VERA LUCIA JORNADA KREBS

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Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina

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  • article 9 Citação(ões) na Scopus
    First-year profile of biomarkers for early detection of renal injury in infants with congenital urinary tract obstruction
    (2019) KOSTIC, Dusan; BEOZZO, Glenda Priscila Neves dos Santos; COUTO, Saulo Brasil do; KATO, Andre Henrique Teruaki; LIMA, Laila; PALMEIRA, Patricia; KREBS, Vera Lucia Jornada; BUNDUKI, Victor; FRANCISCO, Rossana Pulcineli Vieira; ZUGAIB, Marcelo; CARVALHO, Werther Brunow de; KOCH, Vera Hermina Kalika
    Background Diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. Use of renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and prevention or minimization of definitive renal damage. Methods This longitudinal, prospective study analyzed the first-year profile of two serum renal biomarkers: creatinine (sCr) and cystatin C (sCyC); and six urinary renal biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-beta 1), retinol-binding protein (RBP), cystatin C (mu CyC), and microalbuminuria (ALB) in a cohort of 37 infants with UTO divided into three subgroups: 14/37 with unilateral hydro(uretero)nephrosis, 13/37 with bilateral hydro(uretero)nephrosis, and 10/37 patients with lower urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. Results All urine biomarkers showed significantly higher values at the first month of life (p <= 0.009), while NGAL (p = 0.005), TGF-beta 1 (p<0.001), and mu ALB (p<0.001) were high since birth compared to controls. Best single biomarker performances were RBP in bilateral hydronephrosis and LUTO subgroups and KIM-1 in unilateral hydronephrosis subgroup. Best biomarker combination results for all subgroups were obtained by matching RBP with TGF-beta 1 or KIM-1 and NGAL with CyC ([AUC] <= 0.934; sensitivity <= 92.4%; specificity <= 92.8%). Conclusions RBP, NGAL, KIM-1, TGF-beta 1, and CyC, alone and especially in combination, are relatively efficient in identifying surgically amenable congenital UTO and could be of practical use in indicating on-time surgery.
  • article 23 Citação(ões) na Scopus
    The role of renal biomarkers to predict the need of surgery in congenital urinary tract obstruction in infants
    (2019) KOSTIC, D.; BEOZZO, G. P. N. S.; COUTO, S. B. do; KATO, A. H. T.; LIMA, L.; PALMEIRA, P.; KREBS, V. L. J.; BUNDUKI, V; V, R. P. Francisco; ZUGAIB, M.; DENES, F. T.; CARVALHO, W. B. de; KOCH, V. H. K.
    Introduction The diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. The use of new renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and the prevention or minimization of definitive renal damage. Objective The aim of the study was to investigate a selection of promising biomarkers of renal injury with the intention of evaluating and comparing their profile with clinically based decisions for surgical intervention of infants with congenital obstructive uropathies. Study design The first-year profile of renal biomarkers, serum creatinine (sCr), serum and urine cystatin C (CyC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-beta 1), retinolbinding protein (RBP), and microalbuminuria (mu ALB), was analyzed in a cohort of 37 infants with congenital UTO, divided into three subgroups, 14 cases with grade III unilateral hydro (uretero)nephrosis, 13 cases with grade III bilateral hydro (uretero)nephrosis, and 10 cases with low urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. Serum and urine samples were stored at -70 degrees C and thereafter analyzed by quantitative enzymatic immunoassay. Results Compared with the control group (Figure), all renal biomarker values were significantly increased in patients (P <= 0.02). In the unilateral hydronephrosis and LUTO group, RBP (P <= 0.043), NGAL (P <= 0.043), KIM-1 (P <= 0.03), and TGF-beta 1 (P <= 0.034) values dropped significantly after surgery. Neutrophil gelatinase-associated lipocalin alone and in combination with urine and serum CyC demonstrated the best performance in determining the need for surgery (area under the curve, 0.801 and 0.881, respectively). Biomarker profile analysis was suggestive of surgical intervention in 55.4% (7/13) of non-operated cases, and most of the biomarker values were above the cutoff levels within at least 3 months before the clinically based surgical decision in 58% (14/24) of all operated patients. Discussion To the best of the authors' knowledge, this is the first study to present the clinical use of selected group of serum and urinary biomarkers in the setting of UTO to distinguish between patients who would benefit from surgery intervention. The most promising results were obtained using NGAL, RBP, TGF-beta 1, and KIM-1, especially in the unilateral hydro(uretero)nephrosis and LUTO subgroups when compared with the control group. Conclusions Urine biomarkers, alone and in combination, demonstrated high potential as a non-invasive diagnostic tool for identifying infants who may benefit from earlier surgical intervention. [GRAPHICS] .
  • article 6 Citação(ões) na Scopus
    Nonimmune fetal ascites: identification of ultrasound findings predictive of perinatal death
    (2016) BACCEGA, Felipe; BRIZOT, Maria de Lourdes; KREBS, Vera Lucia Jornada; FRANCISCO, Rossana Pulcineli Vieira; ZUGAIB, Marcelo
    Aim: To determine the ultrasonographic findings that predict death in fetal ascites. Methods: This was a retrospective cohort study involving pregnancies with ultrasonographic findings related to fetal ascites. The inclusion criteria were as follows: single pregnancy with a live fetus; ultrasound findings of ascites; ascites unrelated to maternal fetal alloimmunization; and pregnancy follow-up at our institution. The chi(2)-test was used to evaluate the association of ultrasound findings and death. Multiple logistic regression analysis was performed to determine the ultrasound findings that are predictive of death prior to hospital discharge. Results: A total of 154 pregnancies were included in the study. In 8 (5.19%) cases, ascites was an isolated finding, and in 146 cases, other alterations were observed during the ultrasound evaluation. Death before hospital discharge occurred in 117 cases (76.00%). The following ultrasonographic findings were significantly associated with death: gestational age at diagnosis <24 weeks (P < 0.0001); stable/progressive ascites evolution (P = 0.004); the presence of hydrops (P < 0.0001); and the presence of cystic hygroma (P < 0.0001). The presence of hydrops, the presence of respiratory tract malformations, and stable/progressive ascites evolution were significantly associated with the prediction of death. Conclusions: Based on ultrasound examination, the presence of hydrops, malformation of the respiratory tract, and stable/progressive evolution of ascites increase the chances of death in cases of fetal ascites.
  • article 18 Citação(ões) na Scopus
    Early fluid overload is associated with mortality and prolonged mechanical ventilation in extremely low birth weight infants
    (2020) MATSUSHITA, Felipe Yu; KREBS, Vera Lucia Jornada; FERRARO, Alexandre Archanjo; CARVALHO, Werther Brunow de
    Recent studies revealed that fluid overload is associated with higher mortality in critically ill children and adults. This study aimed to evaluate the association between fluid overload in the first 3 days of life and mortality in extremely low birth weight infants. This single-center retrospective cohort study included two hundred nineteen newborns with birth weight less than 1000 g who were admitted to the neonatal intensive care between January 2012 and December 2017. Overall mortality was 32.4%, the median gestational age was 27.3 (26.1-29.4) weeks, and birth weight was 770 (610-900) grams. In the group with severe fluid overload, we found a higher rate of deaths (72.2%); mean airway pressure was significantly higher and with longer invasive mechanical ventilation necessity. Conclusion: Early fluid overload in extremely low birth weight infants is associated with higher mortality rate, higher mean airway pressure in invasive mechanically ventilated patients, and longer mechanical ventilation duration in the first 7 days of life.What is Known:center dot Fluid overload is associated with a higher mortality rate and prolonged mechanical ventilation in children and adults.What is New:center dot Fluid overload in the first 72 h of life in an extremely premature infant is associated with higher mortality rate, higher mean airway pressure in invasive mechanically ventilated patients, and longer mechanical ventilation duration the first 7 days of life.
  • article 0 Citação(ões) na Scopus
    Definitions of Sepsis in Neonatology: A Fundamental Tool
    (2015) KREBS, Vera Lucia Jornada; YOSHIDA, Renata de Araujo Monteiro; DELGADO, Artur Figueiredo; CARVALHO, Werther Brunow de
  • article 5 Citação(ões) na Scopus
    Identifying clinical phenotypes in extremely low birth weight infants-an unsupervised machine learning approach
    (2022) MATSUSHITA, Felipe Yu; KREBS, Vera Lucia Jornada; CARVALHO, Werther Brunow de
    There is increasing evidence that patient heterogeneity significantly hinders advancement in clinical trials and individualized care. This study aimed to identify distinct phenotypes in extremely low birth weight infants. We performed an agglomerative hierarchical clustering on principal components. Cluster validation was performed by cluster stability assessment with bootstrapping method. A total of 215 newborns (median gestational age 27 (26-29) weeks) were included in the final analysis. Six clusters with different clinical and laboratory characteristics were identified: the ""Mature"" (Cluster 1; n= 60, 27.9%), the mechanically ventilated with ""adequate ventilation"" (Cluster 2; n=40, 18.6%), the mechanically ventilated with ""poor ventilation"" (Cluster 3; n=39, 18.1%), the ""extremely immature"" (Cluster 4; n= 39, 18.1%%), the neonates requiring ""Intensive Resuscitation"" in the delivery room (Cluster 5; n=20, 9.3%), and the ""Early septic"" group (Cluster 6; n= 17, 7.9%). In-hospital mortality rates were 11.7%, 25%, 56.4%, 61.5%, 45%, and 52.9%, while severe intraventricular hemorrhage rates were 1.7%, 5.3%, 29.7%, 47.2%, 44.4%, and 28.6% in clusters 1, 2, 3, 4, 5, and 6, respectively (p<0.001). Conclusion: Our cluster analysis in extremely preterm infants was able to characterize six distinct phenotypes. Future research should explore how better phenotypic characterization of neonates might improve care and prognosis.
  • article 4 Citação(ões) na Scopus
    Prevalence and Outcomes of Congenital Heart Disease in Very Low Birth Weight Preterm Infants: An Observational Study From the Brazilian Neonatal Network Database
    (2021) ANDERSON, Daniela; ARAGON, Davi Casale; GONCALVES-FERRI, Walusa A.; MANSO, Paulo H.; LEAL, Gabriela; KREBS, Vera L. J.; CALDAS, Jamil P. S.; ALMEIDA, Joao H. C. L.; RIBEIRO, Manoel A. S.; SILVEIRA, Rita C.; DUARTE, Jose L. M. B.; PENIDO, Marcia G.; FERREIRA, Daniela M. L. M.; JR, Jose M. S. Alves; SAKANO, Karen M. K.; SANTOS, Juliana P. F.; GIMENES, Carolina B.; SILVA, Nathalia M. M.; MELO, Fernanda P. G.; VENZON, Paulyne S.; MENESES, Jucille; MARQUES, Patricia F.; RUGOLO, Ligia M. S. S.; TESTONI, Daniela; CARMONA, Fabio
    Objectives: To evaluate the prevalence of congenital heart disease and their outcomes in a Brazilian cohort of very low birth weight preterm infants. Design: Post hoc analysis of data from the Brazilian Neonatal Network database, complemented by retrospective data from medical charts and a cross-sectional survey. Setting: Twenty public tertiary-care university hospitals. Patients: A total of 13,955 newborns weighing from 401 to 1,499 g and between 22 and 36 weeks of gestational age, born from 2010 to 2017. Interventions: None. Measurements and Main Results: The prevalence of congenital heart disease was 2.45% (95% CI, 2.20-2.72%). In a multivariate regression analysis, risk factors associated with congenital heart disease were maternal diabetes (relative risk, 1.55; 95% CI, 1.11-2.20) and maternal age above 35 years (relative risk, 2.09; 95% CI, 1.73-2.51), whereas the protection factors were maternal hypertension (relative risk, 0.54; 95% CI, 0.43-0.69), congenital infection (relative risk, 0.45; 95% CI, 0.21-0.94), and multiple gestation (relative risk, 0.73; 95% CI, 0.55-0.97). The pooled standardized mortality ratio in patients with congenital heart disease was 2.48 (95% CI, 2.22-2.80), which was significantly higher than in patients without congenital heart disease (2.08; 95% CI, 2.03-2.13). However, in multiple log-binomial regression analyses, only the presence of major congenital anomaly, gestational age (< 29 wk; relative risk, 2.32; 95% CI, 2.13-2.52), and Score for Neonatal Acute Physiology and Perinatal Extension II (> 20; relative risk, 3.76; 95% CI, 3.41-4.14) were independently associated with death, whereas the effect of congenital heart disease was spotted only when a conditional inference tree approach was used. Conclusions: The overall prevalence of congenital heart disease in this cohort of very low birth weight infants was higher and with higher mortality than in the general population of live births. The occurrence of a major congenital anomaly, gestational age (< 29 wk), and Score for Neonatal Acute Physiology and Perinatal Extension II (> 20) were significantly and independently associated with death, whereas the association of congenital heart disease and death was only evident when a major congenital anomaly was present.
  • article 6 Citação(ões) na Scopus
    Thombolytic therapy in preterm infants: Fifteen-year experience
    (2020) GRIZANTE-LOPES, Priscila; GARANITO, Marlene Pereira; CELESTE, Daniele Martins; KREBS, Vera Lucia Jornada; CARNEIRO, Jorge David Aivazoglou
    Objective To report a single-center experience with thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) in preterm neonates with severe thrombotic events, in terms of thrombus resolution and bleeding complications. Study design This retrospective study included 21 preterm neonates with severe venous thrombotic events admitted to the neonatal intensive care unit, identified in our pharmacy database from January 2001 to December 2016, and treated with rt-PA until complete or partial clot lysis, no-response or bleeding complications. Our primary outcome was thrombus resolution. Results Twenty-one preterm neonates were treated with rt-PA for an average of 2.9 cycles. Seventeen patients (80.9%) had superior vena cava thrombosis and superior vena cava syndrome. All patients had a central venous catheter, parenteral nutrition, mechanical ventilation, and sepsis. Fifteen patients (71.4%) were extremely preterm, 11 (52.4%) were extremely low birth weight, and seven (33.3%) were very low birth weight. The patency rate was 85.7%, complete lysis occurred in 11 (52.4%) patients, and partial lysis in seven (33.3%). Minor bleeding occurred in five (23.8%) patients, three patients (14.2%) had clinically relevant nonmajor bleeding events, and major bleeding occurred in six (28%) patients. Conclusion In this study, the rate of thrombus resolution in preterm neonates treated with rt-PA were similar to the percentages reported in children and adolescents, with a high rate of bleeding. Therefore, rt-PA thrombolytic therapy should only be considered as a treatment option for severe life-threatening thrombosis in premature neonates for whom the benefits of the thrombolytic treatment outweigh the risks of bleeding.
  • article 1 Citação(ões) na Scopus
    Limits of therapeutic intervention in a tertiary neonatal intensive care unit in patients with major congenital anomalies in Brazil
    (2021) GIBELLI, Maria A. B. C.; CARVALHO, Werther B. de; KREBS, Vera L. J.
    Aim Major congenital anomalies are an important cause of death in the neonatal intensive care unit (NICU). Therapeutic interventions and the suspension of those already in place often raise ethical dilemmas in neonatal care. Methods We analysed treatments-such as ventilatory support, vasoactive drugs, antibiotics, sedation/or analgesia, central venous access and other invasive procedures-offered up to 48 h before death to all newborns with major congenital anomalies over a 3-year period in a NICU in Brazil. We also gathered information contained in medical records concerning conversations with the families and decisions to limit therapeutic interventions. Results We enrolled 74 newborns who were hospitalised from 1 January 2015 to 31 December 2017. A total of 81.1% had central venous access, 74.3% were on ventilatory support, 56.8% received antibiotics and 43.2% used some sedative/analgesic drugs in their final moments. Conversations were registered in medical records in 76% of cases, and 46% of the families chose therapeutic intervention limits. Those who chose to limit therapeutic interventions asked for less exposure to vasoactive drugs (P = 0.003) and antibiotics (P = 0.003), as well as fewer invasive procedures (P = 0.046). There was no change in ventilatory support (P = 0.66), and palliative extubation was not performed for any patient. Conclusions The therapeutic intervention was mainly characterised by maintenance of the current treatment when a terminal situation was identified with no introduction of new treatments that could increase suffering. The families' approach proved to be essential for making difficult decisions in the NICU.
  • article 3 Citação(ões) na Scopus
    Severe Hyperbilirubinemia in Exchange Transfusion: Less Indication and Lower Mortality
    (2016) DURANTE, Patricia Prado; KREBS, Vera Lucia Jornada; CARVALHO, Werther Brunow de