Artificial organs最新文献

Background: Left ventricular assist device (LVAD) malposition has been linked to hemocompatibility-related adverse events (HRAEs). This study aimed to identify preoperative anatomical landmarks and postoperative pump position, associated with HRAEs during LVAD support.

Methods: Pre- and postoperative chest X-ray measures (≤14 days pre-implantation, first postoperative standing, 6, 12, 18, and 24 months post-implantation) were analyzed for their association with HRAEs over 24 months in 33 HeartMate 3 (HM3) patients (15.2% female, age 66 (9.5) years).

Results: HM3 patients with any HRAE showed significantly lower preoperative distances between left ventricle and thoracic outline (dLVT) (25.3 ± 10.2 mm vs. 40.3 ± 15.5 mm, p = 0.004). A ROC-derived cutoff dLVT ≤ 29.2 mm provided 85.7% sensitivity and 72.2% specificity predicting any HRAE during HM3 support (76.2% (>29.2 mm) vs. 16.7% (≤29.2 mm) freedom from HRAE, p < 0.001) and significant differences in cardiothoracic ratio (0.58 ± 0.04 vs. 0.62 ± 0.04, p = 0.045). Postoperative X-rays indicated lower pump depths in patients with ischemic strokes (9.1 ± 16.2 mm vs. 38.0 ± 18.5 mm, p = 0.007), reduced freedom from any neurological event (pump depth ≤ 28.7 mm: 45.5% vs. 94.1%, p = 0.004), and a significant correlation between pump depth and inflow cannula angle (r = 0.66, p < 0.001). Longitudinal changes were observed in heart-pump width (F(4,60) = 5.61, p < 0.001).

Conclusion: Preoperative X-ray markers are associated with postoperative HRAE occurrence. Applying this knowledge in clinical practice may enhance risk stratification, guide therapy optimization, and improve HM3 recipient management.

Background: Temporal trends of routinely obtained parameters may provide valuable information for predicting BSIs, but this association has not yet been established in LVAD patients.

Methods: This retrospective analysis included data from 347 consecutive recipients of three rotary LVAD types. Study endpoints included the incidence of BSI, the association of temporal trends of routinely obtained blood biomarkers with the development of BSIs, the incidence of BSIs, and survival on LVAD support.

Results: During follow-up, 47.8% (n = 166) of the patients developed BSI. In multivariate analyses, the development of BSI was a significant predictor of mortality (HR 5.78, 95% CI 4.08-8.19, p < 0.0001). In univariate analyses, after adjusting for potential confounders, albumin (SHR 0.94, 95% CI 0.91-0.97, p < 0.00010), creatinine (SHR 1.49, 95% CI 1.03-2.15, p = 0.033), and C-reactive protein (SHR 1.19, 95% CI 1.08-1.32, p = 0.0007) significantly predicted the development of BSIs during LVAD support. Notably, the strength of the association of parameter changes with the prediction of BSIs demonstrated a time-dependent correlation in the cases of albumin (p = 0.045) and creatinine (p = 0.003).

Conclusion: Bloodstream infections are highly prevalent among LVAD recipients and are independent predictors of mortality. Temporal biomarker trends significantly predict the development of BSIs. These findings suggest opportunities for interventions aiming to reduce the incidence of BSIs.

Background: Von Willebrand factor (VWF) is a critical glycoprotein in hemostasis and is an important factor in diagnosing bleeding disorders. Albeit the analysis of VWF is often compromised by inconsistent methodologies and challenges quantifying multimeric size. Current VWF multimer analysis methods are costly, time-consuming, and often inconsistent; thus, demanding skilled professionals. This study aimed to streamline and optimize the VWF multimer analysis technique, making it more efficient and reproducible, particularly for identifying or predicting mechanical circulatory support (MCS) induced bleeding disorders.

Methods: Blood samples from healthy volunteers were exposed to high shear forces via a Medtronic HeartWare ventricular assist device. VWF multimers were analyzed using vertical-gel agarose electrophoresis and Western blotting. Differences in VWF distribution were determined using densitometry, and two methods of densitometric analysis were compared: proprietary software against open-source software.

Results: Using the developed method: (i) protocol duration was accelerated from three days (in classical methods) to ~ eight hours; (ii) the resolution of the high molecular weight (HMW) VWF multimers were substantially improved; and (iii) densitometric analysis tools were validated. Additionally, the densitometry analysis using two software types showed a strong correlation between results, with the proprietary software reporting slightly higher HMW VWF percentages.

Conclusion: This methodology is recommended for affordable, accurate, and reproducible VWF multimer evaluations during MCS use and testing. Further research comparing this method with semi-automated methods would provide additional insight and improve inter-laboratory comparisons.

Background: Pre-left ventricular assist device (LVAD) pectoralis muscle assessment, an estimate of sarcopenia, has been associated with postoperative mortality and gastrointestinal bleeding, though its association with inflammation, endotoxemia, length-of-stay (LOS), and readmissions remains underexplored.

Methods: This was a single-center cohort study of LVAD patients implanted 1/2015-10/2018. Preoperative pectoralis muscle area was measured on chest computed tomography (CT), adjusted for height squared to derive pectoralis muscle area index (PMI). Those with PMI in the lowest quintile were defined as low-PMI cohort; all others constituted the reference cohort. Biomarkers of inflammation (interleukin-6, adiponectin, tumor necrosis factor-α [TNFα]) and endotoxemia (soluble (s)CD14) were measured in a subset of patients.

Results: Of the 254 LVAD patients, 95 had a preoperative chest CT (median days pre-LVAD: 7 [IQR 3-13]), of whom 19 (20.0%) were in the low-PMI cohort and the remainder were in the reference cohort. Compared with the reference cohort, the low-PMI cohort had higher levels of sCD14 (2594 vs. 1850 ng/mL; p = 0.04) and TNFα (2.9 vs. 1.9 pg/mL; p = 0.03). In adjusted analyses, the low-PMI cohort had longer LOS (incidence rate ratio 1.56 [95% confidence interval 1.16-2.10], p = 0.004) and higher risk of 90-day and 1-year readmissions (subhazard ratio 5.48 [1.88-16.0], p = 0.002; hazard ratio 1.73 [1.02-2.94]; p = 0.04, respectively).

Conclusions: Pre-LVAD PMI is associated with inflammation, endotoxemia, and increased LOS and readmissions.

Background: The microfluidic-based Glomerulus-on-Chips (GoC) are mostly cell based, that is, 3D cell culture techniques are used to culture glomerular cells in order to mimic glomerular ultrafiltration. These chips require high maintenance to keep cell viability intact. There have been some approaches to build non-cell-based GoCs but many of these approaches have the drawback of membrane fouling. This article presents a structural design and simulation study of a dialysate free microfluidic channel for replicating the function of the human glomerular filtration barrier. The key advancement of the current work is addressing the fouling issue by combining a pre-filter to eliminate cellular components and performing filtration on the blood plasma.

Methods: The Laminar Flow Mixture Model in COMSOL Multiphysics 5.6 has been utilized to simulate the behavior of blood flow in the microchannels. The geometrical effect of microchannels on the separation of the filtrate was investigated. The velocity at the inlet of the microchannel and pore size of the filtration membrane are varied to see the change in outflow and filtration fraction.

Results: The efficiency of the device is calculated in terms of the filtration fraction (FF%) formed. Simulation results show that the filtrate obtained is ~20% of the plasma flow rate in the channel, which resembles the glomerular filtration fraction.

Conclusion: Given that it is not dependent on the functionality of grown cells, the proposed device is anticipated to have a longer lifespan due to its non-cell-based design. The device's cost can be reduced by avoiding cell cultivation inside of it. It can be integrated as a glomerular functional unit with other units of kidney model to build a fully developed artificial kidney.

Background: Consequences of spinal cord injury (SCI) with a sedentary lifestyle will progress to muscle weakness and muscle atrophy, leading to muscle fatigue. This study aimed to determine the feasibility and preliminary effects of high-intensity interval training (HIIT) using functional electrical stimulation (FES) cycling on changes in thigh muscle volume and muscle strength, in patients with incomplete SCI.

Methods: Eight incomplete SCI patients (mean age 50 years; 6 women) with stable SCI paraplegia (mean 6.75 years since injury) participated in the HIIT FES cycling (85%-90% peak Watts; 4 × 4-min intervals) three times a week (over 6 weeks). The main outcomes were adherence, participant acceptability, and adverse events. Secondary outcomes were muscle strength (peak torque) and leg volume changes.

Results: Our findings revealed that the program was well-received by participants, with high levels of adherence, positive feedback, and satisfaction, suggesting that it could be a promising option for individuals seeking to enhance their lower body strength and muscle mass. Additionally, all participants successfully completed the training without any serious adverse events, indicating that the program is safe for use. Finally, we found that the 6-week HIIT FES leg cycling exercise program resulted in notable improvements in isometric peak torque of the quadriceps (range 13.9%-25.6%), hamstring muscle (18.2%-23.3%), and leg volume (1.7%-18.2%).

Conclusions: This study highlights HIIT FES leg cycling exercise program potential as an effective intervention for improving lower limb muscle function.

Objectives: Engineered Heart Tissue (EHT) is a promising tool to repair heart muscle defects and can additionally be used for drug testing. Due to the absence of an in vitro vascularization, EHT geometry crucially impacts nutrient and oxygen supply by diffusion capacity. We analyzed cardiomyocyte survival in different EHT geometries.

Methods: Different geometries with varying surface-area-to-volume-ratios were calculated (structure A (Ring) AS/V = 58.47 mm²/440 μL³, structure B (Infinity) 25.86 mm²/440 μL³). EHTs were generated from hiPSC-derived cardiomyocytes (4 × 10⁶) and a fibrin/thrombin hydrogel. Cell viability was evaluated by RT-PCR, cytometric studies, and Bioluminescence imaging.

Results: Using 3D-printed casting molds, spontaneously beating EHTs can be generated in various geometric forms. At day 7, the RT-PCR analyses showed a significantly higher Troponin-T value in ring EHTs, compared to infinity EHTs. In cytometric studies, we evaluated 15% more Troponin-T positive cells in ring (73% ± 12%), compared to infinity EHTs (58% ± 11%, p = 0.04). BLI visualized significantly higher cell survival in ring EHTs (ROI = A: 1.14 × 10⁶ p/s and B: 8.47 × 10⁵ p/s, p < 0.001) compared to infinity EHTs during longitudinal cultivation process.

Conclusion: Use of 3D-printing allows the creation of EHTs in all desired geometric shapes. The geometry with an optimized surface-area-to-volume-ratio (ring EHT) demonstrated a significantly higher cell survival measured by RT-PCR, Bioluminescence imaging, and cytometric studies using FACS analysis.

Background: Efforts to improve the quality of marginal grafts for transplantation are essential. Machine perfusion preservation appears as a promising solution.

Methods: The United Network for Organ Sharing (UNOS) database was queried for deceased liver donor records between 2016 and 2022. The primary outcome of interest was the organ nonutilization rate. Long-term graft and patient survival among extended criteria donors (ECDs) were also analyzed.

Results: During the study period, out of 54 578 liver grafts recovered for transplant, 5085 (9.3%) were nonutilized. Multivariable analysis identified normothermic machine perfusion (NMP) preservation as the only predictor associated with a reduction in graft nonutilization (OR = 0.12; 95% CI = 0.06-0.023, p < 0.001). Further analysis of ECD grafts that were transplanted revealed comparable 1-,2- and 3-years graft survival (89%/88%/82% vs. 90%/85%/81%, p = 0.60), and patient survival (92%/91%/84% vs. 92%/88%/84%, p = 0.65) between grafts that underwent MP vs. those who did not, respectively.

Conclusions: Liver nonutilization rates in the United States are at an all-time high. Available data, most likely including cases from clinical trials, showed that NMP reduced the odds of organ nonutilization by 12% among the entire deceased donor pool and by 16% among grafts from ECD. Collective efforts and further evidence reflecting day-to-day clinical practice are needed to fully reach the potential of MP for liver transplant.