RESUMO
BACKGROUND: This study aims to genomically characterize melanoma of unknown primary (MUP) in comparison to melanomas of cutaneous primary (MCP). METHODS: Eligible cases were collected from the MSK-IMPACT™ Clinical Sequencing Cohort published in the cBioPortal database. Genomic analysis was performed using a hybridization-capture-based next-generation sequencing assay designed to detect mutations, small insertions and deletions, copy number alterations, and genomic rearrangements. RESULTS: Among 462 patients of whom 18.4% had MUP, brain metastasis was more common among patients with MUP (23% vs 7.1%). The differences in genomic profiling between MCP and MUP did not reach statistical significance. The 187 MCP and 44 MUP patients treated with immune checkpoint inhibitors had a median overall survival of 49 and 44 months, respectively (p = 0.705). CONCLUSIONS: The differences in somatic mutation patterns and survival outcomes were not statistically significant. These findings may allude to similar carcinogenic processes but should be considered exploratory and interpreted with caution.
Assuntos
Melanoma/genética , Neoplasias Primárias Desconhecidas/genética , Neoplasias Cutâneas/genética , Neoplasias Encefálicas/secundário , Variações do Número de Cópias de DNA , Bases de Dados Genéticas , Feminino , Deleção de Genes , Rearranjo Gênico , Genes da Neurofibromatose 1 , Genes p53 , Perfil Genético , Genômica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Neoplasias Pulmonares/secundário , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Melanoma/secundário , Mutação , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Neoplasias Primárias Desconhecidas/mortalidade , Neoplasias Primárias Desconhecidas/patologia , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Telomerase/genéticaRESUMO
The advent of molecular therapy through targeted kinase inhibitors (TKI) has revolutionized the management of renal cell carcinoma. Although surgical resection remains the cornerstone of any therapeutic plan, an increased risk of morbidity and mortality can be of concern in large and complex bulky tumors. Preoperative therapy with TKIs is hypothesized to facilitate resectability, reduce surgical morbidity and allow nephron-sparing surgery. Many concerns on the safety, efficacy and tolerability of these agents before surgery have halted the progress in this setting. In this paper, we will review the indications and safety of preoperative TKIs in RCC as well as the future approaches.
Assuntos
Neoplasias Renais/tratamento farmacológico , Cuidados Pré-Operatórios , Inibidores de Proteínas Quinases/uso terapêutico , Humanos , Neoplasias Renais/patologiaRESUMO
Metastatic urothelial carcinoma of the bladder is a rarely curable disease. Patients receive systemic therapy with limited response rates and survival benefits. The rescue regimens of these patients who have failed first-line treatment had remained problematic until the recent advances. Several trials with novel regimens, including immune checkpoint inhibitors and targeted therapy, to salvage relapsed urothelial carcinoma of the bladder have recently been published. However, the choice of an optimal treatment regimen remains challenging in the absence of randomized trials comparing regimen sequences. Daily clinical cases provoke the question of whether there is a preferred second-line regimen. This paper provides an overview of recent trials and proposes a management algorithm based on subgroup analyses and prognostic features.
Assuntos
Algoritmos , Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/terapia , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/terapia , Ensaios Clínicos como Assunto , HumanosRESUMO
OBJECTIVE: Develop a risk prediction model for severe intraventricular hemorrhage (IVH) in very low birth weight infants (VLBWI). STUDY DESIGN: Prospectively collected data of infants with birth weight 500 to 1249 g born between 2001 and 2010 in centers from the Neocosur Network were used. Forward stepwise logistic regression model was employed. The model was tested in the 2011 cohort and then applied to the population of VLBWI that received prophylactic indomethacin to analyze its effect in the risk of severe IVH. RESULT: Data from 6538 VLBWI were analyzed. The area under ROC curve for the model was 0.79 and 0.76 when tested in the 2011 cohort. The prophylactic indomethacin group had lower incidence of severe IVH, especially in the highest-risk groups. CONCLUSION: A model for early severe IVH prediction was developed and tested in our population. Prophylactic indomethacin was associated with a lower risk-adjusted incidence of severe IVH.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Hemorragia Cerebral , Indometacina/uso terapêutico , Recém-Nascido de muito Baixo Peso , Medição de Risco/métodos , Hemorragia Cerebral/prevenção & controle , Feminino , Humanos , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Modelos Logísticos , Masculino , Curva ROCRESUMO
OBJECTIVE: To evaluate whether early treatment with inhaled nitric oxide (iNO) will prevent newborns with moderate respiratory failure from developing severe hypoxemic respiratory failure (oxygenation index (OI)>or=40). STUDY DESIGN: A total of 56 newborns with moderate respiratory failure (OI between 10 and 30) were randomized before 48 h after birth to early treatment with 20 p.p.m. of iNO (Early iNO group, n=28) or conventional mechanical ventilation with FiO(2) 1.0 (Control group, n=28). Infants received iNO and/or high-frequency oscillatory ventilation (HFOV) if they developed an OI>40. RESULT: 7 of 28 early iNO patients (25%) compared to 17 of 28 control patients (61%) developed an OI>40 (P<0.05). In the Early iNO group mean OI significantly decreased from 22 (baseline) to 19 at 4 h (P<0.05) and remained lower over time: 19 (12 h), 18 (24 h) and 16 at 48 h. In contrast, OI increased in the Control group and remained significantly higher than the Early iNO group during the first 48 h of study: 22 (baseline), 29, 35, 32 and 23 at 4, 12, 24 and 48 h, respectively (P<0.01). Of 17, 6 control patients who developed an OI>40 were successfully treated with iNO. Nine of the remaining eleven control patients and six of seven Early iNO patients who had an OI>40 despite use of iNO responded with the addition of HFOV. One patient of the Early iNO group and two of the Control group died. Median (range) duration of oxygen therapy was significantly shorter in the Early iNO group: 11.5 (5 to 90) days compared to 18 (6 to 142) days of the Control group (P<0.03). CONCLUSION: Early use of iNO in newborns with moderate respiratory failure improves oxygenation and decreases the probability of developing severe hypoxemic respiratory failure.
Assuntos
Ventilação de Alta Frequência , Hipóxia/prevenção & controle , Óxido Nítrico/administração & dosagem , Síndrome da Persistência do Padrão de Circulação Fetal/terapia , Insuficiência Respiratória/prevenção & controle , Administração por Inalação , Feminino , Humanos , Recém-Nascido , Masculino , Síndrome da Persistência do Padrão de Circulação Fetal/complicações , Insuficiência Respiratória/etiologia , Análise de SobrevidaRESUMO
Antibiotic resistance among Gram-negative pathogens in hospitals is a growing threat to patients and is driving the increased use of carbapenems. Carbapenems are potent members of the beta-lactam family of antibiotics, with a history of safety and efficacy for serious infections that exceeds 20 years. Original and review articles were identified from a Medline search (1979-2008). Reference citations from identified publications, abstracts from the Interscience Conferences on Antimicrobial Agents and Chemotherapy and package inserts were also used. Carbapenems are effective in treating severe infections at diverse sites, with relatively low resistance rates and a favourable safety profile. Carbapenems are the beta-lactams of choice for the treatment of infections caused by multidrug-resistant organisms. Optimized dosing of carbapenems should limit the emergence of resistance and prolong the utility of these agents. The newly approved doripenem should prove to be a valuable addition to the currently available carbapenems: imipenem, meropenem and ertapenem.
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Carbapenêmicos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Carbapenêmicos/administração & dosagem , Carbapenêmicos/efeitos adversos , Carbapenêmicos/uso terapêutico , Resistência Microbiana a Medicamentos , HumanosRESUMO
In South American countries, the class A extended-spectrum beta-lactamases (ESBLs) so far recognised belong to the CTX-M, Pseudomonas Extended Resistance (PER), SHV and TEM families. ESBL rates in South America are among the highest in the world, probably due to multiple factors. SHV- and TEM-type ESBLs have been frequently encountered, but CTX-M is endemic and widely dominant. PER-type ESBLs seem to be restricted to the southern 'cone' of South America. Community-acquired ESBLs are starting to appear.
Assuntos
Bactérias Gram-Negativas/enzimologia , Infecções por Bactérias Gram-Negativas/epidemiologia , beta-Lactamases/biossíntese , beta-Lactamases/classificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pré-Escolar , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Prevalência , América do Sul/epidemiologia , Resistência beta-LactâmicaRESUMO
Extracorporeal membrane oxygenation (ECMO) is a therapy that ensures adequate tissue oxygen delivery in patients suffering cardiac and/or respiratory failure that are unresponsive to conventional therapy. During ECMO, it is common to see a decrease in urine output that may be associated with acute renal failure. In this context, continuous renal replacement therapy (CRRT) should be considered. Our aim is to evaluate a pioneer experience in Latin America, related to the use of CRRT in a group of neonatal-pediatric patients during ECMO. We conducted a retrospective review of patients treated with ECMO at our institution between May 2003 and May 2005. Twelve infants were treated with ECMO, six of them also underwent CRRT. The main reasons for CRRT initiation were fluid overload and progressive azotemia. Observed complications were clots in the filter and excessive ultrafiltration. CRRT was successful in fluid management and solute clearance in all patients. Discharge survival rate was 83%, all of them with normal renal function. Concurrent CRRT with ECMO is technically feasible and efficacious in the management of fluid overload and solute clearance. We report the first experience with these therapies in a Latin American neonatal-pediatric ECMO program associated with the Extracorporeal Life Support Organization.
Assuntos
Injúria Renal Aguda/terapia , Oxigenação por Membrana Extracorpórea , Hemodiafiltração , Injúria Renal Aguda/complicações , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Testes de Função Renal , Masculino , Transtornos Respiratórios/complicações , Transtornos Respiratórios/terapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
El incremento de los cánceres incidentales del riñón podría significar un aumento de la cirugía conservadora en el tratamiento del cáncer renal. Se analiza una serie constituida por 15 casos de la cirugía conservadora en el tratamiento de cánceres renales durante 11 años. Corresponde a alrededor del 8 por ciento del total de operaciones por cáncer renal en ese período. En once oportunidades debió realizarse este tipo de intervenciones por tumores bilaterales sincrónicos (9 casos) o monorrenos reales o funcionales (2 casos). Solo 4 pacientes fueron sometidos a cirugía conservador por tumor unilateral pequeño. Del total de tumores renales incidentales Grado I de Robson (18 casos), candidatos a cirugía parcial, solo se realizó ésta en el 22 por ciento dadas las características de localización y tamaño del tumor. El tiempo de seguimiento para los 15 pacientes varió entre 4 y 119 meses. La sobrevida actuarial es del 93 por ciento. Se discuten las indicaciones, ventajas e inconvenientes de este tipo de tratamiento de los cánceres renales a la luz del claro incremento de los tumores incidentales renales