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INTRODUCTION: Our aim was to investigate the prevalence of atrial fibrillation (AF) and recently diagnosed lung cancer in the outpatient oncology clinic and to describe the clinical profile, management and outcomes of this population. METHODS: Among 6984 patients visited at the outpatient oncology clinics attending lung cancer patients in five university hospitals from 2017 to 2019, all consecutive subjects with recently diagnosed (<1 year) disease and AF were retrospectively selected and events in follow up were registered. RESULTS: A total of 269 patients (3.9 % of all attended, 71 ± 8 years, 91 % male) were included. Charlson, CHA2DS2-VASc and HAS-BLED indexes were 6.7 ± 2.9, 2.9 ± 1.5 y 2.5 ± 1.2, respectively. Tumour stage was I, II, III and IV in 11 %, 11 %, 33 % and 45 % of them, respectively. Anticoagulants were prescribed to 226 patients (84 %): direct anticoagulants (n = 99;44 %), low molecular weight heparins (n = 69;30 %) and vitamin K antagonists (n = 58;26 %). After 46 months of maximum follow-up, 186 patients died (69 %). Cumulative incidences of events at 3 years were 3.3 ± 1.3 % for stroke/systemic embolism (n = 7); 8.9 ± 2.2 % for thrombotic events (n = 18); 9.9 ± 2.6 % for major bleeding (n = 16), and 15.9 ± 3,0 % for cardiovascular events (n = 33). In patients with early stages of cancer (I-II), 2-year mortality was significantly higher in those with cardiovascular events or major bleeding (85 % vs 25 %, p = 0.01). CONCLUSION: Nearly 4 % or all outpatients in the oncology clinic attending lung cancer present recently diagnosed disease and AF. Major bleeding and cardiovascular event rates are high in this population, with an impact on mortality in early stages of cancer.
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Fibrilação Atrial , Neoplasias Pulmonares , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Pacientes Ambulatoriais , Estudos Retrospectivos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/induzido quimicamente , Hemorragia/induzido quimicamente , Acidente Vascular Cerebral/epidemiologia , Anticoagulantes/uso terapêutico , Fatores de Risco , Medição de RiscoRESUMO
PERLA is a global, double-blind, parallel phase II trial (NCT04581824) comparing efficacy and safety of anti-PD-1 antibodies dostarlimab and pembrolizumab, plus chemotherapy (DCT and PCT, respectively) as first-line treatment in patients with metastatic non-squamous NSCLC without known targetable genomic aberrations. Patients stratified by PD-L1 tumor proportion score and smoking status were randomized 1:1, receiving ≤35 cycles 500 mg dostarlimab or 200 mg pembrolizumab, ≤35 cycles 500 mg/m2 pemetrexed and ≤4 cycles cisplatin (75 mg/m2) or carboplatin (AUC 5 mg/ml/min) Q3W. Primary endpoint was overall response rate (ORR) (blinded independent central review). Secondary endpoints include progression-free survival (PFS) based on investigator assessment, overall survival (OS) and safety. Exploratory endpoints include ORR by PD-L1 subgroup and duration of response. PERLA met its pre-specified endpoint. ORR (n/N; 95% CI) is 45% (55/121; 36.4-54.8) for DCT and 39% (48/122; 30.6-48.6) for PCT (data cut-off: 07 July 23), numerically favoring dostarlimab in PD-L1-positive subgroups. Median PFS (months [95% CI]) is 8.8 (6.7-10.4) for DCT and 6.7 (4.9-7.1) for PCT (HR 0.70 [95% CI: 0.50-0.98]; data cut-off: 04 August 22). Median OS (months [95% CI]) is 19.4 (14.5-NR) for DCT and 15.9 (11.6-19.3) for PCT (HR 0.75 [95% CI: 0.53-1.05]) (data cut-off: 07 July 23). Safety profiles are similar between groups. In this study, DCT shows similar efficacy to PCT and demonstrates clinical efficacy as first-line treatment for patients with metastatic non-squamous NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/patologia , Antígeno B7-H1 , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Eosinophilic enteritis (EE) is characterized by intense eosinophilic infiltrate of the gastrointestinal tract. Clinical manifestations depend on the affected segment and intestinal layer. First-line treatment is systemic corticosteroids; surgery is reserved for complications. 84-year-old male patient with a history of right hemicolectomy and two episodes of intestinal obstruction presented to the ED with abdominal pain, distension, nausea, and vomiting. CBC showed leukocytosis and no eosinophilia. Contrast-enhanced CT revealed stenosis with thickening of the distal intestinal wall and partial intestinal obstruction. Colonoscopy found aphthous ulcers. Histopathology reported EE. The patient received budesonide and metronidazole, with resolution within 24 h.
La enteritis eosinofílica (EE) se caracteriza por infiltrado eosinofilico del tracto GI. Las manifestaciones clínicas dependen de la capa intestinal afectada. Se recomiendan esteroides sistémicos como primera línea de tratamiento, reservando la cirugía para complicaciones. Masculino de 84 años con antecedente de hemicolectomía derecha y dos episodios de oclusión intestinal acude al servicio de urgencias con dolor abdominal, distensión, náusea y vómito. Laboratorio reportó leucocitosis, sin eosinofilia. Tomografía con contraste evidenció estenosis, con engrosamiento de la pared del intestino delgado e imagen compatible con oclusión intestinal. La colonoscopía demostró ulceras en íleon terminal la cual reporto EE. Se inició tratamiento con budesonide y metronidazol, con adecuada respuesta y resolución a las 24 h.
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Enterite , Eosinofilia , Gastrite , Obstrução Intestinal , Masculino , Humanos , Idoso de 80 Anos ou mais , Enterite/complicações , Enterite/diagnóstico , Gastrite/complicações , Gastrite/diagnóstico , Eosinofilia/complicações , Eosinofilia/diagnóstico , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Obstrução Intestinal/patologiaRESUMO
RESUMEN Introducción: Desde el inicio de la pandemia, México fue de los países que presentó tasas de mortalidad más altas por COVID 19. Objetivo: Determinar si la diabetes mellitus tipo 2, la hipertensión arterial y la obesidad incrementan la tasa de mortalidad en pacientes con diagnóstico de COVID-19 que requirieron hospitalización en México. Métodos: Revisión sistemática en Pubmed MeSH, Web of Science, Lilas, Scielo y Google Scholar con los términos MeSH "COVID-19", "SARS-COV2", "Coronavirus", y "México" durante los años 2020 y 2021, incluyendo artículos en inglés y español. Para el proceso de selección de artículos, dos revisores seleccionaron los estudios mientras que otros dos revisores adicionales participaron en el análisis de dichos estudios. Resultados: Se incluyeron 73 estudios realizados en México del 2020 al 2021 con información obtenida a través de las bases de datos del Sistema Nacional de Vigilancia Epidemiológica de México. Se incluyeron pacientes con un promedio de edad de 52,9 años ±13,27, el 64% de los pacientes incluidos fueron mujeres, se reportó una tasa de mortalidad de 6.76% (Min-Max 0.77-73.73%). El 71% de los estudios (52), no reportaron la mortalidad específica relacionada con las comorbilidades. La patología más prevalente fue la obesidad con un 24.23% (Min-Max 11.50-71.00%), seguida de la hipertensión arterial con un 22.23% (Min-Max 2.0-53.96%) y finalmente la diabetes mellitus tipo 2 con un 18.10% (Min-Max 1.83-40.00%). Conclusión: La comorbilidad más común entre los pacientes hospitalizados por COVID 19 en México fue la obesidad, seguida de la diabetes mellitus tipo 2 y por último la hipertensión.
ABSTRACT Introduction: Since the start of the pandemic, Mexico was one of the countries with the highest mortality rates from COVID 19. Objective: To determine if type 2 diabetes mellitus, arterial hypertension, and obesity increase mortality in patients diagnosed with COVID-19 who required hospitalization in Mexico. Methods: Systematic review in Pubmed MeSH, Web of Science, Lilas, Scielo, and Google Scholar with the terms MeSH COVID-19, SARS-COV2, Coronavirus, and Mexico for the years 2020 and 2021, in English or Spanish. Two reviewers selected the studies, two additional reviewers participated in the analysis of the studies. Results: Seventy three studies carried out in Mexico from 2020 to 2021 were included with information obtained from the databases of the National Epidemiological Surveillance System of Mexico. With an average age of 52.9 ± 13.27 years, 64% of the included patients were women, in general, a mortality rate of 16.76% (Min-Max 0.77-73.73%) was reported. 71% of the studies (52) did not report specific mortality related to comorbidities the most prevalent pathology was obesity with 24.23% (Min-Max 11.50-71.00%), followed by arterial hypertension 22.23% (Min-Max 2.0-53.96%) and finally Diabetes mellitus with 18.10% (Min-Max 1.83-40.00%). Conclusion: The most common comorbidity among patients hospitalized for COVID in Mexico was obesity, followed by type 2 diabetes mellitus and hypertension.
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BACKGROUND: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. OBJECTIVES: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. METHODS: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. RESULTS: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. CONCLUSION: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.
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Artrite , Mosaicismo , Adulto , Humanos , Masculino , Feminino , Citocinas/genética , Ferritinas , Glucocorticoides , MutaçãoRESUMO
OBJECTIVES: To determine the incidence of ALK translocations in patients with advanced/metastatic NSCLC in Spain, to describe the clinical characteristics of these patients, and to evaluate the effectiveness and safety of treatment with crizotinib in a real-world setting. METHODS: This is an observational prospective and retrospective cohort study to determine the incidence of ALK translocations and to analyze the effectiveness and safety of crizotinib in a real-world setting. Patient characteristics, treatment patterns, time to best overall response, duration of treatment, objective response rates (ORR), rates of adverse events (AE), progression free survival (PFS) and overall survival (OS) were evaluated in the ALK study cohort of patients treated with crizotinib (prospective and retrospective). ALK incidence and quality of life (QoL) questionnaires were measured from patients included in the prospective cohort. RESULTS: The incidence of ALK translocations was 5.5 % (31 of 559 patients). Compared with ALK-negative patients, ALK-positive patients were significantly younger, predominantly female, and non-smokers. In the crizotinib effectiveness and safety study, 91 patients (42 prospective, 49 retrospective) with ALK-positive NSCLC (43.9 % in first-line, 56.1 % in second or more lines) were included. The ORR was 59.3 % and the median duration of response was 13.5 months (IQR, 5.3-26.2). The median PFS was 15.8 months (95 % CI, 11.8-22.3) and the median OS was 46.5 months, with 53 patients (58.2 %) still alive at data cut-off date. Frequently reported AEs included elevated transaminases, gastrointestinal disorders, and asthenia. Most patients (76.5 %) reported improved or stable scores for global QoL during treatment. CONCLUSIONS: The observed incidence of ALK translocations in NSCLC patients is aligned with published reports. This analysis of the real-world clinical experience in Spain confirms the therapeutic benefit and safety of crizotinib in advanced/metastatic ALK-positive NSCLC. CLINICALTRIALS: gov: NCT02679170.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Feminino , Masculino , Crizotinibe/uso terapêutico , Estudos Retrospectivos , Qualidade de Vida , Quinase do Linfoma Anaplásico/genética , Estudos Prospectivos , Espanha/epidemiologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Transaminases/uso terapêuticoRESUMO
Neoadjuvant chemotherapy (NACT) outcomes vary according to breast cancer (BC) subtype. Since pathologic complete response is one of the most important target endpoints of NACT, further investigation of NACT outcomes in BC is crucial. Thus, identifying sensitive and specific predictors of treatment response for each phenotype would enable early detection of chemoresistance and residual disease, decreasing exposures to ineffective therapies and enhancing overall survival rates. We used liquid chromatography-high-resolution mass spectrometry (LC-HRMS)-based untargeted metabolomics to detect molecular changes in plasma of three different BC subtypes following the same NACT regimen, with the aim of searching for potential predictors of response. The metabolomics data set was analyzed by combining univariate and multivariate statistical strategies. By using ANOVA-simultaneous component analysis (ASCA), we were able to determine the prognostic value of potential biomarker candidates of response to NACT in the triple-negative (TN) subtype. Higher concentrations of docosahexaenoic acid and secondary bile acids were found at basal and presurgery samples, respectively, in the responders group. In addition, the glycohyocholic and glycodeoxycholic acids were able to classify TN patients according to response to treatment and overall survival with an area under the curve model > 0.77. In relation to luminal B (LB) and HER2+ subjects, it should be noted that significant differences were related to time and individual factors. Specifically, tryptophan was identified to be decreased over time in HER2+ patients, whereas LysoPE (22:6) appeared to be increased, but could not be associated with response to NACT. Therefore, the combination of untargeted-based metabolomics along with longitudinal statistical approaches may represent a very useful tool for the improvement of treatment and in administering a more personalized BC follow-up in the clinical practice.
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Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Feminino , Humanos , Metabolômica , Terapia Neoadjuvante/métodosRESUMO
A 102-year-old female with a past medical history of sigmoid volvulus resolved by colonoscopy a year ago presents to the emergency department with sigmoid volvulus, which is resolved by colonoscopy and rectal tube placement. Three days later, she presented abdominal distention and recurrence of the volvulus, for which a surgical resolution was decided. Laparotomy was performed, where sigmoid and cecal volvulus was found. A cecal detorsion and a cecopexy were performed, and an extended left hemicolectomy with a terminal colostomy to treat the sigmoid volvulus. The patient presents an adequate postoperative period and is discharged. Three months later, the patient was in good clinical condition, eating normally without complications. Volvulus refers to the torsion of a segment of the gastrointestinal tract. The most common sites for colonic volvulus are sigmoid and cecum; however, it is infrequent for these to occur together. We only found six cases reported in the literature of synchronous volvulus of the cecum and sigmoid colon. None of the cases was the diagnosis made preoperatively, suggesting a difficult diagnosis. Treatment depends on the patient's condition; in most reported cases, a subtotal colectomy was performed. The prognosis depends on prompt surgical intervention.
Se reporta un caso de una femenina de 102 años de edad, con antecedente de vólvulo sigmoideo resuelto por medio de colonoscopia hace un año. Se presenta al servicio de urgencias con vólvulo sigmoideo, el cual se resuelve por medio de colonoscopia y se coloca un tubo rectal. Tres días después, presenta nuevamente distensión y recurrencia del vólvulo, por lo cual se decide resolución quirúrgica. Durante la cirugía se encuentra un vólvulo sigmoideo, así como cecal. Se realiza una detorsión con cecopexia y hemicolectomía izquierda con colostomía terminal. La paciente presenta adecuada evolución. Sin complicaciones tres meses después. Vólvulo se refiere a la torsión de un segmento del tracto gastrointestinal. Los sitios más comunes de vólvulos colónicos son sigmoides y ciego, sin embargo, es extremadamente raro que estos se presenten juntos. Únicamente encontramos seis casos reportados en la literatura de vólvulo sincronico sigmoideo y cecal. En ninguno de los casos, se hizo el diagnóstico preoperatoriamente, lo que sugiere un diagnóstico complicado. El tratamiento depende del estado del paciente; en la mayoría de los casos reportados, se realizó una colectomía subtotal. El pronóstico depende de la intervención quirúrgica oportuna.
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Obstrução Intestinal , Volvo Intestinal , Idoso de 80 Anos ou mais , Ceco/diagnóstico por imagem , Ceco/cirurgia , Colectomia , Colo Sigmoide/diagnóstico por imagem , Colo Sigmoide/cirurgia , Feminino , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Volvo Intestinal/complicações , Volvo Intestinal/diagnóstico por imagem , Volvo Intestinal/cirurgiaRESUMO
ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, keeps spreading globally. Evidence suggests that a subgroup of patients with severe symptomatology might have cytokine storms, which increases mortality. The use of interleukin-6 (IL-6) inhibitors may help in controlling the pathological immune response to the virus. Tocilizumab, a monoclonal antibody against IL-6, stands as an optional treatment for COVID-19 patients presenting this inflammatory hyper-response.We conducted a retrospective, observational, cohort study including 50 patients affected by COVID-19 with severe pneumonia and poor prognosis criteria, who have also undergone standard treatment; 36 of these patients additionally received tocilizumab in an early stage. The need for intensive care unit (ICU) admission, mortality, recovery of respiratory function, and improvement of biochemical and hematological parameters were compared between cohorts.Most patients were men, non-smokers and the most frequently reported comorbidities were hypertension and diabetes. Recurrent symptoms were fever, cough, and dyspnoea. 54.8% of patients from the tocilizumab group needed intubation, while in the control group 85.7% needed it. Treatment with tocilizumab significatively increased IL-6 levels, (554.45; CI 95% 186.69, 1032.93; Pâ<â.05) while C-reactive protein mean levels were reduced (-108.19; CI 95% -140.15, -75.33; Pâ<â.05), but no significant difference was found between cohorts. In comparison with the controls, tocilizumab reduced mortality (25.0% vs 42.9%, Pâ=â.021) and the number of ICU admissions (63.9% vs 100.0%, Pâ=â.021). 44.1% of patients treated with tocilizumab showed favorable radiological evolution, when compared with 15.4% of patients from the control group.Tocilizumab may improve clinical symptoms and mitigate deterioration observed in severe COVID-19 patients, and could be considered as an effective therapeutic option in subjects experiencing a significant inflammatory response to the disease.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Tratamento Farmacológico da COVID-19 , Unidades de Terapia Intensiva/estatística & dados numéricos , Interleucina-6/antagonistas & inibidores , Pneumonia Viral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/diagnóstico , Pneumonia Viral/etiologia , Pneumonia Viral/mortalidade , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: Identifying patient characteristics that define a worse disease prognosis or "high tumor burden" (HTB) status is essential for clinical decision-making and treatment selection in metastatic non-small cell lung cancer (mNSCLC). We aimed to define this concept based on the experience of oncologists in clinical practice. PATIENTS AND METHODS: A representative sample of Spanish experts was selected and asked to complete an online survey regarding the definition of HTB according to their personal experience. RESULTS: HTB was identified by the oncologists (N = 81) as one of the principle factors influencing first-line treatment decision-making. According to the experts, HTB is mainly defined by the number of metastatic lesions (n = 45, 56%), location (n = 34, 42%), tumor size (sum of diameters of target lesions; n = 26, 32%) and liver involvement (n = 24, 30). High lactate dehydrogenase (LDH) levels were also associated with HTB. Almost half of respondents (n = 33, 41%) believed that one metastatic lesion was sufficient to consider a patient as presenting HTB, 72% (n = 58) considered that two were necessary and 99% (n = 80) three. Liver (n = 76, 100%) followed by brain (n = 65, 86%) were the main metastatic sites associated with HTB. Tumor size ranging from 6 cm to 10 cm as well as high LDH levels (three times the upper limit) defined the concept for 82% (n = 62) and 100% (n = 76) of oncologists, respectively. CONCLUSION: In the real-world setting, according to experts, HTB is defined by the number of metastatic lesions, location of metastases, tumor size and by high LDH levels. Given the relevance of this concept, efforts should be made to unify its definition and to further explore its potential as a prognostic factor for mNSCLC patients.
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INTRODUCTION: Flaviviridae family belongs to the Spondweni serocomplex, which is mainly transmitted by vectors from the Aedes genus. Zika virus (ZIKV) is part of this genus. It was initially reported in Brazil in December 2014 as an unknown acute generalized exanthematous disease and was subsequently identified as ZIKV infection. ZIKV became widespread all over Brazil and was linked with potential cases of microcephaly. CASE REPORT: We report a case of a 28-year-old Colombian woman, who came to the Obstetric Department with an assumed conglomerate of fetal abnormalities detected via ultrasonography, which was performed at 29.5 weeks of gestation. The patient presented with multiple abnormalities, which range from a suggested Arnold-Chiari malformation, compromising the lateral and third ventricles, liver calcifications, bilateral pyelocalic dilatations, other brain anomalies, and microcephaly. At 12 weeks of gestation, the vertical transmission of ZIKV was suspected. At 38.6 weeks of gestation, the newborn was delivered, with the weight in the 10th percentile (3,180 g), height in the 10th percentile (48 cm), and cephalic circumference under the 2nd percentile (31 cm). Due to the physical findings, brain magnetic resonance imaging (MRI) was performed, revealing a small and deviated brain stem, narrowing of the posterior fossa, a giant posterior fossa cyst with ventricular dilatation, a severe cortical and white matter thinning, cerebellar vermis with hypoplasia, and superior and lateral displacement of the cerebellum. In addition, hydrocephalus was displayed by the axial sequence, and the cerebral cortex was also compromised with lissencephaly. Schizencephaly was found with left frontal open-lip, and no intracranial calcifications were found. Two novel heterozygous nonsense mutations were identified using whole-exome sequencing, and both are located in exon 8 under the affection of ZIKV congenital syndrome (CZS) that produced a premature stop codon resulting in the truncation of the cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) protein. CONCLUSION: We used molecular and microbiological assessments to report the initial case of vertically transmitted ZIKV infection with congenital syndrome associated with a neurological syndrome, where a mutation in the CDK5RAP2 gene was also identified. The CDK5RAP2 gene encodes a pericentriolar protein that intervenes in microtubule nucleation and centriole attachment. Diallelic mutation has previously been associated with primary microcephaly.
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PURPOSE: The aim of this study is to identify differential metabolomic signatures in plasma samples of distinct subtypes of breast cancer patients that could be used in clinical practice as diagnostic biomarkers for these molecular phenotypes and to provide a more individualized and accurate therapeutic procedure. METHODS: Untargeted LC-HRMS metabolomics approach in positive and negative electrospray ionization mode was used to analyze plasma samples from LA, LB, HER2+ and TN breast cancer patients and healthy controls in order to determine specific metabolomic profiles through univariate and multivariate statistical data analysis. RESULTS: We tentatively identified altered metabolites displaying concentration variations among the four breast cancer molecular subtypes. We found a biomarker panel of 5 candidates in LA, 7 in LB, 5 in HER2 and 3 in TN that were able to discriminate each breast cancer subtype with a false discovery range corrected p-value < 0.05 and a fold-change cutoff value > 1.3. The model clinical value was evaluated with the AUROC, providing diagnostic capacities above 0.85. CONCLUSION: Our study identifies metabolic profiling differences in molecular phenotypes of breast cancer. This may represent a key step towards therapy improvement in personalized medicine and prioritization of tailored therapeutic intervention strategies.
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Echocardiographic alterations have been described in obesity, but their modifications after bariatric surgery (BS) and mechanisms are little known, mostly in normotensive patients. We aimed to analyze cardiac changes 1 year post-BS and to explore possible mechanisms. A cohort of patients with severe obesity (58% normotensives) were prospectively recruited and examined before surgery and after 12 months. Clinical and echocardiographic data, 24 h BP, renin-angiotensin-aldosterone system (RAAS) components, cytokines, and inflammatory markers were analyzed at these two time points. Overall reduction in body weight was mean (IQR) = 30.0% (25.9-33.8). There were statistically significant decreases in left ventricle mass index2.7 (LVMI)2.7 , septum thickness (ST), posterior wall thickness (PWT), relative wall thickness (RWT), and E/e', both in the whole cohort and in patients without RAAS blockers (p ≤ .04 for all). Plasma renin activity (PRA) decreased from (median, IQR) = 0.8 (0.3;1.35) to 0.4 (0.2;0.93) ng/ml/h, plasma aldosterone from 92 (58.6;126) to 68.1 (56.2;83.4) ng/dl, and angiotensin-converting enzyme (ACE)-2 activity from 7.7 (5.7;11.8) to 6.8 (5.3;11.2) RFU/µl/h, p < .05. The body weight loss correlated with a decrease in both 24 h SBP and 24 h DBP (Pearson's coefficient 0.353, p = .022 and 0.384, p = .012, respectively). Variation (Δ) of body weight correlated with ΔE/e' (Pearson's coeff. 0.414, p = .008) and with Δ lateral e' (Pearson's coeff. = -0.363, p = .018). Generalized linear models showed that ΔPRA was an independent variable for the final (12-months post-BS) LVMI2.7 (p = .028). No other changes in cardiac parameters correlated with ΔBP. In addition to the respective baseline value, final values of PWT and RWT were dependent on 12-month Δ of PRA, ACE, and ACE/ACE2 (p < .03 for all). We conclude that there are cardiac changes post-BS in patients with severe obesity, normotensives included. Structural changes appear to be related to modifications in the renin-angiotensin axis.
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Cirurgia Bariátrica , Hipertensão , Aldosterona , Pressão Sanguínea , Humanos , Obesidade/complicações , Obesidade/cirurgia , Renina , Sistema Renina-AngiotensinaRESUMO
BACKGROUND: Lung cancer is currently the leading cause of cancer death. Despite its high incidence and mortality, there are few studies describing its symptoms at diagnosis broken down by tumour stage and tobacco use. Accordingly, this study was proposed to describe the frequency of the most common symptoms of non-small cell lung cancer and small cell lung cancer (SCLC) at diagnosis, with a breakdown by stage and tobacco use. PATIENTS AND METHODS: Cases were collected from the Spanish Thoracic Tumour Registry, a nationwide registry sponsored by the Spanish Lung Cancer Group. More than 50 hospitals recruited histologically confirmed lung cancer cases and information was gathered through personal interview plus data contained in the electronic clinical record. There were no data available on the lag between the appearance of the first symptoms and diagnosis of lung cancer. RESULTS: A total of 9876 patients (74% male, median age 64 years) were recruited from 2016 to 2019. Of these, 12.5% presented with SCLC. Stage IV was the most frequent stage at diagnosis (46.6%), and the most frequent symptom was cough (33.9%), followed by dyspnoea (26.7%). No symptom was present in 59% of patients diagnosed in stage I; 40% of stage I patients presented with at least one symptom, while 27.7% of patients in stage IV had no symptoms at diagnosis. Cough was the most frequent symptom in SCLC (40.6%), followed by dyspnoea (34.3%). The number of symptoms was similar across the respective smoking categories in SCLC, and differences between the symptoms analysed did not exceed 7% in any case. CONCLUSION: The absence of the most frequent symptoms (ie, cough, pain, dyspnoea) should not lead to a decision to rule out the presence of lung cancer. A relevant percentage of stage IV patients displayed no symptoms at diagnosis.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Fumar/efeitos adversos , Fumar/epidemiologiaRESUMO
OBJECTIVES: Progression-free survival (PFS) and response rate to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) varies in patients with non-small-cell lung cancer (NSCLC) driven byEGFR mutations, suggesting that other genetic alterations may influence oncogene addiction. Low BRCA1 mRNA levels correlate with longer PFS in erlotinib-treated EGFR-mutant NSCLC patients. Since the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, may attenuate and/or prevent BRCA1 expression, the addition of olaparib to gefitinib could improve outcome in EGFR-mutant advanced NSCLC. MATERIALS AND METHODS: GOAL was a multicenter, randomized phase IB/II study performed in two countries, Spain and Mexico. Eligible patients were 18 years or older, treatment-naïve, pathologically confirmed stage IV NSCLC, with centrally confirmed EGFR mutations and measurable disease. Patients were randomly allocated (1:1) to receive gefitinib 250â¯mg daily or gefitinib 250â¯mg daily plus olaparib 200â¯mg three times daily in 28-day cycles. The primary endpoint was PFS. Secondary endpoints included overall survival (OS), response rate, safety and tolerability. RESULTS: Between September 2013, and July 2016, 182 patients underwent randomization, 91 received gefitinib and 91 received gefitinib plus olaparib. There were no differences in gender, age, smoking status, performance status, presence of bone and brain metastases or type ofEGFR mutation. Median PFS was 10.9 months (95 % CI 9.3-13.3) in the gefitinib arm and 12.8 months (95 % CI 9.1-14.7) in the gefitinib plus olaparib arm (HR 1.38, 95 % CI 1.00-1.92; pâ¯=â¯0.124). The most common adverse events were anemia, 78 % in gefitinib plus olaparib group, 38 % in gefitinib arm, diarrhea, 65 % and 60 %, and fatigue, 40 % and 32 %, respectively. CONCLUSIONS: The gefitinib plus olaparib combination did not provide significant benefit over gefitinib alone. The combination's safety profile showed an increase in hematological and gastrointestinal toxicity, compared to gefitinib alone, however, no relevant adverse events were noted.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Intervalo Livre de Doença , Receptores ErbB/genética , Gefitinibe/uso terapêutico , Objetivos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , México , Mutação , Ftalazinas , Piperazinas , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , EspanhaRESUMO
PURPOSE: Osimertinib has proven efficacy in EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) patients; however, its benefits have not been evaluated in a real-world setting. METHODS: ASTRIS is a single-arm, open-label, multinational study to evaluate the efficacy and safety of osimertinib for the treatment of EGFR T790M mutation-positive NSCLC. We present the study design and preliminary cut-off analysis results (as of October 2017) describing the baseline characteristics and methodology for T790M mutation detection in the Spanish cohort. RESULTS: The Spanish cohort included 131 patients from a total 3014 patients. Forty patients (28.1%) were still undergoing therapy at the time of cut-off; 68.7% were women and 97.7% were Caucasian, with a mean age of 64.8 (SD 11.7) years. The most common type of sample for evaluating T790M mutations was tissue (55.0%), and samples were obtained from the primary tumor in 61.1% of cases. Mutation analysis was performed by the local laboratory in 60.3% of cases and using the Roche Cobas® EGFR assay in 43.5% of cases. CONCLUSIONS: ASTRIS is expected to confirm the benefits of osimertinib in a real-world setting. Data on real-world practices for the detection of the EGFR T790M mutation may provide additional information for the designing of guidelines for best practices.
Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Acrilamidas/efeitos adversos , Administração Oral , Idoso , Compostos de Anilina/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Técnicas de Genotipagem , Humanos , Internacionalidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , EspanhaRESUMO
INTRODUCTION: Receptor activator of NF-kB ligand stimulates NF-kB-dependent cell signaling and acts as the primary signal for bone resorption. Retrospective analysis of a large trial comparing denosumab versus zoledronic acid in bone metastatic solid tumors suggested significant overall survival (OS) advantage for patients with lung cancer with denosumab (p = 0.01). The randomized open-label phase III SPLENDOUR trial was designed to evaluate whether the addition of denosumab to standard first-line platinum-based doublet chemotherapy improved OS in advanced NSCLC. METHODS: Patients with stage IV NSCLC were randomized in a 1:1 ratio to either chemotherapy with or without denosumab (120 mg every 3-4 wks), stratified by the presence of bone metastases (at diagnosis), Eastern Cooperative Oncology Group performance status, histology, and region. To detect an OS increase from 9 to 11.25 months (hazard ratio [HR] = 0.80), 847 OS events were required. The trial closed prematurely owing to decreasing accrual rate. RESULTS: A total of 514 patients were randomized, with 509 receiving one or more doses of the assigned treatment (chemotherapy: 252, chemotherapy-denosumab: 257). The median age was 66.1 years, 71% were men, and 59% were former smokers. Bone metastases were identified in 275 patients (53%). Median OS (95% confidence interval [CI]) was 8.7 (7.6-11.0) months in the control arm versus 8.2 (7.5-10.4) months in the chemotherapy-denosumab arm (HR = 0.96; 95% CI: 0.78-1.19; one-sided p = 0.36). For patients with bone metastasis, HR was 1.02 (95% CI: 0.77-1.35), whereas for those without, HR was 0.90 (95% CI: 0.66-1.23). Adverse events grade 3 or greater were observed in 40.9%, 5.2%, 8.7% versus 45.5%, 10.9%, 10.5% of patients. Conditional power for OS benefit was less than or equal to 10%. CONCLUSIONS: Denosumab was well-tolerated without unexpected safety concerns. There was no OS improvement for denosumab when added to chemotherapy in the intention-to-treat population and the subgroups with and without bone metastases. Our data do not provide evidence of a clinical benefit for denosumab in patients with NSCLC without bone metastases.