Lost signature: progress and failures in in vivo tracking of implanted stem cells.

Stem cell therapy as a part of regenerative medicine provides promising approaches for the treatment of injuries and diseases. The increasing use of mesenchymal stem cells in various medical treatments created the demand for long-term in vivo cell tracking methods. Therefore, it is necessary to analyze post-transplantational survival, biodistribution, and engraftment of cells. Furthermore, stem cell treatment has been discussed controversially due to possible association with tumor formation in the recipient. For therapeutic purpose, stem cells must undergo substantial manipulation such as differentiation and in vitro expansion, and this can lead to the occurrence of genetic aberrations and altered expression of both tumor suppression and carcinogenic factors. To control therapy, it is necessary to find a reliable and general method to track and identify implanted cells in the recipient. This is especially challenging for autologous transplantations, as standard fingerprinting methods cannot be applied. An optimal technique for in vivo cell monitoring does not yet exist, and its development holds several challenges: small numbers of transplanted cells, possibility of cell number quantification, minimal transfer of the contrast agent to non-transplanted cells, and no genetic modification. This review discusses most of the proposed solutions, including magnetic resonance imaging, magnetic particle imaging, positron emission tomography, single-photon emission computed tomography, and optical imaging methods. Additionally, the recent research on cell labeling for stem cell monitoring after transplantation including in vitro, ex vivo, and in vivo imaging studies is described. Promising future imaging modalities for stem cell monitoring after transplantation are shown.

Management of pain, anxiety, agitation and delirium in burn patients: a survey of clinical practice and a review of the current literature.

Management of pain, agitation and anxiety is crucial in critically ill patients, and has a significant impact on clinical and functional outcome. This study aims to assess current management of analgesia, sedation and delirium in adult burn ICUs, and determine if discrepancies exist between current guidelines and actual practices.An online survey was created and sent to burn specialists worldwide.A total of 40 respondents submitted valuable data. Of all respondents, 20 (50%) were from Europe, 7 (17.5%) from North America, 6 (15%) from Africa and 12 (30%) from other regions. The majority of respondents were from burn centres with more than 60 admissions per year (32 centres, 80%); 36 respondents (90%) were affiliated with a University Hospital. 92.5% reported that they routinely screen severe burn patients for pain, while 27.5% declared that no particular pain assessment tool is used. The most common analgesics were opioids, mainly administered intravenously (90%). 70% affirmed they routinely screen burn ICU patients for sedation, but 30% declared that they do not use a specific sedation scoring scale. The most commonly used sedatives were midazolam (72.5%) and propofol (55%). 70% claimed to assess burn ICU patients routinely for delirium, but 57.5% reported they did not use a specific scoring system. 62.5% stated that they prevent delirium by combining pharmacological and non-pharmacological approaches. Our results indicate that awareness regarding the systematic and correct management of pain, sedation and delirium is increasing among burn specialists. However, a substantial gap between guidelines and clinical practices exist. Efforts should be directed at creating specific burn care guidelines and enhancing the implementation of existing recommendations.

La prise en charge de la douleur, de l'agitation et de l'anxiété est fondamentale chez les patients de réanimation et joue un rôle significatif dans le pronostic vital et fonctionnel. Cette étude a pour but d'évaluer la gestion actuelle de l'analgésie, de la sédation et de la confusion dans les unités de soins intensifs pour brûlés ainsi que leur adéquation avec les recommandations. Un questionnaire d'évaluation en ligne a été envoyé à des brûlologues du monde entier. Quarante réponses ont pu être analysées dont 20 (50%) d'Europe, 7 (17,5%) d'Amérique du Nord, 6 (15%) d'Afrique et 12 (30%) d'autres continents. La majorité des personnes ayant répondu travaillaient dans des Centres de Traitement des Brûlés recevant plus de 60 patients par an (32, 80%), 36 (90%) travaillant dans un CHU. Trente sept (92,5%) déclaraient évaluer régulièrement la douleur des brûlés mais 11 (27,5%) n'utilisaient pas d'outil d'évaluation. Les analgésiques les plus utilisés étaient les opiacés, le plus souvent (90%) utilisés par voie intraveineuse. Vingt huit (70%) réponses attestaient de l'évaluation de la sédation, 12 (30%) n'utilisant pas d'outil spécifique. Les molécules les plus utilisée étaient le midazolam (29; 72,5%) et le propofol (22; 55%). L'état confusionnel était recherché de manière routinière par 28 médecins (70%), aucune échelle n'étant utilisée par 23 d'entre-eux (57.5%). La prévention de la confusion utilisait une approche à la fois pharmacologique et non pharmacologique 25 fois (62,5%). Cette étude confirme l'attention croissante que portent les brûlologues à l'analgésie, la sédation et la confusion. Cependant, il existe des différences importantes entre la pratique et les recommandations. Des efforts seraient nécessaires pour créer des recommandations spécifiques aux brûlés et améliorer l'adhésion à celles déjà existantes.

Analgesia, sedation and arousal status in burn patients: the gap between recommendations and current practices.

Assessment and treatment of pain, agitation and delirium are integral parts of the management of critically ill patients. The purpose of this review is to describe how pain, delirium and agitation are managed in general intensive care units and in burn units, and to address whether management of these issues is compatible with internationally accepted recommendations. A substantial gap exists between the conception of the guidelines, clinical practice and physicians' statements regarding pain, sedation and delirium management. Specific training programs might be required to increase the implementation rate of guidelines and best practices on sedation, pain and delirium assessment and management in burn units.

L'évaluation et le traitement de la douleur, de l'agitation et du délire font partie intégrante de la prise en charge des patients de réanimation. Cette revue a pour but de décrire la prise en charge de ces paramètres en réanimation générale et en centre de brûlés et de discuter si cette prise en charge correspond aux recommandations internationales. Il existe des différences notables entre ces recommandations, la pratique courante et le point de vue des médecins concernant la prise en charge de la douleur, de l'agitation et de la confusion. Des programmes de formation spécifiques pourraient être utiles pour améliorer la concordance entre la vraie vie et les recommandations dans ces situations.

Self-assembled polypeptide nanoparticles for intracellular irinotecan delivery.

In this research poly(l-lysine)-b-poly(l-leucine) (PLys-b-PLeu) polymersomes were developed. It was shown that the size of nanoparticles depended on pH of self-assembly process and varied from 180 to 650nm. The biodegradation of PLys-b-PLeu nanoparticles was evaluated using in vitro polypeptide hydrolysis in two model enzymatic systems, as well as in human blood plasma. The experiments on the visualization of cellular uptake of rhodamine 6g-loaded and fluorescein-labeled nanoparticles were carried out and the possibility of their penetration into the cells was approved. The cytotoxicity of polymersomes obtained was tested using three cell lines, namely, HEK, NIH-3T3 and A549. It was shown that tested nanoparticles did not demonstrate any cytotoxicity in the concentrations up to 2mg/mL. The encapsulation of specific to colorectal cancer anti-tumor drug irinotecan into developed nanocontainers was performed by means of pH gradient method. The dispersion of drug-loaded polymersomes in PBS was stable at 4°C for a long time (at least 1month) without considerable drug leakage. The kinetics of drug release was thoroughly studied using two model enzymatic systems, human blood serum and PBS solution. The approximation of irinotecan release profiles with different mathematical drug release models was carried out and allowed identification of the release mechanism, as well as the morphological peculiarities of developed particles. The dependence of encapsulation efficiency, as well as maximal loading capacity, on initial drug concentration was studied. The maximal drug loading was found as 320±55µg/mg of polymersomes. In vitro anti-tumoral activity of irinotecan-loaded polymersomes on a colon cancer cell line (Caco-2) was measured and compared to that for free drug.

Monitoring and treatment of coagulation abnormalities in burn patients. an international survey on current practices.

The magnitude of coagulation abnormalities, and the definition and treatment of coagulopathy in burn patients are inadequately understood and continue to be discussed in the literature. We aimed to analyse physicians' views on monitoring and treating coagulation abnormalities in burn patients. A total of 350 questionnaires were distributed electronically to burn ICU physicians. Participation was voluntary and anonymous. Responses were analysed electronically and comparisons were made according to the region of the ICU or the specialty of the physician. Of the 350 questionnaires distributed, 55 (15.7%) were returned. The majority of burn specialists consider sepsis-induced coagulopathy to be the most frequent coagulopathy in burn patients, and 74.5% declare that they do not use any specific definition/scoring system in their department to detect coagulopathy. The majority of specialists (70.8%) use standard coagulation tests. The most frequent indications for plasma transfusion are massive bleeding (32.8%) and Disseminated Intravascular Coagulation syndrome treatment (20%). The main specific factors reported in our study are cryoprecipitate (23.2%) and fibrinogen concentrate (18.9%). 21.1% of respondents state that they do not use any specific coagulation factor substitution in burn patients. Specific coagulation factor substitution is not a routine practice. The low response rate precludes the generalization of our results.

La définition, l'importance et le traitement des anomalies de la coagulation chez les patients brûlés sont mal connues et font régulièrement l'objet de controverse dans la littérature. Nous avons analysé le point de vue des praticien sur le monitorage et le traitement de ces anomalies. Trois cent cinquante questionnaires ont été envoyés par voie électronique à des médecins travaillant en USI pour brûlés. La participation était volontaire et anonyme. Les réponses ont été comparées en tenant compte de la géographie et de la spécialité du répondant. Cinquante cinq (15,7%) ont été remplis. La majorité des praticiens considèrent que le sepsis est la cause la plus fréquente de coagulopathie chez les brûlés. Les ¾ n'utilisent pas de définition ni de score spécifiques, 70,8% utilisant les tests standard. Les indication le plus fréquentes de transfusion plasmatique (32,8%) sont le saignement massif et la CIVD (20%). Les facteurs spécifiques le plus souvent utilisés sont les cryoprécipités (23,2%) et le fibrinogène (18,9%), et 21,1% des sondés n'utilisent jamais de tels dérivés du sang. L'utilisation en routine de facteurs de coagulation est donc rare chez les brûlologues. Le faible taux de réponse ne permet pas d'inférer ces résultats à la population brûlologique générale.

Implementation of a procalcitonin-guided algorithm for antibiotic therapy in the burn intensive care unit.

The purpose of this study was to examine the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in burn patients with infectious complications. All burn patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections were eligible. Patients were assigned to either a procalcitonin-guided (study group) or a standard (control group) antibiotic regimen. The following variables were analyzed and compared in both groups: duration of antibiotic treatment, mortality rate, percentage of patients with relapse or superinfection, maximum SOFA score (days 1-28), length of ICU and hospital stay. A total of 46 Burn ICU patients receiving antibiotic therapy were enrolled in this study. In 24 patients antibiotic therapy was guided by daily procalcitonin and clinical assessment. PCT guidance resulted in a smaller antibiotic exposure (10.1±4 vs. 15.3±8 days, p=0.034) without negative effects on clinical outcome characteristics such as mortality rate, percentage of patients with relapse or superinfection, maximum SOFA score, length of ICU and hospital stay. The findings thus show that use of a procalcitonin-guided algorithm for antibiotic therapy in the burn intensive care unit may contribute to the reduction of antibiotic exposure without compromising clinical outcome parameters.

Le but de cette étude était d'examiner si un algorithme basé sur des mesures de la procalcitonine (PCT) peut permettre la réduction de la durée de l'antibiothérapie, sans être dangereuse, chez les patients brûlés infectés. Tous les patients brûlés nécessitant une antibiothérapie en raison d'une infection bactérienne très probable ou confirmée étaient éligibles. Les patients ont été divisés en deux groupes: groupe à l'étude (durée de traitement guidé par PCT), et groupe de contrôle (durée selon les préconisations actuelles). Les variables suivantes ont été analysées et comparées: durée de traitement, mortalité, le pourcentage de patients avec une surinfection ou une rechute, score SOFA maximum entre J1 et J28, durées de séjour en soins intensifs et à l'hôpital. Un total de 46 patients, hospitalisés en soins intensifs et recevant une antibiothérapie ont été inclus dans cette étude, dont 24 dans le groupe PCT. Ces patients ont reçu une exposition aux antibiotiques inférieure (10,1 ± 4 vs 15,3 ± 8 jours, p = 0,034), sans effets négatifs sur le taux de mortalité et la durée du séjour à l'hôpital. Les résultats montrent que cette méthode peut contribuer à la réduction de l'utilisation des antibiotiques chez les brûlés en soins intensifs, sans compromettre leur avenir.

Evaluation of arterial waveform derived variables for an assessment of volume resuscitation in mechanically ventilated burn patients.

OBJECTIVE: The purpose of this study was to assess the usefulness of stroke volume variations to monitor the early fluid resuscitation in mechanically ventilated burn ICU patients. METHODS AND RESULTS: Data of 29 burn patients (APACHE II - 9.8±3.6, SAPS II - 29±5, TBSA - 39.5±14) were prospectively included in this observational study. Hemodynamic parameters were determined using arterial pressure wave analysis for up to 36h after burn. Statistically significant changes in cardiac index (CI), systemic vascular resistance index (SVRI), stroke volume variation (SVV) were recorded during the observation period. There were significant correlations between CI and SVV (r=-0.454, p=0.03), SVV and SVRI (r=0.482, p=0.02) at 16 h postburn; CI and SVV (r=-0.513, p=0.012), SVV and SVRI (r=0.480, p=0.02) at 24 h postburn, CI and SVV at 36 h postburn (r=-0.478, p=0.021). Significant changes in CI (1.9±1 vs. 3.4±0.9), p=0.02 and in SVV (24.9±3 vs. 14.6±2, p=0.01) were observed in patients with low cardiac output state after administration of 10 ml/kg of Ringer lactate. CONCLUSION: Our results suggest that measurement of stroke volume variations by arterial pulse contour analysis is valuable in monitoring volume administration and in predicting volume responsiveness during the early postburn period.

PCT as a diagnostic and prognostic tool in burn patients. Whether time course has a role in monitoring sepsis treatment.

OBJECTIVE: To evaluate the diagnostic and prognostic performance of inflammatory markers for septic and non septic (localized) bacterial infections in patients with severe burn. METHODS AND RESULTS: Data of 145 patients were prospectively included in this study. Serum procalcitonin and other inflammatory markers were measured within 24 h after burn and daily thereafter. Maximum procalcitonin (p=0.004) was independent predictors of outcome in logistic regression analysis. PCT thresholds of 1.5 ng/ml, 0.52 ng/ml and 0.56 ng/ml had adequate sensitivity and specificity to diagnose sepsis, respiratory tract and wound infections respectively. A threshold value of 7.8 ng/ml in PCT concentration on day 3 was associated with the effectiveness of the sepsis treatment with an AUC of 0.86 (95% CI 0.69-1.03, p=0.002). C-reactive protein levels and WBCs showed no significant change over the first 3 days in the patients with successfully treated sepsis (p=0.93). CONCLUSION: The maximum procalcitonin level has prognostic value in burn patients. PCT can be used as a diagnostic tool in patients with infectious complications with or without bacteremia during ICU stay. Daily consecutive PCT measurements may be a valuable tool in monitoring the effectiveness of antibiotic therapy in burn ICU patients.