Impact of telemedical management on hospitalization and mortality in heart failure patients with diabetes: a post-hoc subgroup analysis of the TIM-HF2 trial.

BACKGROUND: The TIM-HF2 study demonstrated that remote patient management (RPM) in a well-defined heart failure (HF) population reduced the percentage of days lost due to unplanned cardiovascular hospital admissions or all-cause death during 1-year follow-up (hazard ratio 0.80) and all-cause mortality alone (HR 0.70). Higher rates of hospital admissions and mortality have been reported in HF patients with diabetes compared with HF patients without diabetes. Therefore, in a post-hoc analysis of the TIM-HF2 study, we investigated the efficacy of RPM in HF patients with diabetes. METHODS: TIM-HF2 study was a randomized, controlled, unmasked (concealed randomization), multicentre trial, performed in Germany between August 2013 and May 2018. HF-Patients in NYHA class II/III who had a HF-related hospital admission within the previous 12 months, irrespective of left ventricular ejection fraction, and were randomized to usual care with or without added RPM and followed for 1 year. The primary endpoint was days lost due to unplanned cardiovascular hospitalization or due to death of any cause. This post-hoc analysis included 707 HF patients with diabetes. RESULTS: In HF patients with diabetes, RPM reduced the percentage of days lost due to cardiovascular hospitalization or death compared with usual care (HR 0.66, 95% CI 0.48-0.90), and the rate of all-cause mortality alone (HR 0.52, 95% CI 0.32-0.85). RPM was also associated with an improvement in quality of life (mean difference in change in global score of Minnesota Living with Heart Failure Questionnaire score (MLHFQ): - 3.4, 95% CI - 6.2 to - 0.6). CONCLUSION: These results support the use of RPM in HF patients with diabetes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01878630.

Preprocedural assessment of coronary artery disease in patients undergoing transcatheter aortic valve implantation: Rationale and design of the EASE-IT CT registry.

BACKGROUND: Invasive coronary angiography (ICA) is the standard for pre-procedural assessment of coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI). However, it requires hospitalization and can be associated with complications. Computed tomography angiography (CTA) may be a viable alternative to rule out prognostically relevant CAD. METHODS: The EASE-IT CT Registry is an investigator-initiated, prospective, observational, multicentre pilot registry involving patients aged ≥75 years with severe aortic stenosis (AS) intended to implant a transcatheter heart valve (THV) of the SAPIEN family. A total of 150 patients will be recruited from four sites in Germany and Austria. The registry will consist of two prospective cohorts: the investigational CTA-only cohort and the CTA + ICA control cohort. The CTA-only cohort will enrol 100 patients in whom significant (≥50%) left main (LM) and/or proximal left anterior descending artery (LAD) stenosis are ruled out on CTA. The CTA + ICA control cohort will enrol 50 patients who have undergone both CTA and ICA before TAVI and in whom ≥50% LM/proximal LAD stenosis has been ruled out by CTA. Three composite endpoints will be assessed at 3 months post-TAVI: CAD-specific endpoints, VARC-3-defined device success and early safety. CONCLUSION: The EASE-IT CT Registry evaluates whether TAVI can be carried out safely without performing ICA if prognostically relevant CAD of the LM/proximal LAD is ruled out with CTA. If so, the omission of ICA would help streamline the pre-procedural workup of TAVI patients.

Detection of Sortase A and Identification of Its Inhibitors by Paramagnetic Nanoparticle-Assisted Nuclear Relaxation.

Sortase A is a virulence factor responsible for the attachment of surface proteins to Staphylococcus aureus and other Gram-positive bacteria. Inhibitors of this enzyme are potential anti-infective agents. Herein, a new highly selective magnetic relaxation-based method for screening potential sortase A inhibitors is described. A 13-amino acid-long peptide substrate of sortase A is conjugated to SiO2-EDTA-Gd NPs. In the presence of sortase A, the LPXTG motif on the peptide strand is cleaved resulting in a shortened peptide as well as a reduced water T2 value whose magnitude is dependent on the concentration of sortase A. The detection limit is determined to be 76 pM. In contrast, the presence of sortase A inhibitors causes the T2 to remain at a higher value. The proposed method is used to characterize inhibition of sortase A by curcumin and 4-(hydroxymercuri)benzoic acid with an IC50 value of 12.9 ± 1.6 µM and 130 ± 1.76 µM, respectively. Furthermore, this method was successfully applied to detect sortase A activity in bacterial suspensions. The feasibility to screen different inhibitors in Escherichia coli and S. aureus suspensions was demonstrated. This method is fast and potentially useful to rapidly screen possible inhibitors of sortase A in bacterial suspensions, thereby aiding in the development of antibacterial agents targeting Gram-positive bacteria.

Nicking enzyme-assisted signal-amplifiable Hg2+ detection using upconversion nanoparticles.

A highly specific and sensitive isothermal method for mercury detection using DNA-conjugated upconversion nanoparticles is reported. A single-stranded DNA containing thymine bases, used as the Hg2+-capturing element through the formation of thymine-Hg2+-thymine complex, is covalently attached to the NaYF4: Yb3+, Tm3+ nanoparticles. Luminescence resonance energy transfer takes place between the NaYF4: Yb3+, Tm3+ nanoparticles as donor and DNA-intercalating SYBR Green I as the acceptor upon excitation of 980 nm. The sensitivity and selectivity toward Hg2+ are enhanced using the nicking enzyme, Nt. Alwl, which leads to signal amplification. By monitoring the ratio of acceptor emission to a reference peak, the presence of Hg2+ ions are quantitatively determined with a lower detection limit of 0.14 nM, which is much lower than the US Environmental Protection Agency (EPA) limit of Hg2+ in drinking water.

Nanoparticle assisted nuclear relaxation-based oligonucleotide detection.

We present a proof-of-concept "on-off" detection scheme, which uses gadolinium phthalocyanine (GdTcPc)-grafted silica nanoparticles as paramagnetic centers, capable of modifying the transverse relaxation time (T2) of water protons in solution. A DNA strand (as probe) was conjugated to the GdTcPc to act as a recognition element. In the presence of the target DNA, which was complementary to the probe, an increase in the T2 value was detected, with magnitude proportional to the target DNA concentration. The linear range was observed from 30 to 140 nM, with limit of detection of 15 nM. The developed nuclear relaxation-based detection scheme is shown to be a simple, fast and selective method to detect DNA and could be useful in point-of-care diagnostic applications.

Naked eye detection of infertility using fructose blue--a novel gold nanoparticle based fructose sensor.

A simple and low cost colorimetric method, requiring no instrumentation, is presented for the detection of fructose in human semen, a marker of seminal vesicle function. In this study we have synthesized a novel gold nanoparticle (AuNP) based sensor, named as fructose blue, by co-functionalizing AuNPs with 3-aminophenyl boronic acid (APB) and L-glutamic acid-(2,2,2)-trichloroethyl ester (GTE). The red-shift in the plasmon absorption spectra of fructose blue with different fructose concentrations accompanied by colour change of the solution from red to blue is the principle applied here for the estimation of fructose. The novel co-functionalized nanoparticles (NPs) have better colour change response for fructose than that of the earlier reported fructose sensors based on AuNPs functionalized by the APB moiety alone. The proposed method showed linearity in the range of 0.5-6 mg/mL with a detection limit of 0.3 mg/mL, and exhibits excellent selectivity for fructose over a collection of sugars. The method was successfully applied for detection of fructose in real samples of semen and agrees well with values obtained from conventional methods. The method depicted here for the detection of semen fructose is indeed superior to the existing methods in the sense that it can be performed at home as a preliminary self-screening test by patients suspecting infertility for warranting further medical attention and provides privacy also. Moreover the method is important, particularly in third world countries where high-tech diagnostic aids are inaccessible to the bulk of the population.