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1.
Article En | MEDLINE | ID: mdl-38513707

BACKGROUND: Gastrointestinal ischemia (GIisch) is challenging to diagnose in patients after cardiothoracic surgery. Computed tomography angiography (CTA) carries substantial false-negative and false-positive rates. The aim of the study was to evaluate if a combination of readily available variables improves the diagnosis of GIisch after cardiothoracic surgery. METHODS: This retrospective study included patients receiving intensive care after cardiothoracic surgery. GIisch was confirmed by surgical and/or endoscopic findings. A GIisch prediction score was developed using the Spiegelhalter-Knill-Jones system in a training cohort then tested in a validation cohort (patients without obvious signs of GIisch on CTA). RESULTS: The training cohort comprised 125 consecutive patients with suspected GIisch in 2008 to 2019, including 85 with confirmed GIisch. CTA, performed in 92 patients, had a high false-negative rate of 17/60 (28%) and a lower false-positive rate of 7/32 (22%). The score included cardiopulmonary bypass, negatively associated with GIisch, and six variables positively associated with GIisch: intraoperative mean arterial pressure < 50 mm Hg, aspartate aminotransferase > 15 N, lactate increase in 24 hour > 20%, and 3 CTA findings, namely, bowel dilation, bowel wall thickening, and mesenteric vasoconstriction. The area under the receiver operating characteristic was 0.82 (95% confidence interval [CI], 0.51-0.93) in the training cohort and 0.82 (95% CI, 0.68-0.96) in the validation cohort (n = 34 patients). Reliability of the predicted probabilities was greatest for probabilities ≤ 30% or ≥ 70%. CONCLUSION: In patients receiving intensive care after cardiothoracic surgery, GIisch cannot be ruled out based solely on CTA findings. A scoring system combining CTA findings with other variables may improve the diagnosis of GIisch in this population.

2.
Crit Care ; 27(1): 219, 2023 06 02.
Article En | MEDLINE | ID: mdl-37269022

BACKGROUND: Bleeding and thrombosis induce major morbidity and mortality in patients under extracorporeal membrane oxygenator (ECMO). Circuit changes can be performed for oxygenation membrane thrombosis but are not recommended for bleeding under ECMO. The objective of this study was to evaluate the course of clinical, laboratory, and transfusion parameters before and after ECMO circuit changes warranted by bleeding or thrombosis. METHODS: In this single-center, retrospective, cohort study, clinical parameters (bleeding syndrome, hemostatic procedures, oxygenation parameters, transfusion) and laboratory parameters (platelet count, hemoglobin, fibrinogen, PaO2) were collected over the seven days surrounding the circuit change. RESULTS: In the 274 patients on ECMO from January 2017 to August 2020, 48 circuit changes were performed in 44 patients, including 32 for bleeding and 16 for thrombosis. Mortality was similar in the patients with vs. without changes (21/44, 48% vs. 100/230, 43%) and in those with bleeding vs. thrombosis (12/28, 43% vs. 9/16, 56%, P = 0.39). In patients with bleeding, numbers of bleeding events, hemostatic procedures, and red blood cell transfusions were significantly higher before vs. after the change (P < 0.001); the platelet counts and fibrinogen levels decreased progressively before and increased significantly after the change. In patients with thrombosis, numbers of bleeding events and red blood cell transfusions did not change after membrane change. No significant differences were demonstrated between oxygenation parameters (ventilator FiO2, ECMO FiO2, and PaO2) and ECMO flow before vs. after the change. CONCLUSIONS: In patients with severe and persistent bleeding, changing the ECMO circuit decreased clinical bleeding and red blood cell transfusion needs and increased platelets and fibrinogen levels. Oxygenation parameters did not change significantly in the group with thrombosis.


Extracorporeal Membrane Oxygenation , Hemostatics , Thrombosis , Humans , Extracorporeal Membrane Oxygenation/methods , Retrospective Studies , Cohort Studies , Hemorrhage/therapy , Hemorrhage/etiology , Thrombosis/etiology , Fibrinogen
4.
Anesth Analg ; 132(4): 1051-1059, 2021 04 01.
Article En | MEDLINE | ID: mdl-33002927

BACKGROUND: Whether train-of-four (TOF) monitoring is more effective than clinical monitoring to guide neuromuscular blockade (NMB) in patients with acute respiratory distress syndrome (ARDS) is unclear. We compared clinical monitoring alone or with TOF monitoring to guide atracurium dosage adjustment with respect to drug dose and respiratory parameters. METHODS: From 2015 to 2016, we conducted a randomized controlled trial comparing clinical assessments every 2 hours with or without corrugator supercilii TOF monitoring every 4 hours in patients who developed ARDS (Pao2/Fio2 <150 mm Hg) in a cardiothoracic intensive care unit. The primary outcome was the cumulative atracurium dose (mg/kg/h). Secondary outcomes included respiratory parameters during the neuromuscular blockade. RESULTS: A total of 38 patients in the clinical + TOF (C + TOF) group and 39 patients in the clinical (C) group were included in an intention-to-treat (ITT) analysis. The cumulative atracurium dose was higher in the C + TOF group (1.06 [0.75-1.30] vs 0.65 [0.60-0.89] mg/kg/h in the C group; P < .001) compared to C group, as well as the atracurium daily dose (C + TOF - C group mean difference = 0.256 mg/kg/h [95% confidence interval {CI}, 0.099-0.416], P = .026). Driving pressures during neuromuscular blocking agent (NMBA) administration did not differ between groups (P = .653). Intensive care unit (ICU) mortality was 22% in the C group and 27% in the C + TOF group (P = .786). Days on ventilation were 17 (8-26) in the C group and 16 (10-35) in the C + TOF group. CONCLUSIONS: In patients with ARDS, adding TOF to clinical monitoring of neuromuscular blockade did not change ICU mortality or days on mechanical ventilation (MV) but did increase atracurium consumption when compared to clinical assessment alone. TOF monitoring may not be needed in all patients who receive neuromuscular blockade for ARDS.


Atracurium/administration & dosage , Electric Stimulation , Neuromuscular Blockade , Neuromuscular Monitoring , Neuromuscular Nondepolarizing Agents/administration & dosage , Peripheral Nerves , Respiration, Artificial , Respiratory Distress Syndrome/drug therapy , Adult , Aged , Atracurium/adverse effects , Female , Humans , Male , Middle Aged , Neuromuscular Blockade/adverse effects , Neuromuscular Nondepolarizing Agents/adverse effects , Paris , Predictive Value of Tests , Prospective Studies , Respiration, Artificial/adverse effects , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/physiopathology , Time Factors , Treatment Outcome , Ventilator Weaning
5.
Anaesth Crit Care Pain Med ; 36(5): 273-277, 2017 Oct.
Article En | MEDLINE | ID: mdl-27867133

INTRODUCTION: Sedation optimizes patient comfort and ease of execution during fiber optic bronchoscopy (FOB). Our objective was to describe the safety and efficacy of remifentanil-TCI during FOB in non-intubated, hypoxaemic, thoracic surgery ICU patients. METHODS: Consecutive spontaneously breathing adults requiring FOB after thoracic surgery were included if they had hypoxaemia (PaO2/FiO2<300mmHg or need for non-invasive ventilation [NIV]) and prior FOB failure under topical anaesthesia. The remifentanil initial target was chosen at 1ng/mL brain effect-site concentration (Cet), then titrated to 0.5ng/mL Cet increments according to patient comfort and coughing. Outcomes were patient-reported pain and discomfort (Visual Analogue Scale scores), ventilatory support intensification within 24hours after bronchoscopy, and ease of FOB execution. RESULTS: Thirty-nine patients were included; all had a successful FOB. Their median PO2/FiO2 before starting FOB was 187±84mmHg and 24 patients received NIV. Median [interquartile range] pain scores were not different before and after FOB (1.0 [0.0-3.0] and 0.0 [0.0-2.0], respectively). Discomfort was reported as absent or minimal by 27 patients (69%; 95% confidence interval [95% CI], 54-81%) and as bothersome but tolerable by 12 patients (31%; 95% CI, 19-46%). Mean FiO2 returned to baseline within 2hours after FOB in 30 patients; the remaining 9 patients (23%; 95% CI, 13-38%) received ventilatory support intensification. Ease of execution was good or very good in 34 patients (87%; 95% CI, 73-94%), acceptable in 4 patients, and poor in 1 patient (persistent cough). CONCLUSION: Sedation with remifentanil-TCI during FOB with prior failure under topical anaesthesia alone was effective and acceptably safe in non-intubated hypoxaemic thoracic surgery patients.


Bronchoscopy/instrumentation , Bronchoscopy/methods , Critical Care/methods , Fiber Optic Technology , Hypnotics and Sedatives/administration & dosage , Hypoxia/therapy , Piperidines/administration & dosage , Respiratory Insufficiency/therapy , Adult , Aged , Cohort Studies , Critical Illness , Female , Humans , Hypoxia/blood , Infusions, Intravenous , Male , Middle Aged , Pain/etiology , Pain Measurement , Prospective Studies , Remifentanil , Respiratory Insufficiency/blood , Thoracic Surgical Procedures/methods
7.
Respir Care ; 61(3): 324-32, 2016 Mar.
Article En | MEDLINE | ID: mdl-26701366

BACKGROUND: Non-ventilator ICU-acquired pneumonia after cardiothoracic surgery is challenging to diagnose, and little is known about its impact on patient outcomes. Here, our primary objective was to compare the sensitivity and specificity of cultures of 2 types of fiberoptic bronchoscopy (FOB) specimens: endotracheal aspirates (FOB-EA) and bronchoalveolar lavage fluid (FOB-BAL). The secondary objectives were to evaluate the sensitivity and specificity of spontaneous sputum cultures and of the modified Clinical Pulmonary Infection Score (CPIS) and to describe patient outcomes. METHODS: We conducted a prospective observational study of consecutive cardiothoracic surgery subjects with suspected non-ventilator ICU-acquired pneumonia. Using FOB-BAL cultures ≥10(4) cfu/mL as the reference standard, we evaluated the accuracy of FOB-EA ≥10(5) cfu/mL and spontaneous sputum ≥10(7) cfu/mL. On the day of FOB, we determined the modified CPIS. Mortality and antibiotic treatments were recorded. RESULTS: Of 105 subjects, 57 (54.3%) received a diagnosis of non-ventilator ICU-acquired pneumonia. FOB-EA cultures had 82% (95% CI 69-91%) sensitivity and 100% (95% CI 89-100%) specificity and were significantly less sensitive than FOB-BAL cultures (P < .004). Spontaneous sputum was obtained from one-third of subjects. Spontaneous sputum cultures had 82% (95% CI 56-95%) sensitivity and 94% (95% CI 68-100%) specificity and were non-significantly less sensitive than FOB-BAL (P = .061). A modified CPIS >6 had 42% (95% CI 29-56%) sensitivity and 87% (95% CI 74-95%) specificity for non-ventilator ICU-acquired pneumonia. Antibiotic therapy was stopped in all subjects without non-ventilator ICU-acquired pneumonia, after 1.6 ± 1.2 d, without deleterious effects. CONCLUSIONS: The modified CPIS has low diagnostic accuracy for non-ventilator ICU-acquired pneumonia. FOB-EA cultures perform less well than do FOB-BAL cultures for diagnosing non-ventilator ICU-acquired pneumonia. Spontaneous sputum is valuable when FOB cannot be performed but could be obtained in only a minority of subjects. When cultures are negative, antibiotic discontinuation is safe.


Cardiac Surgical Procedures/adverse effects , Cross Infection/diagnosis , Intensive Care Units , Pneumonia/diagnosis , Postoperative Complications/microbiology , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Bronchoalveolar Lavage Fluid/microbiology , Bronchoscopy/methods , Cross Infection/drug therapy , Cross Infection/microbiology , Female , Humans , Male , Middle Aged , Pneumonia/drug therapy , Pneumonia/microbiology , Prospective Studies , Sensitivity and Specificity , Sputum/microbiology , Trachea/microbiology
8.
JAMA ; 313(23): 2331-9, 2015 Jun 16.
Article En | MEDLINE | ID: mdl-25980660

IMPORTANCE: Noninvasive ventilation delivered as bilevel positive airway pressure (BiPAP) is often used to avoid reintubation and improve outcomes of patients with hypoxemia after cardiothoracic surgery. High-flow nasal oxygen therapy is increasingly used to improve oxygenation because of its ease of implementation, tolerance, and clinical effectiveness. OBJECTIVE: To determine whether high-flow nasal oxygen therapy was not inferior to BiPAP for preventing or resolving acute respiratory failure after cardiothoracic surgery. DESIGN AND SETTING: Multicenter, randomized, noninferiority trial (BiPOP Study) conducted between June 15, 2011, and January 15, 2014, at 6 French intensive care units. PARTICIPANTS: A total of 830 patients who had undergone cardiothoracic surgery, of which coronary artery bypass, valvular repair, and pulmonary thromboendarterectomy were the most common, were included when they developed acute respiratory failure (failure of a spontaneous breathing trial or successful breathing trial but failed extubation) or were deemed at risk for respiratory failure after extubation due to preexisting risk factors. INTERVENTIONS: Patients were randomly assigned to receive high-flow nasal oxygen therapy delivered continuously through a nasal cannula (flow, 50 L/min; fraction of inspired oxygen [FiO2], 50%) (n = 414) or BiPAP delivered with a full-face mask for at least 4 hours per day (pressure support level, 8 cm H2O; positive end-expiratory pressure, 4 cm H2O; FiO2, 50%) (n = 416). MAIN OUTCOMES AND MEASURES: The primary outcome was treatment failure, defined as reintubation, switch to the other study treatment, or premature treatment discontinuation (patient request or adverse effects, including gastric distention). Noninferiority of high-flow nasal oxygen therapy would be demonstrated if the lower boundary of the 95% CI were less than 9%. Secondary outcomes included mortality during intensive care unit stay, changes in respiratory variables, and respiratory complications. RESULTS: High-flow nasal oxygen therapy was not inferior to BiPAP: the treatment failed in 87 of 414 patients with high-flow nasal oxygen therapy (21.0%) and 91 of 416 patients with BiPAP (21.9%) (absolute difference, 0.9%; 95% CI, -4.9% to 6.6%; P = .003). No significant differences were found for intensive care unit mortality (23 patients with BiPAP [5.5%] and 28 with high-flow nasal oxygen therapy [6.8%]; P = .66) (absolute difference, 1.2% [95% CI, -2.3% to 4.8%]. Skin breakdown was significantly more common with BiPAP after 24 hours (10% vs 3%; 95% CI, 7.3%-13.4% vs 1.8%-5.6%; P < .001). CONCLUSIONS AND RELEVANCE: Among cardiothoracic surgery patients with or at risk for respiratory failure, the use of high-flow nasal oxygen therapy compared with intermittent BiPAP did not result in a worse rate of treatment failure. The findings support the use of high-flow nasal oxygen therapy in similar patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01458444.


Hypoxia/therapy , Oxygen Inhalation Therapy/methods , Positive-Pressure Respiration , Postoperative Complications/therapy , Respiratory Insufficiency/therapy , Thoracic Surgical Procedures , Aged , Cardiac Surgical Procedures , Humans , Hypoxia/etiology , Middle Aged , Oxygen Inhalation Therapy/instrumentation , Respiratory Insufficiency/complications
9.
Intensive Care Med ; 39(5): 872-80, 2013 May.
Article En | MEDLINE | ID: mdl-23370827

PURPOSE: Venous thromboembolism (VTE) is a frequent and serious problem in intensive care units (ICU). Anticoagulant treatments have demonstrated their efficacy in preventing VTE. However, when the bleeding risk is high, they are contraindicated, and mechanical devices are recommended. To date, mechanical prophylaxis has not been rigorously evaluated in any trials in ICU patients. METHODS: In this multicenter, open-label, randomized trial with blinded evaluation of endpoints, we randomly assigned 407 patients with a high risk of bleeding to receive intermittent pneumatic compression (IPC) associated with graduated compression stockings (GCS) or GCS alone for 6 days during their ICU stay. The primary endpoint was the occurrence of a VTE between days 1 and 6, including nonfatal symptomatic documented VTE, or death due to a pulmonary embolism, or asymptomatic deep vein thrombosis detected by ultrasonography systematically performed on day 6. RESULTS: The primary outcome was assessed in 363 patients (89.2%). By day 6, the incidence of the primary outcome was 5.6% (10 of 179 patients) in the IPC + GCS group and 9.2% (17 of 184 patients) in the GCS group (relative risk 0.60; 95% confidence interval 0.28-1.28; p = 0.19). Tolerance of IPC was poor in only 12 patients (6.0%). No intergroup difference in mortality rate was observed. CONCLUSIONS: With the limitation of a low statistical power, our results do not support the superiority of the combination of IPC + GCS compared to GCS alone to prevent VTE in ICU patients at high risk of bleeding.


Intermittent Pneumatic Compression Devices , Stockings, Compression , Venous Thromboembolism/prevention & control , Female , Hemorrhage/complications , Humans , Intensive Care Units , Male , Middle Aged , Risk Factors , Treatment Outcome , Ultrasonography , Venous Thromboembolism/diagnostic imaging
10.
Prehosp Emerg Care ; 16(3): 356-60, 2012.
Article En | MEDLINE | ID: mdl-22494150

INTRODUCTION: Drowning following a fall from a bridge can lead to cardiac arrest caused by hypoxia, hypothermia, or severe traumatic injury. Every year patients are brought to our hospital who have nearly drowned in the local river after a jump from a bridge (approximate height 16-22 meters). We report traumatic injuries in patients admitted to our hospital for out-of-hospital cardiac arrest due to drowning. METHODS: We retrospectively reviewed the charts of all patients admitted to the intensive care units of our hospital for out-of-hospital cardiac arrest due to drowning after a jump from a bridge in the Seine River between 2002 and 2010. All clinical or radiologic evidence of trauma was recorded. RESULTS: A total of 37 patients where admitted to our hospital for out-of-hospital cardiac arrest due to drowning. Fourteen patients had radiologic examinations. Five of these examinations showed evidence of severe trauma. In one case, clinical examination showed evidence of severe peripheral neurologic trauma. Seven of these patients (19%) were discharged from the hospital alive. CONCLUSIONS: Patients found nearly drowned in a river spanned by a medium-height bridge should undergo spinal immobilization and complete radiologic examination as soon as possible.


Emergency Medical Services/methods , Multiple Trauma , Near Drowning/therapy , Rivers , Suicide, Attempted , Adult , Female , France , Humans , Intensive Care Units , Male , Medical Audit , Middle Aged , Near Drowning/etiology , Retrospective Studies
11.
Chest ; 142(4): 837-844, 2012 Oct.
Article En | MEDLINE | ID: mdl-22406956

BACKGROUND: The diagnosis of heparin-induced thrombocytopenia (HIT) is problematic in the surgical ICU, as there are multiple potential explanations for thrombocytopenia. We conducted a study to assess the incidence, clinical presentation, and outcome of HIT in a cardiothoracic surgical ICU. METHODS: From January 2005 to December 2010, all patients with suspicion of HIT were prospectively identified, and data were collected retrospectively. Detection of anti-PF4/heparin antibodies and functional assays were systematically performed. RESULTS: During the study period, 5,949 patients were admitted to the ICU (2,751 after cardiac surgery and 3,198 after thoracic surgery), of whom 101 were suspected to have HIT(1.7% [95% CI, 1.4%-2.0%]). Suspicion of HIT occurred at a median of 5 (4-9) days after ICU admission. Diagnosis was confirmed in 28 of 5,949 patients (0.47% [95% CI, 0.33%-0.68%]).Thrombosis was detected in 14 patients with HIT (50%) and in 12 patients without HIT (16%)( P 5 .0006). After receiver operating characteristic analysis (area under curve 5 0.78 0.06),a 4Ts score ≥ 5 had a sensitivity of 86% and a specificity of 70%. Course of platelet count was similar between the two groups. Six patients (21%) with HIT and 20 (27%) without died( P 5 .77). CONCLUSIONS: Even with a prospective platelet monitoring protocol, suspicion for HIT arose in <2% of patients in a cardiothoracic ICU. Most were found to have other causes of thrombocytopenia,with HIT confirmed in 28 of 101 suspected cases (0.47% of all patients in the ICU). The 4Ts score may have value by identifying patients who should have laboratory testing performed.The mortality of patients with HIT was not different from other very ill thrombocytopenic patients in the ICU.


Biomarkers/blood , Cardiac Surgical Procedures , Heparin/adverse effects , Intensive Care Units , Thoracic Surgical Procedures , Thrombocytopenia/diagnosis , Aged , Antibodies/blood , Anticoagulants/adverse effects , Anticoagulants/immunology , Female , Follow-Up Studies , France/epidemiology , Heparin/immunology , Humans , Incidence , Male , Middle Aged , Platelet Count , Prospective Studies , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Thrombosis/prevention & control
13.
Crit Care Med ; 38(1): 59-64, 2010 Jan.
Article En | MEDLINE | ID: mdl-19633539

OBJECTIVES: Data collected from two cohorts of patients aged > or =80 yrs and admitted to an intensive care unit in France were compared to determine whether intensive care unit care and survival had evolved from the 1990s to the 2000s. DESIGN: Retrospective cohort study on patient data attained during intensive care unit stays. SETTING: 18-bed intensive care unit in an academic medical center. PATIENTS: Two cohorts of patients aged > or =80 yrs, admitted to an intensive care unit at a 10-yr interval. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The first cohort comprised 348 patients admitted between January 1992 and December 1995, and the second cohort, 373 patients admitted between January 2001 and December 2004. There was no difference in age between the two cohorts, but patients in the second had significantly less history of functional limitation and significantly more acute illness (Simplified Acute Physiology Score II 43 +/- 18 vs. 57 +/- 25, respectively, p < .0001). Patients in the second cohort had a significantly higher Omega Score, had a higher occurrence of renal replacement therapy, and received vasopressors more frequently than the patients in the first cohort, even when adjusted for age, sex, Knaus classification, Simplified Acute Physiology Score II, and intensive care unit admission cause. Intensive care unit mortality was 65% and 64% for the first and second cohorts, respectively. In multivariate analysis (including age, Knaus classification, Simplified Acute Physiology Score II and first vs. second period) for association with intensive care unit survival, the 2001-2004 period was associated with a near tripling of chances of survival (odds ratio 2.9; 95% confidence interval, 1.92-4.47, p < .0001). CONCLUSIONS: The characteristics and intensity of treatment for elderly people admitted to the intensive care unit changed significantly over a decade. The intensity of treatments has increased over time and survival has improved over time as well. A potential link between increased treatment and improved survival in the elderly may be evoked.


Critical Care/trends , Hospital Mortality/trends , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Age Factors , Aged, 80 and over , Cause of Death , Chi-Square Distribution , Cohort Studies , Combined Modality Therapy , Female , Follow-Up Studies , Geriatric Assessment , Health Care Surveys , Hospitals, University , Humans , Male , Retrospective Studies , Risk Assessment , Statistics, Nonparametric , Survival Analysis , Treatment Outcome
14.
Clin Gastroenterol Hepatol ; 7(11): 1230-5, 2009 Nov.
Article En | MEDLINE | ID: mdl-19560555

BACKGROUND & AIMS: Patients with Budd-Chiari syndrome can present with acute, subacute, or chronic disease; the definitions and significance of these variants have been disputed. An increased level of serum alanine aminotransferase (ALT) is an objective marker for acute liver injury. We analyzed the significance of changes in ALT levels in Budd-Chiari syndrome patients. METHODS: We performed a retrospective analysis of data from 96 consecutive Budd-Chiari syndrome patients. RESULTS: A threshold peak ALT level that was 5-fold the upper limit of normal distinguished 2 groups of patients: patients with high levels of ALT (40% of patients) presented with more severe liver disease, less frequent liver fibrosis, and more frequent liver cell necrosis, compared with those with ALT levels below this threshold. Patients with levels of ALT that started out high but slowly declined (<50% of starting concentration within 3 days) had significantly lower odds of survival than those with a rapid decline and those with low levels of ALT (40 months transplantation-free survival, 31%, 63%, and 71%, respectively). When ALT level and the velocity of its decline are used as criterion, these data add significant prognostic information to Child-Pugh, to Clichy, and to Rotterdam Budd-Chiari syndrome scores. CONCLUSIONS: Determination of ALT levels at patient presentation allows 2 variants of Budd-Chiari syndrome to be distinguished. High levels of ALT reflect acute, severe, but potentially reversible, ischemic liver cell necrosis. High levels of ALT that decrease slowly predict a poor outcome for patients and might justify rapid aggressive management.


Alanine Transaminase/blood , Budd-Chiari Syndrome/diagnosis , Adult , Budd-Chiari Syndrome/pathology , Budd-Chiari Syndrome/therapy , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Serum/chemistry , Survival Analysis , Time Factors
15.
Eur J Gastroenterol Hepatol ; 20(10): 1036-9, 2008 Oct.
Article En | MEDLINE | ID: mdl-18787475

Fanconi anaemia is an autosomal recessive disease, causing secondary aplastic anaemia and congenital abnormalities, associated with an increased risk of tumours. Liver cell adenoma and hepatocellular carcinoma have rarely been described. Clinical, radiological and histopathological features in three patients with Fanconi anaemia and liver tumours were analyzed. Only one patient had received androgens and none had chronic viral hepatitis. All had elevated serum ferritin with significant parenchymal iron overload. Alpha-fetoprotein levels were normal in all cases. Patient 1 had moderately differentiated hepatocellular carcinoma with venous invasion and satellite nodules. The patient underwent two consecutive resections. Patient 2 had hepatic nodules diagnosed at routine examination with radiological features of adenomas. The patient underwent resection, which showed liver cell adenoma with foci of carcinoma. Patient 3 had three nodules, with radiological and histological diagnosis of adenoma. In patients with Fanconi anaemia, androgen therapy and iron overload may contribute to the development of liver cell adenoma and hepatocellular carcinoma. Hepatocellular carcinoma may occur as a transformation of liver cell adenoma. With prolongation of survival, continued development of liver tumours can be expected. Routine detection should therefore be considered in these patients as curative resection can be performed.


Adenoma, Liver Cell/etiology , Carcinoma, Hepatocellular/etiology , Fanconi Anemia/complications , Liver Neoplasms/etiology , Adenoma, Liver Cell/diagnostic imaging , Adult , Carcinoma, Hepatocellular/diagnostic imaging , Fanconi Anemia/diagnostic imaging , Fanconi Anemia/pathology , Female , Humans , Liver Neoplasms/diagnostic imaging , Male , Tomography, X-Ray Computed , Tongue Neoplasms/diagnostic imaging , Tongue Neoplasms/etiology
16.
Pharmacogenet Genomics ; 15(5): 311-9, 2005 May.
Article En | MEDLINE | ID: mdl-15864132

A genetic dimorphism incorporates either alanine (Ala) or valine (Val) in the mitochondrial targeting sequence (MTS) of manganese superoxide dismutase (MnSOD). The Ala-MTS confers a 40% higher MnSOD activity than the Val-MTS after import into isolated mitochondria in vitro. The present study aimed to characterize functional consequences in whole cells. HuH7 human hepatoma cells were transfected with vectors encoding for the human Ala- or Val-MnSOD variants fused to a Myc-His-tag. The Ala-variant resulted in four-fold higher levels of the mature exogenous protein and MnSOD activity than the Val-variant. Studies with a proteasome inhibitor indicated that precursor proteins are either imported into the mitochondria or degraded by the proteasome. Despite identical levels 8 h after transfection, mRNA levels at 36 h were two-fold higher for the Ala-encoding mRNA than the Val-mRNA. Decreasing the mitochondrial membrane potential decreased both MnSOD mitochondrial import and its mRNA levels. Much larger differences in the activity of the human Val- and Ala-MnSOD variants are observed in whole cells rather than after import experiments performed in vitro. First, the slowly imported Val-MnSOD is degraded by the proteasome in cells. Second, the slower mitochondrial import of the Val-variant may be associated with decreased mRNA stability, possibly due to impaired cotranslational import.


Mitochondria/enzymology , Mitochondrial Proteins/genetics , RNA Stability , RNA, Messenger/metabolism , Superoxide Dismutase/genetics , Alanine/genetics , Cell Line, Tumor , Humans , Mitochondrial Proteins/metabolism , Polymorphism, Genetic , Protein Transport , Superoxide Dismutase/metabolism , Valine/genetics
17.
Gastroenterol Clin Biol ; 29(12): 1294-5, 2005 Dec.
Article Fr | MEDLINE | ID: mdl-16518292

Selective inhibitors of cyclooxygenase-2 have less gastroduodenal toxicity than non selective anti-inflammatory drugs. However, there is little information on their effect on the distal gut. A 91 year old woman presented with acute diarrhoea 5 weeks after beginning celecoxib treatment. Laboratory results showed an inflammatory syndrome and increased alanine aminotransferase (ALT) to 13 N. Endoscopic examination of the colon showed diffuse erythematous lesions of the sigmoid and of part of the right colon. No aetiology has been found for colitis or hepatitis. Diarrhea and blood test anomalies disappeared one week after celecoxib was stopped. The role of celecoxib in the etiology of colitis was considered plausible but not for liver damage. This report and a few other cases in the literature suggest that cyclooxygenase-2 selective non-steroidal anti-inflammatory drug inhibitor toxicity should be investigated in case of unexplained acute colitis.


Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Colitis/chemically induced , Pyrazoles/adverse effects , Sulfonamides/adverse effects , Acute Disease , Aged, 80 and over , Alanine Transaminase/blood , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Back Pain/drug therapy , Celecoxib , Diarrhea/chemically induced , Female , Humans , Pyrazoles/administration & dosage , Sulfonamides/administration & dosage
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