Cardiac troponin I as an early prognosis biomarker after trauma: a retrospective cohort study.

BACKGROUND: The significance of cardiac troponin I (cTnI) elevation after trauma is debated. We therefore explored the association between cTnI elevation at admission after trauma and ICU mortality. METHODS: We performed a retrospective analysis from a prospectively constituted database, of patients admitted to ICU after trauma at a single centre, over a 36 month period. According to cTnI plasma concentration at admission, patients were categorised into three groups: normal (<0.05 ng ml-1), intermediate (0.05-0.99 ng ml-1), or high concentration (≥1.0 ng ml-1). Associations of pre-hospital conditions or cTnI elevation and mortality were analysed by multivariate logistic regression. RESULTS: Among the 994 patients, 177 (18%) had cTnI elevation at ICU admission. Of this total, 114 (11%) patients died in the ICU. The cTnI release was an independent predictor of ICU mortality with a concentration-response relationship [odds ratio (OR) 4.90 (2.19-11.16) and 14.83 (4.68-49.90) for intermediate and high concentrations, respectively] and Day 2 mortality [OR 2.23 (1.18-5.80) and 7.49 (2.77-20.12) for intermediate and high concentrations, respectively]. The severity of thoracic trauma [OR 2.25 (1.07-4.55) and 3.23 (2.00-5.27) for Abbreviated Injury Scale scores 1-2 and ≥3, respectively], out-of-hospital maximal heart rate ≥120 beats min-1 [OR 2.22 (1.32-3.69)], and out-of-hospital shock [OR 2.02 (1.20-3.38)] were independently associated with cTnI elevation. CONCLUSIONS: Release of cTnI was an independent predictor of ICU mortality, suggesting that this biomarker can be used in daily practice for early stratification of the risk of ICU death. Thoracic trauma was strongly associated with cTnI elevation.

Score for pulmonary tuberculosis in patients with clinical presumption of tuberculosis in a low-prevalence area.

OBJECTIVES: To develop a diagnostic predictive model for the identification of patients with presumptive pulmonary tuberculosis (PTB) at high risk for active disease and those requiring nucleic acid amplification (NAAT) testing and/or preventive respiratory isolation in low-incidence, high-income countries. DESIGN: A 1:1 case-control study was conducted in consecutive immunocompetent patients with presumed PTB hospitalised between 2009 and 2012 in Paris, France. Cases were defined as individuals with culture-confirmed PTB, regardless of smear result. Those with presumed PTB and three smear- and culture-negative samples were selected as controls. A score was derived using conditional logistic regression. Internal validity of the score was assessed using the bootstrap method. RESULTS: A total of 354 patients were included in the analysis (177 cases, 177 controls). Among the 177 cases, 74 (42%) were smear-negative but culture-positive. Factors independently associated with PTB were age <50 years (adjusted OR [aOR] 4.7, 95%CI 1.8-12), diabetes (aOR 3.2, 95%CI 1.1-9.8), absence of cough with or without sputum (aOR 3.7, 95%CI 1.7-8.3), fever >15 days (aOR 3.5, 95%CI 1.3-9.5), apical infiltration without cavity (aOR 3.4, 95%CI 1.4-8.5) and cavitation or miliary pattern (aOR 19.7, 95%CI 7.6-51.1). Score C-index was 0.84 (95%CI 0.79-0.88). Calibration for the overall population (P = 0.770) and in smear-negative patients (P = 0.980) was appropriate. A score of 3.3 had 90% sensitivity, 50% specificity and 79% (IQR 28-95) median probability of PTB. CONCLUSIONS: This score could be used to build an algorithm to determine the need for respiratory isolation and/or NAAT use in PTB disease.

Effect of appendicectomy on colonic inflammation and neoplasia in experimental ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) promotes cancer, and can be ameliorated by early appendicectomy for appendicitis. The aim of the study was to explore the effect of appendicectomy on colitis and colonic neoplasia in an animal model of colitis and a cohort of patients with UC. METHODS: Five-week old IL10/Nox1(DKO) mice with nascent colitis and 8-week-old IL10/Nox1(DKO) mice with established colitis underwent appendicectomy (for experimental appendicitis or no appendicitis) or sham laparotomy. The severity and extent of colitis was assessed by histopathological examination, and a clinical disease activity score was given. From a cohort of consecutive patients with UC who underwent colectomy, the prevalence of appendicectomy and pathological findings were collected from two institutional databases. RESULTS: Appendicectomy for appendicitis ameliorated experimental colitis in the mice; the effect was more pronounced in the 5-week-old animals. Appendicectomy in the no-appendicitis group was associated with an increased rate of colonic high-grade dysplasia (HGD) or cancer compared with rates in sham and appendicitis groups (13 of 20 versus 0 of 20 and 0 of 20 respectively; P < 0·001). Fifteen of 232 patients who underwent colectomy for UC had previously had an appendicectomy, and nine of these had colonic cancer or HGD. Thirty (13·8 per cent) of 217 patients with the appendix in situ had colonic neoplastic lesions. Multivariable analysis showed that previous appendicectomy was associated with colorectal neoplasia (odds ratio 16·88, 95 per cent c.i. 3·32 to 112·69). CONCLUSION: Appendicectomy for experimental appendicitis ameliorated colitis. The risk of colorectal neoplasia appeared to increase following appendicectomy without induced appendicitis in a mouse model of colitis, and in patients with UC who had undergone appendicectomy. Surgical relevance Appendicectomy for appendicitis protects against UC. In this murine model of colitis, appendicectomy for experimental appendicitis protected against colitis, but appendicectomy without appendicitis promoted colorectal carcinogenesis. In patients with ulcerative colitis who underwent colectomy, absence of the appendix (proof of previous appendicectomy) in the resection specimen was independently associated with colorectal neoplasia. Although patients with UC and a history of appendicectomy represent a small subset, they may need closer monitoring for colorectal neoplasia.

Lack of clinical or haemodynamic rebound after abrupt interruption of beta-blockers in patients with cirrhosis.

BACKGROUND: Beta-blockers may have to be interrupted in patients with cirrhosis. The concept of a rebound after interruption of beta-blockers is based on an animal study and on isolated case reports of variceal bleeding. AIM: To determine if a rebound occurs in patients with cirrhosis following abrupt interruption of beta-blockers. METHODS: We prospectively included all consecutive patients with cirrhosis undergoing right heart and hepatic vein catheterisation. Four groups were defined: 'no beta-blockers' including patients not receiving beta-blockers; '≤1 day', '2-3 days' and '≥4 days' classified according to the time patients had interrupted beta-blockers before catheterisation. Results were expressed as median (interquartile range). RESULTS: A total of 150 patients were included. Among the 25 patients in the groups '2-3 days' and '≥4 days', median duration of beta-blockers interruption was 4 (3-6) days. No gastrointestinal bleeding occurred during that period, nor during the following month. Hepatic venous pressure gradient was not different among patients in usually treated with beta-blockers. After adjustment, beta-blockers interruption was not associated with hepatic venous pressure gradient. Cardiac index was higher in the '≥4 days' group [4.6 L/min/m(2) (3.5-5.1)] than in the '≤1 day' group [3.4 (2.6-4.0); P = 0.001] or in the '2-3 days' group [3.1 (2.7-3.7); P = 0.007], but not different from the 'no beta-blockers' group. CONCLUSIONS: Abrupt interruption of beta-blockers is associated neither with an apparent increase in the risk of variceal bleeding nor with a haemodynamic rebound. Thus, interruption of beta-blockers in patients with cirrhosis may not require particular dosing or surveillance.

Performance and impact of a rapid method combining mass spectrometry and direct antimicrobial susceptibility testing on treatment adequacy of patients with ventilator-associated pneumonia.

Inappropriate antibiotic therapy in ventilator-associated pneumonia (VAP) is associated with increased mortality. Using broad-spectrum antibiotics for 48 h until the results of conventional cultures and antimicrobial susceptibility testing (AST) are available, may promote the emergence of drug-resistant bacteria. Performing AST directly on clinical respiratory samples would hasten the process by at least 24 h. Here, we analysed the diagnostic performance of a rapid method combining mass spectrometry and direct AST (DAST), and compared it with the conventional method (mass spectrometry with conventional AST (CAST)). Additionally, we assessed its potential impact on antimicrobial use in patients. Over a period of 18 months, the two methods were performed on 85 bronchoalveolar lavages obtained from intensive care unit patients with suspected VAP, and in which Gram-negative bacilli were observed on direct examination. Only the CAST results were reported to the clinicians. DAST produced useable results in 85.9% of the patients. The sensitivity and negative predictive values of DAST were 100% for all antibiotics tested, except gentamicin (97.1%, (95% CI 93.3-101) and 97.4% (93.7-101), respectively) and amikacin (88.9% (81.7-96.1) and 96.4% (92.1-100.7), respectively), compared with CAST. Specificity and positive predictive values ranged from 82.9 (74.2-91.5) to 100%, and from 86.4 (78.5-94.2) to 100%, respectively. If the DAST results had been reported to the clinicians, treatment could have been optimized 24 h earlier in 35/85 (41.2%) patients, with 17 carbapenem patient-days saved. Overall, routine use of the DAST method could help optimize earlier antibiotic treatment in patients with suspected VAP.

Clinical spectrum and outcomes of patients with encephalitis requiring intensive care.

BACKGROUND AND PURPOSE: Our aim was to characterize the clinical profile, temporal changes and outcomes of patients with severe encephalitis. METHODS: A retrospective cohort study was conducted on adult patients with encephalitis admitted to the medical intensive care unit (ICU) of a university hospital over a 20-year period. Patients' characteristics and outcomes were compared between two 10-year periods: (i) 1991-2001 and (ii) 2002-2012. Multivariate logistic regression was used to analyze factors associated with a poor outcome, as defined by a modified Rankin scale (mRS) score of 4-6 (severe disability or death) 90 days after admission. RESULTS: A total of 279 patients were studied. Causes of encephalitis were infections (n = 149, 53%), immune-mediated causes (n = 41, 15%) and undetermined causes (n = 89, 32%). The distribution of causes differed significantly between the two periods, with an increase in the proportion of encephalitis recognized to be of immune-mediated causes. At day 90, 208 (75%) patients had an mRS = 0-3 and 71 (25%) had an mRS = 4-6. After adjustment for functional status before admission, the following parameters were independently associated with a poor outcome: coma [odds ratio (OR) 7.09, 95% confidence interval (95% CI) 3.06-17.03], aspiration pneumonia (OR 4.02, 95% CI 1.47-11.03), a lower body temperature (per 1 degree, OR 0.72, 95% CI 0.53-0.97), elevated cerebrospinal fluid protein levels (per 1 g/l, OR 1.55, 95% CI 1.17-2.11) and delayed ICU admission (per 1 day, OR 1.04, 95% CI 1.01-1.07). CONCLUSIONS: Indicators of outcome in adult patients with severe encephalitis reflect both the severity of illness and systemic complications. Our data suggest that patients with acute encephalitis may benefit from early ICU admission.

US appearance of partial-thickness supraspinatus tendon tears: Application of the string theory. Pictorial essay.

The supraspinatus tendon is composed of 5 different layers consisting of intertwining bundles. On a front portion of the tendon, the layers become coated bundles which insert on the trochanter. At the insertion, the superficial or bursal surface of the tendon corresponding to the tendon fibers in contact with the subacromial bursa can be distinguished from the deep surface corresponding to the fibers in contact with the glenohumeral joint. A tendon tear may involve partial or total disruption of the tendon fibers and is called full-thickness tear if it affects the entire tendon, and partial-thickness tear if it involves only part of the tendon. Partial-thickness tears of the supraspinatus tendon include lesions of the superficial, deep and central surface or tendon delamination.A contrast enhanced examination requires injection of contrast agent into the joint (arthrography followed by computed tomography (CT) or magnetic resonance imaging (MRI)) to study the deep surface, and injection into the subacromial bursa (bursography followed by CT) to study the superficial surface. MRI and ultrasound (US) examination allow the study of these different tendon layers without the use of contrast agent (which is not possible at CT).

Cobalt toxicity: chemical and radiological combined effects on HaCaT keratinocyte cell line.

Cobalt (Co) is an essential trace element well known as a constituent of vitamin B(12), but different compounds of Co are also described as highly toxic and/or radiotoxic for individuals or the environment. In nuclear power plants, (58)Co and (60)Co are radioactive isotopes of cobalt present as activation products of stable Co and Ni used in alloys. Skin exposure is a current occupational risk in the hard metal and nuclear industries. As biochemical and molecular cobalt-induced toxicological mechanisms are not fully identified, we investigated cobalt toxicity in a model human keratinocyte cell line, HaCaT. In this study, we propose a model to determine the in vitro chemical impact on cell viability of a soluble form of cobalt (CoCl(2)) with or without gamma-ray doses to mimic contamination by (60)Co, to elucidate the mechanisms of cobalt intracellular chemical and radiological toxicity. Intracellular cobalt concentration was determined after HaCaT cell contamination and chemical toxicity was evaluated in terms of cellular viability and clonogenic survival. We investigated damage to DNA in HaCaT cells by combined treatment with chemical cobalt and a moderate gamma-ray dose. Additive effects of cobalt and irradiation were demonstrated. The underlying mechanism of cobalt toxicity is not clearly established, but our results seem to indicate that the toxicity of Co(II) and of irradiation arises from production of reactive oxygen species.

Diel variation in egg-laying by the freshwater fish louse Argulus foliaceus (Crustacea: Branchiura).

Removal of deposited eggs could be a useful control strategy for the damaging fish ectoparasite Argulus foliaceus, but focused control requires knowledge of egg-laying patterns. Here, we investigated diel changes in the egg-laying behaviour of a natural population of A. foliaceus. Data were collected from 17-28 May 2004. Days were divided into 3 time periods: 06:00-14:00, 14:00-22:00 and 22:00-06:00 h. Significantly more egg clutches were laid from 06:00-14:00 h than during the other 2 time periods, which were not significantly different from each other. Significantly more egg clutches per hour were laid during hours of daylight as compared to hours of darkness. Significantly more egg clutches were laid in the top 1 m of the water column than at the bottom, and this was consistent throughout all 3 time periods. It is suggested that the increase in egg-laying activity during daylight hours may be due to a higher motivation to search for hosts during the night and an increased ability to locate silhouetted egg-laying sites during the day. These data can provide information useful for egg removal and control strategies.

A comparison of cellular irradiation techniques with alpha particles using the Geant4 Monte Carlo simulation toolkit.

A comparison of three cellular irradiation techniques using the Monte Carlo simulation toolkit Geant4 is presented in this paper. They involve electrodeposited source of alpha particle-emitting radionuclides, random classical alpha beam irradiation and single cell targeted irradiation using a focused alpha microbeam line. The simulation allows the calculation of hit distributions among the cellular population as well as the absorbed dose for two typical cellular geometries.

An interdisciplinary approach to investigate the impact of cobalt in a human keratinocyte cell line.

Since in nuclear power plants, risks of skin contact contamination by radiocobalt are significant, we focused on the impact of cobalt on a human cutaneous cell line, i.e. HaCaT keratinocytes. The present paper reports an interdisciplinary approach aimed at clarifying the biochemical mechanisms of metabolism and toxicity of cobalt in HaCaT cells. Firstly, a brief overview of the used instrumental techniques is reported. The following parts present description and discussion of results concerning: (i) toxicological studies concerning cobalt impact towards HaCaT cells (ii) structural and speciation fundamental studies of cobalt-bioligand systems, through X-ray absorption spectroscopy (XAS), ab initio and thermodynamic modelling (iii) preliminary results regarding intracellular cobalt speciation in HaCaT cells using size exclusion chromatography/inductively coupled plasma-atomic emission spectroscopy (SEC/ICP-AES) and direct in situ analysis by ion beam micropobe analytical techniques.

Seasonal and vertical patterns of egg-laying by the freshwater fish louse Argulus foliaceus (Crustacea: Branchiura).

Argulus foliaceus is a damaging fish ectoparasite for which new control measures are being developed based on egg-removal. In an attempt to develop further understanding of seasonal and vertical egg-laying patterns in this parasite, egg-laying activity was monitored over the period 14 April to 17 November 2003 in 2 rainbow trout Oncorhynchus mykiss fisheries in Northern Ireland, UK. At Site 1, egg-laying was continuous from 21 April to 17 November, when water temperature was above 8 to 10 degrees C. At Site 2, egg-laying was continuous from 4 June to 29 October. In the early months of the season, egg-laying was recorded mainly within the top 1 m of the water column; however, a significant shift to deep water egg-laying was recorded between 7 July and 17 November at Site 1 and between 20 August and 29 October at Site 2. Egg clutches were preferentially laid at depths of up to 8.5 m during this time (Site 2), a feature of egg-laying hitherto unappreciated. Temperature and dissolved oxygen did not differ significantly among depths, but there was an increase in water clarity over time. However, the precise environmental triggers for deep water egg-laying are still unclear. These new insights into the reproductive behaviour of this species will be useful in developing control methods based on egg-removal.

Promoter sequences involved in transforming growth factor beta1 gene induction in HaCaT keratinocytes after gamma irradiation.

Transforming growth factor beta 1 (TGFB1) is a cytokine involved in the development of both acute and late cutaneous radiation syndromes. We previously demonstrated that ionizing radiation induces TGFB1 expression in vivo in pig skin within a few hours. The purpose of the present study was to develop an in vitro human model to identify the mechanisms of this early activation. Accordingly, human HaCaT keratinocytes were irradiated with a single dose of 20 Gy. First, radiation-induced TGFB1 overexpression was checked at both the transcriptional and transductional levels in HaCaT cells. Then electrophoretic mobility shift assays (EMSA) and transient transfection with various TGFB1 promoter constructs were used to identify the sequences involved in regulating this promoter. EMSA analysis showed the induction of nuclear protein binding activity by gamma irradiation to the -365 AP1 sequence (TGTCTCA), suggesting the involvement of AP1 sequences in the regulation of TGFB1 transcription. In gene reporter assays, maximal TGFB1 promoter activation was found for the longest construct, which contains two AP1 sequences. However, assays with constructs including deletions showed that these two AP1 sequences were not sufficient to confer TGFB1 inducibility. These results showed for the first time, to our knowledge, that transcriptional regulation is involved in radiation-induced activation of TGFB1 gene expression.

Antifibrotic action of Cu/Zn SOD is mediated by TGF-beta1 repression and phenotypic reversion of myofibroblasts.

Skin fibrosis is characterized by the proliferation and accumulation of activated fibroblasts called myofibroblasts. They exhibit specific cytoskeletal differentiation, overexpress the fibrogenic cytokine TGF-beta1, synthesize excess extracellular matrix compounds and exhibit a depleted antioxidant metabolism. Recently, SOD was successfully used as an antifibrotic agent in vivo, thus challenging the postulate of established fibrosis irreversibility. We postulated that myofibroblasts could be a direct target for this therapeutic effect. To test this hypothesis, we used three-dimensional co-culture models of skin, in which specific phenotypes of normal fibroblasts versus myofibroblasts are retained. These 3-D models were treated with liposomal and carrier-free Cu/Zn SOD, and examined for their effects on cell number, cell death, and phenotypic differentiation. The results show that SOD did not induce myofibroblast cell death, whereas it significantly reduced TGF-beta1 expression, thus demonstrating that SOD might be proposed as a potent antagonist of this major fibrogenic growth factor. We also found that SOD significantly lowered the levels of the myofibroblast marker alpha-sm actin, of beta-actin, and of the extracellular matrix components alpha1(I) collagen and tenascin-C. In conclusion, our results suggest that SOD antifibrotic action occurred in vitro through the reversion of myofibroblasts into normal fibroblasts.

Effect of some electrical stimulation variables on wing flapping, post-mortem glycolysis and eating quality characteristics of broiler pectoralis major muscle.

1. The influence of different rates of wing flapping on the rate of post-mortem glycolysis in the Pectoralis major (PMI) muscles of commercially-processed broilers was investigated. This was achieved by applying 300 pulses of low voltage electrical stimulation (ES) shortly after slaughter at various frequencies and pulse widths. The rate of post-mortem glycolysis was assessed by measuring muscle pH values at 20 min post mortem (pH(20 min)). 2. ES gave a mean pH(20 min) value of 6.01, significantly lower than that of the control carcases which had a mean value of 6.45. Within ES treatments, variation in pulse frequency between 1/s and 10/s and in pulse width from 5 to 20 ms had no influence on pH(20 min) values as measured by direct probe. However, differences between mean pH(20 min) values attributable to pulse frequency were detected when measured by the iodoacetate method. 3. A further experiment was carried out to determine how different rates of wing flapping would affect the eating quality of PM muscles from commercially-processed broilers stored at chill temperatures for 24 h post mortem. This was achieved by using pulse frequencies of 1/s, 5/s and 10/s, all other ES variables being standardised. Pulse frequency had no effect on ultimate pH, sarcomere length, cooking loss or tenderness of PM muscle compared to controls. 4. We concluded that the rate of wing flapping post-slaughter has no effect, per se, on the extent of post-mortem glycolysis in broiler PM muscle or on its subsequent meat quality assessed after holding the carcases under chill storage conditions for 24 h.

Relationship between early post-mortem muscle pH and shortening-induced toughness in the Pectoralis major muscle of processed broilers air-chilled at 0 degrees C and -12 degrees C.

1. An experiment was conducted to investigate the development of shortening-induced toughness in the Pectoralis major (PM) muscles of commercially processed broilers, air-chilled at 0 degrees C and -12 degrees C, as a function of muscle pH early post-mortem. Electrical stimulation was used immediately after stunning and neck cutting to provide carcases with pH values 15 min post-mortem (pH15 min) ranging between 6.79 and 5.85. 2. The deep PM muscle temperatures of carcases chilled at -12 degrees C were lower (cooler) after primary chilling and at 215 min post-mortem than those chilled at 0 degrees C, although chilling regimen had no major effect on pH values over the 24 h post-mortem period. However, carcases chilled at -12 degrees C had longer sarcomeres, lower cooking losses and lower shear force values than those chilled at 0 degrees C. 3. Correlation analysis of the results for both chilling regimens clearly demonstrated that over the pH15min range 6.79 to 5.85, carcases with the lowest pH15min values had the shortest sarcomeres, the highest cooking losses and the toughest meat. In addition, there was no evidence to support the occurrence of cold shortening within this population. This suggests that an early onset of rigor at higher temperatures in broiler carcases, as well as inducing rigor shortening and toughness, might also induce greater protein denaturation and subsequent loss of water holding capacity as manifested in increased cooking losses. 4. Quadratic regression curves showed that over the pH15min range 6.80 to 6.30, only the fast chilling regimen at -12 degrees C could inhibit rigor shortening and minimise changes in cooking loss and shear force values. However, neither chilling regimen was effective in preventing severe rigor shortening, increased cooking losses and adverse toughness in carcases with pH15min values below 6.30. 5. The benefits of fast chilling carcases with pH15min values above 6.3 can also be quantified in terms of carcases exceeding a 4.00 kg/cm2 toughness threshold. Only 1.9% of these carcases chilled at -12 degrees C exceeded this limit (maximum shear force value of 4.72 kg/cm2) compared to 34.9% of the carcases chilled at 0 degrees C (maximum shear force value of 8.46 kg/cm2), further emphasising the considerable reduction in textural variability and improvement in tenderness gained by fast air-chilling at -12 degrees C.

Histopathological and cellular studies of a case of cutaneous radiation syndrome after accidental chronic exposure to a cesium source.

This study was designed for the histopathological, cellular and biochemical characterization of a skin lesion removed surgically from a young male several months after accidental exposure to cesium-137, with an emphasis on expression of transforming growth factor beta1 (TGFB1) and tumor necrosis factor alpha (TNFA) and the occurrence of apoptosis. Under a hypertrophic epidermis, a highly inhomogeneous inflammatory dermis was observed, together with fibroblastic proliferation in necrotic areas. Immunostaining revealed overexpression of TGFB1 and TNFA inside the keratinocytes of the hypertrophic epidermis as well as in the cytoplasm of the fibroblasts and connective tissue of the mixed fibrotic and necrotic dermis. Inside this dermis, the TUNEL assay revealed areas containing numerous apoptotic fibroblasts next to areas of normal viable cells. Overexpression of TGFB1 was found in the conditioned medium and cellular fractions of both hypertrophic keratinocytes and fibrotic fibroblasts. This overexpression lasted for at least three passages in tissue culture. The present observations were consistent with the central role of TGFB1 in the determination of chronic radiation-induced damage to the skin and a significant involvement of TNFA. In addition, programmed cell death appeared to take place during the remodeling of the mixed fibrotic and necrotic tissue.