Outcome of patients treated with molecular adsorbent recirculating system albumin dialysis: A national multicenter study.

BACKGROUND AND AIM: The molecular adsorbent recirculating system (MARS) is the most widely used device to treat liver failure. Nevertheless, data from widespread real-life use are lacking. METHODS: This was a retrospective multicenter study conducted in all French adult care centers that used MARS between 2004 and 2009. The primary objective was to evaluate patient survival according to the liver disease and listing status. Factors associated with mortality were the secondary objectives. RESULTS: A total of 383 patients underwent 393 MARS treatments. The main indications were acute liver failure (ALF, 32.6%), and severe cholestasis (total bilirubin >340 µmol/L) (37.2%), hepatic encephalopathy (23.7%), and/or acute kidney injury-hepatorenal syndrome (22.9%) most often among patients with chronic liver disease. At the time of treatment, 34.4% of the patients were listed. Overall, the hospital survival rate was 49% (95% CI: 44-54%) and ranged from 25% to 81% depending on the diagnosis of the liver disease. In listed patients versus those not listed, the 1-year survival rate was markedly better in the setting of nonbiliary cirrhosis (59% vs 15%), early graft nonfunction (80% vs 0%), and late graft dysfunction (72% vs 0%) (all P < 0.001). Among nonbiliary cirrhotic patients, hospital mortality was associated with the severity of liver disease (HE and severe cholestasis) and not being listed for transplant. In ALF, paracetamol etiology and ≥3 MARS sessions were associated with better transplant-free survival. CONCLUSION: Our study suggests that MARS should be mainly used as a bridge to liver transplantation. Survival was correlated with being listed for most etiologies and with the intensity of treatment in ALF.

Epidemiology and prognosis of anti-infective therapy in the ICU setting during acute pancreatitis: a cohort study.

BACKGROUND: Recent international guidelines for acute pancreatitis (AP) recommend limiting anti-infective therapy (AIT) to cases of suspected necrotizing AP or nosocomial extrapancreatic infection. Limited data are available concerning empirical and documented AIT prescribing practices in patients admitted to the intensive care unit (ICU) for the management of AP. METHODS: Using a multicentre, retrospective (2009-2014), observational database of ICU patients admitted for AP, our primary objective was to assess the incidence of AIT prescribing practices during the first 30 days following admission. Secondary objectives were to assess the independent impact of centre characteristics on the incidence of AIT and to identify factors associated with crude hospital mortality in a logistic regression model. RESULTS: In this cohort of 860 patients, 359 (42%) received AIT on admission. Before day 30, 340/359 (95%) AIT patients and 226/501 (45%) AIT-free patients on admission received additional AIT, mainly for intra-abdominal and lung infections. A large heterogeneity was observed between centres in terms of the incidence of infections, therapeutic management including AIT and prognosis. Administration of AIT on admission or until day 30 was not associated with an increased mortality rate. Patients receiving AIT on admission had increased rates of complications (septic shock, intra-abdominal and pulmonary infections), therapeutic (surgical, percutaneous, endoscopic) interventions and increased length of ICU stay compared to AIT-free patients. Patients receiving delayed AIT after admission and until day 30 had increased rates of complications (respiratory distress syndrome, intra-abdominal and pulmonary infections), therapeutic interventions and increased length of ICU stay compared to those receiving AIT on admission. Risk factors for hospital mortality assessed on admission were age (adjusted odds ratio [95% confidence interval] 1.03 [1.02-1.05]; p < 0.0001), Balthazar score E (2.26 [1.43-3.56]; p < 0.0001), oliguria/anuria (2.18 [1.82-4.33]; p < 0.0001), vasoactive support (2.83 [1.73-4.62]; p < 0.0001) and mechanical ventilation (1.90 [1.15-3.14]; p = 0.011), but not AIT (0.63 [0.40-1.01]; p = 0.057). CONCLUSIONS: High proportions of ICU patients admitted for AP receive AIT, both on admission and during their ICU stay. A large heterogeneity was observed between centres in terms of incidence of infections, AIT prescribing practices, therapeutic management and outcome. AIT reflects the initial severity and complications of AP, but is not a risk factor for death.

Complex liver resection under hepatic vascular exclusion and hypothermic perfusion with versus without veno-venous bypass: a comparative study.

BACKGROUND: While hypothermic liver perfusion has been shown to improve parenchymal tolerance to complex resections in patients requiring prolonged hepatic vascular exclusion (HVE), the benefit of associated veno-venous bypass (VVB) in this setting remains poorly evaluated. METHODS: All patients undergoing liver resection requiring HVE and hypothermic liver perfusion for at least 55 min between 2006 and 2017 were retrospectively reviewed. Perioperative outcomes were compared between patients with (VVB+) or without VVB (VVB-). RESULTS: Twenty-seven patients were analyzed, including 13 VVB+ and 14 VVB-. Median HVE duration was similar in VVB+ and VVB- patients (96 vs. 75 min, respectively). VVB+patients had longer operative time (460 vs. 375 min, p = 0.023) but less blood loss (p = 0.010). Five (19%) patients died postoperatively from liver failure or sepsis, without difference between groups. Postoperative major morbidity rate was similar between VVB+ and VVB- patients (30% vs. 50%, respectively) such as rates of liver failure, haemorrhage, renal insufficiency and sepsis, but VVB- patients experienced more respiratory complications (64% vs. 15%, p = 0.012). CONCLUSION: During liver resection under HVE and hypothermic liver perfusion, use of VVB allows for reducing blood loss and postoperative respiratory complications. VVB should be recommended in case of liver resection with prolonged HVE.

Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial.

BACKGROUND: Acute acidaemia is frequently observed during critical illness. Sodium bicarbonate infusion for the treatment of severe metabolic acidaemia is a possible treatment option but remains controversial, as no studies to date have examined its effect on clinical outcomes. Therefore, we aimed to evaluate whether sodium bicarbonate infusion would improve these outcomes in critically ill patients. METHODS: We did a multicentre, open-label, randomised controlled, phase 3 trial. Local investigators screened eligible patients from 26 intensive care units (ICUs) in France. We included adult patients (aged ≥18 years) who were admitted within 48 h to the ICU with severe acidaemia (pH ≤7·20, PaCO2 ≤45 mm Hg, and sodium bicarbonate concentration ≤20 mmol/L) and with a total Sequential Organ Failure Assessment score of 4 or more or an arterial lactate concentration of 2 mmol/L or more. We randomly assigned patients (1:1), by stratified randomisation with minimisation via a restricted web platform, to receive either no sodium bicarbonate (control group) or 4·2% of intravenous sodium bicarbonate infusion (bicarbonate group) to maintain the arterial pH above 7·30. Our protocol recommended that the volume of each infusion should be within the range of 125-250 mL in 30 min, with a maximum of 1000 mL within 24 h after inclusion. Randomisation criteria were stratified among three prespecified strata: age, sepsis status, and the Acute Kidney Injury Network (AKIN) score. The primary outcome was a composite of death from any cause by day 28 and the presence of at least one organ failure at day 7. All analyses were done on data from the intention-to-treat population, which included all patients who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02476253. FINDINGS: Between May 5, 2015, and May 7, 2017, we enrolled 389 patients into the intention-to-treat analysis in the overall population (194 in the control group and 195 in the bicarbonate group). The primary outcome occurred in 138 (71%) of 194 patients in the control group and 128 (66%) of 195 in the bicarbonate group (absolute difference estimate -5·5%, 95% CI -15·2 to 4·2; p=0·24). The Kaplan-Meier method estimate of the probability of survival at day 28 between the control group and bicarbonate group was not significant (46% [95% CI 40-54] vs 55% [49-63]; p=0·09. In the prespecified AKIN stratum of patients with a score of 2 or 3, the Kaplan-Meier method estimate of survival by day 28 between the control group and bicarbonate group was significant (37% [95% CI 28-48] vs 54% [45-65]; p=0·0283). [corrected] Metabolic alkalosis, hypernatraemia, and hypocalcaemia were observed more frequently in the bicarbonate group than in the control group, with no life-threatening complications reported. INTERPRETATION: In patients with severe metabolic acidaemia, sodium bicarbonate had no effect on the primary composite outcome. However, sodium bicarbonate decreased the primary composite outcome and day 28 mortality in the a-priori defined stratum of patients with acute kidney injury. FUNDING: French Ministry of Health and the Société Française d'Anesthésie Réanimation.

Short-course antibiotic therapy for critically ill patients treated for postoperative intra-abdominal infection: the DURAPOP randomised clinical trial.

PURPOSE: Shortening the duration of antibiotic therapy (ABT) is a key measure in antimicrobial stewardship. The optimal duration of ABT for treatment of postoperative intra-abdominal infections (PIAI) in critically ill patients is unknown. METHODS: A multicentre prospective randomised trial conducted in 21 French intensive care units (ICU) between May 2011 and February 2015 compared the efficacy and safety of 8-day versus 15-day antibiotic therapy in critically ill patients with PIAI. Among 410 eligible patients (adequate source control and ABT on day 0), 249 patients were randomly assigned on day 8 to either stop ABT immediately (n = 126) or to continue ABT until day 15 (n = 123). The primary endpoint was the number of antibiotic-free days between randomisation (day 8) and day 28. Secondary outcomes were death, ICU and hospital length of stay, emergence of multidrug-resistant (MDR) bacteria and reoperation rate, with 45-day follow-up. RESULTS: Patients treated for 8 days had a higher median number of antibiotic-free days than those treated for 15 days (15 [6-20] vs 12 [6-13] days, respectively; P < 0.0001) (Wilcoxon rank difference 4.99 days [95% CI 2.99-6.00; P < 0.0001). Equivalence was established in terms of 45-day mortality (rate difference 0.038, 95% CI - 0.013 to 0.061). Treatments did not differ in terms of ICU and hospital length of stay, emergence of MDR bacteria or reoperation rate, while subsequent drainages between day 8 and day 45 were observed following short-course ABT (P = 0.041). CONCLUSION: Short-course antibiotic therapy in critically ill ICU patients with PIAI reduces antibiotic exposure. Continuation of treatment until day 15 is not associated with any clinical benefit. CLINICALTRIALS. GOV IDENTIFIER: NCT01311765.

Diagnosis biomarkers in acute intestinal ischemic injury: so close, yet so far.

Acute intestinal ischemic injury (i3) is a life-threatening condition with disastrous prognosis, which is currently difficult to diagnose at the early stages of the disease; a rapid diagnosis is mandatory to avoid irreversible ischemia, extensive bowel resection, sepsis and death. The overlapping protein expression of liver and gut related to the complex physiopathology of the disease, the heterogeneity of the disease and its relative rarity could explain the lack of a useful early biochemical marker of i3. Apart from non-specific biological markers of thrombosis, hypoxia inflammation, and infection, several more specific biomarkers in relation with the gut barrier dysfunction, the villi injury and the enterocyte mass have been used in the diagnosis of acute i3. It includes particularly D-lactate, intestinal fatty acid-binding protein (FABP) and citrulline. Herein, we will discuss leading publications concerning these historical markers that point out the main limitations reagrding their use in routine clinical practice. We will also introduce the first and limited results arising from omic studies, underlying the remaining effort that needs to be done in the field of acute i3 biological diagnosis, which remains a challenge.

Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol.

INTRODUCTION: Severe trauma represents the leading cause of mortality worldwide. While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP). Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP. Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP. The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients. METHODS AND ANALYSIS: This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours. Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group). The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28. The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION: Clinical Trials NCT02534974.

Predictive Factors of Intestinal Necrosis in Acute Mesenteric Ischemia: Prospective Study from an Intestinal Stroke Center.

OBJECTIVES: To identify predictive factors for irreversible transmural intestinal necrosis (ITIN) in acute mesenteric ischemia (AMI) and establish a risk score for ITIN. METHODS: This single-center prospective cohort study was performed between 2009 and 2015 in patients with AMI. The primary outcome was the occurrence of ITIN, confirmed by specimen analysis in patients who underwent surgery. Patients who recovered from AMI with no need for intestinal resection were considered not to have ITIN. Clinical, biological and radiological data were compared in a Cox regression model. RESULTS: A total of 67 patients were included. The origin of AMI was arterial, venous, or non-occlusive in 61%, 37%, 2% of cases, respectively. Intestinal resection and ITIN concerned 42% and 34% of patients, respectively. Factors associated with ITIN in multivariate analysis were: organ failure (hazard ratio (HR): 3.1 (95% confidence interval (CI): 1.1-8.5); P=0.03), serum lactate levels >2 mmol/l (HR: 4.1 (95% CI: 1.4-11.5); P=0.01), and bowel loop dilation on computerized tomography scan (HR: 2.6 (95% CI: 1.2-5.7); P=0.02). ITIN rate increased from 3% to 38%, 89%, and 100% in patients with 0, 1, 2, and 3 factors, respectively. Area under the receiver operating characteristics curve for the diagnosis of ITIN was 0.936 (95% CI: 0.866-0.997) depending on the number of predictive factors. CONCLUSIONS: We identified three predictive factors for irreversible intestinal ischemic injury requiring resection in the setting of AMI. Close monitoring of these factors could help avoid unnecessary laparotomy, prevent resection, as well as complications due to unresected necrosis, and possibly lower the overall mortality.

Multicenter testing of the rapid quantification of radical oxygen species in cerebrospinal fluid to diagnose bacterial meningitis.

PURPOSE: Meningitis is a serious concern after traumatic brain injury (TBI) or neurosurgery. This study tested the level of reactive oxygen species (ROS) in cerebrospinal fluid (CSF) to diagnose meningitis in febrile patients several days after trauma or surgery. METHODS: Febrile patients (temperature > 38°C) after TBI or neurosurgery were included prospectively. ROS were measured in CSF within 4 hours after sampling using luminescence in the basal state and after cell stimulation with phorbol 12-myristate 13-acetate (PMA). The study was conducted in a single-center cohort 1 (n = 54, training cohort) and then in a multicenter cohort 2 (n = 136, testing cohort) in the Intensive Care and Neurosurgery departments of two teaching hospitals. The performance of the ROS test was compared with classical CSF criteria, and a diagnostic decision for meningitis was made by two blinded experts. RESULTS: The production of ROS was higher in the CSF of meningitis patients than in non-infected CSF, both in the basal state and after PMA stimulation. In cohort 1, ROS production was associated with a diagnosis of meningitis with an AUC of 0.814 (95% confidence interval (CI) [0.684-0.820]) for steady-state and 0.818 (95% CI [0.655-0.821]) for PMA-activated conditions. The best threshold value obtained in cohort 1 was tested in cohort 2 and showed high negative predictive values and low negative likelihood ratios of 0.94 and 0.36 in the basal state, respectively, and 0.96 and 0.24 after PMA stimulation, respectively. CONCLUSION: The ROS test in CSF appeared suitable for eliminating a diagnosis of bacterial meningitis.

Effects of a multimodal management strategy for acute mesenteric ischemia on survival and intestinal failure.

BACKGROUND & AIMS: Acute mesenteric ischemia (AMI) is an emergency with a high mortality rate; survivors have high rates of intestinal failure. We performed a prospective study to assess a multidisciplinary and multimodal management approach, focused on intestinal viability. METHODS: In an Intestinal Stroke Center, we developed a multimodal management strategy involving gastroenterologists, vascular and abdominal surgeons, radiologists, and intensive care specialists; it was tested in a pilot study on 18 consecutive patients with occlusive AMI, admitted to a tertiary center from July 2009 to November 2011. Patients with left ischemic colitis, nonocclusive AMI, chronic mesenteric ischemia, and other emergencies were excluded. Patients received specific medical management: revascularization of viable small bowel and/or resection of nonviable small bowel; 12 patients received arterial revascularization. We evaluated the percentages of patients who survived for 30 days or 2 years, the number with permanent intestinal failure, and morbidity. Lengths and rates of intestinal resection were compared with or without revascularization, and in patients with early or late-stage disease. RESULTS: Patients were followed up for a mean of 497 days (range, 7-2085 d); 95% survived for 30 days, 89% survived for 2 years, and 28% had morbidities within 30 days. Intestinal resection was necessary for 7 cases (39%), with mean lengths of intestinal resection of 30 cm and 207 cm, with or without revascularization, respectively (P = .03). Among patients with early or late-stage AMI, rates of resection were 18% and 71%, respectively (P = .049). Patients with early stage disease had shorter lengths of intestinal resection than those with late-stage disease (7 vs 94 cm; P = .02), and spent less time in intensive care (2.5 vs 49.8; P = .02). CONCLUSIONS: A multidisciplinary and multimodal management approach might increase survival of patients with AMI and prevent intestinal failure.

Extended liver resection for polycystic liver disease can challenge liver transplantation.

OBJECTIVE: In an attempt to refine the indications for liver resection (LR) for highly symptomatic polycystic liver disease (PLD), we focused on the characteristics, technical difficulties, postoperative outcome, and long-term follow-up of PLD patients who underwent either LR or liver transplantation (LT). METHODS: Since 1995, among 72 patients with massive hepatomegaly, 45 patients underwent LR associated with contralateral cyst fenestration whereas 27 underwent LT associated with simultaneous kidney transplantations in 23. The LR group was characterized by absence of end-stage renal insufficiency, absence of ascites, and better nutrition status. In the LR group, the volumetry of the spared noncystic parenchyma was preoperatively assessed whereas pathological analysis focused on fibrosis and vascular congestion. RESULTS: After LR, the mortality was nil and overall morbidity was 71%, including biliary leak in 20% and ascites in 42%. Persistent and massive ascites was observed in 8 patients who have undergone extensive resection and had significantly more frequently fibrosis on the analysis of their resected surgical specimens (P = 0.002). A volume of the remnant noncystic parenchyma less than 30% and the presence of vascular changes on the specimen were associated with higher risk of complications. The 5-year survival was 95% and among the 43 survivors, after a mean follow-up of 41 months, 36 (83%) patients stated that they were satisfied, with complete relief of symptoms in 30 (70%). After LT, the postoperative mortality was 15% and the overall morbidity was 85%, including 12 patients who required reoperation. Severe complications were more frequent in the presence of denutrition and preoperative ascites. The 5-year survival was 85% and after a mean follow-up of 36 months all survivors had complete relief of symptoms due to hepatomegaly. CONCLUSIONS: In case of massive hepatomegaly from PLD without end-stage renal failure, LR should be considered first when preserved remnant liver volume represents at least 30% of the total volume liver in the absence of vascular changes or fibrosis.

Safety of liver resections in obese and overweight patients.

BACKGROUND: The new global epidemic, overweight and obesity, has a significant role in the etiology of liver tumors. However, the impact of body weight on the outcome after liver resection is unknown. METHODS: We carried out a prospective study of 684 patients who underwent liver resections. Patients were stratified according their body mass index (BMI) as follows: normal (<25 kg/m(2)) (52%), overweight (25-29 kg/m(2)) (34%), and obese (≥30 kg/m(2)) (14%), and according to the extent of resection, as either minor or major hepatectomy. Preoperative and intraoperative characteristics and outcomes were prospectively studied. The Dindo-Clavien classification of morbidity was used. RESULTS: Overall postoperative morbidity and morbidity rates were not influenced by BMI. Pulmonary complications were significantly more frequent in obese patients irrespective of the extent of resection. During major resection obese had longer pedicular clamping and more frequently required blood transfusion. After major resection, major morbidity (Dindo-Clavien grade III or more) was more frequent in obese (57%) and overweight (54%) patients than in patients of normal body weight (35%; P < 0.05), including a higher rate of respiratory complications and ascites and longer intensive care unit (ICU) and hospital stays. Obesity and overweight were independent predictors of major morbidity (OR 2.6, 95% CI 1.2-5.8 and OR 1.9, 95% CI 1.2-3.2, respectively), and obesity was a predictor of the need for blood transfusion (OR 3.3, 95% CI 1.4-7.9) after major resections. CONCLUSIONS: Obese and overweight patients are at increased risk of potentially life-threatening morbidity after major hepatic resections. Because the risk of mortality is not increased significantly, there is no justification for a compromise in the indication or extent of surgery.

Cytokeratin 19 fragments in patients with acute lung injury: a preliminary observation.

OBJECTIVE: Cytokeratin 19 (CK19) is a specific cytoskeletal structure for alveolar epithelium. We hypothesized that the levels of CK19 fragments in bronchoalveolar lavage (BAL) fluid could serve as an index of epithelial injury and as a prognosis marker in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). The aims of our study were, in patients with ALI/ARDS: (1) to measure CK19 fragments concentrations in BAL fluid, (2) to assess its prognostic value, and (3) to identify the cellular source of CK19 in the alveolar space. DESIGN: Prospective preliminary study. SETTING: University hospital surgical ICU. PATIENTS: Twenty-two mechanically ventilated patients with ALI/ARDS and 10 non-ventilated control patients. Plasma samples were obtained for 11 ALI/ARDS patients. MEASUREMENTS AND RESULTS: The concentration of BAL CK19 fragments was higher in patients (median 4916 pg/ml, 25th-75th percentile 2717-10533) than in controls (2208 pg/ml. 767-3923; p =0.05), and higher in 10 non-survivors (7051 pg/ml, 4372-13371) than in 12 survivors (2888 pg/ml, 1315-5639; p =0.03 among ALI/ARDS patients). BAL CK19 fragment concentration did not correlate with simplified acute physiologic score, lung injury score or PaO(2)/FIO(2) ratio, but correlated positively with BAL albumin concentration (p =0.002) and with number of BAL macrophages (p=0.0001). Plasma CK19 fragment concentrations were 10 times lower than those in BAL. Immunohistochemical staining for CK19 showed a strong labelling of injured detached epithelial cells and hyperplastic epithelium in ALI/ARDS lung samples. CONCLUSION: CK19 fragment concentrations were found to be elevated in BAL fluid in ALI/ARDS patients compared with control subjects. High BAL CK19 fragment levels were associated with a poor prognosis.

Parathyroid hormone-related protein in epithelial lining fluid in humans negatively correlates with the severity of lung injury.

OBJECTIVE: To determine the concentration of parathyroid hormone-related protein (PTHrP; an autocrine/paracrine regulator of type-2 alveolar epithelial cells proliferation and apoptosis) in the epithelial lining fluid (ELF) from patients without pulmonary disease and from patients with acute lung injury (ALI), and to evaluate whether PTHrP concentrations correlated with the intensity of lung injury. DESIGN: Prospective study. SETTING: An adult trauma/surgical ICU in an urban teaching hospital. PATIENTS: A total of 20 patients with ALI receiving mechanical ventilation (patients), and 10 patients without pulmonary disease not receiving mechanical ventilation (control subjects). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: PTHrP was detected in all BAL fluids, and ELF PTHrP concentrations (median; 25% to 75% percentiles) tended to be higher in patients (52.2 nmol/mL; 20.8 to 65.6 nmol/mL) than in control subjects (25.4 nmol/mL; 20.5 to 35.4 nmol/mL; p = 0.18). In patients, ELF PTHrP concentration correlated positively with the PaO(2)/fraction of inspired oxygen ratio (r = 0.53; p = 0.005), and negatively with lung injury score (r = - 0.44; p = 0.02), radiologic score (r = - 0.40; p = 0.04), and BAL albumin concentration (r = - 0.42; p = 0.02). CONCLUSION: PTHrP is present in biologically significant concentrations in the alveolar milieu in humans. In patients with ALI, the PTHrP concentration correlates negatively with the degree of lung injury.

Hepatocyte growth factor is produced by blood and alveolar neutrophils in acute respiratory failure.

We tested the novel hypothesis that neutrophils in the lung or the airspaces may produce hepatocyte growth factor (HGF) in ventilated patients with acute respiratory failure. Neutrophils were purified from blood and bronchoalveolar lavage (BAL) fluid samples from 16 mechanically ventilated patients who underwent BAL for a diagnostic workup of ventilator-acquired pneumonia. Most of the patients had pneumonia (n = 11). Ten nonventilated patients served as controls. Both blood and BAL neutrophils released HGF in vitro. Basal HGF secretion by blood neutrophils from controls was 823 (666) pg x ml(-1) x 10(-7) neutrophils (median, 25th-75th percentile) and doubled to 1,730 (1,684-2,316) pg x ml(-1) x 10(-7) neutrophils (P = 0.001) with lipopolysaccharide (LPS) stimulation. Basal HGF secretion by blood neutrophils from patients was similar [956 (655-2,140) pg x ml(-1) x 10(-7) neutrophils, P = 0.4] and doubled with LPS stimulation [2,767 (2,165-3,688) pg x ml(-1) x 10(-7) neutrophils, P < 0.0001 vs. controls]. Alveolar neutrophils released HGF in vitro [653 (397-1,209) pg x ml(-1) x 10(-7) neutrophils]. LPS stimulation did not significantly increase the HGF release from alveolar neutrophils [762 (434-1,305) pg x ml(-1) x 10(-7) neutrophils]. BAL HGF positively correlated with the BAL neutrophil count (P = 0.01, R = 0.58). We conclude that blood and alveolar neutrophils from patients with acute respiratory failure can produce HGF, a mitogenic factor that may enhance the alveolar repair process.