Dried Blood Spot Analyses for the Diagnosis of Anti-cytokine Autoantibodies

Background: High-titer neutralizing anti-cytokine autoantibodies have been shown to be involved in several acquired diseases, including pulmonary alveolar proteinosis, cryptococcal meningitis, and disseminated/extrapulmonary Nocardia infections (anti-GM-CSF autoantibodies), disseminated mycobacterial disease (anti-IFN-gamma autoantibodies), and some cases of severe COVID-19 infection (anti-type 1 interferons). Currently, patient blood samples are shipped via courier and require temperaturecontrolled conditions for transfer. This method is expensive and requires patients to have access to medical personnel to draw the blood. However, the well-established technique of collecting blood on a paper card as a dried blood spot (DBS) for diagnosis offers a point of care alternative which can be performed with a simple finger prick. This method is less invasive, cheaper, and allows for easy transport of patient samples. Method(s): 30 uL of whole blood from patients was blotted on filter paper and stored at 4C until use. The filter paper was hole punched and each punched spot was eluted with 150 uL of a 0.05% Tween PBS solution at room temperature overnight. The eluate was screened for anti-cytokine autoantibodies using a particle-based approach. Patient plasma was also screened in conjunction for comparison. Result(s): We confirmed the presence of autoantibodies in the DBS eluate from 4 previously diagnosed patients with anti-GM-CSF autoantibodies and 2 patients with anti-IFN-gamma autoantibodies. Functional studies showed the DBS eluate from a patient with anti-GM-CSF autoantibodies was able to block GM-CSF-induced STAT-5 phosphorylation in normal PBMC. As a proof of concept and to increase the number of patients evaluated, we also confirmed the presence of anti-cytokine autoantibodies using dried plasma eluate from 9 patients with known anti-GM-CSF autoantibodies and 9 patients with anti-IFN-gamma autoantibodies. Levels detected in DBS analyses were comparable to the levels found in plasma from the same patients not subjected to blotting and elution. Temperature studies showed that the autoantibodies were detected at similar levels when stored at 4C, 25C, and 40C for a week. Conclusion(s): The diagnosis of pathogenic anti-cytokine autoantibodies should be considered in the context of unusual or adult-onset infections, and screening for this diagnosis can be performed with dried blood spot testing.Copyright © 2023 Elsevier Inc.

Analysis of approaches to sterility testing of COVID-19 prevention vaccines.

Preventive vaccination against SARS-CoV-2 infection is currently receiving close attention in the Russian Federation. Improving public confidence in immunisation with new vaccines largely depends on a guarantee of the absence of side effects caused by contamination. A high risk of contamination is inherent to biological products, including coronavirus prevention vaccines, due to their properties and the nature of raw materials used. This risk adds to the need for using effective contaminant detection approaches. The aim of the study was to evaluate the possibility to improve sterility testing of preventive vaccines against SARS-CoV-2 infection. This article presents an analysis of the procedures proposed by pharmaceutical developers for sterility testing of ten Russian vaccines approved in the country for COVID-19 prevention. The authors considered specific characteristics of these vaccines, including their physical and chemical properties, the presence of antimicrobial components, and other critical factors affecting the correctness of the experimental setup. The results suggest that it is possible to improve sterility testing. According to the authors, the main directions for its improvement are the proposal to develop an alternative procedure based on compendial method 2 (OFS.1.2.4.0003.15, Ph. Rus. XIV), as well as the use of a universal culture medium. If used for refining the established procedures and developing new ones, the authors' recommendations will improve the reliability and applicability of sterility testing during both manufacturing and pre-approval regulatory assessment of updated coronavirus vaccines for subsequent release to the market. The proposed approaches can be applied to testing other medicinal products for sterility.Copyright © 2023 National Electronic-Information Consortium (NEICON). All rights reserved.

Hemoperfusion with CytoSorb as Adjuvant Therapy in Critically Ill Patients with SARS-CoV2 Pneumonia

Background: Several pro- and anti-inflammatory cytokines involved in COVID-19 and it is reasonable to speculate that their removal from blood might limit organ damage. Hemoperfusion with CytoSorb is a technique developed to adsorb molecules in the middle molecular weight range (up to 55 kDa). Studies in vitro and in vivo have shown that HP is highly effective in clearing blood from a number of cytokines. Method(s): We report a case series of 9 consecutive COVID-patients admitted to our COVID Intensive Care Unit (ICU). Five of them were treated with HP using CytoSorb (T), due to the heavy emergency overload it was impossible to deliver blood purification in the other 4 patients (C), who were also considered as potential candidates by the attending medical team. All patients had pneumonia and respiratory failure requiring continuous positive airway pressure. Different antibacterial prophylaxes, antiviral, and anti-inflammatory therapies including steroids were delivered. Result(s): Our results show a better clinical course of T compared to control patients (C), in fact all T except 1 survived, and only 2 of them were intubated, while all C required intubation and died. CRP decreased in both groups, but to a greater extent after HP. Lymphocytopenia worsened in control patient but not in treated patient after HP. Procalcitonin increased in 2 of the not treated patients. In all survived patients (n = 4) HP reduced pro-inflammatory cytokines, as IL-6, TNF-alpha, and IL-8. Notably, a striking effect was observed on IL-6 levels that at the end of the second session were decreased by a 40% than before the first treatment. Serum levels of IL-8 and TNF-alpha were lowered within normal range. In all patients the treatment was safe and there were no complications. Conclusion(s): Our study suggests a potential efficacy of HP in an early phase of viral infection not only for improving survival in the treated patients but also by the remodeling treatment-associated cytokine levels.

Online or In-Person Course? Meaningful Discussion of Learning Effectiveness and Satisfaction of Microwave Filter Design Course in Graduate Students

Contribution: A research on applying blended teaching in microwave filter design in graduate students. Background: The Covid-19 epidemic has caused many universities worldwide to switch to online courses. Taiwan did not have a large-scale local infection in 2020, so the school has implemented a blended teaching plan, combining online and in-person courses. Intended Outcomes: Discuss the effectiveness and satisfaction of the Microwave Filter Design Course in Graduate Students for two classes, Online or In-person course. Application Design: This study uses a quasi-experiment to teach microwave filter courses in the two classes. The teacher integrated into the Flipped Classroom and Interactive Response System (IRS). Students must use the APP to complete the preclass preview and prepare materials. Class A [Formula Omitted] uses in-person classrooms for the whole course;Class B uses blended teaching. The first eight weeks are synchronized online, then mid-term exams, and in-person courses are used for the next ten weeks. Students in two classes in the last week filled out the course satisfaction questionnaire. Findings: Class B achieved better results in the eighth midterm exam week, showing better learning results. Although students in both classes are highly satisfied with the course, Class A is more satisfied than Class B. For graduate students participating in the microwave filter design course, in-person classrooms and blended teaching can achieve good learning results and satisfaction. However, teachers must pay attention to students' reception and understanding of flipped classrooms when using online teaching. And timely and in-depth guidance on the accuracy of APP use.

Dual-band Air-Ground Radio Performance: Example Flight Test Results

We recently concluded a four-year University Leadership Initiative (ULI) project sponsored by NASA, which investigated multiple aviation communications technology areas aimed at enhancing future aviation safety. These areas were dual-band air-ground communications for air traffic management, detection and interdiction of small drones, and high-capacity terrestrial airport communications networking. In this paper we report on flight test results of our dual-band radios. These radios were designed to use a spectrally efficient multi-carrier modulation, filterbank multicarrier (FBMC), which we had previously shown to improve resilience to high-power distance measurement equipment (DME) adjacent-channel interference, in comparison to existing orthogonal frequency division multiplexing (OFDM) schemes. In our NASA project, we designed the FBMC radios to extend performance even further, using the following techniques: (i) simultaneous dual-band transmission and reception;(ii) ground station (GS) spatial diversity;(iii) higher-order modulation for a factor of 5 capacity increase over QPSK;(iv) a Doppler-resilient option using a smaller number of subcarriers;and, (v) 5-MHz bandwidth C-band transmissions for an order of magnitude capacity increase over existing 500-kHz channel schemes. To our knowledge, these are novel achievements for civil aviation, and our flight test results attained a technology readiness level (TRL) of 5. In this paper we briefly describe the project history, in which we spent approximately one year working with Boeing to participate in one of their Eco-Demonstrator flight trials, and obtained special temporary authorizations to transmit in both the L-band and C-band, from the FAA, the FCC, and the DoD. When COVID-19 dispersed worldwide, Boeing was no longer able to support us, so we revised our plans and teamed with the South Carolina Civil Air Patrol (SC CAP) to conduct smaller-scale flight tests. This paper summarizes the radio designs and the novel features we employed, as well as analyses, computer simulations, and laboratory tests prior to terrestrial mobile testing, all of which culminated in our successful flight tests. We show example flight test results that serve as proof of concept for all the five aforementioned radio performance enhancements. Example results include signal-to-noise ratio and bit error ratio, diversity gains, and throughput gains through both higher-order modulation and wider bandwidth channels. We also report on some lessons learned, and some ideas for future advancement of our work. © 2023 IEEE.

Critical points in randomized research on DCD donor in-situ perfusion (NRP): the interim DONARE Study clinical evaluation

Background/aims: Controlled DCD organ donation (cDCD) is a strategic target for the Italian transplantation network. Italian peculiarities in cDCD donation make published results questionable and raise concern over organ ischemic damage. Consequently, normothermic regional perfusion (NRP) has been strongly recommended in potential cDCD donors. In 2019 the randomized multicenter DONARE study was designed to describe ischemic-reperfusion and inflammatory biomarkers during NRP and to test the potential benefit of apheresis by an adsorbent filter (CytoSorb) included in the NRP circuit. The aim of this report is to describe the modulation of the clinical characteristics and of the NRP in the DONARE study enrolled cases. Method(s): The study protocol was defined by the DCD national working group and proposed to all the Italian DCD donation centers. The coordinating center (CNT) has monitored the evolving cDCD activity to preserve the study capacity of representing the Italian scenario. Samples have been blindly centralized to an independent laboratory for cytokines profiling. The outcomes of transplanted organs have been recorded in the national quality database. Result(s): From September 2020 to June 2022, 27 out of the 40 planned cases have been enrolled in six centers: 4 in 2020, 12 in 2021 and 11 within June 2022. Approval is still pending in other centers. Main causes of exclusion among potential cDCD donors were: age above 65 (in 2020), e-CPR prior- to-death, shortage in personnel and COVID-19 restrictions. The age limit for enrolment (<65yrs) was abolished by amendment due to the national trend: mean age of enrolled cases increased from 57+/-6 in 2020 to 67+/-6 years in 2022. Mean NRP duration decreased from 223,3+/-39,2 in 2020 to 168,9+/-42,6 minutes in 2022;serial samples (4/2 with/without Cytosorb, from T0 to T4) from different points of the NRP circuit have been completed throughout the procedure in all the cases. All the enrolled cases became utilized donors. No study-related adverse event has been reported. Conclusion(s): Coordination of multicenter studies in the rapidly evolving scenario of controlled DCD donation should take advantage of continuous monitoring of real-life procedures and auditing of adherence to operational recommendations. The interim evaluation confirms the feasibility and safety of the study.

Cytokine elimination in suspected COVID-19 perymyocarditis

Background: Only recently studies have been able to demonstrate the safety and efficacy of purification therapies in inflammatory diseases. Here we present the management of a young (21y) male patient in severe cardiogenic shock due to COVID-19 perymyocarditis admitted to the ICU at Bolzano Central Hospital. November 30th 2020 the patient developed high fever (>40 C) and diarrhea. After unsuccessfully being treated orally with a macrolide he was admitted to a peripheral hospital the 4th of December. The day after he deteriorated, required transfer to the ICU, endotracheal intubation and pharmacological cardiovascular support (Norepinephrine, Levosimendan). Antimicrobial treatment was started with piperacillin/tazobactam, linezolid and metronidazole. Despite multiple radiological and microbiological diagnostic attempts the origin of this severe septic shock remained unclear. December 6th the patient was transferred to Bolzano Central Hospital for VA-ECMO evaluation. Method(s): The transesophageal echocardiography revealed 15-20% of EF, lactate (5,2 mmol/l), cardiac enzymes (TropT 1400 mcg/l) and inflammatory parameters (PCT 35 ng/ml, IL-6 685 pg/ml) were elevated. We performed cardiac monitoring via Swan-Ganz catheter. The cardiac index was 1,6 l/min/m2. The peak dosage for Norepinephrine reached 7,5mg/h (1,47 mcg/kg/min). At Bolzano ICU we facilitate the pharmacological therapy with milrinone, vasopressin and low dose epinephrine. Furthermore, we impost continuous hemodiafiltration with CytoSorb filter. Result(s): Only hours after the start of filtration therapy the patient improved and we were able to gradually reduce catecholamine therapy, lactate values decreased. A VA-ECMO implantation was no more necessary. December 10th, we saw a stable patient without ventilatory or cardiovascular support, at echocardiography we revealed a normal EF. Conclusion(s): Clinically we saw a young patient in severe septic/cardiogenic shock due to perimyocarditis. Yet diagnostic attempts (CT-scan, multiple blood/urinary/liquor cultures) remained negative. Despite multiple negative PCR tests for SARS-CoV2 infection we performed specific immunoglobulin analysis and received a positive result for IgM. We therefore conclude on a COVID-19 associated perymyocarditis. Furthermore, this case illustrates the potential benefit of cytokine filtration and elimination in COVID-19 patients with altered IL6 levels.

The use of CytoSorb in a septic shock patient with ARDS due to Sars Cov-2

Background: Septic shock is a clinical condition of sepsis aggravated by circulatory, cellular and metabolic dysregulation. Diagnostic criteria include the need for vasopressors to maintain a PAM>65 and serum lactate levels>2 under adequate fluid therapy. Early identification of critically septic patients is necessary to allow early and adequate treatment with improved prognosis. In this case report we evaluate the haemodynamic impact of CytoSorb therapy in a case of septic shock in a patient with ARDS Sars cov2. Method(s): Patient with Sars Cov-2 ARDS was admitted to our department. He was intubated and had a SOFA Score 7. On day 15 the patient presented an increase in PCT CRP and WBC levels with the need for norepinephrine infusion. Empirical antibiotic therapy was started and after 24 hours also CytoSorb Therapy. Four CytoSorb cartridge columns were used. The first two were changed every 12 h and then the next two were changed every 24 h. Result(s): Two days after CytoSorb therapy there was an improvement in haemodynamic without the need of vasopressor support. There was also a reduction in inflammatory parameters and lactates. The trend of these values was shown in figure 1. Conclusion(s): In this case report we evaluated the impact of CytoSorb therapy in a case of septic shock in a patient with ARDS Sars Cov-2. The early use of hemadsorption with CytoSorb combined with re-evaluation of antibiotic therapy resulted in a marked improvement in the patient's clinical status.

CytoSorb on the Septic Shock

Background: Septic shock, defined as organ dysfunction caused by a dysregulated host response to infection, is a condition associated with high morbidity and mortality. One of the hallmarks of sepsis is the excessive release of cytokines and other inflammatory mediators that cause septic shock and multi-organ failure (MOF). New adsorbents are now available as adjuvant therapy aimed at modulating the cytokine "storm" in sepsis. They are thought to be useful if adopted early (within 8-24 hours of the diagnosis of septic shock) in patients who are unresponsive to standard therapy. Here we report our experience with CytoSorb. Method(s): From January 2021 to May 2022, 46 patients with septic shock were treated with continuous renal replacement therapy (CRRT) associated with hemoadsorption with CytoSorb. All cases presented organ failure including AKI. Surgical patients (n = 13) were treated with surgery, COVID patients (n = 15) and medical patients (n = 16) with medical therapy;all surgery cases were operated on before starting the haemadsorption and in some cases reoperation with the need to suspend the adsorption. The mean age was 69 +/- 17 years (SD). On admission the mean SAPSII score was 50 +/- 11 (SD). CRRT as hemodiafiltration (CVVHDF) was performed. All patients received at least one CytoSorb treatment and additional treatments (up to 21 filters in a Covid patient) according to our indication. The CytoSorb cartridge was installed in series to the high cut-off filter;blood flow rates were maintained between 120 and 150 mL/min while dialysis doses from 18 to 45 mL/kg/hour. CytoSorb was renewed every 24 hours. We evaluated the impact of CytoSorb on 30-day survival, haemodynamics and relevant outcomes. Result(s): The 30-day survival was 30%. During treatment with CytoSorb, patients had a hemodynamic stabilization with a significant improvement in MAP, a reduction in amines and a decrease in PCR and PCT (Figure 1). Mortality at 30 days among medical patients was almost comparable to that of COVID patients and higher than that of surgical patients (70%, 69% and 61%, respectively). It should be noted that almost half of the deceased patients arrived late in the hospital, thus leading to a late start of treatment. Conclusion(s): We confirm the efficacy and usefulness of the CytoSorb if adopted early in patients who do not respond to standard therapy. CytoSorb treatment was safe and well tolerated with no device-related adverse events during or after treatment sessions.

A mixed-method study on the barriers of industry 4.0 adoption in the Indonesian SMEs manufacturing supply chains

PurposeThis paper aims to investigate the adoption barriers of Industry 4.0 in the Indonesian manufacturing supply chains.Design/methodology/approachThe mixed method was deployed to validate the findings. First, the qualitative study was conducted based on the interviews. Then, the companies were approached using filter questions on the involvement in adopting industry 4.0 and its impact on the supply chain.FindingsBased on the qualitative study, nine main barriers were found in the thematic analysis. Thus, to get a consensus on the barriers in the industry, the barrier indicators were tested using a structural equation model retrieved from 173 small and medium Indonesian manufacturing firms. Results indicate that five main barriers (e.g. unclear Industry 4.0 policy, higher-risk investment, insecure data sharing, lack of expertise and lack of incentive) are confirmed as the adoption barriers.Practical implicationsThe successful adoption of supply chain integration with Industry 4.0 technology can strengthen the manufacturing sector and competitiveness. Therefore, this study can be a complimentary assessment to evaluate the Indonesia Industry 4.0 Readiness Index (INDI 4.0) and the effectiveness of the government support program.Originality/valueThe results can be used as the framework to foresee the successful implementation of smart manufacturing supply chain management and its integration. Therefore, the authors proposed the framework to foresee the successful implementation of smart manufacturing, supply chain management and integration.

Extracorporeal cytokine hemadsorption in severe COVID-19 respiratory failure

Background: At least 20% of coronavirus disease 2019 (COVID-19) patients develop acute hypoxemic respiratory failure requiring admission to intensive care unit in 5-32% of the cases. Hyper-inflammatory activation characterized by immune cell infiltration and elevated levels of cytokines was reported as the main mechanism leading to critical illness and severe acute respiratory distress syndrome (ARDS). CytoSorb is currently used for all the conditions where elevated levels of cytokines are present. Along with the beneficial effect on systemic inflammation, CytoSorb can be easily integrated with all extracorporeal circulation systems. Case Presentation: Here, we present the laboratory and clinical outcomes of 11 patients with microbiological confirmed SARS-CoV-2 infection. These patients were treated with CytoSorb to remove the excess of cytokine. All patients were male, overweight and only 3 (27%) were over 70 years old. Median age was 62 years and median body mass index was 28. Best supportive care was provided according to hospital guidelines of that moment and included antibiotic therapy, antiretroviral therapy and protective ventilation. Result(s): Cytokines levels were evaluated before and after treatment. A significant reduction of IL-6, IL-8, IL-10 and IL-1beta was observed. A significant drop of C-reactive protein (CRP) median levels was observed starting from 48 hours after treatment start levels. The decrease in the inflammatory status was associated with a progressive improvement in the respiratory function, with a significant increase in P/F from the first day after the end of the therapy. A similar trend was observed for procalcitonin. Conclusion(s): CytoSorb therapy proved to be safe in COVID-19 patients. A clinical improvement was observed in most of the treated patients despite the severity of the disease. In this study CytoSorb was used empirically for 24- 48 hours based on previous experience in septic shock. The persistence of significant levels of IL-6 and CRP after CytoSorb treatment may suggest that a prolonged treatment can improve the efficacy in controlling COVID-19 hyperinflammatory status.

Hemoadsorption by CytoSorb in septic no-Covid and Covid patients: a case series

Background: Septic shock is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The reduction of pro-inflammatory and anti-inflammatory mediators by hemoadsorption represents a new tool in the treatment of sepsis. In the present case series, we evaluated the impact of CytoSorb on adult patients with septic shock. Method(s): Patients with septic shock, admitted to Intensive Care Unit (ICU) from March 1, 2021 to February 28, 2022 who received CytoSorb therapy within 72 hours of admission were enrolled in the study. The severity of clinical conditions at admission was assessed by the SAPS II and SOFA scores;The magnitude of the inflammatory response was estimated using the plasmatic levels of C reactive protein (CRP) and interleukin-6 (IL-6). The effect of CytoSorb therapy on the inflammatory state, was evaluated measuring the percentage reduction of IL-6 and CRP. Time elapsed from ICU admission and the start of CytoSorb therapy was also assessed. T-test was used to compare the means of the groups of Survivors and No survivors. Fisher's test was used to evaluated the difference in mortality between Covid and No covid patients. Result(s): Twelve patients were evaluated. Six patients tested positive for covid-19, while the other six did not. Table 1 shows the values of age, SAPSII, SOFA, IL-6, CRP, PCT and timing between the survivors and the no survivors. Overall, there was no significant difference between the two groups in terms of SAPSII, SOFA, age, CRP. There was a significant difference in the timing of Cytosorb start and percentage of IL-6 removal: In surviving patients the timing of intervention was shorter (3,3+/-1,8 vs 23,5+/-18,9 hours) than in non- survivors. The IL-6 removal rate was significantly higher in the survivor group (70,8+/-15,87 vs 33,2+/-12,26). Conclusion(s): In survivors the timing of CytoSorb therapy was shorter and the IL-6 removal rate was higher than in non-survivors. This suggest that the early applying of CytoSorb adsorber in combination with Continuous Renal Replacement Therapy (CRRT) techniques, could increase the survival rate of septic shock patients. Using CytoSorb was safe and well tolerated with no device-related adverse events during or after the treatment.

COMPARATIVE EFFECTS OF TOCILIZUMAB AND CYTOSORB ON BLOOD CYTOKIENE LEVELS IN PATIENTS WITH SARS-CoV-2 PNEUMONIA

Background/aims: SARS-CoV-2 is responsible of respiratory failure and also causes a massive release of inflammatory mediators such as IL-6, IL-1, CRP etc. This hyperinflammatory condition, often indicated as Cytokine Release Syndrome (CRS), could led to life-threatening events. The clinical course resembles septic shock and the elevated values of inflammatory mediators are associated with a higher viral load and reduced survival. The use of techniques aiming to contrast the surge of inflammatory mediators has been advocated in the treatment of this condition. Method(s): Four patients were retrospectively admitted in Intensive Care Unit with respiratory failure caused by SARS-CoV-2 infection. Two patients were treated with Tocilizumab (TCZ) alone, the others received TCZ in association with hemoadsorption (HA) treatment. The HA procedure was performed with CytoSorb responsible of removing hydrophobic molecules with a molecular weight of up to approximately 60 kDa including cytokines and other inflammatory mediators involved in CRS. Each procedure lasts 24 hours. Blood values of IL-6, C-reactive protein (CRP) and other biochemical variables were measured in two patients who received Tocilizumab (TCZ) alone and in other two in whom it was associated with hemoadsorption (TCZ- HA). All variables were measured before, during and after the treatment. The aim of the study is to assess the variations of IL-6 in patients with SARS-CoV-2 infection treated with TCZ alone or in association with hemoadsorption (HA). Result(s): All patients full-filled the criteria of severe SARS-CoV-2 infection. In all patients the administration of TCZ was followed by an increasing in IL-6 values. Its values remained elevated in patients given TCZ but sharply decreased in the following days in those treated also with HA. The percentage variations of IL-6 from the baseline between the two groups was +344% and +89% in the two patients treated with TCZ alone and - 56% and -15% in TCZ-HA group. Both TCZ and TCZ-HA were well tolerated. Conclusion(s): The increase of the IL-6 can be ascribed to its displacement from cellular and soluble receptors, whereas its decrease is likely due to the scavenging effect exerted by the HA. Although the association TCZ- HA could be valuable in the treatment of the Cytokine Release Storm (CRS) associated with SARS-CoV-2, the HA could be more effective as it neutralizes a wider panel of inflammatory mediators. More experience is needed to identify the best candidate for TCZ or TCZ-HA.

A systematic review of the use of CytoSorb© Hemoadsorption in patients undergoing veno-venous ECMO support for severe acute respiratory distress syndrome

Objectives: Acute respiratory distress syndrome (ARDS) often results in high mortality and morbidity. Hemoadsorption therapy, such as CytoSorb©, is being increasingly used to target the underlying hyperinflammation that occurs with ARDS. This review aims to evaluate the available data on the use of CytoSorb in combination with veno-venous extracorporeal membrane oxygenation (V-V ECMO) in severe ARDS cases, and to assess its effects on inflammatory, laboratory, and clinical parameters, as well as on patient outcomes. Method(s): A systematic literature review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement. Whenever possible, an analysis of changes in relevant biomarkers and clinical parameters was performed. Result(s): CytoSorb© therapy was associated with significant reductions in circulating levels of C-reactive protein and interleukin-6 (p = 0.039 and p = 0.049, respectively), as well as an increase in PaO2/FiO2 levels (p = 0.028). There was also a trend towards reduced norepinephrine dosage (p = 0.067). Mortality rates in patients treated with CytoSorb©tended to be lower than in the control groups, but these studies had high heterogeneity and low power. In an exploratory analysis of 90-day mortality in COVID19 patients receiving V-V ECMO, the therapy was associated with a reduced risk of death. Conclusion(s): Overall, the reviewed data suggests that CytoSorb© therapy can effectively reduce inflammation and potentially improve survival in ARDS patients treated with V-V ECMO. Therefore, early initiation of CytoSorb ©in conjunction with ECMO may offer a promising approach to enhance lung rest and promote recovery in patients with severe ARDS. A randomised trial is warranted to confirm our findings.

A Successful Treatment of a Critically Patient with SARS-CoV2

Background: The role of inflammatory cytokines is known in the pathogenesis of organ damage and is also confirmed in the context of COVID-19 disease. The modulation of the cytokine storm seems to determine endothelial protection, which can translate into a reduction of the "capillary leak syndrome", and, consequently, in a better control of the formation of edema and pulmonary infiltrates. CytoSorb stands in this context as a cartridge capable of adsorbing cytokines and allowing a better clinical course. Case Report: A 69 years-old woman with a history of arterial hypertension, diabetes mellitus and CKD, was admitted to ICU for SARS Cov 2 related critical illness staged with chest CT, blood gas analysis and PCR. At the admission, the patient presented with ubiquitous interstitial pneumonia, PaO2 60 mmHg with 90% Airvo2 and PCR 36.67. Therefore, in order to remove inflammatory cytokines, the patient underwent hemoperfusion treatment with the CytoSorb adsorbent cartridge. Method(s): The protocol used is approved by the FDA for the treatment of covid patients and consists of the use of 4 cartridges 12h, 12h, 24h, 24h with measurement for each cycle of PCR, PaO2 and chest CT control. Result(s): During the hemoperfusion whit CytoSorb, respiratory failure improved until the patient was discharged from the ICU on the tenth day, with oxygen support via simple facial mask. Below the progressive values of the PCR, PaO2 and the chest CT control on the twelfth day. Conclusion(s): The hemoperfusion treatment with the CytoSorb adsorbent cartridge proved to be a valid adjuvant therapy in determining a better clinical course both in terms of the need for invasive mechanical ventilation and survival.

Efficient COVID-19 super pixel segmentation algorithm using MCFO-based SLIC.

In computer vision segmentation field, super pixel identity has become an important index in the recently segmentation algorithms especially in medical images. Simple Linear Iterative Clustering (SLIC) algorithm is one of the most popular super pixel methods as it has a great robustness, less sensitive to the image type and benefit to the boundary recall in different kinds of image processing. Recently, COVID-19 severity increased with the lack of an effective treatment or vaccine. As the Corona virus spreads in an unknown manner, th-ere is a strong need for segmenting the lungs infected regions for fast tracking and early detection, no matter how small. This may consider difficult to be achieved with traditional segmentation techniques. From this perspective, this paper presents an efficient modified central force optimization (MCFO)-based SLIC segmentation algorithm to discuss chest CT images for detecting the positive COVID-19 cases. The proposed MCFO-based SLIC segmentation algorithm performance is evaluated and compared with the thresholding segmentation algorithm using different evaluation metrics such as accuracy, boundary recall, F-measure, similarity index, MCC, Dice, and Jaccard. The outcomes demonstrated that the proposed MCFO-based SLIC segmentation algorithm has achieved better detection for the small infected regions in CT lung scans than the thresholding segmentation.

Ratiometric fluorescence immunoassay of SARS-CoV-2 nucleocapsid protein via Si-FITC nanoprobe-based inner filter effect.

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has necessitated rapid, easy-to-use, and accurate diagnostic methods to monitor the virus infection. Herein, a ratiometric fluorescence enzyme-linked immunosorbent assay (ELISA) was developed using Si-fluorescein isothiocyanate nanoparticles (FITC NPs) for detecting SARS-CoV-2 nucleocapsid (N) protein. Si-FITC NPs were prepared by a one-pot hydrothermal method using 3-aminopropyl triethoxysilane (APTES)-FITC as the Si source. This method did not need post-modification and avoided the reduction in quantum yield and stability. The p-nitrophenyl (pNP) produced by the alkaline phosphatase (ALP)-mediated hydrolysis of p-nitrophenyl phosphate (pNPP) could quench Si fluorescence in Si-FITC NPs via the inner filter effect. In ELISA, an immunocomplex was formed by the recognition of capture antibody/N protein/reporter antibody. ALP-linked secondary antibody bound to the reporter antibody and induced pNPP hydrolysis to specifically quench Si fluorescence in Si-FITC NPs. The change in fluorescence intensity ratio could be used for detecting N protein, with a wide linearity range (0.01-10.0 and 50-300 ng/mL) and low detection limit (0.002 ng/mL). The concentration of spiked SARS-CoV-2 N protein could be determined accurately in human serum. Moreover, this proposed method can accurately distinguish coronavirus disease 2019 (COVID-19) and non-COVID-19 patient samples. Therefore, this simple, sensitive, and accurate method can be applied for the early diagnosis of SARS-CoV-2 virus infection. Electronic Supplementary Material: Supplementary material (characterization of Si-FITC NPs (FTIR spectrum, XRD spectra, and synchronous fluorescence spectra); condition optimization of ALP response (fluorescence intensity ratio change); mechanism investigation of ALP response (fluorescence lifetime decay curves and UV-vis absorption spectra); detection of N protein using commercial ELISA Kit; analytical performance of assays for ALP detection or SARS-CoV-2 N protein detection; and determination results of SARS-CoV-2 N protein in human serum) is available in the online version of this article at 10.1007/s12274-022-4740-5.

Transfer learning for segmentation with hybrid classification to Detect Melanoma Skin Cancer.

Melanoma is an abnormal proliferation of skin cells that arises and develops in most of the cases on surface of skin that is exposed to copious amounts of sunlight. This common type of cancer may develop in areas of the skin that are not exposed to a much abundant sunlight. The research addresses the problem of Segmentation and Classification of Melanoma Skin Cancer. Melanoma is the fifth most common skin cancer lesion. Bio-medical Imaging and Analysis has become more promising, interesting, and beneficial in recent years to address the eventual problems of Melanoma Skin Cancerous Tissues that may develop on Skin Surfaces. The evolved research finds that Attributes Selected for Classification with Color Layout Filter model. The research has produced an optimal result in terms of certain performance metrics accuracy, precision, recall, PRC (what is PRC? Expansion is needed in Abstract), The proposed method has yielded 90.96% of accuracy and 91% percent of precise and 0.91 of recall out of 1.0, 0.95 of ROC AUC, 0.87 of Kappa Statistic, 0.91 of F-Measure. It has been noticed a lowest error with reference to proposed method on certain dataset. Finally, this research recommends that the Attribute Selected Classifier by implementing one of the image enhancement techniques like Color Layout Filter is showing an efficient outcome.

A Novel Packaging of the MEMS Gas Sensors Used for Harsh Outdoor and Human Exhale Sampling Applications.

Dust or condensed water present in harsh outdoor or high-humidity human breath samples are one of the key sources that cause false detection in Micro Electro-Mechanical System (MEMS) gas sensors. This paper proposes a novel packaging mechanism for MEMS gas sensors that utilizes a self-anchoring mechanism to embed a hydrophobic polytetrafluoroethylene (PTFE) filter into the upper cover of the gas sensor packaging. This approach is distinct from the current method of external pasting. The proposed packaging mechanism is successfully demonstrated in this study. The test results indicate that the innovative packaging with the PTFE filter reduced the average response value of the sensor to the humidity range of 75~95% RH by 60.6% compared to the packaging without the PTFE filter. Additionally, the packaging passed the High-Accelerated Temperature and Humidity Stress (HAST) reliability test. With a similar sensing mechanism, the proposed packaging embedded with a PTFE filter can be further employed for the application of exhalation-related, such as coronavirus disease 2019 (COVID-19), breath screening.

Bayesian Noise Modelling for State Estimation of the Spread of COVID-19 in Saudi Arabia with Extended Kalman Filters.

The epistemic uncertainty in coronavirus disease (COVID-19) model-based predictions using complex noisy data greatly affects the accuracy of pandemic trend and state estimations. Quantifying the uncertainty of COVID-19 trends caused by different unobserved hidden variables is needed to evaluate the accuracy of the predictions for complex compartmental epidemiological models. A new approach for estimating the measurement noise covariance from real COVID-19 pandemic data has been presented based on the marginal likelihood (Bayesian evidence) for Bayesian model selection of the stochastic part of the Extended Kalman filter (EKF), with a sixth-order nonlinear epidemic model, known as the SEIQRD (Susceptible-Exposed-Infected-Quarantined-Recovered-Dead) compartmental model. This study presents a method for testing the noise covariance in cases of dependence or independence between the infected and death errors, to better understand their impact on the predictive accuracy and reliability of EKF statistical models. The proposed approach is able to reduce the error in the quantity of interest compared to the arbitrarily chosen values in the EKF estimation.