Involving Health Professionals in the Development of Quality and Safety Dashboards: Qualitative Study.

BACKGROUND: Dashboards are an important tool for hospitals to improve quality and safety performance. However, implementing quality and safety dashboards often does not increase performance due to a lack of use by health professionals. Including health professionals in the development process of quality and safety dashboards can improve their use in practice. Yet, it remains unclear how a development process involving health professionals can be executed successfully. OBJECTIVE: The aim of this study is twofold: (1) to delineate how a process whereby health professionals are included in the development of quality and safety dashboards can be facilitated and (2) to identify the factors that are important to consider in order to make that process successful. METHODS: We conducted a qualitative, in-depth exploratory case study in which we analyzed 150 pages of internal documents and interviewed 13 staff members regarding the development of quality and safety dashboards within 2 care pathways of a hospital that has experience in such development. The data were analyzed inductively using the constant comparative method. RESULTS: We found that the development of quality and safety dashboards in collaboration with health professionals was facilitated through a five-stage process: (1) familiarizing participants with dashboards and the development process; (2) brainstorming about potential indicators to be included in the dashboard; (3) prioritizing, defining, and selecting indicators to be included in the dashboard; (4) examining how the indicators can be visualized; and (5) implementing the dashboard and following up on its use. To enhance the success of the process, 3 factors were deemed important. The first is to create and maintain broad involvement, ensuring that various professions are represented and take ownership of the dashboard. Here, potential barriers include gaining engagement from peers not directly involved in the process and maintaining involvement after the initial implementation of the dashboard. Second, unburdening, whereby quality and safety staff facilitate a structured process that has little additional burden for professionals. For this, time management and a lack of collaboration with departments responsible for delivering the data might be an issue. Lastly, focusing on relevance for health professionals, which refers to the inclusion of indicators with value for health professionals. For this factor, a lack of consensus on how indicators should be defined and registered might be a barrier. CONCLUSIONS: Health care organizations seeking to develop quality and safety dashboards in collaboration with health professionals can use a 5-stage process. To enhance the success of the process, organizations are advised to focus on 3 key factors. For each of the key factors, potential barriers should be taken into account. Engaging in this process and attaining the key factors could increase the likelihood that the dashboards are used in practice.

Large neutral amino acid levels tune perinatal neuronal excitability and survival.

Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.

Prognostic Impact of the International Society on Thrombosis and Hemostasis Disseminated Intravascular Coagulation Score in Sepsis: A Systematic Review.

The International Society on Thrombosis and Haemostasis (ISTH) diagnostic criteria for disseminated intravascular coagulation (DIC) are widely used for DIC diagnosis. However, the prognostic value of the score may vary between different patient populations and settings. This systematic review investigated the association between the ISTH DIC score and mortality in sepsis patients. A literature search was conducted in PubMed and Embase. Inclusion criteria were studies including adult and pediatric patients hospitalized with sepsis, using any sepsis definition, and investigating the association between mortality and the ISTH DIC score. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. In total, 42 studies were included. A positive association between the ISTH DIC score and mortality was consistently reported, with odds ratios of death in DIC versus non-DIC patients ranging from 1.125 (95% confidence interval [CI]: 0.838-1.511) to 21.008 (95% CI: 1.408-313.405) in adults and from 1.378 (95% CI: 1.004-1.893) to 2.99 (95% CI: 0.54-16.6) in pediatric populations. However, the DIC score only had a low-moderate positive predictive value for mortality, as area under receiver-operator characteristics ranged from 0.602 (95% CI: 0.575-0.630) to 0.815 (95% CI: 0.676-0.954) in adults. Of note, only few studies adjusted for potential confounders such as age, gender, and comorbidity. The ISTH DIC score is consistently associated with sepsis-related mortality but is not a strong positive predictor for mortality. Nevertheless, the score may still have a prognostic value and its use in sepsis is encouraged.

The detection and prevention of adverse drug events in nursing home and home care patients: Study protocol of a quasi-experimental study.

AIM: To estimate the cost-effectiveness of an intervention facilitating the early detection of adverse drug events through the means of health professional training and the application of a digital screening tool. DESIGN: Multi-centred non-randomized controlled trial from August 2018 to March 2020 including 65 nursing homes or home care providers. METHODS: We aim to estimate the effect of the intervention on the rate of adverse drug events as primary outcome through a quasi-experimental empirical study design. As secondary outcomes, we use hospital admissions and falls. All outcomes will be measured on patient-month level. Once the causal effect of the intervention is estimated, cost-effectiveness will be calculated. For cost-effectiveness, we include all patient costs observed by the German statutory health insurance. RESULTS: The results of this study will inform about the cost-effectiveness of the optimized drug supply intervention and provide evidence for potential reimbursement within the German statutory health insurance system.

Isolated Pectoralis Minor Tendon Rupture with Subclavian Vein Thrombosis.

Isolated insertional ruptures of the pectoralis minor tendon at the coracoid process are a rare condition. Hitherto, very few cases have been reported in the literature. A precise diagnosis is often difficult to obtain and commonly requires advanced imaging to confirm the suspicion and rule out concomitant injuries. All cases reported in the literature to date have been treated conservatively, with excellent results and no further complications. Here, however, we present the case of a patient who had developed a subclavian vein thrombosis. Furthermore, we provide an overview over and draw comparisons to the cases described in the literature. Despite the effectiveness of the conservative treatment, physicians should be aware that adverse events may occur.

Klebsiella pneumoniae Reduces SUMOylation To Limit Host Defense Responses.

Klebsiella pneumoniae is an important cause of multidrug-resistant infections worldwide. Understanding the virulence mechanisms of K. pneumoniae is a priority and timely to design new therapeutics. Here, we demonstrate that K. pneumoniae limits the SUMOylation of host proteins in epithelial cells and macrophages (mouse and human) to subvert cell innate immunity. Mechanistically, in lung epithelial cells, Klebsiella increases the levels of the deSUMOylase SENP2 in the cytosol by affecting its K48 ubiquitylation and its subsequent degradation by the ubiquitin proteasome. This is dependent on Klebsiella preventing the NEDDylation of the Cullin-1 subunit of the ubiquitin ligase complex E3-SCF-ßTrCP by exploiting the CSN5 deNEDDylase. Klebsiella induces the expression of CSN5 in an epidermal growth factor receptor (EGFR)-phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-extracellular signal-regulated kinase (ERK)-glycogen synthase kinase 3 beta (GSK3ß) signaling pathway-dependent manner. In macrophages, Toll-like receptor 4 (TLR4)-TRAM-TRIF-induced type I interferon (IFN) via IFN receptor 1 (IFNAR1)-controlled signaling mediates Klebsiella-triggered decrease in the levels of SUMOylation via let-7 microRNAs (miRNAs). Our results revealed the crucial role played by Klebsiella polysaccharides, the capsule, and the lipopolysaccharide (LPS) O-polysaccharide, to decrease the levels of SUMO-conjugated proteins in epithelial cells and macrophages. A Klebsiella-induced decrease in SUMOylation promotes infection by limiting the activation of inflammatory responses and increasing intracellular survival in macrophages.IMPORTANCEKlebsiella pneumoniae has been singled out as an urgent threat to human health due to the increasing isolation of strains resistant to "last-line" antimicrobials, narrowing the treatment options against Klebsiella infections. Unfortunately, at present, we cannot identify candidate compounds in late-stage development for treatment of multidrug-resistant Klebsiella infections; this pathogen is exemplary of the mismatch between unmet medical needs and the current antimicrobial research and development pipeline. Furthermore, there is still limited evidence on K. pneumoniae pathogenesis at the molecular and cellular levels in the context of the interactions between bacterial pathogens and their hosts. In this research, we have uncovered a sophisticated strategy employed by Klebsiella to subvert the activation of immune defenses by controlling the modification of proteins. Our research may open opportunities to develop new therapeutics based on counteracting this Klebsiella-controlled immune evasion strategy.

Gold-Catalyzed Cycloisomerization of Sulfur Ylides to Dihydrobenzothiepines.

The metal-promoted nucleophilic addition of sulfur ylides to π-systems is a well-established reactivity. However, the driving force of such transformations, elimination of a sulfide moiety, entails stoichiometric byproducts making them unfavorable in terms of atom economy. In this work, a new take on sulfur ylide chemistry is reported, an atom-economical gold(I)-catalyzed synthesis of dihydrobenzo[b]thiepines. The reaction proceeds under mild conditions at room temperature.

Sepsis-related Organ Failure Assessment Score is a strong predictor of survival in acute-on-chronic liver failure.

INTRODUCTION: The mortality of patients with an exacer-bation of decompensated liver cirrhosis is high even if treated in the intensive care unit (ICU), and the criteria for referral to ICU are not well defined. The objective of this study was to identify variables associated with mortality. METHODS: A single-centre retrospective cohort analysis was conducted in a university-affiliated ICU. A total of 53 adult patients with decompensated alcoholic liver cirrhosis were admitted from January 2012 to June 2015. Variables associated with survival were identified using Cox regression analysis. RESULTS: The ten-day, 30-day, 90-day, and one-year mortality were 36%, 57%, 66%, and 80%, respectively. Univariate Cox regression analysis showed that mortality was significantly associated with a low oxygen saturation, low diastolic blood pressure, terlipressin treatment, high Acute Physiology And Chronic Health Evaluation II score, high Simplified Acute Physiology Score II score, high Sepsis-related Organ Failure Assessment (SOFA) score and high Model For End-Stage Liver Disease score, but only a high SOFA score and old age were independently associated with increased mortality. These two variables were combined to the Age-SOFA index to predict the probability of surviving a given period. CONCLUSIONS: The mortality was high in these severely ill patients, even when they received optimum supportive therapy in the ICU. The finding that the SOFA score and age best predicted mortality shows that the increased mortality was caused mainly by insufficiency of organs other than the liver. FUNDING: none. TRIAL REGISTRATION: not relevant.

C-H Activation Enables a Concise Total Synthesis of Quinine and Analogues with Enhanced Antimalarial Activity.

We report a novel approach to the classical natural product quinine that is based on two stereoselective key steps, namely a C-H activation and an aldol reaction, to unite the two heterocyclic moieties of the target molecule. This straightforward and flexible strategy enables a concise synthesis of natural (-)-quinine, the first synthesis of unnatural (+)-quinine, and also provides access to unprecedented C3-aryl analogues, which were prepared in only six steps. We additionally demonstrate that these structural analogues exhibit improved antimalarial activity compared with (-)-quinine both in vitro and in mice infected with Plasmodium berghei.

Economy of Catalyst Synthesis-Convenient Access to Libraries of Di- and Tetranaphtho Azepinium Compounds.

Efficient optimization procedures in chiral catalysis are usually linked to a straightforward strategy to access groups of structurally similar catalysts required for fine-tuning. The ease of building up such ligand libraries can be increased when the structure-modifying step (introduction of a substituent) is done at a later stage of the synthesis. This is demonstrated for the extended family of di- and tetranaphtho azepinium compounds, widely used as chiral phase transfer catalysts (PTC). Using 2,6-diiodo-4,5-dihydro-3H-dinaphtho[2,1-c:1',2'-e]azepine and 4,8-diiodo-6,7-dihydro-5H-dibenzo[c,e]azepine, respectively, as key intermediates, 18 spiro-azepinium compounds were synthesized in a total yield of 25-42% over 6-7 steps from 1,1'-binaphthyl-2,2'-dicarboxylic acid or diphenic acid, respectively. The replacement of iodo groups with aryl substituents was performed as the last or the penultimate step of the synthesis.

Prediction of clinical response to drugs in ovarian cancer using the chemotherapy resistance test (CTR-test).

BACKGROUND: In order to validate if the test result of the Chemotherapy Resistance Test (CTR-Test) is able to predict the resistances or sensitivities of tumors in ovarian cancer patients to drugs, the CTR-Test result and the corresponding clinical response of individual patients were correlated retrospectively. Results were compared to previous recorded correlations. METHODS: The CTR-Test was performed on tumor samples from 52 ovarian cancer patients for specific chemotherapeutic drugs. Patients were treated with monotherapies or drug combinations. Resistances were classified as extreme (ER), medium (MR) or slight (SR) resistance in the CTR-Test. Combination treatment resistances were transformed by a scoring system into these classifications. RESULTS: Accurate sensitivity prediction was accomplished in 79% of the cases and accurate prediction of resistance in 100% of the cases in the total data set. The data set of single agent treatment and drug combination treatment were analyzed individually. Single agent treatment lead to an accurate sensitivity in 44% of the cases and the drug combination to 95% accuracy. The detection of resistances was in both cases to 100% correct. ROC curve analysis indicates that the CTR-Test result correlates with the clinical response, at least for the combination chemotherapy. Those values are similar or better than the values from a publication from 1990. CONCLUSIONS: Chemotherapy resistance testing in vitro via the CTR-Test is able to accurately detect resistances in ovarian cancer patients. These numbers confirm and even exceed results published in 1990. Better sensitivity detection might be caused by a higher percentage of drug combinations tested in 2012 compared to 1990. Our study confirms the functionality of the CTR-Test to plan an efficient chemotherapeutic treatment for ovarian cancer patients.

New in vitro system to predict chemotherapeutic efficacy of drug combinations in fresh tumor samples.

BACKGROUND: To find the best individual chemotherapy for cancer patients, the efficacy of different chemotherapeutic drugs can be predicted by pretesting tumor samples in vitro via the chemotherapy-resistance (CTR)-Test®. Although drug combinations are widely used among cancer therapy, so far only single drugs are tested by this and other tests. However, several first line chemotherapies are combining two or more chemotherapeutics, leading to the necessity of drug combination testing methods. METHODS: We established a system to measure and predict the efficacy of chemotherapeutic drug combinations with the help of the Loewe additivity concept in combination with the CTR-test. A combination is measured by using half of the monotherapy's concentration of both drugs simultaneously. With this method, the efficacy of a combination can also be calculated based on single drug measurements. RESULTS: The established system was tested on a data set of ovarian carcinoma samples using the combination carboplatin and paclitaxel and confirmed by using other tumor species and chemotherapeutics. Comparing the measured and the calculated values of the combination testings revealed a high correlation. Additionally, in 70% of the cases the measured and the calculated values lead to the same chemotherapeutic resistance category of the tumor. CONCLUSION: Our data suggest that the best drug combination consists of the most efficient single drugs and the worst drug combination of the least efficient single drugs. Our results showed that single measurements are sufficient to predict combinations in specific cases but there are exceptions in which it is necessary to measure combinations, which is possible with the presented system.

A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host defences and promotes virulence.

Klebsiella pneumoniae is an important cause of multidrug-resistant infections worldwide. Recent studies highlight the emergence of multidrug-resistant K. pneumoniae strains which show resistance to colistin, a last-line antibiotic, arising from mutational inactivation of the mgrB regulatory gene. However, the precise molecular resistance mechanisms of mgrB-associated colistin resistance and its impact on virulence remain unclear. Here, we constructed an mgrB gene K. pneumoniae mutant and performed characterisation of its lipid A structure, polymyxin and antimicrobial peptide resistance, virulence and inflammatory responses upon infection. Our data reveal that mgrB mutation induces PhoPQ-governed lipid A remodelling which confers not only resistance to polymyxins, but also enhances K. pneumoniae virulence by decreasing antimicrobial peptide susceptibility and attenuating early host defence response activation. Overall, our findings have important implications for patient management and antimicrobial stewardship, while also stressing antibiotic resistance development is not inexorably linked with subdued bacterial fitness and virulence.

In vitro pharmacokinetics/pharmacodynamics of the combination of avibactam and aztreonam against MDR organisms.

OBJECTIVES: The combination of aztreonam and avibactam has been proposed for the treatment of infections caused by metallo-ß-lactamase-producing Gram-negative organisms, given the stability of aztreonam against metallo-ß-lactamases plus the broad coverage of avibactam against AmpC ß-lactamases and ESBLs. This study aimed to evaluate the efficacy of the combination against four clinical isolates with defined but diverse ß-lactamase profiles. METHODS: The MICs of aztreonam were determined without and with avibactam (1, 2, 4, 8 and 16 mg/L). Using the MIC values, the static time-kill kinetic studies were designed to encompass aztreonam concentrations of 0.25, 0.5, 1, 2 and 4 times the MIC at the respective avibactam concentrations from 0 to 8 mg/L. Aztreonam and avibactam concentrations were determined by LC-MS/MS during the course of the time-kill kinetic studies to evaluate whether avibactam protects aztreonam from degradation. RESULTS: Three of the four isolates had aztreonam MICs ≥128 mg/L in monotherapy. Dramatically increasing susceptibility associated with a decrease in aztreonam MIC was observed with increasing avibactam concentration. Against all isolates, the combinations resulted in greater killing with a much lower dose requirement for aztreonam. The resulting changes in base-10 logarithm of cfu/mL at both the 10 h and 24 h references (versus 0 h) were synergistic. In contrast, a significantly higher concentration of aztreonam in the monotherapy was required to produce the same kill as that in the combination therapy, due to rapid aztreonam degradation in two isolates. CONCLUSIONS: The aztreonam/avibactam combination protects aztreonam from hydrolysis and provides synergy in antimicrobial activity against multiple ß-lactamase-expressing strains with a wide MIC range.

Application of Cervical Collars - An Analysis of Practical Skills of Professional Emergency Medical Care Providers.

BACKGROUND/OBJECTIVE: The application of a cervical collar is a standard procedure in trauma patients in emergency medicine. It is often observed that cervical collars are applied incorrectly, resulting in reduced immobilization of the cervical spine. The objective of this study was to analyze the practical skills of trained professional rescue personnel concerning the application of cervical collars. MATERIAL AND METHODS: Within emergency medical conferences, n = 104 voluntary test subjects were asked to apply a cervical collar to a training doll, wherein each step that was performed received an evaluation. Furthermore, personal and occupational data of all study participants were collected using a questionnaire. RESULTS: The test subjects included professional rescue personnel (80.8%) and emergency physicians (12.5%). The average occupational experience of all study participants in pre-clinical emergency care was 11.1±8.9 years. Most study participants had already attended a certified training on trauma care (61%) and felt "very confident" in handling a cervical collar (84%). 11% applied the cervical collar to the training doll without errors. The most common error consisted of incorrect adjustment of the size of the cervical collar (66%). No association was found between the correct application of the cervical collar and the occupational group of the test subjects (trained rescue personnel vs. emergency physicians) or the participation in certified trauma courses. CONCLUSION: Despite pronounced subjective confidence regarding the application of cervical collars, this study allows the conclusion that there are general deficits in practical skills when cervical collars are applied. A critical assessment of the current training contents on the subject of trauma care must, therefore, be demanded.

Deciphering tissue-induced Klebsiella pneumoniae lipid A structure.

The outcome of an infection depends on host recognition of the pathogen, hence leading to the activation of signaling pathways controlling defense responses. A long-held belief is that the modification of the lipid A moiety of the lipopolysaccharide could help Gram-negative pathogens to evade innate immunity. However, direct evidence that this happens in vivo is lacking. Here we report the lipid A expressed in the tissues of infected mice by the human pathogen Klebsiella pneumoniae. Our findings demonstrate that Klebsiella remodels its lipid A in a tissue-dependent manner. Lipid A species found in the lungs are consistent with a 2-hydroxyacyl-modified lipid A dependent on the PhoPQ-regulated oxygenase LpxO. The in vivo lipid A pattern is lost in minimally passaged bacteria isolated from the tissues. LpxO-dependent modification reduces the activation of inflammatory responses and mediates resistance to antimicrobial peptides. An lpxO mutant is attenuated in vivo thereby highlighting the importance of this lipid A modification in Klebsiella infection biology. Colistin, one of the last options to treat multidrug-resistant Klebsiella infections, triggers the in vivo lipid A pattern. Moreover, colistin-resistant isolates already express the in vivo lipid A pattern. In these isolates, LpxO-dependent lipid A modification mediates resistance to colistin. Deciphering the lipid A expressed in vivo opens the possibility of designing novel therapeutics targeting the enzymes responsible for the in vivo lipid A pattern.

Mycophenolic acid reverses TGF beta-induced cell motility, collagen matrix contraction and cell morphology in vitro.

The aim of this study was to elucidate functional and molecular effects of mycophenolic acid (MPA) on non-lymphatic, kidney epithelial cells treated with transforming growth factor (TGF). MPA effects were studied using HK2 cells incubated with EGF and TGF. The reversibility of these effects was verified using guanosine and 8-aminoguanosine. The following assays were applied: cell proliferation, viability, collagen matrix contraction, scratch wound closure, spindle index, FACS with anti-CD29 and anti-CD326, promoter demethylation of RAS protein activator like 1 (RASAL1), as well as gene expression of RASAL1, integrin 1ß (ITGB1) (CD29) and epithelial cell adhesion molecule (EpCam) (CD326). Cell proliferation was inhibited by increasing concentrations of MPA, whereas neither apoptosis nor cytotoxicity was detected. Stimulation with EGF and/or TGF led to a significant collagen matrix contraction that was successfully inhibited by MPA. In addition, scratch wound closure was inhibited by incubation with TGF alone or with EGF. Under the same conditions, cell morphology (spindle shape) and molecular phenotype (ITGB1(High)EpCam(Low)/ITGB1(Low)EpCam(High)) were both significantly changed, suggesting an epithelial to mesenchymal transformation. Cell morphology and motility, as well as molecular phenotype, were reversible after MPA treatment with TGF transformation in both presence/absence of EGF, thereby suggesting a correlation with the previously described antifibrotic effects of MPA. Dysregulation of TGF signal transduction appears to be related to progression of fibrosis. A TGF-transformed kidney epithelial cell line derived from human proximal tubules was used to study whether the immunosuppressive drug: MPA possesses any functional or molecular antifibrotic effects. Functional and morphological in vitro changes induced by both the TGF and epithelial-growth-factor were reversible by treatment with MPA. An inhibitory effect of MPA on the TGF pathway appears to be responsible for the previously described antifibrotic effects of the MPA in the COL4A3-deficient mouse model of renal fibrosis.

Association between biomarkers of endothelial injury and hypocoagulability in patients with severe sepsis: a prospective study.

INTRODUCTION: Patients with severe sepsis often present with concurrent coagulopathy, microcirculatory failure and evidence of vascular endothelial activation and damage. Given the critical role of the endothelium in balancing hemostasis, we investigated single-point associations between whole blood coagulopathy by thrombelastography (TEG) and plasma/serum markers of endothelial activation and damage in patients with severe sepsis. METHODS: A post-hoc multicenter prospective observational study in a subgroup of 184 patients from the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial. Study patients were admitted to two Danish intensive care units. Inclusion criteria were severe sepsis, pre-intervention whole blood TEG measurement and a plasma/serum research sample available from baseline (pre-intervention) for analysis of endothelial-derived biomarkers. Endothelial-derived biomarkers were measured in plasma/serum by enzyme-linked immunosorbent assay (syndecan-1, thrombomodulin, protein C (PC), tissue-type plasminogen activator and plasminogen activator inhibitor-1). Pre-intervention TEG, functional fibrinogen (FF) and laboratory and clinical data, including mortality, were retrieved from the trial database. RESULTS: Most patients presented with septic shock (86%) and pulmonary (60%) or abdominal (30%) focus of infection. The median (IQR) age was 67 years (59 to 75), and 55% were males. The median SOFA and SAPS II scores were 8 (6 to 10) and 56 (41 to 68), respectively, with 7-, 28- and 90-day mortality rates being 21%, 39% and 53%, respectively. Pre-intervention (before treatment with different fluids), TEG reaction (R)-time, angle and maximum amplitude (MA) and FF MA all correlated with syndecan-1, thrombomodulin and PC levels. By multivariate linear regression analyses, higher syndecan-1 and lower PC were independently associated with TEG and FF hypocoagulability at the same time-point: 100 ng/ml higher syndecan-1 predicted 0.64 minutes higher R-time (SE 0.25), 1.78 mm lower TEG MA (SE 0.87) and 0.84 mm lower FF MA (SE 0.42; all P < 0.05), and 10% lower protein C predicted 1.24 mm lower TEG MA (SE 0.31). CONCLUSIONS: In our cohort of patients with severe sepsis, higher circulating levels of biomarkers of mainly endothelial damage were independently associated with hypocoagulability assessed by TEG and FF. Endothelial damage is intimately linked to coagulopathy in severe sepsis. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00962156. Registered 13 July 2009.

Lack of correlation between Treg quantification assays in inflammatory bowel disease patients.

AIM: To compare the number of regulatory T-cells (Tregs) measured by flow cytometry with those obtained using a real-time quantitative PCR (qPCR) method in patients suffering from inflammatory bowel disease (IBD). METHODS: Tregs percentages obtained by both flow cytometry and qPCR methods in 35 adult IBD patients, 18 out of them with Crohn´s disease (CD) and 17 with ulcerative colitis (UC) were compared to each other as well as to scores on two IBD activity questionnaires using the Harvey Bradshaw Index (HBI) for CD patients and the Simple Colitis Clinical Activity Index (SCCAI) for UC patients. The Treg percentages by flow cytometry were defined as CD4(+)CD25(high)CD127(low)FOXP3(+) cells in peripheral blood mononuclear cells, whereas the Treg percentages by qPCR method were determined as FOXP3 promoter demethylation in genomic DNA. RESULTS: We found an average of 1.56% ± 0.78% Tregs by using flow cytometry, compared to 1.07% ± 0.53% Tregs by using qPCR in adult IBD patients. There were no significant correlations between either the percentages of Tregs measured by flow cytometry or qPCR and the HBI or SCCAI questionnaire scores in CD or UC patients, respectively. In addition, there was no correlation between Treg percentages measured by qPCR and those measured by flow cytometry (r = -0.06, P = 0.73; Spearman Rho). These data suggest that, either Treg-related immune function or the clinical scores in these IBD patients did not accurately reflect actual disease activity. Until the cause(s) for these differences are more clearly defined, the results suggest caution in interpreting studies of Tregs in various inflammatory disorders. CONCLUSION: The two methods did not produce equivalent measures of the percentage of total Tregs in the IBD patients studied which is consistent with the conclusion that Tregs subtypes are not equally detected by these two assays.

Additional bone graft accelerates healing of clavicle non-unions and improves long-term results after 8.9 years: a retrospective study.

BACKGROUND: Clavicle non-unions can occur after both conservative and operative treatment failure. Here, we investigated the outcome of patients with delayed fracture healing or non-unions of the clavicle. Patients underwent revision surgery by plate osteosynthesis of the clavicle with or without bone grafting. Our aim was to determine rates of bone healing and the functional long-term outcome. METHODS: The study population of 58 consecutive patients was divided into group 1 (n = 25; no bone graft) and group 2 (n = 33; iliac crest bone graft). Bone consolidation was determined by the Lane-Sandhu score preoperatively and after 2.2 ± 1.8 years, respectively. The functional long-term outcome was determined after 8.9 ± 2.7 years in all available patients (n = 30) by the Constant score, DASH (Disabilities of the Arm, Shoulder and Hand) score and SF-36, and clavicle length was measured by ultrasound as compared to the healthy side. RESULTS: Clavicle consolidation was achieved in 54 out of 58 patients (93.1%) after revision surgeries. The radiographic score and bone consolidation rates were significantly higher in group 2 (93.3%) as compared with 72% in group 1 (p = 0.02), resulting in a significantly shorter time to bone consolidation in group 2. Similarly, the relative risk for additional surgery after the first revision surgery was 4.7-fold higher in group 1 (p = 0.02). The long-term results showed overall very good results in DASH score (14.9 ± 16.5) and good results in Constant scores (77.9 ± 19.9). The group analyses found significantly better Constant scores and better visual analogue pain scale (VAS) numbers in group 2. Clavicle shortening appeared to affect the clinical results, and a mild correlation between shortening and Constant scores (R = -0.31) was found. CONCLUSIONS: This study shows high rates of bone healing and good functional outcomes after surgical revision of clavicle non-unions and further demonstrates that additional bone graft could significantly accelerate bone healing. This indicates that revision surgery of clavicle non-unions might preferably be done with additional bone graft, even if the surgeon considers that bone healing might be achieved without bone grafting.