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Aims: Cardiogenic shock (CS) and cardiac arrest (CA) are serious complications in ST-elevation myocardial infarction (STEMI) patients, with lack of long-term data according to their timing of occurrence. This study sought to determine the incidence and relationship between the timing of occurrence and prognostic impact of CS and CA complicating STEMI in the long-term follow-up. Methods and results: We conducted a retrospective analysis of consecutive STEMI patients treated between 2004 and 2017. Patients were divided into four groups based on the occurrence of neither CA nor CS, CA only, CS only, and both CA and CS (CA-CS-, CA+, CS+, and CA+CS+, respectively). Adjusted Cox regression analysis was used to assess the independent association between the CS and CA categories and mortality. A total of 1603 STEMI patients were followed for a median of 3.6 years. CA and CS occurred in the 12.2% and 15.9% of patients, and both impacted long-term mortality [adjusted hazard ratio (HR) = 2.59, 95% confidence interval (CI): 1.53-4.41, P < 0.001; HR = 3.16, 95% CI: 2.21-4.53, P < 0.001, respectively). CA+CS+ occurred in 7.3%, with the strongest association with higher mortality (adjusted HR = 5.36; 95% CI: 3.80-7.55, P < 0.001). Using flexible parametric models with B-splines, the increased mortality was restricted to the first â¼10 months. In addition, overall mortality rates were higher at all timings (all with P < 0.001), except for CA during initial cardiac catheterization (P < 0.183). Conclusion: CS and CA complicating patients presenting with STEMI were associated with higher long-term mortality rate, especially in the first 10 months. Both CS+ and CA+ at any timeframe impacted outcomes, except for CA+ during the initial cardiac catheterization, although this will have to be confirmed in larger future studies, given the relatively small number of patients.
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BACKGROUND: The incidence of adenocarcinoma of the ampulla of Vater has been increasing over the past years. Nevertheless, it is still a rare disease and the prognostic factors predicting long-term survival are not sufficiently clarified. This study aims to evaluate the association between histopathological characteristics and long-term survival of patients with ampullary cancer after curative resection, as well as the efficiency of immunohistochemical expression of CK7, CK20, and CDX2 to distinguish the histopathological (intestinal or pancreaticobiliary) patterns. METHODS: Demographic, histopathological data, pTNM stage, and immunohistochemical expression patterns were collected from 65 patients with adenocarcinoma of the ampulla of Vater. Five and 10-year overall and disease-free survival rates after curative resection were determined. RESULTS: Of the 65 patients with ampullary carcinoma, 47 (72%) underwent radical resection. The 5- and 10-year overall survival rate was 46% and 37%, respectively. Our results demonstrate that the main prognostic factors were the presence and number of lymph node metastases, lymph node ratio (LNR), differentiation grade, and lymphovascular invasion. After multivariate analysis, only lymph node ratio ≥ 20% remained an independent prognostic factor of survival (HR: 2.63 95% CI: 1.05-6.61; p = 0.039). CONCLUSION: Here, we demonstrated more evidence that the lymph node metastases are associated with poor prognosis in ampullary carcinoma. Particularly, the relation between the number of metastatic lymph nodes and the number of harvested lymph node (LNR) should be considered a major prognostic factor.
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Adenocarcinoma/epidemiología , Adenocarcinoma/patología , Ampolla Hepatopancreática/patología , Neoplasias del Conducto Colédoco/epidemiología , Neoplasias del Conducto Colédoco/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Ampolla Hepatopancreática/cirugía , Biomarcadores de Tumor , Brasil , Factor de Transcripción CDX2 , Neoplasias del Conducto Colédoco/cirugía , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Queratina-20 , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
In this article, we introduce a long-term survival model in which the number of competing causes of the event of interest follows the zero-modified geometric (ZMG) distribution. Such distribution accommodates equidispersion, underdispersion, and overdispersion and captures deflation or inflation of zeros in the number of lesions or initiated cells after the treatment. The ZMG distribution is also an appropriate alternative for modeling clustered samples when the number of competing causes of the event of interest consists of two subpopulations, one containing only zeros (cure proportion), while in the other (noncure proportion) the number of competing causes of the event of interest follows a geometric distribution. The advantage of this assumption is that we can measure the cure proportion in the initiated cells. Furthermore, the proposed model can yield greater or lower cure proportion than that of the geometric distribution when modeling the number of competing causes. In this article, we present some statistical properties of the proposed model and use the maximum likelihood method to estimate the model parameters. We also conduct a Monte Carlo simulation study to evaluate the performance of the estimators. We present and discuss two applications using real-world medical data to assess the practical usefulness of the proposed model.
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Melanoma , Modelos Estadísticos , Humanos , Funciones de Verosimilitud , Melanoma/tratamiento farmacológico , Método de Montecarlo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Thoracic transplantation is considered for patients with Eisenmenger syndrome (ES) who have refractory right ventricular failure despite optimal therapy for pulmonary arterial hypertension. This study compared the outcomes of bilateral lung transplantation (BLT) with cardiac defect repair vs combined heart-lung transplantation (HLT). RESEARCH QUESTION: This study presents an updated analysis using a US national registry to evaluate the outcomes of patients diagnosed with ES who underwent HLT or BLT with repair of cardiac defects. STUDY DESIGN AND METHODS: This study identified patients with ES who underwent thoracic transplantation from 1987 to 2018 from the United Network for Organ Sharing database. Survival curves were estimated by using the Kaplan-Meier method and were compared by using the log-rank test. RESULTS: During the study period, 442 adults with ES underwent thoracic transplantation (316 HLTs and 126 BLTs). Following BLT, overall survival 1, 5, and 10 years' posttransplant was 63.1%, 38.5%, and 30.2%, respectively. Following HLT, overall survival 1, 5, and 10 years' posttransplant was 68.0%, 47.3%, and 30.5% (P = .6). When survival analysis was stratified according to type of defect, patients with an atrial septal defect had better survival following BLT than following HLT (88.3% vs 63.2% 1 year posttransplant, P < .01; 71.1% vs 49.8% 3 years' posttransplant, P < .01; and 37.4% vs 29.9% 10 years' posttransplant, P = .08). Patients with a ventricular septal defect (VSD) exhibited better survival following HLT than following BLT (78.2% vs 49.6% 1 year posttransplant, P < .01; 55.6% vs 34.3% 5 years' posttransplant, P < .01; and 35.7% vs 26.5% 10 years' posttransplant, P = .03). The most common cause of mortality in patients with VSD undergoing BLT was cardiac ventricular failure. INTERPRETATION: This study suggests that the best transplant option for patients with VSD remains HLT, which prevents subsequent development of ventricular failure. BLT with cardiac defect repair should be considered as the first-line treatment option in patients with ES due to an uncorrected atrial septal defect. These patients can be considered to have isolated and reversible right ventricular failure akin to patients with advanced pulmonary arterial hypertension.
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Complejo de Eisenmenger/cirugía , Trasplante de Corazón-Pulmón/métodos , Trasplante de Pulmón/métodos , Sistema de Registros , Receptores de Trasplantes , Adulto , Complejo de Eisenmenger/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiologíaRESUMEN
In this paper, we propose a generalization of the power series cure rate model for the number of competing causes related to the occurrence of the event of interest. The model includes distributions not yet used in the cure rate models context, such as the Borel, Haight and Restricted Generalized Poisson distributions. The model is conveniently parameterized in terms of the cure rate. Maximum likelihood estimation based on the Expectation Maximization algorithm is discussed. A simulation study designed to assess some properties of the estimators is carried out, showing the good performance of the proposed estimation procedure in finite samples. Finally, an application to a bone marrow transplant data set is presented.
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Algoritmos , Modelos Estadísticos , Funciones de Verosimilitud , Distribución de Poisson , Análisis de SupervivenciaRESUMEN
AIM AND OBJECTIVE: The aim and objective of this study is to test the effect of an optimized caloric supply in the first week of intensive care unit (ICU) stay in mechanically ventilated patients on the ability to perform their activities of daily living (ADL) in the long-term. MATERIALS AND METHODS: A prospective observational study comparing patients who achieved an adequate caloric target (≥80%) vs those whose target was inadequate (<80%). The primary outcome under study is the instrumental ADL (IADL) scale after 6 months of discharge. RESULTS: Ninety-two patients were evaluated in the ICU and 50 were alive at 6 months. Follow-up was lost for 3 patients and 47 patients were evaluated at ICU and after 6 months. Thirty-four patients reached the energetic target and 13 did not reach it. There was no significant variation in IADL. CONCLUSION: The energy adequacy in the first week of hospitalization was achieved by most survivors; however, this conduct does not seem to have influenced the ability to perform ADL after 6 months of discharge. HOW TO CITE THIS ARTICLE: Dariano AP, Couto CFL, Rubin BA, Viana MV, Friedman G. Caloric Adequacy in the First Week of Mechanically Ventilated Patients has No Impact on Long-term Daily Life Activities. Indian J Crit Care Med 2020;24(12):1206-1212.
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Trisomy 18 is a genetic disease resulting from an extra chromosome 18, characterized by a broad clinical spectrum, poor prognosis and low rates of survival. This is the case of a 12 year-old girl diagnosed with full trisomy 18, and multiple malformations, including Dandy-Walker Syndrome and congenital heart defects on long term survival. At nine months, a new echocardiogram showed a double outlet right ventricle, significant pulmonary stenosis, patent ductus arteriosus and ventricular septal defect. Cardiac surgery was performed at one year and seven months. Early surgical intervention and multidisciplinary follow-up may change the clinical outcome of the disease. Further studies are required to evaluate the benefit of invasive procedures such as cardiac surgery on survival of patients with trisomy 18.
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Síndrome de Dandy-Walker/complicaciones , Factores de Tiempo , Síndrome de la Trisomía 18/complicaciones , Niño , Síndrome de Dandy-Walker/diagnóstico por imagen , Síndrome de Dandy-Walker/mortalidad , Femenino , Humanos , Tomografía Computarizada por Rayos X/métodos , Síndrome de la Trisomía 18/diagnóstico por imagen , Síndrome de la Trisomía 18/mortalidadRESUMEN
BACKGROUND: Progress in immunotherapy has revolutionized the treatment landscape for advanced lung cancer, with emerging evidence of patients experiencing long-term survivals. The goal of this study was to explore the existence of short- and long-term survival populations and to assess the effect of immunotherapy on them. METHODS: Data from two randomized, multicenter, controlled clinical trials was used to evaluate the effect of two therapeutic vaccines (anti-idiotypic vaccine VAXIRA and anti-EGF vaccine CIMAVAX) on survival curves in advanced non-small cell lung cancer patients. Data were fitted to Kaplan-Meier, standard Weibull survival, and two-component Weibull mixture models. Bayesian Information Criterion was used for model selection. RESULTS: VAXIRA did not modify, neither the fraction of patients with long-term survivals (0.18 in the control group v 0.19 with VAXIRA, P = .88), nor the median overall survival of the patients in the short-term survival subpopulation (6.8 v 7.8 months, P = .24). However, this vaccine showed great benefit for the patients belonging to the subpopulation of patients with long-term survival (33.8 v 76.6 months, P <.0001). CIMAVAX showed impact in the overall survival of both short- and long-term populations (6.8 v 8.8 months, P = .005 and 33.8 v 61.8 months, P = .007). It also increased the proportion of patients with long-term survival (from 0.18 to 0.28, P = .02). CONCLUSIONS: This study shows that therapeutic vaccines produce differential effects on short- and long-term survival populations and illustrates the application of advanced statistical methods to deal with the long-term evolution of patients with advanced lung cancer in the era of immunotherapy.
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Vacunas contra el Cáncer/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inmunoterapia/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Cuba , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos Teóricos , Sistema de Registros/estadística & datos numéricos , Factores de TiempoRESUMEN
In this article, we propose an alternative gap time model based on a multiplicative marginal rate function, which is formulated considering each gap time conditional on the previous recurrence times. In this formulation, the gap times are treated equally and the relation between successive events is no longer a problem. Furthermore, this article considers the inclusion of a proportion of zero-recurrence units (for which the event of interest will not occur) into the model to analyze recurrent event data. Inference aspects of the proposed model are discussed through maximum likelihood approach. A simulation study is carried out to examine the performance of the estimation procedure. The model is applied to hospital readmission data among colorectal cancer patients.
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Modelos Estadísticos , Recurrencia , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/terapia , Humanos , Funciones de Verosimilitud , Readmisión del Paciente/estadística & datos numéricos , Estadística como Asunto , Factores de TiempoRESUMEN
BACKGROUND: Propionibacterium freudenreichii is an Actinobacterium widely used in the dairy industry as a ripening culture for Swiss-type cheeses, for vitamin B12 production and some strains display probiotic properties. It is reportedly a hardy bacterium, able to survive the cheese-making process and digestive stresses. RESULTS: During this study, P. freudenreichii CIRM-BIA 138 (alias ITG P9), which has a generation time of five hours in Yeast Extract Lactate medium at 30 °C under microaerophilic conditions, was incubated for 11 days (9 days after entry into stationary phase) in a culture medium, without any adjunct during the incubation. The carbon and free amino acids sources available in the medium, and the organic acids produced by the strain, were monitored throughout growth and survival. Although lactate (the preferred carbon source for P. freudenreichii) was exhausted three days after inoculation, the strain sustained a high population level of 9.3 log10 CFU/mL. Its physiological adaptation was investigated by RNA-seq analysis and revealed a complete disruption of metabolism at the entry into stationary phase as compared to exponential phase. CONCLUSIONS: P. freudenreichii adapts its metabolism during entry into stationary phase by down-regulating oxidative phosphorylation, glycolysis, and the Wood-Werkman cycle by exploiting new nitrogen (glutamate, glycine, alanine) sources, by down-regulating the transcription, translation and secretion of protein. Utilization of polyphosphates was suggested.
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Adaptación Fisiológica , Propionibacterium freudenreichii/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Carbono/metabolismo , Medios de Cultivo/química , Regulación hacia Abajo , Glucólisis/genética , Concentración de Iones de Hidrógeno , Metaboloma , Fosforilación Oxidativa , Oxígeno/metabolismo , Propionibacterium freudenreichii/genética , Propionibacterium freudenreichii/crecimiento & desarrollo , ARN Bacteriano/química , ARN Bacteriano/aislamiento & purificación , ARN Bacteriano/metabolismo , Análisis de Secuencia de ARNRESUMEN
BACKGROUND: Gliomas display a high degree of intratumor heterogeneity, including changes in physiological parameters and lipid composition of the plasma membrane, which may contribute to the development of drug resistance. Biophysical interactions between therapeutic agents and the lipid components at the outer plasma membrane interface are critical for effective drug uptake. Amphipathic molecules such as perillyl alcohol (POH) have a high partition coefficient and generally lead to altered lipid acyl tail dynamics near the lipid-water interface, impacting the lipid bilayer structure and transport dynamics. We therefore hypothesized that glioma cells may display enhanced sensitivity to POH-induced apoptosis due to plasma membrane alterations, while in non-transformed cells, POH may be expelled through thermal agitation. METHODS: Interactions between POH and the plasma membrane was studied using molecular dynamics simulations. In this phase I/II trial, we set up to evaluate the clinical effectiveness of long-term (up to 5 years) daily intranasal administration of POH in a cohort of 19 patients with low-grade glioma (LGG). Importantly, in a series of clinical studies previously published by our group, we have successfully established that intranasal delivery of POH to patients with malignant gliomas is a viable and effective therapeutic strategy. RESULTS: POH altered the plasma membrane potential of the lipid bilayer of gliomas and prolonged intranasal administration of POH in a cohort of patients with LGG halted disease progression with virtually no toxicity. CONCLUSION: Altogether, the results suggest that POH-induced alterations of the plasma membrane might be contributing to its therapeutic efficacy in preventing LGG progression.
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BACKGROUND: The aim was to assess the incidence of prosthesis-patient mismatch (PPM) after mitral valve replacement (MVR) in patients receiving Biocor® porcine or mechanical valves, and to evaluate the effect of PPM on long-term survival. METHODS: All patients undergoing MVR between 2009 and 2013 received either mechanical or bioprosthetic valves (Biocor® porcine). PPM was defined as severe when the indexed effective ori-fice area was < 0.9 cm2/m2, moderate between 0.9 cm2/m2 and 1.2 cm2/m2 or absent > 1.2 cm2/m2. The primary endpoint was all-cause long-term mortality. RESULTS: Among a total of 136 MVR, PPM was severe in 27%, moderate in 44% and absent in 29% of patients. Implanted valves were 57% mechanical and 43% bioprosthetic. Only 3% of patients with mechanical valves had severe PPM vs. 59% with bioprostheses (p < 0.0001). Sixty-month survival with severe mismatch was 0.559 (SE 0.149) and with no mismatch 0.895 (SE 0.058) (p = 0.043). Survival of patients suffering from severe mismatch, or moderate mismatch with pulmonary hypertension (PH) was 0.749 (SE 0.101); while for patients with no mismatch or with moderate mismatch without PH, survival was 0.951 (SE 0.028) (p = 0.016). CONCLUSIONS: About one-fourth of patients had severe PPM and almost all of them had received a bioprosthesis. Sixty-month survival was significantly lower in patients with severe mismatch, or moderate mismatch with PH. Specifically, when a bioprothesis is chosen and while further evidence on the impact of PPM on clinical outcomes appears, surgeons are recommended to follow a preoperative strategy to implant a mitral prosthesis of adequate size in order to prevent PPM.
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Bioprótesis/efectos adversos , Prótesis Valvulares Cardíacas/efectos adversos , Hipertensión Pulmonar/etiología , Insuficiencia de la Válvula Mitral/cirugía , Válvula Mitral/cirugía , Complicaciones Posoperatorias , Anciano , Argentina/epidemiología , Ecocardiografía , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Pulmonar/epidemiología , Incidencia , Masculino , Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/diagnóstico , Insuficiencia de la Válvula Mitral/mortalidad , Diseño de Prótesis , Falla de Prótesis , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
AIMS: Propionibacterium freudenreichii is an actinobacterium widely used in dairy industry during the ripening process of Swiss-type cheeses and which presents probiotic properties. P. freudenreichii is reportedly a hardy bacterium, able to survive during the cheese-making process and when subjected to digestive stresses. During this study the long-term survival (LTS) of P. freudenreichii was investigated for 11 days by means of phenotypic characterization in a culture medium without the addition of any nutrients. METHODS AND RESULTS: For 11 days, in a non-nutrient supplemented culture medium, eight strains were monitored by measuring their optical density, counting colony-forming units (CFU) and using LIVE/DEAD staining and microscopy observation. Under these conditions, all strains displayed high survival rates in the culture medium, their culturability reaching more than 9 log10 CFU ml(-1) after 2 days. After 11 days, this value ranged from 7·8 to 8·2 log10 CFU ml(-1) depending on the strain, and at least 50% of the P. freudenreichii population displayed an intact envelope. As lysis of part of a bacterial population may be a microbial strategy to recover nutrients, in CIRM-BIA 138 (the strain with the highest population at day 11), cell lysis was assessed by quantifying intact bacterial cells using qPCR targeting the housekeeping gene tuf. No lysis was observed. CONCLUSION: Taken together, our results suggest that P. freudenreichii strains use a viable but nonculturable state to adapt to the LTS phase. SIGNIFICANCE AND IMPACT OF THE STUDY: Assessing the viability of P. freudenreichii and understanding their mechanisms for survival should be of great interest regarding their potential probiotic applications.
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Medios de Cultivo/metabolismo , Propionibacterium/crecimiento & desarrollo , Medios de Cultivo/análisis , Viabilidad Microbiana , Propionibacterium/metabolismoRESUMEN
Glioblastoma multiforme (GBM) is the most common glial tumor of the brain system; nevertheless, the giant cell (GC) subtype is uncommon. Recent reviews report for an incidence of 1% in adults and 3% in children. The GCs usually have a better prognosis than GBM and also an increasing long-term survival rate. It is known that the diagnosis of this tumor is due to its histological findings and patterns, such as the unusual increased number of giant cells. Unfortunately, due to its rarity, the immunohistochemical and cytogenetical analysis of this tumor is not well known. Some authors also suggest that there are few subtypes of GCs and their patterns of aggressiveness could be due to cytogenetical markers. It is recognized that maximum safe resection treatment and adjuvant radiotherapy can improve survival rate (5-13 months) similar to GBM patients.
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A new flexible cure rate survival model is developed where the initial number of competing causes of the event of interest (say lesions or altered cells) follow a compound negative binomial (NB) distribution. This model provides a realistic interpretation of the biological mechanism of the event of interest as it models a destructive process of the initial competing risk factors and records only the damaged portion of the original number of risk factors. Besides, it also accounts for the underlying mechanisms that leads to cure through various latent activation schemes. Our method of estimation exploits maximum likelihood (ML) tools. The methodology is illustrated on a real data set on malignant melanoma, and the finite sample behavior of parameter estimates are explored through simulation studies.