State-of-the-art aortic imaging: part I - fundamentals and perspectives of CT and MRI

Over the last two decades, imaging of the aorta has undergone a clinically relevant change. As part of the change non-invasive imaging techniques have replaced invasive intra-arterial digital subtraction angiography as the former imaging gold standard for aortic diseases. Computed tomography (CT) and magnetic resonance imaging (MRI) constitute the backbone of pre- and postoperative aortic imaging because they allow for imaging of the entire aorta and its branches. The first part of this review article describes the imaging principles of CT and MRI with regard to aortic disease, shows how both technologies can be applied in every day clinical practice, offering exciting perspectives. Recent CT scanner generations deliver excellent image quality with a high spatial and temporal resolution. Technical developments have resulted in CT scan performed within a few seconds for the entire aorta. Therefore, CT angiography (CTA) is the imaging technology of choice for evaluating acute aortic syndromes, for diagnosis of most aortic pathologies, preoperative planning and postoperative follow-up after endovascular aortic repair. However, radiation dose and the risk of contrast induced nephropathy are major downsides of CTA. Optimisation of scan protocols and contrast media administration can help to reduce the required radiation dose and contrast media. MR angiography (MRA) is an excellent alternative to CTA for both diagnosis of aortic pathologies and postoperative follow-up. The lack of radiation is particularly beneficial for younger patients. A potential side effect of gadolinium contrast agents is nephrogenic systemic fibrosis (NSF). In patients with high risk of NSF unenhanced MRA can be performed with both ECG- and breath-gating techniques. Additionally, MRI provides the possibility to visualise and measure both dynamic and flow information.

State-of-the-art aortic imaging: Part II - applications in transcatheter aortic valve replacement and endovascular aortic aneurysm repair.

Transcatheter aortic valve replacement (TAVR) as well as thoracic and abdominal endovascular aortic repair (TEVAR and EVAR) rely on accurate pre- and postprocedural imaging. This review article discusses the application of imaging, including preprocedural assessment and measurements as well as postprocedural imaging of complications. Furthermore, the exciting perspective of computational fluid dynamics (CFD) based on cross-sectional imaging is presented. TAVR is a minimally invasive alternative for treatment of aortic valve stenosis in patients with high age and multiple comorbidities who cannot undergo traditional open surgical repair. Given the lack of direct visualization during the procedure, pre- and peri-procedural imaging forms an essential part of the intervention. Computed tomography angiography (CTA) is the imaging modality of choice for preprocedural planning. Routine postprocedural follow-up is performed by echocardiography to confirm treatment success and detect complications. EVAR and TEVAR are minimally invasive alternatives to open surgical repair of aortic pathologies. CTA constitutes the preferred imaging modality for both preoperative planning and postoperative follow-up including detection of endoleaks. Magnetic resonance imaging is an excellent alternative to CT for postoperative follow-up, and is especially beneficial for younger patients given the lack of radiation. Ultrasound is applied in screening and postoperative follow-up of abdominal aortic aneurysms, but cross-sectional imaging is required once abnormalities are detected. Contrast-enhanced ultrasound may be as sensitive as CTA in detecting endoleaks.

Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.

OBJECTIVES It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. METHODS This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. RESULTS Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. CONCLUSIONS Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.

State of the art of integrated therapy approaches in the treatment of schizophrenia: empirical evidence and clinical relevance

Objective: Integrated behavior therapy approaches are defined by the combination of behavioral and or cognitive interventions targeting neurocognition combined with other goal-oriented treatment targets such as social cognition, social skills, or educational issues. The Integrated Psychological Therapy Program (IPT) represents one of the very first behavior therapy approaches combining interventions of neurocognition, social cognition, and social competence. This comprehensive group-based bottom-up and top-down approach consists of five subprograms, each with incremental steps. IPT has been successfully implemented in several countries in Europe, America, Australia and in Asia. IPT worked as a model for some other approaches designed in the USA. IPT was undergone two further developments: based on the social competence part of IPT, the three specific therapy programs focusing residential, occupational or recreational topics were developed. Recently, the cognitive part of INT was rigorously expanded into the Integrated Neurocognitive Therapy (INT) designed exclusively for outpatient treatment: INT includes interventions targeting all neurocognitive and social cognitive domains defined by the NIMH-MATRICS initiative. These group and partially PC-based exercises are structured into four therapy modules, each starting with exercises on neurocognitive domains followed by social cognitive targets. Efficacy: The evidence of integrated therapy approaches and its advantage compared to of one-track interventions was becoming a discussion tool in therapy research as well as in mental health systems. Results of meta-analyses support superiority of integrated approaches compared to one-track interventions in more distal outcome areas such as social functioning. These results are in line with the large body of 37 independent IPT studies in 12 countries. Moreover, IPT research indicates the maintenance of therapy effects after the end of therapy and some evidence generalization effects. Additionally, the international randomized multi-center study on INT with 169 outpatients strongly supports the successful therapy of integrated therapy in proximal and distal outcome such as significant effects in cognition, functioning and negative symptoms. Clinical implication: therapy research as well as expert’s clinical experience recommends integrated therapy approaches such as IPT to be successful agents within multimodal psychiatric treatment concepts. Finally, integrated group therapy based on cognitive remediation seems to motivate and stimulate schizophrenia inpatients and outpatients to more successful and independent life also demanded by the recovery movement.

State of the art: Reproduction and pregnancy in rheumatic diseases

Throughout the last decade, increasing awareness has been raised on issues related to reproduction in rheumatic diseases including basic research to clarify the important role of estrogens in the etiology and pathophysiology of immune/inflammatory diseases. Sub- or infertility is a heterogeneous condition that can be related to immunological mechanisms, to pregnancy loss, to disease burden, to therapy, and to choices in regard to family size. Progress in reproductive medicine has made it possible for more patients with rheumatic disease to have children. Active disease in women with rheumatoid arthritis (RA) affects their children's birth weight and may have long-term effects on their future health status. Pregnancy complications as preeclampsia and intrauterine growth restriction are still increased in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), however, biomarkers can monitor adverse events, and several new therapies may improve outcomes. Pregnancies in women with APS remain a challenge, and better therapies for the obstetric APS are needed. New prospective studies indicate improved outcomes for pregnancies in women with rare diseases like systemic sclerosis and vasculitis. TNF inhibitors hold promise for maintaining remission in rheumatological patients and may be continued at least in the first half of pregnancy. Pre-conceptional counseling and interdisciplinary management of pregnancies are essential for ensuring optimal pregnancy outcomes.