Plasma Exchange Research Articles

Ineffectiveness of therapeutic plasma exchange as a last resort in severe COVID-19 cases: Experience from a tertiary intensive care unit.

Several studies have suggested that cytokine release syndrome (CRS) can be controlled by therapeutic plasma exchange (TPE) treatment. In this study, it was aimed to evaluate the efficacy of TPE treatment in patients who developed life-threatening respiratory failure syndrome (SARS) due to COVID-19 infection. In this retrospective, case-control study, patients, who developed SARS, were infected with the COVID-19 virus, and required intensive care unit (ICU) admission were included. Patients included in the study were divided into groups according to whether TPE experience or not and if so, how many sessions were applied. Mortality rates of patients in the ICU and 30-day mortality ratios were evaluated. A total of 110 patients, 71.8% of whom were male, with a mean age of 59.7 ± 13.3 years, were included in our study. It was observed that 70% of the patients died within a month and 80% of them died during the ICU follow-up period. The 30-day mortality rates of patients who underwent TPE at least once and those who never underwent TPE were 72.2% and 67.9%, respectively (p: 0.617). CRP, D-dimer, fibrinogen and platelet levels showed to have a decreasing trend after plasmapheresis and fluctuated thereafter. It was observed that procalcitonin and IL-6 levels were increased in the group that underwent plasmapheresis but decreased in those who did not receive plasmapheresis. Patients severely infected with SARS-CoV-2 showed fluctuations in inflammatory parameters despite TPE treatment; CRS was not suppressed by TPE; and this treatment did not confer survival benefit in this patient group.

Plasma exchange and intravenous immunoglobulin prolonged the survival of a porcine kidney xenograft in a sensitized, deceased human recipient.

The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. We conducted a kidney xenotransplantation in a deceased human recipient using a porcine kidney with five gene edits (5GE) on March 25th, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.

A case series: Three cases of Morvan's syndrome as a rare autoimmune disorder with anti-Caspr2 antibody.

Morvan syndrome (MoS) is an uncommon male-dominant autoimmune disorder marked by peripherally innervated hyperexcitability, autonomic disturbances, and encephalopathic encephalopathy, frequently with mass complaints manifesting as neuromyotonia (involuntary jerking, twitching, and stiffening of muscles), myotonia, neuropathic pain, hyperhidrosis, severe constipation, and severe sleep disturbances accompanied by dream reenactments, agrypnia agitation, and delusions, associated with autoantibodies to voltage-gated and potassium channel complexes such as anti-contactin-associated protein-like 2 (Caspr2) antibody. All this misery can be very disabling and even life-threatening. Reported cases show an unforeseeable outcome, with fatalities occurring even in those who initially responded. It has been reported that patients have reacted to immunologic therapies-corticosteroids, intravenous immunoglobulins, plasma exchanges, azathioprine, cyclophosphamide, rituximab, or carbamazepine, gabapentin, and clonazepam. However, no long-term effective cure has yet been found for this condition. Clinicians and researchers increasingly emphasize alternative and complementary medicine, with a growing trend toward traditional Chinese medicine (TCM). Following glucocorticoid therapy, all 3 patients experienced a recurrence of the disease. Patients 1 and 2 observed symptomatic relief after intravenous immunoglobulin administration; however, upon discontinuation of the treatment, their conditions relapsed and worsened compared with the previous state. The 3 patients were definitively diagnosed with serum Caspr2-positive MoS, accompanied by a constellation of neurological manifestations. The 3 patients were treated under the guidance of TCM theory. According to the principles of TCM, the patients were characterized by the deficiency of Yin, so the prescriptions were as follows: Shaoyao-Gancao decoction combined with Sanjia-Fumai decoction. After the application of TCM, there was a reversal of neuropsychiatric manifestations such as unintentional rippling, jerking, muscle stiffness, myokymia, hyperhidrosis, and extreme constipation. Patients' quality of life improved significantly; to date, they have achieved Karnofsky Performance Status scores of 100, and the anti-Caspr2 antibody result in case 2 dropped from 1:32 to normal. We first report the effective treatment of the MoS case series with TCM as complementary and alternative medicine.

Evaluation of patients undergoing therapeutic plasma exchange in the pediatric intensive care unit and determining the factors affecting prognosis.

Therapeutic plasma exchange (TPE), an extracorporeal method targeting the removal of large molecular weight pathogens, is explored in this study for indications, complications, prognosis, safety, and effectiveness. The patients' data were collected retrospectively. Overall, 334 sessions of TPE were applied to 57 patients. Per the American Society for Apheresis classification, 24.6% of indications fell under Category I, 14% Category II, and 50.9% Category III. Sepsis-induced multiorgan dysfunction syndrome (MODS) emerged as the leading indication, correlating with elevated needs for mechanical ventilation (MV), increased failed organs, and heightened mortality. Patients undergoing continuous renal replacement therapy faced a 16.06 times higher mortality risk. Non-survivors exhibited higher comorbidity, prolonged MV, increased inotropic drug requirement, more failed organs, and a higher PRISM score. 33.2% of complications occurred, primarily catheter-related. Sepsis-induced MODS and extracorporeal modalities are associated with increased mortality in TPE patients, with comorbidities, ventilation, and PRISM scores potentially influencing outcomes.

Effects of external parameters on plasma characteristics and uniformity in a dual cylindrical inductively coupled plasma

The dual cylindrical inductively coupled plasma source, compared to the conventional structure of inductively coupled plasma source, can significantly improve the uniformity of plasma. It has an enhanced potential for application in processes, such as etching and ashing. A uniform plasma can be obtained by allowing the remote plasma from the upper chamber modulate the main plasma generated in the lower chamber. In this study, a fluid model was employed to investigate a dual cylindrical inductively coupled Ar/O2 discharge. The effects of external parameters on electron density, electron temperature, O atomic density, and plasma uniformity in the main chamber were studied, and the reasons were analyzed. The results of this study show that remote power can control the plasma uniformity and increase the plasma density in the main chamber. As the remote power increased, plasma uniformity improved initially and then deteriorated. The main power affected the plasma density at the edge of the main chamber and can modulate the plasma density in the main chamber. The gas pressure affected both the uniformity and density of the plasma. As the gas pressure increased, the plasma uniformity deteriorated, but the free radical density improved.

Toward a Restrictive Use of Plasma Exchanges in Thrombotic Microangiopathies.

Toward a Restrictive Use of Plasma Exchanges in Thrombotic Microangiopathies.

Nanoparticles Fueled by Enzyme for the Treatment of Hyperlipidemic Acute Pancreatitis.

Hyperlipidemic acute pancreatitis (HAP) is a serious inflammatory pancreatic disease commonly seen in patients with disorders of lipid metabolism. Decreasing blood triglyceride levels and proinflammatory factors can alleviate hyperlipidemic pancreatitis. The lipase that enhanced the Brownian motion of mesoporous silica in triglyceride solutions could accelerate decomposition of the lipid and improve the efficiency of absorption. In this study, we developed a mesoporous silica nanoparticle with dual modification of IL-6 aptamer and lipase for the treatment of HAP. The nanoparticle could increase the ability of particles to absorb inflammatory factor IL-6 and decompose triglycerides. For every 10 mg of the dual-modified nanoparticles, the efficiency of capturing IL-6 was approximately 9.67 pg/mL and of decomposing triglycerides was approximately 3.88 mg/mL in the plasma of HAP patients within 2 h. In summary, the mesoporous silica nanoparticle could absorb the IL-6 inflammatory factor through IL-6 aptamers and decompose triglycerides through lipase. Furthermore, based on clinically available plasma exchange technology, combined with our developed dual-modified nanoparticles, we designed an absorption device for the treatment of hyperlipidemic pancreatitis; it works to promote the treatment of hyperlipidemic pancreatitis.

Alteration in sB7-H4 Serum Levels and Placental Biomarker Expression after Therapeutic Plasma Exchange in Early-Onset Preeclampsia Patients.

Therapeutic plasma exchange (TPE) is a widely used treatment for numerous diseases including pregnancy-related conditions. Our prior study on 20 early-onset preeclampsia patients undergoing TPE revealed a significant extension in pregnancy duration and reduced serum levels of sFlt-1, sFlt-1/PlGF, and sEndoglin. Here, we investigated the impact of TPE on serum sB7-H4, an immunological checkpoint molecule, and placental proteins (Flt-1, Eng, B7-H4, iNOS, TNF-α) in TPE-treated early-onset preeclampsia patients (N = 12, 23 + 2-28 + 5 weeks), conventionally treated counterparts (N = 12, 23 + 5-30 weeks), and gestational age-matched controls (N = 8, 22 + 4-31 + 6 weeks). Immunoblotting, ELISA, and co-immunohistochemistry were used for biomarker analysis, including placental inflammation factors (iNOS, TNF-α). The results showed that TPE extended pregnancy by a median of 6.5 days in this cohort of early-onset preeclampsia. Serum sB7-H4, sFlt-1, and sEndoglin levels decreased, along with reduced expression of their membrane-bound proteins in placental tissue upon TPE treatment. Moreover, TPE-treated patients displayed reduced placental inflammation compared to preeclampsia patients receiving standard-of-care treatment. In conclusion, TPE may improve pregnancy outcomes in early-onset preeclampsia by lowering circulating levels of sB7-H4, sFlt-1, and sEndoglin, as well as reducing placental inflammation. This translational approach holds promise for enhancing placental function and extending gestation in high-risk pregnancies including very preterm PE or HELLP cases.

One-year survival benefit of plasma exchange in idiopathic inflammatory myositis patients with progressive interstitial lung disease-a systemic review and meta-analysis

ObjectivesThis study aimed to systematically evaluate the efficacy of plasma exchange (PLEX) in patients with idiopathic inflammatory myositis (IIM) complicated by interstitial lung disease (ILD). MethodWe conducted a comprehensive literature search in Medline and EMBASE from their inception to August 2023, focusing on randomized controlled trials, cohort studies, and case-control studies involving IIM patients with ILD treated with PLEX compared to those treated with standard therapies. The primary outcome was the one-year survival rate. All the statistical analyses were performed using RevMan version 4.12.0. ResultsOut of 438 retrieved studies, 16 were selected for full-text review. Six cohort studies involving 148 patients with anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis or antisynthetase syndrome-related dermatomyositis with rapidly progressive ILD refractory to standard treatments (including glucocorticoids, immunosuppressive agents, or intravenous immunoglobulin) met the inclusion criteria. Patients receiving PLEX in addition to other therapies demonstrated a greater one-year survival rate (relative risk [RR] 1.59, 95 % CI 0.96–2.65, I2 52 %) than did patients in the non-PLEX group. Significance was reached in a sensitivity analysis after excluding one outlier (RR 1.71, 95 % confidence intervals [CI] 1.30–2.25; I2 0 %). Additionally, there was a trend suggesting that PLEX improved lung function, radiographic outcomes, and key serum biomarkers, such as Krebs von den Lungen-6 and ferritin. Funnel plot asymmetry suggested publication bias due to the lack of reporting of negative trials. All studies had a low risk of bias. ConclusionsAs an adjunctive therapy, PLEX improved one-year survival in IIM patients with rapidly progressive ILD who were unresponsive to standard treatments.

A novel plasma source concept for negative ion generation in neutral beam injectors for fusion applications

Abstract A low-temperature plasma can very well be confined by a simple magnetic dipole, such as in the Van Allen belts of Earth’s magnetoshpere. This configuration can be reproduced in laboratory as a small experimental device, designed in such a way that the magnetic field lines remain within a vacuum-tight container and are virtually not intercepted by the container wall. In this paper we propose to use a dipole field for the realization of an efficient negative Ion source. To this purpose, we analyze the plasma confinement capabilities of such plasma source, in order to assess the equilibrium pressure and estimate the particle trajectories and drifts.

Treatment of myasthenia gravis in france: A retrospective claims database study (STAMINA).

This study aimed to describe treatment patterns in patients with myasthenia gravis (MG) in France. A retrospective cohort analysis was performed using the French National Health Data System (SNDS) database between 2008 and 2019. MG patients were identified using ICD-10 codes during hospitalization and/or long-term disease. We defined two adult subpopulations: a prevalent MG population of patients alive on 31/12/2019and an incident population of newly identified patients with MG in 2012 and 2013. Among the 22,079 prevalent patients, 53.1% (n = 11,498) received at least one chronic MG treatment in 2019. Among these treated patients, 52.5% received Acetylcholinesterase inhibitors (AChEIs) only, 10.2% were treated with corticosteroids (CS) ± AChEIs, 7.3% with non-steroidal immunosuppressive treatments (NSIST) and CS, 24.2% with NSIST w/o CS, and 5.8% received immunoglobulin and/or plasma exchange. Among the 2,661 incident patients, 84.6% received at least one chronic MG treatment over the 6-year follow-up period, and among them, 79.0% had at least one treatment category change. During the first semester of follow-up, 28.1% of patients were treated with an immunomodulator (CS, NSIST). Among patients starting treatment with immunomodulator, the proportion of those treated with CS decreased from 35.3% at initiation to 10.9% at 6years. This study illustrates the complexity of MG management. Significant CS sparing was observed over time. The frequent treatment changes especially in patients with an immunomodulator treatment reflect the high variability of the disease severity. The need for personalised treatment approaches in the management of MG to reduce the burden of disease remains.

Exploring the role of plasmapheresis prior to thyroidectomy in managing thyrotoxicosis: a comprehensive scoping review.

A thyroid storm is the most extreme and life-threatening presentation of thyrotoxicosis. Thyroidectomy can be used for definitive treatment. It should be performed after euthyroidism is accomplished. The use of therapeutic plasma exchange (TPE) is a last resort option in cases where standard pharmacological therapy proves to be ineffective. Due to its rare prevalence, there are limited data evaluating the usefulness and efficacy of TPE as a bridging therapy to thyroidectomy. The absence of relevant literature prompted us to conduct a scoping review. The following bibliographic databases were searched for articles dated 30 November 2023: Medline, EMBASE, Web of Science and Google Scholar. The search identified 1047 records, of which 42 articles were accepted with a total of 234 patients. The dominant indications for TPE were side effects due to conventional treatment. The mean fT4 level decreased 51.9% of baseline after TPE, while the mean fT3 level decreased 66.6% of baseline. The main side effects observed with FFP were allergic reactions, while the use of an albumin solution was associated with perioperative bleeding. Based on the limited data available in the literature, we recognize plasmapheresis as an effective treatment option for reducing thyroid hormone levels prior to thyroidectomy in patients with thyrotoxicosis. Available data suggest that it might be reasonable to limit the number of sessions in favor of an earlier surgical intervention. To reduce the risk of bleeding, FFP may be a better option as a replacement fluid, especially in the session prior to thyroidectomy.

Short-term efficiency of plasma exchange in combination with immunosuppressants and/or biologics in the treatment of idiopathic inflammatory myopathy with rapidly progressive interstitial lung disease: a systematic review and meta-analysis

Objective Rapidly progressive interstitial lung disease (RP-ILD) is a frequent and serious manifestation of idiopathic inflammatory myopathy (IIM) associated with poor outcomes. Plasma exchange (PE) can quickly remove pathogenic substances from the blood. Therefore, PE may be efficacious in IIM patients who have elevated levels of autoantibodies, cytokines and chemokines, fighting for time for immunosuppressive therapy. However, the value of adding PE to immunosuppressants remains unclear. The purpose of this study was to determine the short-term outcomes, including the survival rate at 6 months and change of the laboratory data, of PE in combination with immunosuppressants and/or biologics in the treatment of IIM-RP-ILD. Methods We searched PubMed, Embase and Cochrane Library to find reports of interest published from inception to March 4, 2024. STATA 15.1 was used for data analysis. A fixed or random-effects model with inverse-variance weighting was used to estimate the pooled risk ratio (RR) and 95% confidence interval (CI). Results Two hundred and thirty studies were identified. Eleven studies, including five retrospective cohort studies, four case-control studies and two case series, were included. PE was performed on 114 patients. The survival rate at 6 months was 80% (95%CI = 64%–92%), with moderate heterogeneity (I 2=63.45%, p < 0.05). Moreover, the 6-month survival rate was significantly better in the PE group than in the non-PE group (RR, 1.34; 95% CI = 1.05–1.71, I 2=30.7%; p = 0.194). ILD-related serum markers, including ferritin, KL-6 and anti-MDA-5 antibody titres, were significantly suppressed by a series of PE treatments (p < 0.05). Conclusion The application of PE therapy plus treatment with corticosteroids, immunosuppressants and/or biologics was effective for patients with IIM-RP-ILD. PE may have additional supportive effect in intractable disease.

Fast simulation strategy for capacitively-coupled plasmas based on fluid model

Fluid simulations are widely used in optimizing the reactor geometry and improving the performance of capacitively coupled plasma (CCP) sources in industry, so high computation speed is very important. In this work, a fast method for CCP fluid simulation based on the framework of Multi-physics Analysis of Plasma Sources (MAPS) is developed, which includes a multi-time-step explicit upwind scheme to solve electron fluid equations, a semi-implicit scheme and an iterative method with in-phase initial value to solve Poisson's equation, an explicit upwind scheme with limited artificial diffusion to solve heavy particle fluid equations, and an acceleration method based on fluid equation modification to reduce the periods required to reach equilibrium. In order to prove the validity and efficiency of the newly developed method, benchmarking against COMSOL and comparison with experimental data have been performed in argon discharges on the Gaseous Electronics Conference (GEC) reactor. Besides, the performance of each acceleration method is tested, and the results indicated that the multi-time-step explicit Euler scheme can effectively decline the computational burden in the bulk plasma and reduce the time cost on the electron fluid equations by half. The in-phase initial value method can greatly decrease the iteration times required to solve linear equations and lower the computational time of Poisson's equation by 77 %. The acceleration method based on equation modification can reduce the periods required to reach equilibrium by two-thirds.

The role of therapeutic plasma exchange using membrane plasma separation in the late onset myasthenic crisis: a case report

Myasthenia gravis (MG) is an autoimmune disease, in which antibodies bind to receptors in the neuromuscular junction (NMJ), causing muscle weakness. This disease is relatively challenging to diagnose due to its late onset and comorbidities. Several treatment options include therapeutic plasma exchange (TPE) with membrane plasma separation, that aims to remove large molecular-weight toxins such as pathogenic antibodies and lipoproteins. A 61-year-old male patient was admitted to the ICU post-sternotomy due to mediastinal tumor resection. Extubation failed, so we decided to undergo a tracheostomy. The lung pathology result showed lymphocyte-predominant thymoma, and along with symptoms of chest weakness and ptosis, the patient was suspected for MG. Electromyography results confirmed the occurrence of functional lesions in post-synaptic NMJ consistent with MG. We assessed patient with myasthenic crisis (MC), then gave pyridostigmine 60 mg 6x/day, and planned for TPE using membrane plasma separation. Plasma exchange was done by 1.5 of blood volume. The patient developed sepsis pneumonia and was administered levofloxacin based on his culture results. Patient still had weakness. We re-evaluated the drugs that might have exacerbated MG. Aztreonam in combination with co-trimoxazole was administered to combat Stenotrophomonas maltophilia pneumonia. The patient was eventually weaned from the ventilator and gradually recovered. Keywords: Membrane Plasma Separation; Myasthenia Gravis Crisis; Therapeutic Plasma Exchange; TPE Citation: Kurnia D, Manggala SK, Irawany V. The role of therapeutic plasma exchange using membrane plasma separation in the late onset myasthenia gravis crisis: a case report. Anaesth. pain intensive care 2024;28(5):969−973; DOI: 10.35975/apic.v28i5.2557 Received: July 17, 2024; Reviewed: August 01, 2024; Accepted: August 01, 2024

Relationship between septic acute kidney injury and adiponectin: A retrospective study in patients undergoing continuous plasma exchange with dialysis.

Adiponectin (APN) is a multimeric protein with anti-inflammatory properties that is specifically secreted by adipocytes. Continuous plasma exchange with dialysis (cPED) is a blood purification therapy in which plasma exchange is performed using a selective membrane plasma separator while the dialysate flows outside the hollow fibers. Patients with sepsis were divided into two groups based on the presence or absence of acute kidney injury (AKI) complications: AKI and non-AKI group. Plasma APN levels significantly increased after cPED in both groups. The creatinine levels in the AKI group before cPED were significantly higher than those in the non- AKI group. The plasma APN levels in the AKI group before cPED were significantly higher than those in the non-AKI group. cPED increased APN levels in both patients with and without AKI. Therefore, cPED therapy may be a promising intervention for increasing APN levels in patients with sepsis.

Extracorporeal pediatric renal replacement therapy: diversifying application beyond kidney failure.

The utilization of extracorporeal renal replacement therapy (RRT), including continuous renal replacement therapy (CRRT) and hemodialysis (HD), beyond the treatment of volume overload and acute kidney injury (AKI) has witnessed a significant shift, demonstrating the potential to improve patient outcomes for a range of diseases. This comprehensive review explores the non-kidney applications for RRT platforms in critically ill children, focusing on diverse clinical scenarios such as sepsis, inborn errors of metabolism, liver failure, drug overdose, tumor lysis syndrome, and rhabdomyolysis. In the context of sepsis and septic shock, RRT not only facilitates fluid, electrolyte, and acid/base homeostasis, but may offer benefits in cytokine regulation, endotoxin clearance, and immunomodulation which may improve multi-organ dysfunction as well as hemodynamic challenges posed by this life-threatening condition. RRT modalities also have an important role in caring for children with inborn errors of metabolism, liver failure, and tumor lysis syndrome as they can control metabolic derangements with the efficient clearance of endogenous toxins in affected children. In cases of drug overdose, RRT is a crucial tool for rapid extracorporeal clearance of exogenous toxins, mitigating potential organ damage. The intricate interplay between liver failure and kidney function is examined, elucidating the role of RRT and plasma exchange in maintaining fluid and electrolyte balance when hepatic dysfunction complicates the clinical picture. Furthermore, RRT and HD are explored in the context of rhabdomyolysis, highlighting their utility in addressing AKI secondary to traumatic events and crush syndrome.

Plasma-Functionalized Liquids for Decontamination of Viable Tissues: A Comparative Approach

Plasma-functionalized liquids (PFLs) are rich in chemical species, such as ozone, hydrogen peroxide, singlet oxygen, hydroxyl radical and nitrogen oxides, commonly referred to as reactive oxygen and nitrogen species (RONS). Therefore, manifold applications are being investigated for their use in medicine, agriculture, and the environment. Depending on the goal, a suitable plasma source concept for the generation of PFLs has to be determined because the plasma generation setup determines the composition of reactive species. This study investigates three PFL-generating plasma sources—two spark discharges and a flow dielectric barrier discharge (DBD) system—for their efficacy in eliminating microbial contaminants from tissue samples aiming to replace antibiotics in the rinsing process. The final goal is to use these tissues as a cell source for cell-based meat production in bioreactors and thereby completely avoid antibiotics. Initially, a physicochemical characterization was conducted to better understand the decontamination capabilities of PFLs and their potential impact on tissue viability. The results indicate that the flow DBD system demonstrated the highest antimicrobial efficacy due to its elevated reactive species output and the possibility of direct treatment of tissues while tissue integrity remained. Achieving a balance between effective large-scale decontamination and the biocompatibility of PFLs remains a critical challenge.

Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers.

Liquid biopsy (LB) is an essential tool for obtaining tumor-derived materials with minimum invasion. Bile has been shown to contain much higher free nucleic acid levels than blood plasma and can be collected through endoscopic procedures. Therefore, bile possesses high potential as a source of tumor derived cell-free DNA (cfDNA) for bile duct cancers. In this study, we show that a multigene panel for plasma LB can also be applied to bile cfDNA for comparing driver gene mutation detection in other sources (plasma and tumor tissues of the corresponding patients). We collected cfDNA samples from the bile of 24 biliary tract cancer cases. These included 17 cholangiocarcinomas, three ampullary carcinoma, two pancreatic cancers, one intraductal papillary mucinous carcinoma, and one insulinoma. Seventeen plasma samples were obtained from the corresponding patients before surgical resection and subjected to the LiquidPlex multigene panel LB system. We applied a machine learning approach to classify possible tumor-derived variants among the prefiltered variant calls by a LiquidPlex analytical package with high fidelity. Among the 17 cholangiocarcinomas, we could detect cancer driver mutations in the bile of 10 cases using the LiquidPlex system. Of the biliary tract cancer cases examined with this method, 13 (54%) and 4 (17%) resulted in positive cancer driver mutation detection in the bile and plasma cfDNAs, respectively. These results suggest that bile is a more reliable source for LB than plasma for multigene panel analyses of biliary tract cancers.

On the Piezoelectric Properties of Zinc Oxide Thin Films Synthesized by Plasma Assisted DC Sputter Deposition

AbstractThis work presents a study of piezoelectric zinc oxide (ZnO) thin films deposited by a novel post‐reactive sputtering method. The process utilizes a rotating drum with DC magnetron sputtering deposition onto substrates with subsequent DC plasma‐assisted oxidation of the deposited metal to metal oxide. The paper analyzes the influence of plasmaassisted magnetron sputtering (PA‐MS) deposition parameters (O2 plasma source power, O2 flow, and Ar flow) on the morphological, structural, optical, and piezoelectric properties of ZnO thin films. Design of experiments has been utilized to evaluate the role of these parameters on the growth rate (rg) and the properties of resulting films. Results indicate a predominant influence of the plasma power on the rg over other parameters. Among the eight tested samples, three of them show high crystal quality with high intensity (0001) diffraction peak, characteristic of the wurtzite crystalline structure of ZnO, and one of them exhibits piezoelectric coefficient values of ≈11pC N−1. That sample corresponding to a ZnO film deposited at the lowest rg of 0.075 nm s−1, confirmed the key role of the deposition parameters on the piezoelectric response of films, and demonstrated PA‐MS as a promising technique to produce high‐quality piezoelectric thin films.