Mitral Regurgitation: Advanced Imaging Parameters and Changing Treatment Landscape.

Mitral regurgitation is a common valvular heart disease with increasing prevalence due to the aging population. In degenerative (primary) mitral regurgitation, medical therapies are limited and the mainstay of treatment is mitral valve surgery. Patients are referred for mitral valve surgery based on the American College of Cardiology/American Heart Association guidelines, which recommend surgery in patients with severe mitral regurgitation. Echocardiography uses multiple parameters that lack reproducibility and accuracy. Studies comparing cardiovascular magnetic resonance (CMR) and echocardiography have shown that CMR is a better predictor of clinical outcome and postsurgical left ventricular remodeling than echocardiography.

The relationship between mitral regurgitant severity, symptoms, and exercise capacity in primary degenerative mitral regurgitation.

Although it is assumed that more severe MR is associated with a greater burden of symptoms and lower exercise capacity, the relationship between symptoms, exercise capacity, and mitral regurgitant severity has not been well studied. We prospectively studied 67 (63 ± 11 years, 72% male) patients with at least mild degenerative MR and left ventricular ejection fraction ≥ 50% who underwent stress echocardiography, CMR, and evaluation with the Kansas City Cardiomyopathy questionnaire (KCCQ). Symptoms and exercise capacity were evaluated in the context of MR severity. Patients reporting dyspnea had lower KCCQ symptom scores (79 ± 23 vs. 96 ± 9, p = 0.01) and achieved lower percentage of age and gender predicted METs (114 ± 37 vs. 152 ± 43%, p < 0.001) compared to those without dyspnea. There was no significant difference in MR volume between those with vs. without dyspnea by CMR (43 ± 26 ml vs. 51 ± 28 ml, p = 0.3) or echocardiography (64 ± 28 vs. 73 ± 41ml, p = 0.4). Those with severe MR by CMR had similar KCCQ symptom scores (96 ± 10 vs. 89 ± 17, p = 0.04) and percentage of age and gender predicted METs (148 ± 42 vs. 133 ± 47%, p = 0.2) to those without severe MR. Those with severe MR by echocardiography had similar KCCQ symptom score (93 ± 15 vs. 89 ± 16, p = 0.3) and percentage of age and gender predicted METs (138 ± 43 vs. 153 ± 46%, p = 0.2) to those without severe MR. Patients with degenerative MR assessed by CMR and stress echocardiography, there was no relationship between MR severity and either symptoms or exercise capacity. These findings highlight the disconnect between symptoms and the severity of MR and challenge the assumption that correcting MR can be counted on to improve symptom status in patients with degenerative MR.

Engineering a highly elastic human protein-based sealant for surgical applications.

Surgical sealants have been used for sealing or reconnecting ruptured tissues but often have low adhesion, inappropriate mechanical strength, cytotoxicity concerns, and poor performance in biological environments. To address these challenges, we engineered a biocompatible and highly elastic hydrogel sealant with tunable adhesion properties by photocrosslinking the recombinant human protein tropoelastin. The subcutaneous implantation of the methacryloyl-substituted tropoelastin (MeTro) sealant in rodents demonstrated low toxicity and controlled degradation. All animals survived surgical procedures with adequate blood circulation by using MeTro in an incisional model of artery sealing in rats, and animals showed normal breathing and lung function in a model of surgically induced rat lung leakage. In vivo experiments in a porcine model demonstrated complete sealing of severely leaking lung tissue in the absence of sutures or staples, with no clinical or sonographic signs of pneumothorax during 14 days of follow-up. The engineered MeTro sealant has high potential for clinical applications because of superior adhesion and mechanical properties compared to commercially available sealants, as well as opportunity for further optimization of the degradation rate to fit desired surgical applications on different tissues.

A highly adhesive and naturally derived sealant.

Conventional surgical techniques to seal and repair defects in highly stressed elastic tissues are insufficient. Therefore, this study aimed to engineer an inexpensive, highly adhesive, biocompatible, and biodegradable sealant based on a modified and naturally derived biopolymer, gelatin methacryloyl (GelMA). We tuned the degree of gelatin modification, prepolymer concentration, photoinitiator concentration, and crosslinking conditions to optimize the physical properties and adhesion of the photocrosslinked GelMA sealants. Following ASTM standard tests that target wound closure strength, shear resistance, and burst pressure, GelMA sealant was shown to exhibit adhesive properties that were superior to clinically used fibrin- and poly(ethylene glycol)-based glues. Chronic in vivo experiments in small as well as translational large animal models proved GelMA to effectively seal large lung leakages without the need for sutures or staples, presenting improved performance as compared to fibrin glue, poly(ethylene glycol) glue and sutures only. Furthermore, high biocompatibility of GelMA sealant was observed, as evidenced by a low inflammatory host response and fast in vivo degradation while allowing for adequate wound healing at the same time. Combining these results with the low costs, ease of synthesis and application of the material, GelMA sealant is envisioned to be commercialized not only as a sealant to stop air leakages, but also as a biocompatible and biodegradable hydrogel to support lung tissue regeneration.

A Highly Elastic and Rapidly Crosslinkable Elastin-Like Polypeptide-Based Hydrogel for Biomedical Applications.

Elastin-like polypeptides (ELPs) are promising for biomedical applications due to their unique thermoresponsive and elastic properties. ELP-based hydrogels have been produced through chemical and enzymatic crosslinking or photocrosslinking of modified ELPs. Herein, a photocrosslinked ELP gel using only canonical amino acids is presented. The inclusion of thiols from a pair of cysteine residues in the ELP sequence allows disulfide bond formation upon exposure to UV light, leading to the formation of a highly elastic hydrogel. The physical properties of the resulting hydrogel such as mechanical properties and swelling behavior can be easily tuned by controlling ELP concentrations. The biocompatibility of the engineered ELP hydrogels is shown in vitro as well as corroborated in vivo with subcutaneous implantation of hydrogels in rats. ELP constructs demonstrate long-term structural stability in vivo, and early and progressive host integration with no immune response, suggesting their potential for supporting wound repair. Ultimately, functionalized ELPs demonstrate the ability to function as an in vivo hemostatic material over bleeding wounds.

Ankylosing spondylitis: A state of the art factual backbone.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects 1% of the general population. As one of the most severe types of spondyloarthropathy, AS affects the spinal vertebrae and sacroiliac joints, causing debilitating pain and loss of mobility. The goal of this review is to provide an overview of AS, from the pathophysiological changes that occur as the disease progresses, to genetic factors that are involved with its onset. Considering the high prevalence in the population, and the debilitating life changes that occur as a result of the disease, a strong emphasis is placed on the diagnostic imaging methods that are used to detect this condition, as well as several treatment methods that could improve the health of individuals diagnosed with AS.

H4octapa: highly stable complexation of lanthanide(III) ions and copper(II).

The acyclic ligand octapa(4-) (H4octapa = 6,6'-((ethane-1,2-diylbis((carboxymethyl)azanediyl))bis(methylene))dipicolinic acid) forms stable complexes with the Ln(3+) ions in aqueous solution. The stability constants determined for the complexes with La(3+), Gd(3+), and Lu(3+) using relaxometric methods are log KLaL = 20.13(7), log KGdL = 20.23(4), and log KLuL = 20.49(5) (I = 0.15 M NaCl). High stability constants were also determined for the complexes formed with divalent metal ions such as Zn(2+) and Cu(2+) (log KZnL = 18.91(3) and log KCuL = 22.08(2)). UV-visible and NMR spectroscopic studies and density functional theory (DFT) calculations point to hexadentate binding of the ligand to Zn(2+) and Cu(2+), the donor atoms of the acetate groups of the ligand remaining uncoordinated. The complexes formed with the Ln(3+) ions are nine-coordinated thanks to the octadentate binding of the ligand and the presence of a coordinated water molecule. The stability constants of the complexes formed with the Ln(3+) ions do not change significantly across the lanthanide series. A DFT investigation shows that this is the result of a subtle balance between the increased binding energies across the 4f period, which contribute to an increasing complex stability, and the parallel increase of the absolute values of the hydration free energies of the Ln(3+) ions. In the case of the [Ln(octapa)(H2O)](-) complexes the interaction between the amine nitrogen atoms of the ligand and the Ln(3+) ions is weakened along the lanthanide series, and therefore the increased electrostatic interaction does not overcome the increasing hydration energies. A detailed kinetic study of the dissociation of the [Gd(octapa)(H2O)](-) complex in the presence of Cu(2+) shows that the metal-assisted pathway is the main responsible for complex dissociation at pH 7.4 and physiological [Cu(2+)] concentration (1 µM).

A handy review of carpal tunnel syndrome: From anatomy to diagnosis and treatment.

Carpal tunnel syndrome (CTS) is the most commonly diagnosed disabling condition of the upper extremities. It is the most commonly known and prevalent type of peripheral entrapment neuropathy that accounts for about 90% of all entrapment neuropathies. This review aims to provide an outline of CTS by considering anatomy, pathophysiology, clinical manifestation, diagnostic modalities and management of this common condition, with an emphasis on the diagnostic imaging evaluation.