Reducing the carbon footprint of general anaesthesia: a comparison of total intravenous anaesthesia vs. a mixed anaesthetic strategy in 47,157 adult patients.

Global warming is a major public health concern. Volatile anaesthetics are greenhouse gases that increase the carbon footprint of healthcare. Modelling studies indicate that total intravenous anaesthesia is less carbon intensive than volatile anaesthesia, with equivalent quality of care. In this observational study, we aimed to apply the findings of previous modelling studies to compare the carbon footprint per general anaesthetic of an exclusive TIVA strategy vs. a mixed TIVA-volatile strategy. This comparative retrospective study was conducted over 2 years in two French hospitals, one using total intravenous anaesthesia only and one using a mixed strategy including both intravenous and inhalation anaesthetic techniques. Based on pharmacy procurement records, the quantity of anaesthetic sedative drugs was converted to carbon dioxide equivalents. The primary outcome was the difference in carbon footprint of hypnotic drugs per intervention between the two strategies. From 1 January 2021 to 31 December 2022, 25,137 patients received general anaesthesia in the hospital using the total intravenous anaesthesia strategy and 22,020 in the hospital using the mixed strategy. The carbon dioxide equivalent footprint of hypnotic drugs per intervention in the hospital using the total intravenous anaesthesia strategy was 20 times lower than in the hospital using the mixed strategy (emissions of 2.42 kg vs. 48.85 kg carbon dioxide equivalent per intervention, respectively). The total intravenous anaesthesia strategy significantly reduces the carbon footprint of hypnotic drugs in general anaesthesia in adult patients compared with a mixed strategy. Further research is warranted to assess the risk-benefit ratio of the widespread adoption of total intravenous anaesthesia.

Identification of novel pathogenic copy number variations in Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is a hereditary sensory-motor neuropathy characterized by a strong clinical and genetic heterogeneity. Over the past few years, with the occurrence of whole-exome sequencing (WES) or whole-genome sequencing (WGS), the molecular diagnosis rate has been improved by allowing the screening of more than 80 genes at one time. In CMT, except the recurrent PMP22 duplication accounting for about 60% of pathogenic variations, pathogenic copy number variations (CNVs) are rarely reported and only a few studies screening specifically CNVs have been performed. The aim of the present study was to screen for CNVs in the most prevalent genes associated with CMT in a cohort of 200 patients negative for the PMP22 duplication. CNVs were screened using the Exome Depth software on next generation sequencing (NGS) data obtained by targeted capture and sequencing of a panel of 81 CMT associated genes. Deleterious CNVs were identified in four patients (2%), in four genes: GDAP1, LRSAM1, GAN, and FGD4. All CNVs were confirmed by high-resolution oligonucleotide array Comparative Genomic Hybridization (aCGH) and/or quantitative PCR. By identifying four new CNVs in four different genes, we demonstrate that, although they are rare mutational events in CMT, CNVs might contribute significantly to mutational spectrum of Charcot-Marie-Tooth disease and should be searched in routine NGS diagnosis. This strategy increases the molecular diagnosis rate of patients with neuropathy.

[Duration of seclusion and exit of the seclusion room, study of the impact of anamnestic and institutional factors]. / Durée d'isolement et levée de la mesure ; étude de l'influence des facteurs anamnestiques et institutionnels.

INTRODUCTION: In France, the use of seclusion in psychiatric hospitals is regulated by the Act of January 26th 2016 which enforces a reduction of the use of coercive measures and limiting their duration. Criteria that are unrelated to the patient's symptoms might affect this decision and extend the duration of seclusion. The goal of the current observational study is, firstly, to determine which factors - unrelated to the patient's symptoms - influence the length of stay in seclusion. Secondly, it is to compare the composition of the medical and nursing teams at two times, the beginning and the end of the seclusion time period. METHOD: We conducted this study in a La Rochelle regional hospital from October 2017 to July 2018. There were one hundred and twenty-four episodes of seclusion that occurred in the different psychiatric inpatient wards during this time. The episodes were divided into two groups: short-term and long-term seclusion, defined by the median duration of seclusion. Data were collected using a survey, completed by the nursing teams, based on the recommendations of good clinical practice published in 1998 and revised in 2017 by the French health authority. For each episode of seclusion, we collected the following data: socio-demographic information, history of psychiatric care of the patient and of violent acting-out, admission status, medical indication for seclusion, day of the week and time at the beginning and the end of seclusion, prior administration of a sedative before seclusion, exceptional events that might justify the end of seclusion, transfer to a protected room after seclusion, as well as the composition of the medical and nursing team on duty at the beginning and the end of the seclusion period. We compared the anamnesis between the short-term and the long-term seclusion groups, and we analyzed the composition of the medical and nursing teams at the two time points of seclusion. Statistical analyses were performed using R software (v. 3.5.1). RESULTS: The mean duration of seclusion was 4.7 days and the median was 1.9 days. The average age was 37-years-old, with a ratio of 0.6 for females to males. Variables associated with a long-duration of seclusion were: the male gender (P=0.005), Compulsory Admission at the Request of a State Representative (P=0.008), a prevention measure of any hetero-aggressive action (P=0.007), the lack of psychiatric care (P=0.004), previous medico-legal issues (P=0.006), violent behavior during a previous hospitalization (P=0.022) and the use of seclusion on the weekend (P=0.01). The composition of the medical and nursing teams related to the period of the end of seclusion were: the presence of the physician in charge of the patient (P<0.001), a male caregiver in the team (P<0.001), a specialized psychiatric nurse (P<0.001) and the training of caregivers in the management of violence (P<0.001). The presence of nurses who do not usually work in the psychiatric ward was associated with the period of the beginning of seclusion (P<0.001). CONCLUSION: Our findings showed a strong relationship between several anamnestic factors and the duration of seclusion. Caregivers lacking information about patients, potential violent behaviors and the beginnings of seclusion on weekends are associated with a long-duration of seclusion. Our study also highlights the roles played by the caregivers according to their composition and level of training to determine the ending of patient's seclusion.

Antibiotics associated with acquisition of carbapenem-resistant Pseudomonas aeruginosa in ICUs: a multicentre nested case-case-control study.

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains are involved in severe infections, mostly in ICUs. Exposure to antibiotics other than carbapenems may be associated with isolation of CRPA; therefore, we aimed to identify those antibiotics using the case-case-control study design. Methods: A case-case-control study was conducted in 2015 in a prospective multicentre cohort that included 1808 adults hospitalized in 2009 in 10 French ICUs. Patients were screened for P. aeruginosa at admission to the ICU and then weekly. Cases were patients with CRPA and patients with carbapenem-susceptible P. aeruginosa (CSPA) isolation. Controls were patients without P. aeruginosa isolation, matched with each case according to centre, length of stay and hospitalization period. Effects of antibiotic exposure were explored, after adjusting for prior treatment with carbapenems and confounding factors comprising colonization pressure with two logistic regression models. The two models were compared to identify specific risk factors for CRPA isolation. Results: Fifty-nine CRPA, 83 CSPA and 142 controls were compared. In adjusted multivariable analyses, exposure to carbapenems and to antibiotics belonging to the group of ß-lactams inactive against P. aeruginosa were independent risk factors for CRPA isolation (OR, 1.205; 95% CI, 1.079-1.346 and OR, 1.101; 95% CI, 1.010-1.201, respectively). Conversely, exposure to ß-lactams active against P. aeruginosa was an independent protective factor for CSPA isolation (OR, 0.868; 95% CI, 0.772-0.976). Conclusions: Besides carbapenem exposure, exposure to ß-lactams inactive against P. aeruginosa was a specific risk factor for CRPA isolation. Clinicians should counterweigh the potential benefits of administering these antibiotics against the increased risk of CRPA infection.

Influence of social deprivation and remoteness on the likelihood of sphincter amputation for rectal cancer: a high-resolution population-based study.

BACKGROUND: Medical care in rectal cancer is subject to social inequality. According to the last French guidelines, a 1-cm distal margin below the lower pole of the rectal tumor is now considered sufficient. This extends the limits of the current sphincter preservation gold standard. Like for other innovative technics, the dissemination of such technics is often subject to social and geographical inequalities. The objective was to analyze whether sphincter preservation in rectal cancer is subject to social or geographical inequality. METHODS: The odds of sphincter preservation was modeled by logistic regression among the 1453 patients in the Calvados digestive cancer registry between 1 January 1997 and 31 December 2015 by examining some of the variables that could influence it: social inequalities and geographical remoteness, sex, age, and stage. RESULTS: A total of 69.4% of the population received sphincter preservation. Patients in the more deprived quintiles had a significantly higher probability of having sphincter amputation (odds ratio (OR) = 1.469 (1.046-2.064)). This result was no longer significant after adjustment on stage and travel time. There was a dose-effect pattern of geographical remoteness on likelihood of sphincter preservation with a progressive increase in OR between patients living the nearest and the furthest from the reference center (p-trend = 0.0178). CONCLUSION: This study shows that the probability of receiving sphincter preservation is influenced by the social environment and strongly influenced by remoteness. Although management guidelines have had a huge impact on the rates of sphincter preservation, they have not reduced the influence of the social and geographical environment on sphincter preservation.

Evaluation of Combination Drug Therapy for Treatment of Antibiotic-Resistant Inhalation Anthrax in a Murine Model.

Bacillus anthracis is considered a likely agent to be used as a bioweapon, and the use of a strain resistant to the first-line antimicrobial treatments is a concern. We determined treatment efficacies against a ciprofloxacin-resistant strain of B. anthracis (Cipr Ames) in a murine inhalational anthrax model. Ten groups of 46 BALB/c mice were exposed by inhalation to 7 to 35 times the 50% lethal dose (LD50) of B. anthracis Cipr Ames spores. Commencing at 36 h postexposure, groups were administered intraperitoneal doses of sterile water for injections (SWI) and ciprofloxacin alone (control groups), or ciprofloxacin combined with two antimicrobials, including meropenem-linezolid, meropenem-clindamycin, meropenem-rifampin, meropenem-doxycycline, penicillin-linezolid, penicillin-doxycycline, rifampin-linezolid, and rifampin-clindamycin, at appropriate dosing intervals (6 or 12 h) for the respective antibiotics. Ten mice per group were treated for 14 days and observed until day 28. The remaining animals were euthanized every 6 to 12 h, and blood, lungs, and spleens were collected for lethal factor (LF) and/or bacterial load determinations. All combination groups showed significant survival over the SWI and ciprofloxacin controls: meropenem-linezolid (P = 0.004), meropenem-clindamycin (P = 0.005), meropenem-rifampin (P = 0.012), meropenem-doxycycline (P = 0.032), penicillin-doxycycline (P = 0.012), penicillin-linezolid (P = 0.026), rifampin-linezolid (P = 0.001), and rifampin-clindamycin (P = 0.032). In controls, blood, lung, and spleen bacterial counts increased to terminal endpoints. In combination treatment groups, blood and spleen bacterial counts showed low/no colonies after 24-h treatments. The LF fell below the detection limits for all combination groups yet remained elevated in control groups. Combinations with linezolid had the greatest inhibitory effect on mean LF levels.

Propensity-based study of aminoglycoside nephrotoxicity in patients with severe sepsis or septic shock.

To assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ± 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk = 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI.

Magnetic resonance diffusion-weighted imaging: reproducibility of regional apparent diffusion coefficients for the normal fetal brain.

OBJECTIVE: To evaluate the reproducibility of regional apparent diffusion coefficient (ADC) measurements of the normal fetal brain in the second and third trimesters of pregnancy. METHODS: Fifty normal singleton fetuses from healthy pregnant women between 19 and 37 weeks' gestation were studied without sedation. Single-shot diffusion-weighted images of the fetal brain were obtained using a 1.5-Tesla magnetic resonance scanner and a six-channel body array coil. ADC maps were created using 0 and 1000 b-values along three orthogonal directions. Two examiners independently measured ADC values in the cerebellar hemispheres (CH), pons, thalamus, basal ganglia (BG), centrum semiovale (CSO), and frontal (FWM), parietal (PWM), temporal (TWM) and occipital (OWM) white matter. Correlation between ADC values and menstrual age was assessed by linear regression analysis. The bias and agreement of ADC measurements were determined using Bland-Altman plots. RESULTS: ADC values either remained constant (BG, FWM, PWM, TWM, OWM, CSO) or decreased (CH, pons, thalamus) with advancing menstrual age. Mean intraobserver bias for ADC measurements was not significantly different from zero. Small interobserver differences in mean ADC measurements (i.e. a small mean bias) were detected for CH (1.26 ± 0.20 vs 1.20 ± 0.18 µm(2) /ms, P = 0.006), PWM (1.37 ± 0.29 vs 1.33 ± 0.26 µm(2) /ms, P = 0.02) and CSO (1.36 ± 0.29 vs 1.33 ± 0.28 µm(2) /ms, P < 0.0001). Measurement agreement was acceptable. CONCLUSIONS: ADC measurements in normal unsedated fetuses in the second and third trimesters are reproducible except for small differences for PWM, CH and CSO between examiners.

Handcrafted firearm suicide: About the unusual use of a mole gun.

The body of a man was found in a workshop at the back of his home, a metal pipe embedded in his chest. In the immediate vicinity of the body, among various tools, was a machine containing a holster hit of lead shot evoking a mole-trap-type "taupe gun" (mole gun). The findings at the scene and the presence of a metal tube, sinkers, and a flock in the chest are in favour of the use of a homemade firearm. The autopsy and CT scan revealed atypical ballistic thoracic trauma responsible for a dilaceration of both the heart and thoracic aorta that caused the death. The autopsy also found a contused wound at the back of the skull without intracranial lesion, which may be due to the fall of the victim after the thoracic trauma. There is no other traumatic lesion and in particular no lesion of seizure, constraint, or defense. Toxicological analyses revealed the presence of alcoholic impregnation at the time of death. These findings, confronted with the expertise of a balistician, made it possible to understand how the victim used a mole gun to cause these lesions. A metal tube was used as a cannon to aim more surely at the heart but also as a means of triggering the propulsion mechanism of the trap without having to stretch out the arm. The tube, thinner than the barrel, had disengaged from its tip to be embedded with the lead shot in the chest of the victim.

Atmospheric Carbon and Transport - America (ACT-America) Data Sets: Description, Management, and Delivery.

The ACT-America project is a NASA Earth Venture Suborbital-2 mission designed to study the transport and fluxes of greenhouse gases. The open and freely available ACT-America data sets provide airborne in situ measurements of atmospheric carbon dioxide, methane, trace gases, aerosols, clouds, and meteorological properties, airborne remote sensing measurements of aerosol backscatter, atmospheric boundary layer height and columnar content of atmospheric carbon dioxide, tower-based measurements, and modeled atmospheric mole fractions and regional carbon fluxes of greenhouse gases over the Central and Eastern United States. We conducted 121 research flights during five campaigns in four seasons during 2016-2019 over three regions of the US (Mid-Atlantic, Midwest and South) using two NASA research aircraft (B-200 and C-130). We performed three flight patterns (fair weather, frontal crossings, and OCO-2 underflights) and collected more than 1,140 h of airborne measurements via level-leg flights in the atmospheric boundary layer, lower, and upper free troposphere and vertical profiles spanning these altitudes. We also merged various airborne in situ measurements onto a common standard sampling interval, which brings coherence to the data, creates geolocated data products, and makes it much easier for the users to perform holistic analysis of the ACT-America data products. Here, we report on detailed information of data sets collected, the workflow for data sets including storage and processing of the quality controlled and quality assured harmonized observations, and their archival and formatting for users. Finally, we provide some important information on the dissemination of data products including metadata and highlights of applications of ACT-America data sets.

[Evaluation with chest CT scan of CPAP as a treatment for tracheobronchomalacia in the frame of a Mounier-Kuhn syndrome]. / Évaluation par tomodensitométrie thoracique d'un traitement de la trachéobronchomalacie par pression positive continue dans le cadre d'un syndrome de Mounier­Kuhn.

INTRODUCTION: Tracheobronchomegaly disease is often associated with a tracheobronchomalacia which is responsible for recurrent lower respiratory tract infections. Currently there is no evidence to support any specific treatment for the condition. CASE REPORT: We report the case of a 79 years old patient presenting with tracheobronchomegaly in the context of Mounier-Kuhn syndrome complicated by a tracheobronchomalacia responsible for her symptomatology. The diagnosis of tracheobronchomalacia had been confirmed by high-resolution chest computed tomography (CT) with expiratory slices and virtual bronchoscopy. Treatment with continuous positive airway pressure (CPAP) was proposed, and we confirmed its efficacy using high-resolution chest CT, which showed a decrease in tracheobronchial collapse and a reduction in air trapping. CONCLUSIONS: Three-dimensional virtual bronchoscopy is an interesting tool and a noninvasive method to diagnose tracheobronchomegaly for patients who are at a high anesthetic risk. It is also possible to use it demonstrate the effect of CPAP in tracheobronchomalacia.

Measuring the electrophysiological effects of direct electrical stimulation after awake brain surgery.

OBJECTIVE: Direct electrical stimulation (DES) at 60 Hz is used to perform real-time functional mapping of the brain, and guide tumour resection during awake neurosurgery. Nonetheless, the electrophysiological effects of DES remain largely unknown, both locally and remotely. APPROACH: In this study, we lowered the DES frequency to 1-10 Hz and we used a differential recording mode of electro-corticographic (ECoG) signals to improve the focality with a simple algorithm to remove the artefacts due to the response of the acquisition chain. MAIN RESULTS: Doing so, we were able to observe different components in the evoked potentials triggered by simulating the cortex or the subcortical white matter pathways near the recording electrodes and by stimulating the cortex remotely from the recording site. More particularly, P0 and N1 components were repeatedly observed on raw ECoG signals without the need to average the data. SIGNIFICANCE: This new methodology is important to probe the electrophysiological states and the connectivity of the brain in vivo and in real time, namely to perform electrophysiological brain mapping on human patients operated in the neurosurgical room and to better understand the electrophysiological spreading of DES.

Exogenous acquisition of Pseudomonas aeruginosa in intensive care units: a prospective multi-centre study (DYNAPYO study).

BACKGROUND: Pseudomonas aeruginosa remains one of the most common nosocomial pathogens in intensive care units (ICUs). Although exogenous acquisition has been widely documented in outbreaks, its importance is unclear in non-epidemic situations. AIM: To elucidate the role of exogenous origin of P. aeruginosa in ICU patients. METHODS: A chronological analysis of the acquisition of P. aeruginosa was performed using samples collected in 2009 in the DYNAPYO cohort study, during which patients and tap water were screened weekly. Molecular relatedness of P. aeruginosa isolates was investigated by pulsed-field gel electrophoresis. Exogenous acquisition was defined as identification of a P. aeruginosa pulsotype previously isolated from another patient or tap water in the ICU. FINDINGS: The DYNAPYO cohort included 1808 patients (10,402 samples) and 233 water taps (4946 samples). Typing of 1515 isolates from 373 patients and 375 isolates from 81 tap water samples identified 296 pulsotypes. Analysis showed exogenous acquisition in 170 (45.6%) of 373 patients. The pulsotype identified had previously been isolated from another patient and from a tap water sample for 86 and 29 patients, respectively. The results differed according to the ICU. CONCLUSION: Exogenous acquisition of P. aeruginosa could be prevented in half of patients. The overall findings of this survey support the need for studies on routes of transmission and risk assessment approach to better define how to control exogenous acquisition in ICUs.

Requirement of type III TGF-beta receptor for endocardial cell transformation in the heart.

Transforming growth factor-beta (TGF-beta) signaling is mediated by a complex of type I (TBRI) and type II (TBRII) receptors. The type III receptor (TBRIII) lacks a recognizable signaling domain and has no clearly defined role in TGF-beta signaling. Cardiac endothelial cells that undergo epithelial-mesenchymal transformation express TBRIII, and here TBRIII-specific antisera were found to inhibit mesenchyme formation and migration in atrioventricular cushion explants. Misexpression of TBRIII in nontransforming ventricular endothelial cells conferred transformation in response to TGF-beta2. These results support a model where TBRIII localizes transformation in the heart and plays an essential, nonredundant role in TGF-beta signaling.

Quantitative mathematical modeling of clinical brain metastasis dynamics in non-small cell lung cancer.

Brain metastases (BMs) are associated with poor prognosis in non-small cell lung cancer (NSCLC), but are only visible when large enough. Therapeutic decisions such as whole brain radiation therapy would benefit from patient-specific predictions of radiologically undetectable BMs. Here, we propose a mathematical modeling approach and use it to analyze clinical data of BM from NSCLC. Primary tumor growth was best described by a gompertzian model for the pre-diagnosis history, followed by a tumor growth inhibition model during treatment. Growth parameters were estimated only from the size at diagnosis and histology, but predicted plausible individual estimates of the tumor age (2.1-5.3 years). Multiple metastatic models were further assessed from fitting either literature data of BM probability (n = 183 patients) or longitudinal measurements of visible BMs in two patients. Among the tested models, the one featuring dormancy was best able to describe the data. It predicted latency phases of 4.4-5.7 months and onset of BMs 14-19 months before diagnosis. This quantitative model paves the way for a computational tool of potential help during therapeutic management.

Contribution of tap water to patient colonisation with Pseudomonas aeruginosa in a medical intensive care unit.

This study examined tap water as a source of Pseudomonas aeruginosa in a medical intensive care setting. We prospectively screened specimens of patients, tap water and hands of healthcare workers (HCWs) over a six-month period in a 16-bed medical intensive care unit. Molecular relatedness of P. aeruginosa strains was investigated by pulsed-field gel electrophoresis. A total of 657 tap water samples were collected from 39 faucets and 127 hands of HCWs were sampled. P. aeruginosa was found in 11.4% of 484 tap water samples taken from patients' rooms and in 5.3% of 189 other tap water samples (P<0.01). P. aeruginosa was isolated from 38 patients. Typing of 73 non-replicate isolates (water samples, hands of HCWs and patients) revealed 32 major DNA patterns. Eleven (52.4%) of the 21 faucets were contaminated with a patient strain, found before isolation from tap water in the corresponding room in nine cases, or from the neighbouring room in two cases. Among seven P. aeruginosa strains isolated from HCW hands, the genotype obtained was the same as that from the last patient they had touched in six cases, and in the seventh with the last tap water sample used. More than half of P. aeruginosa carriage in patients was acquired via tap water or cross-transmission. Carriage of P. aeruginosa by patients was both the source and the consequence of tap water colonisation. These results emphasise the need for studies on how to control tap water contamination.

The 5th International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Neurotoxins. Workshop review: assays and detection.

The development of diagnostic tests for the botulinum neurotoxins is complicated by their extremely high potencies and the considerable diversity observed within the neurotoxin family. Current approaches for the detection of the toxins and the organism include amplified immunoassays and PCR techniques. Assays which exploit the biological activities within the botulinum toxins are also in development. These are based on both antibody and mass spectrometric techniques which measure the endopeptidase activities of the neurotoxins. This overview of the Assays and Detection Workshop of the 5th International Conference of on Basic and Therapeutic Aspects of Botulinum and Tetanus Neurotoxins discusses recent progress in the development of these assay systems and the issues that need to be overcome prior to their implementation.

Glucocorticoid treatment in patients with septic shock: effects on vasopressor use and mortality.

Corticosteroids were proposed for the treatment of sepsis as early as 1940. Several RCTs cast serious doubts on the usefulness of high dose corticosteroids and doubt still persists regarding the efficacy of replacement therapy. Adrenal insufficiency (non-responders to the 250 microg corticotropin test: increase in cortisol < 9 microg/dl) is present in about half of patients with septic shock and is associated with higher rates of refractory hypotension and mortality. Peripheral glucocorticoid resistance, which may even occur more frequently, can be easily assessed at bedside using skin tests. Cortisol antagonizes the migration of inflammatory cells, the synthesis or action of virtually all proinflammatory mediators, promotes virtually all anti-inflammatory components and enhances humoral immunity by means of transcriptional interference between its receptor and both AP-1 and NF-kappaB. Cortisol mediates cardiovascular tolerance to endotoxin and the maintenance of vascular sensitivity to catecholamines. Low doses (about 300 mg daily for 5 days or more) of hydrocortisone increase vasoconstrictor response to catecholamines in animals, in healthy volunteers challenged with LPS and in several RCTs. Hydrocortisone also increases arterial pressure and decreases the duration of shock. A meta-analysis of all available clinical controlled studies showed a reduction in 28 days, all-cause mortality with glucocorticoids (RR = 0.88, 95% CI: 0.78 - 1.00; p = 0.04). However, there was a significant heterogeneity across the trials (p = 0.006). On the other hand, analysis of studies where low doses of glucocorticoids were given for prolonged periods showed a 24% reduction in the risk of all-cause mortality at 28 days in treated patients (RR = 0.76, 95% CI: 0.64 - 0.90; p = 0.002) without heterogeneity across the trials (p = 0.28). In conclusion, in severe sepsis, high doses of corticosteroids should not be given. Septic shock should be treated with a replacement dose of hydrocortisone.

Radiation dose reduction in four-dimensional computed tomography.

Four-dimensional (4D) CT is useful in many clinical situations, where detailed abdominal and thoracic imaging is needed over the course of the respiratory cycle. However, it usually delivers a larger radiation dose than the standard three-dimensional (3D) CT, since multiple scans at each couch position are required in order to provide the temporal information. Our purpose in this work is to develop a method to perform 4D CT scans at relatively low current, hence reducing the radiation exposure of the patients. To deal with the increased statistical noise caused by the low current, we proposed a novel 4D penalized weighted least square (4D-PWLS) smoothing method, which can incorporate both spatial and phase information. The 4D images at different phases were registered to the same phase via a deformable model, thereby, a regularization term combining temporal and spatial neighbors can be designed for the 4D-PWLS objective function. The proposed method was tested with phantom experiments and a patient study, and superior noise suppression and resolution preservation were observed. A quantitative evaluation of the benefit of the proposed method to 4D radiotherapy and 4D PET/CT imaging are under investigation.

Molecular analysis of Desulfitobacterium frappieri pcp-1 involved in reductive dehalogenation of pentachlorophenol.

Desulfitobacterium are Gram positive, spore-forming, strictly anaerobic bacteria, that belong to the Firmicutes, Clostridia, Clostridiales, and Peptococcaceae. Most known members of the genus Desulfitobacterium have the ability to dechlorinate several halogenated compounds by a mechanism of reductive dehalogenation and use them as electron acceptors to generate energy (halorespiration). Desulfitobacteria are therefore perfect candidates to be used in bioremediation treatments of environment polluted with halogenated compounds. Understanding the physiology and the molecular mechanisms of these bacteria will help to develop better bioremediation systems. This report summarizes works that have been done in our laboratories with D. frappieri PCP-1 on reductive dehalogenases, genes encoding these dehalogenases and their expression, and the development of lab-scale PCP-degrading reactors using this bacterium.