Study protocol of a cluster-randomised controlled trial assessing a multimodal machine-based exercise training programme in senior care facilities over 6 months - the bestform study (best function of range of motion).

BACKGROUND: Physical functioning is a crucial factor for independence and quality of life in old age. The aim of the "bestform-Best function of range of motion" trial is to investigate the effects of a 6 months multimodal machine-based strength, coordination and endurance training on physical function, risk of falls and health parameters in older adults. METHODS: Bestform is a cluster-randomised trial including older adults ≥ 65 years living in senior care facilities in Southern Germany. Senior care facilities are randomly allocated to the control group with usual care (n ≥ 10 care facilities) and to the intervention group (n ≥ 10 care facilities), overall including ≥ 400 seniors. Residents belonging to the intervention group are offered a supervised machine-based exercise training programme twice weekly over 45-60 min over six months in small groups, while those in the usual care facilities will not receive active intervention. The primary outcome is the change in Short Physical Performance Battery over six months between groups. Secondary outcomes are change in risk of falling, fear of falling, number of falls and fall-related injuries, physical exercise capacity, handgrip strength, body composition, cardiac function, blood parameters, quality of life, risk of sarcopenia, activities of daily living, and cognition over three and six months. DISCUSSION: The bestform study investigates the change in physical function between seniors performing exercise intervention versus usual care over six months. The results of the study will contribute to the development of effective physical activity concepts in senior care facilities. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04207307. Registered December 2019.

Progressive machine-based resistance training for prevention and treatment of sarcopenia in the oldest old: A systematic review and meta-analysis.

The muscle disease sarcopenia, which is characterised by a loss of muscle strength, muscle quantity, and physical performance, restricts mobility and independence in an ageing society. The aim of this systematic review and meta-analysis is to analyse the effects that long-term progressive resistance training interventions performed on weight machines have on sarcopenia (European Working Group on Sarcopenia in Older People) and how the interventions are composed. In total, 779 articles published between 2000 and 2020 were scanned (PubMed, Web of Science, CINAHL) and 14 randomised controlled trials were included within the review. Populations, interventions, control groups and outcomes were analysed. Subsequent meta-analysis (10 studies, 902 participants) revealed that the time needed in a chair-stand-test, as an indicator for leg strength, was predominantly reduced, whereas grip strength remained unchanged after the interventions. Data concerning the effects of machine-based progressive resistance training on muscle quantity were insufficient for meta-analysis. Physical performance measured by undergoing the Timed-Up-and-Go-test, gait speed test, Short Physical Performance Battery and 6 min-walk-test improved significantly as well. The quality of evidence (GRADE) in the analysed studies was low or moderate. In summary, machine-based progressive resistance training has the potential to reverse sarcopenia in the oldest old, as reflected by enhanced muscle strength and physical performance. The systematic review revealed promising initial results for muscle quantity.

Marathon running improves mood and negative affect.

BACKGROUND: Physical activity has beneficial effects on depression, as well as on other mental and somatic diseases. The amount of recommended exercise is still under discussion. We investigated whether marathon runners (MA) exhibit less or more depressive symptoms and negative affects compared to sedentary controls (SC) and how their mood changes in the context of marathon training and marathon running. METHODS: We included 100 amateur marathon runners and 46 age- and gender matched sedentary controls in the ReCaP (Running effects on Cognition and Plasticity) study. Questionnaires contained Beck Depression Inventory (BDI), Hamilton Depression Scale (HAMD), Oxford Happiness Questionnaire (OHQ), Visual Analogue Scale (VAS), Positive And Negative Affect Schedule (PANAS), Global Assessment of Functioning (GAF). SC were evaluated one time at baseline, MA six times during the six months study period. RESULTS: Compared to SC, marathon runners (281.80 ± 131.44 running min/week) exhibited less depressive symptoms, more positive affects (PANAS-PA) and a higher level of functioning (GAF). Within the marathon group, negative affect (PANAS-NA) decreased and general mood states (VAS) further improved throughout the study period with a maximum 24 h after the marathon. DISCUSSION: MA had less depressive symptoms and a higher level of functioning compared to SC. Higher amounts than the recommended duration of 150 min/week aerobic training (WHO/ACSM) and the participation in a marathon seem to even further improve negative affect. These findings give new insight into the relationship between exercise and mood parameters. They can be implemented in future preventive strategies for depressive symptoms.

Implementing shared decision-making on acute psychiatric wards: a cluster-randomized trial with inpatients suffering from schizophrenia (SDM-PLUS).

AIMS: Although shared decision-making (SDM) has the potential to improve health outcomes, psychiatrists often exclude patients with more severe mental illnesses or more acute conditions from participation in treatment decisions. This study examines whether SDM is facilitated by an approach which is specifically adapted to the needs of acutely ill patients (SDM-PLUS). METHODS: The study is a multi-centre, cluster-randomised, non-blinded, controlled trial of SDM-PLUS in 12 acute psychiatric wards of five psychiatric hospitals addressing inpatients with schizophrenia or schizoaffective disorder. All patients fulfilling the inclusion criteria were consecutively recruited for the trial at the time of their admission to the ward. Treatment teams of intervention wards were trained in the SDM-PLUS approach through participation in two half-day workshops. Patients on intervention wards received group training in SDM. Staff (and patients) of the control wards acted under 'treatment as usual' conditions. The primary outcome parameter was the patients' perceived involvement in decision-making at 3 weeks after study enrolment, analysed using a random-effects linear regression model. RESULTS: In total, 161 participants each were recruited in the intervention and control group. SDM-PLUS led to higher perceived involvement in decision-making (primary outcome, analysed patients n = 257, mean group difference 16.5, 95% CI 9.0-24.0, p = 0.002, adjusted for baseline differences: ß 17.3, 95% CI 10.8-23.6, p = 0.0004). In addition, intervention group patients exhibited better therapeutic alliance, treatment satisfaction and self-rated medication compliance during inpatient stay. There were, however, no significant improvements in adherence and rehospitalisation rates in the 6- and 12-month follow-up. CONCLUSIONS: Despite limitations in patient recruitment, the SDM-PLUS trial has shown that the adoption of behavioural approaches (e.g. motivational interviewing) for SDM may yield a successful application to mental health. The authors recommend strategies to ensure effects are not lost at the interface between in- and outpatient treatment.Trial registration: The trial was registered at Deutsches Register Klinischer Studien (DRKS00010880).

Influence of antiretroviral therapy and cardiovascular disease on the immature platelet fraction in patients living with HIV.

Cardiovascular disease is an important contributor to morbidity and mortality in people living with HIV . The immature platelet fraction (IPF) is increased in HIV-negative patients with cardiovascular disease and evidence suggests that an enlarged IPF is associated with adverse cardiovascular events. In this multi-center observational study, we aimed to investigate how the IPF in people living with HIV is influenced by antiretroviral therapy and cardiovascular disease. Subjects without cardiovascular disease that received antiretroviral therapy showed a smaller IPF accompanied by lower D-dimer and C-reactive protein (CRP) levels compared to therapy-naïve subjects (mean IPF: 2.9% vs. 3.9%, p = .016; median D-dimer: 252 µg/L vs. 623 µg/L, p < .001; median CRP: 0.2 mg/dL vs. 0.5 mg/dL, p = .004). No significant differences for the IPF, D-dimer or CRP were found between subjects on antiretroviral therapy with documented cardiovascular disease and therapy-naïve subjects. In conclusion, we observed a reduction in the IPF among subjects on therapy only in the absence of cardiovascular disease. In contrast, subjects receiving therapy that had documented cardiovascular disease showed an IPF comparable to therapy-naïve subjects. Future studies are needed to investigate if an enlarged IPF may serve as a biomarker in predicting adverse cardiovascular events in people living with HIV.

Fetal heart rate variability responsiveness to maternal stress, non-invasively detected from maternal transabdominal ECG.

PURPOSE: Prenatal stress (PS) during pregnancy affects in utero- and postnatal child brain-development. Key systems affected are the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS). Maternal- and fetal ANS activity can be gauged non-invasively from transabdominal electrocardiogram (taECG). We propose a novel approach to assess couplings between maternal (mHR) and fetal heart rate (fHR) as a new biomarker for PS based on bivariate phase-rectified signal averaging (BPRSA). We hypothesized that PS exerts lasting impact on fHR. METHODS: Prospective case-control study matched for maternal age, parity, and gestational age during the third trimester using the Cohen Perceived Stress Scale (PSS-10) questionnaire with PSS-10 over or equal 19 classified as stress group (SG). Women with PSS-10 < 19 served as control group (CG). Fetal electrocardiograms were recorded by a taECG. Coupling between mHR and fHR was analyzed by BPRSA resulting in fetal stress index (FSI). Maternal hair cortisol, a memory of chronic stress exposure for 2-3 months, was measured at birth. RESULTS: 538/1500 pregnant women returned the questionnaire, 55/538 (10.2%) mother-child pairs formed SG and were matched with 55/449 (12.2%) consecutive patients as CG. Maternal hair cortisol was 86.6 (48.0-169.2) versus 53.0 (34.4-105.9) pg/mg (p = 0.029). At 36 + 5 weeks, FSI was significantly higher in fetuses of stressed mothers when compared to controls [0.43 (0.18-0.85) versus 0.00 (- 0.49-0.18), p < 0.001]. CONCLUSION: Prenatal maternal stress affects the coupling between maternal and fetal heart rate detectable non-invasively a month prior to birth. Lasting effects on neurodevelopment of affected offspring should be studied. TRIAL REGISTRATION: Clinical trial registration: NCT03389178.

Three-dimensional fat-saturated T1-weighted Cartesian volumetric interpolated breath-hold examination (VIBE) for the diagnosis of aortitis in patients with suspected large vessel vasculitis: a comparative study with 18F-FDG PET applying fully integrated PET/MRI.

AIM: To evaluate the feasibility of T1-weighted (T1W) three-dimensional (3D) fat saturated Cartesian volumetric interpolated breath-hold examination (VIBE) magnetic resonance imaging (MRI) sequence for the diagnosis of aortitis in patients with suspected large vessel vasculitis (LVV) applying fully integrated 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/MRI. MATERIAL AND METHODS: Fourteen patients with aortitis and 14 patients with a negative study for aortitis using 18F-FDG PET as the standard of reference for the evaluation of inflammatory aortic involvement were included retrospectively. All patients were imaged at 3 T using T1W VIBE pre- and post-contrast. Four aortic segments were evaluated for image quality (IQ), diagnostic confidence (DC), and the degree of inflammatory activity (IA) using a Likert scale. Binomial and generalised estimating equation model tests were used to assess the diagnostic performance of T1W VIBE. Cohen's k was applied to test for interobserver reproducibility with respect to IA. Spearman's rank correlation coefficient was calculated to examine correlations between IQ, DC, IA, and PET results. RESULTS: On a patient- and segment-based analysis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 85.7% and 59.8%, 100% and 100%, 100% and 100%, 87.5% and 68%, and 92.9% and 82.1%, respectively. IQ and DC were acceptable to good in all examinations and substantial interobserver agreement was observed for IA (Cohen's k = 0.69). IQ and DC as well as IA and 18F-FDG vessel wall uptake were significantly correlated (r=0.763 and 0.679, respectively; p<0.0001). CONCLUSION: T1W 3D fat saturated VIBE MRI allows diagnosis of aortitis and may aid in the management of patients with suspected LVV.

T2-relaxation time of cartilage repair tissue is associated with bone remodeling after spongiosa-augmented matrix-associated autologous chondrocyte implantation.

OBJECTIVE: To investigate whether T2 relaxation time measurements of cartilage repair tissue and structural changes of the knee joint are associated with subchondral bone architecture after spongiosa-augmented matrix-associated autologous chondrocyte implantation (MACI). DESIGN: Both knees of 25 patients (25.5 ± 7.8y; 10 women) were examined preoperatively and 2.7 years after unilateral spongiosa-augmented MACI with 3T magnetic resonance (MR) imaging. Cartilage composition was assessed using T2 relaxation time measurements, subchondral trabecular bone microstructure was quantified using a 3D phase-cycled balanced steady state free-precision sequence. Structural knee joint changes were assessed using the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS). The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was used for the postoperative description of the area that underwent MACI. Correlations were assessed using Spearman's rank correlation coefficients. RESULTS: Hypertrophy of the cartilage repair tissue was found in 2 of 25 patients, both after a MACI procedure at the patella, 21 patients showed congruent filling. In subchondral bone of the cartilage repair compartment, apparent trabecular thickness was significantly higher in compartments with elevated cartilage T2 (n = 17; 0.37 ± 0.05 mm) compared to those showing no difference in cartilage T2 compared to the same compartment in the contralateral knee (n = 8; 0.27 ± 0.05 mm; P = 0.042). Significant correlations were found between the overall progression of WORMS and the ipsilateral vs contralateral ratio of average trabecular thickness (r = 0.48, P = 0.031) and bone fraction (r = 0.57, P = 0.007). CONCLUSIONS: After spongiosa-augmented MACI, T2 values of cartilage repair tissue and structural knee joint changes correlated with the quality of the underlying trabecular bone.

Primary Stability of an Acromioclavicular Joint Repair Is Affected by the Type of Additional Reconstruction of the Acromioclavicular Capsule.

BACKGROUND: The synergistic effect of the acromioclavicular (AC) capsule and coracoclavicular (CC) ligaments on AC joint stability has gained recent recognition for its importance. Biomechanical and clinical studies have shown the benefit of combined reconstruction with multiple variations of surgical techniques for AC capsule augmentation. The ideal configuration remains unknown for such capsular repair aimed at achieving optimal stability with anatomic reconstruction. HYPOTHESIS: Primary AC joint stability can be restored by AC capsule augmentation, while position of the additional suture construct is critical. It was hypothesized that techniques that reconstruct the anterior capsular structures would restore native stability against rotations and translations. STUDY DESIGN: Controlled laboratory study. METHODS: Thirty fresh-frozen human cadaveric shoulders were used. Each sample was tested in the native state and served as its own control. After complete capsulotomy, 1 of 5 AC capsular repair configurations was performed: anterior, superior, posterior, O-frame, and X-frame. After testing of the AC capsular repair configurations, the tests were repeated after dissection of the CC ligaments and after CC ligament reconstruction with a suture button system. AC joint stability was immediately tested after each step under rotation and horizontal translation. To accomplish this, the AC joints were anatomically positioned on a custom fixture linked to a servohydraulic testing system. A 3-dimensional optical measuring system was used to evaluate the 3-dimensional joint motion. Clavicle posterior translation in relation to the acromion, rotation around the long axis of the clavicle, and displacement of the lateral clavicle in relation to the center of rotation were measured. The torques and forces required to rotate and translate the clavicle were recorded. RESULTS: In terms of translational testing, after the complete capsulotomy, a significant reduction of resistance force was found across all groups, with a mean 13% to 20% remaining ( P < .05). All AC suture augmentations were able to significantly increase the average resistance force as compared with the native ( P = .01) against posterior translation. Subsequent cutting of the CC ligaments did not result in a significant change in any of the groups ( P = .23). The synergistic effect of AC capsule augmentation and CC ligament reconstruction could be demonstrated without exception. In terms of rotational testing, the complete capsulotomy resulted in a significant reduction of resistance torque in all groups ( P < .05), with a remaining torque ranging between 2% and 11% across the groups. However, all AC suture constructs significantly increased the resistance torque as compared with the capsulotomy ( P = .01). The subsequent cutting of the CC ligaments resulted in a significant change in 2 of the 5 groups (O-frame, P = .01; X-frame, P = .02) and an overall remaining torque reduction ranging from 3% and 42%. The combined reconstruction of the AC capsule and CC ligaments achieved the highest percentage of regained resistance torque but remained significantly weaker than the native specimen ( P = .01). CONCLUSION: Native translational stability could be restored by the addition of AC capsule augmentation, while partial rotational instability remained. The tested constructs revealed no significant individual differences. CLINICAL RELEVANCE: Combined stabilization of the AC capsule and CC ligaments demonstrated the greatest capacity to restore the native stability against translational and rotational loads, with the specific configuration of the AC capsule repair to be chosen according to the personal preferences of the surgeon.

Influence of gestational diabetes on fetal autonomic nervous system: a study using phase-rectified signal-averaging analysis.

OBJECTIVES: Maternal gestational diabetes mellitus (GDM) is known to influence fetal physiology. Phase-rectified signal averaging (PRSA) is an innovative signal-processing technique that can be used to investigate fetal heart signals. The PRSA-calculated variables average acceleration capacity (AAC) and average deceleration capacity (ADC) are established indices of autonomic nervous system (ANS) function. The aim of this study was to evaluate the influence of GDM on the fetal cardiovascular and ANS function in human pregnancy using PRSA. METHODS: This was a prospective clinical case-control study of 58 mothers with diagnosed GDM and 58 gestational-age matched healthy controls in the third trimester of pregnancy. Fetal cardiotocography (CTG) recordings were performed in all cases at entry to the study, and a follow-up recording was performed in 19 GDM cases close to delivery. The AAC and ADC indices were calculated by the PRSA method and fetal heart rate short-term variation (STV) by CTG software according to Dawes-Redman criteria. RESULTS: Mean gestational age of both groups at study entry was 35.7 weeks. There was a significant difference in mean AAC (1.97 ± 0.33 bpm vs 2.42 ± 0.57 bpm; P < 0.001) and ADC (1.94 ± 0.32 bpm vs 2.28 ± 0.46 bpm; P < 0.001) between controls and fetuses of diabetic mothers. This difference could not be demonstrated using standard computerized fetal CTG analysis of STV (controls, 10.8 ± 3.0 ms vs GDM group, 11.3 ± 2.5 ms; P = 0.32). Longitudinal fetal heart rate measurements in a subgroup of women with diabetes were not significantly different from those at study entry. CONCLUSIONS: Our findings show increased ANS activity in fetuses of diabetic mothers in late gestation. Analysis of human fetal cardiovascular and ANS function by PRSA may offer improved surveillance over conventional techniques linking GDM pregnancy to future cardiovascular dysfunction in the offspring. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

TiN x O y coatings facilitate the initial adhesion of osteoblasts to create a suitable environment for their proliferation and the recruitment of endothelial cells.

Titanium-nitride-oxide coatings (TiN x O y ) improve osseointegration of endosseous implants. The exact mechanisms by which these effects are mediated are poorly understood except for an increase of osteoblast proliferation while a high degree of differentiation is maintained. One hypothesis holds that TiN x O y facilitates the initial spreading and adhesion of the osteoblasts. The aim of this work was to investigate the molecular mechanisms of osteoblast adhesion on TiN x O y as compared to microrough titanium SLA. A global view of the osseointegrative process, that is, taking into account other cell groups, especially endothelial cells, is also presented. To this aim, gene expression and focal adhesion analysis, cocultures and wound assays were performed early after seeding, from 6 h to 3 days. We demonstrated that TiN x O y coatings enhance osteoblast adhesion and spreading when compared to the standard microrough titanium. The integrin ß1, either in association with α1 or with α2 plays a central role in these mechanisms. TiN x O y coatings optimize the process of osseointegration by acting at several levels, especially by upregulating osteoblast adhesion and proliferation, but also by supporting neovascularization and the development of a suitable inflammatory environment.

Trends in Patient Safety of Intact Abdominal Aortic Aneurysm Repair: German Registry Data on 36,594 Procedures.

OBJECTIVE/BACKGROUND: The study aim was to determine whether patient safety for non-ruptured abdominal aortic aneurysm (nrAAA) repair has changed between 1999 and 2010 in a large German cohort. METHODS: The data source was the prospective quality assurance registry of the German Vascular Society from 1999 to 2010. Patient characteristics, surgical techniques (open aortic repair [OAR], endovascular aortic repair [EVAR]), procedural time and outcomes, including the length of hospital stay (LOS), were analysed using the Cochran-Armitage test for binary parameters and Spearman's correlation coefficient for quantitative parameters. RESULTS: A total of 36,594 operations (23,037 OAR, 13,557 EVAR) for infrarenal nrAAA in 201 hospitals in Germany were investigated. Patients' mean age increased from 69.6 to 72.0 years (p < .001). The rate of patients with American Society of Anesthesiologists scores of 3 or 4 increased (p < .001). Use of EVAR increased (1999: 16.7%; 2010: 62.7%; p < .001), and since 2009, EVAR has been more frequently used than OAR. The overall in hospital mortality decreased from 3.1% in 1999 to 2.3% in 2010 (p < .001). There were no temporal trends for mortality rates for EVAR (p = .233) or OAR (p = .281) when considered separately. Cardiac (1999: 8.1%; 2010: 5.1%; p < .001) and pulmonary (1999: 7.8%; 2010: 4.8%; p < .001) complications decreased. The rate of post-operative renal failure increased (1999: 3.6%; 2010 4.1%; p = .017), without increasing the rate of patients needing dialysis (1999: 1.7%; 2010: 1.7%; p = .171). The median LOS decreased from 17 days in 1999 to 10 days in 2010 (p < .001). CONCLUSION: This study shows significantly improved post-procedural in hospital outcomes and decreased use of resources for nrAAA repair. This trend can probably be attributed to the implementation of EVAR as a standard technique, but some trends could also possibly be explained by a change in the remuneration system. The main limitation of the registry is the lack of internal and external validation. However, in hospital patient safety for AAA repair seems to have improved significantly in the participating hospitals.

Esophageal bougination: a novel ex vivo endoscopic training model correlated with clinical data.

BACKGROUND: Esophageal bougination is a worldwide standard endoscopic procedure. Clinical methods and recommendations are based on clinical experiences only. Mechanical properties have never been described. Aim of the study was to establish a realistic ex vivo training model. Therefore, detailed assessment of relevant mechanical features of esophageal bougination should be evaluated ex vivo and in patient setting and correlated against. PATIENTS AND METHODS: A three-step concept was used to evaluate mechanical properties at stenosis level. First, insertion forces were evaluated in an ex vivo linear single stenosis model during steady mechanical insertion. Second, adding friction and properties of the pharynx and upper esophagus, the model was integrated in an artificial endoscopic training model (ELITE training model). Third, in vivo measurements were taken to correlate ex vivo data with parameters of a realistic patient setting. RESULTS: With the presented setup, we were able to assess insertion force and pressure levels in an artificial stricture using different sizes of commercially available standard bougies. In all models, there was a relevant increase in insertion force with higher stricture pressure levels. Insertion force levels in the ELITE model show higher levels compared to the linear stenosis model. Having regard to the maximum forces in patients, there is also a constant increase in mean insertion force according to higher bougie sizes, but lower forces were measured as in the ELITE model. DISCUSSION: The applied models are suitable to appraise mechanical properties of esophageal bougination in an ex vivo model and patient setting. Forces could be constituted reliable, significant increase was documented according to stenosis level and results were comparable to patient data. This was comparable to patient data. Further clinical evaluation in different kinds of stenosis is necessary.

Measurements After Image Post-processing Are More Precise in the Morphometric Assessment of Thoracic Aortic Aneurysms: An Intermodal and Intra-observer Evaluation.

OBJECTIVES: Precise pre-procedural anatomical analysis of aneurysmal anatomy is essential for successful thoracic endovascular aortic repair (TEVAR). Since surgeons and radiologists have to perform multiple measurements in the same patient, high intra-observer reliability of any imaging method is mandatory. Commercially available three dimensional (3D) post-processing techniques are expected to be superior to conventional two dimensional multiplanar reconstructions (MPRs) derived from computed tomography angiograms (CTAs). However, few data exist to support this view. This study aims to evaluate the intermodal and intra-observer differences using 3D software (3surgery) in descending thoracic aortic aneurysms (dTAAs). METHODS: Pre-operative CTAs (performed between 2004 and 2010) of 30 dTAAs (mean maximum diameter 61.4 ± 13 mm) were assessed by three independent investigators with different experience in the measurement of aortic pathologies. Intra-observer reliability and intermodal differences (3D vs. 2D) were investigated using pre-specified measurement points (distances of total length, maximum diameter, proximal and distal landing zones). Statistical analyses were performed using the Bland-Altman method and a mixed regression model. RESULTS: Intermodal comparison showed that 2D measurements significantly underestimate the measured distances (maximum diameter 3.7 mm [95% CI -5.3 to -2.1] and landing zone maximum 1.4 mm [95% CI -2.0 to -0.2] shorter with 2D, p < .05). In almost all 3D measurements, all investigators showed lower variability comparing the intra-observer differences, most notably in the measuring point total length (reduction of the SD up to 7.9 mm). CONCLUSIONS: These data show that both techniques led to significant measurement disparity. This occurs especially at the point of indication (maximum diameter) and the total length of the aneurysm (important for correct stent graft selection). But overall the variability is reduced with the 3D technique, which also tends to measure greater distances. The use of post-processing software therefore leads to more precise device selection for TEVAR in TAA.

The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer.

BACKGROUND: Intratumoural lymphocytic infiltration is strongly associated with the outcome of many human epithelial cancers. The current paper investigated whether subpopulations of tumour-infiltrating T lymphocytes are associated with certain clinicopathological parameters and the prognosis of patients with invasive bladder cancer (BCa). PATIENTS AND METHODS: The infiltration densities of the adaptive immune markers CD3 (the whole T cell population), FOXP3 (regulatory T cells; Tregs), CD8 (T effector cells) and CD45R0 (T effector memory cells) were analysed by immunohistochemistry and image analysis with tissue microarrays of tumour tissues from 149 patients with invasive BCa treated with radical cystectomy. The findings were correlated with certain clinicopathological parameters. RESULTS: Higher FOXP3/CD3 [OS: p = 0.016, HR 1.29, 95% confidence intervals (95% CIs 1.05-1.59)] and FOXP3/CD8 (OS: p = 0.013, HR 1.32, 95% CIs 1.06-1.65) ratios were significantly associated with briefer overall survival and time to cancer-specific death; the latter ratio represented an independent prognostic factor according to a multivariate analysis adjusted for pathological T and N stages (HR 1.32, 95% CIs 1.05-1.67, p = 0.018). The infiltration densities of individual markers (CD3, CD8, FOXP3 and CD45R0) were not significantly associated with clinicopathological parameters or survival; however, a trend towards a better outcome was observed for higher log-transformed CD8 (p = 0.070, HR 0.80, 95% CIs 0.63-1.02) and CD3 (p = 0.113, HR 0.84, 95% CIs 0.68-1.04) infiltration values. CONCLUSIONS: A high fraction of Tregs amongst CD3- and CD8-positive lymphocytes indicated a poor prognosis, thereby emphasising the important role that Tregs play in the suppression of the anti-tumour immune response. No single lymphocytic marker was significantly correlated with clinical outcomes, but high CD3 and CD8 infiltration showed trends towards better prognosis.

Patient characteristics and outcomes of carotid endarterectomy and carotid artery stenting: analysis of the German mandatory national quality assurance registry - 2003 to 2014.

AIM: In Germany, every surgical or endovascular procedure on the extracranial carotid artery is documented in a mandatory quality assurance registry. The purpose of this study is to describe the patient characteristics, the indications for treatment, and the short-term outcomes as well as to analyse the corresponding trends from 2003 to 2014. METHODS: Data on demographics, peri-procedural measures, and outcomes were extracted from the annual quality reports published by the Federal Agency for Quality Assurance and the Institute for Applied Quality Improvement and Research in Health Care. Data were available from 2003 to 2014 for carotid endarterectomy (CEA) and from 2012 to 2014 for carotid artery stenting (CAS). The primary outcome event of this study is any stroke or death until discharge from hospital. Temporal trends of categorical variables were statistically analysed using the Cochran-Armitage test for trend. RESULTS: Between 2003 and 2014, 309,405 CEAs and 18,047 CAS procedures were documented in the database; 68.1% of all patients were male. The mean age of patients treated with CEA increased from 68.9 years in 2003 to 70.9 years in 2014. The proportion of patients with ASA stages III to V increased from 65% to 71% in CEA, whereas it decreased from 44% to 41% in CAS patients. 53.1% of all CEAs were performed for asymptomatic patients (group A), 34.4% for symptomatic patients treated electively (group B), and 11.2% a in a collective group including other indications for CEA or CAS (such as recurrent stenosis, carotid aneurysms, emergency treatment due to stroke-in-evolution). The corresponding data for CAS are 49.3%, 26.1% and 26.3% respectively. In group B, the interval between the neurological index event and CEA decreased from 28 to 8 days (P<0.001). In patients treated with CAS, this interval was 9 days in 2012 (no further data available). On average, 67.1% and 48.2% of surgically treated patients as well as 77.8% and 69.8% of CAS patients were neurologically assessed before and after the procedure, respectively. From 2003 to 2014, CEA procedures were performed more frequently in locoregional anesthesia (10.1% to 29.1%, P<0.001). The same trend was observed for the application of the eversion technique (37.0% to 41.6%, P<0.001), the neurophysiological monitoring (49.8% to 61.8%, P<0.001), and the intra-procedural assessment of the treated artery (44.5% to 69.7%, P<0.001). In contrast, shunting was used less frequently (48.1% to 43.0%, P<0.001). Averagely 95.7% of all endovascular procedures were performed using stent-angioplasty. In 54.2% a protection device was used. Nitinol and bare metal stents were used in 74.1% and 21.4% of cases, respectively. The in-hospital rate of any stroke or death decreased from 2.0% to 1.1% in asymptomatic patients treated with CEA without a contralateral stenosis ≥75% or occlusion, P<0.001). In patients treated with CAS this rate did not increase (1.7% to 1.8%, p=0.909). The corresponding rates in CEA and CAS patients with severe contralateral stenosis or occlusion varied between 1.9%-3.1% and 2.2%-2.6%, respectively. In symptomatic patients (group B) with a stenosis of 50 percent or more, the rate of any stroke or death decreased significantly after CEA from 4.2% to 2.4% (P<0.001) and remained stable after CAS (3.9% to 3.5%, P=0.577). CONCLUSION: This report on 327,452 carotid procedures analysed one of the largest quality registries on CEA and CAS worldwide. Data indicate that treated patients became older and sicker, whereas in contrast, the in-hospital rates of stroke or death are decreasing over time.

Endothelial ALK1 Is a Therapeutic Target to Block Metastatic Dissemination of Breast Cancer.

Exploration of new strategies for the prevention of breast cancer metastasis is justifiably at the center of clinical attention. In this study, we combined a computational biology approach with mechanism-based preclinical trials to identify inhibitors of activin-like receptor kinase (ALK) 1 as effective agents for blocking angiogenesis and metastasis in breast cancer. Pharmacologic targeting of ALK1 provided long-term therapeutic benefit in mouse models of mammary carcinoma, accompanied by strikingly reduced metastatic colonization as a monotherapy or part of combinations with chemotherapy. Gene-expression analysis of breast cancer specimens from a population-based nested case-control study encompassing 768 subjects defined endothelial expression of ALK1 as an independent and highly specific prognostic factor for metastatic manifestation, a finding that was corroborated in an independent clinical cohort. Overall, our results suggest that pharmacologic inhibition of endothelial ALK1 constitutes a tractable strategy for interfering with metastatic dissemination of breast cancer.

[Indication-Related Effectivity of Cervical Occlusion Techniques in Women with Threatening Preterm Birth]. / Indikationsbezogene Effektivität von Verschlussoperationen am Muttermund.

The aim of this study was to identify which operation technique [total cervical occlusion (TMV), cerclage (C) or combination of both (TMV+C)] would lead to the greatest pregnancy prolongation in 3 different collectives of patients at risk (history of preterm birth, cervical insufficiency, prolapsing membranes). In this retrospective data collection, 200 cervical occlusions performed between 1997 and 2010 were analysed. In patients with a history of preterm birth/stillbirth (n=80) a prophylactic TMV increased the lifebirth rate from 35% without TMV to 95% with TMV (p<0.001). The risk diminuation after TMV was - 60% for stillbirth (p<0.001) and - 30% for preterm birth (p=0.01). In this subcollective the TMV seemed to be more effective in pregnancy prolongation (days) than C (139 vs. 113 days), however the combination of both (C+TMV) did not add much benefit (142 days). In patients with cervical insuffiency (n=86) the pregnancy could be prolonged by 82 (C), 79 (TMV) und 109 days (C+TMV) (p=0.003-0.017) and in patients with membrane prolaps (n=34) by 63 (C), 61 (TMV) und 76 (C+TMV) days. According to present data, the combination of cerclage and TMV has the highest benefit on pregnancy prolongation. This analysis should provide a basis for randomised controlled studies on this topic.

Impact of baseline atrial fibrillation cycle length on acute and long-term outcome of persistent atrial fibrillation ablation.

BACKGROUND: A short baseline atrial fibrillation (AF) cycle length (CL) has been associated with a worse outcome after catheter ablation for AF, whereas the impact of a long baseline AFCL is unknown. We investigated the influence of AFCL on acute and long-term success in a large series of patients undergoing catheter ablation for persistent AF. METHODS: Overall, 177 consecutive patients undergoing catheter ablation of persistent AF using a sequential ablation approach were included in the analysis. AFCL was measured in the left atrial appendage (LAA) at baseline and following each ablation step. The primary endpoint was freedom from any atrial arrhythmia off antiarrhythmic drugs (AAD) with a single ablation procedure after 12 months. RESULTS: Mean AFCL was 164 ± 24 ms. A shorter AFCL was associated with longer AF duration, larger LA diameter, and longer procedure duration. Termination to sinus rhythm (SR) was achieved in 57 (32 %) patients. Baseline AFCL was shorter (161 ± 24 ms) in patients without AF termination compared to patients with AF termination (169 ± 23 m, p = 0.03). The primary endpoint was reached less frequently in patients with a short (<155 ms) AFCL (18 vs. 38.5 %, p = 0.006). Patients with an AFCL between 155 and 200 ms had the best outcome compared to patients with AFCL <155 or ≥200 ms (40 vs. 18 %, p = 0.003). CONCLUSIONS: Patients with a baseline AFCL between 155 and 200 ms have the best outcome after a single ablation procedure for persistent AF compared to patients with an AFCL of <155 or ≥200 ms.

The founding of Mauritian endemic coffee trees by a synchronous long-distance dispersal event.

The stochastic process of long-distance dispersal is the exclusive means by which plants colonize oceanic islands. Baker's rule posits that self-incompatible plant lineages are unlikely to successfully colonize oceanic islands because they must achieve a coordinated long-distance dispersal of sufficiently numerous individuals to establish an outcrossing founder population. Here, we show for the first time that Mauritian Coffea species are self-incompatible and thus represent an exception to Baker's rule. The genus Coffea (Rubiaceae) is composed of approximately 124 species with a paleotropical distribution. Phylogenetic evidence strongly supports a single colonization of the oceanic island of Mauritius from either Madagascar or Africa. We employ Bayesian divergence time analyses to show that the colonization of Mauritius was not a recent event. We genotype S-RNase alleles from Mauritian endemic Coffea, and using S-allele gene genealogies, we show that the Mauritian allelic diversity is confined to just seven deeply divergent Coffea S-RNase allelic lineages. Based on these data, we developed an individual-based model and performed a simulation study to estimate the most likely number of founding individuals involved in the colonization of Mauritius. Our simulations show that to explain the observed S-RNase allelic diversity, the founding population was likely composed of fewer than 31 seeds that were likely synchronously dispersed from an ancestral mainland species.