CHARACTERISTICS OF PATIENTS WHO RECEIVED BIOLOGICAL TREATMENT AFTER KIDNEY TRANSPLANTATION AND THE INCIDENCE OF SERIOUS INFECTIONS: A MULTICENTER STUDY

BackgroundKidney transplant patients due to both primary kidney involvement of chronic/autoimmune inflammatory diseases and end-stage kidney disease related to amyloidosis are followed up in rheumatology clinics. Biological agents one of the treatment options in kidney transplant recipients with chronic/autoimmune inflammatory disease.ObjectivesHowever, there is insufficient data on the development of infection in kidney transplant recipients who received biological treatment. Herein, we aimed to determine the incidence of serious infections in patients with kidney transplant recipients who are received biological therapy.MethodsKidney transplant recipients who are received biological agents due to rheumatologic disease were included in the study. Patients' demographic features, transplantation data, biological treatment, development of infection and severity of infection were screened retrospectively. Infections that requiring hospitalization were defined as severe infections.ResultsA total of 31 patients were included in the study, 14 (45%) of whom were female and mean age was 41 ±9 years. Twenty-five patients (80%) of them were non-preemptive kidney transplant and mean duration of hemodialysis before the transplantation was 40 ±40 months. Twenty-three patients (74%) had end stage kidney failure due to FMF-amyloidosis(Figure-1-). Seventeen patients (54%) received anakinra, 11 patients (35%) received canakinumab and 3 patients (10%) received etanercept with other immunosuppressive treatment. Mean treatment duration of biological agents was 4.2±2.6 years. Two patients developed solid organ malignancy and one patient developed hematological malignancy after transplantation. Sixteen of the patients (52%) were hospitalized at least once due to infection and 4 patients (13%) died due to infection. The cause of decease in two patients was COVID-19.ConclusionRheumatic diseases are an important cause of end-stage renal disease and definitive treatment is kidney transplantation. Kidney transplant recipients due to rheumatological disease also use biological agents in the post-transplantation period. Kidney transplant recipients have higher risk for the development of infection since they receive immunosuppressive therapy and use of biologic agents may further increase the risk for development infection. Meyer et al reported that infection developed in 54 of 187 solid organ transplant recipients using biological agents.[1] Mean treatment duration of biological agents was 12 months in this study. The incidence of infection was 54% in our study. Mean treatment duration of biological agent was 4.2 year was considered main reason for higher incidence of infection in our study.Reference[1]Meyer F, Weil-Verhoeven D, Prati C, Wendling D, Verhoeven F. Safety of biologic treatments in solid organ transplant recipients: A systematic review. Semin Arthritis Rheum. 2021 Dec;51(6):1263-1273. doi: 10.1016/j.semarthrit.2021.08.013. Epub 2021 Aug 26. Erratum in: Semin Arthritis Rheum. 2022 Aug;55:152015. PMID: 34507811.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

COVID Cholangiopathy Can Occur Despite Mild COVID

Introduction/Objective Post-COVID-19 cholangiopathy is a novel entity first noted in patients recovering from critical COVID-19 infection. Since its initial description in May 2021, all cases reported to date have been in patients with a history of critical COVID-19, defined as requiring ICU admission, the development of respiratory or circulatory failure requiring intubation or ECMO, or vasopressor support. Here we report three cases of post-COVID-19 cholangiopathy arising in patients who recovered from non-severe COVID-19. Methods/Case Report Six cases of COVID-19-related cholangiopathy were identified by retrospective review, three of which involved patients who verifiably did not develop critical COVID-19. Histology slides for each case were reviewed and all showed features of secondary sclerosing cholangitis. Patient 1 is a 41yo female who developed COVID-19 after liver transplant (LT). Despite administration of monoclonal antibodies, she required re-transplantation 6 weeks later. Explant histology showed bile infarcts, severe hepatocytic and canalicular cholestasis, ductular reaction, organizing portal vein thrombi, and necrotic bile ducts accompanied by bile lakes. Patient 2 is a 47yo male with alcoholic cirrhosis who was diagnosed with COVID-19 at the time of LT workup, and underwent LT 90 days later. In addition to alcohol-related cirrhosis, explant histology showed dilated bile ducts with periductal fibrosis, as well as severe ductular reaction with proliferating ductules containing thick, inspissated bile. Patient 3 is a 54yo male with history of LT for PSC who developed mild COVID-19 five years after LT. Allograft function subsequently worsened and biopsy 6 months later showed bile duct damage and loss of ~35% of bile ducts;repeat biopsy 14 months after his COVID diagnosis showed periportal fibrosis with edema, ductular reaction, marked hepatocellular and canalicular cholestasis, and ductopenia with loss of 60% bile ducts. Average time between COVID-19 diagnosis and onset of COVID-related cholangiopathy was 3 months (range: 6 weeks-6 months). These patients were also all immunocompromised with two due to prior LT and one being cirrhotic. Results (if a Case Study enter NA) NA. Conclusion Although previously reported only in patients with severe COVID-19, the cases described represent the first evidence that cholangiopathy, manifested by sclerosing cholangitis, can arise even in patients who were not critically ill, although this may require an immunocompromised state to develop.

Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome.

The human gut microbiome contains the largest number of bacteria in the body and has the potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, and diverse microbiome and overall health. When the gut microbiome becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, and ageing, this has a profound effect on our health and is linked to many diseases, including lifestyle diseases, metabolic diseases, inflammatory diseases, and neurological diseases. While this link in humans is largely an association of dysbiosis with disease, in animal models, a causative link can be demonstrated. The link between the gut and the brain is particularly important in maintaining brain health, with a strong association between dysbiosis in the gut and neurodegenerative and neurodevelopmental diseases. This link suggests not only that the gut microbiota composition can be used to make an early diagnosis of neurodegenerative and neurodevelopmental diseases but also that modifying the gut microbiome to influence the microbiome-gut-brain axis might present a therapeutic target for diseases that have proved intractable, with the aim of altering the trajectory of neurodegenerative and neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, and attention-deficit hyperactivity disorder, among others. There is also a microbiome-gut-brain link to other potentially reversible neurological diseases, such as migraine, post-operative cognitive dysfunction, and long COVID, which might be considered models of therapy for neurodegenerative disease. The role of traditional methods in altering the microbiome, as well as newer, more novel treatments such as faecal microbiome transplants and photobiomodulation, are discussed.

Evaluation of tixagevimab-cilgavimab in pre-exposure prophylaxis of COVID-19

Background and ImportanceIn the context of pre-exposure prophylaxis of COVID-19 in adults and adolescents aged 12 years and older (> 40 kg), tixagevimab-cilgavimab is currently included in clinical guidelines. The recommended dose is administered as two separate sequential intramuscular injections (150 mg of tixagevimab and 150 mg of cilgavimab), preferably in the gluteal muscles. Due to their recent authorisation, effectiveness and security of this treatment is not well known.Aim and ObjectivesThe aim of this study was to analyse the effectiveness and security of tixagevimab-cilgavimab in patients with COVID-19 risk after a complete vaccination regimen, collated with the data from PROVENT clinical trial.Material and MethodsRetrospective observational study in a cohort of COVID-19 risk patients. Electronic medical record and prescription application were used to collect the following data: sex, age, comorbidities, anticoagulation, and titles of anti-Spike antibodies, and COVID-19 infections after administration.ResultsThe study includes 41 patients (52.5% women, median age 64.5 years (SD 13.5)), who were candidates to prophylaxis because of their comorbidities: anti-CD20 active treatment (21), solid organ transplantation (renal (10) and pulmonary (14)), chronic kidney disease (2), immunosuppression (1), cytotoxic chemotherapy (1) or haematopoietic Stem Cell transplant (1). After the last vaccination, 97.5% of the patients had low antibodies (< 260 BAU/mL), which demonstrates an inadequate response to active immunisation. These comorbidities and clinical conditions were similar in PROVENT.In PROVENT, the duration of protection is estimated to be at least 6 months (0.2% COVID-19 positive cases after administration prior to day 183). In our study population, 3 patients were COVID-19 positive (7.5%) prior to day 90 after administration without severe or critical symptomatic illness.As with any other intramuscular injections, should be given with caution to patients with thrombocytopenia or coagulation disorders;5 patients were on anticoagulation therapy and no bleeding events were recorded. Therefore, non-hypersensitivity reactions have been observed.Conclusion and RelevanceEffectiveness and security of the pre-exposure prophylaxis with tixagevimab-cilgavimab was adequate in most of the patients treated, and similar to the data of the clinical trials. Even so, pre-exposure prophylaxis is not a substitute for vaccination. Nevertheless, further studies were necessary to establish the effective and security profile.References and/or AcknowledgementsConflict of InterestNo conflict of interest

Regulatory Competition, Coordination and Polity Convergence in the Covid Ecosystemic Crisis: A Policy Approach

The paper briefly sketches different "adaptations” possible to address the Covid crisis and then advances three possible avenues for future policy analysis of Covid-related measures, each of these avenues being based on a "conjecture”, respectively an evolutionary, a critical, and a cosmopolitan, and conjecture. The evolutionary conjecture implies regulatory transplants, the critical conjecture elicits competition of Covid-related measures, and the cosmopolitan conjecture assumes coordination of policies. The paper discusses how these conjectures based on pre-Covid literature could explain the regulatory dynamics and then asserts that growing evidence shows that regulatory measures appear to naturally lead to a "polity convergence” based on a common core of "Covid-biopower” and "Covid-biopolitics”. This convergence defies the initial expectations that the fragmented reactions to the Covid crisis could be explained by using the traditional research tools and also poses unprecedented critical issues that demand an expansion of the horizon of policy research.

Implementation of Blockchain Technology Could Increase Equity and Transparency in Organ Transplantation: A Narrative Review of an Emergent Tool.

In the last few years, innovative technology and health care digitalization played a major role in all medical fields and a great effort worldwide to manage this large amount of data, in terms of security and digital privacy has been made by different national health systems. Blockchain technology, a peer-to-peer distributed database without centralized authority, initially applied to Bitcoin protocol, soon gained popularity, thanks to its distributed immutable nature in several non-medical fields. Therefore, the aim of the present review (PROSPERO N° CRD42022316661) is to establish a putative future role of blockchain and distribution ledger technology (DLT) in the organ transplantation field and its role to overcome inequalities. Preoperative assessment of the deceased donor, supranational crossover programs with the international waitlist databases, and reduction of black-market donations and counterfeit drugs are some of the possible applications of DLT, thanks to its distributed, efficient, secure, trackable, and immutable nature to reduce inequalities and discrimination.

Patients who are candidates for treatment with monoclonal antibodies for pre-exposure prophylaxis of COVID-19

Background and ImportanceCilgavimab/tixagevimab are recombinant human IgG1ĸ monoclonal antibodies, which are indicated for COVID-19 pre-exposure prophylaxis in adults and adolescents ≥12 years of age weighing ≥40 kg.Aim and ObjectivesTo assess patients who are potential candidates for treatment with cilgavimab/tixagevimab in a tertiary care hospital and to describe the search strategy.Material and MethodsIn Spain, potential candidates for treatment with cilgavimab/tixagevimab are people with a high degree of immunosuppression (due to pathology or treatment) who do not respond adequately to vaccination. The Spanish Agency of Medicines and Health Products establishes the conditions for patients who are candidates for treatment with cilgavimab/tixagevimab1 . A search for patients was carried out, prioritising the following criteria: haematological patients on treatment with rituximab during the last 9 months, patients with solid organ transplant, patients with multiple sclerosis on treatment with ocrelizumab/rituximab, and patients with recent infection by COVID-19 who belong to any risk group. All of them underwent serology, including in the study those with negative serology (anti-anati-S antibodies < 260 BAU/ml). Those patients were scheduled for cilgavimab/tixagevimab administration.Results112 patients (38 = haematological patients on rituximab treatment, 50 = multiple sclerosis patients on rituximab/ocrelizumab treatment and 24 = kidney transplantation) were enrolled. 72 patients were included, 38 women (52.8%), median age 59.5 years old (27-77). The cause of exclusion was positive serology in all cases. 64 patients (88.9%) were on treatment with biologic immunomodulators (35 haematologic patients treated with rituximab <9 months, 27 patients with multiple sclerosis on treatment with rituximab/ocrelizumab/interferon beta-1A and 1 patient on treatment with adalimumab) and the rest were kidney transplant patients. Cilgavimab/tixagevimab was administered to 62 patients (86.1%), 7 patients with unknown reasons, 2 patients had COVID-19 infection and 1 patient had to be excluded for deep vein thrombosis due to the development of symptoms at the time of the appointment.Conclusion and RelevanceMore than half of the patients enrolled did not have an adequate response to COVID-19 vaccination. The search strategy was a good tool for administering pre-exposure prophylaxis of COVID-19 to these more vulnerable patients. Further studies are needed to evaluate the effectiveness of the treatment.References and/or Acknowledgements1. https://www.aemps.gob.es/la-aemps/ultima-informacion-de-la-aemps-acerca-del-covid%E2%80%9119/prevencion-frente-a-la-covid-19/personas-candidatas-a-recibir-evusheld-en-espana/#:~:text=En%20Espa%C3%B1a%2C%20son%20potenciales%20candidatas,responden%20adecuadamente%20a%20la%20vacunaci%C3%B3n.Conflict of InterestNo conflict of interest

UPSKILLING ONCOLOGY NURSES TO COMPETENCY WITH CAR-T INFUSION AND MANAGEMENT

The COVID-19 pandemic has forever changed the way we manage transplant patients. With the additional challenge of maintaining safety for transplant patients while accounting for COVID infections, there was a need to expand bed availability beyond the dedicated HSCT (Hematopoietic Stem Cell Transplant) Unit at New York Presbyterian: Weill-Cornell. Due to HEPA filtration and inability to change rooms to negative pressure, the dedicated HSCT unit, 10 West, is unable to accommodate COVID+ patients. The purpose of this initiative was to increase bed capacity and broaden oncology nurse knowledge by training them in administration and management of CAR-T patients. HSCT nurses identified the Autologous HSCT/Oncology unit, 10 North, as the target for this intervention due to the nurses' baseline transplant knowledge. 10 West nurses noted education gaps among 10 North nurses' knowledge of CAR-T using a 10-question electronic assessment. From January to March 2022, the team planned, coordinated, and executed multiple educational sessions for nurses and ancillary staff which were built on the previous autologous transplant education they had received in 2017. The first educational sessions were performed at multiple morning huddles. These focused on CAR-T management including education about chemotherapy, cell administration, patient monitoring post infusion, and emergencies. More in-depth educational sessions were offered in an hour-long lecture format. After these educational sessions were completed by 100% of the 10 North staff, we identified additional learning gaps and follow-up education was created and dispersed amongst the staff. Follow-up education was provided at regular monthly intervals. Upskilling the 10 North nursing team resulted in the successful administration of 10 CAR-T transplants in 2022. As of September 2022, the CAR-T program at New York Presbyterian has surpassed 2021 total CAR-T administrations, with 37 CAR-T transplants year-to-date.

ACIP Approves 2023 Child/Adolescent and Adult Immunization Schedules

The 2023 child/adolescent and adult immunization schedules have been approved by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) and are accessible at https://www.aafp.org/family-physician/patient-care/prevention-wellness/immunizations-vaccines.html. These schedules include links to COVID-19 vaccination information, vaccination information statements, adverse event reporting, and a QR code for online schedules. Notable changes include updates to COVID-19 recommendations and mpox (formerly monkeypox) vaccination.

Smartphones as a Platform for Tourism Management Dynamics during Pandemics: A Case Study of the Shiraz Metropolis, Iran

During the past three years and with the spread of the pandemic, smartphones were the most important communication bridge between tourists and organizations;now more than ever, they are intertwined with the lives of tourists and destination management organizations. Although much research has been conducted in this field, the investigation of the effects of the pandemic on the technology and functionality of smartphones is one of the topics that has been less discussed. Therefore, the current research was conducted to determine the role of smartphones in tourism management dynamics during the pandemic. The research method was qualitative (content analysis, theme analysis), and 32 people participated in the interview process as a statistical sample. Then, the oral interviews were transcribed, and a thematic analysis was performed. For the analysis of the interviews, MAXQDA 2020 software was used. The results of the research indicate that smartphones were one of the most important platforms for tourism management dynamics during the pandemic, and in the event of a pandemic in the future, they can help contain the destruction to a great extent in their current position.

COVID-19 in pediatric lung transplant recipients: Clinical course and outcome.

BACKGROUND: COVID-19 causes high morbidity and mortality in adult lung transplant (LTX) recipients. Data on COVID-19 in children after LTX is limited. We report the clinical presentation and outcome of SARS-CoV-2 infection in 19 pediatric LTX recipients. METHODS: Between March 2020 and June 2022, SARS-CoV-2 testing was performed on all pediatric LTX patients with COVID-19 symptoms or contact with a SARS-CoV-2 infected person. Positive patients were prospectively evaluated for symptoms, treatment and outcome. Vaccination status and immune response were recorded. RESULTS: Nineteen out of 51 pediatric LTX recipients had a SARS-CoV-2 infection. Mean age was 12.3 years (IQR 9-17), 68% were female, 84% had preexisting comorbidities. Mean time between LTX and SARS-CoV-2 infection was 4.8 years (IQR 2-6). No patients experienced severe COVID-19: 11% were asymptomatic, and 89% had mild symptoms, primarily rhinitis (74%), fever (47%), and cough (37%). One SARS-CoV-2 positive patient was hospitalized due to combined fungal and bacterial infection. Mean duration of symptoms was 10.5 days (IQR 3-16), whereas mean period of positivity by antigen test was 21 days (IQR 9-27, p = 0.013). Preventive antiviral therapy was initiated in 3 patients. After a mean follow-up of 2.5 months (IQR 1.1-2.4), no patient reported persistent complaints related to COVID-19. Lung function tests remained stable. CONCLUSIONS: Unlike adult LTX recipients, children and adolescents are at low risk for severe COVID-19, even with risk factors beyond immunosuppression. Our findings cast doubt on the necessity of excessive isolation for these patients and should reassure clinicians and caregivers of LTX patients.

Viral Cultures, Cycle Threshold Values and Viral Load Estimation for Assessing SARS-CoV-2 Infectiousness in Haematopoietic Stem Cell and Solid Organ Transplant Patients: A Systematic Review.

BACKGROUND: Solid organ and haematopoietic stem cell transplant recipients are at increased vulnerability to SARS-CoV-2 due to immunosuppression and may pose a continued transmission risk especially within hospital settings. Detailed case reports including symptoms, viral load and infectiousness, defined by the presence of replication-competent viruses in culture, provide an opportunity to examine the relationship between clinical course, burden and contagiousness, and provide guidance on release from isolation. OBJECTIVES: We performed a systematic review to investigate the relationship in transplant recipients between serial SARS-CoV-2 RT-PCR cycle threshold (Ct) value or cycle of quantification value (Cq), or other measures of viral burden and the likelihood and duration of the presence of infectious virus based on viral culture including the influence of age, sex, underlying pathologies, degree of immunosuppression, and/or vaccination on this relationship. METHODS: We searched LitCovid, medRxiv, Google Scholar and WHO Covid-19 databases, from 1 November 2019 until 26 October 2022. We included studies reporting relevant data for transplantees with SARS-CoV-2 infection: results from serial RT-PCR testing and viral culture data from the same respiratory samples. We assessed methodological quality using five criteria, and synthesised the data narratively and graphically. RESULTS: We included 13 case reports and case series reporting on 41 transplantees including 22 renal, 5 cardiac, 1 bone marrow, 2 liver, 1 bilateral lung, and 10 blood stem cell transplants. We observed a relationship between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Three individuals shed replication-competent viruses for over 100 days after infection onset. Lack of standardisation of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, the majority of transplantees stopped shedding replication-competent viruses when the RT-PCR cycle threshold was above 30 despite differences across platforms. CONCLUSIONS: Viral burden is a reasonable proxy for infectivity when considered within the context of the clinical status of each patient. Standardised study design and reporting are essential to standardise guidance based on an increasing evidence base.

A Brief Review on Covid-19 associated Mucormycosis

Risk factors include uncontrolled diabetes mellitus, especially ketoacidosis, steroid use, age, neutropenia Mucormycosis diagnosis involves a careful examination of clinical manifestations, magnetic resonance imaging modalities, early use of computed tomography (CT). No Types Route of transmission 1 Rhinocerebral (sinus and brain) Mucormycosis Inhalation of spores into the of spores into the paranasal sinuses and the invasion of blood vessels in the tissue 2 Pulmonary (lung) Mucormycosis Inhalation of infectious material 3 Gastrointestinal Mucormycosis The ingestion of contaminated food/ herbal medicine 4 Cutaneous (skin) Mucormycosis Skin infection by direct inoculation and in secondary form, by dissemination from other locations. 5 Disseminated Mucormycosis Blood stream Etiopathogenesis: The mucous membrane penetrates deep tissues, swallowing or inhaling spores and injecting them into the skin. Risk factors include uncontrolled diabetes mellitus, especially ketoacidosis, steroid use, age, neutropenia;Voriconazole, especially for the prevention of blood cancer, AIDS, renal failure, organ or stem cell transplantation, iron overload, skin trauma, broad-spectrum antibiotics, intravenous drug use, aspergillosis and malnutrition7,11 Mucormycosis can also occur in patients without overt immunodeficiency. According to statistics

A rare case of central diabetes insipidus unmasked after renal transplantation in a young male

Background: The diagnosis of central Diabetes insipidus (DI) requires intact renal function to manifest polyuria. Therefore, it may not become evident in patients with oliguric or anuric renal failure such as in chronic kidney disease (CKD) or end stage renal disease (ESRD). This might get manifested after renal transplantation, however there are only 5 cases reported so far of Central DI post renal transplantation. Here we report a case of central DI that was unmasked in a patient with CKD after kidney transplantation leading to polyuria. Case Report: RV, 26-year-old male had one episode of febrile illness with hematuria at age of 20 years and was diagnosed IgA nephropathy by renal biopsy following which he recovered completely. Hypertension was detected in Feb 2021, and he has been on Cilnidipine 10 mg OD, Clonidine 0.1 mg TDS, Metoprolol XL 40 mg OD. At age of 25 years, he had covid illness and his kidney function deteriorated to ESRD for which he was started on twice weekly hemodialysis for 8 months and then underwent live donor renal transplantation in October 2021. Two months later, he was admitted for polyuria, polydipsia, and nocturia. After renal transplantation, his urine volume increased to 9-10 L/ d, while it had been less than 500 mL/day before the transplantation. His serum creatinine level improved from 3.2 mg/dL prior to transplant to 0.8 mg/dL after transplant. He had not been diagnosed with diabetes before, and his blood glucose levels were within the normal range. He showed no symptoms of polyuria or polydipsia before transplantation and had no history of head trauma or neurosurgery. Diagnosed to have primary hypothyroidism in Feb 2021 during pre-transplant workup, for which he was started on levothyroxine 50 ug and was euthyroid. The patient received prednisolone, tacrolimus, mycophenolate mofetil, and sulfamethoxazole/trimethoprim after the transplantation. During evaluation for polyuria, urine volume was >100 ml/kg in 24 Hour. Serum osmolality of 295 mOsm/kg, urine osmolality of 101 mOsm/kg, and serum sodium of 138 mEq/L, RBS 86 mg/dl, Urea 24 mg/dl. Anterior pituitary hormone profile workup was normal. To evaluate the cause of polyuria, water deprivation test was performed which confirmed complete central diabetes insipidus. He was started on oral desmopressin 120 ug in divided doses. His urine output subsequently decreased to about 2.5 L/d with resolution of excessive thirst and nocturia. MRI sella revealed normal anterior pituitary, infundibulum and diminished posterior pituitary bright spot in the T1-weighted image. Patient is continued on desmopressin therapy at 6 months with marked improvement in symptoms. Conclusion: In this case, the water deprivation test and diminished posterior pituitary bright spot-on MRI and the responsiveness to desmopressin therapy confirm the diagnosis of central DI. Hence, any case of polyuria after renal transplantation must be evaluated for Central Diabetes Insipidus.

Overcoming the post-processing barriers for 3D-printed medical models

Purpose>The purpose of this study is to identify, analyse and model the post-processing barriers of 3D-printed medical models (3DPMM) printed by fused deposition modelling to overcome these barriers for improved operational efficiency in the Indian context.Design/methodology/approach>The methodology used interpretive structural modelling (ISM), cross-impact matrix multiplication applied to classification (MICMAC) analysis and decision-making trial and evaluation laboratory (DEMATEL) to understand the hierarchical and contextual relations among the barriers of the post-processing.Findings>A total of 11 post-processing barriers were identified in this study using ISM, literature review and experts' input. The MICMAC analysis identified support material removal, surface finishing, cleaning, inspection and issues with quality consistency as significant driving barriers for post-processing. MICMAC also identified linkage barriers as well as dependent barriers. The ISM digraph model was developed using a final reachability matrix, which would help practitioners specifically tackle post-processing barriers. Further, the DEMATEL method allows practitioners to emphasize the causal effects of post-processing barriers and guides them in overcoming these barriers.Research limitations/implications>There may have been a few post-processing barriers that were overlooked by the Indian experts, which might have been important for other country's perspective.Practical implications>The presented ISM model and DEMATEL provide directions for operation managers in planning operational strategies for overcoming post-processing issues in the medical 3D-printing industry. Also, managers may formulate operational strategies based on the driving and dependence power of post-processing barriers as well as the causal effects relationships of the barriers.Originality/value>This study contributes to identifying, analyzing and modelling the post-processing barriers of 3DPMM through a combined ISM and DEMATEL methodology, which has not yet been reviewed. This study also contributes to decision makers developing suitable strategies to overcome the post-processing barriers for improved operational efficiency.

Nosocomial outbreak of δ (delta) variant SARS-CoV-2 on a liver transplant unit: A complex epidemiologic and genomic investigation

Background: In late September 2021, a cluster of patients with nosocomial COVID-19 was identified on a liver transplant unit at University of Nebraska Medical Center. Methods: The outbreak investigation included contact tracing via patient chart and employee health record reviews and serial prevalence testing for SARS-CoV-2 among potentially exposed patients and healthcare workers (HCWs). Routine admission and preprocedural screening for SARS-CoV-2 was performed, and involved patients had negative admission screening results with positive SARS-CoV-2 tests >5 days from admission. Mitigation strategies involved reinforcement of patient care and visitation procedures. Whole-genome sequencing of positive SARS-CoV-2 specimens was conducted. Results: The potential outbreak cluster included 6 patients in the same quadrant of the liver transplant unit, 1 visitor, and 11 healthcare workers (Fig. 1). Moreover, 4 patients had severe liver disease, including 2 with liver transplants. All HCWs and half of the patients had received 2 doses of mRNA vaccine, albeit >5 months from their second vaccination. Whole-genome sequencing confirmed patients 1–6 and HCWs 1–3 had related transmission of COVID-19. However, infections in HCWs 4–6, who worked in a transplant-related office setting without patient contact, were due to 2 separate introductions of SARS-CoV-2 unrelated to the hospital outbreak. Sequencing could not be performed on HCWs 7–11 due to low viral concentration in the original specimens or unavailable specimen. The SARS-CoV-2 δ (delta) variant (B.1.617.2) was identified in all sequenced samples. HCWs 8–10 were asymptomatic and had had contact with each other and had been involved with an intubation without proper PPE for SARS-CoV-2 on patient 6. HCW 8 had had contact with all 6 patients and HCW 9 had had contact with 5 patients. A clear index case could not be identified;however, we suspect that the index case was either visitor 1, who tested positive during patient 2's admission, or an asymptomatic healthcare worker (HCWs 8–10). Conclusions: We identified a nosocomial outbreak of the SARS-CoV-2 δ (delta) variant in a solid-organ transplant unit including patients, a visitor, and vaccinated healthcare workers with multiple introductions of the virus. Further transmission was not detected after enhanced infection control measures were introduced, including universal masking and eye protection, closing patient doors, and enforcement of visitor masking policy. We describe the difficulties tracing SARS-CoV-2 transmission in the hospital setting, even with advanced sequencing techniques. This outbreak highlights the importance of booster vaccination and strict infection control practices, especially in the setting of the δ (delta) variant.Funding: NoneDisclosures: None

Pathogenetic Mechanisms of Liver-Associated Injuries, Management, and Current Challenges in COVID-19 Patients.

The global outbreak of COVID-19 possesses serious challenges and adverse impacts for patients with progression of chronic liver disease and has become a major threat to public health. COVID-19 patients have a high risk of lung injury and multiorgan dysfunction that remains a major challenge to hepatology. COVID-19 patients and those with liver injury exhibit clinical manifestations, including elevation in ALT, AST, GGT, bilirubin, TNF-α, and IL-6 and reduction in the levels of CD4 and CD8. Liver injury in COVID-19 patients is induced through multiple factors, including a direct attack of SARS-CoV-2 on liver hepatocytes, hypoxia reperfusion dysfunction, cytokine release syndrome, drug-induced hepatotoxicity caused by lopinavir and ritonavir, immune-mediated inflammation, renin-angiotensin system, and coagulopathy. Cellular and molecular mechanisms underlying liver dysfunction are not fully understood in severe COVID-19 attacks. High mortality and the development of chronic liver diseases such as cirrhosis, alcoholic liver disease, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatocellular carcinoma are also associated with patients with liver damage. COVID-19 patients with preexisting or developing liver disease should be managed. They often need hospitalization and medication, especially in conjunction with liver transplants. In the present review, we highlight the attack of SARS-CoV-2 on liver hepatocytes by exploring the cellular and molecular events underlying the pathophysiological mechanisms in COVID-19 patients with liver injury. We also discuss the development of chronic liver diseases during the progression of SARS-CoV-2 replication. Lastly, we explore management principles in COVID-19 patients with liver injury and liver transplantation.

Regulatory Competition, Coordination and Polity Convergence in the Covid Ecosystemic Crisis: A Policy Approach

The paper briefly sketches different "adaptations"possible to address the Covid crisis and then advances three possible avenues for future policy analysis of Covid-related measures, each of these avenues being based on a "conjecture", respectively an evolutionary, a critical, and a cosmopolitan, and conjecture. The evolutionary conjecture implies regulatory transplants, the critical conjecture elicits competition of Covid-related measures, and the cosmopolitan conjecture assumes coordination of policies. The paper discusses how these conjectures based on pre-Covid literature could explain the regulatory dynamics and then asserts that growing evidence shows that regulatory measures appear to naturally lead to a "polity convergence"based on a common core of "Covid-biopower"and "Covid-biopolitics". This convergence defies the initial expectations that the fragmented reactions to the Covid crisis could be explained by using the traditional research tools and also poses unprecedented critical issues that demand an expansion of the horizon of policy research. © 2022 Walter de Gruyter GmbH, Berlin/Boston 2022.

An overview

[...]damage to tissue and blood vessels from Covid-19 infection, treatment with corticosteroids, high background rates of diabetes in the population most brutally affected by the coronavirus are also getting affected by life threating fungal infection called as mucormycosis. Mucorales also found in decomposing food, bird and animal excretions, water and air around construction sites, and moist environments.17 They are more common in soil than in air, and in summer and fall than in winter or spring.18,19 The primary reason that appears to be facilitating Mucorales spores to germinate in people with COVID-19 is an ideal environment of low oxygen (hypoxia), high glucose (diabetes, new-onset hyperglycemia, steroid-induced hyperglycemia), acidic medium (metabolic acidosis, diabetic ketoacidosis [DKA]), high iron levels (increased ferritins) and decreased phagocytic activity of white blood cells (WBC) due to immunosuppression (SARS-CoV-2 mediated, steroid-mediated or background comorbidities) coupled with several other shared risk factors including prolonged hospitalization with or without mechanical ventilators. Damaged tissue can occur after suffering or surgery due to use of drugs which suppress the immune system such as corticosteroids can lead to weakened immune function, as can a range of other immunocompromising conditions, like cancer or transplants.21 There are three ways humans can affect by mucormycosis first by swallowing spores in food or medicines, secondly by inhaling spores and last by swallowing spores in food or medicines, or when spores contaminate wounds.28,29 Among these three ways, inhalation is the most common. Symptoms: Mucormycosis have the different symptoms rhinocerebral mucormycosis include discrete blackish discolouration on the bridge of the nose, pain on only one side of the face, cheekbones, with lack of sensation and bulging sinusitis, along with clogging of the nasal tract and bloody or blackish mucus emission from the nose prominent aching in teeth, jawbone, degrading of tooth structures, objects appearing blurred or in double, with eye pain abnormal blood clotting or thrombosis of tissues, along with skin injury and damage or necrosis of dermal cells and deterioration of respiratory functions, with chest pain.