Low-Resistance, Concentric-Gated Pediatric Artificial Lung for End-Stage Lung Failure.
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ABSTRACT:
SUBMITTER: Thompson AJ
PROVIDER: S-EPMC7293821 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
Low-Resistance, Concentric-Gated Pediatric Artificial Lung for End-Stage Lung Failure.
Thompson Alex J AJ Buchan Skylar S Carr Benjamin B Poling Clinton C Hayes McKenzie M Fernando Uditha Piyumindri UP Kaesler Andreas A Schlanstein Peter P Hesselmann Felix F Arens Jutta J Potkay Joseph A JA Rojas-PeÑa Alvaro A Bartlett Robert H RH Hirschl Ronald B RB
ASAIO journal (American Society for Artificial Internal Organs : 1992) 20200401 4
Children with end-stage lung failure awaiting lung transplant would benefit from improvements in artificial lung technology allowing for wearable pulmonary support as a bridge-to-transplant therapy. In this work, we designed, fabricated, and tested the Pediatric MLung-a dual-inlet hollow fiber artificial lung based on concentric gating, which has a rated flow of 1 L/min, and a pressure drop of 25 mm Hg at rated flow. This device and future iterations of the current design are designed to relieve ...[more]
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Project description:IntroductionFor children with end-stage lung disease that cannot wean from extracorporeal life support (ECLS), a wearable artificial lung would permit extubation and provide a bridge to recovery or transplantation. We evaluate the function of the novel Pediatric MLung-a low-resistance, pumpless artificial lung developed specifically for children-in healthy animal subjects.MethodsAdolescent "mini sheep" weighing 12-20 kg underwent left thoracotomy, cannulation of the main pulmonary artery (PA; inflow) and left atrium (outflow), and connection to the MLung.ResultsThirteen sheep were studied; 6 were supported for 7 days. Mean PA pressure was 23.9 ± 6.9 mmHg. MLung blood flow was 633±258 mL/min or 30.0 ± 16.0% of CO. MLung pressure drop was 4.4 ± 3.4 mmHg. Resistance was 7.2 ± 5.2 mmHg/L/min. Device outlet oxygen saturation was 99.0 ± 3.3% with inlet saturation 53.8 ± 7.3%. Oxygen delivery was 41.1 ± 18.4 mL O2/min (maximum 84.9 mL/min) or 2.8 ± 1.5 mL O2/min/kg. Platelet count significantly decreased; no platelet transfusions were required. Plasma free hemoglobin significantly increased only on day 7, at which point 2 of the animals had plasma free hemoglobin levels above 50 mg/dL.ConclusionThe MLung provides adequate gas exchange at appropriate blood flows for the pediatric population in a PA-to-LA configuration. Further work remains to improve the biocompatibility of the device.Level of evidenceN/A.
| S-EPMC10112847 | biostudies-literature
Project description:The Pediatric End-Stage Liver Disease (PELD) score is intended to determine priority for children awaiting liver transplantation. This study examines the impact of PELD's incorporation of "growth failure" as a threshold variable, defined as having weight or height <2 standard deviations below the age and gender norm (z-score <2). First, we demonstrate the "growth failure gap" created by PELD's current calculation methods, in which children have z-scores <2 but do not meet PELD's growth failure criteria and thus lose 6-7 PELD points. Second, we utilized United Network for Organ Sharing (UNOS) data to investigate the impact of this "growth failure gap." Among 3291 pediatric liver transplant candidates, 26% met PELD-defined growth failure, and 17% fell in the growth failure gap. Children in the growth failure gap had a higher risk of waitlist mortality than those without growth failure (adjusted subhazard ratio [SHR] 1.78, 95% confidence interval [95% CI] 1.05-3.02, P = .03). They also had a higher risk of posttransplant mortality (adjusted HR 1.55, 95% CI 1.03-2.32, P = .03). For children without PELD exception points (n = 1291), waitlist mortality risk nearly tripled for those in the gap (SHR 2.89, 95% CI 1.39-6.01, P = .005). Current methods for determining growth failure in PELD disadvantage candidates arbitrarily and increase their waitlist mortality risk. PELD should be revised to correct this disparity.
| S-EPMC6883133 | biostudies-literature
Project description:BackgroundCOVID-19 may lead to development of irreversible acute respiratory distress syndrome. Some patients sustain severe respiratory failure after infection subsides. They may require lung transplant as a last resort treatment. The aim of the study is to assess the effect and feasibility of lung transplant as a treatment for patients with severe irreversible respiratory failure due to COVID-19.MethodsThis retrospective study pertains to analysis of 119 patients in critical condition who were referred to Lung Transplant Ward (Zabrze, Poland). between July 2020 and June 2021 after developing respiratory failure requiring extracorporeal membrane oxygenation, invasive ventilation, or both, as well as a few patients on high-flow oxygen therapy. Inclusion criteria for referral were confirmed lack of viral disease and exhaustion of other therapeutic options.ResultsOf the referred patients, 21.84% were disqualified from such treatment owing to existing contraindications. Among the suitable patients, 75.8% died without transplant. Among all patients who were qualified for lung transplant, only 9 patients became double lung transplant recipients. Intraoperative mortality for this procedure was 33%. Four patients were discharged after the procedure and are currently self-reliant with full respiratory capacity.ConclusionsPatients with severe irreversible respiratory failure after COVID-19 present significantly high mortality without lung transplant. This procedure may present satisfactory results but must be performed in a timely fashion owing to critical condition and scarcity of lung donors, only aggravated around the time of peak infection waves.
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Project description:Background Transcriptomic studies have contributed to fundamental knowledge of myocardial remodeling in human heart failure (HF). However, the key HF genes reported are often inconsistent between studies, and systematic efforts to integrate evidence from multiple patient cohorts are lacking. Here, we aimed to provide a framework for comprehensive comparison and analysis of publicly available data sets resulting in an unbiased consensus transcriptional signature of human end-stage HF. Methods and Results We curated and uniformly processed 16 public transcriptomic studies of left ventricular samples from 263 healthy and 653 failing human hearts. First, we evaluated the degree of consistency between studies by using linear classifiers and overrepresentation analysis. Then, we meta-analyzed the deregulation of 14 041 genes to extract a consensus signature of HF. Finally, to functionally characterize this signature, we estimated the activities of 343 transcription factors, 14 signaling pathways, and 182 micro RNAs, as well as the enrichment of 5998 biological processes. Machine learning approaches revealed conserved disease patterns across all studies independent of technical differences. These consistent molecular changes were prioritized with a meta-analysis, functionally characterized and validated on external data. We provide all results in a free public resource (https://saezlab.shinyapps.io/reheat/) and exemplified usage by deciphering fetal gene reprogramming and tracing the potential myocardial origin of the plasma proteome markers in patients with HF. Conclusions Even though technical and sampling variability confound the identification of differentially expressed genes in individual studies, we demonstrated that coordinated molecular responses during end-stage HF are conserved. The presented resource is crucial to complement findings in independent studies and decipher fundamental changes in failing myocardium.
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Project description:Stationary hemodialysis machines hinder mobility and limit activities of daily life during dialysis treatments. New hemodialysis technologies are needed to improve patient autonomy and enhance quality of life. We conducted a FDA-approved human trial of a wearable artificial kidney, a miniaturized, wearable hemodialysis machine, based on dialysate-regenerating sorbent technology. We aimed to determine the efficacy of the wearable artificial kidney in achieving solute, electrolyte, and volume homeostasis in up to 10 subjects over 24 hours. During the study, all subjects remained hemodynamically stable, and there were no serious adverse events. Serum electrolytes and hemoglobin remained stable over the treatment period for all subjects. Fluid removal was consistent with prescribed ultrafiltration rates. Mean blood flow was 42 ± 24 ml/min, and mean dialysate flow was 43 ± 20 ml/min. Mean urea, creatinine, and phosphorus clearances over 24 hours were 17 ± 10, 16 ± 8, and 15 ± 9 ml/min, respectively. Mean β2-microglobulin clearance was 5 ± 4 ml/min. Of 7 enrolled subjects, 5 completed the planned 24 hours of study treatment. The trial was stopped after the seventh subject due to device-related technical problems, including excessive carbon dioxide bubbles in the dialysate circuit and variable blood and dialysate flows. Treatment with the wearable artificial kidney was well tolerated and resulted in effective uremic solute clearance and maintenance of electrolyte and fluid homeostasis. These results serve as proof of concept that, after redesign to overcome observed technical problems, a wearable artificial kidney can be developed as a viable novel alternative dialysis technology. ClinicalTrials.gov NCT02280005. The Wearable Artificial Kidney Foundation and Blood Purification Technologies Inc.
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Project description:BackgroundChronic kidney disease (CKD) contributes significant morbidity and mortality among Asians; hence interventions should focus on those most at-risk of progression. However, current end stage renal failure (ESRF) risk stratification tools are complex and not validated in multi-ethnic Asians. We hence aimed to develop an ESRF risk prediction model by taking into account ethnic differences within a fairly homogenous socioeconomic setting and using parameters readily accessible to primary care clinicians managing the vast majority of patients with CKD.MethodsWe performed a prospective cohort study of 1970 adults with CKD estimated glomerular filtration rate <60 ml/min/1.73m2 or albuminuria >30 mg/g from the population-based Singapore Epidemiology of Eye Diseases study (n = 10,033). Outcome was incident ESRF, ascertained by linkage to the Singapore Renal Registry until 2015.ResultsMean follow up was 8.5 ± 1.8 years and ESRF occurred in 32 individuals (1.6%). ESRF incidence rates were 2.8, 0.8 and 2.6 per 1000 patient years in Malays, Indians and Chinese respectively. The best ESRF prediction model included age, gender, eGFR and albuminuria (calibration ?2 = 0.45, P = 0.93; C-statistic 0.933, 95% confidence interval (CI) 0.889-0.978, p = 0.01; AIC 356). Addition of ethnicity improved discrimination marginally (C statistic 0.942, 95% CI 0.903-0.981, p = 0.21). Addition of clinical variables such as diabetes and hyperlipidemia did not improve model performance significantly.ConclusionWe affirmed the utility of commonly available clinical information (age, gender, eGFR and UACR) in prognosticating ESRF for multi-ethnic Asians with CKD.
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Project description:BackgroundCortical bone represents nearly 80 % of human bone mass and is the major determinant of bone strength; however, cortical bone parameters and their relationship to trabecular bone in the pediatric chronic kidney disease (CKD) population have not been evaluated.MethodsBiochemical values and cortical and trabecular bone parameters were assessed in 22 pediatric dialysis patients: 12 with high and 10 with normal to low trabecular bone turnover.ResultsTrabecular bone turnover and osteoid volume correlated with parathyroid hormone (PTH) levels (r = 0.86, p < 0.01 and r = 0.93, p < 0.01, respectively). Internal cortical osteonal bone formation rate was directly related to alkaline phosphatase (r = 0.45, p < 0.05) and inversely related to insulin-like growth factor (IGF)-1 values (r = -0.55, p < 0.01), and internal cortical porosity was also related to serum alkaline phosphatase levels (r = 0.57, p < 0.01). A similar relationship was not found between external cortical bone formation rate and parameters of bone turnover and porosity, however. No relationship was found between trabecular and cortical bone formation rates.ConclusionsSecondary hyperparathyroidism was associated with increased external cortical, relative to internal cortical, osteonal activity in pediatric dialysis patients. The clinical consequences of these changes and their response to therapy for secondary hyperparathyroidism remain to be defined.
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Project description:Little is known about the right ventricular (RV) proteome in human heart failure (HF), including possible differences compared to the left ventricular (LV) proteome. We used 2-dimensional differential in-gel electrophoresis (pH: 4-7, 10-150 kDa), followed by liquid chromatography tandem mass spectrometry, to compare the RV and LV proteomes in 12 explanted human hearts. We used Western blotting and multiple-reaction monitoring for protein verification and RNA sequencing for messenger RNA and protein expression correlation. In all 12 hearts, the right ventricles (RVs) demonstrated differential expression of 11 proteins relative to the left ventricles (LVs), including lesser expression of CRYM, TPM1, CLU, TXNL1, and COQ9 and greater expression of TNNI3, SAAI, ERP29, ACTN2, HSPB2, and NDUFS3. Principal-components analysis did not suggest RV-versus-LV proteome partitioning. In the nonischemic RVs (n = 6), 7 proteins were differentially expressed relative to the ischemic RVs (n = 6), including increased expression of CRYM, B7Z964, desmin, ANXA5, and MIME and decreased expression of SERPINA1 and ANT3. Principal-components analysis demonstrated partitioning of the nonischemic and ischemic RV proteomes, and gene ontology analysis identified differences in hemostasis and atherosclerosis-associated networks. There were no proteomic differences between RVs with echocardiographic dysfunction (n = 8) and those with normal function (n = 4). Messenger RNA and protein expression did not correlate consistently, suggesting a major role for RV posttranscriptional protein expression regulation. Differences in contractile, cytoskeletal, metabolic, signaling, and survival pathways exist between the RV and the LV in HF and may be related to the underlying HF etiology and differential posttranscriptional regulation.
| S-EPMC4556499 | biostudies-literature
Project description:Objectives: Many studies indicate the involvement of transient receptor potential (TRP) channels in the development of heart hypertrophy. However, the data is often conflicted and has originated in animal models. Here, we provide systematic analysis of TRP channels expression in human failing myocardium. Methods and results: Left-ventricular tissue samples were isolated from explanted hearts of NYHA III-IV patients undergoing heart transplants (n = 43). Quantitative real-time PCR was performed to assess the mRNA levels of TRPC, TRPM and TRPV channels. Analysis of functional, clinical and biochemical data was used to confirm an end-stage heart failure diagnosis. Compared to myocardium samples from healthy donor hearts (n = 5), we detected a distinct increase in the expression of TRPC1, TRPC5, TRPM4 and TRPM7, and decreased expression of TRPC4 and TRPV2. These changes were not dependent on gender, clinical or biochemical parameters, nor functional parameters of the heart. We detected, however, a significant correlation of TRPC1 and MEF2c expression. Conclusions: The end-stage heart failure displays distinct expressional changes of TRP channels. Our findings provide a systematic description of TRP channel expression in human heart failure. The results highlight the complex interplay between TRP channels and the need for deeper analysis of early stages of hypertrophy and heart failure development.
| S-EPMC6681334 | biostudies-literature