Patients requiring pediatric palliative care for advanced heart disease in France: A descriptive study.

INTRODUCTION: Pediatric palliative care (PPC) teams address unmet needs and improve the quality of life of patients with life-limiting conditions across pediatric subspecialties. However, little is known about the timing, reasons, and nature of PPC team interventions in advanced heart diseases (AHD). OBJECTIVES: Here we describe how, when, and why PPC teams interact with referred teams of children suffering from AHD. METHODS: We conducted a retrospective nationwide survey among PPC teams in France. All patients referred to participating PPC teams for a cardiologic disease in 2019 were studied. RESULTS: Among six PPC teams, 18 patients with AHD had a PPC consultation in 2019. Six of these patients had cardiomyopathy and 12 had congenital heart disease (CHD). The median age at referral was 0.9 months for CHD and 72 months for cardiomyopathy. An antenatal diagnosis had been made for six families with CHD, and two of them were referred to PPC before birth allowing for a prenatal palliative care plan. The main reason for referral was ethical considerations (50%) followed by organization for home-based palliative care (28%). PPC teams participated in ethical discussions when asked to but also provided family support (12/18), home-based PPC (9/18), coordination of care (5/18), support of the referred team (4/18), and symptoms management (3/18) CONCLUSION: The main reason for referral to PPC was ethical considerations, but PPC interventions followed a holistic model of care. Prospective outcomes measurement and partnerships should be further developed.

Perioperative fluid management for major elective surgery.

BACKGROUND: Adequate fluid balance before, during and after surgery may reduce morbidity. This review examines current concepts surrounding fluid management in major elective surgery. METHOD: A narrative review was undertaken following a PubMed search for English language reports published before July 2019 using the terms 'surgery', 'fluids', 'fluid therapy', 'colloids', 'crystalloids', 'albumin', 'starch', 'saline', 'gelatin' and 'goal directed therapy'. Additional reports were identified by examining the reference lists of selected articles. RESULTS: Fluid therapy is a cornerstone of the haemodynamic management of patients undergoing major elective surgery. Both fluid overload and hypovolaemia are deleterious during the perioperative phase. Zero-balance fluid therapy should be aimed for. In high-risk patients, individualized haemodynamic management should be titrated through the use of goal-directed therapy. The optimal type of fluid to be administered during major surgery remains to be determined. CONCLUSION: Perioperative fluid management is a key challenge during major surgery. Individualized volume optimization by means of goal-directed therapy is warranted during high-risk surgery. In most patients, balanced crystalloids are the first choice of fluids to be used in the operating theatre. Additional research on the optimal type of fluid for use during major surgery is needed.

ANTECEDENTES: Un equilibrio de líquido adecuado antes, durante y después de la cirugía puede reducir la morbilidad. Esta revisión presenta los conceptos actuales del manejo de líquidos en cirugía mayor electiva. MÉTODOS: Se realizó una revisión descriptiva tras llevar a cabo una búsqueda en PubMed de artículos publicados en inglés antes de julio 2019, utilizando los términos 'cirugía ' (surgery), 'líquidos' (fluids), `fluidoterapia` (fluid therapy), 'coloides' (colloids), 'cristaloides' (crystalloids), 'albúmina' (albumin), 'hidroxietil-almidón' (starch), 'salino' (saline), 'gelatina' (gelatin) y 'terapia dirigida por objetivo' (goald directed therapy). Se identificaron artículos adicionales a través de la lista de referencias bibliográficas de los artículos seleccionados. RESULTADOS: El tratamiento con líquidos constituye la piedra angular del manejo hemodinámico de los pacientes sometidos a cirugía mayor electiva. Tanto la sobrecarga de líquidos como la hipovolemia son perjudiciales durante el periodo perioperatorio. El tratamiento de líquidos con balance cero debe considerarse el objetivo. En pacientes de alto riesgo, el manejo hemodinámico personalizado se debe ajustar mediante la utilización del tratamiento dirigido por objetivos. El tipo óptimo de líquido que debe ser administrado durante la cirugía mayor todavía no se ha determinado. CONCLUSIÓN: El manejo perioperatorio de líquidos es un desafío clave durante la cirugía mayor. La optimización del volumen individualizado a través de un tratamiento dirigido por objetivos está justificada durante la cirugía de alto riesgo. En la mayoría de los casos, la administración equilibrada de cristaloides es la primera fluidoterapia de elección en el quirófano. Se necesitan más investigaciones sobre el tipo de líquidos más adecuado para utilizar durante la cirugía mayor.

Pharmacodynamic modelling of intravenous antibiotic prophylaxis in elective colorectal surgery.

Surgical-site infections are the leading cause of post-operative morbidity and mortality as well as increased costs following colorectal surgery. The purpose of this study was to evaluate different ß-lactam antimicrobial dosing regimens currently used for prophylaxis in elective colorectal procedures with the aim of identifying optimal antibiotics and dosing regimens. Serum pharmacokinetic (PK) parameters specific to each drug for use in pharmacodynamic (PD) modelling were obtained from the published literature. Susceptibility data for Escherichia coli, Bacteroides fragilis and Staphylococcus aureus for use in modelling simulations were obtained from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Monte Carlo simulation was used to evaluate the influence of dose and dosing frequency of tested antibiotics to achieve a prophylaxis target fT>MIC (time during which the free drug concentration exceeds the pathogen minimum inhibitory concentration) of 100% for up to 4h. Ertapenem 1g, cefuroxime 1.5 g and cefazolin 2 g were the only antibiotic regimens that consistently yielded target fT>MIC of 100% for the entire 4-h post-dose interval and against all targeted organisms more than 90% of the time. In contrast, cefoxitin, cefotetan and ampicillin/sulbactam yielded very poor predicted PK/PD performances. In conclusion, this study demonstrates the value of, and need for, applied PD research in the area of surgical prophylaxis. Whether cefoxitin, cefotetan or ampicillin/sulbactam should continue to be advocated as first-line agents for prophylaxis during elective colorectal surgery, particularly at the standard doses currently being used, is debatable.

Procedure volume is one determinant of centre effect in mechanically ventilated patients.

Survival rates vary significantly between intensive care units, most notably in patients requiring mechanical ventilation (MV). The present study sought to estimate the effect of hospital MV volume on hospital mortality. We included 179,197 consecutive patients who received mechanical ventilation in 294 hospitals. Multivariate logistic regression models with random intercepts were used to estimate the effect of annual MV volume in each hospital, adjusting for differences in severity of illness and case mix. Median annual MV volume was 162 patients (interquartile range 99-282). Hospital mortality in MV patients was 31.4% overall, 40.8% in the lowest annual volume quartile and 28.2% in the highest quartile. After adjustment for severity of illness, age, diagnosis and organ failure, higher MV volume was associated with significantly lower hospital mortality among MV patients (OR 0.9985 per 10 additional patients, 95% CI 0.9978-0.9992; p = 0.0001). A significant centre effect on hospital mortality persisted after adjustment for volume effect (p < 0.0001). Our study demonstrated higher hospital MV volume to be independently associated with increased survival among MV patients. Significant differences in outcomes persisted between centres after adjustment for hospital MV volume, supporting a role for other significant determinants of the centre effect.

Effectiveness of nitrous oxide and analgesic cream (lidocaine and prilocaine) for prevention of pain during intramuscular botulinum toxin injections in children.

AIMS: To evaluate the effectiveness of an analgesic protocol with nitrous oxide and anaesthetic cream (lidocaine and prilocaine, EMLA) for children undergoing botulinum toxin injections. PATIENTS AND METHODS: Prospective study including 51 injection sessions, 34 children with a mean age of 5.94 (range 2-15) and 209 injected muscles. Pain was evaluated with the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), the Visual Analogue Scale (VAS) and the Face Pain Scale (FPS) for the children and with a VAS for the parents. RESULTS: CHEOPS score for the 51 sessions was 8.50 (S.D. 3.56). Forty-nine percent of scores were above the therapeutic threshold of 9; 25% of the children evaluated the pain above the therapeutic threshold of 3; 44.74% of the parents' estimations exceeded 3. No correlation was found between age, weight, number of injected muscle and CHEOPS score. CONCLUSION: The association of MEOPA and anaesthetic cream is only effective for 50% of children. This is much lower than treatments for other types of acute induced pain in children. Botulinum toxin injections and cerebral palsy children present certain specificities which require improvements in this analgesic protocol.

Hematopoietic progenitor cell mobilization and harvesting in children with malignancies: do the advantages of pegfilgrastim really translate into clinical benefit?

Our purpose was to assess success rates in children of achieving optimal hematopoietic progenitor cells (HPCs) harvest after mobilization with 300 microg/kg pegfilgrastim. Between January 2005 and January 2007, 26 children with solid malignancies who were referred for HPC collection were consecutively included. Hematopoietic progenitor cell mobilization consisted of one s.c. injection of 300 microg/kg body weight (BW) of pegfilgrastim. The success criterion was defined as at least 5 x 10(6) CD34+ cells/kg during the first standard apheresis (less than 3 blood volumes processed (BVP)). After 26 inclusions, the Bayesian analysis gave a mean estimated success rate of 60.7% (95% credibility interval: 42.0-78.0%). The first apheresis allowed the collection of 8.3 x 10(6) CD34+ cells/kg BW (range 0.6-37.8), with a median of 2.8 BVP (range 1.4-3.0). Overall, the median of CD34+ cells collected was 12.4 x 10(6)/kg (range 2.7-37.8). The cumulative dose of anthracyclin was the only variable associated with the total number of CD34+ collected cells (P<0.05). Mobilization was clinically well tolerated in 20 patients. No drug-related adverse events of grade > or =3 occurred. We conclude that a single injection of 300 microg/kg pegfilgrastim in the hematological steady state is an efficient and well-tolerated method of HPC mobilization in children with solid malignancies.

[Potential benefits of non-anti-infective treatments of septic shock: a critical analysis of literature]. / Bénéfices potentiels des traitements non anti-infectieux du choc septique: analyse critique de la littérature.

Among numerous non anti-infective treatments proposed in the management of severe sepsis and septic shock, early administration of steroids and recombinant human activated protein C are the most studied and the major source of debate. Patients with functional adrenal insufficiency appear to be the best cases for early treatment with low doses of hydrocortisone. However, definition of adrenal dysfunction, interpretation of cortisol blood concentration and its appropriateness, investigation of the hypothamalo-pituitary-adrenal axis and value of corticotropin stimulation test are matter of discussion. Similarly, recombinant human activated protein C might be beneficial in patients with severe sepsis and septic shock but the results of clinical trials are controversial. Structure of the PROWESS pivotal study, post hoc analyses of numerous subgroups, use of severity scoring system for selection of the patients, unproven mechanisms of action of activated Protein C, interactions with combined treatments represent major sources of confusion and of debate in the analysis of the trials. Non anti-infective treatments should be considered in selected patients when appropriate conventional treatments have been implemented. Use of these new treatments should bring additional improvement in the prognosis in severely ill patients at high risk of death.

[ICU performance: results of a French study involving 80,000 ICU stays]. / Performance en réanimation: résultats du PHRC Sfar-SRLF.

OBJECTIVE: The Standard Mortality Ratio (SMR), comparing the observed in-hospital mortality to the predicted, may measure the intensive care units (ICU) performance. STUDY DESIGN: Multicentric retrospective national study. METHODS: A probability model using a severity score such SAPS II calculated the predicted mortality rate. A national French study has been undertaken to compare the SMR of ICUs and looked for explanation. RESULTS: One hundred six units, 34 were medical (32%), 18 surgical (17%) and 57 medical/surgical (51%) participated to the study. Forty-six ICUs (43%) were located in teaching hospitals. The SMR of the 87,099 stays was 0.84 (0.82-0.85). The SMR of ICUs varied from 0.41 to 1.55. Ten units had a SMR>0.85, which suggested a low performance. They had more stays for cardiovascular failures, as compared with others. The best units (SMR<0.82) had more stays for drug overdose. The SMR increased with the number of organ failures, from 0.47 with zero failure to 1.11 with 4 or more organ failures. The stays with cardiovascular failure, either unique or associated, had a higher SMR. The 7935 stays with a drug overdose had a SMR of 0.12 (0.10-0.14), which suggested a bad calibration of the model in theses cases. CONCLUSION: The case mix must be taken in account when comparing the ICUs performance by the mean of SMR, particularly when the units admitted a lot of drug overdoses.

[Differential modulation of TLR2 and TLR4-induced TNF production by murin haemorrhagic shock]. / Modulation différentielle des effets de la stimulation des récepteurs Toll-like 2 et 4 par l'état de choc hémorragique.

OBJECTIVE: To investigate the influence of haemorrhagic shock in mice on ex vivo TNF production by whole blood cells (WBC) stimulated through Toll-like receptors (TLR) 4 and 2. STUDY DESIGN AND ANIMALS: Experimental study using BALB/c male mice. METHODS: Haemorrhage (0,026+/-0,003 ml/g) by transparietal cardiac puncture under general anaesthesia. Measurement of left intraventricular pressure through a direct subcostal cardiac puncture. Possible restitution of shed blood volume (SBV) in retroorbital venous plexus, 60 minutes following haemorrhage. Lethal exsanguination 120 minutes following general anaesthesia (Control group), cardiac puncture (Sham group), blood sample (Haemorrhage group), or 60 minutes following SBV retransfusion (SBV group). Cultures (24 hours) of whole blood from the exsanguination, alone or with Escherichia coli endotoxin (LPS, TLR 4) or with heat-killed Staphylococcus aureus Cowan (SAC, TLR 2). Assessment of TNF levels in the cultures supernatant (Elisa). RESULTS: Hemorrhage (approximately 30% of calculated blood volume) resulted in arterial hypotension (-50%) which was reversed by SBV retransfusion. TNF production by LPS-stimulated WBC was reduced by haemorrhage (approximately -50%) with or without SBV retransfusion. TNF production by SAC-stimulated WBC remained unchanged. CONCLUSION: The reduction of proinflammatory cytokines production by WBC stimulated with pathogen-associated molecular patterns is not a generalized phenomenon following murin haemorrhagic shock. It depends on the used stimulus and studied signalling pathways.

Activity of gemifloxacin against quinolone-resistant Streptococcus pneumoniae strains in vitro and in a mouse pneumonia model.

Gemifloxacin is a novel fluoronaphthyridone quinolone with enhanced in vitro activity against Streptococcus pneumoniae. We investigated the activities of gemifloxacin and trovafloxacin, their abilities to select for resistance in vitro and in vivo, and their efficacies in a mouse model of acute pneumonia. Immunocompetent Swiss mice were infected with 10(5) CFU of a virulent, encapsulated S. pneumoniae strain, P-4241, or its isogenic parC, gyrA, parC gyrA, and efflux mutant derivatives (serotype 3); and leukopenic mice were infected with 10(7) CFU of two poorly virulent clinical strains (serotype 11A) carrying either a parE mutation or a parC, gyrA, and parE triple mutation. The drugs were administered six times every 12 h, starting at either 3 or 18 h postinfection. In vitro, gemifloxacin was the most potent agent against strains with and without acquired resistance to fluoroquinolones. While control mice died within 6 days, gemifloxacin at doses of 25 and 50 mg/kg of body weight was highly effective (survival rates, 90 to 100%) against the wild-type strain and against mutants harboring a single mutation, corresponding to area under the time-versus-serum concentration curve at 24 h (AUC(24))/MIC ratios of 56.5 to 113, and provided a 40% survival rate against a mutant with a double mutation (parC and gyrA). A total AUC(24)/MIC ratio of 28.5 was associated with poor efficacy and the emergence of resistant mutants. Trovafloxacin was as effective as gemifloxacin against mutants with single mutations but did not provide any protection against the mutant with double mutations, despite treatment with a high dose of 200 mg/kg. Gemifloxacin preferentially selected for parC mutants both in vitro and in vivo.

[Completeness of ICU activity reports sent to French healthcare authorities]. / Exhaustivité des résumés d'unité médicale adressés aux départements d'information médicale.

INTRODUCTION: Hospital units report on their inpatient care activity by writing yearly activity reports, which are used by their Medical Information Department (MID) to develop standardized summaries for communication to healthcare authorities. The data are categorized by uniform patient groups and used to describe inpatient care activity and to guide resource allocation. The objective of this study was to evaluate the completeness of activity reports from intensive care units (ICUs) in France. METHODS: Activity reports sent in 1998 and 1999 by French ICUs participating in the study were collected using dedicated abstracting software supplied to the relevant MIDs. Completeness of data in the activity reports was evaluated, with special attention to the SAPSII score, Omega rating of ICU procedures according to the Classification of Medical Procedures, and primary and secondary diagnoses. RESULTS: The 106 ICUs that volunteered for the study reported data on 107,652-hospital stays. Mean age and SAPSII were 55 +/- 21 years and 35 +/- 21 years, respectively. Mean ICU and hospital lengths of stay were 6.2 +/- 12.4 and 16.1 +/- 21.6 days, respectively. Mean ICU and hospital mortality rates were 15% and 19%. The SAPSII and Omega procedures were reported for 81% and 80% of stays, respectively. The SAPSII and Omega procedures were calculated or coded in 94% (100/106) and 96% (102/106) of ICUs, respectively. Mean number of Omega procedures was 4.3+/-3.9. However, only 5% (5/106) of ICUs entered the SAPSII for every stay, and 21% (22/106) of ICUs failed to enter the SAPSII for over 20% of stays. Similarly, 53% (56/106) of ICUs rated no more than five Omega procedures on average per stay. The primary diagnosis was reported for all stays, and the mean number of secondary diagnoses was 3.5 +/- 3.8. In 80% (86/106) of ICUs, no more than five secondary diagnoses were coded on average per stay. CONCLUSION: The analysis of this national database shows that data communicated to the MIDs and therefore to the healthcare authorities, are incomplete regarding SAPSII, ICU procedures, treatment intensity, and diagnoses. This may lead to the underestimation of ICU activity and resource needs, particularly if the SAPSII and selected procedures identified as markers for high-intensity critical care are used in the future.

Activities of garenoxacin against quinolone-resistant Streptococcus pneumoniae strains in vitro and in a mouse pneumonia model.

Garenoxacin is a novel des-F(6) quinolone with enhanced in vitro activities against both gram-positive and gram-negative bacteria. We compared the activity of garenoxacin with that of trovafloxacin (TVA) against Streptococcus pneumoniae, together with their efficacies and their capacities to select for resistant mutants, in a mouse model of acute pneumonia. In vitro, garenoxacin was more potent than TVA against wild-type S. pneumoniae and against a mutant with a single mutation (parC), a mutant with double mutations (gyrA and parC), and a mutant with triple mutations (gyrA, parC, and parE). Swiss mice were infected with 10(5) CFU of virulent, encapsulated S. pneumoniae strain P-4241 or its derived isogenic parC, gyrA, gyrA parC, and efflux mutants and 10(7) CFU of poorly virulent clinical strains carrying a parE mutation or gyrA, parC, and parE mutations. The drugs were administered six times, every 12 h, beginning at either 3 or 18 h postinfection. The pulmonary pharmacokinetic parameters in mice infected with strain P-4241 and treated with garenoxacin or TVA (25 mg/kg of body weight) were as follows: maximum concentration of drug in serum (C(max); 17.3 and 21.2 micro g/ml, respectively), C(max)/MIC ratio (288 and 170, respectively), area under the concentration-time curve (AUC; 48.5 and 250 microg. h/ml, respectively), and AUC/MIC ratio (808 and 2000, respectively). Garenoxacin at 25 and 50 mg/kg was highly effective (survival rates, 85 to 100%) against the wild-type strain and mutants harboring a single mutation. TVA was as effective as garenoxacin against these strains. TVA at 200 mg/kg and garenoxacin at 50 mg/kg were ineffective against the mutant with the parC and gyrA double mutations and the mutant with the gyrA, parC, and parE triple mutations. The efficacy of garenoxacin was reduced only when strains bore several mutations for quinolone resistance.

[Off-label prescriptions in an adult surgical intensive care unit]. / Prescription hors autorisation de mise sur le marché en réanimation chirurgicale adulte.

OBJECTIVE: The aim of the study was to document off label prescribing in an adult surgical intensive care unit setting and to determine explanatory factors. METHOD: Medical prescriptions of 20 adult patients consecutively admitted in surgical intensive care unit were recorded, from the time of admission to the second day of hospitalisation. Concordance of each prescription to the different sections listed on the approved labeling was checked on the Vidal 1999 dictionary. French guidelines promoted by the two major intensive care societies were looked for to explain the most frequent reason of unapproved use of the 10 main therapeutic classes concerned by off label prescription. RESULTS: In this study, 465 prescriptions were analysed, representing 80 drugs and 35 therapeutic classes. Prescriptions were considered off label in 25.6%. Antibiotics, stress ulcer prophylactic drugs, vitamins, antiepileptic drugs were the main therapeutic classes used off label. The main cause of off label prescription was unapproved indication (66%), dosing schedule (27%) and method of administration (17%). For 5 therapeutic classes, representing 45% of off label prescriptions, a guideline supporting these prescriptions was available or was published in the year following the study. CONCLUSION: Off label prescription is frequent in the setting of adult surgical intensive care unit. Seldom medical situations and the gap between official labeling and medical knowledge are explanatory factors of these off label prescriptions.

Accuracy of a composite score using daily SAPS II and LOD scores for predicting hospital mortality in ICU patients hospitalized for more than 72 h.

UNLABELLED: In most databases used to build general severity scores the median duration of intensive care unit (ICU) stay is less than 3 days. Consequently, these scores are not the most appropriate tools for measuring prognosis in studies dealing with ICU patients hospitalized for more than 72 h. PURPOSE: To develop a new prognostic model based on a general severity score (SAPS II), an organ dysfunction score (LOD) and evolution of both scores during the first 3 days of ICU stay. DESIGN: Prospective multicenter study. SETTING: Twenty-eight intensive care units (ICUs) in France. PATIENTS: A training data-set was created with four ICUs during an 18-month period (893 patients). Seventy percent of the patients were medical (628) aged 66 years. The median SAPS II was 38. The ICU and hospital mortality rates were 22.7% and 30%, respectively. Forty-seven percent (420 patients) were transferred from hospital wards. In this population, the calibration (Hosmer-Lemeshow chi-square: 37.4, P = 0.001) and the discrimination [area under the ROC curves: 0.744 (95 % CI: 0.714-0.773)] of the original SAPS II were relatively poor. A validation data set was created with a random panel of 24 French ICUs during March 1999 (312 patients). MEASUREMENTS AND MAIN RESULTS: The LOD and SAPS II scores were calculated during the first (SAPS1, LOD1), second (SAPS2, LOD2), and third (SAPS3, LOD3) calendar days. The LOD and SAPS scores alterations were assigned the value "1" when scores increased with time and "0" otherwise. A multivariable logistic regression model was used to select variables measured during the first three calendar days, and independently associated with death. Selected variables were: SAPS II at admission [OR: 1.04 (95 % CI: 1.027-1.053) per point], LOD [OR: 1.16 (95 % CI: 1.085-1.253) per point], transfer from ward [OR: 1.74 (95 % CI: 1.25-2.42)], as well as SAPS3-SAPS2 alterations [OR: 1.516 (95 % CI: 1.04-2.22)], and LOD3-LOD2 alterations [OR: 2.00 (95 % CI: 1.29-3.11)]. The final model has good calibration and discrimination properties in the training data set [area under the ROC curve: 0.794 (95 % CI: 0.766-0.820), Hosmer-Lemeshow C statistic: 5.56, P = 0.7]. In the validation data set, the model maintained good accuracy [area under the ROC curve: 0.826 (95 % CI: 0.780-0.867), Hosmer-Lemeshow C statistic: 7.14, P = 0.5]. CONCLUSIONS: The new model using SAPS II and LOD and their evolution during the first calendar days has good discrimination and calibration properties. We propose its use for benchmarking and evaluating the over-risk of death associated with ICU-acquired nosocomial infections.

Long-term-impaired expression of nuclear factor-kappa B and I kappa B alpha in peripheral blood mononuclear cells of trauma patients.

Nuclear factor (NF)-kappa B expression and dimer characteristics were studied in peripheral blood mononuclear cells (PBMCs) of major-trauma patients and healthy controls. Analysis of PBMCs on days 1, 3, 5, and 10 after trauma revealed that expression of both p65p50 heterodimers and p50p50 homodimers was significantly reduced compared with that in controls. In vitro lipopolysaccharide (LPS) stimulation of PBMCs induced NF-kappa B translocation. However, throughout the survey, p65p50 activation remained significantly lower in trauma patients than in controls. After LPS stimulation in vitro, the p65p50/p50p50 ratio was significantly lower in PBMCs from trauma patients than from healthy controls. The ex vivo expression of I kappa B alpha was higher in PBMCs of controls than of trauma patients. LPS did not induce I kappa B expression in PBMCs from trauma patients, but strong induction was obtained with staphylococci, suggesting that this defect is not universal and depends on the nature of the activating signal. Although no direct correlation was found between levels of interleukin-10 or transforming growth factor-beta and NF-kappa B, these immunosuppressive cytokines were significantly elevated in trauma patients by 10 days after admission. The long-term low-basal and LPS-induced nuclear translocation of NF-kappa B recalled long-term immunoparalysis observed in patients with severe inflammatory stress such as trauma.

[Nosocomial pneumopathy acquired under mechanical ventilation. Suspicion criteria, bacteriologic diagnosis, and remission criteria]. / Pneumopathie nosocomiale acquise sous ventilation mécanique. Critères de suspicion, diagnostic bactériologique et critères de guérison.

In intensive care patients, pneumonia acquired under ventilatory assistance is the second most frequent nosocomial infection after urinary tract infection. Duration of ventilatory assistance and stay in the intensive care unit are both increased in this leading cause of death due to nosocomial infection. A large number of studies and national and international consensus conferences have been devoted to determining precise criteria leading to clinical suspicion of pneumonia acquired under ventilatory assistance and the appropriate elements for bacteriological diagnosis. The criteria retained in these different studies are neither precise nor reproductable. Based on data in the literature and our their clinical experience the members of the Outcomerea association constituted working groups to elaborate a set of guidelines that could be applied in routine clinic in response to three questions: 1) what criteria are suggestive of pneumonia acquired under ventilatory assistance, 2) what bacteriological tools are needed to confirm diagnosis, 3) how and why should cure be defined. We present a review of the literature and the conclusions of the working groups.

NF-kappaB expression in mononuclear cells of patients with sepsis resembles that observed in lipopolysaccharide tolerance.

The expression of NF-kappaB was studied in freshly isolated peripheral blood mononuclear cells (PBMC) of patients with severe sepsis and major trauma. The expression of p65p50 heterodimer, the active form of NF-kappaB, was significantly reduced for all patients as compared with control subjects. The p50p50 homodimer, an inhibitory form of NF-kappaB, was reduced in the survivors of sepsis and in patients with trauma. Subsequent in vitro stimulation of PBMC with lipopolysaccharide (LPS) did not induce further NF-kappaB nuclear translocation: the survivors of sepsis and trauma patients showed low expression of both p65p50 and p50p50, whereas nonsurvivors of sepsis showed a predominance of the inactive homodimer and a low p65p50/p50p50 ratio when compared with control subjects. In the later group of patients there was a reverse correlation between plasma IL-10 levels and the p65p50/p50p50 ratio after in vitro LPS stimulation (r = -0.8, p = 0.04). The reduced expression of nuclear NF-kappaB was not due to its inhibition by IkappaBalpha, as very low expression of IkappaBalpha, as well as low levels of p65 and p50 were found in the cytoplasm of PBMC from patients with sepsis and trauma when compared with control subjects. These results demonstrate that upon LPS activation, PBMC of patients with systemic inflammatory response syndrome show patterns of NF-kappaB expression that resemble those reported during LPS tolerance: global down-regulation of NF-kappaB in survivors of sepsis and trauma patients and the presence of large amounts of the inactive homodimer in the nonsurvivors of sepsis.

Nuclear factor-kappaB activation in mouse lung lavage cells in response to Streptococcus pneumoniae pulmonary infection.

OBJECTIVES: To assess the state and activation kinetics of the nuclear transcription regulatory protein nuclear factor-kappB (NF-kappaB) in lung lavage cells in a murine pneumococcal pneumonia model and to determine how the virulence of the infecting organisms altered the activation state of NF-kappaB. DESIGN: Experimental, comparative study of three Streptococcus pneumoniae strains that induced three distinct pulmonary diseases. SETTING: Experimental laboratory in a university-based medical center. SUBJECTS: Female BALB/cby mice, 8-10 wks of age. INTERVENTIONS: We randomly divided the mice into the following five groups: a) the control group; b) animals infected by virulent encapsulated S. pneumoniae P4241 strain; c) animals infected by avirulent encapsulated S. pneumoniae P15986 strain; d) animals infected by avirulent unencapsulated S. pneumoniae R6 strain; e) animals infected by virulent lysed S. pneumoniae P4241 strain. Animals were anesthetized and infected by intratracheal delivery of 4 x 10(5) colony-forming units (CFU) of S. pneumoniae per mouse or bacterial components equivalent to 4 x 10(5) CFU for lysed S. pneumoniae challenge. After intratracheal challenge with virulent encapsulated strain P4241, mice developed acute pneumonia, became bacteremic, and died within 3 to 5 days. None of the mice infected with the avirulent encapsulated strain P15986 or the avirulent unencapsulated strain R6 died. After collection of lung lavage cells and nuclear extraction, NF-kappaB activation was determined 1 hr, 4 hrs, 6 hrs and 24 hrs after pneumococcal infection. At the same time, pulmonary and blood clearance, bronchoalveolar lavage cells population, and tumor necrosis factor-alpha production were assessed (six mice per time point). MEASUREMENTS AND MAIN RESULTS: NF-kappaB was constitutively expressed within nuclear extracts of lung lavage cells from uninfected control mice. A significant increase in NF-kappaB activation was detected within 1 hr after injection of virulent lysed S. pneumoniae P4241 strain (bacterial components equivalent to 4 x 10(5) CFU), and was still present 24 hrs after the injection. After live pneumococcal challenge, significant NF-kappaB activation was detected within 4 hrs with a peak at 24 hrs. Responses to all three strains (P4241, P15986 and R6) were time-dependent (p < .0001), as NF-kappaB activation gradually increased during the first 24 hrs. Moreover, compared with the control uninfected mice, the intensity of the retarded KB oligonucleotide, as determined by densitometry, was increased approximately four- to five-fold and seven-fold in reactions containing nuclear extracts isolated 24 hrs after infection with the avirulent strains P15986 or R6 and the virulent strain P4241, respectively. With the virulent strain P4241, responses were significantly stronger than with the avirulent strains P15986 and R6 (p < .01). Responses were of similar order with avirulent strains P15986 and R6 (p > .05). CONCLUSION: Pulmonary infection by S. pneumoniae induced delayed and time-dependent activation of NF-kappaB in mouse lung lavage cells. The degree of NF-kappaB activation in lung lavage cells correlated with the virulence of the infecting organisms. Our results suggest that the more severe the infection, the higher the rise in NF-kappaB.

Proximal fractures of the fifth metacarpal: a retrospective analysis of 25 operated cases.

The clinical and radiological outcomes of 25 surgically treated fractures of the proximal third of the fifth metacarpal were retrospectively analysed. Many different methods of osteosynthesis were used. At follow-up after a mean of 3.3 years, 15 of 25 patients had no pain. Most patients regained a nearly full range of motion in the adjacent joints and more than 90% of the contralateral grip strength. X-ray signs of degenerative arthritis in the metacarpohamate joint were observed in 10 of 25 patients. Pain was found to be directly correlated with the presence of degenerative changes.