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BACKGROUND: The application of immune checkpoint inhibitors (ICIs) in treating patients with extensive-stage small-cell lung cancer (ES-SCLC) has brought us new hope, but the real-world outcome is relatively lacking. Our aim was to investigate the clinical use, efficacy, and survival benefit of ICIs in ES-SCLC from real-world data analysis. METHODS: A retrospective analysis of ES-SCLC patients was conducted between 2012 and 2022. Progression-free survival (PFS) and overall survival (OS) were assessed between groups to evaluate the value of ICIs at different lines of treatment. PFS1 was defined as the duration from initial therapy to disease progression or death. PFS2 was defined as the duration from the first disease progression to the second disease progression or death. RESULTS: One hundred and eighty patients with ES-SCLC were included. We performed landmark analysis, which showed that compared to the second-line and subsequent-lines ICIs-combined therapy group (2SL-ICIs) and non-ICIs group, the first-line ICIs-combined therapy group (1L-ICIs) prolonged OS and PFS1. There was a trend toward prolonged OS in the 2SL-ICIs group than in the non-ICIs group, but the significance threshold was not met (median OS 11.94 months vs. 11.10 months, P = 0.14). A longer PFS2 was present in the 2SL-ICIs group than in the non-ICIs group (median PFS2 4.13 months vs. 2.60 months, P < 0.001). CONCLUSION: First-line ICIs plus chemotherapy should be applied in clinical practice. If patients did not use ICIs plus chemotherapy in first-line therapy, the use of ICIs in the second line or subsequent lines of treatment could prolong PFS2.
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Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Intervalo Livre de Progressão , Carcinoma de Pequenas Células do Pulmão , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Estudos Retrospectivos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Taxa de SobrevidaRESUMO
INTRODUCTION: The aberrant expression of the inhibitor of DNA binding (ID1) gene has been frequently associated with the leukemogenesis and prognostication acute myeloid leukemia (AML), although its clinical importance has never been investigated in patients treated outside well-controlled clinical trials. METHODS: Using quantitative real-time polymerase chain reaction, we investigated the role of the ID1 expression in the clinical outcomes of non-selected patients with acute myeloid leukemia treated in a real-life setting. RESULTS: Overall, 128 patients were enrolled. Patients with high ID1 expression had a lower 3-year overall survival (OS) rate of 9%, with the 95% confidence interval (95%CI) at 3 to 20%, compared to patients with a low ID1 expression (22%, 95%CI: 11 - 34%) (p = 0.037), although these findings did not retain significance after adjustment (hazard ratio (HR): 1.5, 95%CI: 0.98 - 2.28; p = 0.057). The ID1 expression had no impact on post-induction outcomes (disease-free survival, p = 0.648; cumulative incidence of relapse, p = 0.584). CONCLUSIONS: Although we are aware thar our data are confronted with many variables that cannot be fully controlled, including drug unavailability, risk-adapted treatment, comorbidities and the time from diagnosis to treatment initiation, we are firm believers that such an initiative can provide more realistic data on understudied populations, in particular those from low- and middle-income countries.
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BACKGROUND: Because severe acute respiratory syndrome coronarivus 2 (SARS-CoV-2) leads to severe conditions and thrombus formation, evaluation of the coagulation markers is important in determining the prognosis and phenotyping of patients with COVID-19. METHODS: In a prospective study that included 213 COVID-19 patients admitted to the intensive care unit (ICU) the levels of antithrombin, C-reactive protein (CRP); factors XI, XII, XIII; prothrombin and D-dimer were measured. Spearman's correlation coefficient was used to assess the pairwise correlations between the biomarkers. Hierarchical and non-hierarchical cluster analysis was performed using the levels of biomarkers to identify patients´ phenotypes. Multivariate binary regression was used to determine the association of the patient´s outcome with clinical variables and biomarker levels. RESULTS: The levels of factors XI and XIII were significantly higher in patients with less severe COVID-19, while factor XIII and antithrombin levels were significantly associated with mortality. These coagulation biomarkers were associated with the in-hospital survival of COVID-19 patients over and above the core clinical factors on admission. Hierarchical cluster analysis showed a cluster between factor XIII and antithrombin, and this hierarchical cluster was extended to CRP in the next step. Furthermore, a non-hierarchical K-means cluster analysis was performed, and two phenotypes were identified based on the CRP and antithrombin levels independently of clinical variables and were associated with mortality. CONCLUSION: Coagulation biomarkers were associated with in-hospital survival of COVID-19 patients. Lower levels of factors XI, XII and XIII and prothrombin were associated with disease severity, while higher levels of both CRP and antithrombin clustered with worse prognosis. These results suggest the role of coagulation abnormalities in the development of COVID-19 and open the perspective of identifying subgroups of patients who would benefit more from interventions focused on regulating coagulation.
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RESUMEN Los sobrevivientes de la reanimación cardiopulmonar posterior a un paro cardiaco pueden tener un amplio rango de desenlaces y van desde recuperación neurológica completa, estado de vigilia sin respuesta, compromiso cognoscitivo diverso o la muerte. La lesión del tejido cerebral se presenta inmediatamente después del paro cardíaco, durante la reanimación y al retornar la circulación espontánea. La severidad y duración de la noxa isquémica determinarán el devenir neurológico. El examen clínico es el punto de partida en el abordaje multimodal del neuropronóstico. Se debe complementar con electroencefalograma, potenciales evocados somatosensoriales, neuroimágenes y biomar-cadores séricos. Entre un 10 a 15% de los pacientes con lesión cerebral posterior al paro cardiaco evolucionan hacia muerte por criterios neurológicos y son potenciales candidatos a la donación de órganos. Un retiro temprano de las terapias de sostenimiento de vida puede malograr la posibilidad de un potencial donante de órganos. Se puede estimar de manera temprana qué pacientes tienen mayor riesgo de evolucionar a muerte por criterios neurológicos. El neurólogo tiene un papel protagónico en el manejo de pacientes con lesión cerebral post paro cardiaco y sus decisiones tienen implicaciones éticas y legales.
ABSTRACT People who survive cardiopulmonary resuscitation (CPR) after cardiac arrest, have a wide range of outcomes including complete neurological recovery, coma, compromised cognitive function and death. Injury of the brain parenchyma starts immediately after a cardiac arrest, during CPR and return of spontaneous circulation. The severity of the ischemic injury will define the neurological outcome. The first step needed to determine a neurological prognosis is the clinical exam, with the help of electroencephalography, somatosensory evoked potentials, neuroimaging, and serum biomarkers. Between 10 and 15% of patients with brain injury after a cardiac arrest, develop brain death and become potential candidates for organ donation. A premature withdrawal of vital support can hamper the possibility of organ donation. The patients with higher risk of developing brain death can be identified early based on neurological criteria. The neurologist has a major role in the approach of patients with brain injury after cardiac arrest and the decision making with legal and ethical consequences.
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Morte Encefálica , Hipóxia Encefálica , Parada Cardíaca , Prognóstico , ÉticaRESUMO
The data presented in this article are related to the research article, "The Use of End-Tidal Carbon Dioxide (ETCO2) Measurement to Guide Management of Cardiac Arrest: A Systematic Review" [1]. This article is a systematic review and meta-analysis of existing data on the subject of whether any level of end-tidal carbon dioxide (ETCO2) measured during cardiopulmonary resuscitation (CPR) correlates with return of spontaneous circulation (ROSC) or survival in adult patients experiencing cardiac arrest in any setting. These data are made publicly available to enable critical or extended analyses.
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BACKGROUND: Acute lymphoblastic leukemia (ALL) in adults is an invariably aggressive and rare disease. Its treatment is based on the use of multidrug regimens, which have been improved since the 1970s. Few published data are available on the results of adult ALL treatment in Latin America. MATERIALS AND METHODS: We retrospectively analyzed the data from 59 patients with ALL treated from 2009 to 2015 at Hospital of Clinics of University of São Paulo, using an adapted German Multicenter ALL (GMALL) protocol (07/2003). RESULTS: The median patient age was 35 years (range, 16-71 years), with 76% of new cases of B-cell lineage. Central nervous system involvement was present in 29%. Most patients were in the high-risk group, using the original GMALL criteria (68%). The early death rate was 17%, preventing early evaluation of the response in these patients. Despite a reasonable complete remission rate (76%), most patients eventually died of sepsis, especially during the induction phase and salvage regimens. The median overall survival was 17 months. CONCLUSION: Intensified chemotherapy protocols for adult ALL have succeeded in achieving better survival rates in adults, especially younger adults. The low overall survival found with GMALL in Brazil's public hospital denotes the importance of optimizing the adaptations of international protocols for treatment of ALL in nondeveloped countries and, in parallel, improving supportive care in public services.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mortalidade/tendências , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Terapia de Salvação/métodos , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Brasil/epidemiologia , Intervalo Livre de Doença , Feminino , Alemanha , Humanos , Cooperação Internacional , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Indução de Remissão/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
AIMS: To identify whether any level of end-tidal carbon dioxide (ETCO2) measured during cardiopulmonary resuscitation (CPR) correlates with return of spontaneous circulation (ROSC) or survival in adults experiencing cardiac arrest in any setting. METHODS: Systematic review. We included randomized controlled trials, cohort studies, and case-control studies of adult cardiac arrest in any setting that reported specific (rather than pooled) ETCO2 values and attempted to correlate those values with prognosis. Full-text articles were searched on EmBASE, MEDLINE, and Cochrane Database. The Grades of Recommendation, Assessment, Development and Evaluation (GRADE) guidelines were followed, assigning levels of quality to all evidence used in the meta-analysis. RESULTS: Seventeen observational studies, describing a total of 6198 patients, were included in the qualitative synthesis, and five studies were included in the meta-analysis. The available studies provided consistent but low-quality evidence that ETCO2 measurements ≥10mmHg, obtained at various time points during CPR, are substantially related to ROSC. Additional cut-off values were also found. Initial ETCO2 or 20-min ETCO2>20mmHg appears to be a better predictor of ROSC than the 10mmHg cut off value. A ETCO2<10mmHg after 20min of CPR is associated with a 0.5% likelihood of ROSC. CONCLUSIONS: Based upon existing evidence, ETCO2 levels do seem to provide limited prognostic information for patients who have experienced cardiac arrest. Given the many potential confounders that can influence initial ETCO2 levels, extreme or trending values may be more useful than static mid-range levels. Additional well-designed studies are needed to define optimal timing for the measurement of ETCO2 for prognostic purposes.
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Dióxido de Carbono/análise , Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Parada Cardíaca Extra-Hospitalar/terapia , Adulto , Dióxido de Carbono/metabolismo , Estudos de Casos e Controles , Humanos , Estudos Observacionais como Assunto , Parada Cardíaca Extra-Hospitalar/mortalidade , Valor Preditivo dos Testes , Estudos Prospectivos , Análise de Sobrevida , Volume de Ventilação Pulmonar/fisiologiaRESUMO
OBJECTIVE: The use of palliative care (PC) screening criteria to trigger PC consultations may optimize the utilization of PC services, improve patient comfort, and reduce invasive and futile end-of-life care. The aim of the present study was to assess the criterion validity and inter-rater reliability of a PC screening tool for patients admitted to an emergency department intensive care unit (ED-ICU). METHOD: Observational retrospective study evaluating PC screening criteria based on the presence of advanced diagnosis and the use of two "surprise questions" (traditional and modified). Patients were classified at ED-ICU admission in four categories according to the proposed algorithm.ResultA total of 510 patients were included in the analysis. From these, 337 (66.1%) were category 1, 0 (0.0%) category 2, 63 (12.4%) category 3, and 110 (21.6%) category 4. Severity of illness (Simplified Acute Physiology Score III score and mechanical ventilation), mortality (ED-ICU and intrahospital), and PC-related measures (order for a PC consultation, time between admission and PC consultation, and transfer to a PC bed) were significantly different across groups, more evidently between categories 4 and 1. Category 3 patients presented similar outcomes to patients in category 1 for severity of illness and mortality. However, category 3 patients had a PC consultation ordered more frequently than did category 1 patients. The screening criteria were assessed by two independent raters (n = 100), and a substantial interrater reliability was found, with 80% of agreement and a kappa coefficient of 0.75 (95% confidence interval = 0.62, 0.88).Significance of resultsThis study is the first step toward the implementation of a PC screening tool in the ED-ICU. The tool was able to discriminate three groups of patients within a spectrum of increasing severity of illness, risk of death, and PC needs, presenting substantial inter-rater reliability. Future research should investigate the implementation of these screening criteria into routine practice of an ED-ICU.
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Programas de Rastreamento/normas , Cuidados Paliativos/normas , Índice de Gravidade de Doença , Idoso , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Cuidados Paliativos/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Escore Fisiológico Agudo SimplificadoRESUMO
INTRODUCTION AND AIMS: We aimed to explore the impact of infection diagnosed upon admission and of other clinical baseline parameters on mortality of cirrhotic patients with emergency admissions. MATERIAL AND METHODS: We performed a prospective observational monocentric study in a tertiary care center. The association of clinical parameters and established scoring systems with short-term mortality up to 90 days was assessed by univariate and multivariable Cox regression analysis. Akaike's Information Criterion (AIC) was used for automated variable selection. Statistical interaction effects with infection were also taken into account. RESULTS: 218 patients were included. 71.2% were male, mean age was 61.1 ± 10.5 years. Mean MELD score was 16.2 ± 6.5, CLIF-consortium Acute on Chronic Liver Failure-score was 34 ± 11. At 28, 90 and 365 days, 9.6%, 26.0% and 40.6% of patients had died, respectively. In multivariable analysis, respiratory organ failure [Hazard Ratio (HR) = 0.15], albumin substitution (HR = 2.48), non-HCC-malignancy (HR = 4.93), CLIF-C-ACLF (HR = 1.10), HCC (HR = 3.70) and first episode of ascites (HR = 0.11) were significantly associated with 90-day mortality. Patients with infection had a significantly higher 90-day mortality (36.3 vs. 20.1%, p = 0.007). Cultures were positive in 32 patients with resistance to cephalosporins or quinolones in 10, to ampicillin/sulbactam in 14 and carbapenems in 6 patients. CONCLUSION: Infection is common in cirrhotic ED admissions and increases mortality. The proportion of resistant microorganisms is high. The predictive capacity of established scoring systems in this setting was low to moderate.
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Antibacterianos/uso terapêutico , Infecções Bacterianas/terapia , Serviço Hospitalar de Emergência , Cirrose Hepática/terapia , Admissão do Paciente , Idoso , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Técnicas de Apoio para a Decisão , Farmacorresistência Bacteriana , Feminino , Alemanha , Nível de Saúde , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the risk factors associated with lung cancer (LC) and other second neoplasms (SN) in Hodgkin lymphoma (HL) survivors. METHODS: We retrospectively analyzed the clinical characteristics and outcomes of 604 patients treated in our institution between 1968 and 2012. RESULTS: 90 out of 604 patients developed SN: 27 LC and 63 other SN. The median time elapsed until LC and other SN was 16.5 and 11.8 years, respectively (p = 0.003). In the LC group, 85.5 % of patients were male and 84.6 % smokers (HR 7, 95 % CI 2.4-20.7, p < 0.001). Radiotherapy (RT) doses applied were higher in the SN group with an increased risk of LC (HR: 4.0 95 % CI 1.1-11.6, p = 0.010) and other SN (HR: 3.3 95 % CI 1.6-6.7 p = 0.001) with doses higher than 42 Gy. No association was found between alkylating agents and development of SN. In LC, the most frequent histology was adenocarcinoma with an elapsed time after HL of 13.2 years in early stages and 21.3 in advanced (p = 0.02). Median OS after a diagnosis of LC was 12.6 months ranging from 5.9 (in cases presenting due to symptoms) to 49.1 (incidentally diagnosed cases) (p = 0.005). CONCLUSIONS: RT treatment, especially with doses higher than 42 Gy, and smoking increase the risk of SN after HL. In this series, LC patients with early stages had a shorter elapsed time from HL diagnosis and longer OS, therefore the role of LC screening in HL survivors should be prospectively evaluated and smoking cessation counseling ought to be a key aspect during follow-up.
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Doença de Hodgkin/epidemiologia , Doença de Hodgkin/terapia , Neoplasias Pulmonares/epidemiologia , Neoplasias Induzidas por Radiação/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/efeitos adversos , Dacarbazina/efeitos adversos , Doxorrubicina/efeitos adversos , Doença de Hodgkin/radioterapia , Humanos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Masculino , Mecloretamina/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/patologia , Segunda Neoplasia Primária/patologia , Prednisona/efeitos adversos , Procarbazina/efeitos adversos , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Vimblastina/efeitos adversos , Vincristina/efeitos adversos , Adulto JovemRESUMO
The standard approach to the follow-up of lymphoma includes computed tomography (CT) every 6-12 months for the first 2 years and, then, as clinically indicated. Recent evidence suggests that most relapses are detected clinically, outside scheduled CT which, on the other hand, increases risk of second malignancies and cost. In early-stage lymphomas, involved site CT instead of full body CT may be a reasonable alternative to reduce radiation dose. We analyzed whether regular CT surveillance detects asymptomatic relapses in a single-center Uruguayan early stage non-Hodgkin lymphoma (NHL) population. We evaluated utility of full body CT halfway and at the end-of-treatment evaluation and calculated the radiation exposure. In our study, CT surveillance added nothing to clinical follow-up. Moreover, 44% of our patients received a cumulative effective dose that doubles the risk of malignancies. Involved-site CT scan would be enough to monitor response during treatment in early stage NHL.
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Linfoma não Hodgkin/diagnóstico , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Doses de Radiação , Efeitos da Radiação , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/efeitos adversos , Tomografia Computadorizada por Raios X/normas , Adulto JovemRESUMO
Bone marrow biopsy is recommended for staging of classical Hodgkin lymphoma. The aim of this study was to compare bone marrow evaluation by histology with that obtained by (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET). One hundred and three cases of Classical Hodgkin Lymphoma were reviewed. All patients were submitted to FDG-PET evaluation. Bone marrow biopsy results were compared with clinical data and FDG-PET results. Ninety-one cases had available bone marrow biopsies. Overall, there were 16 positive and one suspect case. In five cases, the FDG-PET scan was positive and biopsy was negative: 1/5 was found to correspond to a bone fracture, 3/5 showed marked reactive bone marrow changes and in 1/5 no explanation for the discrepancy was found. FDG-PET showed high sensitivity, supporting the idea that when it is negative, biopsy could be avoided. Care should be taken in patients with a positive FDG-PET, where confirmation by bone marrow biopsy should be recommended.