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Introducción. El esplenúnculo se ha descrito con una incidencia global del 10 al 30 %. Puede ser una entidad de origen congénito o adquirida, frecuentemente está asociada a trauma abdominal o antecedente de esplenectomía por diversas causas. Caso clínico. Mujer en edad media, con antecedente de trauma abdominal y esplenectomía por ruptura traumática, quien 30 años después presenta un cuadro de dolor abdominal. Los estudios imagenológicos identificaron una masa sólida intrapancreática. Resultados. Fue llevada a pancreatectomía distal. Los hallazgos histológicos e inmunohistoquímicos confirmaron que la masa pancreática correspondía a un esplenúnculo intrapancreático adquirido, asociado al evento traumático previo. Conclusión. Los esplenúnculos suelen constituir un "incidentaloma". Los estudios imagenológicos se encuentran limitados, pues la tomografía computarizada, la resonancia nuclear magnética y la ultrasonografía presentan características imagenológicas similares con los tumores pancreáticos hipervascularizados, por lo que se debe practicar el estudio histopatológico durante su valoración. Esta entidad se debe incluir dentro de los diagnósticos diferenciales, con mayor énfasis en aquellos pacientes con historia de trauma abdominal y esplenectomía asociada, un escenario en el que esta lesión puede simular una neoplasia sólida del páncreas, con características malignas.
Introduction. Splenunculus has been described with an overall incidence of 10 to 30%. It can be an entity of congenital or acquired origin, it is frequently associated with abdominal trauma or a history of splenectomy for various reasons. Clinical case. Middle-aged woman, with a history of abdominal trauma and splenectomy due to traumatic rupture, who 30 years later presents with abdominal pain. Imaging studies identified a solid intrapancreatic mass. Results. She was taken to OR for distal pancreatectomy. The histological and immunohistochemical findings confirmed that the pancreatic mass corresponded to an acquired intrapancreatic splenunculus, associated with the previous traumatic event. Conclusion. Splenuncles usually constitute an "incidentaloma". Imaging studies are limited, since computed tomography, magnetic resonance imaging, and ultrasonography present similar imaging characteristics with hypervascularized pancreatic tumors, so histopathological study must be included during their evaluation. This entity should be included in the differential diagnoses, with greater emphasis on those patients with a history of abdominal trauma and associated splenectomy, a scenario in which this lesion can simulate a solid neoplasm of the pancreas, with malignant characteristics.
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Humanos , Pâncreas , Neoplasias Pancreáticas , Esplenectomia , Pancreatectomia , Baço , Esplenose , Diagnóstico DiferencialRESUMO
Background: The COVID-19 pandemic in Latin America generated the need to develop low-cost, fast-manufacturing mechanical ventilators. The Universidad de La Sabana and the Fundacion Neumologica Colombiana designed and manufactured the Unisabana-HERONS (USH) ventilator. Here, we present the preclinical and clinical study results to evaluate its effectiveness and safety characteristics in an animal model (Yorkshire Sow) and five patients with acute respiratory failure receiving mechanical ventilatory support for 24 h. Methods: The effectiveness and safety outcomes included maintaining arterial blood gases and pulse oximetry saturation (SpO2), respiratory pressures and volumes (during continuous monitoring) in the range of ARDS and lung-protective strategy goals, and the occurrence of barotrauma. A significance level of 0.05 was used for statistical tests. This clinical trial was registered on Clinicaltrials.gov (NCT04497623) and approved by the ethics committee. Results: Among patients treated with the Unisabana-HERONS, the most frequent causes of acute respiratory failure were pneumonia in 3/5 (60 %) and ARDS in 2/5 (40 %). During the treatment, the ventilatory parameters related to lung protection protocols were kept within the safety range, and vital signs and blood gas were stable. The percentage of time that the respiratory pressures or volumes were out of safety range were plateau pressure >30 cm H2O: 0.00 %; driving pressure >15 cm H2O: 0.06 %; mechanical power >15 J/min: 0.00 %; and Tidal volume >8 mL/kg: 0.00 %. There were no adverse events related to the ventilator. The usability questionnaire retrieved a median score for all items between 9 and 10 (best score: 10), indicating great ease of use. Conclusion: The Unisabana-HERONS ventilator effectively provided adequate gas exchange and maintained the ventilatory parameters in the range of lung protection strategies in humans and an animal model. Furthermore, it is straightforward to use and is a low-cost medical device.
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Latin American populations, characterized by intricate admixture patterns resulting from the intermingling of ancestries from European, Native American (NA) Asian, and African ancestries which result in a vast and complex genetic landscape, harboring unique combinations of novel variants. This genetic diversity not only poses challenges in traditional population genetics methods but also opens avenues for a deeper understanding of its implications in health. In cancer, the interplay between genetic ancestry, lifestyle factors, and healthcare disparities adds a layer of complexity to the varying incidence and mortality rates observed across different Latin American subpopulations. This complex interdependence has been unveiled through numerous studies, whether conducted on Latin American patients residing on the continent or abroad, revealing discernible differences in germline composition that influence divergent disease phenotypes such as higher incidence of Luminal B and Her2 breast tumors, EGFR and KRAS mutated lung adenocarcinomas in addition to an enrichment in BRCA1/2 pathogenic variants and a higher than expected prevalence of variants in colorectal cancer associated genes such as APC and MLH1. In prostate cancer novel risk variants have also been solely identified in Latin American populations. Due to the complexity of genetic divergence, inputs from each individual ancestry seem to carry independent contributions that interplay in the development of these complex disease phenotypes. By understanding these unique population characteristics, genomic ancestries hold a promising avenue for tailoring prognostic assessments and optimizing responses to oncological interventions.
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Neoplasias , Humanos , América Latina/epidemiologia , Neoplasias/genética , Neoplasias/epidemiologia , Masculino , Feminino , Genômica , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologiaRESUMO
Introducción: El cáncer de pulmón (CP) es una enfermedad con gran impacto a nivel mundial en el número de muertes y en costos en salud. La alta incidencia y mortalidad de esta enfermedad asociada al diagnóstico tardío, y la mejoría del pronóstico ante una detección temprana, determinan que sea una patología pasible de beneficiarse mediante detección temprana. La tomografía de baja dosis de radiación (TCBD) demostró ser un método que se pue- de realizar periódicamente a un grupo de personas con alto riesgo de desarrollar CP y así reducir la mortalidad por esta enfermedad. Sin embargo, este beneficio es tal cuan- do se encuentra desarrollado bajo un programa organizado y con participación multi- disciplinaria especializada en cáncer de pulmón. Métodos: Se plantea determinar lineamientos básicos para el desarrollo de la detección temprana de cáncer de pulmón en América Latina para que pueda ser realizada en forma uniforme, con el menor riesgo y el máximo beneficio esperado. Se analizaron las principales publicaciones referidas a este tema, contemplando la diversidad de atención y acceso de América Latina. Resultado: Se desarrollan requerimientos mínimos para la implementación de un pro- grama. Discusión: El número de programas en la región es escaso y depende más de esfuerzos individuales que de políticas generales de salud. Consideramos que estos lineamien- tos pueden servir de apoyo para el desarrollo de más programas en la región y de for- ma más homogénea.
Introduction: Lung cancer (LC) is a disease with a great impact worldwide in the number of deaths and health costs. The high incidence and mortality of this disease associated with late diagnosis and the improved prognosis with early detection determine that it is a pathology that can benefit from early detection. Low radiation dose tomography (LDCT) demonstrated a method that can be performed periodically to a group of people at high risk of developing CP and thus reduce mortality from this disease. However, this benefit is such when it is developed under an organized program with multidisciplinary participation specialized in lung cancer. Methods: It is proposed to determine basic guidelines for the development of early de- tection of lung cancer in Latin America so that it can be carried out uniformly, with the lowest risk and the maximum expected benefit. The main publications referring to this topic were analyzed, considering the diversity of care and access in Latin America. Result: Minimum requirements are developed for the implementation of a program. Discussion: The number of programs in the region is small and depends more on individual efforts than on general health policies. We consider that these guidelines can serve as support for the development of more programs in the region and in a more ho- mogeneous way.
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Humanos , Planos e Programas de Saúde , Detecção Precoce de Câncer , Neoplasias Pulmonares/diagnóstico , Equipe de Assistência ao Paciente/organização & administração , Serviços Preventivos de Saúde/organização & administração , Tomografia/métodos , Incidência , Mortalidade , Educação Profissionalizante , Política de Saúde , América LatinaRESUMO
Aim: To describe the clinical picture and diagnosis of an episode of severe hypocalcemia in a patient with systemic lupus erythematosus (SLE) in remission, with chronic diarrhea that led to the diagnosis of celiac disease (CD). Case presentation: 22-year-old patient, diagnosed with SLE at age 10, in remission. He consulted for a two-month history of paresthesias, muscle spasms, myalgias, and episodes of tetany in the previous week, associated with malabsorptive postprandial diarrhea. His laboratory tests showed severe hypocalcemia, vitamin D deficiency, severe hypomagnesemia, and mild hypokalemia. In the study for CD, serology reported normal anti-tissue transglutaminase IgA, antigliadin IgA, and IgG and low total IgA levels. Enteroscopy revealed erosive bulbo-duodenitis, with villous atrophy and increased intraepithelial lymphocytes in the pathology, which, together with the immunohistochemical study, allowed the diagnosis of CD, Marsh 3a type. Management was initiated with a gluten-free diet, with a positive clinical response. Conclusion: CD should be suspected in patients with SLE who present with diarrhea, abdominal pain, nausea/vomiting, recurrent oral aphthosis, and anemia. In rare seronegative CD cases, other causes of villous atrophy, mainly infectious, toxic, and immunological, must be ruled out. There is an association between CD and SLE, so diagnosis must be early and timely with the best testing scheme available to achieve effective treatment before complications occur.
Objetivo: Describir la presentación clínica y diagnóstico de un episodio de hipocalcemia grave en un paciente con lupus eritematoso sistémico (LES) en remisión, con diarrea crónica que condujo al diagnóstico de enfermedad celíaca (EC). Presentación del caso: Paciente de 22 años, con diagnóstico de LES a los 10 años, en remisión. Consultó por 2 meses de evolución de parestesias, espasmos musculares, mialgias y episodios de tetania en la semana previa, asociado a diarrea posprandial malabsortiva. Sus laboratorios mostraron hipocalcemia grave, déficit de vitamina D, hipomagnesemia grave e hipopotasemia leve. En el estudio para EC la serología reportó antitransglutaminasa tisular IgA, antigliadina IgA e IgG normales y niveles de IgA total bajos. La enteroscopia evidenció bulboduodenitis erosiva, con atrofia de las vellosidades y aumento de linfocitos intraepiteliales en la patología, que junto al estudio inmunohistoquímico permitieron concluir el diagnóstico de EC, tipo Marsh 3a. Se inició el manejo con una dieta libre de gluten, con una respuesta clínica positiva. Conclusión: La EC debe sospecharse en pacientes con LES que inicien con diarrea, dolor abdominal, náuseas/vómitos, aftosis oral recurrente y anemia. En los casos de EC seronegativa, los cuales son poco comunes, se deben descartar otras causas de atrofia de las vellosidades principalmente infecciosas, tóxicas e inmunitarias. Existe una asociación entre EC y LES, por lo cual el diagnóstico debe ser precoz y oportuno con el mejor esquema de pruebas disponible para lograr realizar un tratamiento efectivo antes de que se presenten las complicaciones.
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In Colombia, coccidioidomycosis is a rare entity, and the intestinal manifestation is infrequent, with around a dozen cases reported in the world literature. This article reports the case of a 29-year-old male Venezuelan immigrant with a 4-month history of abdominal pain, jaundice, nausea, and vomiting. The tomography and the endoscopic study revealed a circumferential exophytic mass in the second portion of the duodenum. The biopsy revealed multiple spherules filled with round fungal endospores with a final diagnosis of disseminated coccidioidomycosis. The patient was discharged before the final pathology report with fluconazole doses of 200 mg every other day and an order for outpatient magnetic resonance cholangiography for outpatient follow-up, which he has not attended.
La coccidioidomicosis en Colombia es una entidad infrecuente y la presentación intestinal es extremadamente rara, con alrededor de una docena de casos reportados en la literatura mundial. En el presente artículo se reporta el caso de un paciente inmigrante venezolano masculino de 29 años con historia de dolor abdominal, ictericia, náuseas y vómito de 4 meses de evolución. La tomografía y el estudio endoscópico evidenciaron una masa exofítica circunferencial en la segunda porción del duodeno. La biopsia reveló múltiples esférulas llenas de endosporas fúngicas redondas con diagnóstico final de coccidioidomicosis diseminada. El paciente fue dado de alta antes del reporte final anatomopatológico con dosis de fluconazol de 200 mg interdiario y orden de colangiorresonancia ambulatoria para control ambulatorio, mismo al cual no ha asistido.
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The current landscape of targeted therapies directed against oncogenic driver alterations in non-small cell lung cancer (NSCLC) is expanding. Patients with EGFR-mutant NSCLC can derive significant benefit from EGFR tyrosine kinase inhibitor (TKI) therapy, including the third-generation EGFR TKI osimertinib. However, invariably, all patients will experience disease progression with this therapy mainly due to the adaptation of cancer cells through primary or secondary molecular mechanisms of resistance. The comprehension and access to tissue and cell-free DNA next-generation sequencing have fueled the development of innovative therapeutic strategies to prevent and overcome resistance to osimertinib in the clinical setting. Herein, we review the biological and clinical implications of molecular mechanisms of osimertinib resistance and the ongoing development of therapeutic strategies to overcome or prevent resistance.
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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/tratamento farmacológico , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Mutação , Resistencia a Medicamentos Antineoplásicos/genética , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS syndrome) is a recently described genetic disorder that gathers autoinflammatory symptoms and myeloid dysplasia. The first description was reported in 2020, and subsequently, a growing number of cases have been described worldwide. Herein, we describe a case of a 72-year-old male patient with VEXAS syndrome with p.Met41Val mutation of the UBA1 gene, prominent supraglottic larynx involvement, and costochondritis. To our knowledge, this is the first report of VEXAS syndrome in Colombia and South America. This disease could present features of relapsing polychondritis, polyarteritis nodosa, giant cell arteritis, and Sweet syndrome, associated with hematologic involvement, including cytopenias, myelodysplastic syndrome, or thromboembolic disease. Supraglottic larynx chondritis and costochondritis are atypical manifestations. These features were proposed previously to differentiate relapsing polychondritis from VEXAS syndrome but are not entirely reliable like in the case described. A diagnosis of VEXAS should be considered in male patients with incomplete or complete features of the previously described conditions, refractory to treatment, requiring high-dose glucocorticoids, and associated progressive hematologic abnormalities. Key Points ⢠VEXAS syndrome is a recently described genetic (somatic mutations in UBA1 gene) disorder that gathers autoinflammatory and hematologic manifestations. ⢠VEXAS syndrome should be considered in male patients with incomplete or complete features of relapsing polychondritis, polyarteritis nodosa, giant cell arteritis, and Sweet syndrome, refractory to treatment, associated with hematologic involvement, including cytopenias, myelodysplastic syndrome, or thromboembolic disease. ⢠Glucocorticoids ameliorate symptoms effectively. However, other treatment options are limited due to a lack of evidence. Traditional immunosuppressants and biological therapy have been used empirically with limited efficacy and a transient effect. Bone marrow transplant offers a curative approach, but it has high morbidity and mortality.
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Arterite de Células Gigantes , Laringe , Síndromes Mielodisplásicas , Poliarterite Nodosa , Policondrite Recidivante , Síndrome de Sweet , Idoso , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/genética , Humanos , Imunossupressores/uso terapêutico , Masculino , Síndromes Mielodisplásicas/complicações , Policondrite Recidivante/complicações , Policondrite Recidivante/diagnóstico , Policondrite Recidivante/genética , Síndrome de Sweet/complicações , VacúolosRESUMO
EGFR exon 20 insertions represent a subgroup of NSCLC patients posed with a therapy dilemma. In this issue of Cancer Cell, Elamin and colleagues demonstrate that only insertions localized in the near loop respond to poziotinib. Pharmacological inhibition of spindle assembly checkpoint components inhibits tumor growth in poziotinib-resistant exon 20 insertions.
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Receptores ErbB , Neoplasias Pulmonares , Receptores ErbB/genética , Éxons/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Small cell lung cancer (SCLC) is a highly proliferative lung cancer that is not amenable to surgery in most cases due to the high metastatic potential. Precision medicine has not yet improved patients' survival due to the lack of actionable mutations. Intra- and intertumoral heterogeneity allow the neoplasms to adapt to various microenvironments and treatments. Further studying this heterogeneous cancer might yield the discovery of actionable mutations. First-line SCLC treatment has added immunotherapy to its armamentarium. There has been renewed interest in SCLC, and numerous clinical trials are underway with novel therapeutic approaches. Understanding the molecular and genetic landscape of this heterogeneous and lethal disease will pave the way for novel drug development.
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KRAS mutations are one of the most prevalent oncogenic alterations in cancer. Until recently, drug development targeting KRAS did not convey clinical benefits to patients. Specific KRASG12C inhibitors, such as sotorasib and adagrasib, have been designed to bind to the protein's mutant structure and block KRASG12C in its GDP-bound inactive state. Phase 1/2 trials have shown promising anti-tumor activity, especially in pretreated non-small cell lung cancer patients. As expected, both primary and secondary resistance to KRASG12C inhibitors invariably occurs, and molecular mechanisms have been characterized in pre-clinical models and patients. Several mechanisms such as tyrosine kinase receptors (RTKs) mediated feedback reactivation of ERK-dependent signaling can result in intrinsic resistance to KRAS target therapy. Acquired resistance to KRASG12C inhibitors include novel KRAS mutations such as Y96D/C and other RAS-MAPK effector protein mutations. This review focuses on the intrinsic and acquired mechanisms of resistance to KRASG12C inhibitors in KRASG12C mutant non-small cell lung cancer and the potential clinical strategies to overcome or prevent it.
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OBJECTIVES: The objectives of this study are to evaluate the relationship between authorship networking, socioeconomic factors, and scientific productivity across Latin America. METHODS: In a bibliometric analysis of cancer-related Latin-American publications, the relationship between authorship network indicators, sociodemographic factors, and number of peer-reviewed indexed publications per country was explored. A systematic review of the literature for cancer publications between 2000 and 2018 using the Scopus database limited to Latin-American authors was used for the construction of coauthorship and publication networks and their respective metrics. Sociodemographic variables including percentage of invested gross domestic product in research, population, and cancer incidence were also estimated. Multiple linear regression models were constructed to determine the relationship between productivity and the aforementioned variables. RESULTS: A total of 8,528 articles across nine countries were included. Brazil was the most productive nation with 41.8% of identified references followed by Mexico (16.6%) and Argentina (12.9%). Latin America experienced a 9% growth in number of publications across the studied time frame. After analyzing networking and sociodemographic variables, number of authors in a collaboration network and percentage of invested gross domestic product were associated with high productivity yielding a multiple regression model with an R2 value of 0.983. CONCLUSIONS: This study indicates that extensive authorship networking and a high investment in research strongly predict cancer-related productivity.
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Indexação e Redação de Resumos/estatística & dados numéricos , Autoria/normas , Revisão da Pesquisa por Pares/métodos , Publicações/estatística & dados numéricos , Bibliometria , Gerenciamento de Dados , Eficiência , Humanos , Incidência , América Latina/epidemiologia , Neoplasias/epidemiologia , Publicações/tendências , Fatores SocioeconômicosRESUMO
RESUMEN Se expone el caso de una mujer de 19 años a quien se le realizó el diagnóstico de un xantoastrocitoma pleomórfico anaplásico parietooccipital izquierdo, neoplasia poco frecuente que suele presentarse en la población pediátrica y en los adultos jóvenes. Dicho tumor debuta generalmente con crisis convulsivas y sus características histológicas patognomónicas son el pleomorfismo celular, la vacuolización lipídica de su citoplasma y la reactividad a la proteína ácida fibrilar glial (PAFG) y S100. El estudio de nuevos marcadores que puedan brindar otras oportunidades terapéuticas ha permitido encontrar mutaciones en el oncogén BRAF. Este tumor presenta una variante anaplásica más agresiva que se trata con cirugía y quimiorradiación. En nuestro caso, después de varias progresiones a otras intervenciones, se utilizó bevacizumab y carmustine como tratamiento de segunda línea con respuesta completa.
SUMMARY The case of a young woman of 19-years-old is presented; whom the diagnosis was made of a left parietal-occipital xanthoastrocytoma pleomorphic anaplastic; this neoplasia is rare and usually affects the pediatric and young adult population. This generally debuts with seizures and their pathognomonic histologic characteristics are the pleomorphic cells with cytoplasmatic lipid vacuolation and the reactivity of glial fibrillary acidic protein (GFAP) and S100. The study of new markers that may provide other therapeutic opportunities has allowed finding mutations in the BRAF oncogene. This tumor has a more aggressive anaplastic variant that is treated with surgery and chemoradation. In our case after several progressions to other interventions, we used bevacizumab and carmustine as second-line treatment obtaining complete response.
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Radioterapia , Carmustina , Bevacizumab , Glioma , AntineoplásicosRESUMO
OBJECTIVE: To evaluate the efficacy and safety of pemetrexed, carboplatin and bevacizumab (PCB) followed by maintenance therapy with pemetrexed and bevacizumab (PB) in chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer (NSCLC) through the influence of thymidylate synthase (TS) protein and mRNA expression on several outcomes. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). METHODS: A cohort of 144 patients were administered pemetrexed (500 mg/m2), carboplatin (AUC, 5.0 mg/ml/min) and bevacizumab (7.5 mg/kg) intravenously every three weeks for up to four cycles. Maintenance PB was administered until disease progression or unacceptable toxicity. RESULTS: One hundred forty-four Colombian patients with a median follow-up of 13.8 months and a median number of 6 maintenance cycles (range, 1-32) were assessed. The ORR among the patients was 66% (95% CI, 47% to 79%). The median PFS and (OS) rates were 7.9 months (95% CI, 5.9-10.0 months) and 21.4 months (95% CI, 18.3 to 24.4 months), respectively. We documented grade 3/4 hematologic toxicities, including anemia (14%), neutropenia (8%), and thrombocytopenia (16%). The identified grade 3/4 non-hematologic toxicities were proteinuria (2%), venous thrombosis (4%), fatigue (11%), infection (6%), nephrotoxicity (2%), and sensory neuropathy (4%). No grade >3 hemorrhagic events or hypertension cases were reported. OS was significantly higher in patients with the lowest TS mRNA levels [median, 29.6 months (95% CI, 26.2-32.9)] compared with those in patients with higher levels [median, 9.3 months (95% CI, 6.6-12.0); p = 0.0001]. TS expression (mRNA levels or protein expression) did not influence the treatment response. CONCLUSION: Overall, PCB followed by maintenance pemetrexed and bevacizumab was effective and tolerable in Hispanic patients with non-squamous NSCLC. This regimen was associated with acceptable toxicity and prolonged OS, particularly in patients with low TS expression. We found a role for Ki67 and TS expression as prognostic factors.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Timidilato Sintase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Biópsia , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada , Feminino , Humanos , Quimioterapia de Indução , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Pemetrexede/administração & dosagem , Prognóstico , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, not malignant, disease of the hematopoietic stem cells, associated with significant morbidity and mortality. It is a rare disease with an estimated incidence of 1.3 new cases per one million individuals per year. The treatment of PNH has been largely empirical and symptomatic, with blood transfusions, anticoagulation, and supplementation with folic acid or iron. Eculizumab, a biological agent that inhibits complement cascade, was developed for preventing hemolytic anemia and severe thrombotic episodes. OBJECTIVES: To assess the clinical benefits and harms of eculizumab for treating patients with paroxysmal nocturnal hemoglobinuria (PNH). SEARCH METHODS: We conducted a comprehensive search strategy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2014, Issue 5), Ovid MEDLINE (from 1946 to 15 May 2014), EMBASE (from 1980 to 25 June 2014), and LILACS (from 1982 to 25 June 2014). We did not apply any language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) irrespective of their publication status or language. No limits were applied with respect to period of follow-up. We excluded quasi-RCTs. We included trials comparing eculizumab with placebo or best available therapy. We included any patient with a confirmed diagnosis of PNH. Primary outcome was overall survival. DATA COLLECTION AND ANALYSIS: We independently performed a duplicate selection of eligible trials, risk of bias assessment, and data extraction. We estimated risk ratios (RRs) and 95% confidence interval (CIs) for dichotomous outcomes, and mean differences (MDs) and 95% CIs for continuous outcomes. We used a random-effects model for analysis. MAIN RESULTS: We identified one multicenter (34 sites) phase III RCT involving 87 participants. The trial compared eculizumab versus placebo, and was conducted in the US, Canada, Europe, and Australia with 26 weeks of follow-up. This small trial had high risk of bias in many domains (attrition and selective reporting). It was sponsored by a pharmaceutical company. No patients died during the study. By using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (scores can range from 0 to 100, with higher scores on the global health status and functioning scales indicating improvement), the trial showed improvement in health-related quality of life in patients treated with eculizumab (mean difference (MD) 19.4, 95% CI 8.25 to 30.55; P = 0.0007; low quality of evidence). By using the Functional Assessment of Chronic Illness Therapy Fatigue instrument (scores can range from 0 to 52, with higher scores indicating improvement in fatigue), the trial showed a reduction in fatigue (MD 10.4, 95% CI 9.97 to 10.83; P = 0.00001; moderate quality of evidence) in the eculizumab group compared with placebo. Eculizumab compared with placebo showed a greater proportion of patients with transfusion independence: 51% (22/43) versus 0% (0/44); risk ratio (RR) 46.02, 95% CI 2.88 to 735.53; P = 0.007; moderate quality of evidence; and withdrawal for any reason: 4.7% (2/43) versus 22.72% (10/44); RR 0.20, 95% CI 0.05 to 0.88; P = 0.03; moderate quality of evidence. Due to the low rate of events observed, the included trial did not show any difference between eculizumab and placebo in terms of serious adverse events: 9.3% (4/43) versus 20.4% (9/44); RR 0.15, 95% CI 0.15 to 1.37; P = 0.16; low quality of evidence. We did not observe any difference between intervention and placebo for the most frequent adverse events. One participant receiving placebo showed an episode of thrombosis. The trial did not assess overall survival, transformation to myelodysplastic syndrome and acute myelogenous leukemia, or development or recurrence of aplastic anemia on treatment. AUTHORS' CONCLUSIONS: This review has detected an absence of evidence for eculizumab compared with placebo for treating paroxysmal nocturnal hemoglobinuria (PNH), in terms of overall survival, nonfatal thrombotic events, transformation to myelodysplastic syndrome and acute myelogenous leukemia, and development and recurrence of aplastic anemia on treatment. Current evidence indicates that compared with placebo, eculizumab increases health-related quality of life and increases transfusion independence. During the execution of the included trial, no patients died. Furthermore, the intervention seems to reduce fatigue and withdrawals for any reason. The safety profile of eculizumab is unclear. These conclusions are based on one small trial with risk of attrition and selective reporting bias.Therefore, prescription of eculizumab for treating patients with PNH can neither be supported nor rejected, unless new evidence from a large high quality trial alters this conclusion. Therefore, we urge the reader to interpret the trial results with much caution. Future trials on this issue should be conducted according to the SPIRIT statement and reported according to the CONSORT statement by independent investigators, and using the Foundation of Patient-Centered Outcomes Research recommendations.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Hemoglobinúria Paroxística/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Humanos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Sepsis is a common and frequently fatal condition. Human recombinant activated protein C (APC) has been introduced to reduce the high risk of death associated with severe sepsis or septic shock. This systematic review is an update of a Cochrane review originally published in 2007. OBJECTIVES: We assessed the benefits and harms of APC for patients with severe sepsis or septic shock. SEARCH METHODS: We searched CENTRAL (The Cochrane Library 2012, Issue 6); MEDLINE (2010 to June 2012); EMBASE (2010 to June 2012); BIOSIS (1965 to June 2012); CINAHL (1982 to June 2012) and LILACS (1982 to June 2012). There was no language restriction. SELECTION CRITERIA: We included randomized clinical trials assessing the effects of APC for severe sepsis or septic shock in adults and children. We excluded studies on neonates. We considered all-cause mortality at day 28 and at the end of study follow up, and hospital mortality as the primary outcomes. DATA COLLECTION AND ANALYSIS: We independently performed trial selection, risk of bias assessment, and data extraction in duplicate. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I(2) statistic. We used a random-effects model. MAIN RESULTS: We identified one new randomized clinical trial in this update which includes six randomized clinical trials involving 6781 participants in total, five randomized clinical trials in adult (N = 6307) and one randomized clinical trial in paediatric (N = 474) participants. All trials had high risk of bias and were sponsored by the pharmaceutical industry. APC compared with placebo did not significantly affect all-cause mortality at day 28 compared with placebo (780/3435 (22.7%) versus 767/3346 (22.9%); RR 1.00, 95% confidence interval (CI) 0.86 to 1.16; I(2) = 56%). APC did not significantly affect in-hospital mortality (393/1767 (22.2%) versus 379/1710 (22.1%); RR 1.01, 95% CI 0.87 to 1.16; I(2) = 20%). APC was associated with an increased risk of serious bleeding (113/3424 (3.3%) versus 74/3343 (2.2%); RR 1.45, 95% CI 1.08 to 1.94; I(2) = 0%). APC did not significantly affect serious adverse events (463/3334 (13.9%) versus 439/3302 (13.2%); RR 1.04, 95% CI 0.92 to 1.18; I(2) = 0%). Trial sequential analyses showed that more trials do not seem to be needed for reliable conclusions regarding these outcomes. AUTHORS' CONCLUSIONS: This updated review found no evidence suggesting that APC should be used for treating patients with severe sepsis or septic shock. APC seems to be associated with a higher risk of bleeding. The drug company behind APC, Eli Lilly, has announced the discontinuation of all ongoing clinical trials using this drug for treating patients with severe sepsis or septic shock. APC should not be used for sepsis or septic shock outside randomized clinical trials.
Assuntos
Anti-Infecciosos/uso terapêutico , Proteína C/uso terapêutico , Sepse/tratamento farmacológico , Adulto , Fatores Etários , Anti-Infecciosos/efeitos adversos , Causas de Morte , Criança , Recall de Medicamento , Término Precoce de Ensaios Clínicos , Mortalidade Hospitalar , Humanos , Proteína C/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Sepse/mortalidade , Choque Séptico/tratamento farmacológico , Choque Séptico/mortalidadeRESUMO
Introducción: en Colombia el carcinoma de cuello uterino representa la segunda causa de muerte por cáncer entre las mujeres. Objetivo: describir el valor pronóstico de la densidad microvascular (DMV) y de la expresión proteica de varios genes relacionados con la supervivencia y proliferación del cáncer de cérvix localmente avanzado tratado con quimiorradiación/braquiterapia intracavitaria. Se estimaron la tasa de respuesta global (TRG), la supervivencia libre de progresión (SLP) y la supervivencia global (SG). Resultados: se incluyeron 61 mujeres con una edad media de 52 ± 10 años; todas tenían diagnóstico de cáncer de cérvix localmente avanzado (IIA 2.3%/IIB 47.5%/IIIA 4.9%/IIIB 37.7%/IVA 3.3%/no definido 3.3%), con un volumen tumoral promedio de 6.4cm (DE± 1.8cm) e infección por VPH en 46% de los casos; 58 sujetos (95%) tenían un patrón escamoso, dos fueron adenocarcinomas y >50% presentaba neoplasias moderada o pobremente diferenciadas. Todas fueron tratadas con quimiorradiación (interrupción transitoria de la teleterapia por toxicidad y otras causas en 19 y 21.4%, respectivamente/media de ciclos de platino concomitante 4.8 series ± 1.0) y braquiterapia (77% completaron el tratamiento intracavitario). La mediana para la SLP y global fue de 6.6 meses (4.0-9.1) y 30 meses (1148), respectivamente. Ninguna de las variables tuvo efecto sobre la SLP, mientras el análisis multivariado demostró que los niveles de expresión del VEGF (p=0.026), EGFR (p=0.030), y el volumen tumoral <6 cm (p=0.02) influyeron sobre este desenlace. Conclusión: la tipificación de genes relacionados con angiogénesis y proliferación celular en el cáncer de cérvix localmente avanzado tratado con quimiorradiación basada en platino tiene una influencia positiva sobre el pronóstico. (Acta Med Colomb 2012; 37: 106-117).
Introduction: cervical carcinoma is the second leading cause of cancer death among women in Colombia. Objective: to describe the prognostic value of microvascular density (MVD) and protein expression of several genes related to survival and proliferation of locally advanced cervical cancer (LACC) treated with chemoradiation / intracavitary brachytherapy. We estimated the overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: we included 61 women with a mean age of 52 ± 10 years; all were diagnosed with locally advanced cervical cancer (IIA 2.3% / IIB 47.5% / IIIA 4.9% / IIIB 37.7% / IVA 3.3% / 3.3% undefined ), with an average tumor volume of 6.4cm (SD ± 1.8cm) and HPV infection in 46% of cases. 58 subjects (95%) had a squamous pattern; two were adenocarcinomas and >50% had moderate or poorly differentiated neoplasms. All were treated with chemoradiation (temporary interruption of teletherapy due to toxicity, and other causes was documented in 19% and 21.4% respectively / mean of concomitant platinum cycles 4.8 ± 1.0) and brachytherapy (77% completed intracavitary treatment). The median PFS and OS was 6.6 months (4.0-9.1) and 30 months (11-48), respectively. None of the variables had an effect on the PFS, while multivariate analysis demonstrated that the levels of VEGF expression (p = 0.026), EGFR (p = 0.030), and tumor volume <6 cm (p = 0.02) influenced this outcome. Conclusion: the characterization of genes related to angiogenesis and cell proliferation in locally advanced cervical cancer treated with platinum-based chemoradiation had a positive influence on the prognosis. (Acta Med Colomb 2012; 37: 106-117).
RESUMO
BACKGROUND: Sepsis is a common and frequently fatal condition. Human recombinant activated protein C (APC) has been used to reduce the high rate of death by severe sepsis or septic shock. This is an update of a Cochrane review (originally published in 2007 and updated in 2008). OBJECTIVES: We assessed the clinical effectiveness and safety of APC for the treatment of patients with severe sepsis or septic shock. SEARCH METHODS: For this updated review we searched CENTRAL (The Cochrane Library 2010, Issue 6); MEDLINE (1966 to June 2010); EMBASE (1980 to July 1, 2010); BIOSIS (1965 to July 1, 2010); CINAHL (1982 to 16 June 2010) and LILACS (1982 to 16 June 2010). There was no language restriction. SELECTION CRITERIA: We included randomized controlled trials (RCTs) assessing the effects of APC for severe sepsis in adults and children. We excluded studies on neonates. We considered all-cause mortality at day 28, at the end of study follow up, and hospital mortality as the primary outcomes. DATA COLLECTION AND ANALYSIS: We independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using the I(2) statistic. We used a random-effects model. MAIN RESULTS: We identified one new RCT in this update. We included a total of five RCTs involving 5101 participants. For 28-day mortality, APC did not reduce the risk of death in adult participants with severe sepsis (pooled RR 0.97, 95% confidence interval (CI) 0.78 to 1.22; P = 0.82, I(2) = 68%). APC use was associated with an increased risk of bleeding (RR 1.47, 95% CI 1.09 to 2.00; P = 0.01, I(2) = 0%). In paediatric patients, APC did not reduce the risk of death (RR 0.98, 95% CI 0.66 to 1.46; P = 0.93). Although the included trials had no major limitations most of them modified their original completion or recruitment protocols. AUTHORS' CONCLUSIONS: This updated review found no evidence suggesting that APC should be used for treating patients with severe sepsis or septic shock. Additionally, APC is associated with a higher risk of bleeding. Unless additional RCTs provide evidence of a treatment effect, policy-makers, clinicians and academics should not promote the use of APC.Warning: On October 25th 2011, the European Medicines Agency issued a press release on the worldwide withdrawal of Xigris (activated protein C / drotrecogin alfa) from the market by Eli Lilly due to lack of beneficial effect on 28-day mortality in the PROWESS-SHOCK study. Furthermore, Eli Lily has announced the discontinuation of all other ongoing clinical trials. The final results of the PROWESS-SHOCK study are expected to be published in 2012. This systematic review will be updated when results of the PROWESS-SHOCK or other trials are published.