Impact of left ventricular assist device therapy on the cardiac proteome and metabolome composition in ischemic cardiomyopathy

The changes in the myocardial proteome and metabolome associated with left ventricular assist device (LVAD) therapy in patients with ischemic cardiomyopathy (ICM) are poorly characterized. We investigated the impact of mechanical unloading following LVAD therapy on the myocardial proteome and metabolome. Matched samples of 5 patients’ myocardial tissue, harvested at the time of LVAD implant (“pre-LVAD”) or heart transplant (“post-LVAD”), were studied by quantitative proteomics and metabolomics as well as being probed for T-tubule structure and connexin-43 distribution. Moreover, pre-LVAD proteome profiles of ICM context were bioinformatically compared to pre-LVAD proteome profiles of dilated cardiac myopathy (DCM). More than 2120 proteins were reliably identified and quantified in paired patient samples. LVAD therapy led to proteomic remodeling, including reduced levels of α-1-antichymotrypsin together with an overall decrease of immune response proteins and an increase of proteins involved in membrane biology. Metabolomics highlighted increased glucose and glucose-6-phosphate levels in the left ventricle upon LVAD therapy. Wheat germ agglutinin staining demonstrated improved T-tubule structure. Connexin-43 displayed a trend for more pronounced intercalated disc localization. In comparing pre-LVAD proteome profiles of ICM context with pre-LVAD proteome profiles of dilated cardiac myopathy (DCM), we noticed an overrepresentation in ICM of proteins associated with humoral immune response. Our findings underline an impact of LVAD therapy on left ventricular biology in ICM. The proteomic, metabolomic, and structural alterations described here are typically associated with cardiac recovery. On the molecular level, our findings indicate the possibility of cardiac remodeling under LVAD therapy in ICM.     

Nonlinear optical microscopy is a novel tool for the analysis of cutaneous alterations in pseudoxanthoma elasticum

Lasers in Medical Science - Pseudoxanthoma elasticum (PXE, OMIM 264800) is a rare autosomal recessive disorder with ectopic mineralization and fragmentation of elastin fibers. It is caused by...     

Effects of High-Intensity Resistance Training on Osteopenia and Sarcopenia Parameters in Older Men with Osteosarcopenia—One-Year Results of the Randomized Controlled Franconian Osteopenia and Sarcopenia Trial (FrOST)

Dynamic resistance exercise (DRT) might be the most promising agent for fighting sarcopenia in older people. However, the positive effect of DRT on osteopenia/osteoporosis in men has still to be confirmed. To evaluate the effect of low-volume/high-intensity (HIT)-DRT on bone mineral density (BMD) and skeletal muscle mass index (SMI) in men with osteosarcopenia, we initiated the Franconian Osteopenia and Sarcopenia Trial (FrOST). Forty-three sedentary community-dwelling older men (aged 73 to 91 years) with osteopenia/osteoporosis and SMI-based sarcopenia were randomly assigned to a HIT-RT exercise group (EG; n = 21) or a control group (CG; n = 22). HIT-RT provided a progressive, periodized single-set DRT on machines with high intensity, effort, and velocity twice a week, while CG maintained their lifestyle. Both groups were adequately supplemented with whey protein, vitamin D, and calcium. Primary study endpoint was integral lumbar spine (LS) BMD as determined by quantitative computed tomography. Core secondary study endpoint was SMI as determined by dual-energy X-ray absorptiometry. Additional study endpoints were BMD at the total hip and maximum isokinetic hip−/leg-extensor strength (leg press). After 12 months of exercise, LS-BMD was maintained in the EG and decreased significantly in the CG, resulting in significant between-group differences (p < 0.001; standardized mean difference [SMD] = 0.90). In parallel, SMI increased significantly in the EG and decreased significantly in the CG (p < 0.001; SMD = 1.95). Total hip BMD changes did not differ significantly between the groups (p = 0.064; SMD = 0.65), whereas changes in maximum hip−/leg-extensor strength were much more prominent (p < 0.001; SMD = 1.92) in the EG. Considering dropout (n = 2), attendance rate (95%), and unintended side effects/injuries (n = 0), we believe our HIT-RT protocol to be feasible, attractive, and safe. In summary, we conclude that our combined low-threshold HIT-RT/protein/vitamin D/calcium intervention was feasible, safe, and effective for tackling sarcopenia and osteopenia/osteoporosis in older men with osteosarcopenia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Is it safe to remove an infected cardiac implantable electronic device at the time of heart transplantation? Report of two cases

Cardiac implantable electronic device (CIED) infections are treated with antibiotics and device explantation. Lack of CIED removal is associated with infection recurrence. However, CIED removal can be associated with major complications including death. We reported two patients with advanced heart disease who developed CIED infection due Staphylococcus epidermidis while awaiting for orthotopic heart transplantation (OHT). Both patients were managed with a different approach. They were treated with antibiotic therapy and had their CIED removal postponed until OHT. Both patients were kept on suppressive antibiotic treatment until undergoing simultaneous OHT and removal of infected CIED. None of the patients had infection recurrence. Large studies are needed to assess whether the approach of delaying CIED removal until OHT is safe among carefully selected patients with CIED infection.     

MicroRNA Profiling Reveals Distinct Signatures in Degenerative Rotator Cuff Pathologies

MicroRNAs (miRNAs) have emerged as key regulators orchestrating a wide range of inflammatory and fibrotic diseases. However, the role of miRNAs in degenerative shoulder joint disorders is poorly understood. The aim of this explorative case-control study was to identify pathology-related, circulating miRNAs in patients with chronic rotator cuff tendinopathy and degenerative rotator cuff tears (RCT). In 2017, 15 patients were prospectively enrolled and assigned to three groups based on the diagnosed pathology: (i) no shoulder pathology, (ii) chronic rotator cuff tendinopathy, and (iii) degenerative RCTs. In total, 14 patients were included. Venous blood samples (“liquid biopsies”) were collected from each patient and serum levels of 187 miRNAs were determined. Subsequently, the change in expression of nine candidate miRNAs was verified in tendon biopsy samples, collected from patients who underwent arthroscopic shoulder surgery between 2015 and 2018. Overall, we identified several miRNAs to be progressively deregulated in sera from patients with either chronic rotator cuff tendinopathy or degenerative RCTs. Importantly, for the several of these miRNAs candidates repression was also evident in tendon biopsies harvested from patients who were treated for a supraspinatus tendon tear. As similar expression profiles were determined for tendon samples, the newly identified systemic miRNA signature has potential as novel diagnostic or prognostic biomarkers for degenerative rotator cuff pathologies. © 2019 The Authors. Journal of Orthopaedic Research^® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. Inc. J Orthop Res 38:202–211, 2020     

Disinfection of contaminated metal implants with an Er:YAG laser

Infections related to orthopedic procedures are considered particularly severe when implantation materials are used, because effective treatments for biofilm removal are lacking. In this study, the relatively new approach for infection control by using an erbium:yttrium-aluminum-garnet (Er:YAG) laser was tested. This laser vaporizes all water containing cells in a very effective, precise, and predictable manner and results in only minimal thermal damage. For preliminary testing, 42 steel plates and 42 pins were seeded with mixed cultures. First, the minimally necessary laser energy for biofilm removal was determined. Subsequently, the effectiveness of biofilm removal with the Er:YAG laser and the cleansing of the metal implants with octenidine-soaked gauze was compared. Then, we compared the effectiveness of biofilm removal on 207 steel pins from 41 patients directly after explantation. Sonication and scanning electron microscopy were used for analysis. Laser fluences exceeding 2.8 J/cm² caused a complete extinction of all living cells by a single-laser impulse. Cleansing with octenidine-soaked gauze and irradiation with the Er:YAG laser are both thoroughly effective when applied to seeded pins. In contrast, when explanted pins with fully developed biofilms were analyzed, we found a significant advantage of the laser procedure. The Er:YAG laser offers a secure, complete, and nontoxic eradication of all kinds of pathogens from metal implants without damaging the implant and without the possible development of resistance. The precise noncontact removal of adjacent tissue is a decisive advantage over conventional disinfectants. Therefore, laser irradiation could become a valuable method in every debridement, antibiotics, and implant retention procedure.     

Occurrence of inadequate ACL healing after Dynamic Intraligamentary Stabilization and functional outcome—a multicentre case series

Introduction

Dynamic Intraligamentary Stabilization (DIS) is a technique for preservation, anatomical repair and stabilization of a freshly injured anterior cruciate ligament (ACL). The main purpose of this study was to evaluate the short-term re-operation rate when compared to traditional autograft reconstruction.

Methods

Four, from the developer independent, centres enrolled patients that underwent ACL repair by DIS, according to the specific indications given by MRI imaging at a minimum follow-up of 12 months. The re-operation rate was recorded as primary outcome. Secondary outcome measures were the postoperative antero-posterior knee laxity (using a portable Rolimeter®), as well as the Tegner, Lysholm and IKDC Scores.

Results

A total of 105 patients were investigated with a median follow-up of 21 months. Thirteen patients were lost to follow-up. Of the remaining 92 patients 15 (16.3%) had insufficient functional stability and required subsequent ACL reconstruction. These patients were excluded from further analysis, leaving 77 consecutive patients for a 12 months follow-up. The median age at time of surgery was 30 years for that group. At time of follow-up a median antero-posterior translation difference of 2 mm was measured. None of these patients reported subjective insufficiency (giving way), but in 14 patients (18.2%), the difference of antero-posterior translation was more than 3 mm. We found a median Tegner Score of 5.5, a median Lysholm Score of 95.0 and a median IKDC Score of 89.4.

Conclusion

The main finding of this multicentre study is a relevant re-operation rate of 16.3%. Another 18.2% showed objective antero-posterior laxity (≥ 3 mm) during testing raising the suspicion of postoperative non-healing. The failure rate of DIS in this study is higher than for reconstruction with an autologous tendon graft. However, our successfully treated patients had a good clinical and functional outcome based on antero-posterior knee laxity and clinical scores, comparable to patients treated by autograft reconstruction.