Participation, retention and uptake in a multicentre pre-exposure prophylaxis cohort using online, smartphone-compatible data collection.

OBJECTIVES: The aim of the study was to assess the feasibility of a national pre-exposure prophylaxis (PrEP) programme using smartphone-compatible data collection. METHODS: This was a multicentre cohort study (NCT03893188) enrolling individuals interested in PrEP in Switzerland. All centres participate in the SwissPrEPared programme, which uses smartphone-compatible data collection. Feasibility was assessed after centres had enrolled at least one participant. Participants were HIV-negative individuals presenting for PrEP counselling. Outcomes were participation (number enrolled/number eligible), enrolment rates (number enrolled per month), retention at first follow-up (number with first follow-up/number enrolled), and uptake (proportion attending first visit as scheduled). Participant characteristics were compared between those retained after baseline assessment and those who dropped out. RESULTS: Between April 2019 and January 2020, 987 individuals were assessed for eligibility, of whom 969 were enrolled (participation: 98.2%). The median enrolment rate was 86 per month [interquartile range (IQR) 52-137]. Retention at first follow-up and uptake were both 80.7% (782/969 and 532/659, respectively). At enrolment, the median age was 40 (IQR 33-47) years, 95% were men who have sex with men, 47% had a university degree, and 75.5% were already taking PrEP. Most reported multiple casual partners (89.2%), previous sexually transmitted infections (74%) and sexualized drug use (73.1%). At baseline, 25.5% tested positive for either syphilis, gonorrhoea or chlamydia. Participants who dropped out were at lower risk of HIV infection than those retained after baseline assessment. CONCLUSIONS: In a national PrEP programme using smartphone-compatible data collection, participation, retention and uptake were high. Participants retained after baseline assessment were at considerable risk of HIV infection. Younger, less educated individuals were underrepresented in the SwissPrEPared cohort.

[Meta-analysis to estimate the economic losses caused by reduced milk yield and reproductive performance associated with bovine paratuberculosis in Switzerland]. / Eine Meta-Analyse zur Schätzung der wirtschaftlichen Einbussen durch Milch- und Reproduktionsverluste infolge boviner Paratuberkulose in der Schweiz.

INTRODUCTION: Especially in regions with intensive cattle farming, paratuberculosis in ruminants can cause considerable economic losses for example through loss of sick animals, reduced milk yield and decreased reproduction performance. Although quantifying the actual economic losses is complex, this study attempts to quantify the losses caused by paratuberculosis in infected dairy farms in Switzerland by means of meta-analyses. For this purpose, in an elaborate selection process, data from 12 studies on milk yield and from three studies on the calving to conception interval were finally selected for further calculations. In addition, data from eight studies each on milk fat concentration and milk protein concentration were evaluated. For the meta-analyses, only studies in which «sick¼ (seropositive) and «healthy¼ (seronegative) animals based on the results of serum ELISA tests were compared at the individual animal level were considered. With a paratuberculosis prevalence of 5,99 % in cattle in Switzerland, a total loss of CHF 12 034 329,96 (95 % CI [CHF 8 625 406,02; CHF 16 409 276,30]; 11 095 652,20 € [7 952 624,35 €; 15 129 352,70 €]) per year was calculated for a population of 559 900 dairy cows. The main part of the losses is caused by an extended calving to conception interval: Seropositive animals need an average of 14,93 days longer (95 % CI [1,73; 28,13]) from calving to successful insemination as seronegative animals. This results in total costs for the extended calving to conception interval due to paratuberculosis of CHF 7 365 591,21 per year (95 % CI [CHF 900 394,95; CHF 14 838 087,61]; 6 791 075,10 € [830 164,14 €; 13 680 716,80 €]). Milk yield reduction based on a lactation period of 305 days results in an economic loss of CHF 4 668 738,75 per year (95 % CI [CHF 1 571 188,69; CHF 7 725 011,07]; 4 304 577,13 € [1 448 635,97 €; 7 122 460,21 €]). Milk fat and milk protein content were not found to be significantly changed. Despite a large number of studies in the screening phase, it was not possible to calculate all types of losses attributable to paratuberculosis due to lack of comparability between the studies, which is essential for meta-analyses. Nevertheless, it was possible to carry out four different meta-analyses, the results of which give a first impression of the economic importance of paratuberculosis in dairy cows in Switzerland.

INTRODUCTION: La paratuberculose des ruminants cause, particulièrement dans les régions ayant une industrie laitière intensive, des pertes économiques considérables, par exemple par la perte d'animaux malades, la réduction de la production laitière et une reproduction diminuée. Malgré la complexité de la quantification des pertes économiques effectives, on a essayé dans l'étude présentée ici de calculer les pertes causées par la paratuberculose dans les exploitations laitières en Suisse au moyen de méta-analyses. Dans ce but, des données extraites par un processus de sélection compliqué de 12 études sur la production laitière et de trois études sur la période de tarissement ont été utilisées pour calculer les pertes dues à la paratuberculose. De plus, huit études chacune sur la concentration de graisse et des protéines du lait ont été prises en compte. Seules des études où les animaux étaient classifiés comme «sains¼ (séronégatifs) et «malades¼ (séropositifs) sur la base d'un test ELISA sérique ont été prises en considération pour les méta-analyses. Pour une prévalence de la paratuberculose de 5,99 % chez les bovins en Suisse, on a pu calculer pour une population de 559 900 vaches laitières une perte totale de 12 034 329,96 CHF (IC 95 % [8 625 406,02 CHF; 16 409 276,30 CHF]; 11 095 652,20 € [7 952 624,35 €; 15 129 352,70 €]) par année. La plus grande partie de ces pertes sont dues à une période de tarissement prolongée: les vaches séropositifs ont besoin en moyenne de 14,93 jours de plus (IC 95 % [1,73; 28,13]) du vêlage à une insémination menant à une gestation que les animaux séronégatifs. Il en résulte des coûts dus à la paratuberculose en raison d'une période de tarissement prolongée de 7 365 591,21 CHF par année (IC 95 % [900 394,95 CHF; 14 838 087,61 CHF]; 6 791 075,10 € [830 164,14 €; 13 680 716,80 €]). La diminution de la production laitière cause pour une durée de lactation de 305 jours une perte économique de 4 668 738,75 CHF par année (IC 95 % [1 571 188,69 CHF; 7 725 011,07 CHF]; 4 304 577,13 € [1 448 635,97 €; 7 122 460,21 €]). Les pertes en valeurs de graisse et de protéines du lait n'étaient pas significatives. Malgré le nombre élevé d'études prises en compte dans la phase de recherche de publications pertinentes, il n'a pas été possible de calculer tous les types de pertes, car les études n'étaient pas suffisamment comparables entre elles, ce qui est une condition essentielle pour une méta-analyse. Il a cependant été possible de procéder à quatre méta-analyses différentes, dont les résultats donnent une idée de l'importance économique des pertes liées à la paratuberculose chez les vaches laitières en Suisse.

Using longitudinally sampled viral nucleotide sequences to characterize the drivers of HIV-1 transmission.

OBJECTIVES: Understanding the drivers of HIV-1 transmission is of importance for curbing the ongoing epidemic. Phylogenetic methods based on single viral sequences allow us to assess whether two individuals are part of the same viral outbreak, but cannot on their own assess who potentially transmitted the virus. We developed and assessed a molecular epidemiology method with the main aim to screen cohort studies for and to characterize individuals who are 'potential HIV-1 transmitters', in order to understand the drivers of HIV-1 transmission. METHODS: We developed and validated a molecular epidemiology approach using longitudinally sampled viral Sanger sequences to characterize potential HIV-1 transmitters in the Swiss HIV Cohort Study. RESULTS: Our method was able to identify 279 potential HIV-1 transmitters and allowed us to determine the main epidemiological and virological drivers of transmission. We found that the directionality of transmission was consistent with infection times for 72.9% of 85 potential HIV-1 transmissions with accurate infection date estimates. Being a potential HIV-1 transmitter was associated with risk factors including viral load [adjusted odds ratiomultivariable (95% confidence interval): 1.86 (1.49-2.32)], syphilis coinfection [1.52 (1.06-2.19)], and recreational drug use [1.45 (1.06-1.98)]. By contrast for the potential HIV-1 recipients, this association was weaker or even absent [1.18 (0.82-1.72), 0.89 (0.52-1.55) and 1.53 (0.98-2.39), respectively], indicating that inferred directionality of transmission is useful at the population level. CONCLUSIONS: Our results indicate that longitudinally sampled Sanger sequences do not provide sufficient information to identify transmitters with high certainty at the individual level, but that they allow the drivers of transmission at the population level to be characterized.

Cefepime neurotoxicity: thresholds and risk factors. A retrospective cohort study.

OBJECTIVES: Toxic serum cefepime trough concentrations are not well defined in the current literature. We aimed to define a more precise plasma trough concentration threshold for this antibiotic's neurological toxicity and to identify individuals at risk for developing neurotoxic side effects. METHODS: Retrospective study including all individuals who underwent cefepime therapeutic drug monitoring (TDM) between 2013 and 2017. Individuals with cefepime concentrations other than trough were excluded. The primary outcome was to assess the incidence of neurotoxicity and its relationship with cefepime plasma trough concentrations. Secondary outcomes were the relationship of renal function, cefepime daily dose, age, and cerebral and general co-morbidities with the occurrence of neurotoxicity. We also compared the mortality rate during hospitalization in individuals with and without neurotoxicity, and the possible impact of neuroprotective co-medications on outcomes. RESULTS: Cefepime concentrations were determined in 584 individuals. Among 319 individuals with available trough concentrations included, the overall incidence of neurotoxicity was 23.2% (74 of 319 individuals). Higher cefepime plasma trough concentrations were significantly associated with risk of neurotoxicity (no neurotoxicity 6.3 mg/L (interquartile range (IQR) 4.1-8.6) versus with neurotoxicity 21.6 mg/L (IQR 17.0-28.6), p <0.001). Individuals with presumed cefepime neurotoxicity had a significantly lower renal function (estimated glomerular filtration rate 82.0 mL/min/1.73 m2 (IQR 45.0-105.0) versus 35.0 mL/min/1.73 m2 (IQR 23.3-53.3], p <0.001), and significantly higher in-hospital mortality (19 (7.8%) versus 26 (35.1%) individuals, p <0.001). No neurotoxic side effects were seen below a trough concentration of 7.7 mg/L. Levels ≥38.1 mg/L always led to neurological side effects. CONCLUSION: In individuals with risk factors for cefepime neurotoxicity, such as renal insufficiency, TDM should be systematically performed, aiming at trough concentrations <7.5 mg/L.

Danger signals from mitochondrial DAMPS in trauma and post-injury sepsis.

In all multicellular organisms, immediate host responses to both sterile and infective threat are initiated by very primitive systems now grouped together under the general term 'danger responses'. Danger signals are generated when primitive 'pattern recognition receptors' (PRR) encounter activating 'alarmins'. These molecular species may be of pathogenic infective origin (pathogen-associated molecular patterns) or of sterile endogenous origin (danger-associated molecular patterns). There are many sterile and infective alarmins and there is considerable overlap in their ability to activate PRR, but in all cases the end result is inflammation. It is the overlap between sterile and infective signals acting via a relatively limited number of PRR that generally underlies the great clinical similarity we see between sterile and infective systemic inflammatory responses. Mitochondria (MT) are evolutionarily derived from bacteria, and thus they sit at the crossroads between sterile and infective danger signal pathways. Many of the molecular species in mitochondria are alarmins, and so the release of MT from injured cells results in a wide variety of inflammatory events. This paper discusses the known participation of MT in inflammation and reviews what is known about how the major.

Mast cells decrease efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme B.

Resistance towards VEGF-centered anti-angiogenic therapy still represents a substantial clinical challenge. We report here that mast cells alter the proliferative and organizational state of endothelial cells which reduces the efficacy of anti-angiogenic therapy. Consequently, absence of mast cells sensitizes tumor vessels for anti-angiogenic therapy in different tumor models. Mechanistically, anti-angiogenic therapy only initially reduces tumor vessel proliferation, however, this treatment effect was abrogated over time as a result of mast cell-mediated restimulation of angiogenesis. We show that mast cells secrete increased amounts of granzyme b upon therapy, which mobilizes pro-angiogenic laminin- and vitronectin-bound FGF-1 and GM-CSF from the tumor matrix. In addition, mast cells also diminish efficacy of anti-angiogenic therapy by secretion of FGF-2. These pro-angiogenic factors act beside the targeted VEGFA-VEGFR2-axis and reinduce endothelial cell proliferation and angiogenesis despite the presence of anti-angiogenic therapy. Importantly, inhibition of mast cell degranulation with cromolyn is able to improve efficacy of anti-angiogenic therapy. Thus, concomitant mast cell-targeting might lead to improved efficacy of anti-angiogenic therapy.Resistance towards VEGF-centered anti-angiogenic therapy is an important clinical challenge. Here, the authors show that mast cells mediate resistance to anti-angiogenetic inhibitors by altering the proliferative and organizational state of endothelial cells through mobilization of FGF-1 and GM-CSF from the tumor matrix and secretion of FGF-2.

Rhinophototherapy in chronic rhinosinusitis: a double blind randomized placebo-controlled trial.

BACKGROUND: This study evaluated the efficacy of rhinophototherapy in patients with chronic rhinosinusitis (CRS) without nasal polyps. METHOD: In this randomized double-blind, placebo-controlled trial, CRS patients (n=50) received either mixed visible and ultraviolet (UVA and UVB) light source application (mUV/VIS) or visible light alone that served as placebo. Both groups were treated for 3 weeks. RESULTS: Results in the rhinophototherapy and placebo group were not significantly different and failed to reduce patient-reported outcomes measures (Rhinosinusits Disability Index, Visual Analogic Scale of symptom severity) and objective scores (rhinomanometry, olfactory thresholds, nasal Nitic Oxide concentrations), immediately and one month after treatment. CONCLUSIONS: The present data suggest that rhinophototherapy is not an efficient treatment for chronic rhinosinusitis without nasal polyps.

Antimicrobial activity of Olea europaea Linné extracts and their applicability as natural food preservative agents.

The antimicrobial activity of phenolic compounds from Olea (O.) europaea Linné (L.) is part of the scientific discussion regarding the use of natural plant extracts as alternative food preservative agents. Although, the basic knowledge on the antimicrobial potential of certain molecules such as oleuropein, hydroxytyrosol or elenolic acid derivatives is given, there is still little information regarding their applicability for food preservation. This might be primarily due to the lack of information regarding the full antimicrobial spectrum of the compounds, their synergisms in natural or artificial combinations and their interaction with food ingredients. The present review accumulates available literature from the past 40 years, investigating the antimicrobial activity of O. europaea L. derived extracts and compounds in vitro and in food matrices, in order to evaluate their food applicability. In summary, defined extracts from olive fruit or leaves, containing the strongest antimicrobial compounds hydroxytyrosol, oleacein or oleacanthal in considerable concentrations, appear to be suitable for food preservation. Nonetheless there is still need for consequent research on the compounds activity in food matrices, their effect on the natural microbiota of certain foods and their influence on the sensorial properties of the targeted products.

[Robotic-Assisted Oesophageal Surgery]. / Roboterchirurgie am Ösophagus.

BACKGROUND: Abdominothoracic oesophageal resections, also known as Ivor Lewis procedures, are complex visceral surgery procedures. In recent years, substeps have increasingly been performed using minimally invasive techniques. However, intrathoracic anastomosis is still a challenge given the instrumental and technological possibilities available to date. This article provides a detailed description of the use of the Da Vinci robotic system and our techniques in oesophageal surgery. METHODS: In a prospective data collection, we analysed the robotic-assisted oesophageal surgeries performed at the University Hospital of Schleswig-Holstein, Campus Kiel, between November 2013 and November 2015. RESULTS: A total of 56 patients underwent robotic-assisted oesophageal surgery, with 43 patients undergoing the Ivor Lewis technique, 10 patients undergoing the McKeown procedure and 3 patients undergoing enucleation of a leiomyoma. A complete tumour resection (R0 margin) was achieved in 53 patients (93.4%); the mean number of resected lymph nodes was 23 (14-75). Forty-five (80.5%) patients received an induction therapy. Mean operative time was 412 min (120-610); mean hospital stay was 19 days (4-145). A conversion to open surgery was necessary in 19 (34.1%) cases, most notably in the thoracic part of the surgical procedure (17 patients). Forty-three patients received intrathoracic oesophagogastrostomy; 4 out of 5 patients with an initial side-to-side anastomosis developed a leakage, whereupon the technique was switched to a hand-sewn procedure (leakage in 3 out of 20 patients). Other major morbidities included leakage of the gastric conduit in 2 patients (3.6%), airway fistula in 2 patients (3.6%), mesenteric ischaemia in one patient (1.8%), and peritonitis due to a dislocated feeding tube in one other patient. Pulmonary complications occurred in 19 patients (34%). Four patients (7.1%) died of pulmonary embolism, heart attack, and septic organ failure. CONCLUSION: Robotic-assisted, minimally invasive oesophagectomy is a feasible and useful approach for oncological surgery. This technique should be implemented in a structured program with an extensive and critical evaluation of the users' own results and an exchange with other experienced work teams. This helps to avoid pitfalls and to speed up the learning curve. Further technological developments and increasing experience might lead to a more widespread use of this technique.

Does neoadjuvant treatment before oncologic esophagectomy affect the postoperative quality of life? A prospective, longitudinal outcome study.

To evaluate the cancer patients' quality of life (QoL) following esophagectomy the focus was placed on the impact of neoadjuvant treatment before surgery. For patients undergoing oncologic surgery, the QoL is generally accepted as an important outcome parameter in addition to clinical parameters. This prospective nonrandomized study evaluated QoL in patients treated by preoperative chemo(radio)therapy followed by either surgery or surgery alone with special focus on the postoperative course. QoL was assessed in 131 consecutive patients who underwent surgery for esophageal cancer. The EORTC-QLQ-C30 and a tumor-specific module were administered before surgery, at discharge, 3, 6, 12, and 24 months after surgery. Clinical data were collected prospectively and a follow up was performed every 6 months. The histological type of cancer was squamous cell carcinoma in 49.6% and adenocarcinoma in 50.4%. There was no significant difference between patients that were treated neoadjuvantly and those that were first operated on with regard to morbidity, mortality, and survival rates (5-year survival rate of 34%). Most QoL scores dropped significantly below the baseline in the early postoperative period and recovered slowly during the follow-up period to almost preoperative levels in many scores. There was no statistically significant difference in any of the QoL scales between neoadjuvantly treated or primary operated patients. Esophageal resections are associated with significant deterioration of QoL, which slowly recovers during the follow-up period to an almost preoperative level. Neoadjuvant treatment seems to not further negatively affect the QoL deterioration.

Antimicrobial activity of hop extracts against foodborne pathogens for meat applications.

AIMS: The objective of this study was the fundamental investigation of the antimicrobial efficiency of various hop extracts against selected foodborne pathogens in vitro, as well as their activity against Listeria monocytogenes in a model meat marinade and on marinated pork tenderloins. METHODS AND RESULTS: In a first step, the minimum inhibitory concentrations (MIC) of three hop extracts containing either α- or ß-acids or xanthohumol were determined against test bacteria including L. monocytogenes, Staphylococcus aureus, Salmonella enterica and Escherichia coli by a colorimetric method based on the measurement of bacterial metabolic activity. Moreover, the influence of either lactic or citric acid on the antimicrobial activity of the hop extracts was evaluated. The efficiency of hop extracts as a natural food preservative was then tested in a model meat marinade at 2 and 8°C, respectively, and finally on marinated pork. The experiments showed that Gram-positive bacteria were strongly inhibited by hop extracts containing ß-acids and xanthohumol (MIC values of 6.3 and 12.5 ppm, respectively), whereas the antimicrobial activity of the investigated α-acid extract was significantly lower (MIC values of 200 ppm). Gram-negative bacteria were highly resistant against all tested hop extracts. Acidification of the test media led to a decrease of the MIC values. The inhibitory activity of the hop extracts against L. monocytogenes was strongly reduced in a fat-containing model meat marinade, but the efficiency of ß-acids in this matrix could be increased by lowering pH and storage temperatures. By applying 0.5 % ß-acids at pH = 5 in a model marinade, the total aerobic count of pork tenderloins was reduced up to 0.9 log10 compared with marinated pork without hop extract after 2 weeks of storage at 5°C. CONCLUSIONS: ß-acid containing hop extracts have proven to possess a high antimicrobial activity against Gram-positive bacteria in vitro and in a practice-related application for food preservation. SIGNIFICANCE AND IMPACT OF THE STUDY: Antimicrobial hop extracts could be used as natural preservatives in food applications to extend the shelf life and to increase the safety of fresh products.

c-Rel is a critical mediator of NF-κB-dependent TRAIL resistance of pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest malignancies with an overall life expectancy of 6 months despite current therapies. NF-κB signalling has been shown to be critical for this profound cell-autonomous resistance against chemotherapeutic drugs and death receptor-induced apoptosis, but little is known about the role of the c-Rel subunit in solid cancer and PDAC apoptosis control. In the present study, by analysis of genome-wide patterns of c-Rel-dependent gene expression, we were able to establish c-Rel as a critical regulator of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in PDAC. TRAIL-resistant cells exhibited a strong TRAIL-inducible NF-κB activity, whereas TRAIL-sensitive cells displayed only a small increase in NF-κB-binding activity. Transfection with siRNA against c-Rel sensitized the TRAIL-resistant cells in a manner comparable to siRNA targeting the p65/RelA subunit. Gel-shift analysis revealed that c-Rel is part of the TRAIL-inducible NF-κB complex in PDAC. Array analysis identified NFATc2 as a c-Rel target gene among the 12 strongest TRAIL-inducible genes in apoptosis-resistant cells. In line, siRNA targeting c-Rel strongly reduced TRAIL-induced NFATc2 activity in TRAIL-resistant PDAC cells. Furthermore, siRNA targeting NFATc2 sensitized these PDAC cells against TRAIL-induced apoptosis. Finally, TRAIL-induced expression of COX-2 was diminished through siRNA targeting c-Rel or NFATc2 and pharmacologic inhibition of COX-2 with celecoxib or siRNA targeting COX-2, enhanced TRAIL apoptosis. In conclusion, we were able to delineate a novel c-Rel-, NFATc2- and COX-2-dependent antiapoptotic signalling pathway in PDAC with broad clinical implications for pharmaceutical intervention strategies.

Single-dose rituximab for remission induction and maintenance therapy in ANCA-associated vasculitis: a retrospective analysis of 17 patients.

OBJECTIVES: The aim of this study was to evaluate the efficacy of a repeated single-dose rituximab (RTX) regimen for remission induction and maintenance in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHOD: We performed a retrospective analysis of all patients with an established diagnosis of AAV who were treated with single-dose RTX infusions at our institution. Clinical outcome data were assessed over a period of 24 months. RESULTS: Sixteen patients were treated for remission induction and maintenance and one patient was treated for only maintenance therapy. Remission (absence of disease activity during the past 3 months and a prednisolone dose of ≤ 7.5 mg) was achieved in 11 patients (68%) with a mean time to remission of 9.4 (range 3-24) months. At 6 months, six patients (37.5%) were in remission and the mean prednisolone dose of all responding patients was 8.2 mg. Five patients had treatment failure due to early relapsing (n = 4) or persistently active (n = 1) disease. At 24 months, nine of the 11 responding patients (82%) were in remission. All patients still had concomitant steroid and/or disease-modifying anti-rheumatic drug (DMARD) therapy at 24 months. Overall, 11 relapses were seen in nine patients (five non-responders and four responders) with a mean time to relapse of 5.3 (range 4-24) months. No major relapses were observed in the responding patients. Severe infections were only seen in patients who had been previously treated with cyclophosphamide (CYC). CONCLUSIONS: The combination of single-dose RTX with other immunosuppressants seems less effective than the standard RTX regimen for the induction of remission of AAV.

Lactic acidosis is associated with multiple organ failure and need for ventilator support in patients with severe hemorrhage from trauma.

PURPOSE: Lactate is a biomarker for hypoperfusion and subsequent resuscitation in trauma. It is also a predictor of mortality, but few studies have correlated lactate levels with relevant morbidities after trauma. METHODS: A retrospective review was performed of severely injured trauma patients entered into the Trauma Registry of the German Society for Trauma Surgery (TR-DGU) between 2002 and 2008. Adults requiring intensive care were categorized into two groups: lactate and no lactate. The lactate group had three subgroups: normal, elevated, and high lactate. Mean multiple organ failure (MOF) rates and composite endpoint of time (days) to complete organ failure resolution (CTCOFR) for 14 and 21 days and ventilator-free days (VFD) were compared, as well as other endpoints. RESULTS: We analyzed 2,949 patients, of which 1,199 had lactate measurements. The percentage of patients with MOF increased in each higher lactate subgroup (p < 0.001), as did the mean CTCOFR14 and CTCOFR21 scores (p < 0.001 and < 0.001, respectively). Conversely, the mean VFD decreased in each higher lactate subgroup (p < 0.001). Thus, patients in the elevated and high lactate subgroups had greater MOF rates; required more days, on average, to resolve organ failure; and required more days of ventilator support than patients in the normal lactate subgroup. CONCLUSION: Elevated blood lactate levels from trauma were closely correlated with worse outcomes. Thus, lactate shows promise as a biomarker for resuscitation as well as a predictor of mortality. Furthermore, this study supports its use in critical care trials as an outcome measure.

Technological advancements in the care of the trauma patient.

INTRODUTION: Medical technology has benefited many types of patients, but trauma care has arguably benefited more from technologic development than almost any other field. METHODS: A literature review to identify key technological advances in the care of trauma patients was performed. RESULTS: The advances in trauma care are in great measure due to the integration of many different systems. Medical technology impacts care in the field at the site of the trauma, in the transport to trauma facilities, and care at the trauma center itself. Once at the hospital, technology has impacted care in the trauma bay, intensive care units, the operating room, and in postoperative and long-term care settings. The integration of advancements, however, needs to be examined in a careful systematic fashion to insure that patients will actually derive benefit.

[Antiseptic anaphylaxis]. / Anaphylaxie aux antiseptiques.

Antiseptics are widely used in medical practice. Their cutaneous secondary effects such as allergic contact dermatitis are well known. However, anaphylactic reactions are less. The scope of this article is to describe antiseptics currently used which cause immediate hypersensitivity reactions. Finally, the diagnostic tools and therapeutic approach will be discussed.

Suppressing flashes of items surrounding targets during calibration of a P300-based brain-computer interface improves performance.

Since the introduction of the P300 brain-computer interface (BCI) speller by Farwell and Donchin in 1988, the speed and accuracy of the system has been significantly improved. Larger electrode montages and various signal processing techniques are responsible for most of the improvement in performance. New presentation paradigms have also led to improvements in bit rate and accuracy (e.g. Townsend et al (2010 Clin. Neurophysiol. 121 1109-20)). In particular, the checkerboard paradigm for online P300 BCI-based spelling performs well, has started to document what makes for a successful paradigm, and is a good platform for further experimentation. The current paper further examines the checkerboard paradigm by suppressing items which surround the target from flashing during calibration (i.e. the suppression condition). In the online feedback mode the standard checkerboard paradigm is used with a stepwise linear discriminant classifier derived from the suppression condition and one classifier derived from the standard checkerboard condition, counter-balanced. The results of this research demonstrate that using suppression during calibration produces significantly more character selections/min ((6.46) time between selections included) than the standard checkerboard condition (5.55), and significantly fewer target flashes are needed per selection in the SUP condition (5.28) as compared to the RCP condition (6.17). Moreover, accuracy in the SUP and RCP conditions remained equivalent (∼90%). Mean theoretical bit rate was 53.62 bits/min in the suppression condition and 46.36 bits/min in the standard checkerboard condition (ns). Waveform morphology also showed significant differences in amplitude and latency.

[Skin barrier defects in atopic dermatitis: new treatments?]. / Anomalies de la barrière cutanée dans la dermatite atopique: une piste pour de nouveaux traitements?

Atopic dermatitis (AD) is a chronic inflammatory skin disorder and the most frequent skin disease in children. Skin barrier defects play a crucial role in its pathogenesis. 50% of patients suffering from AD present mutations in the filaggrin gene, coding for a key protein of the upper layer of the skin. However these mutations alone are not sufficient for disease development, suggesting that environmental factors are also of great importance in the genesis of AD. In particular skin infections frequently provoke clinical exacerbations in patients suffering from AD. New insights into skin barrier dysfunctions have facilitated the development of drugs targeting the sustainable restitution of the skin's physiologic function. These agents could modify the pharmacological approach of AD treatments in the future.

A novel P300-based brain-computer interface stimulus presentation paradigm: moving beyond rows and columns.

OBJECTIVE: An electroencephalographic brain-computer interface (BCI) can provide a non-muscular means of communication for people with amyotrophic lateral sclerosis (ALS) or other neuromuscular disorders. We present a novel P300-based BCI stimulus presentation - the checkerboard paradigm (CBP). CBP performance is compared to that of the standard row/column paradigm (RCP) introduced by Farwell and Donchin (1988). METHODS: Using an 8x9 matrix of alphanumeric characters and keyboard commands, 18 participants used the CBP and RCP in counter-balanced fashion. With approximately 9-12 min of calibration data, we used a stepwise linear discriminant analysis for online classification of subsequent data. RESULTS: Mean online accuracy was significantly higher for the CBP, 92%, than for the RCP, 77%. Correcting for extra selections due to errors, mean bit rate was also significantly higher for the CBP, 23 bits/min, than for the RCP, 17 bits/min. Moreover, the two paradigms produced significantly different waveforms. Initial tests with three advanced ALS participants produced similar results. Furthermore, these individuals preferred the CBP to the RCP. CONCLUSIONS: These results suggest that the CBP is markedly superior to the RCP in performance and user acceptability. SIGNIFICANCE: The CBP has the potential to provide a substantially more effective BCI than the RCP. This is especially important for people with severe neuromuscular disabilities.