Assessment of palliative approach in the pain management in endodontic emergencies during Covid-19 outbreak: Retrospective cohort study

Aim: During the coronavirus disease, a palliative approach was recommended for the management of endodontic emergencies. This retrospective cohort study was conducted to investigate the effectiveness of dexamethasone or ibuprofen-acetaminophen combination for pain management in endodontic emergencies. Material(s) and Method(s): One hundred and eight records of patients who presented to the emergency department with dental pain were evaluated retrospectively. Since interventional procedures were not performed during the pandemic period, Specific analgesics/antibiotics for the management of pain were preferred. A follow-up protocol with a questionnaire was developed to observe the effectiveness of palliative treatment and make changes if necessary. All participants received a questionnaire to rate the pain levels 6, 12, 18, 24, 48, and 72 hours after taking the drug. All data were collected from the patient file and assessed. After inclusion and exclusion criteria, 32 patients were included (n = 19, ibuprofen + acetaminophen;n = 13, dexamethasone). Data were analyzed using the chi-square test (P = 0.05). Result(s): In both groups, a significant decrease in pain was experienced immediately after medication and at 6, 12, and 18 hours, with no significant difference (P >.05). However, dexamethasone (Group II) resulted in lower pain levels than ibuprofen\acetaminophen (Group I) at 24 and 48 hours (P <.05) Discussion: Both dexamethasone and ibuprofen-acetaminophen can be good palliative choices in endodontic emergencies in pandemic conditions. However, at 24 and 48 hours, dexamethasone resulted in lower pain levels.Copyright © 2022, Derman Medical Publishing. All rights reserved.

INTAKE OF ACETAMINOPHEN SUPPRESSES ANTIVIRAL HUMORAL IMMUNE RESPONSES IN PATIENTS WITH RA FOLLOWING VACCINATION WITH ANTI SARS-CoV-2 mRNA BASED VACCINES

BackgroundAcetaminophen (APAP = paracetamol) may potentially impact vaccine-associated immune responses as the intake of APAP has been associated with a worse outcome in tumor patients receiving checkpoint inhibitors.[1]Different DMARD regimen have been shown to impair the humoral immune response to mRNA SARS-CoV-2 vaccines in patients with rheumatoid arthritis but the effect of paracetamol has not been explored thus far.ObjectivesTo analyse whether the intake of APAP may interfere with antiviral humoral immune responses following two doses of an anti-SARS-CoV-2 mRNA based vaccine in patients with rheumatoid arthritis (RA) on DMARD therapy.MethodsThe RECOVER trial (Rheumatoid Covid-19 Vaccine Immune Response) was a non-randomised, prospective observational control group trial and enrolled 77 RA patients on DMARD therapy and 21 healthy controls (HC). We performed a posthoc analysis of blood samples taken before the first vaccine dose (T0), two (T1) and three (T2) weeks after the first and second vaccine dose, and at 12 (T3) weeks. APAP intake was measured using ELISA. The antibody response (anti-S) to the receptor binding domain (RBD) within the SARS-CoV-2 S1 protein was measured with the Elecsys Anti-SARS-CoV-2-S (Roche Diagnostics GmbH) test. The neutralizing activity NT50 at week 12 was assessed using an HIV-based pseudovirus neutralization assay against Wuhan-Hu-1.ResultsBaseline characteristics of participants are detailed in Table 1. The immunogenicity analyses were based on 73 RA patients after exclusion of 4 patients with previously unnoticed SARS-CoV-2 infection (positive for anti-nucleoprotein at baseline). APAP was detected in serum samples from 34/73 (25%) RA patients and in 7/21 (33%) HC (least at one timepoint T0, T1 and/or T2). APAP intake in HC did not affect levels of anti-S at any timepoint and all HC developed potent neutralizing activity (NT50 ≥ 250) at week 12. RA patients, who tested positive for APAP at T1, showed comparable anti-S levels at T1, T2 and T3 compared to RA patients not exposed to APAP. The detection of APAP at T2 corresponded to lower anti-S levels at T2 (Figure 1 A, B). The detection of APAP at T2 was associated with a significantly lower SARS-CoV-2 neutralizing activity at week 12 compared to patients without perivaccination APAP exposure (p =0.04) (Figure 1 C).ConclusionA decrease of antiviral humoral immune responses was observed in RA patients (but not in HC) who were exposed to APAP at the time of the second mRNA vaccine dose compared to patients in whom APAP was not detected. Our data suggest that the use of paracetamol within the time period around vaccination may impair vaccine-induced immune responses in patients with an already higher risk for blunted immune responses.Reference[1]Bessede A et al. Ann Oncol 2022;33: 909-915Table 1.Baseline characteristics: RA patients and HC with/without APAP exposureRA APAP – n = 37RA APAP + n = 36p-valueHC APAP – n = 8HC APAP + n = 13p-valueAge (yrs), mean (± SD)62 (13)67 (10)0.07 (NS)45 (12)44 (14)0.90 (NS)Female sex, n (%)24 (65)19 (53)0.29 (NS)2 (25)5 (38)0.53 (NS)Vaccination type/schedulemRNA-1273, n (%)4 (11)8 (22.2)0.19 (NS)0 (0)0 (0)BNT162b2, n (%)33 (89)28 (77.8)0.19 (NS)8 (100)13 (100)RA disease characteristicsACPA ± RF, n (%)17/37 (46)19/36 (53)0.56 (NS)NANANARA disease duration (yrs ± SD)9.2 (9.8)10.2 (8.1)0.67 (NS)NANANADMARD therapycsDMARD-mono, n (%)13/37 (35)9/36 (25)0.35 (NS)NANANAbDMARD-mono/combo, n (%)16/37 (43)16/36 (44)0.92 (NS)NANANAtsDMARDs-mono/combo, n (%)8/37 (22)11/36 (31)0.38 (NS)NANANAPrednisone, n (%)15/37 (41)12/36 (33.3)0.52 (NS)NANANAMean daily dose prednisone (mg ± SD)4.6 ± 1.13.9 ± 2.30.39 (NS)NANANA* APAP = acetaminophenFigure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

IDDF2023-ABS-0045 Spatiotemporal immune landscape of Mas-driven pro-inflammatory microenvironment with hyperactivated glycolysis in acetaminophen-induced liver injury

IDDF2023-ABS-0045 Figure 1 IDDF2023-ABS-0045 Figure 2 IDDF2023-ABS-0045 Figure 3 IDDF2023-ABS-0045 Figure 4

Drug utilization study in patients affected with COVID-19 in a dedicated COVID hospital

Background: There exists a treatment dilemma regarding the optimal and effective use of therapeutic drugs (hydroxychloroquine/chloroquine/azithromycin) for COVID-19. Furthermore, with changing guidelines, the data on drug utilization patterns across India are limited. Hence, this study was conducted to assess the prescription pattern and drug utilization trends in COVID-19 patients with the aim to study the drug utilization pattern in patients affected with COVID-19 in a dedicated COVID-19 hospital. Aims and Objectives: The objectives of the study are as follows: (1) To study drug utilization patterns according to the severity of the disease. (2) To study the prevalence of adverse drug reactions (ADRs). Materials and Methods: Data were collected retrospectively from 100 medical records of patients 18 years irrespective of sex admitted in the COVID ward and ICU of a dedicated COVID hospital from May to August 2020. Pregnant and lactating women were excluded from the study. ADRs reported were also analyzed. Results: About 71% were mild in this study, 18% were moderate, and 11% were severe COVID-19 patients. Overall, the most common drugs prescribed were multivitamins, followed by pantoprazole, paracetamol, and azithromycin. Hydroxychloroquine was prescribed in 22%, favipiravir in 7%, and remdesivir in 3% of cases. The majority of moderate COVID patients received injectables piperacillin-tazobactam, methylprednisolone, and enoxaparin. The mean number of medications, duration of admission, and number of days on oxygen were higher and significant in moderate compared to mild and severe COVID patients. Overall, ADRs were encountered in 9% of cases. Conclusion: The prescribed pattern of drugs was by the national standard guidelines. Multivitamins, followed by pantoprazole, paracetamol, and azithromycin dominated the prescription pattern. Polypharmacy was encountered, which needs to be addressed for the rational use of drugs.

Relationship of clinical symptoms, comorbidities and treatment options along with disease outcomes in individuals tested for COVID-19 in Pakistan: a national survey

Background: This web-based survey is done to collect and assess data from people tested for COVID-19 with PCR in Pakistan. Methods: This 3-month study is a cross-sectional online survey, conducted by Pakistan Islamic Medical Association (PIMA), Health Research Advisory Board (HealthRAB) and National Institute of Health (NIH). Data collection was done using Google Forms. People who were tested for COVID-19 using Polymerase Chain Reaction (PCR) were included in the study. The sample size of the study was 1,537. SPSS version 22 was used for data analysis. Results: Majority of the respondents belonged to the age group 20 - 39 years. The most common symptoms found were fever 633 (41%), cough 534 (34%), generalized body aches 432 (28%) and sore throat 392 (25%). The mean COVID-19 mental health score was 3.59 (SD: 5.808, range: 0-18). Treatment with antibiotics and painkillers had a strong correlation (p-value < 0.05) with the disease outcomes. The disease outcomes had moderate correlation (p-value < 0.05) with anti-allergy, steroids, plasma and oxygen therapy, and weak correlation (p-value < 0.05) with Antiviral and Antimalarial therapy. Out of the total respondents, 561 (36.1%) were cured from COVID-19, 14 (0.9%) were expired during/after hospitalization, 15 (1%) were still infected and 962 (62%) were not infected. Conclusion: Pakistani population has a better cure rate than some of its neighboring countries. However, further research in this area is required to draw a definite conclusion.

Use of First-Line Oral Analgesics during and after COVID-19: Results from a Survey on a Sample of Italian 696 COVID-19 Survivors with Post-Acute Symptoms.

Background-Analgesics could be used to manage painful symptoms during and after COVID-19. Materials and methods-Persistence of painful symptoms was assessed during and after COVID-19 in a sample of patients admitted to a post-acute COVID-19 outpatient service in Rome, Italy. Data on type and frequency of use of first-line analgesics were collected. Pain severity was evaluated with a numeric rating scale (NRS) from 0 to 10. Results-Mean age of 696 participants was 57.1 ± 20.3 years and 61.7% were women. During COVID-19, the most prevalent symptoms were fever, fatigue, arthralgia, myalgia and headache. Acetaminophen was used by 40% of the sample. Only 6.7% needed to continue analgesic therapy after COVID-19. Frequent causes of analgesics consumption were persistent arthralgia and myalgia. The most common analgesics used amongst those who continued taking analgesics in the post-acute phase of COVID-19 were the following: acetaminophen (31%), ibuprofen (31%) and other non-steroidal anti-inflammatory drug (NSAID) (29.5%); in older subjects the most common analgesic used was acetaminophen (54%). Most of the subjects in this group said there was an improvement in pain perception after taking analgesic therapy (84%). Conclusions-Use of analgesics in the post-acute COVID-19 is common in subjects with persistent arthralgia and myalgia, and common analgesics were acetaminophen and ibuprofen. Further research on the safety and efficacy of those medications in COVID-19 is warranted.

Discomfort relief after paracetamol administration in febrile children admitted to a third level paediatric emergency department.

Background: international guidelines recommend treating fever in children not at a predefined body temperature limit but based on the presence of discomfort. However few studies evaluated discomfort relief after administration of antipyretics in children. Methods: Between 1st January and 30th September 2021 a single-center prospective observational study was performed in febrile children consecutively admitted to a pediatric emergency department and treated with paracetamol orally. For each child, body temperature, presence and severity of discomfort, defined using a previously published semiquantitative likert scale, were evaluated at baseline and 60 min after administration of paracetamol, and differences were analyzed. Results: 172 children (males: 91/172; 52.9%; median age: 41.7 months) were included. Significant reductions in body temperature (median body temperature at T0: 38.9 °C; IQR: 38.3-39.4, median body temperature at T60: 36.9 °C; IQR: 36.4-37.5; P < 0.0001), and in the level of discomfort (proportion of children with severe discomfort at T0: 85% and at T60:14%; P < 0.0001) were observed. Severe discomfort at T60 persisted in a minority of children (24/172; 14%) and it was not related to body temperature values. Conclusions: paracetamol in febrile children is associated not only with significantly reduction in body temperature but also with discomfort relief.

Increase in Rate of Hospitalizations for Pediatric Intentional Acetaminophen Ingestion at a Single Center During the COVID-19 Pandemic.

OBJECTIVES: Social disruption due to COVID-19 has detrimentally affected American adolescents' emotional well-being. Within our system, pediatric acetaminophen ingestions increased in 2020, compared with previous years. We sought to evaluate the rate of hospitalizations for acetaminophen self-harm ingestions and self-harm of adolescents during the COVID-19 pandemic. STUDY DESIGN: We identified patients (aged 0-23) from billing data with diagnosis of acetaminophen ingestion with self-harm intent (ICD-10 code T391X2A), from a multicenter urban, quaternary health care system. We performed retrospective chart review from 2016 to 2020 and performed statistics using a generalized estimating equation (GEE) logistic regression model. RESULTS: From 2016 to 2020, there were 25 790 discharges of adolescents with 65 acetaminophen self-harm ingestion and 148 self-harm discharges. Of the 65 acetaminophen patients, 75% identified as female and 54% identified as non-white; 71% with Medicaid insurance. The proportion of acetaminophen ingestion and self-harm admissions increased from 0.13% in 2016 to 0.46% by 2020 and 0.42% in 2016 to 0.73% by 2020, respectively. The odds of acetaminophen ingestion admission increased by 28% each additional year (odds ratio = 1.28; 95% confidence interval: 1.08, 1.53; P = .006). There was not enough evidence to conclude that the log-odds of a self-harm ingestion were linearly related to time (P = .06). CONCLUSIONS: Acetaminophen ingestion for self-harm has significantly increased, while overall self-harm has increased to a lesser, nonsignificant degree. Primarily females of color and those with Medicaid insurance are affected. It is important to note this growing, disturbing trend, and to continue to screen for depression in our adolescent community and ensure access to mental health resources.

Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Population-Based Cohort Study.

Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) have been widely prescribed to infected patients; however, the safety of them has not been investigated in patients with serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to evaluate the association between the previous use of acetaminophen or NSAIDs and the clinical outcomes of SARS-CoV-2 infection. A nationwide population-based cohort study was conducted using the Korean Health Insurance Review and Assessment Database through propensity score matching (PSM). A total of 25,739 patients aged 20 years and older who tested for SARS-CoV-2 were included from 1 January 2015 to 15 May 2020. The primary endpoint was a positive result for a SARS-CoV-2 test, and the secondary endpoint was serious clinical outcomes of SARS-CoV-2 infection, such as conventional oxygen therapy, admission to the intensive care unit, need for invasive ventilation care, or death. Of 1058 patients, after propensity score matching, 176 acetaminophen users and 162 NSAIDs users were diagnosed with coronavirus disease 2019. After PSM, 162 paired data sets were generated, and the clinical outcomes of the acetaminophen group were not significantly different from those of the NSAIDs group. This suggests that acetaminophen and NSAIDs can be used safely to control symptoms in patients suspected of having SARS-CoV-2.

Adverse drugs reactions to paracetamol and ibuprofen in children: a 5-year report from a pediatric poison control center in Italy.

BACKGROUND: This study aimed to analyze all the patients who contacted the hospital's pediatric poison control center (PPCC) for exposure to ibuprofen and acetaminophen, in order to assess the incidence of any adverse reactions. METHODS: We retrospectively reported the clinical data of children who accessed the PPCC of the Bambino Gesù Children's Hospital, IRCCS, Rome, from January 1, 2018 to September 30, 2022 due to wrong, accidental or intentional intake of inappropriate doses of acetaminophen and/or ibuprofen. In addition, we compared patients according to the intake of one of the two drugs and reported the trimestral distribution of cases during the study period. RESULTS: A total of 351 patients accessed the PPCC during the study period. The median age was 3.0 years. Most patients were females (57.8%). The most common reason for inappropriate oral intake of paracetamol or ibuprofen was a wrong use or an accidental intake (78.6%), with a fifth of patients taking the drug with suicidal intent (21.1%). According to the PPCC evaluation, most patients were not intoxicated (70.4%). Hospitalization was required for 30.5% of patients. Adverse reactions were reported in 10.5% of cases, with a similar incidence in patients who took paracetamol or ibuprofen. Nausea and vomiting were the most commonly reported adverse reactions. A higher frequency of moderate intoxication was found in patients who took paracetamol compared to ibuprofen (p = 0.001). The likelihood of intoxication was also higher in the paracetamol cohort. A spike of cases was registered at the end of 2021. CONCLUSIONS: We analyze exposures to the two most commonly used pediatric molecules, paracetamol and ibuprofen, to assess the frequency of adverse reactions. We demonstrated that these relatively "safe" drugs may be associated with intoxications and adverse reactions when inappropriately administered.

Fomepizole should not be used more liberally in paracetamol overdose.

Fomepizole is a promising new treatment for preventing liver injury following paracetamol (acetaminophen) overdose. However, we need robust clinical trials to be performed to demonstrate its effect on clinical outcomes that are important to our patients and important to healthcare providers. Until such trials are performed, the toxicology community should learn the lessons from the COVID pandemic-potential novel therapeutic options may be theoretically appealing, but their effectiveness needs to be assessed in robust clinical trials before they are used in clinical practice.

Post obturation analgesia in patients recently vaccinated against Covid-19, after Root canal treatment: A short observational study

Aim: The aim of this study was to evaluate the need for analgesia in patients undergoing single-visit root canal treatment, within 2 days after COVID-19 immunisation. Method(s): Two days after receiving the COVID-19 vaccination, 50 patients undergoing Single visit root canal treatments for acute pulpits in molar teeth were divided into two groups of 25 each (Group M for males and Group F for females). Each patient was given a prescription for 650 mg of acetaminophen (Dolo 650 mg) tablets to be taken eight hours a day, with instructions to use the same only if needed for pain. They were instructed to keep a record of the number of tablets consumed as per record sheet 1, and if the pain did not subside then a stronger analgesic, Ketorolac DT 10 mg twice a day, had to be taken and recorded. Result(s): In Group M, the mean number of analgesic tablets required was 0.44+/-0.64 and in Group F, the mean number of analgesic tablets required was 0.80+/-1.09. Although the mean analgesic requirement was higher in females as compared to males, the difference of 0.80+/-1.09 between the two groups was not significant statistically (0.360). Conclusion(s): Within the limitations of this study, it is concluded that acetaminophen is effective in relieving post-obturation pain after a single-visit RCT in patients recently vaccinated against the CoVid-19. Copyright © 2022 Ubiquity Press. All rights reserved.

Sensitive electrochemical assay of acetaminophen based on 3D-hierarchical mesoporous carbon nanosheets.

Acetaminophen plays a key role in first-line Covid-19 cure as a supportive therapy of fever and pain. However, overdose of acetaminophen may give rise to severe adverse events such as acute liver failure in individual. In this work, 3D-hierarchical mesoporous carbon nanosheet (hMCNS) microspheres with superior properties were fabricated using simple and quick strategy and applied for sensitive quantification of acetaminophen in pharmaceutical formulation and rat plasmas after administration. The hMCNS microspheres are prepared via chemical etching of zinc oxide (ZnO) nanoparticles from a zinc-gallic acid precursor composite (Zn-GA) synthesized by high-temperature anaerobic pyrolysis. The obtained hMCNS could enhance analytes accessibility and accelerate proton transfer in the interface, hence increasing the electrochemical performance. Under optimized experimental conditions, the proposed electrochemical sensor achieves a detection limit of 3.5 nM for acetaminophen. The prepared electrochemical sensor has been successfully applied for quantification of acetaminophen in pharmaceutical formulations and the rat plasma samples before and after administration. Meanwhile, this sensor is compared with high-performance liquid chromatography (HPLC) as a reference technology, showing an excellent accuracy. Such an electrochemical sensor has great potential and economic benefits for applications in the fields of pharmaceutical assay and therapeutic drug monitoring (TDM).

Formation of Larger Molecular Weight Disinfection Byproducts from Acetaminophen in Chlorine Disinfection.

Acetaminophen is widely used to treat mild to moderate pain and to reduce fever. Under the worldwide COVID-19 pandemic, this over-the-counter pain reliever and fever reducer has been drastically consumed, which makes it even more abundant than ever in municipal wastewater and drinking water sources. Chlorine is the most widely used oxidant in drinking water disinfection, and chlorination generally causes the degradation of organic compounds, including acetaminophen. In this study, a new reaction pathway in the chlorination of acetaminophen, i.e., oxidative coupling reactions via acetaminophen radicals, was investigated both experimentally and computationally. Using an ultraperformance liquid chromatograph coupled to an electrospray ionization-triple quadrupole mass spectrometer, we detected over 20 polymeric products in chlorinated acetaminophen samples, some of which have structures similar to the legacy pollutants "polychlorinated biphenyls". Both C-C and C-O bonding products were found, and the corresponding bonding processes and kinetics were revealed by quantum chemical calculations. Based on the product confirmation and intrinsic reaction coordinate computations, a pathway for the formation of the polymeric products in the chlorination of acetaminophen was proposed. This study suggests that chlorination may cause not only degradation but also upgradation of a phenolic compound or contaminant.

Hepatic, Extrahepatic and Extracellular Vesicle Cytochrome P450 2E1 in Alcohol and Acetaminophen-Mediated Adverse Interactions and Potential Treatment Options.

Alcohol and several therapeutic drugs, including acetaminophen, are metabolized by cytochrome P450 2E1 (CYP2E1) into toxic compounds. At low levels, these compounds are not detrimental, but higher sustained levels of these compounds can lead to life-long problems such as cytotoxicity, organ damage, and cancer. Furthermore, CYP2E1 can facilitate or enhance the effects of alcohol-drug and drug-drug interactions. In this review, we discuss the role of CYP2E1 in the metabolism of alcohol and drugs (with emphasis on acetaminophen), mediating injury/toxicities, and drug-drug/alcohol-drug interactions. Next, we discuss various compounds and various nutraceuticals that can reduce or prevent alcohol/drug-induced toxicity. Additionally, we highlight experimental outcomes of alcohol/drug-induced toxicity and potential treatment strategies. Finally, we cover the role and implications of extracellular vesicles (EVs) containing CYP2E1 in hepatic and extrahepatic cells and provide perspectives on the clinical relevance of EVs containing CYP2E1 in intracellular and intercellular communications leading to drug-drug and alcohol-drug interactions. Furthermore, we provide our perspectives on CYP2E1 as a druggable target using nutraceuticals and the use of EVs for targeted drug delivery in extrahepatic and hepatic cells, especially to treat cellular toxicity.

Hypoxia and R-factor: predictors of abnormal lft in covid-19

IDDF2022-ABS-0170 Table 1Demographics, comorbidities, laboratory investigations and clinical outcomes of COVID-19 patients stratified by ALT All (n=163) Status of ALT P-value¶ Characteristics Abnormal (n=50) Normal (n=113) Age in years, median (IQR) 56 (43–65) 60 (50–67) 55 (37–64) 0.022 Gender, n (%) 0.124 Male 96 (58.9) 34 (68.0) 62 (54.9) Female 67 (41.1) 16 (32.0) 51 (45.1) Ethnic group, n (%) 0.520 Chinese 98 (60.1) 34 (68.0) 64 (56.6) Malay 18 (11.0) 4 (8.0) 14 (12.4) Indian 20 (12.3) 6 (12.0) 14 (12.4) Others 27 (16.6) 6 (12.0) 21 (18.6) Comorbidities, n (%) Diabetes 32 (19.6) 13 (26.0) 19 (16.8) 0.201 Hyperlipidemia 57 (35.0) 24 (48.0) 33 (29.2) 0.032 Hypertension 61 (37.4) 26 (52.0) 35 (31.0) 0.014 Ischemic heart disease 15 (9.2) 7 (14.0) 8 (7.1) 0.238 Chronic liver disease 4 (2.5) 1 (2.0) 3 (2.7) 1.000 Charlson Comorbidity Index, median (IQR) 0 (0–1) 0 (0–1) 0 (0–1) 0.400 BMI, kg/m2, median (IQR), n=46 24.3 (23.2–27.9) 22.9 (22.1–24.2) 24.6 (23.6–28.7) 0.011 GI symptoms, n (%) Diarrhoea 29 (17.8) 12 (24.0) 17 (15.0) 0.186 Abdominal pain 4 (2.5) 0 (0.0) 4 (3.5) 0.313 Nausea/vomiting 10 (6.1) 0 (0.0) 10 (8.8) 0.032 Abnormal chest radiography on admission 55 (33.7) 22 (44.0) 33 (29.2) 0.074 Laboratory investigations on admission, median (IQR) ALT, U/L 23 (18–31) 29 (22–33) 21 (17–26) <0.0005 ALT/LDH ratio, n=162 0.05 (0.04–0.07) 0.06 (0.04–0.07) 0.05 (0.03–0.06) 0.039 ALP 72 (60–89) 72 (61–90) 72 (60–89) 0.700 R factor 0.94 (0.70–1.26) 1.15 (0.86–1.49) 0.87 (0.63–1.19) <0.0005 WBC, x109/L 4.70 (3.80–5.70) 4.75 (3.80–5.83) 4.70 (3.85–5.70) 0.844 Lymphocyte, x109/L 1.11 (0.84–1.49) 0.99 (0.74–1.23) 1.20 (0.87–1.65) 0.002 PLT, x 109/L 188 (150–225) 177 (142–223) 193 (155–226) 0.306 CRP, mg/L, n=162 10.75 (3.15–39.40) 30.10 (11.28–50.65) 6.85 (1.95–23.88) <0.0005 LDH, U/L, n=162 420 (350–547) 482 (378–572) 408 (342–525) 0.033 Creatinine, μmol/L 72 (61–87) 76 (65–88) 71 (59–87) 0.288 Albumin, g/L, n=156 39 (37–42) 39 (37–41) 40 (37–43) 0.044 BIL, μmol/L, n=152 11 (9–14) 11 (9–14) 12 (9–15) 0.555 Medication used, n (%) NSAIDs 22 (13.5) 4 (8.0) 18 (15.9) 0.218 β-lactam 47 (28.8) 22 (44.0) 25 (22.1) 0.008 Hydroxychloroquine 7 (4.3) 1 (2.0) 6 (5.3) 0.677 Lopinavir/Ritonavir (Kaletra) 25 (15.3) 16 (32.0) 9 (8.0) <0.0005 Remdesivir 12 (7.4) 5 (10.0) 7 (6.2) 0.516 Interferon 9 (5.5) 6(12.0) 3 (2.7) 0.025 Days of symptoms before admission, median (IQR) 4 (3–7) 4 (2–7) 5 (3–7) 0.396 Length of stay in days, median (range) 13(8–17) 16(13–24) 11 (7–16) <0.0005 Clinical severity HDU/ICU, n (%) 29 (17.8) 16 (32.0) 13 (11.5) 0.003 Required supplementary oxygen, n (%) 50 (30.7) 29 (58.0) 21 (18.6) <0.0005 Days on supplementary oxygen, median (IQR), n=50 11 (6–18) 12 (6–21) 8 (5–15) 0.15 Intubated, n (%) 13 (8.0) 10 (20.0) 3 (2.7) <0.0005 Death, n (%) 5 (3.1) 3 (6.0) 2 (1.8) 0.169 Sample size, n=163, except where indicated.¶ P values are from Fisher’s exact test or chi-square test for categorical variables and Mann-Whitney U test for continuous variables. P values< 0.05 are in bold.ALP, alkaline phosphatase;ALT, alanine aminotransferase;AST, aspartate aminotransferase;BIL, bilirubin;BMI, body mass index;CRP, c-reactive protein;GI, gastrointestinal;ICU, intensive care unit;IQR, interquartile range;LDH, lactate dehydrogenase;HDU, high dependency unit;PLT, platelet count;WBC, white blood cell.Results30.7% of patients developed abnormal ALT: they were more likely to be older and had comorbidities of hyperlipidaemia and hypertension. Multivariate logistic regression (IDDF2022-ABS-0170 Table 2) showed that R-factor ≥1 on admission (aOR 3.13, 95%CI 1.41–6.95) and hypoxia (aOR3.54, 95%CI 1.29–9.69) were independent risk factors for developing abnormal ALT, but not medications or comorbidities. The R-factor on admission trended higher for patients who developed abnormal LFT as compared to those who didn’t, regardless of the day of illness (IDDF2022-ABS-0170 Figure 1. R-factor). The patients who developed abnormal ALT also ran a more severe course of illness with a greater proportion needing supplementary oxygen (58%vs18.6%, p <0.0005), admission to Intensive Care/High Dependency Unit (32%vs11.5%, p=0.003) and intubation (20%vs2.7%, p<0.0005). The death rate between the 2 groups was similar. IDDF2022-ABS-0170 Table 2Odds ratio of risk factors for development of abnormal ALTVariable Univariable model Multivariable model ‡ cOR (95% CI) P value aOR (95% CI) P value Age in years <45 1.00 Referent 1.00 Referent 45–64 3.42 (1.28–9.11) 0.014 2.69 (0.84–8.47) 0.096 65+ 4.31 (1.49–12.42) 0.007 2.84 (0.66–12.19) 0.160 Gender Male 1.00 Referent Female 0.57 (0.28–1.15) 0.118 Diabetes 1.74 (0.78–3.87) 0.176 Hyperlipidemia 2.24 (1.13–4.45) 0.022 1.14 (0.43–3.00) 0.796 Hypertension 2.41 (122–4.78) 0.0110.89 (0.31–2.58) 0.835 Ischemic heart disease 2.14 (0.73–6.26) 0.166 Presence of GI symptom(s) on admission 1.17 (0.53–2.58) 0.695 Abnormal chest x-ray on admission 1.90 (0.96–3.80) 0.067 0.91 (0.36–2.25) 0.833 R factor on admission <1 1.00 Referent 1.00 Referent ≥1 3.12 (1.56–6.24) 0.001 3.13 (1.41–6.95) 0.005 Use of acetaminophen No 1.00 Referent Yes, <2 g/day 1.48 (0.39–5.65) 0.567 Yes, ≥2 g/day 2.86 (0.71–11.46) 0.139 Use of β-lactam 2.77 (1.35–5.65) 0.005 1.12 (0.38–3.24) 0.840 Use of Hydroxychloroquine 0.36 (0.04–3.11) 0.355 Use of Lopinavir/Ritonavir (Kaletra) 5.44 (2.20–13.43) <0.0005 2.20 (0.57–8.45) 0.252 Use of Remdesivir 1.68 (0.51–5.58) 0.395 Use of interferon 5.00 (1.20–20.88) 0.027 0.80 (0.12–5.22) 0.813 Hypoxia 6.05 (2.9–12.62) <0.0005 3.54 (1.29–9.69) 0.014 ‡ Variables in the multivariable logistic regression model were age group, hyperlipidemia, hypertension, whether there was abnormal chest x-ray on admission, R factor on admission, use of β-lactam, use of LPV/r, use of interferon, and hypoxia, P values<0.05 are in bold, aOR, adjusted odds ratio, cOR, crude odds ratio IDDF2022-ABS-0170 Figure 1ConclusionsLiver injury is associated with poorer clinical outcomes in COVID-19 patients. R-factor ≥1 on admission and hypoxia are independent risk factors for developing abnormal ALT in COVID-19. More studies are required to see if the incorporation of the R-factor into conventional clinical risk scores can improve the performance in predicting disease progression/discriminating disease severity and applicability in emerging virus variants.

Caveolin-1 Alleviates Acetaminophen-Induced Hepatotoxicity in Alcoholic Fatty Liver Disease by Regulating the Ang II/EGFR/ERK Axis.

Acetaminophen (APAP) is a widely used antipyretic analgesic which can lead to acute liver failure after overdoses. Chronic alcoholic fatty liver disease (AFLD) appears to enhance the risk and severity of APAP-induced liver injury, and the level of angiotensin II (Ang II) increased sharply at the same time. However, the underlying mechanisms remain unclear. Caveolin-1 (CAV1) has been proven to have a protective effect on AFLD. This study aimed to examine whether CAV1 can protect the APAP-induced hepatotoxicity of AFLD by affecting Ang II or its related targets. In vivo, the AFLD model was established according to the chronic-plus-binge ethanol model. Liver injury and hepatic lipid accumulation level were determined. The levels of Angiotensin converting enzyme 2 (ACE2), Ang II, CAV1, and other relevant proteins were evaluated by western blotting. In vitro, L02 cells were treated with alcohol and oleic acid mixture and APAP. CAV1 and ACE2 expression was downregulated in APAP-treated AFLD mice compared to APAP-treated mice. The overexpression of CAV1 in mice and L02 cells alleviated APAP-induced hepatotoxicity in AFLD and downregulated Ang II, p-EGFR/EGFR and P-ERK/ERK expression. Immunofluorescence experiments revealed interactions between CAV1, Ang II, and EGFR. The application of losartan (an Ang II receptor antagonist) and PD98059 (an ERK1/2 inhibitor) alleviated APAP-induced hepatotoxicity in AFLD. In conclusion, our findings verified that CAV1 alleviates APAP-aggravated hepatotoxicity in AFLD by downregulating the Ang II /EGFR/ERK axis, which could be a novel therapeutic target for its prevention or treatment.

Egyptian perspectives on potential risk of paracetamol/acetaminophen-induced toxicities: Lessons learnt during COVID-19 pandemic.

Paracetamol/Acetaminophen was widely used as a first-line antipyretic and analgesic for COVID-19 patients without giving any attention to the potential risk of related toxicities. A survey was conducted on 176 Egyptians using an online survey portal to assess their knowledge, and attitude regarding potential risk of paracetamol toxicities and whether COVID-19 pandemic affected their practices regarding safe use of paracetamol. The self-administered questionnaire was developed by the researchers and was validated by expert opinions. A pilot testing of the questionnaire was done. Alpha Cronbach test used to assess the internal consistency reliability of the survey revealed good reliability. Overall percent-score revealed that only 24.4% of participants had good knowledge about paracetamol and its related potential toxicities. 62.5% of participants considered paracetamol safer than other medications of the same indications. 42.6% of participants could advise others to use paracetamol without prescription. According to the participants' responses, physicians were less concerned to give instructions about possibility of overdosage. Our results also revealed that participants' administration of paracetamol without physician prescription was more during COVID-19. Practice of paracetamol administration more than the allowed number of tablets/day was significantly more evident during the pandemic. We concluded that the unsupervised use of paracetamol is an alarming sign that should be addressed as this could lead to a high rate of accidental paracetamol toxicity. A lesson learnt from COVID-19 pandemic is the need to implement behavior change measures to mitigate the risk of accidental paracetamol toxicity.