Features of liver function in pediatric patients infected with Delta variant versus Omicron variant of severe acute respiratory syndrome coronavirus 2.

Objective To summarize and analyze the features of liver function in pediatric patients infected with Delta variant versus Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2). Methods In this study,an analysis was performed for the liver function test results of the locally transmitted or imported pediatric patients with SARS - CoV - 2 infection during isolation who were admitted to Guangzhou Eighth People's Hospital,Guangzhou Medical University,since May 21,2021,and the clinical data and the constituent ratio of liver injury were compared between the pediatric patients infected with Delta variant and those infected with Omicron variant. The independent samples t - test or the Mann - Whitney U test was used for comparison of continuous data between two groups,and the chi - square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results A total of 85 pediatric patients infected with SARS - CoV - 2 were enrolled,among whom there were 32 (37. 6%)pediatric patients infected with Delta variant and 53 (62. 4%)pediatric patients infected with Omicron variant,and there were no significant differences between the two groups in age,sex, body height,body weight,and comorbidities (all P > 0. 05). There were no significant differences between the two groups in alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),gamma - glutamyl transpeptidase,total bilirubin,albumin,and cholinesterase (all P > 0. 05),and the pediatric patients infected with Omicron variant had a significantly higher level of total bile acid (TBA)than those infected with Delta variant (Z = - 2. 336,P = 0. 020). However,the median values of TBA were within the normal range and the ratios of abnormal TBA were no significant difference between the two groups (P > 0. 05). Among the 85 pediatric patients,10 (11. 8%)had a mild increase in liver function parameters,among whom 7 had an increase in TBA,1 had an increase in ALT, 1 had increases in ALT and AST,and 1 had an increase in ALP. The analysis of liver injury in the pediatric patients infected with Delta variant or Omicron variant showed that there was no significant difference in the constituent ratio of liver injury caused by the two variants (6. 3% vs 15. 1%,chi2 = 0. 691,P = 0. 406). Conclusion Mild liver injury is observed in pediatric patients infected with Delta and Omicron variants of SARS - CoV - 2,but further studies are needed to evaluate the long - term influence of such infection on liver function.Copyright © 2022 Editorial Board of Jilin University

Immunotherapy: ALLOGENEIC UMBILICAL CORD BLOOD REGULATORY T CELLS DECREASE INFLAMMATION AND PRESERVE ANTI-TUMOR ACTIVITY OF CAR T CELLS

Background & Aim: With larger accessibility and increased number of patients being treated with CART cell therapy, real-world toxicity continues to remain a significant challenge to its widespread adoption. We have previously shown that allogeneic umbilical cord blood derived (UCB) regulatory T cells (Tregs) can resolve uncontrolled inflammation and can treat acute and immune mediated lung injury in a xenogenic model as well as in patients suffering from COVID-19 acute respiratory distress syndrome. The unique properties of UCB Tregs including: i) lack of plasticity when exposed to inflammatory micro-environments;ii) no requirement for HLA matching;iii) long shelf life of cryopreserved Tregs;and iv) immediate product availability for on demand treatment, makes them an attractive source for treating acute inflammatory syndromes. Therefore, we hypothesized that add-on therapy with UCB derived Tregs may resolve uncontrolled inflammation responsible for CART cell therapy associated toxicity. Methods, Results & Conclusion(s): UCB Tregs were added in 1:1 ratio to CART cells, where no interference in their ability to kill CD19+ Raji cells, was detected at different ratios : 8:1 (80.4% vs. 81.5%);4:1 (62.0% vs. 66.2%);2:1 (50.1% vs. 54.7%);1:1 (35.4% vs. 44.1%) (Fig 1A). In a xenogenic B cell lymphoma model, multiple injections of Tregs were administered after CART injection (Fig 1B), which did not impact distribution of CD8+ T effector cells (Fig 1C) or CART cells cells (Fig 1D) in different organs. No decline in the CAR T levels was observed in the Tregs recipients (Fig 1E). Specifically, no difference in tumor burden was detected between the two arms (Fig 2A). No tumor was detected in CART+Tregs in liver (Fig 2B) or bone marrow (Fig 2C). A corresponding decrease in multiple inflammatory cytokines in peripheral blood was observed in CART+Tregs when compared to CART alone (Fig 2D). Here we show "proof of concept" for add-on therapy with Tregs to mitigate hyper-inflammatory state induced by CART cells without interference in their on-target anti-tumor activity. The timing of Tregs administration after CART cells have had sufficient time for forming synapse with tumor cells allows for preservation of their anti-tumor cytotoxicity, such that the infused Tregs home to the areas of tissue damage to bind to the resident antigen presenting cells which in turn collaborate with Tregs to resolve inflammation. Such differential distribution of cells allow for a Treg "cooling blanket" and lays ground for clinical study. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

Using implementation science in youth mental health workforce development: Adapting to the COVID-19 pandemic in Australia

Aims: Globally, mental illness and substance use disorders are the leading cause of disability and disease burden for young people. Orygen is an Australian youth mental health organization with a mission to reduce the impact of mental ill-health on young people, families and society, and one of only a few known research and clinical centres with a dedicated Knowledge Translation division. This paper provides a case study of the workforce development team within Orygen Knowledge Translation, outlining how implementation science informs their work and how the division has adapted its model of service support in the face of COVID-19. Method(s): Process data on training and resources developed and delivered by the workforce development team at Orygen over the period 2017-2021 was collated and synthesized with team reflections about the adaptations made by team in response to the COVID-19 pandemic. Results and Conclusion(s): Since 2017, the team has delivered training to more than 4000 youth mental health workers across Australia, on the topics of trauma, psychosis, mood and anxiety disorders, brief interventions, cognition and other areas of youth mental health. The COVID-19 pandemic generated abrupt and dramatic changes to the delivery of workforce and service development initiatives in Australia due to significant restrictions to travel and in-person events. It also placed major delivery demands on youth mental health services. The COVID-19 pandemic facilitated profound and rapid changes to service delivery and development in Australian youth mental health. Implementation science offers flexible models to support a changing system.

Assessment of biventricular myocardial systolic function in COVID-19 patients: A Tissue Doppler Imaging echocardiography study

Background: The 2019 novel coronavirus disease (COVID-19) has been reported as pandemy and the number of patients continues to rise. Based on recent data, cardiac injury is a prominent feature of the disease, leading to increased morbidity and mortality. In the present study we aimed to evaluate myocardial dysfunction using transthoracic echocardiography (TTE) and tissue Doppler imaging (TDI) in hospitalized COVID-19 patients. Methods and Results: We recruited 30 patients (56.7% male, 55.80 +/- 14.949 years) who were hospitalized with the diagnosis COVID-19 infection. We analyzed left ventricular (LV) and right ventricular (RV) conventional and TDI parameters at the time of hospitalization and during the course of the disease. Patients without any cardiac disease and with preserved LV ejection fraction (EF) were included. TTE examination was performed and all the variables were recorded and analyzed retrospectively. We observed that both LV and RV conventional echocardiographic parameters were similar when the day of admission to the hospital was compared to the 5th day of the disease. Regarding TDI analysis, we demonstrated significant impairment in LV septal and lateral deformation (P < 0.001). In the correlation analysis no marked correlation was observed between impairment in LV deformation and inflammation biomarkers. Conclusion(s): Cardiac involvement is an important feature of the COVID-19 infection but the exact mechanism is still undefined. Echocardiography is an essential technique to describe myocardial injury and provide new concepts for the possible definitions of cardiac dysfunction.Copyright © 2023 The Author(s).

Characteristics of liver injury in cases of COVID-19.

In novel coronavirus disease 2019 (COVID-19), liver injury was found at a high rate, and reports from outside Japan revealed that such injury was related to severity. We examined the characteristics of liver injury in 15 cases of COVID-19. Thirteen of these patients received antiviral therapy, such as favipiravir, remdesivir, and hydroxychloroquine. Liver injury was observed in eight cases at admission for COVID-19. The hepatic CT attenuation values at admission were significantly lower in nine patients who developed liver damage or showed its exacerbation during the treatment than in the remaining patients. Drug-induced liver injury due to antiviral drug was suspected in six cases. Liver injury due to COVID-19 may be related to low hepatic CT attenuation values and be modified by antiviral drugs.Copyright © 2021 The Japan Society of Hepatology.

Salt steps and sugar checks - Making arterial line use safer in our trust

Introduction: Arterial lines are used within our intensive care unit to allow invasive blood pressure monitoring and regular blood gas analysis. Inadvertent use of dextrose containing fluids in the flush have been associated with falsely high glucose readings. When these are acted on with insulin, it can cause devastating hypoglycaemic brain injury. There have been a number of deaths and other incidents relating to the wrong fluid being used in arterial line set up reported within the UK in recent years. In 2014 the AAGBI released a safety guideline on the use of arterial lines specifically to reduce to the risk of hypoglycaemic brain injury. Objective(s): Our objective was to ensure that 100% of arterial lines in use within Royal Victoria Hospital's intensive care unit were compliant with our trust policy on the management of arterial lines. Method(s): We audited our intensive care unit's compliance with our trust policy and found that we were 80% compliant. We formed a multi-disciplinary arterial line working group in order to tackle the problem. Our quality improvement project consisted of two main approaches: 1. To educate staff on how to manage arterial lines correctly. We divided the management of arterial lines into S.A.L.T steps (a 7 step bundle on "Setting up an Arterial Line Transducer") and SUGAR checks ( a series of red flag moments to prompt staff to review the patient prior to starting or increasing insulin administration).We developed educational posters for key areas in ICU and presented our findings at departmental meetings. 2. To change the system, in order to make it easier to do the right thing. We developed a Universal Adult Arterial Pack (UAAP) containing key components in the setup of an arterial line. This also included aide memoires for the S.A.L.T steps and SUGAR checks. In order to measure the effect of these changes, we: 1. Audited compliance on a regular basis. 2. Monitored serious bundle breaches ( for example no label, wrong fluid used) 3. Assessed usage of the UAAP. Result(s): 1. Bundle compliance improved during the first half of 2021, however then reduced in the second half with the number of serious bundle breaches increasing. This coincided with COVID surge 4 - associated with reduced nursing ratios and staff redeployment. 2. UAAP usage increased throughout the project, from an average of 6 to 9 per day. 86% of staff found the packs useful and 85% thought that they reduced the potential for error. Conclusion(s): The presence of a policy does not ensure that staff will know about it or adhere to it. Although we have not yet achieved our target of 100% compliance, we have seen evidence of how our project has the potential to do so in the near future. We aim to roll out our new e-learning module for staff education, manufacture our UAAP on a bigger scale, and disseminate the project to other departments within the trust.

Association of apolipoprotein E4 to the number of cerebral microbleeds in patients recovered from COVID-19

Background: COVID-19 has been associated with cerebral microbleeds (CMB). Previously, an association of ApoE4 with COVID-19 severity and CMBs in autopsy was found. In this study, we investigated if carrying the Apoe4 allele relates to the number of CMBs in magnetic resonance imaging (MRI) in patients recovered from COVID-19. Material(s) and Method(s): Adult patients recovered from COVID-19 and a control group without a history of COVID-19 was recruited. Exclusion criteria were major neurologic disease, developmental disability or pregnancy. The participants underwent brain MRI 6 months after infection, and a blinded neuroradiologist analyzed the findings. ApoE was genotyped using a microarray. Statistical analysis was performed using the statistical software R. A negative binomial model was chosen based on the distribution of CMBs. Result(s): Of the 216 subjects that underwent MRI, 168 consented to genetic testing, additionally 2 patients were excluded due to extensive CMBs and 1 due to diffuse axonal injury. We included 113 COVID-19 patients (49 ICU-treated, 29 ward-treated and 35 home-isolated) and 52 controls. The most prevalent comorbidities were hypertension, asthma and diabetes. CMBs was found in 47 subjects, with the number of CMBs ranging from 0 to 26. The ApoeE4 allele was carried by 37%, equally distributed among the groups. After adjustment, age (aRR = 1.06, p = 0.007) and COVID-19 (aRR = 2.59, p = 0.038) were independently associated with CMBs. The ApoE4 allele (aRR = 2.16, p = 0.07, CI = 0.94-5.10) was not significant. Conclusion(s): Age and previous COVID-19, but not possession of the ApoeE4 allele, were independently associated with the number of CMBs.

Re-humanisation, Recognising the person behind the patient

Submission content Introduction: At the end of a particularly hectic night shift on the intensive care unit (ICU) I found myself sitting in the relatives' room with the mother and aunt of a young patient, listening to their stories of her hopes and aspirations as she grew up. She had been diagnosed with lymphoma aged 14 and received a bone marrow transplant from her younger sister. Fighting through treatment cycles interposed with school studies, she eventually achieved remission and a portfolio of A-levels. Acceptance into university marked the start of a new era, away from her cancer label, where she studied forensic science and took up netball. Halfway through her first year she relapsed. Main body: When I met this bright, ambitious 20-year-old, none of this history was conveyed. She had been admitted to ICU overnight and rapidly intubated for type-1 respiratory failure. The notes contained a clinical list of her various diagnoses and treatments, with dates but no sense of the context. Rules regarding visitation meant her family were not allowed onto the unit, with next-of-kin updates carried out by designated non-ICU consultants to reduce pressures on ICU staff. No photos or personal items surrounded her bedside, nothing to signify a life outside of hospital. She remained in a medically-induced coma from admission onwards, while various organ systems faltered and failed in turn. Sitting in that relatives' room I had the uncomfortable realisation that I barely saw this girl as a person. Having looked after her for some weeks, I could list the positive microbiology samples and antibiotic choices, the trends in noradrenaline requirements and ventilatory settings. I had recognised the appropriate point in her clinical decline to call the family in before it was too late, without recognising anything about the person they knew and loved. She died hours later, with her mother singing 'Somewhere Over the Rainbow' at her bedside. Poignant as this was, the concept of this patient as more than her unfortunate diagnosis and level of organ failure had not entered my consciousness. Perhaps a coping mechanism, but dehumanisation none-the-less. Conclusion(s): Striking a balance between emotional investment and detachment is of course vital when working in a clinical environment like the ICU, where trauma is commonplace and worst-case-scenarios have a habit of playing out. At the start of my medical career, I assumed I would need to consciously take a step back, that I would struggle to switch off from the emotional aspects of Medicine. However, forgetting the person behind the patient became all too easy during the peaks of Covid-19, where relatives were barred and communication out-sourced. While this level of detachment may be understandable and necessary to an extent, the potential for this attitude to contribute to the already dehumanising experience of ICU patients should not be ignored. I always thought I was more interested in people and their stories than I was in medical science;this experience reminded me of that, and of the richness you lose out on when those stories are forgotten.

The preventive effect and mechanism of Dayuanyin in hypoxic pulmonary hypertension through NF-kappaB signaling pathway.

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg.kg-1), and positive control sildenafil group (100 mg.kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% +/- 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF- kappaB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF- kappaB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-kappaB and signal transducer and activator of transcription 3 (STAT3) by DYY.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

Particularities of hemostasis changes in COVID-19 patients.

COVID-19 infection is characterized by different clinical presentations. The thrombotic complications play the leading role in COVID-19 infection. SARS-CoV-2 virus can activate hemostasis at different levels: pulmonary tissue damage with subsequent plasma coagulation activation;local endothelial dysfunction and platelet activation during the course of the disease. Routine use of the anticoagulation treatment seems reasonable in hospitalized patients with COVID-19.Copyright © Creative Cardiology 2021.

Preoperative COVID-19 RT-PCR Testing of Asymptomatic Patients for Ophthalmic Surgery: Experience from Two Tertiary Referral Centers

Purpose: The aim of this study was to evaluate how prevalent asymptomatic SARS-CoV-2 virus infection (COVID-19) is among patients undergoing ophthalmic surgery at two tertiary referral hospitals. Material(s) and Method(s): This retrospective study included patients without COVID-19 symptoms who underwent preoperative screening using reverse transcription-polymerase chain reaction (RT-PCR) before ophthalmic surgery at the Kocaeli University and Gaziantep University departments of ophthalmology [between September 1, 2020, and December 15, 2020 (group 1);between March 1, 2021, and May 30, 2021 (group 2)]. Patients scheduled for surgery and followed up in the retina, glaucoma, pediatric ophthalmology and strabismus, cataract and refractive surgery, and cornea departments were examined. Result(s): RT-PCR was positive for SARS-CoV-2 in 12 (1.4%) of 840 patients in group 1 and 7 (1.1%) out of 600 patients in group 2. None of the patients were symptomatic of COVID-19. The majority of the patients were scheduled for retina or cataract and refractive surgery in both groups (group 1;retina: 29.2%, cataract and refractive: 57.0%, group-2;retina: 31.3%, cataract and refractive: 54.5%). SARS-CoV-2 RT-PCR testing was positive for seven patients in group 1 (7/245, 2.9%) and five patients in group 2 (5/188, 2.6%) who were scheduled for retinal surgery. Conclusion(s): The necessity, availability, and practicality of COVID-19 RT-PCR testing prior to ophthalmic surgeries varies depending on the protocols of each institution. COVID-19 RT-PCR testing is suggested especially before vitreoretinal surgeries and general anesthesia procedures, because of the difficulty in managing postoperative complications.Copyright © 2023 Gazi Eye Foundation. All rights reserved.

Relationship between COVID-19 and liver diseases: The role of hepatologists in clinical practice.

COVID-19 due to severe acute respiratory syndrome coronavirus 2, which has become a global pandemic, produces elevated liver enzymes, especially in severe cases. The mechanism suggests involvement of an administrated drug, cytokine storm, or hypoxia, etc., as opposed to virus-induced direct damage. If liver enzymes are elevated in COVID-19, we should evaluate for the presence of other liver diseases, and strictly follow-up liver enzyme values. In patients with COVID-19 complicated by chronic liver disease, we will use telemedicine/visits by phone, so as not to interrupt the treatment of the underlying disease, avoid unnecessary outpatient visits, and strive to halt the spread of the infection. Metabolism-associated fatty liver disease, which is often related to obesity, diabetes, and hypertension, may be a risk factor for COVID-19 severity. International academic societies have recommended guidance outlining the evidence to date regarding the management of patients with COVID-19 and liver disorders, and chronic liver disease under the COVID-19 pandemic.Copyright 2020 The Japan Society of Hepatology.

A case of possible drug-induced liver injury due to COVID-19 vaccine.

The patient presented with nausea, appetite loss, and fatigue. She had received two doses of Pfizer/BioN-Tech BNT162b2 mRNA vaccine (COMIRNATY) for coronavirus disease 2019 (COVID-19). Acute liver injury was noted 14 days after the first dose of the vaccine. Re-exposure through the second dose worsened the liver injury. After liver biopsy on the third day of admission, methylprednisolone (1000 mg) was administered. Liver histology showed acute hepatitis with diffuse lobular inflammation/necrosis and lymphocyte-dominant infiltra-tion in the portal areas. The patient was diagnosed with drug-induced liver injury due to the COVID-19 vaccine based on the Digestive Disease Week Japan 2004 (DDW-J) scale, which assesses the temporal relationship, liver biopsy, and laboratory findings. With improvements in the blood test parameters, prednisolone was gradually tapered and stopped. One month later, no biochemical signs of relapse were noted. To our knowledge, this is the first report describing liver injury after the administration of the Pfizer COVID-19 vaccine in Japan.Copyright © 2022 The Japan Society of Hepatology.

Invasive aspergillosis in patients with COVID-19 in intensive care units: results of a multicenter study.

Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.

Concomitant hemorrhagic fever with renal syndrome and COVID-19.

Udmurt Republic is an endemic region for hemorrhagic fever with renal syndrome (HFRS). An extremely high incidence of COVID-19 in 2020-2021 worldwide and in Udmurt Republic in particular suggests that patients might bear these two infections simultaneously. In this article, we report a case of mixed COVID-19 plus HFRS infection. Specific clinical manifestations of HFRS in a COVID-19-coinfected patient included long-term fatigue, thrombocytopenia, iso(hypo)sthenuria, polyuria, episodes of sinus tachycardia and hypertension. On the other hand, the main clinical characteristics of COVID-19 in a HFRS-coinfected patient included no clinical signs of respiratory failure and relatively high saturation despite a substantial lung damage. In general, mixed infection is a risk factor that aggravates the disease and can worsen outcome. However, simultaneous infection of a cell with more than one virus probably causes viral interference, which results in suppression of one or both viruses.Copyright © 2023, Dynasty Publishing House. All rights reserved.

Complications Associated with Catheter Ablation of Atrial Fibrillation in Current Practice: Insights from a Large, Real-World Collaboration

Background: Catheter ablation is a cornerstone treatment for symptomatic atrial fibrillation (AF) with major improvements in safety over time. However, rates of adverse events with use of current techniques in a contemporary quality-focused network remain undefined. Objective(s): Across a large, real-world sample, we sought to describe (1) rates of major, adverse events associated with catheter ablation of AF and (2) patient-level factors associated with complications. Method(s): Utilizing the REAL-AF collaboration, a registry of contemporary AF ablation procedures with granular patient, procedural and follow-up data comprised of cases from over 50 operators across academic and non-academic sites, we evaluated all patients undergoing their first ablation procedure from January 2018 - June 2022. Risk-adjusted analyses were conducted to evaluate the relationship between patient factors and complications. Result(s): Among 3144 patients (age 66.1 +/- 11.0 years, 42% female, 67.1% paroxysmal, 32.9% persistent) who underwent AF ablation, procedure-related complications (n =77) were identified in 65 patients (2.1%) with multiple complications occurring in 9 patients (0.2%). Most complications (n=70, 93.5%) occurred in the peri-procedural (within 30 days) period and 6.5% (n=5) after 30 days, the latter of which all represented vascular injuries (Figure). Major complications (18 of 72 peri-procedural complications, 25.0%) are defined, detailed, and associated data reported in the Figure. Unadjusted (16.0% without CHF vs. 33.3% with CHF, p = 0.045) and risk-adjusted (OR 2.8, 95% CI 1.03-7.60, p=0.045) analyses indicated history of CHF was associated with a composite outcome of major complications. Analyses of independent complications showed those who suffered from peri-procedural stroke (n=3) were of significantly greater age (77.3 +/- 5.5 years vs. 66.1 +/- 10.9 years, p=0.035). Risk-adjusted analyses showed history of vascular disease (OR 2.9, 95% CI 1.02-8.20, p=0.045) was associated with vascular injury (n=18). From 0-695 days post-procedure, 31 deaths occurred (unknown cause: 17, COVID-19 related: 4, heart failure: 2, cardiac arrest: 2). Conclusion(s): Major complications represent rare events among those undergoing AF ablation in current practice. Risk-adjusted analyses suggest a history of CHF is associated with major complications. Similarly, older age and a history of vascular disease are associated with stroke and vascular complications, respectively. [Formula presented]Copyright © 2023

Oncolytic virus TG6002 safety and activity after intrahepatic artery administration in patients with liverdominant metastatic colorectal cancer

The TG6002.03 trial is a dose-escalation phase 1 clinical trial of TG6002 infusion via the hepatic artery in patients with liver-dominant colorectal cancer metastases. TG6002 is an engineered Copenhagen strain oncolytic Vaccinia virus, deleted of thymidine kinase and ribonucleotide reductase to enhance tumor selective viral replication and expressing FCU1, an enzyme converting the non-cytotoxic prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). In this trial, patients with advanced unresectable liver-dominant metastatic colorectal cancer who had failed previous oxaliplatin and irinotecan-based chemotherapy were treated with up to 2 cycles of TG6002 infusion 6 weeks apart via the hepatic artery on day 1 combined with oral 5-FC on days 5 to 14 (where day 1 = TG6002 infusion). TG6002 infusion was performed over 30 minutes via selective catheterization of the hepatic artery proper. 5-FC oral dosing was 50mg/kg x4 daily. Blood was sampled for TG6002 pharmacokinetics and 5-FC and 5-FU measurements. Sampling of liver metastases was performed at screening and on day 4 or day 8 for virus detection and 5-FC and 5-FU quantification. In total, 15 patients (median age 61 years, range 37-78) were treated in 1 UK centre and 2 centres in France and received a dose of TG6002 of 1 x 106 (n=3), 1 x 107 (n=3), 1 x 108 (n=3), or 1 x 109 pfu (n=6). Fourteen of the 15 patients received a single cycle of treatment, including one patient who did not received 5-FC, and one patient received two cycles. TG6002 was transiently detected in plasma following administration, suggesting a strong tissue selectivity for viral replication. In the highest dose cohort, a virus rebound was observed on day 8, concordant with replication time of the virus. In serum samples, 5-FU was present on day 8 in all patients with a high variability ranging from 0.8 to 1072 ng/mL and was measurable over several days after initiation of therapy. Seven of the 9 patients evaluable showed the biodistribution of the virus in liver lesions by PCR testing on day 4 or day 8. Translational blood samples showed evidence for T-cell activation and immune checkpoint receptor-ligand expression. At 1 x 109 pfu, there was evidence for T-cell proliferation and activation against tumour-associated antigens by ELISpot and for immunogenic cell death. In terms of safety, a total of 34 TG6002-related adverse events were reported, of which 32 were grade 1-2 and 2 were grade 3. The maximum tolerated dose was not reached, and a single dose-limiting toxicity was observed consisting of a myocardial infarction in a context of recent Covid-19 infection in a 78-year-old patient. These results indicate that TG6002 infused via the hepatic artery in combination with oral 5-FC was well tolerated, effectively localized and replicated in the tumor tissues, expressed its therapeutic payload and showed anti-tumoral immunological activity.

Roots and resiliency for native American young people

Aim: The presentation shares traditional Native American knowledge about wellbeing and caring for a person's body, heart, connection to the Creator, ancestors, and the land Methods: Drawing upon community narratives and traditional ancestral knowledge themes pertinent to the topic will be presented. Narrative Review Results: Ancestral knowledge is essential to access and practice in? community care and healing. This knowledge is sacred to the lives wellbeing, and continuation of traditional ways for Confederated Tribes of Warm Springs (CTWS) people. CTWS young people play an important role in these practices for their community and elders. The practice of taking CTWS children from families was a pivotal moment that pushed forward the concept of mental health for the CTWS. The threat of climate change, and the COVID-19 pandemic's activation of memories of imposed isolation between our people and from traditional ways continues to impact our young people. The process of healing from historical and present-day traumas includes grieving those losses and healing from addictions, as well as physical and sexual abuse Conclusion(s): Rebuilding and strengthening connections to the land Chuush (water in Sahaptin language), food gathering, and being with each other, is central to our young people's, and community's, healing The path of returning to our traditional understanding of the knowledge of what the Creator has provided for the CTWS people will be shared. This knowledge is useful for the care of young people Native and non-Native alike.