C-P bond formation of cyclophanyl-, and aryl halides via a UV-induced photo Arbuzov reaction : a versatile portal to phosphonate-grafted scaffolds

A new versatile method for the C-P bond formation of (hetero)aryl halides with trimethyl phosphite via a UV-induced photo-Arbuzov reaction, accessing diverse phosphonate-grafted arenes, heteroarenes and co-facially stacked cyclophanes under mild reaction conditions without the need for catalyst, additives, or base is developed. The UV-induced photo-Arbuzov protocol has a wide synthetic scope with large functional group compatibility exemplified by over 30 derivatives. Besides mono-phosphonates, di- and tri-phosphonates are accessible in good to excellent yields. Mild and transition metal-free reaction conditions consolidate this method's potential for synthesizing pharmaceutically relevant compounds and precursors of supramolecular nanostructured materials.Peer reviewe

Follow-up of CRT-D patients downgraded to CRT-P at the time of generator exchange

Background: Some patients with cardiac resynchronisation therapy (CRT) experience super-response (LVEF improvements to ≥50%). At generator exchange (GE), downgrading (DG) from CRT-defibrillator (CRT-D) to CRT-pacemaker (CRT-P) could be an option for these patients on primary prevention ICD indication and no required ICD therapies. Long-term data on arrhythmic events in super-responders is scarce. Methods: CRT-D patients with LVEF improvement to ≥50% at GE were identified in four large centres for retrospective analysis. Mortality, significant ventricular tachyarrhythmia and appropriate ICD-therapy were determined, and patient analysis was split into two groups (downgraded to CRT-P or not). Results: Sixty-six patients (53% male, 26% coronary artery disease) on primary prevention were followed for a median of 129 months [IQR: 101–155] after implantation. 27 (41%) patients were downgraded to CRT-P at GE after a median of 68 [IQR: 58–98] months (LVEF 54% ± 4%). The other 39 (59%) continued with CRT-D therapy (LVEF 52% ± 6%). No cardiac death or significant arrhythmia occurred in the CRT-P group (median follow-up (FU) 38 months [IQR: 29–53]). Three appropriate ICD-therapies occurred in the CRT-D group [median FU 70 months (IQR: 39–97)]. Annualized event-rates after DG/GE were 1.5%/year and 1.0%/year in the CRT-D group and the whole cohort, respectively. Conclusions: No significant tachyarrhythmia were detected in the patients downgraded to CRT-P during follow-up. However, three events were observed in the CRT-D group. Whilst downgrading CRT-D patients is an option, a small residual risk for arrhythmic events remains and decisions regarding downgrade should be made on a case-by-case basis.</p

Augmentation Index in Patients with Thoracic Aortic Aneurysm: A Matched Case-Control Study

Thoracic aortic aneurysms (TAA) may be associated with complications such as rupture and dissection, which can lead to a fatal outcome. Increased central arterial stiffness has been proposed to be present in patients with TAA compared to unmatched controls. We aimed to assess whether wall properties in patients with TAA are also altered when compared to a matched control group. Applanation tonometry was performed in 74 adults with TAA and 74 sex, age, weight, height, and left ventricular ejection fraction matched controls. Subsequently analysis of the pulse wave was done using the SphygmoCor System. For comparing the two groups, AIx was adjusted to a heart rate of 75/min (AIx@75). 148 1-to-1 matched participants were included in the final model. There was no significant difference in the Alx@75 between the TAA group and the matched control group [mean (SD) of 24.7 (11.2) % and 22.8 (11.2) %, p = 0.240]. Adjusted for known cardiovascular risk factors, there was no association between TAA and AIx@75. Patients with TAA showed comparable arterial wall properties to cardiovascular risk factor matched controls. Since higher arterial stiffness is associated with TAA progression, it remains to be investigated if increased central arterial stiffness is a relevant factor of TAA emergence. Keywords: thoracic aortic aneurysm; augmentation index; arterial stiffnes

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

Efficient Enzymatic Amine Resolution at High Substrate Input Using Diethyl Malonate as an Acyl Donor of Low Hazard Potential

Simon S, Osswald S, Roos J, Gröger H. Efficient Enzymatic Amine Resolution at High Substrate Input Using Diethyl Malonate as an Acyl Donor of Low Hazard Potential. Zeitschrift für Naturforschung Section B-A Journal Of Chemical Sciences. 2012;67b(10):1123-1126.Diethyl malonate turned out to be both a "green" and highly efficient acyl donor in the lipase-catalyzed resolution of amines, thus representing an attractive alternative to currently applied acyl donors. By means of this acyl donor a highly efficient enzymatic process for the resolution of amines, running at high substrate input of up to 200 g/L in an organic solvent classified as "usable" according to the Pfizer Solvent Selection Guide, is presented

The Medtronic Sprint

Due to high failure rates, Medtronic withdrew the Sprint Fidelis lead (SFL) from the market. Passive fixation lead models exhibited better survival than active models, but most studies have limited follow-up. Aim of this study was to give insights into passive lead survival with a follow-up of 10 years.; In two large Swiss centers, patients with passive SFLs were identified and data from routine implantable cardioverter defibrillator (ICD) follow-ups were collected. Patients were censored at time of death, last device interrogation (if lost to follow-up), time of lead revision (in non-SFL-related problems), or at database closure (31th December 2017). We defined lead failure as any of the following: lead fracture with inappropriate discharge; sudden increase in low-voltage impedance to >1500 or high-voltage impedance to >100 Ω; >300 nonphysiological short VV-intervals.; We identified 145 patients. Age at implant was 60 ± 12 years with a median follow-up of 10.2 (interquartile range [IQR]: 5.0-11.2) years. Thirty-five percent of patients died after 5.4 ± 2.7 years. A total of 19 leads (13%) failed after 6.7 ± 3.2 years (range: 1.2-12.0). Overt malfunction with shocks existed in four patients (3%). Cumulative lead survival was 93.1% at 6, 88.2% at 8, 83.8% at 10, and 77.6% at 11 years, respectively, with 35% of implanted leads under monitoring at 10 years. Lead survival fits best a Weibull distribution with accelerating failure rates (k = 1.95, 95% CI 1.32-2.87, P < 0.001).; During very long-term follow-up, failure rate of the passive SFL shows an increase resulting in an impaired lead survival of 84% at 10 years

Prevalence of Obstructive Sleep Apnea in Patients with Thoracic Aortic Aneurysm: A Prospective, Parallel Cohort Study

Background: The pathogenesis and etiology of thoracic aortic aneurysms (TAA) are largely unknown. Preliminary data from patients with aortic dissection and abdominal aneurysms suggest a causal link of obstructive sleep apnea (OSA) on aortic disease. Objectives: The aim of the study was to assess the prevalence of OSA in patients with TAA compared to a matched control group. Method: In this prospective parallel-cohort study, we 2-to-1 matched 208 patients with verified TAA (at the aortic sinus and/or ascending aorta) to 104 controls without TAA according to sex, age, height, weight, and left ventricular ejection fraction. All participants underwent an ultrasound of the thoracic aorta and a level III respiratory polygraphy. OSA was defined as apnea-hypopnea index ≥5/h. The prevalence of OSA was compared with conditional logistic regression and controlling for the matching variables. Results: A total of 312 patients (mean age 65 ± 11 years, 82% male, mean body mass index 27 ± 4 kg/m2) were successfully 2-to-1 matched in the final model. Prevalence of OSA was significantly higher in the TAA-group when compared to the matched control group (63 vs. 47%; odds ratio 1.87 [95% CI 1.05–3.34]; p = 0.03). When applying a higher apnea-hypopnea index threshold (≥15/h), the odds ratio increased to 3.25 (95% CI 1.65–6.42; p < 0.001). The median apnea-hypopnea index was higher in patients with TAA (9.2/h [3.3–20.0] vs. 4.5/h [2.2–11.1], p < 0.001). Conclusions: Patients with TAA have a higher prevalence of OSA when compared to the general population. Since OSA is effectively treatable and might contribute to the pathogenesis of TAA, further longitudinal trials are needed to assess the association between OSA and TAA

A study towards efficient L-threonine aldolase-catalyzed enantio- and diastereoselective aldol reactions of glycine with substituted benzaldehydes: biocatalyst production and process development

Baer K, Dückers N, Rosenbaum T, et al. A study towards efficient L-threonine aldolase-catalyzed enantio- and diastereoselective aldol reactions of glycine with substituted benzaldehydes: biocatalyst production and process development. Tetrahedron Asymmetry. 2011;22(9):925-928.The development of aldol reactions of glycine with substituted benzaldehydes in the presence of recombinant L-threonine aldolases from Escherichia coil or Saccharomyces cerevisiae, which were obtained with excellent overexpression data, has been carried out. When using glycine and ortho-chlorobenzaldehyde, a high conversion of >95%, an enantioselectivity of >99% ee, and a diastereoselectivity with d.r.(syn/anti) = 80:20 was obtained for the resulting beta-hydroxy alpha-amino acid in such a biotransformation. It should be noted that this enzymatic process can be conducted at an elevated substrate concentration of 250 mM. (C) 2011 Elsevier Ltd. All rights reserved