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1.
Crit Care Med ; 51(5): 657-676, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-37052436

RESUMEN

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. DESIGN: The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. INTERVENTIONS: In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. CONCLUSIONS: Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Adulto , Humanos , Insuficiencia Hepática Crónica Agudizada/terapia , Infectología , Unidades de Cuidados Intensivos , Revisiones Sistemáticas como Asunto , Metaanálisis como Asunto , Práctica Clínica Basada en la Evidencia
2.
Crit Care ; 27(1): 432, 2023 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-37940985

RESUMEN

BACKGROUND: Given the success of recent platform trials for COVID-19, Bayesian statistical methods have become an option for complex, heterogenous syndromes like sepsis. However, study design will require careful consideration of how statistical power varies using Bayesian methods across different choices for how historical data are incorporated through a prior distribution and how the analysis is ultimately conducted. Our objective with the current analysis is to assess how different uses of historical data through a prior distribution, and type of analysis influence results of a proposed trial that will be analyzed using Bayesian statistical methods. METHODS: We conducted a simulation study incorporating historical data from a published multicenter, randomized clinical trial in the US and Canada of polymyxin B hemadsorption for treatment of endotoxemic septic shock. Historical data come from a 179-patient subgroup of the previous trial of adult critically ill patients with septic shock, multiple organ failure and an endotoxin activity of 0.60-0.89. The trial intervention consisted of two polymyxin B hemoadsorption treatments (2 h each) completed within 24 h of enrollment. RESULTS: In our simulations for a new trial of 150 patients, a range of hypothetical results were observed. Across a range of baseline risks and treatment effects and four ways of including historical data, we demonstrate an increase in power with the use of clinically defensible incorporation of historical data. In one possible trial result, for example, with an observed reduction in risk of mortality from 44 to 37%, the probability of benefit is 96% with a fixed weight of 75% on prior data and 90% with a commensurate (adaptive-weighting) prior; the same data give an 80% probability of benefit if historical data are ignored. CONCLUSIONS: Using Bayesian methods and a biologically justifiable use of historical data in a prior distribution yields a study design with higher power than a conventional design that ignores relevant historical data. Bayesian methods may be a viable option for trials in critical care medicine where beneficial treatments have been elusive.


Asunto(s)
Sepsis , Choque Séptico , Adulto , Humanos , Teorema de Bayes , Polimixina B/uso terapéutico , Proyectos de Investigación , Sepsis/tratamiento farmacológico , Choque Séptico/tratamiento farmacológico
3.
J Biomed Inform ; 146: 104483, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37657712

RESUMEN

OBJECTIVE: To evaluate the technical feasibility and potential value of a digital assistant that prompts intensive care unit (ICU) rounding teams to use evidence-based practices based on analysis of their real-time discussions. METHODS: We evaluated a novel voice-based digital assistant which audio records and processes the ICU care team's rounding discussions to determine which evidence-based practices are applicable to the patient but have yet to be addressed by the team. The system would then prompt the team to consider indicated but not yet delivered practices, thereby reducing cognitive burden compared to traditional rigid rounding checklists. In a retrospective analysis, we applied automatic transcription, natural language processing, and a rule-based expert system to generate personalized prompts for each patient in 106 audio-recorded ICU rounding discussions. To assess technical feasibility, we compared the system's prompts to those created by experienced critical care nurses who directly observed rounds. To assess potential value, we also compared the system's prompts to a hypothetical paper checklist containing all evidence-based practices. RESULTS: The positive predictive value, negative predictive value, true positive rate, and true negative rate of the system's prompts were 0.45 ± 0.06, 0.83 ± 0.04, 0.68 ± 0.07, and 0.66 ± 0.04, respectively. If implemented in lieu of a paper checklist, the system would generate 56% fewer prompts per patient, with 50%±17% greater precision. CONCLUSION: A voice-based digital assistant can reduce prompts per patient compared to traditional approaches for improving evidence uptake on ICU rounds. Additional work is needed to evaluate field performance and team acceptance.

4.
Clin Transplant ; 35(6): e14298, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33764591

RESUMEN

BACKGROUND: Orthotopic liver transplantation (OLT) is the only treatment option for various end-stage liver diseases. Ischemia and reperfusion (I/R) injury is one of the unavoidable complications/conditions in OLT. In 2019, a total of 8896 livers were transplanted of which >94% organs were procured from deceased donors. An increase in the use of extended criteria donor (ECD) livers for transplantation further unraveled the role of hepatic I/R injury on short-term and long-term graft outcomes. Despite promising outcomes with the use of antioxidants, free radical scavengers, and vasodilators; I/R-mediated liver injury persists and significantly influences the overall clinical outcomes. Treprostinil, a synthetic prostacyclin I2  (PGI2 ) analog, due to its vasodilatory property, antiplatelet activity, and its ability to downregulate pro-inflammatory cytokines can potentially minimize I/R injury. AIM: We investigated the safety and preliminary efficacy of continuous intravenous infusion of treprostinil in liver transplant recipients in a prospective, single-center, non-randomized, interventional study. MATERIAL AND METHODS: This was a dose escalation (3 + 3 design) phase 1/2 study. Deceased donor liver transplant recipients received 5 ng/kg/min for two days, or 2.5, 5, and 7.5 ng/min/kg for 5 days as a continuous infusion. Multiple blood samples were collected for biochemical parameter assessment and for measuring treprostinil levels. Indocyanine green plasma disappearance rate was used as a measure of hepatic functional capacity. RESULTS: Subjects tolerated continuous infusion of treprostinil up to 5 ng/kg/min for 120 h with no occurrence of primary graft non-function (PNF), minimized need for ventilation support, reduced hospitalization time, 100% graft and patient survival, and improved hepatobiliary excretory function comparable to normal healthy adults. DISCUSSION: Treprostinil can be administered to liver transplant patients safely during the perioperative period. CONCLUSION: Based on this phase 1/2 study, further efficacy studies of treprostinil in preventing I/R injury of liver should be conducted to potentially increase the number of livers available for transplantation.


Asunto(s)
Trasplante de Hígado , Daño por Reperfusión , Adulto , Epoprostenol/análogos & derivados , Humanos , Isquemia , Hígado , Donadores Vivos , Estudios Prospectivos , Daño por Reperfusión/etiología , Daño por Reperfusión/prevención & control
5.
Crit Care ; 25(1): 185, 2021 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-34059102

RESUMEN

BACKGROUND: Persistent acute kidney injury (AKI) portends worse clinical outcomes and remains a therapeutic challenge for clinicians. A recent study found that urinary C-C motif chemokine ligand 14 (CCL14) can predict the development of persistent AKI. We aimed to externally validate urinary CCL14 for the prediction of persistent AKI in critically ill patients. METHODS: This was a secondary analysis of the prospective multi-center SAPPHIRE study. We evaluated critically ill patients with cardiac and/or respiratory dysfunction who developed Kidney Disease: Improving Global Outcomes (KDIGO) stage 2-3 AKI within one week of enrollment. The main exposure was the urinary concentration of CCL14 measured at the onset of AKI stage 2-3. The primary endpoint was the development of persistent severe AKI, defined as ≥ 72 h of KDIGO stage 3 AKI or death or renal-replacement therapy (RRT) prior to 72 h. The secondary endpoint was a composite of RRT and/or death by 90 days. We used receiver operating characteristic (ROC) curve analysis to assess discriminative ability of urinary CCL14 for the development of persistent severe AKI and multivariate analysis to compare tertiles of urinary CCL14 and outcomes. RESULTS: We included 195 patients who developed KDIGO stage 2-3 AKI. Of these, 28 (14%) developed persistent severe AKI, of whom 15 had AKI ≥ 72 h, 12 received RRT and 1 died prior to ≥ 72 h of KDIGO stage 3 AKI. Persistent severe AKI was associated with chronic kidney disease, diabetes mellitus, higher non-renal APACHE III score, greater fluid balance, vasopressor use, and greater change in baseline serum creatinine. The AUC for urinary CCL14 to predict persistent severe AKI was 0.81 (95% CI, 0.72-0.89). The risk of persistent severe AKI increased with higher values of urinary CCL14. RRT and/or death at 90 days increased within tertiles of urinary CCL14 concentration. CONCLUSIONS: This secondary analysis externally validates urinary CCL14 to predict persistent severe AKI in critically ill patients.


Asunto(s)
Lesión Renal Aguda/diagnóstico , Quimiocinas CC/análisis , APACHE , Lesión Renal Aguda/fisiopatología , Anciano , Área Bajo la Curva , Biomarcadores/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC
6.
Crit Care Med ; 48(3): e173-e191, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32058387

RESUMEN

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute or acute on chronic liver failure in the ICU. DESIGN: The guideline panel comprised 29 members with expertise in aspects of care of the critically ill patient with liver failure and/or methodology. The Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy were followed throughout. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. SETTING: The panel was divided into nine subgroups: cardiovascular, hematology, pulmonary, renal, endocrine and nutrition, gastrointestinal, infection, perioperative, and neurology. INTERVENTIONS: We developed and selected population, intervention, comparison, and outcomes questions according to importance to patients and practicing clinicians. For each population, intervention, comparison, and outcomes question, we conducted a systematic review aiming to identify the best available evidence, statistically summarized the evidence whenever applicable, and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: In this article, we report 29 recommendations (from 30 population, intervention, comparison, and outcomes questions) on the management acute or acute on chronic liver failure in the ICU, related to five groups (cardiovascular, hematology, pulmonary, renal, and endocrine). Overall, six were strong recommendations, 19 were conditional recommendations, four were best-practice statements, and in two instances, the panel did not issue a recommendation due to insufficient evidence. CONCLUSIONS: Multidisciplinary international experts were able to formulate evidence-based recommendations for the management acute or acute on chronic liver failure in the ICU, acknowledging that most recommendations were based on low-quality indirect evidence.


Asunto(s)
Fallo Hepático Agudo/terapia , Guías de Práctica Clínica como Asunto/normas , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia , Insuficiencia Hepática Crónica Agudizada/epidemiología , Insuficiencia Hepática Crónica Agudizada/terapia , Corticoesteroides/uso terapéutico , Adulto , Aminoácidos de Cadena Ramificada/administración & dosificación , Anticoagulantes/clasificación , Anticoagulantes/uso terapéutico , Glucemia , Presión Sanguínea , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Proteínas en la Dieta/administración & dosificación , Nutrición Enteral/métodos , Práctica Clínica Basada en la Evidencia , Fluidoterapia/métodos , Hemodinámica , Hemoglobinas/análisis , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Síndrome Hepatopulmonar/epidemiología , Síndrome Hepatopulmonar/terapia , Humanos , Hipoxia/epidemiología , Hipoxia/terapia , Unidades de Cuidados Intensivos , Fallo Hepático Agudo/epidemiología , Trasplante de Hígado/métodos , Derivación Portosistémica Intrahepática Transyugular/métodos , Terapia de Reemplazo Renal/métodos , Respiración Artificial/métodos , Tromboelastografía/métodos , Vasoconstrictores/uso terapéutico , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control
7.
Liver Transpl ; 26(4): 582-590, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31883291

RESUMEN

There are disparities in liver transplant anesthesia team (LTAT) care across the United States. However, no policies address essential resources for liver transplant anesthesia services similar to other specialists. In response, the Society for the Advancement of Transplant Anesthesia appointed a task force to develop national recommendations. The Conditions of Transplant Center Participation were adapted to anesthesia team care and used to develop Delphi statements. A Delphi panel was put together by enlisting 21 experts from the fields of liver transplant anesthesiology and surgery, hepatology, critical care, and transplant nursing. Each panelist rated their agreement with and the importance of 17 statements. Strong support for the necessity and importance of 13 final items were as follows: resources, including preprocedure anesthesia assessment, advanced monitoring, immediate availability of consultants, and the presence of a documented expert in liver transplant anesthesia credentialed at the site of practice; call coverage, including schedules to assure uninterrupted coverage and methods to communicate availability; and characteristics of the team, including membership criteria, credentials at the site of practice, and identification of who supervises patient care. Unstructured comments identified competing time obligations for anesthesia and transplant services as the principle reason that the remaining recommendations to attend integrative patient selection and quality review committees were reduced to a suggestion rather than being a requirement. This has important consequences because deficits in team integration cause higher failure rates in service quality, timeliness, and efficiency. Solutions are needed that remove the time-related financial constraints of competing service requirements for anesthesiologists. In conclusion, using a modified Delphi technique, 13 recommendations for the structure of LTATs were agreed upon by a multidisciplinary group of experts.


Asunto(s)
Anestesia , Anestesiología , Trasplante de Hígado , Anestesiólogos , Cuidados Críticos , Técnica Delphi , Humanos , Estados Unidos
9.
J Intensive Care Med ; 34(9): 687-695, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30060683

RESUMEN

The development of acute kidney injury in the setting of liver disease is a significant event both before and after liver transplant. Whether acute kidney injury is the cause of or merely associated with worse outcomes, the development of renal failure is significant from a prognostic as well as from a diagnostic and therapeutic standpoint. Although not every etiology is reversible, there are number of etiologies that are correctable, to include hypovolemia, nephrotoxic medications, and acute tubular necrosis. In the post-liver transplant period, renal failure is associated with graft failure as well as worse outcomes overall. Prompt recognition, workup, and intervention can significantly impact outcomes and survival both before and after liver transplant.


Asunto(s)
Lesión Renal Aguda , Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Humanos , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Periodo Perioperatorio , Pronóstico , Factores de Riesgo
11.
Liver Transpl ; 24(3): 380-393, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29171941

RESUMEN

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380-393 2018 AASLD.


Asunto(s)
Circulación Extracorporea/métodos , Hepatitis Alcohólica/terapia , Hepatoblastoma/metabolismo , Neoplasias Hepáticas/metabolismo , Adulto , Australia , Línea Celular Tumoral , Circulación Extracorporea/efectos adversos , Circulación Extracorporea/mortalidad , Femenino , Hepatitis Alcohólica/sangre , Hepatitis Alcohólica/diagnóstico , Hepatitis Alcohólica/mortalidad , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Reino Unido , Estados Unidos
12.
Hepatology ; 66(5): 1592-1600, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28586126

RESUMEN

Clinical guidelines recommend using Kidney Disease Improving Global Outcomes (KDIGO) criteria for the diagnosis and classification of acute kidney injury (AKI) in patients with chronic liver disease (CLD). Concerns have been raised about the use of urine output (UO) criteria in CLD. We examined the significance of oliguria meeting the urine output criteria for AKI (AKI-UO) and examined its association with clinical outcomes in CLD patients. Using an 8-year clinical database from a large university medical center, 3458 patients with CLD were identified. AKI occurred in 2854 (82.5%) patients when they fulfilled any KDIGO criteria. When serum creatinine (SC) and UO criteria were used, 604 patients (17.5%) had no evidence of AKI and had the lowest hospital mortality rate (5%). Using AKI-UO criteria alone, 2103 patients (60.8%) were classified as stage 2-3 AKI. When only SC criteria were applied, 1281 (61%) of those patients with stage 2-3 AKI-UO were misclassified as either no AKI or AKI stage 1. Patients reclassified with AKI according to UO criteria (AKI-UO) had nearly a 3-fold increased rate of hospital mortality compared with patients without any AKI (14.6% versus 5%; P < 0.001) and more than a 50% increased mortality compared with stage 1 AKI-SC (14.6% versus 9%; P < 0.001). Patients with transient oliguria (AKI-UO stage 1) had increased mortality rates compared with patients without oliguria (14.9% versus 6.9%; P < 0.001). CONCLUSION: CLD patients have a high incidence of AKI. Compared with creatinine criteria alone, incorporating UO into the diagnostic criteria increased the measured incidence of AKI. Stage 2-3 AKI-UO has a high negative impact on hospital mortality. (Hepatology 2017;66:1592-1600).


Asunto(s)
Lesión Renal Aguda/diagnóstico , Insuficiencia Hepática/complicaciones , Oliguria/etiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/orina , Adulto , Enfermedad Crítica , Femenino , Insuficiencia Hepática/orina , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo
13.
J Wound Ostomy Continence Nurs ; 45(6): 516-520, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30395128

RESUMEN

The rectal trumpet (RT) is a nasopharyngeal airway device that is inserted into the rectum for management of fecal incontinence. No published data exist on adverse events caused by the use of an RT. The purpose of this quality improvement project was to determine the rate of RT-associated hemorrhage among patients treated with an RT in our transplant intensive care unit (TICU). This quality improvement initiative and retrospective medical record review included all patients (N = 3933) cared for in a single specialty intensive care unit at a tertiary academic medical center between January 1, 2014, and May 31, 2016. We estimate that approximately 400 patients were treated with an RT. We found 3 possible and 9 probable cases of RT-associated hemorrhage, resulting in an estimated incident rate of 3% among RT-treated patients. All of these patients underwent invasive procedures for hemostasis. They received a mean of 4.9 units of packed red blood cell transfusions, and 9 experienced hypotension. Eight out of the 9 probable RT-associated hemorrhage patients experienced hemorrhage only after greater than 7 days of treatment with an RT. Following this initiative, RT use was banned in our TICU. The use of RTs can cause hemorrhage with clinically significant consequences.


Asunto(s)
Cateterismo/efectos adversos , Incontinencia Fecal/enfermería , Hemorragia/terapia , Mejoramiento de la Calidad , Recto/lesiones , APACHE , Anciano , Cateterismo/enfermería , Incontinencia Fecal/complicaciones , Femenino , Hemorragia/epidemiología , Hemorragia/fisiopatología , Humanos , Unidades de Cuidados Intensivos/organización & administración , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Pennsylvania/epidemiología , Recto/irrigación sanguínea , Estudios Retrospectivos , Encuestas y Cuestionarios
16.
Liver Transpl ; 21(9): 1179-85, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25980614

RESUMEN

Acute kidney injury (AKI) is a common complication after liver transplantation (LT). Few studies investigating the incidence and risk factors for AKI after living donor liver transplantation (LDLT) have been published. LDLT recipients have a lower risk for post-LT AKI than deceased donor liver transplantation (DDLT) recipients because of higher quality liver grafts. We retrospectively reviewed LDLTs and DDLTs performed at the University of Pittsburgh Medical Center between January 2006 and December 2011. AKI was defined as a 50% increase in serum creatinine (SCr) from baseline (preoperative) values within 48 hours. One hundred LDLT and 424 DDLT recipients were included in the propensity score matching logistic model on the basis of age, sex, Model for End-Stage Liver Disease score, Child-Pugh score, pretransplant SCr, and preexisting diabetes mellitus. Eighty-six pairs were created after 1-to-1 propensity matching. The binary outcome of AKI was analyzed using mixed effects logistic regression, incorporating the main exposure of interest (LDLT versus DDLT) with the aforementioned matching criteria and postreperfusion syndrome, number of units of packed red blood cells, and donor age as fixed effects. In the corresponding matched data set, the incidence of AKI at 72 hours was 23.3% in the LDLT group, significantly lower than the 44.2% in the DDLT group (P = 0.004). Multivariate mixed effects logistic regression showed that living donor liver allografts were significantly associated with reduced odds of AKI at 72 hours after LT (P = 0.047; odds ratio, 0.31; 95% confidence interval, 0.096-0.984). The matched patients had lower body weights, better preserved liver functions, and more stable intraoperative hemodynamic parameters. The donors were also younger for the matched patients than for the unmatched patients. In conclusion, receiving a graft from a living donor has a protective effect against early post-LT AKI.


Asunto(s)
Lesión Renal Aguda/prevención & control , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Donadores Vivos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/epidemiología , Adulto , Factores de Edad , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Creatinina/sangre , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Pennsylvania/epidemiología , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Factores Protectores , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo
17.
Am J Respir Crit Care Med ; 189(8): 932-9, 2014 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-24559465

RESUMEN

RATIONALE: We recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest. OBJECTIVES: We now validate a clinical test for urinary [TIMP-2]·[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients. METHODS: We conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]·[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test. MEASUREMENTS AND MAIN RESULTS: Urinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]·[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2]·[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]·[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2]·[IGFBP7]). CONCLUSIONS: Urinary [TIMP-2]·[IGFBP7] greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962).


Asunto(s)
Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/orina , Enfermedad Crítica , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Inhibidores de Proteasas/orina , Inhibidor Tisular de Metaloproteinasa-2/orina , Anciano , Anciano de 80 o más Años , Biomarcadores/orina , Muerte Celular , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Factores de Tiempo , Estados Unidos
19.
Crit Care ; 17(1): R25, 2013 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-23388612

RESUMEN

INTRODUCTION: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. METHODS: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. RESULTS: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. CONCLUSIONS: Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01209169.


Asunto(s)
Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/orina , Puntos de Control del Ciclo Celular/fisiología , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Inhibidor Tisular de Metaloproteinasa-2/orina , Anciano , Biomarcadores/orina , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad
20.
Chemosphere ; 336: 139266, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37339707

RESUMEN

In this study, an innovative nanomaterial was synthesized for hydrogen production from methanolysis on sodium borohydride (NaBH4) in order to be a solution for future energy problems. The nanocomposite containing FeCo, which does not contain noble metals, and whose support material is Polyvinylpyrrolidone (PVP), was synthesized by means of a thermal method. TEM, XRD and FTIR characterization methods were used for the analysis of the morphological and chemical structure of the nanocomposite. Nanocomposite particle size was found to be 2.59 nm according to XRD analysis, and 5.45 nm according to TEM analysis for scale of 50 nm. For catalytic properties of nanomaterial in the methanolysis reaction of NaBH4, temperature, catalyst, substrate, and reusability experiments were carried out and kinetic calculations were obtained. Among the activation parameters of FeCo@PVP nanoparticles, turnover frequency, enthalpy, entropy and activation energy were calculated as 3858.9 min-1, 29.39 kJ/mol, -139.7 J/mol.K, and 31.93 kJ/mol, respectively. As a result of the reusability test of the obtained FeCo@PVP nanoparticles catalysts, which was carried out for 4 cycles, the catalytic activity was 77%. Catalytic activity results are given in comparison with the literature. In addition, the photocatalytic activity of FeCo@PVP NPs was evaluated against MB azo dye under solar light irradiation for 75 min and was found to be as 94%.


Asunto(s)
Nanocompuestos , Nanopartículas , Luz Solar , Compuestos Azo , Iluminación , Nanocompuestos/química , Hidrógeno
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