SARS-CoV-2 spike S1 mediated lung tumor regression in a mouse model

Lung cancer is the leading cause of cancer related deaths worldwide, with a relatively low 5-year survival rate. Although there are some therapies against lung cancer, new effective treatment options are urgently required. Recently during the COVID-19 pandemic, we have seen that SARSCoV-2 binds to its receptor angiotensin-converting enzyme 2 (ACE2) via spike S1 to enter the cells. This study underlines the importance of SARS-CoV-2 spike S1 in inducing death in human lung cancer cells. Interestingly, we have seen that recombinant spike S1 treatment at very low doses led to death of human A549 lung cancer cells. On the other hand, boiled recombinant SARS-CoV-2 spike S1 remained unable to induce death, suggesting that the induction of cell death in A549 cells was due to native SARS-CoV-2 spike S1 protein. SARS-CoV-2 spike S1-induced A549 cell death was also inhibited by neutralizing antibodies against spike S1 and ACE2. Moreover, our newly designed wild type ACE2-interacting domain of SARS-CoV-2 (wtAIDS), but not mAIDS, peptide also attenuated SARS-CoV-2 spike S1-induced cell death, suggesting that SARS-CoV-2 spike S1- induced death in lung cancer cells depends on its interaction with ACE2 receptor. Similarly, recombinant spike S1 treatment also led to death of H1299 and H358 human lung cancer cells. Finally, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) intoxication led to the formation tumors in lungs of A/J mice and alternate day intranasal treatment with low dose of recombinant SARS-CoV-2 spike S1 from 22-weeks of NNK insult (late stage) led to induced apoptosis and tumor regression in the lungs. These studies indicate that recombinant SARS-CoV-2 Spike S1 protein may have implications in the treatment of lung cancer.

Nanosponges: As a Dynamic Drug Delivery Approach for Targeted Delivery

Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.

A new strategy to integrate silver nanowires with waterborne coating to improve their antimicrobial and antiviral properties

PurposeThis study aims to focus on the preparation and characterization of the silver nanowire (AgNWs), as well as their application as antimicrobial and antivirus activities either with incorporation on the waterborne coating formulation or on their own.Design/methodology/approachPrepared AgNWs are characterized by different analytical instruments, such as ultraviolet-visible spectroscope, scanning electron microscope and X-ray diffraction spectrometer. All the paint formulation's physical and mechanical qualities were tested using American Society for Testing and Materials, a worldwide standard test procedure. The biological activities of the prepared AgNWs and the waterborne coating based on AgNWs were investigated. And, their effects on pathogenic bacteria, antioxidants, antiviral activity and cytotoxicity were also investigated.FindingsThe obtained results of the physical and mechanical characteristics of the paint formulation demonstrated the formulations' greatest performance, as well as giving good scrub resistance and film durability. In the antimicrobial activity, the paint did not have any activity against bacterial pathogen, whereas the AgNWs and AgNWs with paint have similar activity against bacterial pathogen with inhibition zone range from 10 to 14 mm. The development of antioxidant and cytotoxicity activity of the paint incorporated with AgNWs were also observed. The cytopathic effects of herpes simplex virus type 1 (HSV-1) were reduced in all three investigated modes of action when compared to the positive control group (HSV-1-infected cells), suggesting that these compounds have promising antiviral activity against a wide range of viruses, including DNA and RNA viruses.Originality/valueThe new waterborne coating based on nanoparticles has the potential to be promising in the manufacturing and development of paints, allowing them to function to prevent the spread of microbial infection, which is exactly what the world requires at this time.

Graphene-Based Electrochemical Nano-Biosensors for Detection of SARS-CoV-2

COVID-19, a viral respiratory illness, is caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), which was first identified in Wuhan, China, in 2019 and rapidly spread worldwide. Testing and isolation were essential to control the virus's transmission due to the severity of the disease. In this context, there is a global interest in the feasibility of employing nano-biosensors, especially those using graphene as a key material, for the real-time detection of the virus. The exceptional properties of graphene and the outstanding performance of nano-biosensors in identifying various viruses prompted a feasibility check on this technology. This paper focuses on the recent advances in using graphene-based electrochemical biosensors for sensing the SARS-CoV-2 virus. Specifically, it reviews various types of electrochemical biosensors, including amperometric, potentiometric, and impedimetric biosensors, and discusses the current challenges associated with biosensors for SARS-CoV-2 detection. The conclusion of this review discusses future directions in the field of electrochemical biosensors for SARS-CoV-2 detection, underscoring the importance of continued research and development in this domain.

Teclistamab in combination with daratumumab and lenalidomide in multiple myeloma (MajesTEC-2 study)

Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.

Prospects of TiO2-based photocatalytic degradation of microplastic leachates related disposable facemask, a major COVID-19 waste

COVID-19 is one of the serious catastrophes that have a substantial influence on human health and the environment. Diverse preventive actions were implemented globally to limit its spread and transmission. Personnel protective equipment (PPE) was an important part of these control approaches. But unfortunately, these types of PPE mainly comprise plastics, which sparked challenges in the management of plastic waste. Disposable face masks (DFM) are one of the efficient strategies used across the world to ward off disease transmission. DFMs can contribute to micro and nano plastic pollution as the plastic present in the mask may degrade when exposed to certain environmental conditions. Microplastics (MPs) can enter the food chain and devastate human health. Recognizing the possible environmental risks associated with the inappropriate disposal of masks, it is crucial to avert it from becoming the next plastic crisis. To address this environmental threat, titanium dioxide (TiO2)-based photocatalytic degradation (PCD) of MPs is one of the promising approaches. TiO2-based photocatalysts exhibit excellent plastic degradation potential due to their outstanding photocatalytic ability, cost efficiency, chemical, and thermal stability. In this review, we have discussed the reports on COVID-19 waste generation, the limitation of current waste management techniques, and the environmental impact of MPs leachates from DFMs. Mainly, the prominence of TiO2 in the PCD and the applications of TiO2-based photocatalysts in MPs degradation are the prime highlights of this review. Additionally, various synthesis methods to enhance the photocatalytic performance of TiO2 and the mechanism of PCD are also discussed. Furthermore, current challenges and the future research perspective on the improvement of this approach have been proposed.

Antimicrobial Effect of Silver Nanoparticle-Based Thin Films

The global pandemic of disease COVID-19 caused by the pathogenic SARS-Cov-2 virus brought more interest in the public health community for known silver with its potential antimicrobial properties to fight infection. One of the ways to stop virus to protect community transmission is the application of nanotechnology of silver nanoparticles on the exposed surfaces of daily used materials in public, e.g., transportation, community spaces, hospitals, and everywhere where the potential infection load is increased. Published technology to coat AgNPs on surfaces differs in the preparation of nanocomposites and substrates, which results in different mechanical and antimicrobial properties. In our study, we focused on the properties of AgNPs prepared by HiTUS and PVD technology with a challenge to test the antimicrobial effect towards the model of gram-negative bacteria (Escherichia coli), fungi (Trichoderma harzianum) and related enteroviruses (Poliovirus and Coxsackie). All tested materials showed 59% or more growth inhibition of E. coli. Growth of T. harzianum was inhibited by 16% in the presence of AgTiB2 50W, and other materials caused 37% to 68% inhibition. Enteroviruses infection was completely inhibited after 1 hour of AgNPs treatment. Only Coxsackie A7 retained infection capability after 30 minutes of treatment with AgNPs. Moreover, the ICP-OES-measured amounts of silver released in cultivation media are lower than most published studies of silver nanoparticles with a comparable antimicrobial effect. Keeping silver concentration at the lowest possible limit is one of the most critical factors for producing environmentally safe antimicrobial materials for everyday use.

Carnosic acid as potential anti-SARS-CoV-2 therapeutics: a mechanistic insight

Background/Objectives: Rosmarinus Officinalis L.(Rosemary) extract Carnosic acid(CA) has been investigated for its antimicrobial and antioxidative properties(1). Only limited number of publications reported the utilization of this extract in SARSCoV-2 infection. Also, the mechanistic understanding of CA remains to be determined. Our goal was to elucidate the potential role of CA in COVID19. To obtain mechanistic insight of pharmacogenomic action of CA, comprehensive in silico analyses were performed. Further in vitro experiments were done to illustrate the cytotoxicity of CA and confirm in silico findings. Method(s): CA was extracted from Rosmarinus Officinalis L. by HPLC. Stimulation assays were performed using the COVID19 samples. In silico pharmacogenomic properties of CA were performed by using SwissADME. SwissTargetPrediction tool was utilized to define the possible targets. SARS-CoV-2-interacting proteins were evaluated using STRING(2). To verify in silico findings, gene expression levels were analyzed using qPCR. Result(s): Among the top 15 SwissTargetPrediction target molecules(out of 100), Prostaglandin E synthase(PTGES) had the highest probability for CA. Among 332 proteins identified using the STRING, PGES2 was found to be interacting with the nsp7, important molecule for viral replication. The stimulation assays and gene expression analyses confirmed the viral inhibitory role of CA through PTGES pathway. Conclusion(s): To our knowledge, our work is the first to reveal the inhibitory role of CA in COVID19 through PTGES pathway. Given the crucial role of PTGES in inflammation, it is noteworthy to examine CA as potential anti-SARS-CoV2 therapeutics.

Cannabis-Induced Catatonia in a 15-Year-Old Male: A Case Report

Introduction: Catatonia is a syndrome of primarily psychomotor disturbances most common in psychiatric mood disorders but that also rarely has been described in association with cannabis use. Case Presentation: A 15-year-old White male presented with left leg weakness, altered mental status, and chest pain, which then progressed to global weakness, minimal speech, and a fixed gaze. After ruling out organic causes of his symptoms, cannabis-induced catatonia was suspected, and the patient responded immediately and completely to lorazepam administration. Discussion(s): Cannabis-induced catatonia has been described in several case reports worldwide, with a wide range and duration of symptoms reported. There is little known about the risk factors, treatment, and prognosis of cannabis-induced catatonia. Conclusion(s): This report emphasizes the importance of clinicians maintaining a high index of suspicion to accurately diagnose and treat cannabis-induced neuropsychiatric conditions, which is especially important as the use of high-potency cannabis products in young people increases.Copyright © 2023, State Medical Society of Wisconsin. All rights reserved.

Mesenchymal Stem/Stromal Cells: BIOLOGICAL THREAT AGENT RICIN INTOXICATION OF THE LUNGS IS EFFECTIVELY TREATED BY MESENCURE, A PROFESSIONALIZED ALLOGENEIC MESENCHYMAL CELL THERAPY, PREFERABLY VIA THE SUBCUTANEOUS ROUTE

Background & Aim: Ricin is one of the most lethal toxins, particularly if inhaled, and is considered a biological threat agent due to its wide availability and ease of production. Pulmonary ricin intoxication manifests in ARDS, cytokine storm, immune infiltration, and severe edema. Passive immunization is the preferred measure against pulmonary ricinosis, but only if administered shortly after exposure. Despite their potential to remedy pulmonary injury and inflammation, mesenchymal cell (MSC) therapies were never investigated in ricinosis. Here, we report the potential for treating pulmonary ricinosis with MesenCure, a professionalized allogeneic MSC therapy shown to reduce the mortality of patients suffering from severe pulmonary manifestations of COVID by 68%. Methods, Results & Conclusion(s): Preliminary studies demonstrated positive MesenCure effects in a sub-lethal pulmonary ricinosis model in CD1 mice. This model is regarded as highly translational due to the broad heterogeneity of these outbred mice. Positive effects included a reduction in excess protein content of the bronchoalveolar lavage fluid (BALF) by 45% when MesenCure was injected intravenously (IV) at 125k cells/animal, 48h post-exposure (PE) and evaluated one day later (p<0.05, Fig. 1A). Moreover, we found up to 52% reduction in the excess BALF leukocytes, when MesenCure was injected IV, 24h PE using the same dose (p<0.05, Fig. 1B) or 6h PE using a double dose (p<0.01, Fig. 1C), and evaluated two days PE. Optimizing the dose and administration route further improved the therapeutic outcome of MesenCure applied 6h PE as assessed by weight loss. As shown in Fig. 1D-E, IV injection of 250k-500k MesenCure cells/animal slightly protected the intoxicated animals against weight loss (p for treatment x time interaction <0.01 or <0.05 for 250k and 500k cells/animal, respectively). Interestingly, one million cells IV resulted in a lesser effect (not shown), however when injected subcutaneously (SC), 1M cells were very effective (p<0.001, Fig. 1F), seemingly even more effective than 2M cells/animal SC (Fig. 1G). Surprisingly, 2M thawed cells/animal injected SC protected the animals against weight loss almost completely (p<0.0001, Fig. H). In conclusion, we provide evidence for the potential of SC MSCs, specifically MesenCure, for treating pulmonary ricinosis and possibly other forms of ARDS. In agreement with Giri and Galipeau (2020), we provide further evidence for the dependency of MSC outcomes on their specific state and administration route. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

Neurological complications encountered in imaging studies in association with COVID-19 - a single center analysis

Introduction and aim. COVID-19 is a viral infectious disease, which was first reported in patients with unusual pneumonia in December 2019. However, as the pandemic progressed, extrapulmonary manifestations including various neurologic complications have been started to be increasingly reported. In this retrospective study, we tried to search the neurological complications seen in our patients with positive rRT-PCR test for COVID-19 and examine the underlying associated risk factors. Material and methods. We have retrospectively analyzed the neuroimaging studies performed in our patients with positive rRT-PCR test for COVID-19 between April, 2020 and August, 2021. Both computed tomography (CT) scans and magnetic resonance imagings (MRI) of brain, head & neck region and the spine were retrospectively evaluated for the presence of any complications in patients with positive rRT-PCR test for COVID-19. Results. There were 147 patients having neuroradiological imaging studies performed for various neurological symptoms. Among these patients we detected 10 acute neurologicalcomplications.The most common was acute ischemic stroke in 5 patients and intracranial hemorrhage in 3 patients, two of which were intraventricular hemorrhage. The other complications included a preasumed cytotoxic lesion of corpus callosum in a 18 year old girl and lumbar spondylodiscitis complicated with psoas abcess in a 47 year-old man. Conclusion. In COVID-19 patients severe neurological complications can occur even as a presenting manifestation. Early cytotoxic endothelial injury can be the underlying cause in these patients and should be further studied in larger series in terms of what the susceptibility factors in these patients. © 2022 Publishing Office of the University of Rzeszow. All Rights Reserved.

LANGERHANS CELL HISTIOCYTOSIS IN A CHILD WITH MULTISYSTEMIC LESIONS ASSOCIATED WITH INFECTED POLIOMYELITIS AND SARS-COV-2, FEATURES OF DIAGNOSTICS. CLINICAL CASE.

Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells. The prognosis varies depending on the form of the disease and organ damage. Any organs and systems can be involved in the pathological process in various combinations. A poor response to standard therapy and an unfavorable prognosis are characteristic of patients with a multisystem form of LCH and involvement of organs at risk. Skin lesions are a classic sign of LCH. Purpose - to describe the complexity and duration of diagnosis of LCH with multisystem damage in a boy aged 2 years and 2 months, infected with poliomyelitis and coronavirus. Clinical case. The first clinical manifestations of LCH in the child debuted with an eczematous-seborrheic rash on the scalp with spread to the limbs and trunk. The child was treated for toxicoderma, hemorrhagic vasculitis at the place of residence for 6 months. The boy lost 1.5 kg of body weight in 1 month. At the time of hospitalization, seborrheic-eczematous rashes on the skin with a hemorrhagic component, trophic-inflammatory changes in the nails of the hands, signs of protein-energy deficiency, stomatitis, gingivitis, hepatosplenomegaly, polyserositis, diabetes insipidus, osteolytic foci of the frontal bones were found. Results of the tests: anemia, thrombocytopenia, hypoproteinemia and hypoalbuminemia, coagulation disorders. The patient had the onset of lower flaccid paraparesis, muscle hypotonia. The boy was diagnosed with a number of infectious complications, including poliomyelitis (a derivative of vaccine poliovirus type 2), COVID-19. The child received LCH-III cytostatic therapy with a positive effect. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies.Copyright © 2023 Institute of Physics of the Russian Academy of Sciences. All rights reserved.

Phenytoin Toxicity with High Dose, Concomitant Ascorbic Acid Dosing.

High dose ascorbic acid may increase risk of phenytoin toxicity. This case report demonstrates high phenytoin levels resulting in adverse drug reactions subsequent to dosing concomitantly with high dose vitamin C, or ascorbic acid (AA), as a precaution against acquiring corona virus (COVID) infection. This patient suffered from a major seizure when he ran out of his phenytoin prescription. Subsequent initiation of phenytoin and later addition of high dose AA resulted in truncal ataxia and falls with bilateral wrist and finger extension weakness. Phenytoin and AA were discontinued, and the patient returned to baseline on a new medication regimen of lacosamide and gabapentin without any other major seizures one year later.

Toxicological Effects of Fine Particulate Matter (PM2.5): Health Risks and Associated Systemic Injuries-Systematic Review.

Previous studies focused on investigating particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) have shown the risk of disease development, and association with increased morbidity and mortality rates. The current review investigate epidemiological and experimental findings from 2016 to 2021, which enabled the systemic overview of PM2.5's toxic impacts on human health. The Web of Science database search used descriptive terms to investigate the interaction among PM2.5 exposure, systemic effects, and COVID-19 disease. Analyzed studies have indicated that cardiovascular and respiratory systems have been extensively investigated and indicated as the main air pollution targets. Nevertheless, PM2.5 reaches other organic systems and harms the renal, neurological, gastrointestinal, and reproductive systems. Pathologies onset and/or get worse due to toxicological effects associated with the exposure to this particle type, since it can trigger several reactions, such as inflammatory responses, oxidative stress generation and genotoxicity. These cellular dysfunctions lead to organ malfunctions, as shown in the current review. In addition, the correlation between COVID-19/Sars-CoV-2 and PM2.5 exposure was also assessed to help better understand the role of atmospheric pollution in the pathophysiology of this disease. Despite the significant number of studies about PM2.5's effects on organic functions, available in the literature, there are still gaps in knowledge about how this particulate matter can hinder human health. The current review aimed to approach the main findings about the effect of PM2.5 exposure on different systems, and demonstrate the likely interaction of COVID-19/Sars-CoV-2 and PM2.5.

Factors associated with increased financial toxicity after the completion of radiation treatment for gynecologic cancer.

PURPOSE: We evaluated financial toxicity (FT) in patients with gynecologic cancer treated with radiation and assessed the impact of the COVID-19 pandemic on patients' financial wellbeing. METHODS: Patients completed a survey 1 month after completing radiation from August 2019-March 2020 and November 2020-June 2021. The survey included the COmprehensive Score for Financial Toxicity (COST) tool, EQ-5D to measure quality of life (QOL) and pandemic-related questions for the second survey period. High FT was COST score ≤ 23. RESULTS: Of 97 respondents (92% response rate), 49% completed the survey pre-pandemic and 51% after; the majority were white (76%) and had uterine cancer (64%). Sixty percent received external beam radiation with or without brachytherapy; 40% had only brachytherapy. High FT was associated with worse QOL (r = -0.37, P < 0.001), younger age and type of insurance (both p ≤ 0.03). Respondents with high FT were 6.0 (95% CI 1.0-35.9) times more likely to delay/avoid medical care, 13.6 (95% CI 2.9-64.3) times more likely to borrow money, and 6.9 (95% CI 1.7-27.2) times as likely to reduce spending on basic goods. The pandemic cohort had a smaller proportion of respondents with high FT than the pre-pandemic cohort (20% vs. 35%, p = 0.10) and a higher median COST score (32 (IQR 25-35) vs. 27 (IQR 19-34), p = 0.07). CONCLUSION: Privately insured, younger respondents who received radiation for gynecologic cancer were at risk for FT. High FT was associated with worse QOL and economic cost-coping strategies. We observed less FT in the pandemic cohort, though not statistically different from the pre-pandemic cohort.

Case Report: tacrolimus toxicity in the setting of concurrent Paxlovid use in a heart-transplant recipient.

Background: Tacrolimus toxicity in patient's status post-orthotropic heart transplantation is not commonly reported. Given its narrow therapeutic window and drug-drug interactions, it must be closely monitored by providers who are experienced in transplant management. There are no case series of patients with tacrolimus toxicity in the setting of treatment for Sars-2-CoV-19 (COVID 19) for heart-transplant recipients. We present a case of tacrolimus toxicity in the setting of concurrent ritonavir-nirmatrelvir (Paxlovid) use. Case summary: The patient was a 74-year-old male with a prior significant history of heart transplantation and on maintenance immunosuppression with tacrolimus. He contracted COVID-19 and was prescribed antiviral therapy with Paxlovid by an outside provider prior to admission. The patient complained of severe headaches, dehydration, and tremors. After eliminating acute intracranial processes with imaging, laboratory investigation revealed a severely elevated tacrolimus level with acute renal injury. The patient was taken off tacrolimus and treated conservatively with intravenous hydration. The symptoms improved, particularly the headaches. He was discharged with instructions to resume his home dosing of tacrolimus and return to clinic in 1 week with a repeat trough level. The subsequent trough level was no longer supra-therapeutic. Discussion: Tacrolimus has a potent drug-drug interaction with Paxlovid (ritonavir-nirmatrelvir) and can be supra-therapeutic. Toxicity is associated with multiple adverse effects, including but not limited to, acute renal injury, neurotoxicity, and infections due to over-immunosuppression. As Paxlovid is effective in treating Sars-2-CoV-19 in heart-transplant recipients, knowledge and understanding of drug-drug interactions is crucial in preventing and mitigating toxicity.

Inhalation Pneumonitis Caused by Nebulized Hydrogen Peroxide.

Hydrogen peroxide is a chemical commonly used as a household antiseptic for cleaning and disinfecting. No cases of acute hydrogen peroxide inhalation-induced lung injury are previously described. We present a case of acute chemical pneumonitis caused by mixing hydrogen peroxide in a nighttime continuous positive airway pressure device's humidifier used for obstructive sleep apnea to prevent COVID-19 infection. The patient endorsed mixing hydrogen peroxide with distilled water in his nighttime continuous positive airway pressure device's humidifier at a ratio of 1:3-1:2 for the previous week before admission based on a friend's advice in preventing COVID-19. The presenting chest X-ray showed new multifocal consolidations with interstitial markings and alveolar edema throughout both lungs. Chest computed tomography (CT) imaging demonstrated multifocal, bilateral, hazy consolidations with increased interstitial markings and bilateral pleural effusions. The patient was subsequently initiated on systemic glucocorticoid therapy, significantly improving hypoxemia and dyspnea. Inhalation of hydrogen peroxide may produce acute pneumonitis distinct from what has been described previously with chronic inhalation. Given this case, systemic glucocorticoid therapy may be considered a viable treatment option for acute hydrogen peroxide-associated inhalation lung injury causing pneumonitis.

Combating Toxicity, Harassment, and Abuse in Online Social Spaces: A Workshop at CHI 2023

Online social spaces provide much needed connection and belonging - particularly in a context of continued lack of global mobility due to the ongoing Covid-19 pandemic and climate crisis. However, the norms of online social spaces can create environments in which toxic behaviour is normalized, tolerated or even celebrated. This can occur without consequence, leaving its members vulnerable to hate, harassment, and abuse. A vast majority of adults have experienced toxicity online and the harm is even more prevalent for members of marginalized and minoritized groups, who are more often the targets of online abuse. Although there is significant work on toxicity in the SIGCHI community, approaches and knowledge have typically been siloed by the domain of investigation (e.g., social media, multiplayer games, social VR). We argue that cross-disciplinary efforts will benefit not only the various communities and situations in which abuse occurs, but that bringing together researchers from different backgrounds and specialties will provide a robust and rich understanding of how to tackle online toxicity at scale. © 2023 Owner/Author.

Supplement Gone Wrong: Drug-Induced Liver Injury Caused by Artemisinin

Introduction: Drug-induced liver injury (DILI) is defined as hepatic dysfunction caused by prescription medications, supplements, or xenobiotics after alternative causes have been excluded. As one of the leading causes of acute liver failure, DILI should be considered when patients present with hepatic dysfunction. We present a case of symptomatic DILI secondary to artemisinin use. Case Description/Methods: A 78-year-old Chinese man with no medical history presented to the hepatology clinic with 10 weeks of jaundice, weakness, and pruritis. He started taking Artemisinin/ Bioperine 12 weeks ago to prevent COVID-19 but stopped 3 weeks ago. He denied abdominal pain, a family history of liver disease, substance/alcohol use, and taking other concomitant drugs. Physical examination revealed scleral icterus and no other signs of chronic liver disease. Laboratory studies showed total bilirubin 11 mg/dL, alkaline phosphatase 293 U/L, aspartate transaminase 170 U/L, and alanine transaminase 196 U/L with negative workup for hepatitis A, B, and C. CT abdomen and MRCP were unremarkable for liver or biliary pathology. Further serological workup was negative and follow-up labs revealed normalization of liver enzymes and bilirubin. Given the patient's improvement, liver biopsy was not pursued. The patient was instructed to avoid supplements unless prescribed by a physician. Discussion(s): DILI is a global issue with an estimated annual incidence rate of 13.9 to 24.0 per 100,000 persons. Diagnosing DILI is important as it can cause acute liver injury and liver failure in certain cases. Since COVID-19 emerged, supplement use has increased given claims of boosting the immune system. Artemisinin is an herb used in traditional Chinese medicine with antimalarial activity investigated to be a possible COVID-19 treatment, but no current evidence exists to support it being effective against COVID-193. Our patient's supplement also contained Bioperine, a black pepper extract, which is likely benign. Contrarily, artemisinin is a well-described cause of idiosyncratic acute liver injury and hepatotoxicity, causing self-limited mild to moderate transaminitis but also severe cases requiring emergent livertransplantation. Our patient's unrevealing workup, his spontaneous improvement correlating with supplement discontinuation, and RUCAM score of 7 led to high suspicion of DILI secondary to artemisinin. Providers should always ask patients about supplement use and consider DILI when patients present with liver injury. (Table Presented).