Beatriz Pinto Costa

Value of MELD and MELD-Based Indices in Surgical Risk Evaluation of Cirrhotic Patients: Retrospective Analysis of 190 Cases

BackgroundRecent studies have suggested that the Model for End-Stage Liver Disease (MELD) may represent a promising alternative to the Child-Turcotte-Pugh classification as a predictive factor of operative mortality and morbidity. This study was designed to evaluate the value of MELD and four MELD-based indices (iMELD: integrated MELD; MESO: MELD to sodium ratio; MELD-Na: MELD with incorporation of sodium; MELD-XI: MELD excluding the International Normalized Ratio) in the quantification of surgical risk for patients with cirrhosis and compare its prognostic value with the Child-Turcotte-Pugh classification and two derived scores (proposed by Huo and Giannini, respectively).MethodsA retrospective study of 190 patients with cirrhosis, operated on in our department between 1993 and 2008, was undertaken.ResultsForty-three percent of patients were included in Child-Turcotte-Pugh A class, and their mean MELD score was 12.2 ± 4.9 (range, 6.4–35.2). Mortality and morbidity rates were 13% and 24%, respectively. In global analysis of mortality, MELD-based indices presented an acceptable prognostic performance (auROC = 71–77%), similar to the three analyzed Child-Turcotte-Pugh-derived scores. iMELD demonstrated the highest prognostic capacity (auROC = 77%; 95% confidence interval (CI), 66–88; p = 0.0001); operative death probability was 4% (95% CI, 3.6–4.4) when the score was inferior to 35, 16.1% (95% CI, 14.4–17.9) between 35 and 45, and 50.1% (95% CI, 42.2–58.1) when superior to 45. In elective surgical procedures, iMELD represented a useful prognostic factor of operative mortality (auROC = 80%; 95% CI, 63–97; p = 0.044) with significant correlation and better accuracy then MELD and Child-Turcotte-Pugh-derived indices.ConclusionsIn this study, iMELD was a useful predictive parameter of operative mortality for patients with cirrhosis submitted to elective procedures. Further studies are necessary to define the relevance of MELD-based indices in the individual surgical risk evaluation.

Citrullinemia stimulation test in the evaluation of the intestinal function

BACKGROUND Citrullinemia is been reported as a quantitative parameter of the enterocyte mass and function. AIM The objective of this research is to analyse the value of fasting and stimulated citrullinemias in the intestinal function evaluation. METHODS A case-control study was undertaken, including 11 patients with short bowel syndrome, 13 patients submitted to malabsorptive bariatric surgery and 11 healthy controls. Plasma levels of amino acids were determined, before and after a stimulation test with oral Lglutamine, by ion exchange chromatography. RESULTS Citrullinemia was inferior in short bowel patients (28,6 ± 11,3 versus 35,5 ± 11 in operated obese versus 32,2 ± 6,6 μmol/L in controls; n.s.) and lower than 25,5 μmol/L in 54,5% of them (versus 16,7%; p = 0,041; accuracy = 74%; odds ratio = 3, 95%CI 1,2-7,6). ΔCitrullinemia80 (relative variation of citrullinemia at the 80th minute of test) was lower in short bowel patients; its diagnostic accuracy was similar to baseline citrullinemia and also not significant. ΔCitrullinemia80 revealed a high predictive capacity of a short bowel inferior or equal to 50 cm (auR.O.C. = 82,3%; 95%CI 61,7-102,8; p = 0,038). CONCLUSIONS In short bowel syndrome context, citrullinemia stimulation test with oral L-glutamine is feasible and it may improve the predictive capacity of severity. Further investigation is required to determine its clinical relevance and applicability.

Intestinal Epithelial Stem Cells: Distinct Behavior After Surgical Injury and Teduglutide Administration

ABSTRACT Background: Previous studies suggest that intestinal epithelial stem cells (IESC), critical drivers of homeostasis and regeneration, include two subpopulations: crypt-based columnar and “position +4” stem cells, identified by Lgr5 and Bmi1 biomarkers, respectively. Teduglutide is an enterotrophic counterpart of glucagon-like peptide 2. This study aimed to investigate the response of putative IESC to surgical injury and teduglutide administration on an animal model of intestinal resection and anastomosis. Methods: Wistar rats (n = 59) were distributed into four groups: “Ileal Resection” versus “Laparotomy”, subsequently subdivided into “Postoperative Teduglutide Administration” versus “No Treatment”; and sacrificed at third or seventh days, with ileal sample harvesting. Flow cytometry was used to analyze epithelial stem cells with monoclonal antibodies against Lgr5, Bmi1 and also CD44, CD24, CD166, and Grp78 surface markers. Results: Surgical trauma induced an increase of epithelial stem cells population at third day (9.0 ± 0.3 versus 5.7 ± 0.3%, p = 0.0001), which was more intense and involved all subpopulations after ileal resection. At seventh day, teduglutide was significantly associated with higher proportion of Lgr5+/Bmi1− cells (5.8 ± 0.1 versus 2.9 ± 0.3%, p = 0.005) and, on the contrary, lower percentage of Lgr5−/Bmi1+ cells (0.03 ± 0.01 versus 1.9 ± 0.1%, p = 0.049) after ileal resection; and higher proportion of Lgr5+/Bmi1+ cells (1.7 ± 0.1 versus 1.1 ± 0.2%, p = 0.028) after isolated laparotomy. After surgery, Lgr5+/Bmi1− and Lgr5−/Bmi1+ subpopulations demonstrated an inverse correlation and both correlated negatively with Grp78 labeling index. Lgr5−/Bmi1+ and CD44+/CD24low/CD166+/Grp78+ cells proportions exhibited a high grade positive correlation. Conclusion: Those observations support the existence of two epithelial stem cells subpopulations with distinct behavior after surgical injury and teduglutide treatment.

Myeloid sarcoma of the small intestine in a patient without overt acute myeloid leukaemia: a challenging diagnosis of a rare condition

Myeloid sarcoma (MS) is a rare condition that most commonly occurs in the setting of acute myeloidleukaemia (AML) or other chronic myeloproliferative disorders. It presents as an abnormal growth that can develop anywhere in the human body, and its clinical manifestations are often non-specific. We present the case of a patient admitted to the emergency room with bowel obstruction. After careful clinical assessment, she underwent a right hemicolectomy. After a thorough examination of the surgical pathology specimen, including testing a wide array of immunohistochemical markers, the patient was timely diagnosed with MS, allowing for the implementation of the appropriate treatment to achieve complete remission. This is crucial, since non-leukaemic patients with untreated MS always progress to AML, and have a better prognosis if adequate therapy is implemented early. Our patient is now in the second postoperative year and shows no signs of relapse.

Intestinal dysfunction in the critical trauma patients – An early and frequent event

BACKGROUND Small-bowel dysfunction exerts a relevant prognostic impact in the critically ill patients. Citrullinemia has been used in the evaluation of the intestinal function and it is considered an objective parameter of the functional enterocyte mass. Present study proposes to determine the intestinal dysfunction prevalence and the citrullinemia kinetic profile in severe trauma patients and to investigate its correlation with severity indicators and clinical outcome. METHODS A prospective study including 23 critical trauma patients was performed. Aminoacidemias were quantified, by ion exchange chromatography, at the admission and at the first and third days. Severity and outcome parameters were registered. RESULTS In severe trauma patients, severe hypocitrullinemia (< 20 μmol/L) prevalence at admission was high (69.6%) and mean citrullinemia was low (19.5 ± 11.1 μmol/L). Baseline citrullinemia was inversely and significantly correlated with shock index (r = -55.1%, p = 0.008) and extent of invasive ventilation support (r = -42.7%, p = 0.042). Citrullinemia < 13.7 μmol/L at admission, observed in 17.4% of patients, was associated with higher shock index (1.27 ± 0.10 versus 0.75 ± 0.18, p = 0.0001) and longer duration of invasive ventilation support (20.3 ± 7 versus 11.2 ± 7.1 days, p = 0.029) and intensive care unit stay (22 ± 5.9 versus 12.2 ± 8.8 days, p = 0.048). A citrullinemia decrease in the first day after admittance superior to 12.7% constituted a significant predictive factor of in-hospital mortality (75 versus 14.3%, p = 0.044; odds ratio = 7.8; accuracy = 65.2%; specificity = 92.3%; negative predictive value = 85.7%] and lower actuarial survival (69.8 ± 41.6 versus 278.1 ± 37.4 days, p = 0.034). CONCLUSIONS Those results confirm the high prevalence and the prognostic relevance of hypocitrullinemia, considered a biomarker of enterocyte dysfunction, in severe trauma patients.

Glutaminemia prognostic signifi cance in critical surgical patients - An analysis of plasma aminogram profile

BACKGROUND Glutamine depletion is common in the critically-ill patients. Glutaminemia lower than 420 μmol/l has been considered as an independent predictive factor of mortality, but the indications for exogenous glutamine supplementation remain controversial. This study intends to determine the glutaminemia profile in critical surgical patients and to investigate its correlation with the severity indexes and the prognosis. METHODS A prospective study of 28 adult critical surgical patients was performed. Plasma amino acid concentrations were quantified, by ion exchange chromatography, at the moment of admission and at the first and third days, and compared with those of 11 reference healthy individuals. Severity indexes and parameters of prognosis were registered. RESULTS In critical surgical patients, mean glutaminemia at admission was lower than that of control individuals (385.1 ± 123.1 versus515 ± 57.9 μmol/l, p = 0.002) and decreased until the third day (p = 0.042). Prevalence of severe hypoglutaminemia (< 420 μmol/l) at admission was 64.3%. Baseline glutaminemia correlated with the Simplified Acute Physiology Score II (SAPS II score) (Pearsons correlation coefficient r = -39.4%, p = 0.042), and it was lower in cases of erythrocytes transfusion (339.9 ± 78.8 versus 454.9 ± 148.8 μmol/l, p = 0.013). Glutaminemia at the third day correlated with the duration of invasive ventilation support (r = -65%, p = 0 .012) and ICU stay (r = -66.5%, p = 0.009). Glutaminemia below 320 μmol/l, observed in 25% of the patients, was associated with higher in-hospital mortality (42.9 versus19%, statistically not significant [n.s.]) and lower actuarial survival (212.1 ± 77.9 versus 262.3 ± 32.4 days, n.s.). CONCLUSIONS Those results underscore the relevance of hypoglutaminemia as an adverse predictive factor in the critical surgical patients. Determination of glutaminemia may contribute to a better definition of the indications for glutamine supplementation.