[Curative effect of percutaneous microwave ablation therapy on hepatocellular carcinoma survival: a 15-year real-world study].

Objective: To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma. Methods: 2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival. Results: A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P < 0.001, especially for liver cancer 3.1~5.0 cm (P < 0.001). Conclusion: Microwave ablation therapy is a safe and effective method for BCLC stage 0-B, with significantly enhanced technical efficacy and survival rate over time.

Measurement of polarization observables T, P, and H in π0 and η photoproduction off quasi-free nucleons.

The target asymmetry T, recoil asymmetry P, and beam-target double polarization observable H were determined in exclusive π0 and η photoproduction off quasi-free protons and, for the first time, off quasi-free neutrons. The experiment was performed at the electron stretcher accelerator ELSA in Bonn, Germany, with the Crystal Barrel/TAPS detector setup, using a linearly polarized photon beam and a transversely polarized deuterated butanol target. Effects from the Fermi motion of the nucleons within deuterium were removed by a full kinematic reconstruction of the final state invariant mass. A comparison of the data obtained on the proton and on the neutron provides new insight into the isospin structure of the electromagnetic excitation of the nucleon. Earlier measurements of polarization observables in the γp→π0p and γp→ηp reactions are confirmed. The data obtained on the neutron are of particular relevance for clarifying the origin of the narrow structure in the ηn system at W=1.68GeV. A comparison with recent partial wave analyses favors the interpretation of this structure as arising from interference of the S11(1535) and S11(1650) resonances within the S11-partial wave.

Janus face of complement-driven neutrophil activation during sepsis.

During local and systemic inflammation, the complement system and neutrophil granulocytes are activated not only by pathogens, but also by released endogenous danger signals. It is recognized increasingly that complement-mediated neutrophil activation plays an ambivalent role in sepsis pathophysiology. According to the current definition, the onset of organ dysfunction is a hallmark of sepsis. The preceding organ damage can be caused by excessive complement activation and neutrophil actions against the host, resulting in bystander injury of healthy tissue. However, in contrast, persistent and overwhelming inflammation also leads to a reduction in neutrophil responsiveness as well as complement components and thus may render patients at enhanced risk of spreading infection. This review provides an overview on the molecular and cellular processes that link complement with the two-faced functional alterations of neutrophils in sepsis. Finally, we describe novel tools to modulate this interplay beneficially in order to improve outcome.

COVID or not COVID: attributing and reporting cause of death in a community cohort.

OBJECTIVES: In Germany, deaths of SARS-CoV-2-positive persons are reported as 'death related to SARS-CoV-2/COVID-19' to the Robert Koch Institute, Germany's main infectious disease institution. In 177 COVID-19-associated deaths reported in Regensburg, Germany, from October 2020 to January 2021, we investigated how deaths following SARS-CoV-2 infection were reported and whether cases with a death attributed to SARS-CoV-2 (COVID-19 death [CD]) differed from cases with a reported death from other causes (non-COVID-19 death [NCD]). STUDY DESIGN: This was an observational retrospective cohort study. METHODS: We analysed descriptive data on the numbers of cases, deaths, age, sex, symptoms and hospitalizations. We calculated odds ratios (ORs) with 95% confidence intervals (95% CIs) and performed Chi-squared/Fisher's exact test for categorical variables and the Wilcoxon rank-sum test for comparison of medians. RESULTS: Deaths attributed to COVID-19 occurred primarily in elderly patients. The mortality rate and the case fatality ratio (CFR) increased with age. The median age and the prevalence of risk factors were similar between CD and NCD. Respiratory symptoms and pneumonia at the time of diagnosis were associated with death reported as CD. The odds of CD attribution in cases hospitalized because of COVID-19 were 6-fold higher than the odds of NCD (OR: 6.00; 95% CI: 1.32 to 27.22). CONCLUSIONS: Respiratory symptoms/pneumonia at the time of diagnosis and hospitalization due to COVID-19 were associated with attributing a death to COVID-19. Numbers of COVID deaths need to be interpreted with caution. Criteria that facilitate attributing the cause of death among SARS-CoV-2 cases more uniformly could make these figures more comparable.

Measurement of the helicity asymmetry E for the reaction γ p → π 0 p : The CBELSA/TAPS Collaboration.

A measurement of the double-polarization observable E for the reaction γ p → π 0 p is reported. The data were taken with the CBELSA/TAPS experiment at the ELSA facility in Bonn using the Bonn frozen-spin butanol (C 4 H 9 OH) target, which provided longitudinally-polarized protons. Circularly-polarized photons were produced via bremsstrahlung of longitudinally-polarized electrons. The data cover the photon energy range from E γ = 600 to 2310 MeV and nearly the complete angular range. The results are compared to and have been included in recent partial wave analyses.

Crucial role of the terminal complement complex in chondrocyte death and hypertrophy after cartilage trauma.

OBJECTIVE: Innate immune response and particularly terminal complement complex (TCC) deposition are thought to be involved in the pathogenesis of posttraumatic osteoarthritis. However, the possible role of TCC in regulated cell death as well as chondrocyte hypertrophy and senescence has not been unraveled so far and was first addressed using an ex vivo human cartilage trauma-model. DESIGN: Cartilage explants were subjected to blunt impact (0.59 J) and exposed to human serum (HS) and cartilage homogenate (HG) with or without different potential therapeutics: RIPK1-inhibitor Necrostatin-1 (Nec), caspase-inhibitor zVAD, antioxidant N-acetyl cysteine (NAC) and TCC-inhibitors aurintricarboxylic acid (ATA) and clusterin (CLU). Cell death and hypertrophy/senescence-associated markers were evaluated on mRNA and protein level. RESULTS: Addition of HS resulted in significantly enhanced TCC deposition on chondrocytes and decrease of cell viability after trauma. This effect was potentiated by HG and was associated with expression of RIPK3, MLKL and CASP8. Cytotoxicity of HS could be prevented by heat-inactivation or specific inhibitors, whereby combination of Nec and zVAD as well as ATA exhibited highest cell protection. Moreover, HS+HG exposition enhanced the gene expression of CXCL1, IL-8, RUNX2 and VEGFA as well as secretion of IL-6 after cartilage trauma. CONCLUSIONS: Our findings imply crucial involvement of the complement system and primarily TCC in regulated cell death and phenotypic changes of chondrocytes after cartilage trauma. Inhibition of TCC formation or downstream signaling largely modified serum-induced pathophysiologic effects and might therefore represent a therapeutic target to maintain the survival and chondrogenic character of cartilage cells.

High-Precision Determination of Oxygen K_{α} Transition Energy Excludes Incongruent Motion of Interstellar Oxygen.

We demonstrate a widely applicable technique to absolutely calibrate the energy scale of x-ray spectra with experimentally well-known and accurately calculable transitions of highly charged ions, allowing us to measure the K-shell Rydberg spectrum of molecular O_{2} with 8 meV uncertainty. We reveal a systematic ∼450 meV shift from previous literature values, and settle an extraordinary discrepancy between astrophysical and laboratory measurements of neutral atomic oxygen, the latter being calibrated against the aforementioned O_{2} literature values. Because of the widespread use of such, now deprecated, references, our method impacts on many branches of x-ray absorption spectroscopy. Moreover, it potentially reduces absolute uncertainties there to below the meV level.

Observation of the pη

Data on the beam asymmetry Σ in the photoproduction of η mesons off protons are reported for tagged photon energies from 1130 to 1790 MeV (mass range from W=1748 MeV to W=2045 MeV). The data cover the full solid angle that allows for a precise moment analysis. For the first time, a strong cusp effect in a polarization observable has been observed that is an effect of a branch-point singularity at the pη^{'} threshold [E_{γ}=1447 MeV (W=1896 MeV)]. The latest BnGa partial wave analysis includes the new beam asymmetry data and yields a strong indication for the N(1895)1/2^{-} nucleon resonance, demonstrating the importance of including all singularities for a correct determination of partial waves and resonance parameters.

Specific Heat Study of 1D and 2D Excitations in the Layered Frustrated Quantum Antiferromagnets Cs_{2}CuCl_{4-x}Br_{x}.

We report an experimental and theoretical study of the low-temperature specific heat C and magnetic susceptibility χ of the layered anisotropic triangular-lattice spin-1/2 Heisenberg antiferromagnets Cs_{2}CuCl_{4-x}Br_{x} with x=0, 1, 2, and 4. We find that the ratio J^{'}/J of the exchange couplings ranges from 0.32 to ≈0.78, implying a change (crossover or quantum phase transition) in the materials' magnetic properties from one-dimensional (1D) behavior for J^{'}/J<0.6 to two-dimensional (2D) behavior for J^{'}/J≈0.78. For J^{'}/J<0.6, realized for x=0, 1, and 4, we find a magnetic contribution to the low-temperature specific heat, C_{m}∝T, consistent with spinon excitations in 1D spin-1/2 Heisenberg antiferromagnets. Remarkably, for x=2, where J^{'}/J≈0.78 implies a 2D magnetic character, we also observe C_{m}∝T. This finding, which contrasts the prediction of C_{m}∝T^{2} made by standard spin-wave theories, shows that Fermi-like statistics also plays a significant role for the magnetic excitations in spin-1/2 frustrated 2D antiferromagnets.

A pilot study of hyperoxemia on neurological injury, inflammation and oxidative stress.

BACKGROUND: Normobaric hyperoxia is used to alleviate secondary brain ischaemia in patients with traumatic brain injury (TBI), but clinical evidence is limited and hyperoxia may cause adverse events. METHODS: An open label, randomised controlled pilot study comparing blood concentrations of reactive oxygen species (ROS), interleukin 6 (IL-6) and neuron-specific enolase (NSE) between two different fractions of inspired oxygen in severe TBI patients on mechanical ventilation. RESULTS: We enrolled 27 patients in the Fi O2 0.40 group and 38 in the Fi O2 0.70 group; 19 and 23 patients, respectively, completed biochemical analyses. In baseline, there were no differences between Fi O2 0.40 and Fi O2 0.70 groups, respectively, in ROS (64.8 nM [22.6-102.1] vs. 64.9 nM [26.8-96.3], P = 0.80), IL-6 (group 92.4 pg/ml [52.9-171.6] vs. 94.3 pg/ml [54.8-133.1], P = 0.52) or NSE (21.04 ug/l [14.0-30.7] vs. 17.8 ug/l [14.1-23.9], P = 0.35). ROS levels did not differ at Day 1 (24.2 nM [20.6-33.5] vs. 29.2 nM [22.7-69.2], P = 0.10) or at Day 2 (25.4 nM [21.7-37.4] vs. 47.3 nM [34.4-126.1], P = 0.95). IL-6 concentrations did not differ at Day 1 (112.7 pg/ml [65.9-168.9) vs. 83.9 pg/ml [51.8-144.3], P = 0.41) or at Day 3 (55.0 pg/ml [34.2-115.6] vs. 49.3 pg/ml [34.4-126.1], P = 0.95). NSE levels did not differ at Day 1 (15.9 ug/l [9.0-24.3] vs. 15.3 ug/l [12.2-26.3], P = 0.62). There were no differences between groups in the incidence of pulmonary complications. CONCLUSION: Higher fraction of inspired oxygen did not increase blood concentrations of markers of oxidative stress, inflammation or neurological injury or the incidence of pulmonary complications in severe TBI patients on mechanical ventilation.

Assessing the cumulative impacts of geographically isolated wetlands on watershed hydrology using the SWAT model coupled with improved wetland modules.

Despite recognizing the importance of wetlands in the Coastal Plain of the Chesapeake Bay Watershed (CBW) in terms of ecosystem services, our understanding of wetland functions has mostly been limited to individual wetlands and overall catchment-scale wetland functions have rarely been investigated. This study is aimed at assessing the cumulative impacts of wetlands on watershed hydrology for an agricultural watershed within the Coastal Plain of the CBW using the Soil and Water Assessment Tool (SWAT). We employed two improved wetland modules for enhanced representation of physical processes and spatial distribution of riparian wetlands (RWs) and geographically isolated wetlands (GIWs). This study focused on GIWs as their hydrological impacts on watershed hydrology are poorly understood and GIWs are poorly protected. Multiple wetland scenarios were prepared by removing all or portions of the baseline GIW condition indicated by the U.S. Fish and Wildlife Service National Wetlands Inventory geospatial dataset. We further compared the impacts of GIWs and RWs on downstream flow (i.e., streamflow at the watershed outlet). Our simulation results showed that GIWs strongly influenced downstream flow by altering water transport mechanisms in upstream areas. Loss of all GIWs reduced both water routed to GIWs and water infiltrated into the soil through the bottom of GIWs, leading to an increase in surface runoff of 9% and a decrease in groundwater flow of 7% in upstream areas. These changes resulted in increased variability of downstream flow in response to extreme flow conditions. GIW loss also induced an increase in month to month variability of downstream flow and a decrease in the baseflow contribution to streamflow. Loss of all GIWs was shown to cause a greater fluctuation of downstream flow than loss of all RWs for this study site, due to a greater total water storage capacity of GIWs. Our findings indicate that GIWs play a significant role in controlling hydrological processes in upstream areas and downstream flow and, therefore, protecting GIWs is important for enhanced hydrological resilience to extreme flow conditions in this region.

[Single-port VATS-assisted internal fixation of serial rib fractures]. / "Single-port-VATS"-assistierte Osteosynthese von Rippenserienfrakturen.

This article describes the operative stabilization of a flail chest due to traumatic serial rib fractures with extensive chest wall deformation and respiratory insufficiency. Initial conservative treatment including systemic and regional pain management and non-invasive positive pressure ventilation did not improve the pain or ventilation. Therefore, a single-port video-assisted thoracoscopic surgery (VATS) assisted internal fixation of the ribs was performed. The thoracoscopy enabled easy repositioning of the ribs and additionally an estimation of intrathoracic injuries.

[Effect of different medication time prior to corneal refractive surgery on tear film stability].

Objective: To investigate the effect of different medication time prior to corneal refractive surgery on tear film stability. Methods: Prospective cohort study. A total of 60 patients (60 eyes), including 38 males (63.3%) and 22 females (37.7%) with an average age of (24.2±5.1) years (form 18 to 37 years), who had planned for corneal refractive surgery with normal ocular surface disease index score were included in this study. The patients were divided into 1d group (medication of 1 day, 30 eyes) and 3d group (medication of 3 days, 30 eyes) randomly. The first tear break up time (FBUT), the average tear break up time (AVBUT) and the dry eye grade score were recorded on the examination day and the operation day with Keratograph 5M. The difference of FBUT and AVBUI between the two groups was compared with the independent sample t test. The difference of FBUT and AVBUT between the examination day and the operation day was compared with the paired t test. The difference of the dry eye classification between the two groups was compared using chi-square test. Results: The FBUT and AVBUT of 1d group and 3d group were (10.89±5.19)s and (10.88±6.82)s, (16.24±3.62)s and (16.21±4.74)s respectively in preoperative examination, and (10.65±6.03)s and (8.14±5.75)s, (15.14±5.30)s and (12.86±5.92)s respectively in operation day. There was no significant difference in FBUT and AVBUT between the two groups (t=0.01, 1,47, 0.02, 1.44; P>0.05). However, in the 3d group, the AVBUT of operation day decreased as compared with that of the examination day, and the difference was statistically significant (t=2.31, P<0.05). There was no significant difference in the distribution of dry eye classification between the two groups (χ(2)=0.07, 3.36; P>0.05). Conclusion: Both of medication of 1 day and medication of 3 days prior to corneal refractive surgery can provide a similar tear film stability, however more attention should be paid to the medication for patients with asymptomatic but abnormal BUT. (Chin J Ophthalmol, 2018, 54: 744-747).

Complement C5a-Induced Changes in Neutrophil Morphology During Inflammation.

The complement and neutrophil defence systems, as major components of innate immunity, are activated during inflammation and infection. For neutrophil migration to the inflamed region, we hypothesized that the complement activation product C5a induces significant changes in cellular morphology before chemotaxis. Exposure of human neutrophils to C5a dose- and time-dependently resulted in a rapid C5a receptor-1 (C5aR1)-dependent shape change, indicated by enhanced flow cytometric forward-scatter area values. Similar changes were observed after incubation with zymosan-activated serum and in blood neutrophils during murine sepsis, but not in mice lacking the C5aR1. In human neutrophils, Amnis high-resolution digital imaging revealed a C5a-induced decrease in circularity and increase in the cellular length/width ratio. Biomechanically, microfluidic optical stretching experiments indicated significantly increased neutrophil deformability early after C5a stimulation. The C5a-induced shape changes were inhibited by pharmacological blockade of either the Cl-/HCO3--exchanger or the Cl- -channel. Furthermore, actin polymerization assays revealed that C5a exposure resulted in a significant polarization of the neutrophils. The functional polarization process triggered by ATP-P2X/Y-purinoceptor interaction was also involved in the C5a-induced shape changes, because pretreatment with suramin blocked not only the shape changes but also the subsequent C5a-dependent chemotactic activity. In conclusion, the data suggest that the anaphylatoxin C5a regulates basic neutrophil cell processes by increasing the membrane elasticity and cell size as a consequence of actin-cytoskeleton polymerization and reorganization, transforming the neutrophil into a migratory cell able to invade the inflammatory site and subsequently clear pathogens and molecular debris.

High loading of polygenic risk in cases with chronic schizophrenia.

Genomic risk profile scores (GRPSs) have been shown to predict case-control status of schizophrenia (SCZ), albeit with varying sensitivity and specificity. The extent to which this variability in prediction accuracy is related to differences in sampling strategies is unknown. Danish population-based registers and Neonatal Biobanks were used to identify two independent incident data sets (denoted target and replication) comprising together 1861 cases with SCZ and 1706 controls. A third data set was a German prevalent sample with diagnoses assigned to 1773 SCZ cases and 2161 controls based on clinical interviews. GRPSs were calculated based on the genome-wide association results from the largest SCZ meta-analysis yet conducted. As measures of genetic risk prediction, Nagelkerke pseudo-R(2) and variance explained on the liability scale were calculated. GRPS for SCZ showed positive correlations with the number of psychiatric admissions across all P-value thresholds in both the incident and prevalent samples. In permutation-based test, Nagelkerke pseudo-R(2) values derived from samples enriched for frequently admitted cases were found to be significantly higher than for the full data sets (Ptarget=0.017, Preplication=0.04). Oversampling of frequently admitted cases further resulted in a higher proportion of variance explained on the liability scale (improvementtarget= 50%; improvementreplication= 162%). GRPSs are significantly correlated with chronicity of SCZ. Oversampling of cases with a high number of admissions significantly increased the amount of variance in liability explained by GRPS. This suggests that at least part of the effect of common single-nucleotide polymorphisms is on the deteriorative course of illness.

Does obesity complicate regional anesthesia and result in longer decision to delivery time for emergency cesarean section?

BACKGROUND: Maternal obesity can cause problems with anesthesia and surgery which may be reflected in emergency cesarean sections (CS) as an increased decision-to-delivery interval (DDI). AIM: To study the association of elevated maternal BMI with DDI and the failure of regional anesthesia. METHODS: Eight hundred and forty-two consecutive emergency CSs during a period of 1 year in a tertiary hospital were studied retrospectively. DDIs were analyzed in Crash and < 30-min urgency categories (n = 528), while the time required to establish regional anesthesia and its success were analyzed for all emergency CS cases. RESULTS: The urgency distribution of the CSs was 11%, 52%, and 37% in Crash, < 30-min, and > 30-min urgency categories respectively. Increased BMI was associated with longer DDI time in the < 30-min urgency category (33(13-176) vs. 38(18-118) min; P < 0.05 for BMI < 30 and > 35 group respectively). Regional anesthesia failures (new regional anesthesia, conversion to general anesthesia, or complaint of pain during surgery) took place in 3.7%, 6.8%, and 8.5% in the BMI < 30, 30-35, and > 35 groups respectively (P = 0.021). Epidural top-up resulted in shorter DDI and time delay between arrival at the operating room and skin incision across all urgency and BMI groups than combined spinal epidural (CSE) anesthesia. CONCLUSION: Higher BMI was associated with longer DDI and more regional anesthesia failures. Epidural top-up was faster than CSE for establishing CS anesthesia.

[The Ulm trauma track : Trauma care and research as focal points for medical students]. / Der Ulmer Trauma-Track : Traumaversorgung und -forschung als Schwerpunktsetzung im Medizinstudium.

BACKGROUNDS AND OBJECTIVES: As part of the expansion of the site-specific education profile of the medical curriculum MED@ULM of the University of Ulm, a new track "trauma care and trauma research" was established in the winter semester 2012/2013. The acceptance of the track was evaluated during the winter semester 2013/2014. MATERIAL AND METHODS: The 6-semester track extends the existing curriculum by offering subjects in trauma management and trauma research to students of human medicine. A central aim of the track is to promote medical professional competence, expertise in emergency care and competence in trauma-related scientific work and research. Central learning contents could be intensified in newly established emergency simulation training. Additionally, participating students have to perform a doctoral thesis on an obligatory trauma-related experimental subject. A first analysis study focusing on the learning style of the participating students (n = 17) and a control group consisting of members of the same semester (n = 20) was performed using the Kolb learning style inventory. In a validated evaluation in the winter semesters 2013/2014 and 2014/2015, the students were asked about their expectations and experience with the track, criticisms, suggestions and satisfaction with the study conditions. The data were analyzed using descriptive statistics. RESULTS: The analysis of the students' preferred learning styles revealed no differences between track students and the control group. Most of the students considered the track as a form of personal further education. The students had high expectations of practical skills with relevance to the clinical daily routine, learning scientific methods and preparing their thesis. The track students were more critical with regard to the study conditions than the control group students, although the track students of the third semester still judged their studies to be more interesting than the track students of the first semester and the control group. CONCLUSION: With the introduction of the new trauma track into the curriculum of the medical curriculum MED@ULM of the University of Ulm, a further possibility for medical students to focus on their own individual options was established. At least half of the track students wanted to be later active in the triad of patient care, teaching and research. Further investigations are necessary to determine whether the establishment of the trauma track has a positive influence on the number of new recruits in trauma surgery and anesthesiology.

Psychological aptitude evaluation of the special forces candidate.

INTRODUCTION: Changes in recruitment procedures reduced early dismissal rates from Swiss military basic recruitment schools; however, such improvements were not reflected in premature discharge rates from the special forces (SF) (Grenadier) recruitment school. METHOD: A six-item questionnaire designed to identify recruits likely to be subject to premature dismissal on psychological or psychiatric grounds was developed and prospectively validated. The questionnaire was based on an analysis of medical and psychiatric/psychological records of 26 recruits dismissed from a SF recruitment school. Six items were identified that appeared to have prognostic value for early discharge. These six questions were submitted to the remaining applicants in the recruitment school by a suitably qualified psychologist or psychiatrist and effectively identified candidates who would be discharged early. Based on these results a 0-6 scale was developed and applied prospectively to subsequent Grenadier recruitment courses. RESULTS: Statistical analysis showed that 75% of candidates with the lowest scores would eventually complete the course and that no candidates with highest scores would subsequently complete the recruitment course. DISCUSSION: Prospective studies in subsequent recruitment courses candidates with high scores were classified as not qualified to enter the course, and those with intermediate scores were subject to additional in-depth interviews with a psychologist or psychiatrist to determine their suitability. In the following courses a correlation was established between the questionnaire score and week of discharge for those discharged. Application of this method during subsequent recruitment courses has reduced early dismissal from Swiss SF recruitment schools.

The crucial role of neutrophil granulocytes in bone fracture healing.

Delayed bone fracture healing and the formation of non-unions represent an important clinical problem, particularly in polytrauma patients who suffer from posttraumatic systemic inflammation. However, the underlying pathomechanisms remain unclear. Neutrophil granulocytes are crucial effector cells in the systemic immune response and represent the most abundant immune cell population in the early fracture haematoma. Here we investigated the role of neutrophils in a mouse model of uncomplicated fracture healing and compromised fracture healing induced by an additional thoracic trauma. Twenty four hours before injury, 50 % of the mice were systemically treated with an anti-Ly-6G-antibody to reduce neutrophil numbers. In the isolated fracture model, Ly-6G-Ab treatment significantly increased the concentration of both pro- and anti-inflammatory cytokines, including interleukin (IL)-6 and IL-10, and chemokines, for example, C-X-C motif ligand 1 (CXCL1) and monocyte chemotactic protein-1 (MCP-1), in the fracture haematoma. Monocyte/macrophage recruitment was also significantly enhanced. After 21 d, bone regeneration was considerably impaired as demonstrated by significantly diminished bone content and impaired mechanical properties of the fracture callus. These results indicate that undisturbed neutrophil recruitment and function in the inflammatory phase after fracture is crucial to initiate downstream responses leading to bone regeneration. In the combined trauma model, the reduction of neutrophil numbers ameliorated pulmonary inflammation but did not provoke any significant effect on bone regeneration, suggesting that neutrophils may not play a crucial pathomechanistic role in compromised fracture healing induced by an additional thoracic trauma.

Course of hepatitis C virus (HCV) RNA and HCV core antigen testing are predictors for reaching sustained virologic response in liver transplant recipients undergoing sofosbuvir treatment in a real-life setting.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with reduced graft survival in orthotopic liver transplant recipients. Treatment with the new direct-acting antivirals (DAAs) is safe and efficient, but no reliable predictive factors for sustained virologic response (SVR) have been identified so far. The HCV core antigen assay (HCV-core-Ag) is a new, inexpensive, and efficient method to detect viral antigens, but the value of this technique to predict treatment response in orthotopic liver transplantation (OLT) patients is still unclear. METHODS: All OLT patients who were treated with a sofosbuvir-based antiviral regimen at our center between March 2014 and August 2014 were included in the analysis (n = 20). HCV-core-Ag and HCV RNA (polymerase chain reaction [PCR]) were determined at each visit. Primary endpoints of this study were SVR at 4 or 12 weeks after end of treatment (SVR 4 and SVR 12). RESULTS: HCV-core-Ag tested negative after a median of 2 weeks (range 1-16 weeks) while PCR tests became negative after a median of 4 weeks (range 2-12 weeks). Time until PCR negativity and until HCV-core-Ag negativity showed a good correlation (R = 0.711, P < 0.001, Fig. ). Seventeen of 20 patients (85%) achieved SVR 12. SVR 12 was associated with a short time interval between treatment start and HCV PCR negativity (P = 0.005) or HCV-core-Ag negativity (P = 0.003, Mann-Whitney test). No severe side effects were observed. CONCLUSIONS: DAA treatment is safe and well tolerated in OLT. The time points of HCV-core-Ag loss and PCR negativity were predictors of SVR 12.