Metabolic Control, Diabetic Complications and Drug Therapy in a Cohort of Patients with Type 1 and Type 2 Diabetes in Secondary and Tertiary Care between 2004 and 2019.

This paper studies the features of metabolic parameters, diabetic complications and drug therapy of a single-centre cohort of patients with type 1 diabetes (T1DM) or type 2 diabetes (T2DM) in secondary care and tertiary care over a 15-year period. METHODS: Retrospective cross-sectional analysis of four single-centre cohorts between 2004 and 2019. All patients with T1DM or T2DM in secondary care (n = 5571) or tertiary care (n = 2001) were included. Statistical analyses were performed using linear mixed models. RESULTS: Diabetes duration increased in both patients with T1DM and T2DM in secondary care and tertiary care (p < 0.001). Patients in secondary care consistently showed good glycaemic control, while patients in tertiary care showed inadequate glycaemic control. All four cross-sectional cohorts showed a significant increase in the prevalence of nephropathy over time and three out of four cohorts (T1DM and T2DM in secondary care and T2DM in tertiary care) showed an increase in the prevalence of neuropathy (all p < 0.001). The incidence of severe hypoglycaemia was consistently low. The use of insulin pumps and insulin analogues in the therapy of T1DM increased significantly. CONCLUSIONS: The increased prevalence of complications is likely due to older age and longer diabetes duration. Low rates of hypoglycaemia, lower limb amputations and good glycaemic control in secondary care patients indicate a good structure of patient care.

Modulating complex beams in amplitude and phase using fast tilt-micromirror arrays and phase masks.

The Letter proposes a system for the spatial modulation of light in amplitude and phase at kilohertz frame rates and high spatial resolution. The focus is fast spatial light modulators (SLMs) consisting of continuously tiltable micromirrors. We investigate the utilization of such SLMs in combination with a static phase mask in a 4f setup. The phase mask enables the complex beam modulation in a linear optical arrangement. Furthermore, adding so-called phase steps to the phase mask increases both the number of image pixels at constant SLM resolution and the optical efficiency. We illustrate our concept based on numerical simulations.

Long-term outcomes of a rapid deployment aortic valve: data up to 5 years.

OBJECTIVES: Rapid deployment aortic valve replacement (AVR) has been developed to facilitate minimally invasive approaches for cardiac surgery and shorten procedural times. TRITON is a prospectively designed study to assess safety and efficacy of rapid deployment AVR with Edwards INTUITY valve system. This report presents the 5-year outcomes of the TRITON trial. METHODS: A total of 295 patients with aortic valve stenosis were enrolled in the TRITON trial and 287 patients received the study valve. Procedural, early (≤30 days) and late (>30 days) outcomes were collected. Valve haemodynamic performance was evaluated at specified time points by an independent Echocardiography Core Laboratory and clinical events adjudicated by an independent Clinical Events Committee. RESULTS: Mean age was 75.3 ± 6.7 years. A total of 158 patients underwent isolated AVR and 129 patients underwent AVR with concomitant procedures. The 5-year survival rates were 85.7 ± 3.4% and 75.2 ± 4.9% for isolated AVR and concomitant AVR, respectively. Overall, freedom from valve-related death at 5 years was 98.2 ± 0.8%. At 5 years, the valve effective orifice area was 1.6 ± 0.3 cm 2 , mean gradient was 10.5 ± 5.4 mmHg and peak gradient was 18.9 ± 9.3 mmHg. CONCLUSIONS: The 5-year outcomes of the TRITON trial demonstrate acceptable long-term safety and excellent haemodynamic performance of rapid deployment AVR with the Edwards INTUITY valve system. CLINICALTRIALS.GOV: NCT01445171.

Early outcomes after isolated aortic valve replacement with rapid deployment aortic valve.

OBJECTIVE: Minimal access aortic valve replacement is associated with favorable clinical outcomes; however, several meta-analyses have reported significantly longer crossclamp times compared with a full sternotomy. We examined the procedural and early safety outcomes after isolated rapid deployment aortic valve replacement by surgical approach in patients enrolled in the Surgical Treatment of Aortic Stenosis With a Next Generation Surgical Aortic Valve trial. METHODS: The Surgical Treatment of Aortic Stenosis With a Next Generation Surgical Aortic Valve trial was a prospective, multicenter, single-arm study, with successful implants in 287 patients with aortic valve stenosis who underwent rapid deployment aortic valve replacement using the EDWARDS INTUITY Valve System (Edwards Lifesciences, Irvine, Calif). Patients were evaluated perioperatively for procedural times and technical success rates; at discharge, for hospital length of stay; and, at 30 days, for early adverse events. RESULTS: A total of 158 patients underwent isolated aortic valve replacement through a full sternotomy (n = 71), upper hemisternotomy (n = 77), or right anterior thoracotomy (n = 10). Mean age at baseline was 75.7 ± 7.2 years. Mean aortic crossclamp and cardiopulmonary bypass times (minutes) were similar for full sternotomy and upper hemisternotomy, 43.5 ± 32.5/71.6 ± 41.8 and 43.1 ± 13.1/69.6 ± 19.1, respectively, and significantly longer for right anterior thoracotomy, 88.3 ± 18.6/122.2 ± 22.1 (P < .000). Early adverse event rates were similar, and in-hospital mortality rates were low regardless of surgical approach. CONCLUSIONS: These data suggest that isolated rapid deployment aortic valve replacement through an upper hemisternotomy can lead to shorter crossclamp times than has been reported historically in the literature. This may facilitate minimal access aortic valve replacement by eliminating the issue of prolonged crossclamp times. Further, low in-hospital mortality and new permanent pacemaker implant rates were observed regardless of surgical approach.

Three-year hemodynamic performance, left ventricular mass regression, and prosthetic-patient mismatch after rapid deployment aortic valve replacement in 287 patients.

OBJECTIVE: Superior aortic valve hemodynamic performance can accelerate left ventricular mass regression and enhance survival and functional status after surgical aortic valve replacement. This can be achieved by rapid deployment aortic valve replacement using a subannular balloon-expandable stent frame, which functionally widens and reshapes the left ventricular outflow tract, to ensure a larger effective orifice area compared with conventional surgical valves. We report the intermediate-term follow-up data from a large series of patients enrolled in the Surgical Treatment of Aortic Stenosis With a Next Generation Surgical Aortic Valve (TRITON) trial. METHODS: In a prospective, multicenter (6 European hospitals), single-arm study, 287 patients with aortic stenosis underwent rapid deployment aortic valve replacement using a stented trileaflet bovine pericardial bioprosthesis. Core laboratory echocardiography was performed at baseline, discharge, and 3 months, 1 year, and 3 years after rapid deployment aortic valve replacement. RESULTS: The mean patient age was 75.7 ± 6.7 years (range, 45-93; 49.1% women). The mean aortic valve gradient significantly decreased from discharge to 3 years of follow-up. The mean effective orifice area remained stable from discharge to 3 years. At 1 year, the left ventricular mass index had decreased by 14% (P < .0001) and at 3 years by 16% (P < .0001) compared with at discharge. The prevalence of severe patient-prosthesis mismatch was 3% at discharge and remained stable during the follow-up period. CONCLUSIONS: In a large series of elderly patients with symptomatic severe aortic stenosis, rapid deployment aortic valve replacement using a subannular balloon-expandable stent frame demonstrated excellent hemodynamic performance and significant left ventricular mass regression. With continued follow-up, future studies will establish whether these favorable structural changes correlate with improvement in long-term survival and functional status.

Apple procyanidins affect several members of the ErbB receptor tyrosine kinase family in vitro.

Complex polyphenol-rich extracts from apples are known to inhibit the activity of the epidermal growth factor receptor (EGFR) in vitro. The aim of the present study was to identify the bioactive constituents of the apple juice extract which contribute substantially to this potentially chemopreventive effect and to address the question whether the effect is specific to the EGFR or whether other members of the ErbB-receptor family might also be affected. Apple-derived dihydrochalcones and their respective glycosides were found to decrease EGFR activity under cell-free conditions with IC50-values ranging from 0.4 ± 0.1 to 267.0 ± 50.0 µM but showed no activity on human cancer cells. The concentration of quercetin or its glycosides in the extract was too low to contribute substantially to the EGFR-inhibitory properties. In contrast, fractions derived from the apple juice extract comprising ≥86% oligomeric procyanidins (OPCs) suppressed the activity of the EGFR in cell culture with an IC50 ∼ 100 µg mL(-1). In addition, the activity of further members of the ErbB-receptor family was potently inhibited, with ErbB3 receptor activity being most potently decreased (IC50 ∼ 10 µg mL(-1)). From the apple polyphenols identified so far OPCs were found to add the highest contribution to the inhibitory effects towards members of the ErbB-receptor family. Considering the crucial role of the ErbB-receptors in carcinogenesis, these results support the hypothesis that apple-derived OPCs as well as OPC-rich apple preparations might be of interest with respect to chemoprevention.

One-year outcomes of the Surgical Treatment of Aortic Stenosis With a Next Generation Surgical Aortic Valve (TRITON) trial: a prospective multicenter study of rapid-deployment aortic valve replacement with the EDWARDS INTUITY Valve System.

OBJECTIVES: A new class of rapid-deployment aortic valves has emerged with the potential to simplify minimally invasive aortic surgery and reduce crossclamp and cardiopulmonary bypass times. We report the 1-year clinical outcomes of aortic valve replacement with the EDWARDS INTUITY Valve System (Edwards Lifesciences LLC, Irvine, Calif) in the Surgical Treatment of Aortic Stenosis With a Next Generation Surgical Aortic Valve (TRITON) trial. METHODS: Seventeen surgeons from 6 European centers treated 152 consecutive patients with aortic stenosis requiring valve replacement in a prospective, single-arm trial. A stented trileaflet bovine pericardial bioprosthesis with a balloon-expandable, cloth-covered stent frame at the inflow aspect was implanted in 146 patients (mean age, 75.5 ± 6.7 years; 52.7% were female). Five valve sizes were evaluated (19-27 mm); 58.9% of cases had isolated aortic valve replacement, and 41.1% of cases involved concomitant procedures. Minimally invasive surgical approaches occurred in 48.8% of the isolated aortic valve replacements. Patients were followed at discharge, 3 months, and 1 year postoperatively. RESULTS: Implantation success was 96.1% (146/152), early valve-related mortality was 1.4% (2/146), and cumulative survival was 92.5% at a mean follow-up of 9.8 ± 5.1 months. Crossclamp time for isolated aortic valve replacement was 41.1 ± 10.6 minutes. Independent core laboratory-adjudicated mean effective orifice area and aortic valve pressure gradient were 1.7 ± 0.2 cm(2) and 8.8 ± 3.0 mm Hg at 3 months, and 1.7 ± 0.2 cm(2) and 8.4 ± 3.4 mm Hg at 1 year, respectively. CONCLUSIONS: Implantation of the EDWARDS INTUITY Valve System is feasible, safe, and efficacious for aortic valve replacement. Aortic crossclamp and cardiopulmonary bypass times were reduced compared with those for conventional aortic valve replacement. Early hemodynamic performance was excellent and remained so up to 1 year.

Review of Singapore's air quality and greenhouse gas emissions: current situation and opportunities.

Singapore has many environmental accomplishments to its credit. Accessible data on air quality indicates that all criteria pollutants satisfy both U.S. Environmental Protection Agency (EPA) and World Health Organization (WHO) air quality standards and guidelines, respectively. The exception is PM2.5 (particles with an aerodynamic diameter < or = 2.5 microm), which is not currently considered a criteria pollutant in Singapore but may potentially be the major local air pollution problem and cause for health concern. Levels of other airborne pollutants as well as their physical and chemical processes associated with local formation, transformation, dispersion, and deposition are not known. According to available emission inventories, Singapore contribution to the total atmospheric pollution and carbon budget at the regional and global scales is small. Emissions per unit gross domestic product (GDP) are low compared with other countries, although Singapore's per-capita GDP and per-capita emissions are among the highest in the world. Some information is available on health effects, but the impacts on the ecosystem and the complex interactions of air pollution and climate change at a regional level are also unknown. This article reviews existing available information on atmospheric pollution and greenhouse gas emissions and proposes a multipollutant approach to greenhouse gas mitigation and local air quality. Singapore, by reducing its per-capita emissions, increasing the availability of information (e.g., through regularly publishing hourly and/or daily PM2.5 concentrations) and developing a research agenda in this area, would likely be seen to be a model of a high-density, livable, and sustainable city in Southeast Asia and other tropical regions worldwide.

Investigation of bladder deformability within the development process of the artificial urinary diversion system - a pilot study.

PURPOSE: The purpose of this pilot study was to investigate changes in the dimensions of human bladders in different body positions to determine the required deformability of an artificial urinary diversion system (AUDS). This entirely artificial organ is comparable in size to the maximum capacity of natural bladders and is a replacement for diseased bladders, such those damaged by cancer. METHODS: The full bladders (determined by the individual's perception) of 5 healthy adult volunteers were imaged using a fully opened magnetic resonance imaging (MRI) device in different body positions: standing, maximum flexion, and seated. Dimensional changes were measured in four directions (ventral, dorsal, cranial and caudal) using a custom graphical method based on midsagittal images; the standing position was used as the reference position. RESULTS: The maximum flexed position was compared to the reference position, and the largest change was found in the cranial extension of the bladders: 6±4.2 mm (mean±SD). The seated and reference positions were compared; the maximum change was in the cranial extension and was measured to be 18±2.8 mm. CONCLUSIONS: The results indicate the requirement for a highly deformable artificial bladder in specific directions, such as the cranial and dorsal directions, which influences the positions of the technical components within the artificial organ. In a future development stage, artificial bladders will be designed using a computer-aided design system based on the results from this study and possibly a subsequent similar study.

Discriminating biomolecules with coherent control strategies.

The activity of the GAP-Biophotonics research group at the University of Geneva in the field of coherent control for discriminating similar biomolecules, such as flavins, proteins and DNA bases, is presented and future developments are discussed.

Resolution of strongly competitive product channels with optimal dynamic discrimination: application to flavins.

Fundamental molecular selectivity limits are probed by exploiting laser-controlled quantum interferences for the creation of distinct spectral signatures in two flavin molecules, erstwhile nearly indistinguishable via steady-state methods. Optimal dynamic discrimination (ODD) uses optimally shaped laser fields to transiently amplify minute molecular variations that would otherwise go unnoticed with linear absorption and fluorescence techniques. ODD is experimentally demonstrated by combining an optimally shaped UV pump pulse with a time-delayed, fluorescence-depleting IR pulse for discrimination amongst riboflavin and flavin mononucleotide in aqueous solution, which are structurally and spectroscopically very similar. Closed-loop, adaptive pulse shaping discovers a set of UV pulses that induce disparate responses from the two flavins and allows for concomitant flavin discrimination of ∼16σ. Additionally, attainment of ODD permits quantitative, analytical detection of the individual constituents in a flavin mixture. The successful implementation of ODD on quantum systems of such high complexity bodes well for the future development of the field and the use of ODD techniques in a variety of demanding practical applications.

Tissue-engineered cardiac constructs for cardiac repair.

Several recent basic research studies have described surgical methods for cardiac repair using tissue cardiomyoplasty. This review summarizes recent advances in cardiac repair using bioengineered tissue from the viewpoint of the cardiac surgeon. We conclude that the results of many basic and preclinical studies indicate that bioengineered tissue can be adapted to conventional surgical techniques. However, no clinical studies have yet proved bioengineered tissue is effective as a treatment for human heart failure. Today's cardiac surgeons can look forward to the advent of new techniques to benefit patients who respond poorly to existing treatment for heart failure.

Quantum control of tightly competitive product channels.

Fundamental selectivity limits of quantum control are pushed by introducing laser driven optimal dynamic discrimination to create distinguishing excitations on two nearly identical flavin molecules. Even with modest spectral resources, significant specificity is achieved with optimal pulse shapes, which amplify small molecular differences to create distinct, identifying signals. Rather than being a hindrance, system complexity appears to aid the control process and augments control field capability, which bodes well for implementation of quantum control in a variety of demanding applications.

Impact of delphinidin on the maintenance of DNA integrity in human colon carcinoma cells.

Delphinidin has been found to possess DNA strand-breaking properties in cell culture. In the present study, we demonstrated that the extent of DNA damage by delphinidin is not affected by the expression of tyrosyl-DNA-phosphodiesterase 1, indicating that the induction of DNA strand breaks is not predominantly topoisomerase-mediated. However, the DNA-damaging properties of delphinidin were decreased by the addition of catalase to the cell culture medium, counteracting delphinidin-mediated hydrogen peroxide formation. Under these conditions, delphinidin showed clearly antioxidative properties in HT29 cells, preventing menadione-induced oxidative DNA damage. In contrast, in the absence of catalase, delphinidin lacked antioxidative properties. In conclusion, delphinidin acted as an effective antioxidant within intact cells if the formation of hydrogen peroxide was prevented. In the absence of catalase, the accumulated hydrogen peroxide appears to play a substantial role for the observed DNA-damaging properties of delphinidin and the apparent lack of antioxidative properties of this anthocyanidin.

Identification of biological microparticles using ultrafast depletion spectroscopy.

We show how an ultrafast pump-pump excitation induces strong fluorescence depletion in biological samples, such as bacteria-containing droplets, in contrast with fluorescent interferents, such as polycyclic aromatic compounds, despite similar spectroscopic properties. Application to the optical remote discrimination of biotic versus non-biotic particles is proposed. Further improvement is required to allow the discrimination of one pathogenic among other non-pathogenic micro-organisms. This improved selectivity may be reached with optimal coherent control experiments, as discussed in the paper.

Continuous positive airway pressure causes lung injury in a model of sepsis.

Continuous positive airway pressure, aimed at preventing pulmonary atelectasis, has been used for decades to reduce lung injury in critically ill patients. In neonatal practice, it is increasingly used worldwide as a primary form of respiratory support due to its low cost and because it reduces the need for endotracheal intubation and conventional mechanical ventilation. We studied the anesthetized in vivo rat and determined the optimal circuit design for delivery of continuous positive airway pressure. We investigated the effects of continuous positive airway pressure following lipopolysaccharide administration in the anesthetized rat. Whereas neither continuous positive airway pressure nor lipopolysaccharide alone caused lung injury, continuous positive airway pressure applied following intravenous lipopolysaccharide resulted in increased microvascular permeability, elevated cytokine protein and mRNA production, and impaired static compliance. A dose-response relationship was demonstrated whereby higher levels of continuous positive airway pressure (up to 6 cmH(2)O) caused greater lung injury. Lung injury was attenuated by pretreatment with dexamethasone. These data demonstrate that despite optimal circuit design, continuous positive airway pressure causes significant lung injury (proportional to the airway pressure) in the setting of circulating lipopolysaccharide. Although we would currently avoid direct extrapolation of these findings to clinical practice, we believe that in the context of increasing clinical use, these data are grounds for concern and warrant further investigation.

Post-mitral valve repair systolic anterior motion produced by non-obstructive septal bulge.

OBJECTIVE: Systolic anterior motion (SAM) may rarely occur after mitral valve reconstruction due to different anatomic factors. Several techniques have been described to reduce the incidence of post-repair SAM, e.g. leaflet sliding plasty. However, SAM can still occur after these special procedures. We reviewed data of patients developing SAM with significant mitral regurgitation due to non-obstructive septal bulge. METHODS: During a 2-year period mitral valve repair was performed in 358 patients. Five of 358 (1.4%) patients with a mean age of 52+/-10.5 years developed post-repair SAM with severe mitral insufficiency due to non-obstructive septal bulge. Data of these patients were analyzed retrospectively and controlled after a mean follow-up of 18+/-2.7 months. RESULTS: Preoperative echocardiography showed end-diastolic septum diameter of 7, 10, 10, 11 and 15 mm. The ratio between end-diastolic septum diameter and free wall diameter was 1 in four patients and 1.25 in one patient. There was no left ventricular outflow tract obstruction (LVOT). Intraoperative data revealed large myxomatous anterior (four patients) and posterior (three patients) leaflets. Quadrangular resection of posterior leaflet was carried out in four patients and sliding plasty in one patient. Cause for post-repair mitral regurgitation was a non-obstructive septal bulge. During a second pump run septal bulge was resected. Mean aortic cross-clamp time and cardiopulmonary bypass time for this procedure was 15+/-1.4 and 28+/-3.1 min, respectively. Mitral regurgitation disappeared in all patients immediately after this procedure. The grade of mitral regurgitation at follow-up was 0-1 in all patients. One patient had subaortic gradient of 36 mmHg. CONCLUSIONS: If mitral regurgitation occurs after primary successful mitral repair, septum bulge should always be considered as the primary cause for SAM even there is no preoperative gradient in LVOT. Before performing time-consuming corrective operations to relieve SAM, a septum resection should be carried out during a short second pump run.

[Outpatient primary stent-PTA in a symptomatic internal artery stenosis under protection]. / Ambulante primäre Stent-PTA einer symptomatischen Arteria-carotis-interna-Stenose unter Protektion.

In a 69-year old patient, with a symptomatic ICA stenosis a stent implantation was performed under outpatient conditions. An interdisciplinary consensus was reached that the patient was suitable for outpatient therapy. In accordance with the NASCET criteria, the patient was to be classified to the high-risk group. Within 120 days before the intervention, the following clinical symptoms had occurred: 1 TIA, 2 amaurosis fugax. In the diagnostic angiography a right postbulbar ICA stenosis of 97% was verified. The stent application and subsequent PTA were performed under protection using a filter system. The transfemoral route was always fitted with an endovascular closure system. The neck vessels were followed-up by means of colour coded duplex sonography (CCDS) on days 1, 30, 180 and 360. A contrast-medium intensified MRI was performed on the 5th day post-intervention. The implantation of the stent and PTA were done without any complications. Atheromatous plaque fragments were found in the protection system. A plaque embolism was excluded clinically and in the contrast-medium intensified MRI 5 days after the intervention. After 360 days, no restenosis was found in the CCDS, the ECA was perfused. The method presented is low in complications and shows a high success rate. If patient recruitment is adequate, this intervention can be performed on an outpatient basis.

Accessory mitral valve tissue associated with situs inversus in an elderly patient.

We report an unusual case of accessory mitral valve tissue associated with a situs inversus and missing obstruction of the left ventricular outflow tract. To our knowledge our patient is the only elderly patient with an accessory mitral valve with associated situs inversus undergoing surgical resection. The report emphasizes direct cardioscopy through the aortic annulus allowing precise excision of the abnormal tissue.