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.

Optimal dose levels in screening chest CT for unimpaired detection and volumetry of lung nodules, with and without computer assisted detection at minimal patient radiation

OBJECTIVES The aim of this phantom study was to minimize the radiation dose by finding the best combination of low tube current and low voltage that would result in accurate volume measurements when compared to standard CT imaging without significantly decreasing the sensitivity of detecting lung nodules both with and without the assistance of CAD. METHODS An anthropomorphic chest phantom containing artificial solid and ground glass nodules (GGNs, 5-12 mm) was examined with a 64-row multi-detector CT scanner with three tube currents of 100, 50 and 25 mAs in combination with three tube voltages of 120, 100 and 80 kVp. This resulted in eight different protocols that were then compared to standard CT sensitivity (100 mAs/120 kVp). For each protocol, at least 127 different nodules were scanned in 21-25 phantoms. The nodules were analyzed in two separate sessions by three independent, blinded radiologists and computer-aided detection (CAD) software. RESULTS The mean sensitivity of the radiologists for identifying solid lung nodules on a standard CT was 89.7% ± 4.9%. The sensitivity was not significantly impaired when the tube and current voltage were lowered at the same time, except at the lowest exposure level of 25 mAs/80 kVp [80.6% ± 4.3% (p = 0.031)]. Compared to the standard CT, the sensitivity for detecting GGNs was significantly lower at all dose levels when the voltage was 80 kVp; this result was independent of the tube current. The CAD significantly increased the radiologists' sensitivity for detecting solid nodules at all dose levels (5-11%). No significant volume measurement errors (VMEs) were documented for the radiologists or the CAD software at any dose level. CONCLUSIONS Our results suggest a CT protocol with 25 mAs and 100 kVp is optimal for detecting solid and ground glass nodules in lung cancer screening. The use of CAD software is highly recommended at all dose levels.

Organotypic slice cultures from rat brain tissue: a new approach for Naegleria fowleri CNS infection in vitro

The free-living amoeba Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis (PAM), a disease leading to death in the vast majority of cases. In patients suffering from PAM, and in corresponding animal models, the brain undergoes a massive inflammatory response, followed by haemorrhage and severe tissue necrosis. Both, in vivo and in vitro models are currently being used to study PAM infection. However, animal models may pose ethical issues, are dependent upon availability of specific infrastructural facilities, and are time-consuming and costly. Conversely, cell cultures lack the complex organ-specific morphology found in vivo, and thus, findings obtained in vitro do not necessarily reflect the situation in vivo. The present study reports infection of organotypic slice cultures from rat brain with N. fowleri and compares the findings in this culture system with in vivo infection in a rat model of PAM, that proved complementary to that of mice. We found that brain morphology, as present in vivo, is well retained in organotypic slice cultures, and that infection time-course including tissue damage parallels the observations in vivo in the rat. Therefore, organotypic slice cultures from rat brain offer a new in vitro approach to study N. fowleri infection in the context of PAM.

Brain-derived neurotrophic factor protects against multiple forms of brain injury in bacterial meningitis

BACKGROUND Brain-derived neurotrophic factor (BDNF) blocks activation of caspase-3, reduces translocation of apoptosis-inducing factor (AIF), attenuates excitotoxicity of glutamate, and increases antioxidant enzyme activities. The mechanisms of neuroprotection suggest that BDNF may be beneficial in bacterial meningitis. METHODS To assess a potentially beneficial effect of adjuvant treatment with BDNF in bacterial meningitis, 11-day-old infant rats with experimental meningitis due to Streptococcus pneumoniae or group B streptococci (GBS) were randomly assigned to receive intracisternal injections with either BDNF (3 mg/kg) or equal volumes (10 mu L) of saline. Twenty-two hours after infection, brains were analyzed, by histomorphometrical examination, for the extent of cortical and hippocampal neuronal injury. RESULTS Compared with treatment with saline, treatment with BDNF significantly reduced the extent of 3 distinct forms of brain cell injury in this disease model: cortical necrosis in meningitis due to GBS (median, 0.0% [range, 0.0%-33.7%] vs. 21.3% [range, 0.0%-55.3%]; P<.03), caspase-3-dependent cell death in meningitis due to S. pneumoniae (median score, 0.33 [range, 0.0-1.0] vs. 1.10 [0.10-1.56]; P<.05), and caspase-3-independent hippocampal cell death in meningitis due to GBS (median score, 0 [range, 0-2] vs. 0.88 [range, 0-3.25]; P<.02). The last form of injury was associated with nuclear translocation of AIF. CONCLUSION BDNF efficiently reduces multiple forms of neuronal injury in bacterial meningitis and may hold promise as adjunctive therapy for this disease.

Apoptosis of hippocampal neurons in organotypic slice culture models: direct effect of bacteria revisited

Neurons of the hippocampal dentate gyrus selectively undergo programmed cell death in patients suffering from bacterial meningitis and in experimental models of pneumococcal meningitis in infant rats. In the present study, a membrane-based organotypic slice culture system of rat hippocampus was used to test whether this selective vulnerability of neurons of the dentate gyrus could be reproduced in vitro. Apoptosis was assessed by nuclear morphology (condensed and fragmented nuclei), by immunochemistry for active caspase-3 and deltaC-APP, and by proteolytic caspase-3 activity. Co-incubation of the cultures with live pneumococci did not induce neuronal apoptosis unless cultures were kept in partially nutrient-deprived medium. Complete nutrient deprivation alone and staurosporine independently induced significant apoptosis, the latter in a dose-response way. In all experimental settings, apoptosis occurred preferentially in the dentate gyrus. Our data demonstrate that factors released by pneumococci per se failed to induce significant apoptosis in vitro. Thus, these factors appear to contribute to a multifactorial pathway, which ultimately leads to neuronal apoptosis in bacterial meningitis.

Caspase-3 mediates hippocampal apoptosis in pneumococcal meningitis

Bacterial meningitis causes neuronal apoptosis in the hippocampal dentate gyrus, which is associated with learning and memory impairments after cured disease. The execution of the apoptotic program involves pathways that converge on activation of caspase-3, which is required for morphological changes associated with apoptosis. Here, the time course and the role of caspase-3 in neuronal apoptosis was assessed in an infant rat model of pneumococcal meningitis. During clinically asymptotic meningitis (0-12 h after infection), only minor apoptotic damage to the dentate gyrus was observed, while the acute phase (18-24 h) was characterized by a massive increase of apoptotic cells, which peaked at 36 h. In the subacute phase of the disease (36-72 h), the number of apoptotic cells decreased to control levels. Enzymatic caspase-3 activity was significantly increased in hippocampal tissue of infected animals compared to controls at 22 h. The activated enzyme was localized to immature cells of the dentate gyrus, and in vivo activity was evidenced by cleavage of the amyloid-beta precursor protein. Intracisternal administration of the caspase-3-specific inhibitor Ac-DEVD-CHO significantly reduced apoptosis in the hippocampal dentate gyrus. In contrast to a study where the decrease of hippocampal apoptosis after administration of a pan-caspase inhibitor was due to downmodulation of the inflammatory response, our data demonstrate that specific inhibition of caspase-3 did not affect inflammation assessed by TNF-alpha and IL-1beta concentrations in the cerebrospinal fluid space. Taken together, the present results identify caspase-3 as a key effector of neuronal apoptosis in pneumococcal meningitis.

A hybrid method for large-scale short-term scheduling of make-and-pack production processes

Due to the ongoing trend towards increased product variety, fast-moving consumer goods such as food and beverages, pharmaceuticals, and chemicals are typically manufactured through so-called make-and-pack processes. These processes consist of a make stage, a pack stage, and intermediate storage facilities that decouple these two stages. In operations scheduling, complex technological constraints must be considered, e.g., non-identical parallel processing units, sequence-dependent changeovers, batch splitting, no-wait restrictions, material transfer times, minimum storage times, and finite storage capacity. The short-term scheduling problem is to compute a production schedule such that a given demand for products is fulfilled, all technological constraints are met, and the production makespan is minimised. A production schedule typically comprises 500–1500 operations. Due to the problem size and complexity of the technological constraints, the performance of known mixed-integer linear programming (MILP) formulations and heuristic approaches is often insufficient. We present a hybrid method consisting of three phases. First, the set of operations is divided into several subsets. Second, these subsets are iteratively scheduled using a generic and flexible MILP formulation. Third, a novel critical path-based improvement procedure is applied to the resulting schedule. We develop several strategies for the integration of the MILP model into this heuristic framework. Using these strategies, high-quality feasible solutions to large-scale instances can be obtained within reasonable CPU times using standard optimisation software. We have applied the proposed hybrid method to a set of industrial problem instances and found that the method outperforms state-of-the-art methods.

Nachsorge nach bariatrischen Operationen

Mit der stetigen Zunahme an bariatrisch operierten Patienten wird die langfristige Nachsorge dieser Patientengruppe zu einer Herausforderung. Bariatrische Patienten bedürfen einer regelmäßigen und lebenslangen Nachkontrolle, damit die erzielten Erfolge nachhaltig positiv beeinflusst zu werden. Deswegen soll die Nachbetreuung von bariatrisch operierten Patienten in der ersten Phase von einem multidisziplinären Team übernommen werden, was bei stabiler Situation und unter Berücksichtigung einiger grundsätzlichen Überlegungen in der Betreuung der postbariatrischen Patienten auch durch niedergelassene Ärzte außerhalb eines Kompetenzzentrums durchgeführt werden können.

Bariatrische und metabolische Chirurgie

The prevalence of obesity and its comorbidities is constantly rising and is one of the most threatening global health and economic problems worldwide. Whereas bariatric surgery is well accepted in the treatment of morbid obesity, surgical treatment for ist comorbidities (metabolic surgery) such as type 2 diabetes mellitus, dyslipidemia and other diseases are still under discussion. A more profound knowledge of its physiologic mechanisms is crucial for the future implementation of the bariatric and metabolic surgery to treat obesity-related comorbidities.

Optimizing Triage and Hospitalization in Adult General Medical Emergency Patients. The Triage Project

Background: Patients presenting to the emergency department (ED) currently face inacceptable delays in initial treatment, and long, costly hospital stays due to suboptimal initial triage and site-of-care decisions. Accurate ED triage should focus not only on initial treatment priority, but also on prediction of medical risk and nursing needs to improve site-of-care decisions and to simplify early discharge management. Different triage scores have been proposed, such as the Manchester triage system (MTS). Yet, these scores focus only on treatment priority, have suboptimal performance and lack validation in the Swiss health care system. Because the MTS will be introduced into clinical routine at the Kantonsspital Aarau, we propose a large prospective cohort study to optimize initial patient triage. Specifically, the aim of this trial is to derive a three-part triage algorithm to better predict (a) treatment priority; (b) medical risk and thus need for in-hospital treatment; (c) post-acute care needs of patients at the most proximal time point of ED admission. Methods/design: Prospective, observational, multicenter, multi-national cohort study. We will include all consecutive medical patients seeking ED care into this observational registry. There will be no exclusions except for non-adult and non-medical patients. Vital signs will be recorded and left over blood samples will be stored for later batch analysis of blood markers. Upon ED admission, the post-acute care discharge score (PACD) will be recorded. Attending ED physicians will adjudicate triage priority based on all available results at the time of ED discharge to the medical ward. Patients will be reassessed daily during the hospital course for medical stability and readiness for discharge from the nurses and if involved social workers perspective. To assess outcomes, data from electronic medical records will be used and all patients will be contacted 30 days after hospital admission to assess vital and functional status, re-hospitalization, satisfaction with care and quality of life measures. We aim to include between 5000 and 7000 patients over one year of recruitment to derive the three-part triage algorithm. The respective main endpoints were defined as (a) initial triage priority (high vs. low priority) adjudicated by the attending ED physician at ED discharge, (b) adverse 30 day outcome (death or intensive care unit admission) within 30 days following ED admission to assess patients risk and thus need for in-hospital treatment and (c) post acute care needs after hospital discharge, defined as transfer of patients to a post-acute care institution, for early recognition and planning of post-acute care needs. Other outcomes are time to first physician contact, time to initiation of adequate medical therapy, time to social worker involvement, length of hospital stay, reasons fordischarge delays, patient’s satisfaction with care, overall hospital costs and patients care needs after returning home. Discussion: Using a reliable initial triage system for estimating initial treatment priority, need for in-hospital treatment and post-acute care needs is an innovative and persuasive approach for a more targeted and efficient management of medical patients in the ED. The proposed interdisciplinary , multi-national project has unprecedented potential to improve initial triage decisions and optimize resource allocation to the sickest patients from admission to discharge. The algorithms derived in this study will be compared in a later randomized controlled trial against a usual care control group in terms of resource use, length of hospital stay, overall costs and patient’s outcomes in terms of mortality, re-hospitalization, quality of life and satisfaction with care.