A case series of diabetic ketoacidosis associated with SGLT2 inhibitors

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly initiated as treatment for type 2 diabetes due to favourable cardiorenal characteristics. However, studies have identified an increased risk of diabetic ketoacidosis (DKA). We carried out a retrospective, case-based study at East and North Herts NHS Trust between February 2018 and December 2020. Fifteen cases of SGLT2i associated DKA were identified in people with presumed type 2 diabetes;33.3% were classed as euglycaemic DKA with a blood glucose of <11mmol/L. All cases were associated with a significant precipitating factor including diarrhoea, vomiting, reduced oral intake and sepsis. One case was related to COVID-19. Two people were subsequently found to have raised islet autoantibodies suggesting type 1 diabetes or latent autoimmune diabetes in adults. It is important that awareness of SGLT2i associated DKA is raised among users and health care practitioners, including the recognition of euglycaemic DKA. Sick day rules should be emphasised and reiterated at clinical encounters. Non-specialists in primary care, oncology and in perioperative settings should be empowered to advocate for temporary withdrawal and there should be readier access to blood ketone monitoring when required. When SGLT2i associated DKA occurs, due consideration should be given to evaluate the diabetes classification and investigate the circumstances of the event. Copyright © 2023 John Wiley & Sons.Copyright © 2023 John Wiley & Sons, Ltd.

SARS-CoV-2 and sodium transport: a diabolical strategy.

The Covid 19 pandemic remains a serious public health problem until effective drugs and/or vaccines are available. Can we explain why so many people remain asymptomatic but nevertheless highly contagious explaining the speed with which the pandemic has spread around the world? Can we explain why the acute respiratory distress syndrome (ARDS) appears late but can so quickly have a fatal outcome? In the lung, mucociliary clearance (CMC) and alveolar clearance (CA) depend on the transport of sodium through the plasma membrane of epithelial cells. This transport is mediated by a highly selective sodium channel (Epithelial Sodium Channel = ENaC) which could be a key element in the pulmonary pathophysiology of SARS-CoV-2 infection.Copyright © 2020 Editions Medecine et Hygiene. All rights reserved.

Determination of the Effects of Prenatal Remdesivir Exposure on Placenta Morphology, Placental IgG Transfer, and Fetal Growth in a Humanized Mouse Model

Remdesivir (RDV) is an antiviral medication used most recently for the treatment of COVID-19. Although no adverse effects were observed on perinatal parameters in reproductive and development toxicology studies at doses up to four-fold clinical area under the curve (AUC) exposures, some researchers have reported that therapeutic levels of RDV may impair early embryogenesis, as observed by in vitro studies. In addition, the influence of prenatal RDV exposure on maternal IgG transfer in the placenta is still unknown. Administration of RDV in pregnant humanized mouse model (Tg32), which expresses the human Fc gamma receptor and transporter (FCGRT) gene, was used to further evaluate potential effects on IgG transfer and concurrent perinatal endpoints. Animals were dosed daily from gestational days (GDs) 10- 14 with 25 mg/kg RDV (GS-5734) via intravenous injection (n=3-5 per group). Concurrent vehicle control animals were dosed intravenously with 12% sulfobutyl ether- beta-cyclodextrin in water (pH3.5;NaOH/HCl). All animals were administered 2 mg/kg human IgG via intravenous injection on GD 14. Placentae and fetuses were collected from dams on GD 14, 15, 16, and 18 and evaluated using histopathology and qPCR for inflammation markers. No abnormal morphologies (necrosis/apoptosis) of placentae were observed between the concurrent control and RDVdosed groups. Additionally, no differences in maternal body weights were observed. There were no statistically significant differences in placenta weights. There were no statistically significant changes in pregnancy parameters (implantation sites and dead fetuses/litter) and fetal weights between the RDV-dosed group and concurrent controls at GD 14, 15, 16, and 18. No changes were observed in transcript levels of inflammation markers in the RDV-dosed group when compared to the concurrent control group. There was a slightly lower ratio of fetal IgG level to maternal IgG levels in the RDV-dosed group;however, no statistically significant differences were observed between the RDV-dosed group and concurrent controls on GD 14, 15, 16, and 18. Our results suggest that a daily dose of 25 mg/kg RDV on GDs 10-14 in humanized mice did not cause adverse effects on placenta and fetal development. (Funded by the Perinatal Health Center of Excellence: E0300201.).

Enoxaparin Sodium Biosimilar in the Prophylactic Treatment of Veinous Thromboembolism and Thromboembolic Disease: Prophyvar Study

Objectives: Varenox is the first locally manufactured and approved biosimilar in Algeria. It is an enoxaparin sodium (ES) with established good analytical characterization and manufacturing quality control. The aim of the PROPHYVAR study was to generate real-life data in routine practices and to assess the safety and tolerability in the prophylaxis of venous thromboembolism (VTE). Method(s): This is an observational, prospective, multicenter study, conducted between April 2021 and May 2022. The primary safety outcome was the incidence of Adverse Events (AEs) related to the study drug. A sample size of 500 patients was calculated to estimate the proportion of patients with AEs. Assuming that approximately 10% will be lost to follow-up or not evaluable, 550 patients were needed to describe the impact of Varenox use. Result(s): The study was conducted in 25 different sites in Algeria, in 4 therapeutic areas: ICU, orthopedic surgery, obstetrics and nephrology;550 patients were included and received at least one injection of Varenox. The mean age was 47 years, women in majority (62.5%). The patients were overweight or obese (53%), with a history of arterial hypertension (25%), diabetes (7.5%) and renal failure (6.4%). Reasons for hospitalization were mainly fracture (15.5%), pregnancy (8.3%), COVID-19 (7%) or cancer (7%). The majority of patients were treated at prophylactic dose of 0.4ml (80%) or 0.6ml (10%). The median duration of follow-up was 24 days. A total of 38 patients experienced at least one AE (6.9%, CI95=[4.9%;9.4%]). Related AEs were reported in 10 patients (1.8%), mainly in nephrology (N=7 arterio-venous fistula). VTE events were reported in 6 patients (1.1%, CI95=[0.2%;2%]). Conclusion(s): This study suggests that Varenox is safe in the prophylaxis of VTE. To our knowledge this is the first large study describing the use of ES in current medical practice in Algeria.Copyright © 2023

An audit looking at why there is an increase in the number of patients with type 2 diabetes presenting in diabetic ketoacidosis in a tertiary hospital

Objectives: To investigate why a tertiary hospital has a high number of patients with type 2 diabetes presenting with diabetic ketoacidosis. Method(s): An audit was carried out looking at all of the inpatient admissions for diabetic ketoacidosis in patients with type 2 diabetes between 2021 and 2022. Any patient with a coding of diabetic ketoacidosis and type 2 diabetes had their inpatient clinical notes evaluated using the following criteria: 1) Were the criteria for diabetes ketoacidosis met? 2) Patient age. 3) Patient anti-diabetic medications. 4) If relevant, who prescribed a sodium-glucose cotransporter- 2 inhibitor and was sick day rule advice given? 5) Did the patient have a concurrent Covid-19 infection? Results: Almost a quarter of patients (24%) included in this audit did not fulfil the diagnostic criteria for diabetic ketoacidosis. For those that did: -Over a quarter of patients (26%) were on sodium-glucose cotransporter-2 inhibitors with the majority being commenced by GPs (81%). There was no documentation as to whether sick day rule advice had been given. -Only 7% of patients had a concurrent Covid-19 infection. -The majority of patients (68%) were aged less than 75 years. Conclusion(s): Coding on discharge summaries is important and junior doctors may need further guidance with regards to the diagnostic criteria for diabetic ketoacidosis. Sodium-glucose cotransporter-2 inhibitors inhibitors are a significant cause of diabetic ketoacidosis in patients with type 2 diabetes and patient sick day rule advice is needed prior to initiation. Covid-19 infection wasn't found to be a significant causative factor.

Exosomes/EVs: IMMUNOMODULATORY EFFECTS OF AMNITOIC FLUID EXTRACELLULAR VESICLES IN AN IN-VITRO MODEL OF IMMUNE ACTIVATION

Background & Aim: Amniotic fluid (AF)-derived EVs are currently under investigation for use as anti-inflammatory therapeutics in COVID-19 and COVID-19 long haulers. The dysregulation of the immune response induced by SARS-COV-2 is a key driver of both acute COVID-19 induced lung injury and long term COVID-19 sequela. There is a clear need to identify therapeutics that suppress excessive inflammation and reduce immune cell exhaustion to improve patient short term and long-term outcomes. Amniotic fluid (AF)- derived extracellular vesicles (EVs) have previously been shown to deliver anti-inflammatory and immune-modulatory signals to diverse cellular targets. We aimed to test if AF-EVs carry immune-suppressive molecules and can suppress T-cell immune activation and exhaustion in vitro. Methods, Results & Conclusion(s): The AF-EV biologic tested was derived from AF collected from consenting donors during planned, fullterm cesarean sections. AF was centrifuged and filtered to remove cellular debris and create a product containing AF-EVs and soluble extracellular components. Fluorescent EXODOT analysis was performed to demonstrate the presence of EV markers CD9, CD81, ALIX, and immune suppressive molecule PD-L1. T-cell activation/exhaustion was induced in vitro by treating human peripheral blood mononuclear cells with activation agent PHA for 3 days with the addition of AF-EVs or saline control. Immune activation/exhaustion was measured by flow cytometry to determine the expression of PD-1 on CD3+ T-cells. The AF-EV biologic was characterized to contain EVs with positive expression of CD9, CD81, ALIX, and PL-L1. T-cell activation/exhaustion was upregulated in response to PHA and was significantly reduced by 8% in AF-EV treated T-cells compared to saline control (77.7% vs 85.7%, respectively P<0.05). These findings demonstrate that AF-EVs do express PD-L1, a surface marker that has previously been demonstrated to contribute to exosome-mediated immunosuppression. Furthermore, we confirmed in vitro that AF-EVs suppress T-cell activation/ exhaustion in the presence of a T-cell activation agent. COVID-19 long haulers have been described to have upregulated and pro-longed immune activation and T-cell exhaustion, marked by an increase in PD1+ T-cells. Therefore, this finding serves as a starting point for the development of a potential mechanism of action that may describe AF-EV's therapeutic effect in COVID-19 long hauler patients.Copyright © 2023 International Society for Cell & Gene Therapy

Spectrum of Biochemical Alterations in Patients with Covid-19

Background and objective: Millions of people worldwide have died from COVID-19, which has caused the failure of the lungs and other organs. The research assessed biochemical anomalies in COVID-19 patients to comprehend the illness and its effect better. Study Design: Retrospective longitudinal cohort analysis Place of study: ABWA Medical College Faisalabad Methods: A total of 150 adult patients (n=150) who tested positive for COVID-19 via RT-PCR were included in the study. A Roche Diagnostics Cobas C501 used spectrophotometry to measure calcium, magnesium, phosphate, lactate dehydrogenase (LDH), urea, creatinine, ferritin, and chloride in the blood. A NOVA electrolytic analyzer used Ion-selective electrodes to measure sodium, chloride, potassium, and bicarbonate. Result(s): In the study, 33.6% of patients had elevated urea levels, and 22.4% had elevated creatinine levels. Furthermore, 88.8% of patients had elevated ferritin levels, and 93.5% had elevated LDH levels. After 44 weeks, there was a drop in sodium-containing electrolytes, with 9% of patients experiencing a decrease in sodium, 22.4% in potassium, 53.3% in bicarbonate, 48.6% in calcium, and 23.4% in phosphorus. These changes in electrolyte levels suggest a long-term trend in electrolyte depletion among the patient population. There was no significant difference in biochemical anomalies between age groups (p > 0.05). Conclusion(s): These results suggest that COVID-19 patients have lung illness and multi-organ involvement, which should be considered when managing these patients. These biochemical alterations warrant careful monitoring for organ failure by healthcare practitioners. More study is required to comprehend the processes causing these biochemical anomalies in COVID-19 patients.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Clinical evolution of patients with AF and diabetes mellitus in the COVID-19 pandemic. REFADI Registry

Introduction and objectives: To analyze the evolution of patients with atrial fibrillation (AF) and diabetes in the mid-term follow-up during the COVID-19 pandemic and to describe its impact on this population. Method(s): Multicenter and prospective registry that included patients with AF and diabetes attended in cardiology clinics. A multivariate analysis was performed to determine the variables associated with the occurrence of clinical events and mortality. Recruitment was performed in February-December 2019. Result(s): The evolution of 633 patients, 96,2% of those included in the REFADI registry with a median follow-up of 835 days was analyzed (mean age 73.8 +/- 8.5 years, 54.3% male, CHA2DS2-VASc 4,34 +/- 1,4, HAS-BLED 2,47 +/- 0,96) were analyzed. The proportion of anticoagulated patients remained constant (95.6% vs 94.5%;P = .24). There was a decrease in the prescription of vitamin K antagonists (from 31.4% to 19.7%;P < .01), and an increase in the use of direct anticoagulants (from 62.0% to 70.3%;P < .01). During the follow-up there was an increase in the prescription of SGLT2 inhibitors (from 20.0% to 25.5%;P < .01) and GLP1 agonists (from 4.2% to 9.1%;P < .01). During this period, 17.2% of patients died, the majority from cardiovascular causes, 6.4% from COVID-19, 2.8% from stroke, and 1.8% from hemorrhage. Older age, lower ejection fraction, lower hemoglobin levels, and especially lower direct anticoagulants prescription were associated with mortality. Conclusion(s): Patients with AF and diabetes have a high thromboembolic risk and a high risk of developing complications, especially of cardiovascular origin.Copyright © 2023 Sociedad Espanola de Cardiologia

Post-exposure prophylaxis of COVID-19: results of double-blind, placebo-controlled, multicenter clinical study evaluation of efficacy and safety of double-stranded sodium salt RNA drug

The aim of the study was to evaluate the efficacy and safety of an RNA double-stranded sodium salt drug, a lyophilisate for a solution preparation for an intramuscular and subcutaneous administration, as a means of post-exposure COVID-19 prophylaxis in comparison with placebo.Material and methods. A double-blind, placebo-controlled, multicenter, randomized phase III clinical trial was conducted to evaluate the efficacy and safety of a double-stranded sodium salt RNA drug (RADAM IN (R) VIRO), a lyophilisate for preparing a solution for intramuscular and subcutaneous administration as a means of post-exposure prophylaxis of COVID-19. The study was conducted in 10 research centers in the Russian Federation from May 31, 2022 to January 17, 2023. The study included men and women aged =18 years who cohabitate with a person with a documented COVID-19 diagnosis and do not have symptoms characteristic of COVID-19. At the randomization stage, the subjects were assigned to one of two groups: group 1 (n=400) received a study drug RADAM IN (R) VIRO 5 mg (1 vial) intramuscularly once a day;group 2 (n=400) received placebo 1 vial intramuscularly once a day. The total duration of the study for each subject was no more than 30 days.Results. By day 10-11, in the double-stranded sodium salt RNA drug group, the proportion of the subjects with confirmed COVID-19 and at least 1 symptom characteristic of COVID-19 was 5.76% (23/399), and in the placebo group - 11.03% (44/399). The difference in proportions between the study drug and placebo groups was 0.0526 (5.26%), the 95% confidence interval (CI) for the difference in proportions between the groups was [0.0123;0.0937]). More than 94% of single-dose subjects did not become infected with COVID-19 with any symptoms during the 11 days of the follow-up. As a result of a comparative analysis, it was shown that the infection frequency in the study drug group was statistically significantly (almost twice) less than in the comparison group, which indicates a high efficiency and expediency of using the double-stranded sodium salt RNA drug as a means of the post-exposure COVID-19 prophylaxis.Conclusion. Thus, regardless of the vaccination availability, the effectiveness and feasibility of using the study double -stranded sodium salt RNA drug as a means of the post-exposure COVID-19 prophylaxis was demonstrated not only in medical institutions (outpatient clinics and hospitals), but also in caregivers and/or the persons in contact with COVID-19 patients. The situation was the same in the organizations and enterprises in case of evolution of a mass infection threat and the availability of appropriate medical personnels.

Investigation on Bacterial Infection, IL-17 and Some Biomarkers with Related to Covid-19 Patients' Outcome

Since it has been a global pandemic for the past three years, the coronavirus disease 2019, or COVID-19, has spread to all parts of the world. It first appears as pneumonia, which can progress to severe respiratory failure and has as its major hallmark a systemic inflammatory immune response brought on by an increased production of cytokines that causes a cytokine storm. Bacterial co-infections raise the risk of morbidity and mortality in COVID-19 patients. The current study was conducted to investigate the impact of bacterial co-infection, IL-17, D-dimer, fer-ritin and CRP in Covid-19 pneumonia outcome. Four mL of blood samples were collected from 120 patients attending to AL-Amal hospital and Al-Sader medical city, Najaf/Iraq, from July 2021-January 2022;1.5 mL of blood kept in tube containing 3.2% sodium citrate to estimation D-dimer by Minivides and 2.5 mL in plane tube to separate serum that used to detect IL-17, ferritin and CRP. Patient divided into Critical 33 (27.5%), sever 42 (35%) and Mild/Moderate (M/M) 45 (37.5%), In addition to 60 apparently healthy subjects as controls group. The result indicated that a significant increase (p < 0.05) in mean serum level of IL-17 in patients compare to healthy group, and the mean critical and server cases higher than M/M cases (101.79, 74.83, and 27.65) pg/mL. The results founded that most bacterial co-infection within critical and sever cases with 22(44%) and 26 (52%) respectively while M/M cases were 2(4%) only. Finally the results founded an elevated number of leukocyte, higher neutrophil and higher infection-related biomarkers (S. ferritin, D-dimer, and CRP) especially in critical cases (18.5+/- 2.62, 88.42+/-12.6, 738.68+/-154.41, 5.76+/-2.75, and 122.85+/-35.39) respectively. In conclusion the level of IL-17, ferritin and D-dimer highly increased in Covid patients that correlated with severity of Covid pneumonia so by this biomarkers can recognized between two types of patients. Secondary bacterial infection increased progressive state of patients.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.

Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial.

Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.

[Antiviral and virucidal activity of sodium deoxyribonucleate and its complex with iron against viruses of different kingdoms and families].

INTRODUCTION: The urgent problem of modern medicine is the fight against acute respiratory viral infections (ARVI). To combat ARVI, drugs of wide antiviral potency are needed, as well as immunomodulating drugs. Such antiviral and immunomodulatory effects has sodium deoxyribonucleate (DNA-Na) and its complex with iron (DNA-Na-Fe) developed on the basis of double-stranded DNA of natural origin. AIM OF THE STUDY: To assess antiviral and virucidal activity of DNA-Na and DNA-Na-Fe against viruses of different kingdoms and families. MATERIALS AND METHODS: Antiviral and virucidal activity of DNA-Na and DNA-Na-Fe was assessed in cell cultures infected with viruses. RESULTS AND DISCUSSION: DNA-Na and DNA-Na-Fe had antiviral activity against adenovirus at concentrations of 2501000 mcg/ml. Antiviral effect of both drugs was not detected in case of poliovirus. DNA-Na and DNA-Na-Fe had antiviral activity against coronavirus in all administration schemes. EC50 for DNA-Na ~ 2500 mcg/ml, for DNA-Na-Fe ~ 1000 mcg/ml. In cells treated with DNA-Na-Fe, secretion of following proinflammatory cytokines was detected: Interleukin (IL) 1, IL-2, IL-6, IL-18, interferon- (IFN-), IFN-, as well as anti-inflammatory cytokines: IL-4, IL-10, antagonist of IL-1 receptor. Evidently, DNA-Na and DNA-Na-Fe have antiviral effect, but mechanism of action does not seem to be associated with specific effect on viral replication. Presence of virucidal activity of drugs against representatives of Coronaviridae, Adenoviridae, Picornaviridae, Retroviridae, Herpesviridae in vitro test in range of 1.03.0 lg TCID50 was identified. CONCLUSION: Presence of simultaneous antiviral and virucidal activity of DNA-Na and DNA-Na-Fe against adeno- and coronaviruses shows their prospects for prevention and treatment of ARVI.

Clinical features of COVID-19 rapid antigen test exposures reported by an Australian poisons information centre: a prospective study.

INTRODUCTION: Coronavirus disease COVID-19 rapid antigen tests are a useful tool in detecting infection, and their use has increased in many countries since they became commercially available in late 2021. Some rapid antigen tests contain sodium azide, which can be toxic in small doses. This study aimed to describe the clinical characteristics of exposures to COVID-19 rapid antigen tests. METHODS: This is a prospective study conducted by the New South Wales Poisons Information Centre. From 22 January 2022 to 31 August 2022, rapid antigen test exposures were followed up to obtain outcome information. Data collected included: brand/ingredients, exposure route, demographics, symptoms, and disposition. RESULTS: We recorded 218 exposures in the seven-month study period. Complete follow-up information was available in 75% (n = 164). There were 53 exposures to sodium azide-containing products (35 with follow-up data) and 165 to non-sodium azide-containing products and unknown ingredient exposures (129 with follow-up data). Overall, unintentional exposures predominated (n = 182), and 151 were ingestions. The vast majority (>90%) did not develop symptoms, and all symptoms that developed were mild. Most cases (95%, n = 208) did not require referral to a healthcare facility. CONCLUSIONS: In this prospective series, few patients developed symptoms, regardless of the sodium azide content, likely due to low concentration and low volume within the test kits. However, ongoing toxicovigilance is warranted.

Fondaparinux Sodium: Recent Advances in the Management of Thrombosis.

Fondaparinux sodium is a chemically synthesized selective factor Xa inhibitor approved for the prevention and treatment of venous thromboembolic events, that is, deep vein thrombosis, pulmonary embolism, and superficial vein thrombosis, in acutely ill (including those affected by COVID-19 or cancer patients) and those undergoing surgeries. Since its approval in 2002, the efficacy and safety of fondaparinux is well demonstrated by many clinical studies, establishing the value of fondaparinux in clinical practice. Some of the advantages with fondaparinux are its chemical nature of synthesis, minimal risk of contamination, 100% absolute bioavailability subcutaneously, instant onset of action, a long half-life, direct renal excretion, fewer adverse reactions when compared with direct oral anticoagulants, and being an ideal alternative in conditions where oral anticoagulants are not approved for use or in patients intolerant to low molecular weight heparins (LMWH). In the last decade, the real-world use of fondaparinux has been explored in other conditions such as acute coronary syndromes, bariatric surgery, in patients developing vaccine-induced immune thrombotic thrombocytopenia (VITT) and in pregnant women with heparin-induced thrombocytopenia (HIT), or those intolerant to LMWH. The emerging data from these studies have culminated in recent updates in the guidelines that recommend the use of fondaparinux under various conditions. This paper aims to review the recent data and the subsequent updates in the recommendations of various guidelines on the use of fondaparinux sodium.

Surface Disinfection Practice in Public Hospitals in the Era of COVID-19: Assessment of Disinfectant Solution Preparation and Use in Addis Ababa, Ethiopia.

Background: Surface disinfection of healthcare facilities with appropriate disinfectants is among the infection control strategies against the spread of coronavirus disease 2019 (COVID-19). As sodium hypochlorite solution (SHS) is a commonly used surface disinfectant, its preparation and proper use should be given a due attention. The current study aimed at assessing the practice of Addis Ababa public hospitals in the preparation and use of SHS. Methods: A cross-sectional observational study was employed to assess the adequacy of disinfectant solution preparation and use. Checklists were used for data collection. Descriptive statistics were used for data analyses, and categorical variables were described by frequencies and percentages. Results: Out of the twelve public hospitals included in the study; only three hospitals checked the potency of the working SHS. Majority of the hospitals (8 hospitals) stored the concentrated SHS products in cool, dry, and direct sunlight protected places. It was only in one hospital where appropriate personal protective equipment was used during the preparation and quality control activities. Surfaces were not cleaned in all hospitals before disinfection; and the rooms were ventilated only in 2 hospitals during the application of the disinfectant solution. Conclusion: The study revealed that the preparations of SHS in the public hospitals did not comply with most of the requirements of good compounding practice. Moreover, standard practices were not maintained in majority hospitals during the use of SHS for surface disinfection. As a control strategy in the spread of COVID-19 and other infections, appropriate corrective actions shall be implemented in the studied hospitals to mitigate the limitations observed in the preparation and use of SHS.

Coronavirus murine hepatitis virus strain 3 induces intestinal injury via caspase 3 dependent apoptosis

Background: Diarrhea was typical symptoms of the coronavirus disease 2019 (COVID-19). However, the underlying mechanism had not been fully understood. Aim(s): The study aimed to explore the mechanism of intestinal injury during COVID-19 in a coronavirus murine hepatitis virus strain 3 (MHV-3) induced acute mouse model. Method(s): MHV-3 induced acute infection Balb/cJ mice model was established. Intestine samples were collected at indicated time points as 0 h, 24 h, 48 h and 60 h post infection. The mRNA and protein expression of IL1b, TNFalpha, IL6, caspase 3 and cleaved caspase 3 were examined by real-time quantitative PCR (qPCR) and western blot respectively. The intestine injury and apoptosis were measured by HE staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Moreover, Z-DEVD-FMK (caspase 3 inhibitor) pre-treated MHV-3 infection mice model were established, in which the apoptosis of intestine was evaluated as well. Meanwhile, the murine intestinal cell MODE-K was infected by MHV-3 in vitro for evaluation of virus induced apoptosis. Result(s): Post MHV-3 infection, the histopathology of intestine tissue showed extraordinary injury with time dependence, as well as high level of TUNEL positivity. The mRNA levels of inflammatory cytokine IL1b, TNFalpha and IL6 were significantly increased. The protein expressions of caspase 3 and cleaved caspase 3 in the intestine was found significantly elevated from 24 to 48 h post MHV-3 infection. Z-DEVD-FMK pretreatment inhibited caspase 3 and cleaved caspase 3 expression and decreased TUNEL positivity. Meanwhile, alleviated gut injury and inhibited TNFalpha expression were observed. In vitro treated by MHV-3, intestinal cell line MODE-K showed nine-fold increase of apoptosis by comparison with saline treated ones. The expressions of apoptosis crucial protein caspase3 and cleaved caspase3 significantly elevated, as well as TNFalpha. Conclusion(s): Coronavirus murine hepatitis virus strain 3 induces intestinal injury via caspase 3 dependent apoptosis, which might shed light on the treatment of intestinal complications in COVID-19.

Prevention of COVID-19 coronavirus infection with aminodihydrophthalazinedione sodium (Galavit) in medical staff of the "red zone": results of the multicenter observational study

COVID-hospital healthcare workers belong to a high-risk SARS-CoV-2 infection. The aminodihydrophthalazinedione sodium (Galavit) belongs to the group of immunomodulatory and anti-inflammatory drugs. It has been shown that aminodihydrophthalazinedione sodium is effective in the prevention of acute respiratory infections, respiratory tract diseases and ENT-organs of bacterial and viral etiology. The purpose of the study. To evaluate the effectiveness and safety of immunoprophylaxis of new coronavirus infection (COVID-19) with aminodihydrophthalazinedione sodium in healthcare workers providing medical care in the "red zone". Material and methods. A multicenter prospective-retrospective observational comparative non-randomized study in healthcare workers providing medical care in the "red zone" was conducted. 428 participants were included in the study: the observation group - healthcare workers who administered aminodihydrophthalazinedione sodium (Galavit) for prophylactic purposes (n=214), and control group (n=214). The observation period of the participants or the period of collecting retrospective data in the study was 30 days. The results of PCR tests and tests for antibodies to the SARS-CoV-2 were analyzed, clinical status (COVID-19 in any form) was assessed. Descriptive statistic methods and Pearson chi2 test were used. The risk ratios, odds ratios and 95% confidence intervals were calculated with them. The influence of potential confounding factors (age, gender, work place in clinical site, the presence or absence of concomitant disease) on the clinical status were analyzed using logistic regression. The analysis of propensity score matching was carried out. The Stata/IC 14.2 for Windows software used for statistical analysis. Results and discussion. Observational study results describe the risk ratios and odds ratios of infection with a new coronavirus (COVID-19) in healthcare workers providing medical care in the "red zone" considering prophylactic administration of aminodihydrophthalazinedione sodium (Galavit). 205 (95.8%) participants in the group of healthcare workers who took aminodihydrophthalazinedione sodium (Galavit) for prophylactic purposes and 194 (90.7%) participants in control group had a negative PCR test during the observation period, chi2=4.48, p=0.034. The risk of a positive status according to the PCR test for 30 days in the preventive group was 0,04, and in the control group 0.09. The risk difference was -0.05 [95% confidence interval (CI) -0.099;-0.004]. The adjusted odds ratio using multiple logistic regression was - 0.41 (95% CI 0.18-0.93). No adverse events were observed during the prophylactic administration of aminodihydrophthalazinedione sodium over 30 days. Conclusion. Galavit preventive administration in a tablet form at a dose of 50-100 mg per day by employees of medical institutions providing medical care to patients with CIVID-19 significantly reduces the risk of SARS-CoV-2 infection and more than 2 times increases the chances not ill of new coronavirus infection. Galavit administration up to 30 days at a dose of 50-100 mg was well tolerated, no adverse events were registered.Copyright © 2022 by the authors.

Recurrent Liver Abscess in a Non-Toxic Patient

Introduction: Liver abscesses are caused by direct spread from peritonitis, biliary tract infection or via hematogenous seeding from a distant source. Most are polymicrobial, however Escherichia coli and Klebsiella pneumoniae are the most common offending pathogens. Patients usually present with pain, fever, and clinical signs of infection. We describe a case of spontaneous liver abscess in a non-toxic patient that recurred 10 years after a previous abscess. Case Description/Methods: A 73-year-old-man with a history of type 2 diabetes mellitus, hypertension, CAD status post CABG and PCI 3 years ago, and abdominal aortic aneurysm status post endovascular aneurysm repair presented with 2 weeks of dark urine. After receiving his COVID-19 booster and influenza vaccinations, he developed flu-like symptoms with a self-resolving fever of 101.8degreeF. He had dark amber urine without dysuria or hematuria. Later, he experienced generalized weakness and decreased oral intake. Outpatient labs showed elevated liver function tests, and he was told to present to the ED. On arrival, he was afebrile with stable vitals. Physical exam was unremarkable. Laboratory evaluation showed a hemoglobin of 11.7 g/dL, sodium of 133 mEq/L, creatinine of 1.4 mg/dL, aspartate aminotransferase of 117 U/L, alanine aminotransferase of 212 U/L, alkaline phosphatase of 825 U/L, total bilirubin of 4.1 mg/dL, and direct bilirubin of 2.1 mg/dL. Triple-phase CT showed a 2.8 cm mass in the right liver lobe with linear enhancement. Ultrasound showed mixed echogenicity measuring 3.6 x 2.9 x 3.3 cm in segment 8 of the liver. On further evaluation, patient had an E. coli abscess diagnosed 10 years prior, managed with antibiotics and drainage. At that time, the abscess was within the right inferior liver lobe, similar to his current abscess. LFTs downtrended. Abscess was aspirated, with culture growing oxidase negative, gramnegative rods, likely E. coli. Patient started on ceftriaxone and metronidazole, to undergo colonoscopy as an outpatient and rule out colonic bacterial translocation. Discussion(s): Pyogenic liver abscess can result in significant morbidity and mortality because of worsening infection and sepsis. Abscesses occur because of spread from adjacent infection or after recent surgeries. Recurrence is very rare. Here, we describe a very unusual case of a pyogenic liver abscess growing E. coli in a non-toxic patient, with the same location and causative organism as an abscess managed 10 years prior. (Figure Presented).

Evaluating the Effectiveness of Intravenous Ozonated Normal Saline in the Treatment of Severe COVID-19 Disease: A randomized control trial

Background: There is still no specific treatment strategy for COVID-19 other than supportive management. The potential biological benefits of ozone therapy include reduced tissue hypoxia, decreased hypercoagulability, modulated immune function by inhibiting inflammatory mediators, improved phagocytic function, and impaired viral replication. This study aimed to evaluate the effect of intravenous ozonated normal saline on patients with severe COVID-19 disease. Method(s): In this study, a single centralized randomized clinical trial was conducted on 80 hospitalized patients with severe COVID-19. The patients were selected by random allocation method and divided into two groups A and B. In group A (control group), patients were given standard drug treatment, and in group B (intervention group), patients received ozonated normal saline in addition to the standard drug treatment. In the intervention group, 400 mL of normal saline was weighed by 40 mug/ kg of body weight and was injected into patients within 15 to 30 minutes (80 to 120 drops per minute). This process was done daily every morning for a week. Primary and secondary outcomes of the disease included changes in the following items: length of hospital stay, inflammatory markers including C-reactive protein (CRP), clinical recovery, arterial blood oxygen status, improvement of blood disorders such as leukopenia and leukocytosis, duration of ventilator attachment, and rapid clearance of lung lesions on CT scans. The need for intensive care unit (ICU) hospitalization, the length of ICU stay, and the mortality rate in patients of the two groups was compared. Result(s): According to the results of the initial outcome variable analysis, the probability of discharge of patients who received the normal ozonated saline intervention was 33% higher than patients who did not receive this intervention;however, this relationship was not statistically significant (HR = 0.67, 95%, CI = 0.42-1.06, P value = 0.089). The chance of ICU hospitalization in patients of the intervention group was three times more than that of the comparison group, but this relationship was not significant (odds ratio = 4.4 95% CI = 1.32-14.50, P value = 0.016). The use of ozonated normal saline was found to increase the risk of death by 1.5 times but this relationship was not statistically significant (odds ratio = 1.5, 95% CI = .24-9.75, P value = 0.646). Ozonated normal saline had a significant effect on changes in respiration rate (in the intervention group the number of breaths was decreased) and the erythrocyte sedimentation rate (in the intervention group the erythrocyte sedimentation rate was increased);however, it had no significant effect on other indicators. Conclusion(s): The present study showed that ozone therapy in hospitalized patients with severe COVID-19 could help improve some primary and secondary outcomes of the disease. Governments and health policymakers should make ozone therapy an available care service so that the need for advanced treatment facilities decreases;consequently, this measure may improve patient safety, prevent lung tissue destruction, and control cytokine storms in patients. Additionally, health decision-makers need to aim for the effective clinical improvement of patients, especially severe ones, and the reduction of their mortality. However, further large-scale multicenter studies with larger sample sizes considering drug side effects and other variables influencing the clinical course of COVID-19 can provide more information on the effectiveness and importance of ozone therapy.Copyright © 2023 The Author(s);Published by Kerman University of Medical Sciences.