Magnetic Nanostructures and Stem Cells for Regenerative Medicine, Application in Liver Diseases.

The term "liver disease" refers to any hepatic condition that leads to tissue damage or altered hepatic function and can be induced by virus infections, autoimmunity, inherited genetic mutations, high consumption of alcohol or drugs, fat accumulation, and cancer. Some types of liver diseases are becoming more frequent worldwide. This can be related to increasing rates of obesity in developed countries, diet changes, higher alcohol intake, and even the coronavirus disease 2019 (COVID-19) pandemic was associated with increased liver disease-related deaths. Although the liver can regenerate, in cases of chronic damage or extensive fibrosis, the recovery of tissue mass is impossible, and a liver transplant is indicated. Because of reduced organ availability, it is necessary to search for alternative bioengineered solutions aiming for a cure or increased life expectancy while a transplant is not possible. Therefore, several groups were studying the possibility of stem cells transplantation as a therapeutic alternative since it is a promising strategy in regenerative medicine for treating various diseases. At the same time, nanotechnological advances can contribute to specifically targeting transplanted cells to injured sites using magnetic nanoparticles. In this review, we summarize multiple magnetic nanostructure-based strategies that are promising for treating liver diseases.

Assessment of liver function in COVID-19

Introduction: COVID-19 is an infectious disease caused by the SARS-CoV-2 virus that commonly involved the respiratory system. However, the virus can affect any organ in the body including the liver. Hepatic involvement in COVID-19 could be related to the direct cytopathic effect of the virus, an uncontrolled immune reaction, sepsis, or drug-induced liver injury. Background: The current study aims to evaluate the relevance of liver enzyme derangement in COVID-19. Methods: The sample size of 165 patients, tested positive for covid 19 and underwent liver enzyme testing. These patients were categorized into mild, severe, and critical diseases based on clinical evaluation, radiological findings, and biochemical parameters. Results: Of 165 patients selected 103 (62.4%) have mild disease, 40(24.2%) have severe and 12(7.2%) suffered from the critical disease. 48(29.1%) patients show deranged liver function. 83.3% of critical patients and 45% of severe patients show deranged liver function.9.09%of patients died due to severe COVID-19 infections showing moderately to severe liver function derangement. Conclusions: This study concludes that the severity of COVID-19 disease may increase due to chronic liver disease, particularly fatty liver. Atypical ALT and AST levels during hospitalization were indicative of liver injury and correlated with the severity of patients.

Predictors of non-invasive ventilation failure in adult patients with cardiac dysfunction presenting with community-acquired pneumonia: an Egyptian multicenter prospective study

Non-invasive ventilation (NIV) might be successful if carefully selected in adult patients with cardiac dysfunction presenting with community-acquired pneumonia. The main objective of this study was to identify the early predictors of NIV failure. Adult patients with left ventricle ejection fraction (LV EF) <50% admitted to the intensive care unit (ICU) with community-acquired pneumonia and acute respiratory failure were enrolled in this multicenter prospective study after obtaining informed consents (study registrationID: ISRCTN14641518). Non-invasive ventilation failure was defined as the requirement of intubation after initiation of NIV. All patients were assessed using the Acute Physiology and Chronic Health Evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores at admission, while their Heart rate Acidosis Consciousness Oxygenation and Respiratory rate (HACOR) and lung ultrasound (LUS) scores in addition to blood lactate were assessed at NIV initiation and 12 and 24 hours later. A total of 177 patients were prospectively enrolled from February 2019 to July 2020. Of them, 53 (29.9%) had failed NIV. The mean age of the study cohort was 64.1+or- 12.6 years, with a male predominance (73.4%) and a mean LV EF of 36.4 +or- 7.8%. Almost 55.9% of the studied patients had diabetes mellitus, 45.8% had chronic systemic hypertension, 73.4% had ischemic heart disease, 20.3% had chronic kidney disease, and 9.6% had liver cirrhosis. No significant differences were observed between the NIV success and NIV failure groups regarding underlying morbidities or inflammatory markers. Patients who failed NIV were significantly older and had higher mean SOFA and APACHE II scores than those with successful NIV. We also found that NIV failure was associated with longer ICU stay (p < 0.001), higher SOFA scores at 48 hours (p < 0.001) and higher mortality (p < 0.001) compared with the NIV success group. In addition, SOFA (Odds Ratio (OR): 4.52, 95% Confidence Interval (CI): 2.59-7.88, p < 0.001), HACOR (OR: 2.01, 95% CI: 0.97-4.18, p = 0.036) and LUS (OR: 1.33, 95% CI: 1.014-1.106, p = 0.027) scores and blood lactate levels (OR: 9.35, 95% CI: 5.32-43.26, p < 0.001) were independent factors for NIV failure. High initial HACOR and SOFA scores, persistent hyperlactatemia and non-decrementing LUS score were associated with early NIV failure in patients with cardiac dysfunction presenting with community-acquired pneumonia, and could be used as clinical and paraclinical variables for early decision making regarding invasive ventilation.

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

IDDF2023-ABS-0299 Effectiveness of relink initiatives to re-engage diagnosed-but-untreated HCV-positive patients with direct-acting antiviral treatment

BackgroundHepatitis C virus (HCV) infection is a major cause of chronic liver disease that can progress to cirrhosis and hepatocellular carcinoma. The WHO has identified HCV infection as a public health threat and set a global target for HCV elimination by 2030. Simple pangenotypic direct-acting antiviral regimens allow most patients to be cured with minimal pretreatment and on-treatment monitoring. To achieve the WHO goal, patients including previously diagnosed HCV-positive patients who have been lost to follow-up, need to be linked to care. Studies report that up to 60% of patients who test positive for HCV antibodies are lost to follow-up and not treated. This loss has been further exacerbated by the COVID-19 pandemic, and many patients put off receiving care. Here, we explore the effectiveness of care re-engagement programs for patients with HCV.MethodsWe assessed ReLink programs (sponsored by Gilead Sciences, Inc.), designed to identify and re-engage HCV-positive patients with medical care and start/restart HCV treatment. We evaluated these programs by analyzing the number of patients, steps in the care cascade where patients were lost to follow-up, and the efficacy of the engagement program (determined by the number relinked and treated).ResultsSix programs assessed 44,964 patient records, identifying 11,163 patients lost to follow-up and eligible for contact. The main reason for the loss of follow-up was the inability to contact patients. Overall, 3726 patients were relinked with care, and 701 were treated. Several key points were identified for improving patient engagement with care, including the use of electronic databases to identify patients lost to follow-up, securing reliable contact information for patients, and partnership with medical societies.ConclusionsActive case finding, patient navigation, and care coordination in these programs led to increased engagement and treatment rates. Engaging HCV-positive patients with care is urgent, as many may already have developed more advanced liver disease. Adopting and adapting effective strategies from these programs may be a feasible way to improve patient outcomes and increase treatment numbers, thus contributing to meeting the WHO goal of HCV elimination.

2022 IDSOG Annual Meeting, Boston, MA, 4-6 August 2022

This journal issue includes s of papers presented at the conference. Topics discusses are: stillbirth during a pandemic;analysis of the female genital tract (FGT) metabolome;effectiveness of REGEN-COV antibody combination to reduce risk of hospitalization;patterns of nucleic acid amplification testing;delta variant neutralizing antibody response following maternal COVID19 vaccination;integrated prenatal and hepatitis c virus care increases linkage;extended interval gentamicin dosing in obstetrics;maternal and infant cytomegalovirus detection among women living with HIV.

19th Seminar on Tropical Pathology and Public Health 12th Biotechnology Week 1st Physical Therapy Week, Virtual, 23-25 November 2022

These proceedings comprise 85 articles spanning diverse fields such as bacteriology, molecular biology, biotechnology, dermatology, infectious and parasitic diseases, epidemiology, physiotherapy, immunology, mycology, parasitology, pathology, collective health, and virology. The articles delve into a wide range of research topics, from repurposing drugs for Mycobacterium abscessus complex infections to utilising artificial intelligence for SARS-CoV-2 diagnosis. In bacteriology, investigations explore the correlation between smoking and Helicobacter pylori infection in gastric adenocarcinoma patients, as well as the resistance profiles of Staphylococcus aureus and Pseudomonas aeruginosa in tracheostomised children. Molecular biology studies focus on gene polymorphisms related to diseases like paracoccidioidomycosis. Biotechnology research emphasises bioactive molecules in species like Croton urucurana and the development of computational models for cytotoxicity prediction. Dermatology articles address stability characterisation in vegetable oil-based nanoemulsions. The section on infectious and parasitic diseases encompasses studies on COVID-19 vaccine response in pregnant women and the impact of infection prevention measures in rehabilitation hospitals. Epidemiology investigations analyse trends in premature mortality, tuberculosis in diabetic patients, and public adherence to non-pharmacological COVID-19 measures. Physiotherapy research covers topics such as telerehabilitation through a developed game and the prevalence of congenital anomalies. Immunology studies explore immune responses in HIV and Leishmaniasis, whilst mycology investigates the biotechnological potential of fungi from the cerrado biome. Parasitology research evaluates treatment efficacy against vectors parasites such as Aedes aegypti and Toxoplasma gondii. Pathology articles discuss intentional intoxication in cattle and the influence of curcumin on acute kidney injury therapy. Collective health studies focus on intervention plan development in healthcare settings and pesticide use in horticulture. Lastly, virology research investigates parvovirus occurrence in hospitalised children during the COVID-19 pandemic, hidden hepatitis B virus infection in inmates, and the prevalence of HPV and HTLV-1/2 infections in specific populations.

Abdominal imaging findings in patients with COVID-19 part 2: solid organs

Since Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) first appeared in China in December 2019, the globe has been dealing with an ever-increasing incidence of COVID-19 (Corona Virus Disease 2019). In addition to respiratory disorders, 40% of patients present with gastrointestinal (GI) involvement. Abdominal pain is the most common indication for computed tomography (CT) and ultrasonography. After GI tract involvement, solid visceral organ infarction is the most prevalent abdominal abnormality in COVID-19. This review aims to gather the available data in the literature about imaging features of solid abdominal organs in patients with COVID-19. Gallbladder wall thickening and distension, cholelithiasis, hyperdense biliary sludge, acalculous cholecystitis, periportal edema, heterogeneous liver enhancement, and liver hypodensity and infarction are among hepatobiliary imaging findings in CT, particularly in patients admitted to ICU. Pancreatic involvement can develop as a result of direct SARS-CoV2 invasion with signs of acute pancreatitis in abdominal CT, such as edema and inflammation of the pancreas. Infarction was the most prevalent renal and splenic involvement in patients with COVID-19 who underwent abdominal CT presenting with areas of parenchymal hypodensity. In conclusion, although solid abdominal organs are rarely affected by COVID-19, clinicians must be familiar with the manifestations since they are associated with the disease severity and poor outcome.

Prevalence, causes, medical interventions, and mortality outcome of acute gastrointestinal bleeding among COVID-19 inpatients.

OBJECTIVE: This study aimed to evaluate the prevalence, causes, medical interventions, and mortality outcome of acute gastrointestinal bleeding (AGIB) among COVID-19 patients hospitalized during the delta pandemic in Vietnam. METHODS: The medical records of COVID-19 patients hospitalized in a tertiary hospital in Vietnam from July to October 2021 were retrospectively collected. Data regarding age, sex, comorbidities, COVID-19 severity, onset time of AGIB, therapeutic interventions for AGIB, and mortality outcome were analyzed. RESULTS: Of 1567 COVID-19 inpatients, 56 (3.6%) had AGIB. The independent risk factors for AGIB in COVID-19 inpatients included age (OR = 1.03, 95% CI: 1.01-1.04, p = .003), male sex (OR = 1.86, 95% CI: 1.06-3.26, p = .03), chronic liver disease (OR = 6.21, 95% CI: 2.97-13.00, p < .001), and chronic kidney disease (OR = 2.17, 95% CI: 1.01-4.65, p = .047). Among 34 AGIB patients undergoing endoscopy, upper AGIB was determined in 24 (70.6%) patients. Peptic ulcer disease and hemorrhagic erosive gastritis were the most common causes (64.7%, 22/34). The therapeutic interventions for AGIB included blood transfusion (76.8%, 43/56), endoscopic hemostasis (23.5%, 8/34), and surgery (1.8%, 1/56). The mortality rate in the AGIB group was significantly higher than that in the non-AGIB group (46.4% vs. 27.7%, OR = 2.26, 95% CI: 1.32-3.87, p = .002). However, the majority (76.9%) of deaths in COVID-19 inpatients with AGIB were not bleeding-related. CONCLUSIONS: Age, male sex, chronic liver disease, and chronic kidney disease are risk factors for AGIB among COVID-19 inpatients. Peptic ulcer disease is the most common cause. COVID-19 inpatients with AGIB have a higher risk of mortality, but a large percentage of deaths are not bleeding-related.

Since there is not enough information of sudden digestive tract bleeding among Asian populations with COVID-19, this study aimed to measure the proportion of existing cases, causes, medical treatments and deaths of sudden digestive tract bleeding in COVID-19 patients who were hospitalized during the Delta-variant pandemic in Vietnam. We collected medical records of 1567 COVID-19 patients from a specialty hospital in Vietnam from July to October 2021. Sudden digestive tract bleeding was present in 3.6% of COVID-19 inpatients. The risk of sudden digestive tract bleeding was higher in COVID-19 patients who were old, male, or had long-term liver or kidney disease. The most common cause of sudden digestive tract bleeding among COVID-19 inpatients were stomach ulcers. In addition, COVID-19 inpatients with sudden digestive tract bleeding had a higher risk of death, but a large proportion of deaths were not bleeding-related.

Impact of an automated reminder for HIV testing in general practice patient monitoring software during the COVID-19 pandemic

In 2017, the French National Health Authority (HAS) reassessed its human immunodeficiency virus (HIV) screening strategy and in 2018, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set the goal of screening 95% of people living with HIV by 2030. The HAS recommends an approach based on target population and gives the general practitioner (GP) a key role in its implementation. It is therefore important to facilitate HIV testing by GPs and to reduce missed opportunities. To this end, a pilot study was conducted on a panel of 2,000 GPs over a 10-month period in 2020 in order to evaluate the impact of a pop-up displayed within prescription assistance software reminding about the frequency of targeted screening recommended by the HAS. The pop-up was displayed for patients with a history of sexually transmitted infection and/or hepatitis C and/or tuberculosis in the previous 12 months and without a known HIV serology or diagnosis. The impact was measured by comparing the prospective follow-up of consultations made during the "pilot" in 2020 with the retrospective follow-up of consultations made during the "pre-pilot" period in 2019. The results showed a significant increase in HIV serology prescriptions during the pilot study, despite the COVID-19 pandemic. Difficulties in objectively identifying target patient profiles and in organizing regular follow-ups to HIV testing were also revealed. This pop-up tool represents an additional means of facilitating the prescription of HIV testing by GPs.

Functional pleiotropy of calcium binding protein Regucalcin in signaling and diseases.

Regucalcin (Mr ~ 33.38 kDa) is a calcium binding protein, discovered in rat liver. In humans, gene for regucalcin is located on chromosome-11 (p11.3-q11.2) consisting of seven exons and six introns. The protein differs from other calcium binding protein in the way that it lacks EF-hand motif of calcium binding domain. It is also called as Senescence Marker Protein-30 (SMP-30) as previously its weight assumes to be 30 kDa and expression of this protein decreases with aging in androgen independent manner. Among vertebrates, it is a highly conserved protein showing gene homology in Drosophila, Xenopus, fireflies and others too. It is primarily expressed in liver and kidney in addition to brain, lungs, and skeletal muscles. Regucalcin acts as a Ca2+ regulatory protein and controls various cellular functions in liver and other organs. It suppresses protein phosphatase, protein kinase, DNA and RNA synthesis. Published evidences suggest regucalcin to be a reliable biomarker in various disorders of liver, kidney, brain and ocular. In over expressed state, it subdues apoptosis in cloned rat hepatoma cells and also induces hyperlipidemia and osteoblastogenesis by regulating various factors. Owing to the multi-functionality of regucalcin this review is presented to elaborate its importance in order to understand its involvement in cellular signaling during various pathologies.

Study of liver function test in COVID-19 patients and its correlation with inflammatory markers from Hubballi, Karnataka

BACKGROUND: Since its reporting in December 2019, SARC-COV-2 (COVID -19) has infected more than 230 million people over the world by colonising the respiratory tract, however very little is known about its effect on liver and how the liver injury affects disease prognosis. This study was done to assess the hepatic profile in SARC-COV-2 infection along with inflammatory markers. METHODS: This is a single centred prospective observational study. 400 patients with real time polymerase chain reaction (PCR) confirmed COVID 19 infection admitted in KIMS, Hubballi were taken for study. Patients with decompensated liver disease were excluded from the study. Clinical examination and laboratory investigations including liver function test (LFT), renal function test (RFT), complete blood count (CBC), chest X-ray, D-dimer, ferritin, lactate dehydrogenase (LDH), C reactive protein (CRP) was done for all the patients. RESULTS: Out of the 400 covid-19 positive patients admitted, 286 (71.5%) had abnormal liver enzymes. Significantly raised liver enzymes were seen in males. Raised liver enzymes and inflammatory markers were associated with poor outcome of the disease. Significant reduced albumin was associated with poor outcome of the disease. Significantly raised aspartate transaminase (AST), alanine transaminase (ALT) levels were associated with increased severity of the disease. (P = 0.009 and 0.029 respectively). Significant positive relation was found between liver profile and inflammatory markers. CONCLUSIONS: Majority of patients admitted with SARS-CoV-2 had deranged liver profile. Higher proportion of abnormal liver enzymes were seen in males. Degree of liver injury increases with increasing severity of the disease. Even though abnormal liver enzymes were positively associated with elevated inflammatory markers and severity of the disease, more studies are needed to study implications of liver injury in prognosis of SARS-CoV-2 infection.

Secondary Sclerosing Cholangitis due to Severe COVID-19: An Emerging Disease Entity?

INTRODUCTION: Coronavirus disease 2019 (COVID-19) can lead to many extrapulmonary manifestations. In this case series, we report on 7 patients developing secondary sclerosing cholangitis (SSC) after severe COVID-19 with intensive care treatment. METHODS: Between March 2020 and November 2021, 544 patient cases with cholangitis treated at a German tertiary care centre were screened for SSC. Patients found to be suffering from SSC were assigned to COVID-19 group if SSC presented after a severe course of COVID-19 and to non-COVID-19 group if not. Peak liver parameters as well as intensive care treatment factors and data generated from liver elastography were compared between both groups. RESULTS: We identified 7 patients who developed SSC after a severe course of COVID-19. In the same period, 4 patients developed SSC due to other causes. Mean values of gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were higher in the COVID-19 group than in the non-COVID-19 group (GGT: 2,689 U/L vs. 1,812 U/L and ALP: 1,445 U/L vs. 1,027 U/L), whereas intensive care treatment factors were comparable in both groups. Only the mean duration of mechanical ventilation was shorter in the COVID-19 group than in the non-COVID-19 group (22.1 days vs. 36.7 days). Liver elastography indicated a fast progression to liver cirrhosis with a mean liver stiffness of 17.3 kilopascals (kPa) in less than 12 weeks in the COVID-19 group. CONCLUSIONS: Our data suggest a more severe course of SSC when caused by SARS-CoV-2. Reasons for this are probably multifactorial, including a direct cytopathogenic effect of the virus.

Liver involvement in patients with COVID-19 infection: A comprehensive overview of diagnostic imaging features.

During the first wave of the pandemic, coronavirus disease 2019 (COVID-19) infection has been considered mainly as a pulmonary infection. However, different clinical and radiological manifestations were observed over time, including involvement of abdominal organs. Nowadays, the liver is considered one of the main affected abdominal organs. Hepatic involvement may be caused by either a direct damage by the virus or an indirect damage related to COVID-19 induced thrombosis or to the use of different drugs. After clinical assessment, radiology plays a key role in the evaluation of liver involvement. Ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) may be used to evaluate liver involvement. US is widely available and it is considered the first-line technique to assess liver involvement in COVID-19 infection, in particular liver steatosis and portal-vein thrombosis. CT and MRI are used as second- and third-line techniques, respectively, considering their higher sensitivity and specificity compared to US for assessment of both parenchyma and vascularization. This review aims to the spectrum of COVID-19 liver involvement and the most common imaging features of COVID-19 liver damage.

The SAR-based development of small molecular HBV capsid assembly modulators

Hepatitis B virus (HBV) infected about 296 million people worldwidely, while clinical useful therapeutic agents were still limited. Capsid assembly modulators (CAM) have been validated as efficient anti-HBV virus agents with the potential to achieve functional cure, therefore piqued much attention in recent years. There are various novel scaffold agents been developed and more than ten CAM candidates have been progressed into clinical trials with efficient anti-HBV activities. Herein, we summarised the SAR-based development of CAMs with various scaffolds, including heteroaryldihydropyrimidines (HAPs), phenylacrylamides (PPAs), sulfamoylbenzamides (SBAs), pyridazinone, bis-heterocycle, arylformamides, aminothiazoles, and others, which may provide new suggestions for the further development of CAMs.