and other morphological and electronic characteristics of nanomaterials are discussed in terms of their impact on the effective detection of creatinine. In addition, the application of nanomaterials in POC devices is revised pointing to practical applications and looking for more straightforward and less expensive devices to manufacture.
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[This corrects the article DOI: 10.1039/D2RA04479J.].
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Worldwide breast cancer ranks first in mortality and incidence rates in women over 20 years old. Rather than one disease, breast cancer is a heterogeneous group of diseases that express distinct molecular profiles. Neoadjuvant chemotherapy is an important therapeutic strategy for breast cancer patients independently of their molecular subtype, with the drawback of resistance development. In addition, chemotherapy has adverse effects that combined with resistance could contribute to lower overall survival. Although great efforts have been made to find diagnostic and prognostic biomarkers for breast cancer and for response to targeted and immune therapy for this pathology, little has been explored regarding biomarkers of response to anthracyclines and taxanes based neoadjuvant chemotherapy. This work aimed to evaluate the molecular profile of patients who received neoadjuvant chemotherapy to identify differentially expressed genes (DEGs) that could be used as biomarkers of chemotherapy response and overall survival. Breast cancer patients who were candidates for neoadjuvant chemotherapy were enrolled in this study. After treatment and according to their pathological response, they were assigned as sensitive or resistant. To evaluate DEGs, Gene Ontology, Kyoto Encyclopedia Gene and Genome (KEGG), and protein-protein interactions, RNA-seq information from all patients was obtained by next-generation sequencing. A total of 1985 DEGs were found, and KEGG analysis indicated a great number of DEGs in metabolic pathways, pathways in cancer, cytokine-cytokine receptor interactions, and neuroactive ligand-receptor interactions. A selection of 73 DEGs was used further for an analysis of overall survival using the METABRIC study and the ductal carcinoma dataset of The Cancer Genome Atlas (TCGA) database. Nine DEGs correlated with overall survival, of which the subexpression of C1QTNF3, CTF1, OLFML3, PLA2R1, PODN, KRT15, HLA-A, and the overexpression of TUBB and TCP1 were found in resistant patients and related to patients with lower overall survival.
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Neoplasias de la Mama/genética , Resistencia a Antineoplásicos/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Transcriptoma , Biomarcadores de Tumor , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Línea Celular Tumoral , Toma de Decisiones Clínicas , Biología Computacional , Manejo de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ontología de Genes , Humanos , Terapia Neoadyuvante , Pronóstico , Mapeo de Interacción de ProteínasRESUMEN
Breast cancer ranks first in terms of mortality and incidence rates worldwide among women. The HER2+ molecular subtype is one of the most aggressive subtypes; its treatment includes neoadjuvant chemotherapy and the use of a HER2 antibody. Some patients develop resistance despite positive results obtained using this therapeutic strategy. OBJECTIVE: To identify prognostic markers for treatment and survival in HER2+ patients. METHODS: Patients treated with neoadjuvant chemotherapy were assigned to sensitive and resistant groups based on their treatment response. Differentially expressed genes (DEGs) were identified using RNA-seq analysis. KEGG pathway, gene ontology, and interactome analyses were performed for all DEGs. An enrichment analysis Gene set enrichment analysis was performed. All DEGs were analyzed for overall (OS) and disease-free survival (DFS). RESULTS: A total of 94 DEGs were related to treatment resistance. Survival analysis showed that 12 genes (ATF6B, DHRS13, DIRAS1, ERAL1, GRIN2B, L1CAM, IRX3, PRTFDC1, PBX2, S100B, SLC9A3R2, and TNXB) were good predictors of disease-free survival, and eight genes (GNG4, IL22RA2, MICA, S100B, SERPINF2, HLA-A, DIRAS1, and TNXB) were good predictors of overall survival (OS). CONCLUSION: We highlighted a molecular expression signature that can differentiate the treatment response, overall survival, and DFS of patients with HER2+ breast cancer.
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INTRODUCTION: In CheckMate 227, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with tumor programmed death-ligand 1 (PD-L1) greater than or equal to 1% (primary end point) or less than 1% (prespecified descriptive analysis). We report results with minimum 4 years' follow-up. METHODS: Adults with previously untreated stage IV or recurrent NSCLC were randomized (1:1:1) to nivolumab plus ipilimumab, nivolumab, or chemotherapy (PD-L1 ≥1%); or to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Efficacy included OS and other measures. Safety included timing and management of immune-mediated adverse events (AEs). A post hoc analysis evaluated efficacy in patients who discontinued nivolumab plus ipilimumab due to treatment-related AEs (TRAEs). RESULTS: After 54.8 months' median follow-up, OS remained longer with nivolumab plus ipilimumab versus chemotherapy in patients with PD-L1 greater than or equal to 1% (hazard ratio = 0.76; 95% confidence interval: 0.65-0.90) and PD-L1 less than 1% (0.64; 0.51-0.81); 4-year OS rate with nivolumab plus ipilimumab versus chemotherapy was 29% versus 18% (PD-L1 ≥1%); and 24% versus 10% (PD-L1 <1%). Benefits were observed in both squamous and nonsquamous histologies. In a descriptive analysis, efficacy was improved with nivolumab plus ipilimumab relative to nivolumab (PD-L1 ≥1%) and nivolumab plus chemotherapy (PD-L1 <1%). Safety was consistent with previous reports. The most common immune-mediated AE with nivolumab plus ipilimumab, nivolumab, and nivolumab plus chemotherapy was rash; most immune-mediated AEs (except endocrine events) occurred within 6 months from start of treatment and resolved within 3 months after, mainly with systemic corticosteroids. Patients who discontinued nivolumab plus ipilimumab due to TRAEs had long-term OS benefits, as seen in the all randomized population. CONCLUSIONS: At more than 4 years' minimum follow-up, with all patients off immunotherapy treatment for at least 2 years, first-line nivolumab plus ipilimumab continued to demonstrate durable long-term efficacy in patients with advanced NSCLC. No new safety signals were identified. Immune-mediated AEs occurred early and resolved quickly with guideline-based management. Discontinuation of nivolumab plus ipilimumab due to TRAEs did not have a negative impact on the long-term benefits seen in all randomized patients.
Asunto(s)
Neoplasias Pulmonares , Nivolumab , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Humanos , Ipilimumab/efectos adversos , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Nivolumab/efectos adversosRESUMEN
BACKGROUND: Gastric cancer is the fifth cause of cancer incidence worldwide. Multidisciplinary approaches that improve the survival are needed. Perioperative chemotherapies show improvement in pathological complete remission (pCR) and overall survival (OS), but less than 50% of the patients completed the chemotherapeutic regimen. The recent 5-fluorouracil, leucovorin, oxaliplatin, docetaxel-4 (FLOT4) study shows OS 50 months and pCR 16.6%, but only 46% of the patients completed pre- and postoperative treatment. This case series report evaluated pCR and safety in patients that received complete preoperative chemotherapeutic with FLOT. METHODS: Patients received eight cycles FLOT regimen before surgery. Each cycle comprised 50 mg/m2 docetaxel intravenous (iv) on day 1, 85 mg/m2 oxaliplatin iv on day 1, 200 mg/m2 leucovorin iv on day 1 and 2,600 mg/m2 5-fluorouracil iv in a 24-hour infusion on day 1, every 2 weeks. RESULTS: Fifty-nine patients were evaluated, 58 patients received preoperative cycles. Thirty-one patients received all eight cycles of preoperative therapy. 65.5% patients presented any major adverse event. Thirty-nine patients underwent surgery. Thirty-three biopsy reports were obtained. Six patients (18.2%) presented pCR, 13 patients (39.4%) had no lymph node involvement. OS was 21.32 months. Patients with histology of signet ring carcinoma cells had a shorter survival than other histologies. CONCLUSION: Total neoadjuvant with FLOT chemotherapy presents an adequate safety profile, a similar pathologic regression rate, and a slightly higher rate of completing treatment to report in perioperative FLOT regimen studies. A prospective clinical study with suitable diagnostic, staging tools and an adequate follow-up may prove total neoadjuvant chemotherapy's efficacy.
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Breast cancer currently represents one of the largest public health problems in Mexico and in the world, since it is the first cause of death due to neoplasia in women over 25 years. The first official statistical records in Mexico correspond to 1982, and worldwide to 1926. However, records of very ancient civilizations denote their existence for millennia. This review summarizes part of the history of breast cancer, from Egyptians to present day, including beliefs that were held about this disease, as well as contributions of great scientists who helped understanding and marked the course in prevention and treatment of breast cancer.
El cáncer de mama representa en la actualidad uno de los problemas de salud pública más grandes en México y en el mundo, pues es la primera causa de muerte por neoplasia en mujeres mayores de 25 años. Los primeros registros estadísticos oficiales en México corresponden al año 1982 y a nivel mundial a 1926. Sin embargo, existen registros de civilizaciones antiguas que denotan su existencia durante milenios. En esta revisión se resume parte de la historia del cáncer de mama, desde los egipcios hasta nuestros días y se incluyen las creencias que se tenían acerca de esta enfermedad, así como las aportaciones de grandes científicos que ayudaron a la comprensión y marcaron el rumbo en la prevención y el tratamiento del cáncer de mama.
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BACKGROUND / PURPOSE: The aim of this report is to present our experience with a magnetic-assisted single-site cholecystectomy technique ("magnachole") in pediatric patients. METHODS: We performed a retrospective chart review of all patients who underwent magnachole between 2009 and 2019. We evaluated patients' demographics, diagnosis, operative time, complications, conversion rate and length of stay. Additionally, simple lineal regression analysis was conducted to determine if the surgeon's experience, the patient's age at surgery, the patient's gender or the patient's body weight affected operative time. RESULTS: A total of 101 patients were operated during the analyzed period. The mean age at surgery was 12.6 (range 4 to 19) years, and the mean body weight was 53.7 (range 13.5 to 123) kg. The most frequent indication (91%) was symptomatic cholelithiasis. Mean operative time was 85 (range 45 to 240) min. The mean operative time decreased by 22.7â¯min (pâ¯<â¯0.001, 95% [CI] 10.35 to 35.13) when we compared the first 51 cases to the last 50 cases. Simple lineal regression showed a reduction of 2.6â¯min in operative time per year. Age at surgery, gender, and weight did not influence operative time. There were no intraoperative complications. Only 1 case required an additional port to complete the operation. There were no conversions to open cholecystectomy. Median length of stay was 26â¯h (range 10 to 168). CONCLUSION: The magnachole technique is safe and effective, and has become our preferred surgical approach for children who need a cholecystectomy. As expected, the operative time decreased as surgeons gain experience with the technique. The technique is feasible regardless of the patient's body habitus. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level IV.