Comparison of prophylaxis and preemptive strategy as cytomegalovirus prevention in liver transplant recipients.

OBJECTIVES: Prophylaxis (P) or pre-emptive strategy (PS) in high-risk liver transplant recipients (LTRs) are either recommended. We compared the results of each strategy. METHODS: Two groups of LTR transplanted during two consecutive periods were compared. Only cytomegalovirus (CMV)-mismatched LTR (Donor +/ Recipient -) were included. The primary endpoints were: the onset of polymerase chain reaction-based DNAemia and the proportion of patients with CMV disease. A number of episodes of CMV infection, antiviral therapy, ganciclovir resistance, infectious or immunological complications, cost of both strategies, and survival (1, 5, and 10 years) were also compared. RESULTS: Forty-eight and 60 patients were respectively included in the P and PS groups. Eighteen (38%) in the P group and 56 (93%) in the PS group had CMV DNAemia (p <.0001) with a similar CMV disease rate (16.7% and 15%). Duration of curative therapy was longer in the PS group: 91 days versus 16 (p <.0001). Acute rejection was less frequent (p = .04) and more patients experienced a ganciclovir-resistant CMV infection in the PS group (10% vs. 0, p = .03). The drug-associated cost of PS was higher (10 004 vs. 4804€) and the median number of rehospitalization days tended to be higher (6 vs. 4, p = .06). Survival at any time was similar. CONCLUSION: We reported more CMV DNAemias and ganciclovir-resistant CMV events with PS. The cost of the PS strategy was higher.

Can we predict the influence of inflammation on voriconazole exposure? An overview.

Voriconazole is a triazole antifungal indicated for invasive fungal infections that exhibits a high degree of inter-individual and intra-individual pharmacokinetic variability. Voriconazole pharmacokinetics is non-linear, making dosage adjustments more difficult. Therapeutic drug monitoring is recommended by measurement of minimum plasma concentrations. Several factors are responsible for the high pharmacokinetic variability of voriconazole: age, feeding (which decreases absorption), liver function, genetic polymorphism of the CYP2C19 gene, drug interactions and inflammation. Invasive fungal infections are indeed very frequently associated with inflammation, which engenders a risk of voriconazole overexposure. Many studies have reviewed this topic in both the adult and paediatric populations, but few studies have focused on the specific point of the prediction, to evaluate the influence of inflammation on voriconazole pharmacokinetics. Predicting the impact of inflammation on voriconazole pharmacokinetics could help optimize antifungal therapy and improve patient management. This review summarizes the existing data on the influence of inflammation on voriconazole pharmacokinetics in adult populations. We also evaluate the role of C-reactive protein, the impact of inflammation on patient metabolic phenotypes, and the tools that can be used to predict the effect of inflammation on voriconazole pharmacokinetics.

Diagnosis and management of hepatic encephalopathy: The French recommendations.

Hepatic encephalopathy (HE) is a frequent and severe complication of liver disease with poor patient outcomes. However, it is a poorly understood complication, with no consensus for diagnosis. Therefore, HE is often underdiagnosed. Differential diagnosis may be cumbersome because of non-specific symptoms, such as confusion, cognitive disorders, the aetiological factors of cirrhosis and comorbidities, which are often observed in cirrhotic patients. Therefore, an overt or covert form of HE should be systematically investigated. Advice is provided to drive patient work-up. Effective treatments are available to prevent or treat HE bouts, but the issue of single or combination therapy has not been resolved. Transjugular intrahepatic portosystemic shunt (TIPS) placement largely improved the prognosis of cirrhotic patients, but HE occurrence of HE is often a fear, even when post-TIPS HE can be avoided by a careful selection of patients and preventive treatment. HE is an indication of liver transplantation. However, its reversibility post-transplantation and the consequences of transplantation in patients with other causes of neurological disorders remain controversial, which supports the performance of an extensive work-up in expert centres for this subset of patients. The present guidelines assist clinicians in the diagnosis of the overt or covert form of HE to implement curative and preventive treatments and clarify which patients require referral to expert centres for consideration for liver transplantation. These guidelines are very clinically oriented and address different frequent clinical issues to help physicians make bedside decisions.

Contribution of voriconazole N-oxide plasma concentration measurements to voriconazole therapeutic drug monitoring in patients with invasive fungal infection.

BACKGROUND: Voriconazole (VRC), a widely used triazole antifungal, exhibits significant inter- and intra-individual pharmacokinetic variability. The main metabolite voriconazole N-oxide (NOX) can provide information on the patient's drug metabolism capacity. OBJECTIVES: Our objectives were to implement routine measurement of NOX concentrations and to describe the metabolic ratio (MR), and the contribution of the MR to VRC therapeutic drug monitoring (TDM) by proposing a suggested dosage-adjustment algorithm. PATIENTS AND METHODS: Sixty-one patients treated with VRC were prospectively included in the study, and VRC and NOX levels were assayed by LC-MS/MS. A mixed logistic model on repeated measures was implemented to analyse risk factors for the patient's concentration to be outside the therapeutic range. RESULTS: Based on 225 measurements, the median and interquartile range were 2.4 µg/ml (1.2; 4.2), 2.1 µg/ml (1.5; 3.0) and 1.0 (0.6; 1.9) for VRC, NOX and the MR, respectively. VRC Cmin <2 µg/ml were associated with a higher MR during the previous visit. MR values >1.15 and <0.48 were determined to be the best predictors for having a VRC Cmin lower than 2 µg/ml and above 5.5 µg/ml, respectively, at the next visit. CONCLUSIONS: Measurement of NOX resulted useful for TDM of patients treated with VRC. The MR using NOX informed interpretation and clinical decision-making and is very interesting for complex patients. VRC phenotyping based on the MR is now performed routinely in our institution. A dosing algorithm has been suggested from these results.

Renoportal Anastomosis During Liver Transplantation in Patients With Portal Vein Thrombosis: First Long-term Results From a Multicenter Study.

OBJECTIVE: To evaluate the short- and long-term outcomes of RPA in a large multicentric series. SUMMARY BACKGROUND: The current knowledge on RPA for portal reconstruction during LT in patients with diffuse PVT and a large splenorenal shunt is poor and limited to case reports and small case series. METHODS: All consecutive LTs with RPA performed in 5 centers between 1998 and 2020 were included. RPA was physiological provided it drained the splanchnic venous return through a large splenorenal shunt (≥ 1 cm diameter). Complications of PHT, long-term RPA patency, and patient and graft survival were assessed. RPA success was achieved provided the 3 following criteria were all fulfilled: patients were alive with patent RPA and without clinical PHT. RESULTS: RPA was attempted and feasible in 57 consecutive patients and was physiological in 51 patients (89.5%). Ninety-day mortality occurred in 5 (8.5%) patients, and PHT-related complications occurred in 42.9% of patients. With a median follow-up of 63 months, the 1-, 3- and 5-year patient and graft survival rates were 87%, 83%, and 76% and 82%, 80%, and 73%, respectively. The primary and primary-assisted patency rates at 5 years were 84.5% and 94.3%, respectively. Success was achieved in 90% (27/30) of patients with a follow-up ≥5 years. CONCLUSIONS: Despite a high rate of PHT-related complications, excellent long-term patient and graft survival could be achieved. RPA could be considered successful in the vast majority of patients. The expanded use of RPA is warranted.

Tolerance and complications of therapeutic plasma exchange by centrifugation: A single center experience.

INTRODUCTION: Therapeutic plasma exchange (TPE) constitutes an important therapy for hematological, neurological, immunological, and nephrological diseases. Most studies have focused on efficacy, whereas tolerance and complications during sessions have been less well studied and not recently. MATERIAL AND METHODS: We conducted a single center retrospective study of all patients who underwent TPE between 2011 and 2018. TPE sessions using the centrifugation technique were performed by dedicated trained nurses. Specific side effects were identified through surveillance forms completed contemporaneously. The primary outcome was the rate of all-type adverse effects that occurred during the TPE sessions. RESULTS: In total, 1895 TPE sessions performed on 185 patients were analyzed. At least one adverse effect was reported for 805 sessions (42.5% [29.9%-70.1%]), corresponding to 171 patients (92.4% [87.6%-95.8%]). Hypotension occurred during 288 sessions (15.2%), was asymptomatic in 95.8% of cases, and more frequent with the use of 4% albumin than fresh frozen plasma (FFP) (19.8 vs 8.9%, P <.0001). Hypocalcemia occurred during 370 sessions (19.6%) and was more frequent with the use of FFP than with the use of albumin alone (FFP alone: 28.0%, albumin + FFP: 26%, albumin alone: 11.7%; P <.0001). Allergic reactions occurred during 56 sessions (3%), exclusively with FFP. Severe adverse effects were reported for 0.3% of sessions and 5.4% of patients. CONCLUSIONS: TPE is a safe therapy when performed by a trained team. Adverse effects were frequent but mostly not serious. The replacement fluid was the main determinant of the occurrence of complications. (ClinicalTrials.gov ID: NCT03888417).

SARS-CoV-2-Induced ARDS Associates with MDSC Expansion, Lymphocyte Dysfunction, and Arginine Shortage.

PURPOSE: The SARS-CoV-2 infection can lead to a severe acute respiratory distress syndrome (ARDS) with prolonged mechanical ventilation and high mortality rate. Interestingly, COVID-19-associated ARDS share biological and clinical features with sepsis-associated immunosuppression since lymphopenia and acquired infections associated with late mortality are frequently encountered. Mechanisms responsible for COVID-19-associated lymphopenia need to be explored since they could be responsible for delayed virus clearance and increased mortality rate among intensive care unit (ICU) patients. METHODS: A series of 26 clinically annotated COVID-19 patients were analyzed by thorough phenotypic and functional investigations at days 0, 4, and 7 after ICU admission. RESULTS: We revealed that, in the absence of any difference in demographic parameters nor medical history between the two groups, ARDS patients presented with an increased number of myeloid-derived suppressor cells (MDSC) and a decreased number of CD8pos effector memory cell compared to patients hospitalized for COVID-19 moderate pneumonia. Interestingly, COVID-19-related MDSC expansion was directly correlated to lymphopenia and enhanced arginase activity. Lastly, T cell proliferative capacity in vitro was significantly reduced among COVID-19 patients and could be restored through arginine supplementation. CONCLUSIONS: The present study reports a critical role for MDSC in COVID-19-associated ARDS. Our findings open the possibility of arginine supplementation as an adjuvant therapy for these ICU patients, aiming to reduce immunosuppression and help virus clearance, thereby decreasing the duration of mechanical ventilation, nosocomial infection acquisition, and mortality.

Hypothermic Oxygenated Perfusion Improves Extended Criteria Donor Liver Graft Function and Reduces Duration of Hospitalization Without Extra Cost: The PERPHO Study.

Few studies have evaluated the efficacy or the cost of hypothermic oxygenated perfusion (HOPE) in the conservation of extended criteria donor (ECD) grafts from donation after brain death (DBD) donors during liver transplantation (LT). We performed a prospective, monocentric study (NCT03376074) designed to evaluate the interest of HOPE for ECD-DBD grafts. For comparison, a control group was selected after propensity score matching among patients who received transplants between 2010 and 2017. Between February and November 2018, the HOPE procedure was used in 25 LTs. Immediately after LT, the median aspartate aminotransferase (AST) level was significantly lower in the HOPE group (724UI versus 1284UI; P = 0.046) as were the alanine aminotransferase (ALT; 392UI versus 720UI; P = 0.01), lactate (2.2 versus 2.7; P = 0.01) There was a significant reduction in intensive care unit stay (3 versus 5 days; P = 0.01) and hospitalization (15 versus 20 days; P = 0.01). The incidence of early allograft dysfunction (EAD; 28% versus 42%; P = 0.22) was similar . A level of AST or ALT in perfusate >800UI was found to be highly predictive of EAD occurrence (areas under the curve, 0.92 and 0.91, respectively). The 12-month graft (88% versus 89.5%; P = 1.00) and patient survival rates (91% versus 91.3%; P = 1.00) were similar. The additional cost of HOPE was estimated at € 5298 per patient. The difference between costs and revenues, from the hospital's perspective, was not different between the HOPE and control groups (respectively, € 3023 versus € 4059]; IC, -€ 5470 and € 8652). HOPE may improve ECD graft function and reduce hospitalization stay without extra cost. These results must be confirmed in a randomized trial.

The emergence of Staphylococcus aureus as the primary cause of cardiac device-related infective endocarditis.

BACKGROUND: Increasing use of cardiovascular implantable electronic devices (CIED), as permanent pacemakers (PPM), implantable cardioverter defibrillators (ICD), or cardiac resynchronization therapy (CRT), is associated with the emergence of CIED-related infective endocarditis (CIED-IE). We aimed to characterize CIED-IE profile, temporal trends, and prognostic factors. METHODS: CIED-IE diagnosed at Rennes University Hospital during years 1992-2017 were identified through computerized database, and included if they presented all of the following: (1) clinical signs of infection; (2) microbiological documentation through blood and/or CIED lead cultures; (3) lead or valve vegetation, or definite IE according to Duke criteria. Data were retrospectively extracted from medical charts. The cohort was categorized in three periods: 1992-1999, 2000-2008, and 2009-2017. RESULTS: We included 199 patients (51 women, 148 men, median age 73 years [interquartile range, 64-79]), with CIED-IE: 158 PPMs (79%), 24 ICD (12%), and 17 CRT (9%). Main pathogens were coagulase-negative staphylococci (CoNS: n = 86, 43%), Staphylococcus aureus (n = 60, 30%), and other Gram-positive cocci (n = 28, 14%). Temporal trends were remarkable for the decline in CoNS (P = 0.002), and the emergence of S. aureus as the primary cause of CIED-IE (24/63 in 2009-2017, 38%). Factors independently associated with one-year mortality were chronic obstructive pulmonary disease (COPD: hazard ratio 3.84 [1.03-6.02], P = 0.03), left-sided endocarditis (HR 2.25 [1.09-4.65], P = 0.03), pathogens other than CoNS (HR 3.16 [1.19-8.39], P = 0.02), and CIED removal/reimplantation (HR 0.41 [0.20-0.83], P = 0.01). CONCLUSIONS: S. aureus has emerged as the primary cause of CIED-IE. Left-sided endocarditis, COPD, pathogens other than CoNS, and no CIED removal/reimplantation are independent risk factors for one-year mortality.

Advanced donor age does not increase risk of hepatocellular carcinoma recurrence after liver transplantation: a retrospective two-centre analysis using competing risk analysis.

The impact of donor age on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation is still debated. Between 2002 and 2014, all patients transplanted for HCC in 2 European liver transplantation tertiary centres were retrospectively reviewed. Risk factors for HCC recurrence were assessed using competing risk analysis, and the impact of donor age < or ≥65 years and < or ≥80 years was specifically evaluated after propensity score matching. 728 patients transplanted with a median follow-up of 86 months were analysed. The 1-, 3- and 5-year recurrence rates were 4.9%, 10.7% and 13.9%, respectively. In multivariable analysis, recipient age (sHR: 0.96 [0.93; 0.98], P < 0.01), number of lesions (sHR: 1.05 [1.04; 1.06], P < 0.001), maximum size of the lesions (sHR: 1.37 [1.27; 1.48], P < 0.01), presence of a hepatocholangiocarcinoma (sHR: 6.47 [2.91; 14.38], P < 0.01) and microvascular invasion (sHR: 3.48 [2.42; 5.02], P < 0.01) were significantly associated with HCC recurrence. After propensity score matching, neither donor age ≥65 (P = 0.29) nor donor age ≥80 (P = 0.84) years increased the risk of HCC recurrence. In conclusion, donor age was not found to be a risk factor for HCC recurrence. Patients listed for HCC can receive a graft from an elderly donor without compromising the outcome.

Incidence and risk factors for acquired colonization and infection due to extended-spectrum beta-lactamase-producing Gram-negative bacilli: a retrospective analysis in three ICUs with low multidrug resistance rate.

The purpose of this study is to assess risk factors for the acquisition of extended-spectrum ß-lactamase-producing Gram-negative bacilli (ESBL-GNB) colonization and infection (AI) in ICUs with low ESBL-GNB prevalence rate. We conducted a retrospective observational study in three ICUs in Bretagne, France. All patients admitted from January 2016 to September 2017 with a length of stay of 2 days or more were included. Universal screening for ESBL-GNB colonization was performed in all participating ICUs. Of the 3250 included patients, 131 (4.0%) were colonized at admission, 59 acquired colonization while hospitalized (1.9%; 95% CI [1.5-2.5%]), and 15 (0.5%; 95% CI [0.3-0.8%]) acquired ESBL-GNB infections. In the case of infection, the specificity and the negative predictive values of preexistent colonization for the ESBL-GNB etiology were 93.2% [91.5-95.1%] and 95.2% [93.5-97.1%], respectively. Colonization was the main risk factor for ESBL-GNB AI (OR = 9.61; 95% CI [2.86-32.29]; p < 0.001). Antimicrobial susceptibility of non-ESBL-GNB isolates responsible for AI was similar for any non-carbapenem ß-lactam (95%) and imipenem (94%). ESBL-GNB AIs were rare in ICUs with low ESBL-GNB prevalence rate. Prior colonization was the main risk factor for subsequent infection. Empirical carbapenem therapy could be avoided in non ESBL-GNB colonized patients with suspected AI.

Redefining Therapeutic Drug Monitoring of Tacrolimus in Patients Undergoing Liver Transplantation: A Target Trough Concentration of 4-7 ng/mL During the First Month After Liver Transplantation is Safe and Improves Graft and Renal Function.

BACKGROUND: Currently, the recommended tacrolimus (TAC) trough level (Cmin) after liver transplantation (LT) is 6-10 ng/mL (when associated in triple immunosuppressive therapy). However, few studies have achieved the lower limit of this range, especially below 7 ng/mL. This study evaluated the efficacy of a target TAC Cmin of 4-7 ng/mL after LT. METHODS: Of 1677 LTs performed between 2002 and 2017, 904 LT cases were analyzed. The cases were categorized into the following 3 groups and compared: low- (n = 247, 27.3%), intermediate- (n = 344, 37.9%), and high-exposure groups (n = 313, 34.5%) with TAC Cmin of 4-7 ng/mL, 7-10 ng/mL, and >10 ng/mL, respectively. In addition, propensity score matching was performed to reduce heterogeneity and population bias. RESULTS: At months 1 and 3, when compared with the 2 other groups, the low-exposure group had similar grafts (P = 0.75) and patient (P = 0.77) survival, but lower alanine aminotransferase (P < 0.001), bilirubin (P < 0.001), international normalized ratio (P = 0.046), and creatinine (P < 0.001) levels. After propensity score matching, the bilirubin (P < 0.001) and creatinine (P = 0.001) levels in the low-exposure group still improved at months 3, but the graft (P = 0.86) and patient (P = 0.99) survival were still similar. CONCLUSIONS: A TAC Cmin of 4-7 ng/mL seems safe and capable of improving graft and kidney function. This finding should be confirmed in a prospective randomized trial.

Liver transplantation in patients with liver failure related to exertional heatstroke.

BACKGROUND & AIMS: Severe acute liver injury is a grave complication of exertional heatstroke. Liver transplantation (LT) may be a therapeutic option, but the criteria for LT and the optimal timing of LT have not been clearly established. The aim of this study was to define the profile of patients who require transplantation in this context. METHODS: This was a multicentre, retrospective study of patients admitted with a diagnosis of exertional heatstroke-related severe acute liver injury with a prothrombin time (PT) of less than 50%. A total of 24 male patients were studied. RESULTS: Fifteen of the 24 patients (median nadir PT: 35% [29.5-40.5]) improved under medical therapy alone and survived. Nine of the 24 were listed for emergency LT. At the time of registration, the median PT was 10% (5-12) and all had numerous dysfunctional organs. Five patients (nadir PT: 12% [9-12]) were withdrawn from the list because of an elevation of PT values that mainly occurred between day 2 and day 3. Ultimately, 4 patients underwent transplantation as their PT persisted at <10%, 3 days (2.75-3.25) after the onset of exertional heatstroke, and they had more than 3 organ dysfunctions. Of these 4 patients, 3 were still alive 1 year later. Histological analysis of the 4 explanted livers demonstrated massive or sub-massive necrosis, and little potential for effective mitoses, characterised by a "mitonecrotic" appearance. CONCLUSION: The first-line treatment for exertional heatstroke-related severe acute liver injury is medical therapy. LT is only a rare alternative and such a decision should not be taken too hastily. A persistence of PT <10%, without any signs of elevation after a median period of 3  days following the onset of heatstroke, was the trigger that prompted LT, was the trigger adopted in order to decide upon LT. LAY SUMMARY: Acute liver injury due to heatstroke can progress to acute liver failure with organ dysfunction despite medical treatment; in such situations, liver transplantation (LT) may offer a therapeutic option. The classic criteria for LT appear to be poorly adapted to heatstroke-related acute liver failure. We confirmed thatmedication is the first-line therapy acute liver injury caused by heatstroke, with LT only rarely necessary. A decision to perform LT should not be made hastily. Fluctuations in prothrombin time and the patient's clinical status should be considered even in the event of severe liver failure.

Early Expansion of Circulating Granulocytic Myeloid-derived Suppressor Cells Predicts Development of Nosocomial Infections in Patients with Sepsis.

RATIONALE: Sepsis induces a sustained immune dysfunction responsible for poor outcome and nosocomial infections. Myeloid-derived suppressor cells (MDSCs) described in cancer and inflammatory processes may be involved in sepsis-induced immune suppression, but their clinical impact remains poorly defined. OBJECTIVES: To clarify phenotype, suppressive activity, origin, and clinical impact of MDSCs in patients with sepsis. METHODS: Peripheral blood transcriptomic analysis was performed on 29 patients with sepsis and 15 healthy donors. A second cohort of 94 consecutive patients with sepsis, 11 severity-matched intensive care patients, and 67 healthy donors was prospectively enrolled for flow cytometry and functional experiments. MEASUREMENTS AND MAIN RESULTS: Genes involved in MDSC suppressive functions, including S100A12, S100A9, MMP8, and ARG1, were up-regulated in the peripheral blood of patients with sepsis. CD14posHLA-DRlow/neg monocytic (M)-MDSCs were expanded in intensive care unit patients with and without sepsis and CD14negCD15pos low-density granulocytes/granulocytic (G)-MDSCs were more specifically expanded in patients with sepsis (P < 0.001). Plasma levels of MDSC mediators S100A8/A9, S100A12, and arginase 1 were significantly increased. In vitro, CD14pos- and CD15pos-cell depletion increased T-cell proliferation in patients with sepsis. G-MDSCs, made of immature and mature granulocytes expressing high levels of degranulation markers, were specifically responsible for arginase 1 activity. High initial levels of G-MDSCs, arginase 1, and S100A12 but not M-MDSCs were associated with subsequent occurrence of nosocomial infections. CONCLUSIONS: M-MDSCs and G-MDSCs strongly contribute to T-cell dysfunction in patients with sepsis. More specifically, G-MDSCs producing arginase 1 are associated with a higher incidence of nosocomial infections and seem to be major actors of sepsis-induced immune suppression.

Benefits of temporary portocaval shunt during orthotopic liver transplantation with vena cava preservation: A propensity score analysis.

During orthotopic liver transplantation (OLT), clamping of the portal vein induces splanchnic venous congestion and accumulation of noxious compounds. These adverse effects could increase ischemia/reperfusion injury and subsequently the risk of graft dysfunction, especially for grafts harvested from extended criteria donors (ECDs). Temporary portocaval shunt (TPCS) could prevent these complications. Between 2002 and 2013, all OLTs performed in our center were retrospectively analyzed and a propensity score matching analysis was used to compare the effect of TPCS in 686 patients (343 in each group). Patients in the TPCS group required fewer intraoperative transfusions (median number of packed red blood cells-5 versus 6; P = 0.02; median number of fresh frozen plasma-5 versus 6; P = 0.02); had improvement of postoperative biological parameters (prothrombin time, Factor V, international normalized ratio, alkaline phosphatase, and gamma-glutamyltransferase levels); and showed significant reduction of biliary complications (4.7% versus 10.2%; P = 0.006). Survival analysis revealed that TPCS improved 3-month graft survival (94.2% versus 88.6%; P = 0.01) as well as longterm survival of elderly (ie, age > 70 years) donor grafts (P = 0.02). In conclusion, the use of TPCS should be recommended especially when considering an ECD graft. Liver Transplantation 23 174-183 2017 AASLD.

Short-term decline in all-cause acquired infections with the routine use of a decontamination regimen combining topical polymyxin, tobramycin, and amphotericin B with mupirocin and chlorhexidine in the ICU: a single-center experience.

OBJECTIVES: In a multicenter, placebo-controlled, randomized, double-blind trial, we showed that acquired infections in intubated patients were reduced by the combination of topical polymyxin plus tobramycin and nasal mupirocin plus chlorhexidine body wash. Because intubated patients are particularly at risk for acquired infections, we reassessed the impact of this protocol as a routine procedure to control acquired infections in the ICU. DESIGN: Nonrandomized study comparing acquired infections in ICU patients during two 1-year periods: the last year before (group A, n = 925) and the first year after the implementation of the protocol (group B, n = 1,022). Acquired infections were prospectively recorded. SETTING: Polyvalent medical ICU at a university-affiliated hospital. PATIENTS: All patients admitted to the ICU. INTERVENTIONS: Administration of polymyxin/tobramycin/amphotericin B in the oropharynx and the gastric tube plus a mupirocin/chlorhexidine regimen in intubated patients and standard care in the other patients. MEASUREMENTS AND MAIN RESULTS: The comparison of acquired infection rates between groups was adjusted for differences at baseline. Infection rates were lower in group B compared with group A (5.3% vs 11.0%; p < 0.001), as were the incidence rates of total acquired infections (9.4 vs 23.6 per 1,000 patient-days; p < 0.001), intubation-related pneumonia (5.1 vs 17.1 per 1,000 ventilator-days; p < 0.001), and catheter-related bloodstream infections (1.0 vs 3.5 per 1,000 catheter-days; p = 0.03). There were fewer acquired infections caused by ceftazidime-resistant Enterobacteriaceae (0.8‰ vs 3.6‰; p < 0.001), ciprofloxacin-resistant Enterobacteriaceae (0.8‰ vs 2.5‰; p = 0.02), ciprofloxacin-resistant Pseudomonas aeruginosa (0.5‰ vs 1.6‰; p = 0.05), and colistin-resistant Gram-negative bacilli (0.7‰ vs 1.9‰; p = 0.04). Fewer patients got acquired infections due to multidrug-resistant aerobic Gram-negative bacilli (p = 0.008). CONCLUSIONS: In intubated patients, the use of topical polymyxin/tobramycin/amphotericin B plus mupirocin/chlorhexidine was associated with the reduction of all-cause ICU-acquired infections. Long-term emergence of multidrug-resistant organisms deserves further investigation.

Long-term results of combined liver-kidney transplantation for primary hyperoxaluria type 1: the French experience.

Primary hyperoxaluria type 1 (PH1) is a hepatic metabolic defect leading to end-stage renal failure. The posttransplant recurrence of kidney disease can suggest a need for combined liver-kidney transplantation (LKT). However, the risk of LKT is theoretically far higher than the risk of kidney-alone transplantation (KAT). An unselected consecutive series of 54 patients with PH1 was analyzed according to the type of transplantation initially performed between May 1979 and June 2010 at 10 French centers. The duration of dialysis, extrarenal lesions, age, and follow-up were similar between the groups. Postoperative morbidity and mortality did not differ between the groups, and 10-year patient survival rates were similar for the LKT (n = 33) and KAT groups (n = 21; 78% versus 70%). Kidney graft survival at 10 years was better after LKT (87% versus 13%, P < .001) . Four patients (12.1%) lost their first kidney graft in the LKT group, whereas 19 (90%) did in the KAT group (P < .001). The recurrence of oxalosis occurred in 11 renal grafts (52%) in the KAT group but in none in the LKT group (P < .001). End-stage renal failure resulting from rejection was also higher in the KAT group (19% versus 9%, P < 0.0001). A second kidney transplant was performed for 15 patients (71%) in the KAT group versus 4 patients (12%) in the LKT group (P < 0.001). In conclusion, LKT for PH1 provides better kidney graft survival, less rejection, and similar long-term patient survival and is not associated with an increased short-term mortality risk. LKT must be the first-line treatment for PH1 patients with end-stage renal disease.

Can we predict poor hemodynamic tolerance of intermittent hemodialysis with echocardiography in intensive care patients?

OBJECTIVES: Tolerance of intermittent hemodialysis is potentially poor for patients hospitalized in the intensive care unit, particularly those in shock. The aim of this study was to determine whether an evaluation of the hemodynamic state by echocardiography before an intermittent hemodialysis session could predict tolerance during the session. METHODS: Before an intermittent hemodialysis session, transesophageal echocardiography was performed on sedated patients, and transthoracic echocardiography was performed on nonsedated patients. Poor tolerance during intermittent hemodialysis was defined by the following criteria: greater than 20% decrease in mean arterial pressure, need for fluid loading (≥500 mL), a 15% increase in catecholamine if the dose was stable before the session or doubling the speed of catecholamine infusion if necessary, arrhythmia, and the necessity to stop the session before its prescribed end. RESULTS: A total of 54 patients were included: 20 (37%) were intubated under controlled mechanical ventilation (group 1) and underwent transesophageal echocardiography; 14 (26%) were intubated under pressure support ventilation (group 2) and underwent transthoracic echocardiography; and 20 (37%) had no ventilation support (group 3). Twenty-four patients (46%) had poor tolerance criteria. A comparison of groups showed no significant difference in tolerance. Similarly, there was no difference with and without ultrafiltration. Increased respiratory variation of the vena cava was not predictive of poor tolerance in groups 1 and 2. In group 3, there was greater variation in patients with poor tolerance. In patients receiving mechanical ventilation, greater respiratory variability of the maximum velocity measured in the pulmonary artery was predictive of poor tolerance. CONCLUSIONS: The hemodynamic profile of patients receiving mechanical ventilation was unable to predict tolerance of an intermittent hemodialysis session. In patients without mechanical ventilation, hypovolemia before the session appeared to be predictive of poor tolerance.