Potential of remote monitoring to prevent sensing and detection failures in implantable cardioverter defibrillators.

BACKGROUND: Sensing malfunction and misinterpretation of intracardiac electrograms (IEGMs) in patients with implantable cardioverter defibrillators (ICDs) may lead to inadequate device activity such as inappropriate shock delivery or unnecessary mode-switching. Remote monitoring has the potential for early detection of sensing malfunction or misclassification and may thus prevent adverse device activity. Therefore, the authors analyzed the amount, nature, and distribution of misclassification in current ICD and cardiac resynchronization therapy defibrillator technology using the device transmissions of the IN-TIME study population. METHODS: All transmitted tachyarrhythmic episodes in the 664 IN-TIME patients, comprising 2214 device-classified atrial fibrillation (DC-AF) episodes lasting ≥ 30 s and 1330 device-classified ventricular tachycardia or fibrillation (DC-VT/VF) episodes, were manually analyzed by two experienced cardiologists. RESULTS: After evaluation of all DC-VT/VF episodes, a total of 300 VT/VF events (23.1%) were false-positive, with supraventricular tachycardia being the most frequent cause (51.7%), followed by atrial fibrillation (21.3%) and T­wave oversensing (21.0%). A total of 15 patients with false-positive DC-VT/VF received inappropriate shocks. According to the inclusion criteria, 616 IEGMs with DC-AF were assessed. A total of 19.7% were false-positive AF episodes and R­wave oversensing was the most common reason (55.9%). CONCLUSIONS: Remote monitoring offers the opportunity of early detection of signal misclassification and thus early prevention of adverse device reaction, such as inappropriate shock delivery or mode-switching with intermittent loss of atrioventricular synchrony, by correcting the underlying causes.

Molecular Scissors for Tailor-Made Modification of Siloxane Scaffolds.

The controlled design of functional oligosiloxanes is an important topic in current research. A consecutive Si-O-Si bond cleavage/formation using siloxanes that are substituted with 1,2-diaminobenzene derivatives acting as molecular scissors is presented. The method allows to cut at certain positions of a siloxane scaffold forming a cyclic diaminosilane or -siloxane intermediate and then to introduce new functional siloxy units. The procedure could be extended to a direct one-step cleavage of chlorooligosiloxanes. Both siloxane formation and cleavage proceed with good to excellent yields, high regioselectivity, and great variability of the siloxy units. Control of the selectivity is achieved by the choice of the amino substituent. Insight into the mechanism was provided by low temperature NMR studies and the isolation of a lithiated intermediate.

Influence of Hard Segment Content and Diisocyanate Structure on the Transparency and Mechanical Properties of Poly(dimethylsiloxane)-Based Urea Elastomers for Biomedical Applications.

The effect of hard segment content and diisocyanate structure on the transparency and mechanical properties of soft poly(dimethylsiloxane) (PDMS)-based urea elastomers (PSUs) was investigated. A series of PSU elastomers were synthesized from an aminopropyl-terminated PDMS (M¯n: 16,300 g·mol-1), which was prepared by ring chain equilibration of the monomers octamethylcyclotetrasiloxane (D4) and 1,3-bis(3-aminopropyl)-tetramethyldisiloxane (APTMDS). The hard segments (HSs) comprised diisocyanates of different symmetry, i.e., 4,4'-methylenebis(cyclohexyl isocyanate) (H12MDI), 4,4'-methylenebis(phenyl isocyanate) (MDI), isophorone diisocyanate (IPDI), and trans-1,4-cyclohexane diisocyanate (CHDI). The HS contents of the PSU elastomers based on H12MDI and IPDI were systematically varied between 5% and 20% by increasing the ratio of the diisocyanate and the chain extender APTMDS. PSU copolymers of very low urea HS contents (1.0-1.6%) were prepared without the chain extender. All PSU elastomers and copolymers exhibited good elastomeric properties and displayed elongation at break values between 600% and 1100%. The PSUs with HS contents below 10% were transparent and became increasingly translucent at HS contents of 15% and higher. The Young's modulus (YM) and ultimate tensile strength values of the elastomers increased linearly with increasing HS content. The YM values differed significantly among the PSU copolymers depending on the symmetry of the diisocyanate. The softest elastomer was that based on the asymmetric IPDI. The elastomers synthesized from H12MDI and MDI both exhibited an intermediate YM, while the stiffest elastomer, i.e., that comprising the symmetric CHDI, had a YM three-times higher than that prepared with IPDI. The PSUs were subjected to load-unload cycles at 100% and 300% strain to study the influence of HS morphology on 10-cycle hysteresis behavior. At 100% strain, the first-cycle hysteresis values of the IPDI- and H12MDI-based elastomers first decreased to a minimum of approximately 9-10% at an HS content of 10% and increased again to 22-28% at an HS content of 20%. A similar, though less pronounced, trend was observed at 300% strain. First-cycle hysteresis among the PSU copolymers at 100% strain was lowest in the case of CHDI and highest in the IPDI-based elastomer. However, this effect was reversed at 300% strain, with CHDI displaying the highest hysteresis in the first cycle. In vitro cytotoxicity tests performed using HaCaT cells did not show any adverse effects, revealing their potential suitability for biomedical applications.

Azido-functionalized gelatin via direct conversion of lysine amino groups by diazo transfer as a building block for biofunctional hydrogels.

Gelatin is one of the most prominent biopolymers in biomedical material research and development. It is frequently used in hybrid hydrogels, which combine the advantageous properties of bio-based and synthetic polymers. To prevent the biological component from leaching out of the hydrogel, the biomolecules can be equipped with azides. Those groups can be used to immobilize gelatin covalently in hydrogels by the highly selective and specific azide-alkyne cycloaddition. In this contribution, we functionalized gelatin with azides at its lysine residues by diazo transfer, which offers the great advantage of only minimal side-chain extension. Approximately 84-90% of the amino groups are modified as shown by 1 H-NMR spectroscopy, 2,4,6-trinitrobenzenesulfonic acid assay as well as Fourier-transform infrared spectroscopy, rheology, and the determination of the isoelectric point. Furthermore, the azido-functional gelatin is incorporated into hydrogels based on poly(ethylene glycol) diacrylate (PEG-DA) at different concentrations (0.6, 3.0, and 5.5%). All hydrogels were classified as noncyctotoxic with significantly enhanced cell adhesion of human fibroblasts on their surfaces compared to pure PEG-DA hydrogels. Thus, the new gelatin derivative is found to be a very promising building block for tailoring the bioactivity of materials.

Beyond the Modification Degree: Impact of Raw Material on Physicochemical Properties of Gelatin Type A and Type B Methacryloyls.

Gelatin methacryloyl (acetyl) (GM(A)) is increasingly investigated for various applications in life sciences and medicine, for example, drug release or tissue engineering. Gelatin type A and type B are utilized for GA M(A) and GB M(A) preparation, but the impact of gelatin raw material on modification reaction and resulting polymer properties is rather unknown so far. Therefore, the degrees of modification (DMA) and physicochemical properties of five GA M(A) and GB M(A) derivatives are compared: The degrees of methacryloylation (0.32-0.98 mmol g-1 ) are indistinguishable for GA M(A) and GB M(A) as are the sol-gel temperatures. Isoelectric points, solution viscosities, and hydrodynamic radii which are distinct for GA and GB, converge with increasing DMA. Interestingly, differences are measured for the storage moduli and equilibrium degrees of swelling of respective GA and GB derivative-based hydrogels, in spite of their comparable DMA. This underlines the importance of GM(A) characterization beyond the modification degree.

Data on the synthesis and mechanical characterization of polysiloxane-based urea-elastomers prepared from amino-terminated polydimethylsiloxanes and polydimethyl-methyl-phenyl-siloxane-copolymers.

This article contains data on the synthesis and mechanical characterization of polysiloxane-based urea-elastomers (PSUs) and is related to the research article entitled "Influence of PDMS molecular weight on transparency and mechanical properties of soft polysiloxane-urea-elastomers for intraocular lens application" (Riehle et al., 2018) [1]. These elastomers were prepared by a two-step polyaddition using the aliphatic diisocyanate 4,4'-Methylenbis(cyclohexylisocyanate) (H12MDI), a siloxane-based chain extender 1,3-Bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane (APTMDS) and amino-terminated polydimethylsiloxanes (PDMS) or polydimethyl-methyl-phenyl-siloxane-copolymers (PDMS-Me,Ph), respectively. (More details about the synthesis procedure and the reaction scheme can be found in the related research article (Riehle et al., 2018) [1]). Amino-terminated polydimethylsiloxanes with varying molecular weights and PDMS-Me,Ph-copolymers were prepared prior by a base-catalyzed ring-chain equilibration of a cyclic siloxane and the endblocker APTMDS. This DiB article contains a procedure for the synthesis of the base catalyst tetramethylammonium-3-aminopropyl-dimethylsilanolate and a generic synthesis procedure for the preparation of a PDMS having a targeted number average molecular weight M¯n of 3000 g mol-1. Molecular weights and the amount of methyl-phenyl-siloxane within the polysiloxane-copolymers were determined by 1H NMR and 29Si NMR spectroscopy. The corresponding NMR spectra and data are described in this article. Additionally, this DiB article contains processed data on in line and off line FTIR-ATR spectroscopy, which was used to follow the reaction progress of the polyaddition by showing the conversion of the diisocyanate. All relevant IR band assignments of a polydimethylsiloxane-urea spectrum are described in this article. Finally, data on the tensile properties and the mechanical hysteresis-behaviour at 100% elongation of PDMS-based polyurea-elastomers are shown in dependence to the PDMS molecular weight.

Triazole-based cross-linkers in radical polymerization processes: tuning mechanical properties of poly(acrylamide) and poly(N,N-dimethylacrylamide) hydrogels.

Triazole-based cross-linkers with different spacer lengths and different functional end groups (acrylamides, methacrylamides, maleimides and vinylsulfonamides) were synthesized, investigated for cytotoxic and antibacterial activity, and incorporated into poly(acrylamide) (PAAm) and poly(N,N-dimethylacrylamide) (PDMAAm) hydrogels by free-radical polymerization. Hydrogels prepared with different cross-linkers and cross-linker contents between 0.2% and 1.0% were compared by gel yields, equilibrium degrees of swelling (S) and storage moduli (G'). Generally with increasing cross-linker content, G' values of the hydrogels increased, while S values decreased. The different polymerizable cross-linker end groups resulted in a decrease of G' in the following order for cross-linkers with C4 spacers: acrylamide > maleimide > methacrylamide > vinylsulfonamide. Longer cross-linker alkyl spacer lengths caused an increase in G' and a decrease in S. Independent of the cross-linker used, a universal correlation between G' and equilibrium polymer volume fraction ϕ was found. For PAAm hydrogels, G' ranged between 4 kPa and 23 kPa and ϕ between 0.07 and 0.14. For PDMAAm hydrogels, G' ranged between 0.1 kPa and 4.9 kPa and ϕ between 0.02 and 0.06. The collected data were used to establish an empirical model to predict G' depending on ϕ. G' of PAAm and PDMAAm hydrogels is given by G' = 4034 kPa ϕ 2.66 and G' = 4297 kPa ϕ 2.46, respectively.

Antihypertrophic effects of combined inhibition of the renin-angiotensin system (RAS) and neutral endopeptidase (NEP) in progressive, tachycardia-induced experimental heart failure.

Vasopeptidase inhibition (VPI), a therapeutic strategy by dual inhibition of both ACE and neutral endopeptidase 24.11, has not shown a prognostic benefit over ACE inhibition in chronic severe heart failure (CHF). Nevertheless, the effects of early treatment by VPI on cardiac remodelling have not been well assessed. We analysed the effects of early chronic VPI (50 mg/kg/day Omapatrilat) on cardiac remodelling and neurohumoral function during the progression of rapid ventricular pacing-induced heart failure in rabbits (early left ventricular dysfunction [ELVD]: 10 days at 330 bpm, CHF: further 10 days at 360 bpm). VPI-treated animals (ELVD-VPI n = 6; CHF-VPI n = 8) and placebo treated animals (ELVD n = 6; CHF n = 7) were compared with control rabbits (CTRL n = 5). LV fractional shortening (FS) and enddiastolic diameter (LVEDD) were assessed by echocardiography (12 MHz probe). LV BNP- and LV IL-6 gene expression was analysed quantitatively by real time PCR. Neurohumoral function was assessed by ANP, cGMP, plasma renin activity (PRA) and Aldosterone. In ELVD, LVEDD and atrial mass were significantly increased (both p < 0.05). This increase was markedly attenuated by VPI (both p < 0.05 vs. placebo). CHF was associated with a further increase in atrial mass and an increase in LV mass (both p < 0.05), which was again attenuated by VPI (atrial mass, p < 0.05 vs. untreated). LV BNP mRNA was significantly increased in CHF (p < 0.05 vs. control), and chronic VPI completely abolished this increase in ELVD and significantly attenuated it in CHF (p < 0.05 vs. CHF-placebo). Beyond that, the increase of cGMP was augmented by chronic VPI (p < 0.05 vs. placebo in CHF) in heart failure and that of Aldosterone was attenuated (p < 0.05 vs. placebo in ELVD), whereas PRA was temporarily increased (p < 0.05 vs. placebo in ELVD). Combined inhibition of ACE and NEP by VPI significantly inhibits early cardiac remodelling and LV BNP gene expression. If initiated early enough, it may slow down cardiac remodelling and represents a promising therapeutic strategy in progressive heart failure.

Comparison of cytology and nuclear matrix protein 22 (NMP 22) for the detection and follow-up of bladder-cancer.

OBJECTIVES: This study was designed to determine the clinical usefulness of the Nuclear Matrix Protein 22 (NMP 22) Test for the detection of bladder cancer in comparison to urine cytology. METHODS: One hundred sixty-four patients suffering from or being suspicious for bladder cancer and 64 healthy controls participated in a prospective study. Freshly voided spot urine samples were taken for cytological examination and determination of NMP 22-levels by enzyme-linked immunoassay. RESULTS: Sensitivity to the NMP 22 Test according to the tumor grading was (results of cytology in parentheses): GI 25.0% (20.0%), G2 68.2% (59.1%), and G3 100.0% (66.7%); overall sensitivity was 62.5% (45.0%). Sensitivity according to superficial bladder cancer was 46.7% (36.7%), and to invasive bladder cancer 90.0% (70.0%). Specificity was 65.9% (88.9%). CONCLUSIONS: NMP 22 is a reliable tool for detecting invasive bladder cancer. Results for the well-differentiated superficial bladder cancer occurring frequently are as poor as those obtained with cytology. In addition, benign lesions such as urolithiasis or urinary tract infection lead to false positive results. Therefore, cystoscopy has to be performed when trying to detect and follow-up bladder cancer.