Outcomes of open repair of postdissection abdominal aortic aneurysms

Background: Evidence to guide management of postdissection abdominal aortic aneurysms (PDAAA) is lacking. This study describes the outcomes of open repair of PDAAA. Methods: A retrospective cohort study was conducted of all consecutive patients treated with open repair for PDAAA after a Stanford type A or type B thoracic aortic dissection between January 2006 and December 2017 in two vascular referral centers. Preceding type B dissection treatment could include conservative or surgical management. Primary outcomes were 30-day mortality, complication rates, survival, and reintervention-free survival. Survival and reintervention-free survival were analyzed using the Kaplan-Meier method. Reintervention was defined as any endovascular or surgical intervention after the index procedure. Results: Included were 36 patients (27 men [75%]) with a median age of 64 years (range, 35-81 years). The 30-day mortality was 2.7%. The median follow-up was 16 months (range, 0-88 months). The postoperative course was uneventful in 21 patients (58%). The most frequent complications were postoperative bleeding requiring repeat laparotomy (n = 4), pneumonia (n = 3), congestive heart failure (n = 2), new-onset atrial fibrillation (n = 2), mesenteric ischemia requiring left hemicolectomy (n=1), and ischemic cerebrovascular accident (n = 1). Renal failure requiring hemodialysis developed in one patient. The overall survival at 1 year was 88.8%. Reintervention-free survival was 95.5% after 1 year and 88.6% after 2 years. Conclusions: Open repair of PDAAA can be performed with a low mortality rate and an acceptable complication rate, comparable with elective open repair of abdominal aortic aneurysms without dissection

Endograft apposition and infrarenal neck enlargement after endovascular aortic aneurysm repair

BACKGROUND: Sufficient apposition and oversizing of the endograft in the aortic neck are both essential for durable endovascular aneurysm repair (evar). These measures are however not regularly stated on post-evar computed tomography angiography (CTa) scan reports. in this study endograft apposition and neck enlargement (NE) after EVAR with an Endurant II(s) endograft were analyzed and associated with supra- and infrarenal aortic neck morphology. MeThods: in 97 consecutive elective patients, the aortic neck morphology was measured on the pre-evar CTa scan on a 3mensio vascular workstation. The distance between the lowest renal artery and the proximal edge of the fabric (shortest fabric distance, sfd), and the shortest length of circumferential apposition between endograft and aortic wall (shortest apposition length, sal) were determined on the early postEVAR CTA scan. NE, defined as the aortic diameter change between pre- and post-EVAR CTA scan, was determined at eight levels: +40, +30, +20, +15, +10, 0, -5 and -10 mm relative to the lowest renal artery baseline. The aortic neck diameter and preoperative oversizing were correlated to NE with the Pearson correlation coefficient. The effective post-EVAR endograft oversizing is calculated from the nominal endograft diameter and the post-evar neck diameter where the endograft is circumferentially apposed. resulTs: The median time (interquartile range, iQr) between the evar procedure and the pre- and post-evar CTa scan was 40 (25, 71) days and 36 (30, 46) days, respectively. The endurant ii(s) endograft was deployed with a median (iQr) sfd of 1.0 (0.0, 3.0) mm. The sal was <10 mm in 9% of patients and significantly influenced by the pre-EVAR aortic neck length (P=0.001), hostile neck shape (P=0.017), and maximum curvature at the suprarenal aorta (P=0.039). The median (interquartile range) SAL was 21.0 (15.0, 27.0) mm with a median (IQR) pre-evar infrarenal neck length of 23.5 (13.0, 34.8) mm. The median (iQr) difference between the sal and neck length was -5.0 (-12.0, 2.8) mm. Significant (P<0.001) NE of 1.7 (0.9, 2.5) mm was observed 5 mm below the renal artery baseline, which resulted in an effective post-EVAR endograft oversizing <10% in 43% of the patients. No correlation was found between NE and aortic neck diameter or preoperative oversizing. ConClusions: Circumferential apposition between an endograft and the infrarenal aortic neck, sal, and ne can be derived from standard postoperative CT scans. These variables provide essential information about the post-procedural endograft and aortic neck morphology regardless of the preoperative measurements. Patients with SAL<10 mm or effective oversizing <10% due to NE may benefit from intensified followup, but clinical consequences of sal and ne should be evaluated in future longitudinal studies with longer term follow-up

Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data

We report a quasi-differential upper limit on the extremely-high-energy (EHE) neutrino flux above $5\times 10^{6}$ GeV based on an analysis of nine years of IceCube data. The astrophysical neutrino flux measured by IceCube extends to PeV energies, and it is a background flux when searching for an independent signal flux at higher energies, such as the cosmogenic neutrino signal. We have developed a new method to place robust limits on the EHE neutrino flux in the presence of an astrophysical background, whose spectrum has yet to be understood with high precision at PeV energies. A distinct event with a deposited energy above $10^{6}$ GeV was found in the new two-year sample, in addition to the one event previously found in the seven-year EHE neutrino search. These two events represent a neutrino flux that is incompatible with predictions for a cosmogenic neutrino flux and are considered to be an astrophysical background in the current study. The obtained limit is the most stringent to date in the energy range between $5 \times 10^{6}$ and $5 \times 10^{10}$ GeV. This result constrains neutrino models predicting a three-flavor neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\ {\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}$at$10^9\ {\rm GeV}$. A significant part of the parameter-space for EHE neutrino production scenarios assuming a proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review

An evidence-based recommendation on bed head elevation for mechanically ventilated patients

A semi-upright position in ventilated patients is recommended to prevent ventilator-associated pneumonia (VAP) and is one of the components in the Ventilator Bundle of the Institute for Health Care Improvement. This recommendation, however, is not an evidence-based one.status: publishe

Urethral catheters: can we reduce use?

<p>Abstract</p> <p>Background</p> <p>Indwelling urinary catheters are the main cause of healthcare-associated urinary tract infections. It can be expected that reduction of the use of urinary catheters will lead to decreased numbers of urinary tract infection.</p> <p>Methods</p> <p>The efficacy of an intervention programme to improve adherence to recommendations to reduce the use of urethral catheters was studied in a before-after comparison in ten Dutch hospitals. The programme detected barriers and facilitators and each individual facility was supported with developing their own intervention strategy. Outcome was evaluated by the prevalence of catheters, alternatives such as diapers, numbers of urinary tract infections, the percentage of correct indications and the duration of catheterization. The costs of the implementation as well as the catheterization were evaluated.</p> <p>Results</p> <p>Of a population of 16,495 hospitalized patients 3335 patients of whom 2943 were evaluable for the study, had a urethral catheter. The prevalence of urethral catheters decreased insignificantly in neurology (OR 0.93; 95% CI 0.77 - 1.13) and internal medicine wards (OR 0.97; 95% CI 0.83 - 1.13), decreased significantly in surgical wards (OR 0.84; 95% CI 0.75 - 0.96), but increased significantly in intensive care (IC) and coronary care (CC) units (OR 1.48; 95% CI 1.01 - 2.17). The use of alternatives was limited and remained so after the intervention. Duration of catheterization decreased insignificantly in IC/CC units (ratio after/before 0.95; 95% CI 0.78 - 1.16) and neurology (ratio 0.97; 95% CI 0.80 - 1.18) and significantly in internal medicine (ratio 0.81; 95% CI 0.69 - 0.96) and surgery wards (ratio 0.80; 95% CI 0.71 - 0.90). The percentage of correct indications on the day of inclusion increased from 50 to 67% (p < 0.0001). The prevalence of urinary tract infections in catheterized patients did not change. The mean cost saved per 100 patients was € 537.</p> <p>Conclusion</p> <p>Targeted implementation of recommendations from an existing guideline can lead to better adherence and cost savings. Especially, hospitals which use a lot of urethral catheters or where catheterization is prolonged, can expect important improvements.</p

Structure-Based Design of Non-Natural Amino Acid Inhibitors of Amyloid Fibrillation

Many globular and natively disordered proteins can convert into amyloid fibers. These fibers are associated with numerous pathologies1 as well as with normal cellular functions2,3, and frequently form during protein denaturation4,5. Inhibitors of pathological amyloid fibers could serve as leads for therapeutics, provided the inhibitors were specific enough to avoid interfering with normal processes. Here we show that computer-aided, structure-based design can yield highly specific peptide inhibitors of amyloid formation. Using known atomic structures of segments of amyloid fibers as templates, we have designed and characterized an all D-amino acid inhibitor of fibrillation of the tau protein found in Alzheimer’s disease, and a non-natural L-amino acid inhibitor of an amyloid fiber that enhances sexual transmission of HIV. Our results indicate that peptides from structure-based designs can disrupt the fibrillation of full-length proteins, including those like tau that lack fully ordered native structures.We thank M.I. Ivanova, J. Corn, T. Kortemme, D. Anderson, M.R. Sawaya, M. Phillips, S. Sambashivan, J. Park, M. Landau, Q. Zhang, R. Clubb, F. Guo, T. Yeates, J. Nowick, J. Zheng, and M.J. Thompson for discussions, HHMI, NIH, NSF, the GATES foundation, and the Joint Center for Translational Medicine for support, R. Peterson for help with NMR experiments, E. Mandelkow for providing tau constructs, R. Riek for providing amyloid beta, J. Stroud for amyloid beta preparation. Support for JK was from the Damon Runyon Cancer Research Foundation, for HWC by the Ruth L. Kirschstein National Research Service Award, for JM from the programme for junior-professors by the ministry of science, Baden-Württemberg, and for SAS by a UCLA-IGERT bioinformatics traineeship

Covid-19 triage in the emergency department 2.0: how analytics and AI transform a human-made algorithm for the prediction of clinical pathways

The Covid-19 pandemic has pushed many hospitals to their capacity limits. Therefore, a triage of patients has been discussed controversially primarily through an ethical perspective. The term triage contains many aspects such as urgency of treatment, severity of the disease and pre-existing conditions, access to critical care, or the classification of patients regarding subsequent clinical pathways starting from the emergency department. The determination of the pathways is important not only for patient care, but also for capacity planning in hospitals. We examine the performance of a human-made triage algorithm for clinical pathways which is considered a guideline for emergency departments in Germany based on a large multicenter dataset with over 4,000 European Covid-19 patients from the LEOSS registry. We find an accuracy of 28 percent and approximately 15 percent sensitivity for the ward class. The results serve as a benchmark for our extensions including an additional category of palliative care as a new label, analytics, AI, XAI, and interactive techniques. We find significant potential of analytics and AI in Covid-19 triage regarding accuracy, sensitivity, and other performance metrics whilst our interactive human-AI algorithm shows superior performance with approximately 73 percent accuracy and up to 76 percent sensitivity. The results are independent of the data preparation process regarding the imputation of missing values or grouping of comorbidities. In addition, we find that the consideration of an additional label palliative care does not improve the results

Protease-Resistant Prions Selectively Decrease Shadoo Protein

The central event in prion diseases is the conformational conversion of the cellular prion protein (PrPC) into PrPSc, a partially protease-resistant and infectious conformer. However, the mechanism by which PrPSc causes neuronal dysfunction remains poorly understood. Levels of Shadoo (Sho), a protein that resembles the flexibly disordered N-terminal domain of PrPC, were found to be reduced in the brains of mice infected with the RML strain of prions [1], implying that Sho levels may reflect the presence of PrPSc in the brain. To test this hypothesis, we examined levels of Sho during prion infection using a variety of experimental systems. Sho protein levels were decreased in the brains of mice, hamsters, voles, and sheep infected with different natural and experimental prion strains. Furthermore, Sho levels were decreased in the brains of prion-infected, transgenic mice overexpressing Sho and in infected neuroblastoma cells. Time-course experiments revealed that Sho levels were inversely proportional to levels of protease-resistant PrPSc. Membrane anchoring and the N-terminal domain of PrP both influenced the inverse relationship between Sho and PrPSc. Although increased Sho levels had no discernible effect on prion replication in mice, we conclude that Sho is the first non-PrP marker specific for prion disease. Additional studies using this paradigm may provide insight into the cellular pathways and systems subverted by PrPSc during prion disease

STE-QUEST - Test of the Universality of Free Fall Using Cold Atom Interferometry

In this paper, we report about the results of the phase A mission study of the atom interferometer instrument covering the description of the main payload elements, the atomic source concept, and the systematic error sources