Serum cystatin C unmasks renal dysfunction in cirrhosis and performs better in estimation of glomerular filtration rate.

In this study, we aimed to measure glomerular filtration rate (mGFR) using 99Tc DTPA in patients with Child-Pugh C cirrhosis and normal serum creatinine levels; and to compare the performance of creatinine and cystatin C-based equations [estimated GFRs (eGFRs)] to 99TcDTPA GFR in the same group. We selected a group of 65 consecutive patients with advanced liver cirrhosis and apparently normal renal function by serum creatinine alone. Patients with confounding and reversible factors were excluded. Demographic data, blood, urine, and imaging tests along with simultaneous measurement of serum creatinine and cystatin C were analyzed. The GFR was measured by 99Tc DTPAscintigraphy (mGFR) in 41 patients. We compared the performance of chronic kidney disease epidemiology collaboration (CKD-EPI-creatinine, CKD-EPI-cystatinC, CKD-EPI-creatinine-cystatinC) and Modification of Diet in Renal Disease equation equations for bias (mean difference), precision (root mean square error), and accuracy (P10 and P30). Bland-Altman plots were used to show the agreement of eGFR and mGFR. Twenty-five out of 41 patients (61%) had significant renal dysfunction (GFR ≤60 mL/min/ 1.73m2) by 99TcDTPA in our study and three patients were already in Stage 4 CKD. Unlike serum creatinine, serum cystatin C values were deranged in these patients. Among all GFR estimating formulae, CKD-EPI-creatinine-cystatinC combined equation had the least bias (-2.3), superior precision (7.1), highest P30 accuracy (78%), good sensitivity (87.5%), and best specificity (96%) in our study. Two-thirds of patients with cirrhosis had significant renal impairment despite having normal serum creatinine. Isolated serum creatinine values are misleading in cirrhosis. Cystatin C unmasks renal dysfunction in these patients. CKD-EPI-creatinine-cystatinC equation showed the best correlation and accuracy with 99TcDTPA GFR in our study. Creatinine based GFR estimation is fallacious in cirrhosis. Cystatin C and equations based on it may be worthwhile in liver disease.

A rare cause of nephrotic syndrome.

Classical Alport syndrome is a rare X-linked disease of males (85%) presenting early with hematuria, ocular, and hearing defects. Proteinuria and renal failure are less common in the early stages. Here, we report the case of a young female with nephrotic range proteinuria, microscopic hematuria, and renal failure. A keen observation of abundant interstitial foam cells with suspicious glomerular basement membrane changes on kidney biopsy hinted the possibility of Alport syndrome. Further directed testing of the index patient and her family members including genetic analysis revealed a rare pathogenic variant of COL4A homozygous autosomal recessive Alport syndrome. Pedigree analysis showed that the peculiar inheritance could be due to maternal gonadal mosaicism or uniparental isodisomy of paternal genes alone.

Late-onset ventilator-associated pneumonia in nontrauma intensive care unit patients.

BACKGROUND: Most studies designed to determine the factors associated with the acquisition of late-onset ventilator-associated pneumonia (VAP) were performed in critically ill trauma patients. The impact of enteral nutrition (EN) on the risk of acquiring VAP has been discussed. In this study, we assessed factors associated with late-onset VAP in nontrauma patients and determined whether nutrition provided early was associated with development of late-onset VAP in this population. METHODS: We performed a prospective observational cohort study in a 21-bed polyvalent intensive care unit in a university hospital. RESULTS: Three hundred sixty-one intubated adult patients with a duration of mechanical ventilation (MV) of 6 days or more were admitted over a 28-mo period. Late-onset VAP was confirmed in 76 patients (21%) by the presence of at least one microorganism at a concentration >or=10(4) colony-forming units/mL on the bronchoalveolar lavage. Gram-negative bacilli represented 75% and Staphylococcus aureus 21% of recovered organisms. Factors independently associated with late-onset VAP by multivariate analysis included a high simplified acute physiology score II score (odds ratio: 1.021; 95% confidence interval [CI]: 1.005-1.038; P = 0.01), development of acute respiratory distress syndrome during the first 5 days of MV (odds ratio: 1.98; 95% CI: 1.05-3.67; P = 0.04), and size of the endotracheal tube >or=7.5 (odds ratio: 2.06; 95% CI: 1.88-3.90; P = 0.03). EN started within 48 h of MV onset was not associated with a higher risk for late-onset VAP. CONCLUSION: In our nontrauma patient population, early EN was not associated with development of late-onset VAP. In this population, severity of the disease during the first 5 days of MV seemed to be associated with late-onset VAP. In addition, our results suggest that the risk of late-onset VAP is higher in patients with a tube size >or=7.5 than in patients with a tube size <7.5.

At-risk drinkers are at higher risk to acquire a bacterial infection during an intensive care unit stay than abstinent or moderate drinkers.

OBJECTIVES: To determine whether excessive alcohol consumption increases the risk for intensive care unit (ICU)-acquired bacterial infection, especially ventilator-associated pneumonia (VAP), in nontrauma patients. DESIGN: Prospective observational cohort study. SETTING: A 21-bed polyvalent ICU in a university hospital. PATIENTS: A total of 358 adult patients admitted over a 1-yr period who had an ICU stay > or = 3 days and in whom alcohol consumption could be assessed. INTERVENTIONS: None. MEASUREMENTS AND MEAN RESULTS: Thirty-one percent of the patients (111 of 358) were identified as at-risk drinkers according to the National Institute on Alcohol Abuse and Alcoholism criteria. Among these, 61 had a daily intake of five or more drinks per day and 73 had Simplified Michigan Alcohol Short Test scores > or = 3. ICU-acquired bacterial infections were diagnosed in 88 patients, and 69 patients had one or more VAPs. Forty (36%) at-risk drinkers acquired bacterial infections vs. 48 (19%) not-at-risk drinkers (p < .001). Among at-risk drinkers, the proportion of patients who developed bacterial infection was higher in at-risk drinkers consuming five or more drinks per day compared with at-risk drinkers consuming fewer than five drinks per day (p = .048). After adjustment for age, gender, Simplified Acute Physiology Score II, length of hospital stay before ICU admission, prior antibiotic administration within 24 hrs before ICU admission, type of admission, immunosuppression, duration of mechanical ventilation, and central venous and urinary catheter exposure, at-risk drinking remained significantly associated with the acquisition of bacterial infection at any site (hazard ratio 1.92; 95% confidence interval, 1.17-3.14; p = .009) and of VAP (hazard ratio 1.76; 95% confidence interval, 1.05-3.06; p = .04). CONCLUSIONS: At-risk drinking was a significant risk factor for acquisition of ICU-acquired bacterial infection.

Molecular adsorbent recirculating system dialysis in patients with acute liver failure who are assessed for liver transplantation.

OBJECTIVE: To assess the usefulness of dialysis with the molecular adsorbent recirculating system (MARS) in patients with acute liver failure who fulfil criteria for liver transplantation. DESIGN: Observational cohort study. SETTING: ICU at a liver transplantation centre. PATIENTS: Twenty-two patients (23 episodes) received MARS dialysis. They were either listed for LT (n=14), delayed (n=1), or not listed (contra-indication, n=7). INTERVENTIONS: A total of 56 MARS treatments (median per patient 2; mean duration 7.6+/-2.6h) were performed on haemodialysis. MEASUREMENTS AND RESULTS: Clinical and biological variables were assessed before and 24[Symbol: see text]h after MARS therapy. The rate of recovery of liver function without transplantation was compared with an expected rate and survival was analysed. Following MARS dialysis, we observed an improvement in the grade of hepatic encephalopathy (P=0.02) and the Glasgow coma score (P=0.02), a decrease in conjugated bilirubin (P=0.05) and INR (P=0.006), and an increase in prothrombin index (P=0.005). Overall, liver function improved in seven patients (32%): four listed patients in whom transplantation could be avoided and three patients among those not listed due to contra-indications. The transplant-free recovery rate in listed patients was 29% (vs. expected 9%, P=0.036). Listed patients (n=14) had a higher 30-day survival rate [86% (12/14) vs 38% (3/8), P=0.05] and a higher long-term survival rate (P=0.02). CONCLUSIONS: A statistically significant improvement of liver function was observed after MARS therapy. Transplant-free recovery was more frequent than expected. The apparent benefit of MARS dialysis to treat acute liver failure needs to be confirmed by a controlled study.

Early circulating lymphocyte apoptosis in human septic shock is associated with poor outcome.

The role of lymphocyte apoptosis in septic shock remains a controversial issue. Using Annexin V and flow cytometry analysis on freshly isolated cells, we evaluated circulating lymphocyte apoptosis in 23 septic shock, 25 sepsis without shock, 7 nonseptic critically ill, and 25 control patients. In patients with sepsis, we compared day 1 lymphocyte apoptosis (i.e., within 3 days of the onset of infection) with that observed 5-7 days after (day 6) according to shock state, mortality, and seventy factors. At day 1, patients in septic shock exhibited higher lymphocyte apoptosis than that present in controls (16.5% +/- 3.5% vs. 3% +/- 0.5%, respectively, P = 0.0001). At day 6, patients with sepsis without shock restored undamaged CD4+ T and CD8+ T lymphocyte counts, whereas patients in septic shock increased only CD4+ T cells. Similarly, survivors restored undamaged lymphocyte count at day 6 (+70%, P < 0.001), whereas nonsurvivors did not. Day 6 undamaged lymphocyte count negatively correlated with day 1 SAPS II, day 6 LOD score, mechanical ventilation, and ICU stay duration. We observed no apoptotic effect of septic shock plasma or septic shock circulating mononuclear cells on target lymphoid cell lines. We found no alteration in any death receptors Fas, TRAIL-R1, TRAIL-R2, or in their ligands on circulating blood cells. Catecholamines and interleukin 10 levels significantly increased in patients with septic shock, but did not correlate with apoptosis levels. We conclude that lymphocyte apoptosis is rapidly increased in blood of patients in septic shock and that lymphocyte apoptosis leads to a profound and persistent lymphopenia associated with poor outcome. These results suggest that lymphocyte apoptosis is one of the main components of human septic shock immune dysfunction and could be related more to microcirculatory disturbance than to circulating factors.

Survival of patients with bronchiectasis after the first ICU stay for respiratory failure.

STUDY OBJECTIVES: Respiratory failure (RF) is a frequent cause of death among patients with bilateral bronchiectasis. An ICU admission is commonly required, and neither short-term or long-term outcomes have been studied. DESIGN: We performed a retrospective study over a 10-year period (January 1990 to March 2000). All patients with bilateral bronchiectasis admitted for the first time in the medical ICU for RF were reviewed. Patients with cystic fibrosis were excluded. MEASUREMENTS AND RESULTS: Forty-eight patients (mean age +/- SD, 63 +/- 11 years; mean simplified acute physiology score [SAPS] II, 32 +/- 12) of whom 25% received long-term oxygen therapy (LTOT) were identified. All the patients were treated with intensive medical care, associated with noninvasive ventilation in 13 patients (27%), and 26 patients (54%) required intubation. Nine patients (19%) died in the ICU. The 1-year mortality rate was 40%. Among the variables recorded at ICU admission, age > 65 years (p = 0.002), SAPS II score > 32 (p = 0.012), use of LTOT (p = 0.047), and intubation (p = 0.027) were associated with reduced survival in univariate analysis by Cox regression. Multivariate analysis by Cox proportional hazard model showed that age > 65 years (relative risk [RR], 2.70; 95% confidence interval [CI], 1.15 to 6.29) and use of LTOT (RR, 2.52; 95% CI, 1.15 to 5.54) were independently associated with reduced survival. CONCLUSIONS: We performed the first study providing information related to the impact of the first ICU stay for RF on long-term outcomes for patients with bilateral bronchiectasis. Age > 65 years and prior use of LTOT were associated with reduced survival.

Reversible spongiform leucoencephalopathy after inhalation of heated heroin.

OBJECTIVE: To describe the clinical course and imaging findings in a young man who developed a spongiform leucoencephalopathy from heroin-vapour inhalation, and to discuss the treatments which may have contributed to the unexpected favourable outcome in this case. DESIGN: Case report. SETTING: Intensive care unit of a university teaching hospital. PATIENT: A patient who developed a near fatal toxic leucoencephalopathy with impressive clinical recovery and reversible white matter changes on imaging. MEASUREMENTS AND RESULTS: Successive computed tomography scans and magnetic resonance imaging over 7 months showed evolution from bilateral extensive involvement of the cerebral white matter to almost complete resolution accompanied by the development of periventricular lesions suggestive of necrosis. Despite the fact that the patient had stretching spasms for several days, the outcome was favourable with prolonged supportive care and antioxidant therapy by ubiquinone (coenzyme Q). CONCLUSION: This case demonstrates that prolonged intensive care is of paramount importance in patients with spongiform leucoencephalopathy after inhalation of heated heroin, that abnormalities of cerebral white matter may be slowly regressive, and supports the use of coenzyme Q in severe forms of the disease.

Assessment of peri-extubation pain by visual analogue scale in the adult intensive care unit: a prospective observational study.

OBJECTIVE: This prospective observational study was undertaken in order to assess pain experienced by intensive care unit patients at the time of extubation and to identify factors associated with pain of at least moderate intensity. DESIGN: Prospective observational study. SETTING: Intensive care unit at a university hospital. PATIENTS: During a 1-year period the presence, severity and clinical predictors of orofacial and/or chest pain among patients undergoing removal of endotracheal tubes was assessed. MEASUREMENTS AND RESULTS: Pain was evaluated using a visual analogue scale (VAS). Of 332 extubated patients, 203 could be evaluated. During the peri-extubation period, pain was significantly associated with a SAPS II score more than 36 ( p=0.03) and duration of mechanical ventilation (MV) of 6 days or more ( p=0.002), whereas intubation in the operating room was associated with less pain ( p=0.001). Pain of at least moderate intensity (VAS score >30 mm) was reported by 73% of patients and pain of severe intensity (VAS score >50 mm) was reported by 45% of patients. MV duration of 6 days or more was the only independent risk factor for pain of at least moderate intensity (OR 2.4, 95% CI 1.03-5.4, p=0.04). We also observed that pain had resolved 1 h after extubation in the majority of patients. CONCLUSION: Our results suggest that, in intensive care unit patients, peri-extubation pain is frequent and should be considered for treatment, especially in patients with longer intubation.

[Corticosteroid treatment in bacterial meningitis of adults and children]. / Utilisation des corticoïdes au cours des méningites bactériennes communautaires.

The neurologic deleterious effect of bacterial meningitis are the consequences of an inflammatory local response suggesting that an adjunctive anti-inflammatory therapy is able to favoured a better prognostic. Many clinical trials indicate that dexamethasone significantly reduce auditive sequella in children with meningitis due to Haemophilus influenzae, reduce mortality and morbidity of meningitis due to S. pneumoniae in adults but has few effect on Neisseria meningitidis. Corticotherapy should be initiated just before or at the time of first antibiotherapy and prolonged during 2 to 4 days. Major concern is a potential decrease of antibiotics concentration in cerebrospinal fluid that may be detrimental in patients with meningitis caused by S. pneumoniae strains that are highly resistant to penicillin or cephalosporins.

Randomized comparison of 2 protocols to prevent acquisition of methicillin-resistant Staphylococcus aureus: results of a 2-center study involving 500 patients.

OBJECTIVE: To compare an interventional protocol with a standard protocol for preventing the acquisition of methicillin-resistant Staphylococcus aureus (MRSA) in the intensive care unit (ICU). DESIGN: Prospective, randomized, controlled, parallel-group, nonblinded clinical trial. SETTING: Medical ICUs of 2 French university hospitals. PARTICIPANTS: Five hundred adults with an expected length of stay in the ICU greater than 48 hours. INTERVENTIONS: For the intervention group, the protocol required repeated MRSA screening, contact and droplet isolation precautions for patients at risk for MRSA at ICU admission and for MRSA-positive patients, and decontamination with nasal mupirocin and chlorhexidine body wash for MRSA-positive patients. For the standard group, the standard precautions protocol was used, and the results of repeated MRSA screening in the standard group were not communicated to investigators. MAIN OUTCOME MEASURE: MRSA acquisition rate in the ICU. An audit was conducted to assess compliance with hygiene and isolation precautions. RESULTS: In the intent-to-treat analysis ([Formula: see text]), the MRSA acquisition rate in the ICU was similar in the standard (13 [5.3%] of 243) and intervention (16 [6.5%] of 245) groups ([Formula: see text]). The audit showed that the overall compliance rate was 85.5% in the standard group and 84.1% in the intervention group ([Formula: see text]), although compliance was higher when isolation precautions were absent than when they were in place (88.2% vs 79.1%; [Formula: see text]). MRSA incidence rates were higher without isolation precautions (7.57‰) than with isolation precautions (2.36‰; [Formula: see text]). CONCLUSIONS: Individual allocation to MRSA screening, isolation precautions, and decontamination do not provide individual benefit in reducing MRSA acquisition, compared with standard precautions, although the collective risk was lower during the periods of isolation. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00151606.

Liver transplantation avoided in patients with fulminant hepatic failure who received albumin dialysis with the molecular adsorbent recirculating system while on the waiting list: impact of the duration of therapy.

Eighteen patients with fulminant hepatic failure due to various medical causes were listed for emergency liver transplantation and treated with extracorporeal albumin dialysis sessions using the molecular adsorbent recirculating system (MARS) at our center over a 74-month period. Due to improvement of liver function, transplantation could be avoided in 9 patients (50%, 95% confidence interval 29% to 71%) who fully recovered afterwards. This improvement rate was higher than the rate of improvement in the French cohort of fulminant hepatic failure patients with similar etiologies (19.3%, 95% confidence interval 14.9% to 24.6%, P = 0.002). In our 18 patients, there were no statistically significant differences in any baseline characteristics or in the time with liver failure meeting transplant criteria between the patients who improved while waiting and those who did not. However, the patients who improved received a greater number of sessions and a longer total duration of MARS therapy (all P < 0.001). In the whole study population, a MARS therapy duration > or =15 h was significantly associated with improvement of liver function without transplantation (adjusted adds ratio [OR] 65.76, 2.48-1743.11, P = 0.01). Tolerance of therapy was acceptable. These results suggest that MARS therapy could contribute to native liver recovery and is safe in patients on the waiting list for fulminant hepatic failure. A minimum duration of therapy (> or =15 h) could be necessary to expect significant liver function improvement.

Fatal coxsackievirus A-16 pneumonitis in adult.

Coxsackievirus A-16 (CVA-16) is the agent of hand, foot, and mouth disease in children. We report a case of fatal pneumonitis in an adult due to a CVA-16 strain with a low (78.6%) rate of sequence homology with the reference strain. A modified, more virulent, strain of CVA-16 could be emerging.

Increasing incidence of severe Epstein-Barr virus-related infectious mononucleosis: surveillance study.

Older patients are more susceptible to severe Epstein-Barr virus (EBV)-related infectious mononucleosis (IM). This condition may increase in industrialized countries where primary EBV infection occurs later in life. Between 1990 and 2004, 38 patients were admitted to our department with EBV-related IM. Two patients died. The annual incidence increased significantly (r = 0.623; P = 0.013).

Prevention of acquired infections in intubated patients with the combination of two decontamination regimens.

OBJECTIVE: The use of topical polymyxin and tobramycin to prevent intensive care infections is controversial. Moreover, these antibiotics are ineffective against methicillin-resistant Staphylococcus aureus. A decontamination regimen using mupirocin and chlorhexidine could prevent acquired infections, including those involving S. aureus. Because these two regimens could have a complementary role, we evaluated their effects when given both alone and combined. DESIGN: The authors conducted a multiple-center, placebo-controlled, randomized, double-blind study performed according to a 2 x 2 factorial design. SETTING: The study was conducted at three polyvalent medical intensive care units at university-affiliated hospitals in France. PATIENTS: Adult patients (age, > or =18 yrs) intubated for <48 hrs who were likely to be ventilated for >48 hrs. INTERVENTION: Two regimens were used: topical administration of polymyxin/tobramycin (or placebo) and nasal mupirocin with chlorhexidine body washing (or nasal placebo with liquid soap). The patients (n = 515) received polymyxin/tobramycin alone (n = 130), mupirocin/chlorhexidine alone (n = 130), both regimens (n = 129), or all placebos (n = 126) for the period of mechanical ventilation plus 24 hrs. MEASUREMENTS AND MAIN RESULTS: The incidence of total infections acquired from the date of randomization until the termination date of study treatments plus 48 hrs was assessed. There were fewer acquired infections with both regimens than with polymyxin/tobramycin alone (odds ratio, 0.44; 95% confidence interval, 0.26-0.75; p = .003), mupirocin/chlorhexidine alone (0.43; 0.25-0.73; p = .002), or all placebos (0.42; 0.25-0.72; p = .001). There were no differences between polymyxin/tobramycin alone (0.95; 0.59-1.54; p = .84) and mupirocin/chlorhexidine alone (0.98; 0.60-1.58; p = .92) vs. all placebos. The probability of freedom from infection was higher with both regimens than with polymyxin/tobramycin alone (p = .002), mupirocin/chlorhexidine alone (p < .001), or all placebos (p < .001). Infection rates were also significantly lower with both regimens than with polymyxin/tobramycin alone (p = .017), mupirocin/chlorhexidine alone (p < .001), or all placebos (p < .001). CONCLUSION: Acquired infections were substantially reduced by mupirocin/chlorhexidine plus polymyxin/tobramycin, whereas each regimen given alone was ineffective. Whether both regimens could increase Candida infections deserves further investigation.

Monocyte human leukocyte antigen-DR transcriptional downregulation by cortisol during septic shock.

Monocyte deactivation has been identified as a major factor of immunosuppression in sepsis and is associated with a loss of surface human leukocyte antigen-DR (HLA-DR) expression on circulating monocytes. Using flow cytometry, quantitative reverse transcription-polymerase chain reaction, we investigated this phenomenon in septic patients. We confirmed the early loss of monocyte HLA-DR expression in all infected patients and demonstrated that this persistent lowered expression at Day 6 correlated with severity scores, secondary infection, and death. This phenomenon occurred at a transcriptional level via a decrease in the class II transactivator A (CIITA) transcription. Furthermore, these abnormalities correlated with the high cortisol levels observed in sepsis and not with those of other putative factors such as catecholamines or interleukin-10. Finally, in vitro studies evidenced that glucocorticoids decrease HLA-DR expression at a transcriptional level via a decrease in CIITA mRNA levels, mainly by down modulating its isoforms I and III. We conclude that in human sepsis, the loss of HLA-DR expression on circulating monocytes is associated with a poor outcome. We suggest that the high endogenous cortisol level observed in septic shock may be a possible new factor involved in the loss of HLA-DR expression on monocytes via its effect on HLA-DR and CIITA transcription.