[A 44 year old patient presenting with Ewing's sarcoma of the big toe]. / 44-jährige Patientin mit Ewing­Sarkom der Großzehengrundphalanx.

We present the case of a patient with osseous Ewing's sarcoma of the big toe occurring during the healing process after a fracture of the little toe, which significantly delayed diagnosis, despite striking findings on imaging. We subsequently performed further diagnostics, neoadjuvant chemotherapy, tumor resection in the form of a resection of the first ray, and adjuvant chemotherapy. This case shows that the occurrence of a secondary disease should always be considered in untypical courses of healing.

Effects of Rest Interval on Strength Recovery in Breast Cancer Survivors.

The purpose of this study was to compare the acute effect of 2 different resting intervals (RI) between sets of isokinetic knee extension exercise on peak torque (PT) and total work (TW) in breast cancer survivors (BCS) and control group (CNT). 16 BCS (52±4 years) and 14 CNT (53±6 years) performed 3 sets of 10 unilateral isokinetic knee extension repetitions at 60°.s(- 1) on 2 separate days with 2 different RI between sets (1 and 2 min). There was a significant interaction between groups vs. exercise sets (p=0.03) and RI vs. exercise sets (p<0.001) for PT. PT was greater in CNT at 1(st) and 2(nd) sets compared to BCS group (CNT, 133.4±20.8 and BCS 107.6±19.9 Nm, p=0.012 and CNT, 118.9±19.6 and BCS, 97.1±15.9 Nm, p=0.045, respectively). The TW of the knee extensor was significant greater in CNT than BCS group for all 3 knee extension exercise sets. In conclusion, the present study suggests that Breast Cancer Survivors women may need a longer rest interval (longer than 2 min) to be able to fully recover during a 3 sets of isokinetic knee extension exercise training session.

Cardiac Adaptation of the Maternal Heart During Pregnancy: A Color-Coded Tissue Doppler Imaging Study--Feasibility, Reproducibility and Course during Pregnancy.

PURPOSE: Tissue Doppler imaging (TDI) allows the noninvasive quantification of global and regional myocardial function. Since there are changing loading conditions during pregnancy, this study aimed to determine maternal myocardial adaptation in normal pregnancy with TDI and tracking of the heart cycle. PATIENTS AND METHODS: 106 pregnant women, mean age of 33.4 years at baseline, prospectively underwent a total of 161 color-coded tissue Doppler echocardiography samples throughout pregnancy. In further offline analysis of the global and regional myocardial function of the basal segments, maximum tissue velocities at systole (Sm), in the early filling phase of diastole (Em) and during atrial contraction (Am) were assessed. RESULTS: From those stored samples, S-wave, E-wave and A-wave velocities could be obtained with a feasibility of 94.8 % and with good inter- and intra-observer variability. S-wave velocity first showed an increase during early pregnancy followed by a decline to baseline characteristics at the 3 rd trimester. The E-wave velocity declined throughout pregnancy. The A-wave velocity increased continuously. These alterations result in a continuous decline of Em/Am ratio as pregnancy advances. CONCLUSION: Alterations in tissue velocities during pregnancy reflect maturational changes that mimic "diastolic dysfunction". Based on an understanding of those normal physiological changes, TDI may therefore assist in the monitoring and/or detecting of subclinical myocardial dysfunction during pregnancy.

Characteristics and treatment outcomes of 69 cases with early prosthetic joint infections of the hip and knee.

PURPOSE: Early prosthetic joint infection (PJI) can be treated with an intensive surgical debridement and implant retention (DAIR) of the prosthesis if (1) the prosthesis is stable, (2) the pathogen is not a difficult-to-treat microorganism, (3) symptoms have lasted for <3 weeks and (4) a sinus tract is absent. METHODS: We retrospectively evaluated the treatment outcome of early PJI in the hip and knee in a single orthopaedic centre. An early PJI was defined as a prosthesis infection within 3 months after primary implantation or revision surgery for a non-infectious cause. RESULTS: We identified 69 patients with confirmed early PJI, with a median age of 71 (range 33-84) years. Only 64 % presented with ≥2 acute signs of infection. The most commonly isolated bacteria were coagulase-negative staphylococci (38 %) and Staphylococcus aureus (25 %). Surgical procedures included DAIR (50 cases, 69 %) and two-stage exchange (19 cases, 31 %). At last follow-up, five of remaining living 67 patients (7.5 %) had a relapse of infection. The overall relapse-free survival of the prosthesis after 2 years was 92.3 % (95 % confidence interval 82-97 %) with no significant difference between DAIR and exchange of prosthesis. CONCLUSION: Our data suggest that an early PJI should be treated with DAIR as a less invasive procedure whenever possible according to the established treatment algorithm.

Priorities, opportunities, and challenges for integrating microorganisms into Earth system models for climate change prediction.

Climate change jeopardizes human health, global biodiversity, and sustainability of the biosphere. To make reliable predictions about climate change, scientists use Earth system models (ESMs) that integrate physical, chemical, and biological processes occurring on land, the oceans, and the atmosphere. Although critical for catalyzing coupled biogeochemical processes, microorganisms have traditionally been left out of ESMs. Here, we generate a "top 10" list of priorities, opportunities, and challenges for the explicit integration of microorganisms into ESMs. We discuss the need for coarse-graining microbial information into functionally relevant categories, as well as the capacity for microorganisms to rapidly evolve in response to climate-change drivers. Microbiologists are uniquely positioned to collect novel and valuable information necessary for next-generation ESMs, but this requires data harmonization and transdisciplinary collaboration to effectively guide adaptation strategies and mitigation policy.

Relatively high serum vitamin D levels do not impair the antibody response to encapsulated bacteria.

Vitamin D skews the immune system towards a more tolerogenic state. Therefore, a relatively high vitamin D status, i.e., within the normal physiological range, might result in a lower antibody response to infection and vaccination. We hypothesized, however, that vitamin D is primarily important in establishing immune homeostasis, implying that a relatively high vitamin D status would not hamper an adequate antibody response against pathogens. Our results show that the vitamin D status did not differ between responders and hypo-responders in patients infected with Streptococcus pneumoniae, as well as patients vaccinated against S. pneumoniae, Neisseria meningitidis type C (MenC), and/or Haemophilus influenzae type b (Hib). Furthermore, specific IgG titers were not associated with the vitamin D status in patients vaccinated against S. pneumoniae and MenC, while there was a weak inverse association in Hib-vaccinated patients. These data indicate that a relatively high vitamin D status does not seem to hamper an adequate antibody response upon infection or vaccination, suggesting that vitamin D, in this setting, is not immunosuppressive.

Characteristics and outcome of 16 periprosthetic shoulder joint infections.

PURPOSE: Shoulder arthroplasties are increasingly performed, but data on periprosthetic joint infections (PJI) in this anatomical position are limited. We retrospectively investigated the characteristics and outcome of shoulder PJI after primary arthroplasty from 1998 to 2010 in a single centre. METHODS: Periprosthetic joint infection was defined as periprosthetic purulence, presence of sinus tract or microbial growth. A Kaplan-Meier survival method was used to estimate relapse-free survival of prosthesis. RESULTS: From 1,571 primary shoulder prostheses, we evaluated 16 patients with a PJI at different stages, i.e, early (n = 4), delayed (n = 6) and late (n = 6) infections. The median patient age was 67 (range 53-86) years, and 69 % were females. The most commonly isolated microorganism was Propionibacterium acnes in 38 % of patients (monobacterial in four and polymicrobial in two patients). In 14 of the 16 patients, surgical interventions consisting of debridement and implant retention (6 patients), exchange (7) and explantation (1) were performed. Four patients had a relapse of infection with P. acnes (n = 3) or Bacteroides fragilis (n = 1). The relapse-free survival of the prosthesis was 75 % (95 % confidence interval 46-90 %) after 1 and 2 years, 100 % in six patients following the treatment algorithm for hip and knee PJI and 60 % in 10 patients not followed up. All but one of the relapses were previously treated without exchange of the prosthesis. CONCLUSIONS: As recommended for hip and knee PJI, we suggest treating shoulder PJI with a low-grade infection by microorganisms such as P. acnes with an exchange of the prosthesis. Cohort studies are needed to verify our results.

Factors associated with rifampin resistance in staphylococcal periprosthetic joint infections (PJI): a matched case-control study.

PURPOSE: Rifampin combination therapy plays an important role in the management of staphylococcal periprosthetic joint infection (PJI). However, the emergence of rifampin resistance is a feared complication. We retrospectively analysed predetermined potential risk factors in patients with rifampin-resistant staphylococcal PJI in a multicentre case-control study. METHODS: Cases (n = 48) were defined as PJI caused by rifampin-resistant staphylococci. Rifampin-susceptible controls (n = 48) were matched for microorganism and type of prosthetic joint. Uni- and multivariable conditional logistic regression analyses were performed to estimate odds ratios (OR) with 95 % confidence intervals (95 % CI). RESULTS: Forty-eight cases (31 men; median age 67 years; age range 39-88 years) with hip- (n = 29), knee- (n = 13), elbow- (n = 4), shoulder- (n = 1) or ankle-PJI (n = 1) were enrolled in the study. Staphylococcus aureus and coagulase-negative staphylococci were isolated in ten and 38 episodes, respectively. Most of the cases (n = 44, 92 %) had a previous PJI, and 93 % (n = 41) of these had been treated with rifampin. There was an independent association of emergence of rifampin resistance with male sex (OR 3.6, 95 % CI 1.2-11), ≥ 3 previous surgical revisions (OR 4.7, 95 % CI 1.6-14.2), PJI treatment with high initial bacterial load (inadequate surgical debridement, <2 weeks of intravenous treatment of the combination medication; OR 4.9, 95 % CI 1.6-15) and inadequate rifampin therapy (OR 5.4, 95 % CI 1.2-25). CONCLUSIONS: Based on our results, extensive surgical debridement and adequate antibiotic therapy are needed to prevent the emergence of rifampin resistance.

Replacement of aprotinin by ε-aminocaproic acid in infants undergoing cardiac surgery: consequences for blood loss and outcome.

BACKGROUND: Once aprotinin was no longer available for clinical use, ε-aminocaproic acid (EACA) and tranexamic acid became the only two options for antifibrinolytic therapy. We compared aprotinin and EACA with respect to their blood-sparing efficacy and other major clinical outcome criteria in infants undergoing cardiac surgery. METHODS: We retrospectively analysed data from a large consecutive cohort of infants (n=227) aged 31-365 days undergoing primary cardiac surgery requiring cardiopulmonary bypass encompassing the transition from aprotinin to EACA (aprotinin n=88, EACA n=139); all other aspects including the medical team and departmental protocols remained unchanged. The primary outcome was postoperative blood loss measured as chest tube output (CTO). Secondary outcome parameters were transfusion requirements, reoperation due to bleeding, renal, vascular, and neurological complications, and in-hospital mortality. RESULTS: CTO was significantly higher in the EACA patients {aprotinin 18 (13-27) ml kg(-1) 24 h(-1), EACA 23 (15-37) ml kg(-1) 24 h(-1) [mean (inter-quartile range)], P=0.001}, but transfusion requirements and donor exposures were not significantly different. A sensitivity analysis strengthened our finding that the increased blood loss in the EACA group was attributable to lower efficacy of EACA. There were no significant differences in the other clinical outcome measures. CONCLUSIONS: CTO was lower in aprotinin-treated patients. Nonetheless, EACA remains a suitable substitute without measurable differences in other clinical outcome criteria.

[A rare cause of recurrent monarthritis of the knee]. / Seltene Ursache für rezidivierende Monarthritis.

Isolated monarthritis caused by Tropheryma whipplei without involvement of the gastrointestinal tract is rare but is nowadays often described as an early manifestation of the disease. In a male patient with recurrent knee joint arthritis for several years, we could ultimately diagnose Whipple's disease based on PCR positive biopsies of synovial tissue and fluid. Furthermore, the patient was found to be an asymptomatic T. whipplei carrier. With adequate antibiotic therapy the patient has meanwhile fully recovered.

Generation and characterization of electron bunches with ramped current profiles in a dual-frequency superconducting linear accelerator.

We report on the successful experimental generation of electron bunches with ramped current profiles. The technique relies on impressing nonlinear correlations in the longitudinal phase space using a superconducing radio frequency linear accelerator operating at two frequencies and a current-enhancing dispersive section. The produced ~700-MeV bunches have peak currents of the order of a kilo-Ampère. Data taken for various accelerator settings demonstrate the versatility of the method and, in particular, its ability to produce current profiles that have a quasilinear dependency on the longitudinal (temporal) coordinate. The measured bunch parameters are shown, via numerical simulations, to produce gigavolt-per-meter peak accelerating electric fields with transformer ratios larger than 2 in dielectric-lined waveguides.

Relationship between fetal head station established using an open magnetic resonance imaging scanner and the angle of progression determined by transperineal ultrasound.

OBJECTIVE: We investigated the correlation between the angle of progression measured by transperineal ultrasound and fetal head station measured by open magnetic resonance imaging (MRI), the gold standard, in pregnant women at full term. METHODS: Thirty-one pregnant women at full term with a fetus in the occipitoanterior position were enrolled. First, the distance between the leading part of the skull and the interspinal plane was obtained using an open MRI system with the patient in a supine position. Immediately after MRI, the angle of progression was obtained by transperineal ultrasound without changing the woman's posture. RESULTS: There was a significant correlation between the angle of progression determined by transperineal sonography and the distance between the presenting fetal part and the level of the maternal ischial spines (y = - 0.51x + 60.8, r(2) = 0.38, P < 0.001). None of the fetal heads was engaged at the time of MRI and ultrasound examinations. CONCLUSIONS: The present study demonstrated a predictable relationship between the angle of progression obtained by transperineal ultrasound and the traditional scale used to quantify fetal head descent. Based on our results, station 0 would correspond to a 120° angle of progression. However, this correlation is based on statistical assumptions only and has to be proven in future studies.

Switch from aprotinin to ε-aminocaproic acid: impact on blood loss, transfusion, and clinical outcome in neonates undergoing cardiac surgery.

BACKGROUND: With the withdrawal of aprotinin from worldwide marketing in November 2007, many institutions treating patients at high risk for hyperfibrinolysis had to update their therapeutic protocols. At our institution, the standard was switched from aprotinin to ε-aminocaproic acid (EACA) in all patients undergoing cardiac surgery with extracorporeal circulation including neonates. Although both antifibrinolytic medications have been used widely for many years, there are few data directly comparing their blood-sparing effect and their side-effects especially in neonates. METHODS: Perioperative data from 235 neonates aged up to 30 days undergoing primary cardiac surgery were analysed. Between July 1, 2006 and November 5, 2007, all patients (n=95) received aprotinin. Starting November 6, 2007 until December 31, 2009, all patients (n=140) were treated with EACA. The primary outcome criterion was blood loss; secondary outcome criteria were transfusion requirements, renal, vascular, and neurological complications and also in-hospital mortality. RESULTS: All descriptive and intraoperative data variable were similar. Blood loss was significantly higher in the EACA group (P=0.001), but there was no difference in the rate of re-operation for bleeding (P=0.218) nor the number of transfusions. There were no differences in the incidences of postoperative renal, neurological, and vascular events or in-hospital mortality. CONCLUSIONS: In neonatal patients undergoing cardiac surgery, the switch to EACA treatment led to a higher postoperative blood loss. However, there were no differences in transfusion requirements or major clinical outcomes.

Comparison of blood-sparing efficacy of ε-aminocaproic acid and tranexamic acid in newborns undergoing cardiac surgery.

BACKGROUND: ε-Aminocaproic acid (EACA) and tranexamic acid (TXA) are used for antifibrinolytic therapy in neonates undergoing cardiac surgery, although data directly comparing their blood-sparing efficacy are not yet available. We compared two consecutive cohorts of neonates for the effect of these two medications on perioperative blood loss and allogeneic transfusions. MATERIAL AND METHODS: Data from the EACA group (n = 77) were collected over a 12-month period; data from the tranexamic acid group (n = 28) were collected over a 5-month period. Blood loss, rate of reoperation due to bleeding, and transfusion requirements were measured. RESULTS: There was no significant difference in blood loss at 6 hours (EACA 24 [17-30] mL/kg [median (interquartile range)] vs. TXA 20 [11-34] mL/kg, P = 0.491), at 12 hours (EACA 31 [22-38] mL/kg vs. TXA 27 [19-43] ml/kg, P = 0.496) or at 24 hours postoperatively (EACA 41 [31-47] mL/kg vs. TXA 39 [27-60] mL/kg; P = 0.625) or transfusion of blood products. CONCLUSIONS: ε-Aminocaproic acid and tranexamic acid are equally effective with respect to perioperative blood loss and transfusion requirements in newborns undergoing cardiac surgery.

3-Dimensional sonographic volumetry of fetal brain, liver and myocardial mass--interdisciplinary clinical validation of the method and application in fetuses with and without structural heart disease.

BACKGROUND: Prenatal 3-dimensional (3D) ultrasound allows volumetry of the fetal brain, liver and measurement of myocardial mass (MM). We studied the reliability of this method in an interdisciplinary approach, defined the relation of the values throughout gestation, and evaluated the results in fetuses with congenital heart disease (CHD). METHODS: In 104 fetuses (39 with CHD) between 14 and 38 weeks of gestation 3D ultrasound was prospectively performed. Data sets of brain, abdomen and heart were stored for off-line analysis of volumes and MM. Descriptive statistics, coefficients of correlation and of variation (CV) were performed. RESULTS: Volumetric data set acquirement was feasible in all pregnancies, lasted approximately 10 min, but off-line analysis was feasible in only 66% lasting about 45 min. MM increased in a linear fashion during gestation. CV were 11.0 and 10.8 for the left, 14.39 and 12.66, respectively, for the right MM. Median ratio between right and left MM was 0.88 in normal fetuses, and 8.25 in fetuses with hypoplastic left heart syndrome. Intra- and interobserver variabilities revealed CVs of 2.46 and 11.80, respectively, for brain volumetry, and CVs of 3.16 and 29.2, respectively, for liver volumetry. Both brain and liver volumes were positively associated with gestational age, and did not show different growth patterns in fetuses with CHD. CONCLUSIONS: Prenatal volumetry is time-consuming, but reliable especially for left MM and brain volume. Linear growth of brain and liver volume is present in utero irrespective of CHD. Application of our reference graphs of MM growth allows early differentiation in CHD.

Experimental demonstration of novel beam characterization using a polarizable X-band transverse deflection structure.

The PolariX TDS (Polarizable X-Band Transverse Deflection Structure) is an innovative TDS-design operating in the X-band frequency-range. The design gives full control of the streaking plane, which can be tuned in order to characterize the projections of the beam distribution onto arbitrary transverse axes. This novel feature opens up new opportunities for detailed characterization of the electron beam. In this paper we present first measurements of the Polarix TDS at the FLASHForward beamline at DESY, including three-dimensional reconstruction of the charge-density distribution of the bunch and slice emittance measurements in both transverse directions. The experimental results open the path toward novel and more extensive beam characterization in the direction of multi-dimensional-beam-phase-space reconstruction.

The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappaB.

Opportunistic infections, such as aspergillosis, are among the most serious complications suffered by immunocompromised patients. Aspergillus fumigatus and other pathogenic fungi synthesize a toxic epipolythiodioxopiperazine metabolite called gliotoxin. Gliotoxin exhibits profound immunosuppressive activity in vivo. It induces apoptosis in thymocytes, splenocytes, and mesenteric lymph node cells and can selectively deplete bone marrow of mature lymphocytes. The molecular mechanism by which gliotoxin exerts these effects remains unknown. Here, we report that nanomolar concentrations of gliotoxin inhibited the activation of transcription factor NF-kappaB in response to a variety of stimuli in T and B cells. The effect of gliotoxin was specific because, at the same concentrations, the toxin did not affect activation of the transcription factor NF-AT or of interferon-responsive signal transducers and activators of transcription. Likewise, the activity of the constitutively DNA-binding transcription factors Oct-1 and cyclic AMP response element binding protein (CREB), as well as the activation of protein tyrosine kinases p56lck and p59fyn, was not altered by gliotoxin. Very high concentrations of gliotoxin prevented NF-kappaB DNA binding in vitro. However, in intact cells, inhibition of NF-kappaB did not occur at the level of DNA binding; rather, the toxin appeared to prevent degradation of IkappaB-alpha, NF-kappaB's inhibitory subunit. Our data raise the possibility that the immunosuppression observed during aspergillosis results in part from gliotoxin-mediated NF-kappaB inhibition.

Finasteride treatment inhibits adult hippocampal neurogenesis in male mice.

INTRODUCTION: The 5-alpha-reductase inhibitor finasteride is used for the treatment of androgenic alopecia, benign prostate hyperplasia and prostate cancer. Besides inhibiting the conversion of testosterone to the biologically more active 5alpha-dihydrotestosterone, it also inhibits the production of neurosteroids. Decreased neurosteroid levels are postulated to be involved in the pathophysiology of psychiatric disorders such as depression. As neurosteroids metabolized by 5-alpha-reductase influence neural plasticity, we investigated whether finasteride treatment alters adult hippocampal neurogenesis, implicated in the pathophysiology of depression. METHODS: Male C57BL/6N mice were treated subchronically (7 days) with finasteride or vehicle. Adult neurogenesis was assessed at two different time points after treatment (day 1; day 35) using immunohistochemistry. RESULTS: Finasteride treatment led to a significant decrease in brain 5alpha-dihydrotestosterone levels and induced a reversible reduction in the number of newborn cells and young neurons in the hippocampus. 35 days after the last finasteride injection, neurogenesis had returned to normal. DISCUSSION: These data indicate that inhibition of 5-alpha-reductase activity by finasteride treatment influences neuronal plasticity on a structural level. These changes might contribute to the pathophysiology of depressive episodes observed after finasteride treatment.

Effects of eccentric cycle ergometry in alpine skiers.

Eccentric cycling, where the goal is to resist the pedals, which are driven by a motor, increases muscle strength and size in untrained subjects. We hypothesized that it could also be beneficial for athletes, particularly in alpine skiing, which involves predominantly eccentric contractions at longer muscle lengths. We investigated the effects of replacing part of regular weight training with eccentric cycling in junior male alpine skiers using a matched-pair design. Control subjects ( N=7) executed 1-h weight sessions 3 times per week, which included 4-5 sets of 4 leg exercises. The eccentric group ( N=8) performed only 3 sets, followed by continuous sessions on the eccentric ergometer for the remaining 20 min. After 6 weeks, lean thigh mass increased significantly only in the eccentric group. There was a groupxtime effect on squat-jump height favouring the eccentric group, which also experienced a 6.5% improvement in countermovement-jump height. The ability to finely modulate muscle force during variable eccentric cycling improved 50% (p=0.004) only in the eccentric group. Although eccentric cycling did not significantly enhance isometric leg strength, we believe it is beneficial for alpine skiers because it provides an efficient means for hypertrophy while closely mimicking the type of muscle actions encountered while skiing.