An overview of technologies available to monitor behaviours of mosquitoes.

Mosquito-borne diseases such as malaria, dengue, Zika, and chikungunya cause significant morbidity and mortality globally, resulting in over 600,000 deaths from malaria and around 36,000 deaths from dengue each year, with millions of people infected annually, leading to substantial economic losses. The existing mosquito control measures, such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), helped to reduce the infections. However, mosquito-borne diseases are still among the deadliest diseases, forcing us to improve the existing control methods and look for alternative methods simultaneously. Advanced monitoring techniques, including remote sensing, and geographic information systems (GIS) have significantly enhanced the efficiency and effectiveness of mosquito control measures. Mosquitoes' behavioural traits, such as locomotion, blood-feeding, and fertility are the key determinants of disease transmission and epidemiology. Technological advancements, such as high-resolution cameras, infrared imaging, and artificial intelligence (AI) driven object detection models, including groundbreaking convolutional neural networks, have provided efficient and precise options to monitor various mosquito behaviours, including locomotion, oviposition, fertility, and host-seeking. However, they are not commonly employed in mosquito-based research. This review highlights the novel and significant advancements in behaviour-monitoring tools, mostly from the last decade, due to cutting-edge video monitoring technology and artificial intelligence. These advancements can offer enhanced accuracy, efficiency, and the ability to quickly process large volumes of data, enabling detailed behavioural analysis over extended periods and large sample sizes, unlike traditional manual methods prone to human error and labour-intensive. The use of behaviour-assaying techniques can support or replace existing monitoring techniques and directly contribute to improving control measures by providing more accurate and real-time data on mosquito activity patterns and responses to interventions. This enhanced understanding can help establish the role of behavioural changes in improving epidemiological models, making them more precise and dynamic. As a result, mosquito management strategies can become more adaptive and responsive, leading to more effective and targeted interventions. Ultimately, this will reduce disease transmission and significantly improve public health outcomes.

Culex-Transmitted Diseases: Mechanisms, Impact, and Future Control Strategies using Wolbachia.

Mosquitoes of the Culex genus are responsible for a large burden of zoonotic virus transmission globally. Collectively, they play a significant role in the transmission of medically significant diseases such as Japanese encephalitis virus and West Nile virus. Climate change, global trade, habitat transformation and increased urbanisation are leading to the establishment of Culex mosquitoes in new geographical regions. These novel mosquito incursions are intensifying concerns about the emergence of Culex-transmitted diseases and outbreaks in previously unaffected areas. New mosquito control methods are currently being developed and deployed globally. Understanding the complex interaction between pathogens and mosquitoes is essential for developing new control strategies for Culex species mosquitoes. This article reviews the role of Culex mosquitos as vectors of zoonotic disease, discussing the transmission of viruses across different species, and the potential use of Wolbachia technologies to control disease spread. By leveraging the insights gained from recent successful field trials of Wolbachia against Aedes-borne diseases, we comprehensively discuss the feasibility of using this technique to control Culex mosquitoes and the potential for the development of next generational Wolbachia-based control methods.

Solasodine targets NF-κB signaling to overcome P-glycoprotein mediated multidrug resistance in cancer.

P-glycoprotein (P-gp) mediated multidrug resistance (MDR) is the leading cause of chemotherapy failure since it causes the efflux of chemotherapeutic drugs from the cancer cells. Solasodine, a steroidal alkaloid and oxaspiro compound, present in the Solanaceae family showed significant cytotoxic effects on various cancer cells. However, the effect of solasodine on reversing P-gp mediated drug resistance is still unknown. Primarily in this study, the integrative network pharmacology analysis found 71 common targets between solasodine and cancer MDR, among them NF-κB was found as a potential target. The results of immunofluorescence analysis showed that solasodine significantly inhibits NF-κB-p65 nuclear translocation which caused downregulated P-gp expression in KBChR-8-5 cells. Further, solasodine binds to the active sites of the TMD region of P-gp and inhibits P-gp transport activity. Moreover, solasodine significantly promotes doxorubicin intracellular accumulation in the drug resistant cells. Solasodine reduced the fold resistance and synergistically sensitized doxorubicin's therapeutic effects in KBChR-8-5 cells. Additionally, the solasodine and doxorubicin combination treatment increased the apoptotic cell populations and G2/M phase cell cycle arrest in KBChR-8-5 cells. The MDR tumor bearing xenograft mice showed tumor-suppressing characteristics and P-gp downregulation during the combination treatment of solasodine and doxorubicin. These results indicate that solasodine targets NF-κB signaling to downregulate P-gp overexpression, inhibit P-gp transport activity, and enhance chemosensitization in MDR cancer cells. Considering its multifaceted impact, solasodine represents a potent natural fourth-generation P-gp modulator for reversing MDR in cancer.

Effect of Cold Adaptation on the State of Cardiovascular System and Cardiac Tolerance to Ischemia/Reperfusion Injury.

Despite the unconditional success achieved in the treatment and prevention of AMI over the past 40 years, mortality in this disease remains high. Hence, it is necessary to develop novel drugs with mechanism of action different from those currently used in clinical practices. Studying the molecular mechanisms involved in the cardioprotective effect of adapting to cold could contribute to the development of drugs that increase cardiac tolerance to the impact of ischemia/reperfusion. An analysis of the published data shows that the long-term human stay in the Far North contributes to the occurrence of cardiovascular diseases. At the same time, chronic and continuous exposure to cold increases tolerance of the rat heart to ischemia/ reperfusion. It has been demonstrated that the cardioprotective effect of cold adaptation depends on the activation of ROS production, stimulation of the ß2-adrenergic receptor and protein kinase C, MPT pore closing, and KATP channel.

Variations in morphology of cystic artery: systematic review and meta-analysis.

Background: Variations in cystic artery anatomy are not unusual in occurrence, hence considerably crucial during hepatobiliary surgical planning and execution. This systematic review and meta-analysis of the anatomical variations of cystic artery (CA) was undertaken to emphasize their significance in surgical practice. Methods: The PICO model was adopted, both MeSH term and free keywords were utilized for the search strategy. The risk of bias in each study was calculated by the anatomy quality assurance (AQUA) tool. Result: The search strategy identified 8204 records, extracted 5529 studies, and evaluated 117 abstracts. Out of these 117 studies, 53 met the eligibility criteria. The CA was absent in 2% of instances (95% CI: 0.01-0.04), indicating that 98% of cases had the CA. In 10071 participants from 29 investigations, double cystic arteries were found in 13% (95% CI: 11-16%), with significant heterogeneity (I2 = 91%). In 46 studies with a total of 9928 participants, 89% of the individuals had CA originating from RHA (95% CI: 85%-92%) with significant heterogeneity (I2=94.3%) and a predictive range of 43%-99%. Conclusion: The cystic artery is primarily derived from the right hepatic artery, followed by aberrant, proper, and left hepatic arteries. It is located anterior to common hepatic ducts and cystic ducts. The mean length and diameter of CA were 20.77 mm and 1.91 mm Short cystic arteries are common (20%) Congenital anomalies like absent and double cystic arteries have low prevalence but must be conside-red during surgery.

Increasing Eligibility to Transplant Through the Selective Cytopheretic Device: A Review of Case Reports Across Multiple Clinical Conditions.

A stable, minimum physiological health status is required for patients to qualify for transplant or artificial organ support eligibility to ensure the recipient has enough reserve to survive the perioperative transplant period. Herein, we present a novel strategy to stabilize and improve patient clinical status through extracorporeal immunomodulation of systemic hyperinflammation with impact on multiple organ systems to increase eligibility and feasibility for transplant/device implantation. This involves treatment with the selective cytopheretic device (SCD), a cell-directed extracorporeal therapy shown to adhere and immunomodulate activated neutrophils and monocytes toward resolution of systemic inflammation. In this overview, we describe a case series of successful transition of pediatric and adult patients with multiorgan failure to successful transplant/device implantation procedures by treatment with the SCD in the following clinical situations: pediatric hemophagocytic lymphohistiocytosis, and adult hepatorenal and cardiorenal syndromes. Application of the SCD in these cases may represent a novel paradigm in increasing clinical eligibility of patients to successful transplant outcomes.

Novel case of combination antibiotic therapy for treatment of a complicated polymicrobial urinary tract infection with one organism harboring a metallo-ß-lactamase (MBL) in a pregnant patient.

Carbapenem resistance due to metallo-beta-lactamases (MBLs) is a global phenomenon and an important challenge for antibiotic therapy (Boyd et al., 2020 [1]). While previous reports have demonstrated both in vitro and in vivo synergy using the combination of ceftazidime-avibactam and aztreonam against Stenotrophomonas maltophilia, an MBL-harboring organism, this treatment strategy has not been reported during pregnancy (Mojic et al., 2017 [2], [3], Mojica et al., 2016 [4], Alexander et al., 2020 [5]). We describe a 33-year-old pregnant female with polymicrobial, bilateral pyelonephritis caused by Stenotrophomonas maltophilia and other gram-negative bacteria. The organisms were eradicated with the combination of ceftazidime-avibactam and aztreonam followed by successful delivery with no observed adverse effects in either mother or child post-partum.

Andrographolide reverts multidrug resistance in KBChR 8-5 cells through AKT signaling pathway.

Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy. P-glycoprotein (P-gp) one of the ATP-binding cassette (ABC) transporters plays an important role in MDR. In this study, we examined the sensitizing property of andrographolide (Andro) to reverse MDR in the drug-resistant KBChR 8-5 cells. Andro exhibited increased cytotoxicity in a concentration-dependent manner in the P-gp overexpressing KBChR 8-5 cells. Furthermore, Andro showed synergistic interactions with PTX and DOX in this drug-resistant cells. Andro co-administration enhanced PTX- and DOX-induced cytotoxicity and reduced cell proliferation in the MDR cancer cells. Moreover, reactive oxygen species (ROS) were elevated with a decrease in the mitochondrial membrane potential (MMP) during Andro and chemotherapeutic drugs combination treatment in the drug-resistant cells. Furthermore, Andro and PTX-induced cell cycle arrest was observed in the drug-resistant cell. We also noticed that the expression of ABCB1 and AKT were downregulated during Andro (4 µM) treatment. Furthermore, Andro treatment enhanced the expression of caspase 3 and caspase 9 in the combinational groups that support the enhanced apoptotic cell death in drug-resistant cancer cells. Therefore, the results reveal that Andro plays a role in the reversal of P-gp-mediated MDR in KBChR 8-5 cells which might be due to regulating ABCB1/AKT signaling pathway.

Flight traits of dengue-infected Aedes aegypti mosquitoes.

Understanding the flight behaviour of dengue-infected mosquitoes can play a vital role in various contexts, including modelling disease risks and developing effective interventions against dengue. Studies on the locomotor activity of dengue-infected mosquitoes have often faced challenges in terms of methodology. Some studies used small tubes, which impacted the natural movement of the mosquitoes, while others that used cages did not capture the three-dimensional flights, despite mosquitoes naturally flying in three dimensions. In this study, we utilised Mask RCNN (Region-based Convolutional Neural Network) along with cubic spline interpolation to comprehensively track the three-dimensional flight behaviour of dengue-infected Aedes aegypti mosquitoes. This analysis considered a number of parameters as characteristics of mosquito flight, including flight duration, number of flights, Euclidean distance, flight speed, and the volume (space) covered during flights. The accuracy achieved for mosquito detection and tracking was 98.34% for flying mosquitoes and 100% for resting mosquitoes. Notably, the interpolated data accounted for only 0.31%, underscoring the reliability of the results. Flight traits results revealed that exposure to the dengue virus significantly increases the flight duration (p-value 0.0135 × 10-3) and volume (space) covered during flights (p-value 0.029) whilst decreasing the total number of flights compared to uninfected mosquitoes. The study did not observe any evident impact on the Euclidean distance (p-value 0.064) and speed (p-value 0.064) of Aedes aegypti. These results highlight the intricate relationship between dengue infection and the flight behaviour of Aedes aegypti, providing valuable insights into the virus transmission dynamics. This study focused on dengue-infected Aedes aegypti mosquitoes; future research can explore the impact of other arboviruses on mosquito flight behaviour.

Synthesis of a Novel Gold(I) Complex and Evaluation of Its Anticancer Properties in Breast Cancer Cells.

BACKGROUND: Platinum complexes are commonly used for cancer chemotherapy; however, they are not only highly-priced but also have various side effects. It is, therefore, important to design affordable anticancer drugs with minimal side effects. METHODS: We synthesized a new gold(I) complex, PF6{(BDPEA)(TPPMS) digold(I)} (abbreviated as PBTDG) and tested its cytotoxicity in MCF-7 breast cancer cells. We also evaluated the effects of PBTDG on mitochondrial membrane potential, generation of reactive oxygen species (ROS) and apoptosis in breast cancer cells. RESULTS: The IC50 values for PBTDG and sorafenib were found to be 1.48 µM and 4.45 µM, respectively. Exposure to PBTDG caused significant and concentration-dependent depletion of ATP and disruption of mitochondrial membrane potential. PBTDG induced 2.6, 3.6, and 5.7-fold apoptosis for 1 µM, 3 µM, and 10 µM concentrations, respectively. The induction of apoptosis by the same concentrations of sorafenib was 1.2, 1.3, and 1.6-fold, respectively. The low concentration of PBTDG (1 µM) induced the generation of ROS by 99.83%, which was significantly higher than the ROS generation caused by the same concentration of sorafenib (73.76%). The ROS induction caused by higher concentrations (5 µM) of PBTDG and sorafenib were 104.95% and 122.11%, respectively. CONCLUSION: The lower concentration of PBTDG produced similar cytotoxicity and apoptotic effects that were caused by a comparatively higher concentration of known anticancer drug (sorafenib). The anticancer effects of PBTDG are attributed to its tendency to disrupt mitochondrial membrane potential, induction of apoptosis and generation of ROS. Further studies are warranted to test the anticancer effects of PBTDG in animal models of cancer.

Auranofin sensitizes breast cancer cells to paclitaxel mediated cell death via regulating FOXO3/Nrf2/Keap1 signaling pathway.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor which acts as a regulator for cellular oxidative stress, and tightly regulated by Kelch-like ECH-associated protein 1 (Keap1). In this study, we found that auranofin and paclitaxel combination treatment increased TUNEL positive apoptotic cells and enhanced the DNA damage marker γ-H2AX in MCF-7 and MDA-MB-231 breast cancer cells. The immunoblotting analysis revealed the combination of auranofin and paclitaxel significantly increased the FOXO3 expression in a concentration dependent manner. Further we observed that auranofin and paclitaxel treatment prevents the translocation of Nrf2 in a concentration dependent manner. The increased FOXO3 expression might be involved in the cytoplasmic degradation of Nrf1-Keap1 complex. Further, the molecular docking results confirm auranofin act as the agonist for Foxo3. Therefore, the present results suggest that auranofin sensitize the breast cancer cells to paclitaxel via regulating FOXO3/Nrf2/Keap1signaling pathway.

Utility of long-read sequencing for All of Us.

The All of Us (AoU) initiative aims to sequence the genomes of over one million Americans from diverse ethnic backgrounds to improve personalized medical care. In a recent technical pilot, we compare the performance of traditional short-read sequencing with long-read sequencing in a small cohort of samples from the HapMap project and two AoU control samples representing eight datasets. Our analysis reveals substantial differences in the ability of these technologies to accurately sequence complex medically relevant genes, particularly in terms of gene coverage and pathogenic variant identification. We also consider the advantages and challenges of using low coverage sequencing to increase sample numbers in large cohort analysis. Our results show that HiFi reads produce the most accurate results for both small and large variants. Further, we present a cloud-based pipeline to optimize SNV, indel and SV calling at scale for long-reads analysis. These results lead to widespread improvements across AoU.

Rationale and Design of NEUTRALIZE-AKI: A Multicenter, Randomized, Controlled, Pivotal Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device in Patients with Acute Kidney Injury Requiring Continuous Kidney Replacement Therapy.

INTRODUCTION: NEUTRALIZE-AKI is a pivotal study to evaluate the safety and effectiveness of the selective cytopheretic device (SCD) in adult patients with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT). METHODS/DESIGN: This is a two-arm, randomized, open-label, controlled multi-center pivotal US study which will enroll 200 adult patients (age 18-80 years) in the intensive care unit with acute kidney injury requiring CKRT and at least one additional organ failure across 30 clinical centers. Eligible patients will be randomized to CKRT plus SCD therapy versus CKRT alone. Therapy will be administered for up to 10 days, with the hypothesis that the CKRT plus SCD group will demonstrate a lower mortality rate or better rate of renal recovery than the CKRT alone group by day 90. The primary outcome is a composite of dialysis dependence or all-cause mortality at day 90. CONCLUSION: The SCD is a cell-directed extracorporeal therapy that targets and deactivates pro-inflammatory neutrophils and monocytes, with evidence of efficacy across a variety of critically ill patient populations. Knowledge and experience from many of those studies and other AKI trials were incorporated into the design of this pivotal study, with the aim to investigate the role of effector cell immunomodulation in the intervention of AKI.

Engineered Antiviral Sensor Targets Infected Mosquitoes.

Escalating vector disease burdens pose significant global health risks, as such innovative tools for targeting mosquitoes are critical. CRISPR-Cas technologies have played a crucial role in developing powerful tools for genome manipulation in various eukaryotic organisms. Although considerable efforts have focused on utilizing class II type II CRISPR-Cas9 systems for DNA targeting, these modalities are unable to target RNA molecules, limiting their utility against RNA viruses. Recently, the Cas13 family has emerged as an efficient tool for RNA targeting; however, the application of this technique in mosquitoes, particularly Aedes aegypti, has yet to be fully realized. In this study, we engineered an antiviral strategy termed REAPER (vRNA Expression Activates Poisonous Effector Ribonuclease) that leverages the programmable RNA-targeting capabilities of CRISPR-Cas13 and its potent collateral activity. REAPER remains concealed within the mosquito until an infectious blood meal is uptaken. Upon target viral RNA infection, REAPER activates, triggering programmed destruction of its target arbovirus such as chikungunya. Consequently, Cas13-mediated RNA targeting significantly reduces viral replication and viral prevalence of infection, and its promiscuous collateral activity can even kill infected mosquitoes within a few days. This innovative REAPER technology adds to an arsenal of effective molecular genetic tools to combat mosquito virus transmission.

Antiproliferative effect of Solanum nigrum L. water extract on breast can-cer cells: potential roles of apoptosis and oxidative stress.

Breast cancer is the most progressive cancer among women worldwide. The currently available chemotherapeutic agents induce severe unacceptable adverse effects in breast cancer patients. In this context, natural medicinal herbs are gaining importance to find non-toxic effective anticancer drugs. Solanum nigrum is one of the major traditional medicinal plants widely used in Ayurveda for the treatment of various diseases. This study investigated the anticancer effect of Solanum nigrum water extract (SNWE) against MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines. SNWE significantly induced oxidative stress-mediated apoptotic cell death in a concentration-dependent manner. Real-time PCR results illustrated the upregulation of proapoptotic genes and downregulation of antiapoptotic genes after SNWE treatment in MCF-7 and MDA-MB-231 cell lines. Immunofluorescence analysis showed increased expressions of apoptotic markers like p53, Caspase3 and BAX by SNWE treatment. In conclusion, the findings of this study indicate the antiproliferative effect and apoptosis-inducing property of SNWE in both cell lines. Further studies are warranted on testing the anticancer activity of S. nigrum L. using animal models of cancer.

EggCountAI: a convolutional neural network-based software for counting of Aedes aegypti mosquito eggs.

BACKGROUND: Mosquito-borne diseases exert a huge impact on both animal and human populations, posing substantial health risks. The behavioural and fitness traits of mosquitoes, such as locomotion and fecundity, are crucial factors that influence the spread of diseases. In existing egg-counting tools, each image requires separate processing with adjustments to various parameters such as intensity threshold and egg area size. Furthermore, accuracy decreases significantly when dealing with clustered or overlapping eggs. To overcome these issues, we have developed EggCountAI, a Mask Region-based Convolutional Neural Network (RCNN)-based free automatic egg-counting tool for Aedes aegypti mosquitoes. METHODS: The study design involves developing EggCountAI for counting mosquito eggs and comparing its performance with two commonly employed tools-ICount and MECVision-using 10 microscopic and 10 macroscopic images of eggs laid by females on a paper strip. The results were validated through manual egg counting on the strips using ImageJ software. Two different models were trained on macroscopic and microscopic images to enhance egg detection accuracy, achieving mean average precision, mean average recall, and F1-scores of 0.92, 0.90, and 0.91 for the microscopic model, and 0.91, 0.90, and 0.90 for the macroscopic model, respectively. EggCountAI automatically counts eggs in a folder containing egg strip images, offering adaptable filtration for handling impurities of varying sizes. RESULTS: The results obtained from EggCountAI highlight its remarkable performance, achieving overall accuracy of 98.88% for micro images and 96.06% for macro images. EggCountAI significantly outperformed ICount and MECVision, with ICount achieving 81.71% accuracy for micro images and 82.22% for macro images, while MECVision achieved 68.01% accuracy for micro images and 51.71% for macro images. EggCountAI also excelled in other statistical parameters, with mean absolute error of 1.90 eggs for micro, 74.30 eggs for macro, and a strong correlation and R-squared value (0.99) for both micro and macro. The superior performance of EggCountAI was most evident when handling overlapping or clustered eggs. CONCLUSION: Accurate detection and counting of mosquito eggs enables the identification of preferred egg-laying sites and facilitates optimal placement of oviposition traps, enhancing targeted vector control efforts and disease transmission prevention. In future research, the tool holds the potential to extend its application to monitor mosquito feeding preferences.

Auranofin sensitizes breast cancer cells to paclitaxel chemotherapy by disturbing the cellular redox system.

The intrinsic redox status of cancer cells limits the efficacy of chemotherapeutic drugs. Auranofin, a Food and Drug Administration-approved gold-containing compound, documented with effective pharmacokinetics and safety profiles in humans, has recently been repurposed for anticancer activity. This study examined the paclitaxel-sensitizing effect of auranofin by targeting redox balance in the MDA-MB-231 and MCF-7 breast cancer cell lines. Auranofin treatment depletes the activities of superoxide dismutase, catalase, and glutathione peroxidase and alters the redox ratio in the breast cancer cell lines. Furthermore, it has been noticed that auranofin augmented paclitaxel-mediated cytotoxicity in a concentration-dependent manner in both MDA-MB-231 and MCF-7 cell lines. Moreover, auranofin increased the levels of intracellular reactive oxygen species (observed using 2, 7-diacetyl dichlorofluorescein diacetate staining) and subsequently altered the mitochondrial membrane potential (rhodamine-123 staining) in a concentration-dependent manner. Further, the expression of apoptotic marker p21 was found to be higher in auranofin plus paclitaxel-treated breast cancer cells compared to paclitaxel-alone treatment. Thus, the present results illustrate the chemosensitizing property of auranofin in MDA-MB-231 and MCF-7 breast cancer cell lines via oxidative metabolism. Therefore, auranofin could be considered a chemosensitizing agent during cancer chemotherapy.

Preventive effect of andrographolide against ultraviolet-B radiation-induced oxidative stress and apoptotic signaling in human dermal fibroblasts.

Ultraviolet radiation induces oxidative photoaging in the skin cells. In this study, we investigated the ability of andrographolide (ADP) to protect human dermal fibroblasts (HDFa) from UVB radiation-induced oxidative stress and apoptosis. The HDFa cells were exposed to UVB (19.8 mJ/cm2 ) radiation in the presence or absence of ADP (7 µM) and then oxidative stress and apoptotic protein expression were analyzed. UVB exposure resulted in a significant decline in the activity of antioxidant enzymes and altered mitochondrial membrane potential (MMP). Furthermore, UVB-irradiation causes increased intracellular reactive oxygen species (ROS) production, apoptotic morphological changes, and lipid peroxidation levels in the HDFa. Moreover, the pretreatment with ADP reduced the UVB-induced cytotoxicity, ROS production, and increased antioxidant enzymes activity. Further, the ADP pretreatment prevents the UVB-induced loss of MMP and apoptotic signaling in HDFa cells. Therefore, the present results suggest that ADP protects HDFa cells from UVB-induced oxidative stress and apoptotic damage.

Safety Summary of the Selective Cytopheretic Device: A Review of Safety Data Across Multiple Clinical Trials in ICU Patients With Acute Kidney Injury and Multiple Organ Failure.

OBJECTIVES: Acute kidney injury (AKI) requiring continuous kidney replacement therapy is a significant complication in ICU patients with mortality rates exceeding 50%. A dysregulated immune response can lead to systemic inflammation caused by hyperactivity of pro-inflammatory neutrophils and monocytes leading to tissue damage. The selective cytopheretic device (SCD) is an investigational medical device in a new class of cell-directed extracorporeal therapies distinct from cytokine adsorbers or filters, as it targets activated leukocytes. These leukocytes are the cellular sources driving this hyperinflammatory process. The objective of this report is to summarize the safety experience from clinical studies of the SCD in ICU patients with AKI or acute respiratory distress syndrome (ARDS) and multiple organ dysfunction (MOD). DATA SOURCES AND STUDY SELECTION: The studies included in this report represent all relevant trials of the SCD conducted in patients with AKI or ARDS and MOD. Adverse event data, clinical laboratory data and mortality rates were described and summarized in this report. DATA EXTRACTION AND DATA SYNTHESIS: Five clinical studies were included in this report, including four adult studies of AKI and/or ARDS and one pediatric AKI study, which involved 151 patients treated with the SCD in an ICU setting. Over 800 SCD sessions were deployed with an estimated 19,000 exposure hours with no device-related infections or attributable serious adverse events. Furthermore, there were no safety signals of leukopenia, thrombocytopenia, or other indications of immunodepletion or immunosuppression. CONCLUSIONS: The SCD has shown to be a promising extracorporeal therapy with promising clinical results and a favorable safety profile. These studies support that the SCD can be added as a therapeutic intervention in critically ill AKI patient populations with multiple organ failure without adding additional safety risks.