Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients

Background: Immunotherapy increases overall response rate (ORR) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC). Prognostic and predictive factors are a high need. Patients and methods: Retrospective review of NSCLC patients treated with nivolumab was performed. Analyzed variables included age, sex, stage, performance status (PS), location of metastases, presence of tumour-related symptoms and comorbidities, number of metastasis locations, previous chemotherapy, anti-angiogenic and radiotherapy treatments, and analytical data from the standard blood count and biochemistry. Results: A total of 175 patients were included. Median age was 61.5 years, 73.1% were men, 77.7% were ECOG-PS 0-1, and 86.7% were included with stage IV disease. Histology was non-squamous in 77.1%. Sixty-five received nivolumab in second line (37.1%). Thirty-eight patients had brain metastasis (22%), and 39 (22.3%) liver metastasis and 126 (72%) had more than one metastatic location. The ORR was 15.7% with median Progression free survival (PFS) 2.8 months and median OS 5.81 months. Stage III vs IV and time since the beginning of the previous line of treatment ≥ 6 vs < 6 months were associated with better response. PS 2, time since the previous line of treatment < 6 vs ≥ 6 months, and more than one metastatic location were independently associated with shorter OS in multivariable analysis (7.8 vs 2.7 months, 11.2 vs 4.6 months, and 9.4 vs 5.1 month). Finally, time since the previous treatment < 6 vs ≥ 6 months and more than one metastatic location were independently associated with shorter PFS in multivariable analysis (4.3 vs 2.3 months and 4.7 vs 2.3 months). Conclusion: Poor PS, short period of time since the previous treatment, and more than one metastatic location were associated with poorer prognostic

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Correction to: Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients.

Clinical and Translational Oncology.

Modelo de docencia basado en competencias: revisión breve y aplicación práctica en anestesia para cirugía torácica / Teaching model based on competencies: Brief review and practical application in anesthesia for thoracic surgery

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Predictive and prognostic clinical and pathological factors of nivolumab efficacy in non-small-cell lung cancer patients.

BACKGROUND: Immunotherapy increases overall response rate (ORR) and overall survival (OS) in patients with non-small-cell lung cancer (NSCLC). Prognostic and predictive factors are a high need. PATIENTS AND METHODS: Retrospective review of NSCLC patients treated with nivolumab was performed. Analyzed variables included age, sex, stage, performance status (PS), location of metastases, presence of tumour-related symptoms and comorbidities, number of metastasis locations, previous chemotherapy, anti-angiogenic and radiotherapy treatments, and analytical data from the standard blood count and biochemistry. RESULTS: A total of 175 patients were included. Median age was 61.5 years, 73.1% were men, 77.7% were ECOG-PS 0-1, and 86.7% were included with stage IV disease. Histology was non-squamous in 77.1%. Sixty-five received nivolumab in second line (37.1%). Thirty-eight patients had brain metastasis (22%), and 39 (22.3%) liver metastasis and 126 (72%) had more than one metastatic location. The ORR was 15.7% with median Progression free survival (PFS) 2.8 months and median OS 5.81 months. Stage III vs IV and time since the beginning of the previous line of treatment ≥ 6 vs < 6 months were associated with better response. PS 2, time since the previous line of treatment < 6 vs ≥ 6 months, and more than one metastatic location were independently associated with shorter OS in multivariable analysis (7.8 vs 2.7 months, 11.2 vs 4.6 months, and 9.4 vs 5.1 month). Finally, time since the previous treatment < 6 vs ≥ 6 months and more than one metastatic location were independently associated with shorter PFS in multivariable analysis (4.3 vs 2.3 months and 4.7 vs 2.3 months). CONCLUSION: Poor PS, short period of time since the previous treatment, and more than one metastatic location were associated with poorer prognostic.

Epidemiological characteristics of a Spanish cohort of patients diagnosed with squamous cell carcinoma of head and neck: distribution of risk factors by tumor location

Purpose. Head and neck cancer is a highly heterogeneous disease comprising a large number of tumors located in the cervicofacial area. This study aimed to determine the epidemiological characteristics of squamous-cell carcinomas of the head and neck in the Spanish population, and the distribution of risk factors based on tumor locations. Methods/patients. A cohort of 459 patients (75 oral cavity, 167 oro-/hypopharyngeal and 217 laryngeal cancers) recruited in 19 hospitals participating in the Spanish head and neck cancer cooperative group were included over 3 years (2012-2014). Epidemiological parameters and risk factors were obtained from a self-administered questionnaire, and tumor characteristics were obtained from clinical records. Multivariate multinomial logistic regression was used to assess factors associated with tumor location. Results. Most patients were males (88.4 %), smokers (95 %) and drinkers (76.5 %). Relative to laryngeal cancer, pharyngeal cancer and oral cancer were more common in women than men (OR 3.58, p = 0.003 and 4.33, p = 0.001, respectively); pharyngeal cancer was more associated with rural environment (OR 1.81, p = 0.007) and weekly alcohol intake (10-140 g: OR 2.53, p = 0.012; 141-280 g: OR 2.47, p = 0.023; >280 g: OR 3.20, p = 0.001) and less associated with pack-years of smoking (21-40 packs: OR 0.46, p = 0.045; 41-70 packs: OR 0.43, p = 0.023; ≥71 packs: OR 3.20, p = 0.015). Conclusions. The distribution of these tumors differs between the sexes, with a higher proportion of oral cavity and pharyngeal tumors in women than in men. Oro-/hypopharyngeal cancers were more strongly associated with rural areas and with alcohol consumption, although less strongly associated with smoking than laryngeal tumors (AU)

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Epidemiological characteristics of a Spanish cohort of patients diagnosed with squamous cell carcinoma of head and neck: distribution of risk factors by tumor location.

PURPOSE: Head and neck cancer is a highly heterogeneous disease comprising a large number of tumors located in the cervicofacial area. This study aimed to determine the epidemiological characteristics of squamous-cell carcinomas of the head and neck in the Spanish population, and the distribution of risk factors based on tumor locations. METHODS/PATIENTS: A cohort of 459 patients (75 oral cavity, 167 oro-/hypopharyngeal and 217 laryngeal cancers) recruited in 19 hospitals participating in the Spanish head and neck cancer cooperative group were included over 3 years (2012-2014). Epidemiological parameters and risk factors were obtained from a self-administered questionnaire, and tumor characteristics were obtained from clinical records. Multivariate multinomial logistic regression was used to assess factors associated with tumor location. RESULTS: Most patients were males (88.4 %), smokers (95 %) and drinkers (76.5 %). Relative to laryngeal cancer, pharyngeal cancer and oral cancer were more common in women than men (OR 3.58, p = 0.003 and 4.33, p = 0.001, respectively); pharyngeal cancer was more associated with rural environment (OR 1.81, p = 0.007) and weekly alcohol intake (10-140 g: OR 2.53, p = 0.012; 141-280 g: OR 2.47, p = 0.023; >280 g: OR 3.20, p = 0.001) and less associated with pack-years of smoking (21-40 packs: OR 0.46, p = 0.045; 41-70 packs: OR 0.43, p = 0.023; ≥71 packs: OR 3.20, p = 0.015). CONCLUSIONS: The distribution of these tumors differs between the sexes, with a higher proportion of oral cavity and pharyngeal tumors in women than in men. Oro-/hypopharyngeal cancers were more strongly associated with rural areas and with alcohol consumption, although less strongly associated with smoking than laryngeal tumors.

Listeria y embarazo: a propósito de un caso / Listeria and pregnancy: a case report

Se presenta el caso de una mujer que, en la semana 35 de gestación, tuvo un parto por cesárea urgente debido a un desprendimiento prematuro de placenta. El recién nacido presentó un pico febril a las 30 horas de vida y empeoramiento clínico; se aisló en frotis periférico Listeria monocytogenes. Para prevenir la listeriosis, es preciso establecer medidas seguras durante el embarazo que eviten la contaminación y el crecimiento de L. monocytogenes en la cadena alimentaria

We report the case of a woman who with 35 weeks of gestation had a emergency cesarean section because she had a placental abruption. The newborn has a fever peak at 30 hours of life and clinical worsening, is isolated peripheral smear Listeria monocytogenes. To prevent listeriosis establish reliable measurements during pregnancy to prevent contamination and growth of L. monocytogenes in the food chain

Actualidad de los cuidados paliativos. Revisión de una situación poco estandarizada / The current situation of palliative care. Review of a non-standardized situation

En los últimos 50 años la medicina ha evolucionado más que en los dos siglos anteriores. Sin embargo, existen en la actualidad multitud de patologías que la medicina contemporánea no ha sido capaz de solventar. Hasta hace tan solo unas décadas, los niños diagnosticados de cáncer fallecían en poco tiempo. Así pues, esto ha ido modificándose y más de la mitad llegan a ser supervivientes a largo plazo. Los cuidados paliativos como especialidad se han desarrollado de forma marcada en los últimos años. Sin embargo, destaca una parcela de ella que todavía se encuentra muy lejos de estar establecida, los cuidados paliativos pediátricos (CPP). Los niños presentan necesidades diferentes que es necesario atender. Se pretende revisar el concepto de CPP, haciendo hincapié en las diferencias que presentan los niños con respecto a los adultos y en su problemática específica (AU)

In the last 50 years medicine has evolved more than in the previous two centuries but there are currently many pathologies that modern medicine has not been able to cure. Until a mere few decades ago, children diagnosed with cancer died within a short time. However, this has gradually changed and, nowadays, over half of them become long-term survivors. Palliative care as a medical specialization has markedly developed in recent years. Nevertheless, there is a specific part that is still far from being established, pediatric palliative care (PPC). Children have different needs to be attended. PPC should be reviewed with a special focus on the precise differences present in children and their specific problems (AU)

Timectomía toracoscópica con insuflación de dióxido de carbono / Thoracoscopic thymectomy with carbon dioxide insufflation in the mediastinum

Presentamos el caso de un varón de 71 años diagnosticado de timoma. Se interviene al paciente mediante timectomía con visión mediante toracoscopia e insuflación del mediastino con dióxido de carbono. Durante el procedimiento, en ventilación unipulmonar, el paciente sufre un deterioro respiratorio importante. Se observa el colapso del pulmón debido al paso del dióxido de carbono del mediastino al tórax contralateral por la apertura de la pleura. Se decide volver a la ventilación bipulmonar, con mejoría de la oxigenación en gasometría arterial, presiones en la vía respiratoria y estabilización de pCO2 y pH. Se pudo mantener el abordaje y la técnica con dióxido de carbono, puesto que no afectó al campo quirúrgico. Esta técnica presenta complicaciones importantes asociadas, y en caso de realizarse estaría indicado hacerlo en ventilación bipulmonar (AU)

The case is presented of a 71 year-old male, diagnosed with a thymoma. A thoracoscopic thymectomy was performed using the carbon dioxide insufflation technique in the mediastinum. During the procedure, while performing one-lung ventilation, the patient's respiration worsened. The contralateral lung had collapsed, as carbon dioxide was travelling from the mediastinum to the thorax through the opened pleura. Two-lung ventilation was decided upon, which clearly improved oxygenation in the arterial gases and airway pressures. Both pH and pCO2 stabilized. The surgical approach and the carbon dioxide technique were continued because 2-lung ventilation did not affect the surgical procedure. This technique has many serious complications and it should always be performed using 2-lung ventilation (AU)

[Thoracoscopic thymectomy with carbon dioxide insufflation in the mediastinum]. / Timectomía toracoscópica con insuflación de dióxido de carbono.

The case is presented of a 71 year-old male, diagnosed with a thymoma. A thoracoscopic thymectomy was performed using the carbon dioxide insufflation technique in the mediastinum. During the procedure, while performing one-lung ventilation, the patient's respiration worsened. The contralateral lung had collapsed, as carbon dioxide was travelling from the mediastinum to the thorax through the opened pleura. Two-lung ventilation was decided upon, which clearly improved oxygenation in the arterial gases and airway pressures. Both pH and pCO2 stabilized. The surgical approach and the carbon dioxide technique were continued because 2-lung ventilation did not affect the surgical procedure. This technique has many serious complications and it should always be performed using 2-lung ventilation.

[Evaluation of the safety of stress echocardiography in Spain and Portugal]. / Evaluación de la seguridad de la ecocardiografía de estrés en España y Portugal.

UNLABELLED: INTRODUCTION. There are few studies that evaluate the safety of stress echocardiography with discordant results. They are done in well-trained centers with highly selected populations leading to selection bias. OBJECTIVE: To assess the safety of the different modalities of stress echocardiography in Spain and Portugal. METHOD: Severe complications were retrospectively analyzed during the stress echocardiography performed in 29 hospitals in Portugal and Spain, from the beginning of their activity to September, 1999. In this period 22,105 stress echocardiograms were performed: 10,975 exercise echos, 2,969 low dose dobutamine echos, 6,832 high dose dobutamine echocardiograms, 1,276 dypiridamole echocardiograms, 41 paced echocardiograms and 12 with adenosine. A complication was defined as severe when it was life-threatening or led to hospital admission. RESULTS: We registered 26 complications, one death, 3 ventricular fibrillations, 10 sustained ventricular tachycardias, 2 complete atrioventricular blocks, 6 acute myocardial infarctions, 2 ruptures of the free wall or ventricular septal defects, 1 transient ischemic attack and 1 severe symptomatic hypotension. We had one severe complication for every 2,743 exercise stress, 1 every 1,231 dypiridamole, 1 every 325 high dose dobutamine without any complications with low dose dobutamine stress. We found a relationship between experience in dobutamine stress echocardiography and the frequency of complications. Three complications appeared once the test was finished. CONCLUSIONS: The stress echocardiography is a safe technique, but not harmless. The exercise stress echo is the safest of all the modalties of stress echocardiography. There is a relation between experience and the number of complications.

[Influence of pre-infarction angina on mid-term mortality after acute myocardial infarction]. / Influencia de la angina preinfarto en la mortalidad a medio plazo tras infarto agudo de miocardio.

INTRODUCTION AND OBJECTIVES: Pre-infarction angina may reduce the extent of myocardial cell necrosis and improves the prognosis after myocardial infarction. The aim of this study was to analyze the total mortality six-month after acute myocardial infarction according to the presence or absence of pre-infarction angina. METHODS: One hundred seventy-five consecutive patients with acute myocardial infarction were prospectively included, 72 (41.4%) with pre-infarction angina. They were followed for 6 months. There were 16 deaths (15.5%) in the group of patients without pre-infarction angina and 7 (9.7%) in the group with pre-infarction angina (log-rank = 1.03; p = 0.311). The hazard-risk function curves showed a higher risk of death during the entire follow-up in the group without pre-infarction angina. In the multivariate logistic regression model, the presence of pre-infarction angina does not significantly reduce the risk of death (OR = 0.43; CI 95% = 0.09-2. 22; p = 0.303). We detected a significant interaction between treatment with sulfonylureas before the infarction and the presence of pre-infarction angina (p = 0.017). CONCLUSIONS: In this study no significant differences were observed in total mortality six months after acute myocardial infarction according to the presence of pre-infarction angina. However, the risk of death seemed to be higher in the group of patients without pre-infarction angina during the entire follow-up. A significant interaction was found between the treatment with sulfonylurea drugs before infarction and the presence of pre-infarction angina.

[Doppler tissue imaging of the mitral annulus in patients with left ventricular systolic dysfunction. Assessment of diastolic function]. / Doppler tisular del anillo mitral en pacientes con disfunción sistólica ventricular izquierda. Análisis de la función diastólica.

INTRODUCTION AND OBJECTIVES: We assessed the Doppler tissue imaging technique in the left mitral annulus of patients with left ventricular systolic dysfunction since the technique has been used to evaluate diastolic function of the left ventricle and the values obtained have been considered to be relatively independent of the preload. PATIENTS AND METHODS: Patients (n = 46) with an ejection fraction < 40% in sinus rhythm without mitral regurgitation underwent pulsed wave Doppler analyses of mitral inflow (E and A waves), pulmonary venous flow (S, D and Ar waves) and Doppler tissue imaging of the mitral annulus (Ea and Aa waves). RESULTS: Overall, the linear correlations between the different Doppler measurements were poor. When sub-grouped with respect to E/A < 1 and E/A >= 1 (Groups 1 and 2, respectively), the Ea value did not significantly differ between the two groups: 5.0 cm/s (4.2/6.0) vs 6.2 cm/s (5.5/8. 2) respectively; p = 0.129 and neither did the E/Ea quotient: 10.2 (8.2/14.5) vs 12.9 (9.1/17.4) respectively; p = 0.160. Atrial size was significantly greater in Group 2: 20.0 cm2 (18.0/22.0) vs 25.0 cm2 (20.0/29.0) respectively; p = 0.000. The Ea/Aa quotient was pseudo-normalized in Group 2: 0.65 (0.48/0.83) vs 1.15 (0.75/1.71) respectively; p = 0.001. CONCLUSIONS: In patients with left ventricular systolic dysfunction the Ea/Aa value tends towards pseudo-normalization when the preload is increased. This does not apply to the values of Ea, E/Ea or to size of the left atrium. Therefore, Doppler tissue imaging of the left mitral annulus is valuable in the assessment of left ventricular dysfunction and the problem of pseudo-normalization due to preloading.

[The effect of pre-infarction unstable angina on the size of myocardial necrosis]. / Efecto de la angina inestable preinfarto en el tamaño de la necrosis miocárdica.

INTRODUCTION AND OBJECTIVES: Recent studies suggest that preinfarction angina (PA) might induce less myocardial necrosis. The objective of this study is to evaluate whether patients with PA have smaller myocardial infarctions. METHODS: Patients with acute myocardial infarction of less than 12 hours since the onset symptoms were included. PA was defined as unstable angina at rest during the 7 days before the infarction. Infarct size was assessed with the area under the curve of CK-MB levels in the 24 hours following the onset of the infarct. RESULTS: One hundred-seventy nine patients were included, 75 (41.9%) with PA. There were more men in the group with PA (89.3% vs 70.2%, p = 0.004) and a higher prevalence of ex-smokers (38.7% vs 19.2%, p = 0.006). We did not find significant differences in myocardial infarction size between both groups, but a statistically significant interaction between PA and pre-treatment with sulfonylurea drugs was noted (p = 0.050). CONCLUSIONS: Preinfarction angina does not seem to induce less myocardial necrosis in this study. There is a significant interaction between preinfarction angina and pre-treatment with sulfonylurea drugs.

Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis.

BACKGROUND: The use of antidepressant medications and the resulting costs have increased dramatically in recent years, partly because of the introduction of selective serotonin reuptake inhibitors (SSRIs). An assessment of the clinical and economic aspects of SSRIs compared with the older tricyclic antidepressants (TCAs) was initiated to generate information for purchasers of these drugs as well as clinicians. One component of this study was an examination of the adverse effects associated with the use of these drugs. METHODS: Searches of bibliographic databases (for January 1980 through May 1996) and manual scanning of both peer-reviewed publications and other documents were used to identify double-blind, randomized controlled trials involving at least one SSRI and one TCA. For the study of adverse effects, only trials that had at least 20 patients in each trial arm and that reported rates of adverse effects in both arms were retained. In total 84 trials reporting on 18 adverse effects were available. Meta-analyses were undertaken to calculate pooled differences in rates of adverse effects. The question of whether the method of eliciting information from patients about adverse effects made a difference in the findings was also examined. Finally, differences in drop-out rates due to adverse effects were calculated. RESULTS: The crude rates of occurrence of adverse effects ranged from 4% (palpitations) to 26% (nausea) for SSRIs and from 4% (diarrhea) to 27% (dry mouth) for TCAs. The differences in the rates of adverse effects between the 2 types of drugs ranged from 14% more with SSRIs (for nausea) to 11% more with TCAs (for constipation). The results did not depend on the method of eliciting information from patients. There were no statistically significant differences between drug classes in terms of drop-outs due to adverse effects. INTERPRETATION: SSRIs and TCAs are both associated with adverse effects, although the key effects differ between the drug classes. Further explanation of the adverse effects and their relation to discontinuation of medication will require better studies involving prospective collection of quality-of-life data.