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Background & Aim: Immunocompromised patients are susceptible to high-risk opportunistic infections and malignant diseases. If available, most antiviral and antifungal drugs are quite toxic, relatively ineffective, and induce resistance in the long term. Methods, Results & Conclusion(s): We have previously demonstrated the safety of adoptive cell therapy for COVID-19 patients with CD45RA negative cells containing SARS-CoV-2-specific T cells from a donor, chosen based on HLA compatibility and cellular response to SARS-CoV-2 peptide pools. After finishing a Phase 2 randomized multicenter clinical trial (RELEASE, NCT04578210), we concluded that the infusion is safe, effective, accelerates lymphocyte recovery and shows hallmarks of an immune response. To use adoptive cell therapy to treat COVID-19 it would be necessary to develop a biobank of living drugs. For that, we examined the immune evolution performing a longitudinal analysis from previously SARS-CoV-2 infected and infection- naive individuals covering 21 months from infection. Cellular responses were maintained over time while humoral responses increased after vaccination but were gradually lost. Therefore, the best donors would be recovered individuals and two months after vaccination. We also evaluated the effect of dexamethasone (current standard of care treatment for COVID-19 and other infections involving lymphopenia) and Interleukin-15 (cytokine involved in T-cell maintenance and survival) on CD45RA negative. Dexamethasone did not alter cell functionality, proliferation or phenotype at a clinical-practice concentration, while interleukin-15 increased the memory T-cell and T-regulatory cell activation state, and interferon gamma release. Furthermore, we applied the adoptive passive transfer of CD45RA negative cells containing pathogen-specific memory T-cells to other infectious diseases characterized by sustained lymphopenia. We infused six immunocompromised patients with Cytomegalovirus, BK virus, Aspergillus, and Epstein-Barr virus lymphoproliferative disease. Patients experienced pathogen clearance, resolution of symptoms and lymphocyte increase. Transient microchimerism was detected in three patients. The use of CD45RA negative cells containing specific memory T cells of a third-party donor for treating severe pathogenic diseases in immunocompromised patients is feasible, safe, and effective, and has an advantage over other cell therapies such as lower costs and a less complex regulatory environment.Copyright © 2023 International Society for Cell & Gene Therapy
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The importance of providing emotional support and assistance to older adults has been highlighted by the COVID-19 pandemic. An increasing number of older adults live alone, which promotes loneliness and depression risks. Also, the digital divide exacerbates these issues and other social difficulties, since older adults are not able to use technology to communicate. A socially assistive robot could help to address these loneliness and digital divide problems. However, it is critical to incorporate affectiveness and naturalness to promote the user acceptance of the robot. This project makes use of the existing EVA open-source robotics platform. The aim is to improve the quality of life of older adults by boosting their independence and alleviating loneliness or other emotional issues that can arise. To improve the user acceptance and to get a more natural, affective, non-passive behavior, this paper contributes to integrate several aspects to the EVA robot: a) assistiveness through conversations and a social messaging end-user skill to reduce the digital divide;b) proactivity by means of proactive interventions so EVA is able to start conversations;c) affectivity by means of showing emotions with eyes expressions, user recognition and emotion analysis in user input;and d) naturalness by blending all these characteristics with a low response time in the interaction and the novel wakeface activation method. Finally, a technical evaluation of the proposed solution provides evidence of its appropriate performance. © 2023, The Author(s), under exclusive license to Springer Nature Switzerland AG.
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Background: The EPISER study is the frst Spanish epidemiological study that has confrmed the great burden of rheumatic diseases in the general population: they consume a large quantity of health resources (doctor visits, medical products) and imply a high social impact in terms of work absenteeism. Rheumatic diseases represent almost 30% of Primary Care medical consultations in Spain1,2. Electronic consultation could be an alternative response to the increase of this demand, both to make an early diagnosis and derivation and to improve communication with Primary Care physicians3,4. Objectives: To analyze the demand of Primary Care and its resolution through the electronic consultation system of the Rheumatology Department of a tertiary hospital. Methods: Retrospective descriptive study of the data collected in the request and information system (Sistema de Peticiones Electrónicas, SIPE) that supports electronic consultation between primary care physicians of the health area and the Rheumatology Department of a tertiary hospital, between July 2020 and May 2021.The following variables were collected: age, sex, reason for consultation, response time in days and destination (primary care/outpatient follow-up). Descriptive statistics were used to present the results. Results: The last 500 consecutive electronic consultations registered in the system, referring to 496 patients, were collected. Mean age was 59.5±17.7 years;74.2% women. Mean response time was 2 days, median response time 1 day and range 0-45. The reasons for consultation (see Graph 1) were: osteoporosis assessment 55 (11%), treatment adjustment 50 (10%), appointment request 49 (9.8%), loss to follow-up 43 (8.6%), local-regional pathology assessment 39 (7.8%), infltration request 28 (5, 6%), suspected rheumatoid arthritis 19 (3.8%), fare 18 (3.6%), suspected polymyalgia rheumatica or giant cell arteri-tis 16 (3.2%), COVID vaccine consultation 14 (2.8%), Raynaud's phenomenon 13 (2.6%), monoarthritis assessment 12 (2.4%), assessment of polyarthritis 11 (2.2%), adverse effects of treatment 11 (2.2%), suspected spondyloarthritis 11 (2.2%), suspected psoriatic arthritis 8 (1, 6%), generalized pain 7 (1.4%), suspected Sjögren's syndrome 5 (1%), suspected systemic lupus erythematosus 1 (0.2%), suspected other systemic autoimmune diseases 9 (1.8%), others 81 (16.2%). Fifty-seven and four % (287) of the patients required an appointment at the Rheumatology outpatient clinic and in 42.6% of the patients (213) the electronic consultation was successful, so it was not necessary to refer the patient to the hospital. Conclusion: Forty-two and six percent of the queries were resolved thanks to the electronic consultation system in an average of two days, otherwise that patients would have been referred to specialized care. The main reasons for consultation were osteoporosis assessment and clarifcation of doubts about the treatment of patients who were already being followed up by the Rheumatology Department.
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Background and aims: Small fiber neuropathy (SFN) is a polymorphous disease affecting thin nervous fibers conducting temperature and pain sensations and involved in autonomic transmission. Etiology is diverse and remains elusive in 70% of cases. Methods: We describe a case series of 6 patients who developed symptoms of SFN following SARS-COV-19 vaccination. Neurologic examination was normal whilst paraclinical results were consistent with SFN. Confirmation by skin biopsy was obtained in 4 cases. Results: Six patients, 5 female and 1 male, ages 31, 34, 39, 42, 44 and 62 years, consulted our department with intense pain and numbness involving the arms and legs 2 to 15 days following SARS-COV-19 vaccination. Neurologic examination was normal. A preliminary diagnostic protocol comprising autoimmune, metabolic, infectious and inflammatory panel, cerebral and spinal cord magnetic resonance imaging and electromyography was normal. Functional neurophysiologic testing showed reduced activation of fibers involved in sweat gland control indicating SFN. Skin biopsy of distal calf and thigh in 4 patients, three female and one male, showed rarefaction of thin intraepidermic nerve fibers in a non length dependent manner, allowing for a diagnosis of SFN. Conclusion: Whereas autoimmune, infectious, metabolic, toxic and genetic causes are well described in SFN, evidence of possible association with vaccination is confounding. Given their small caliber and richness of surface antigens, small nervous fibers are vulnerable to a wide spectrum of disease. Immunologic factors intervening on a predisposing substrate could be a hypothesis for the mechanism involved in development of SFN following SARS-COV-19 and possibly other vaccination.
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The implementation of preparedness strategies to prevent and mitigate the impact of global health threats poses several challenges. It should promptly identify cross-cutting drivers of pandemic threats, assess context-specific risks, engage multiple stakeholders, and translate complex data from multiple sources into accessible information for action. This requires a coordinated, multidisciplinary and multisectoral effort engaging systems that, most of the time, work in isolation. The One Health (OH) approach promotes the collaboration and communication among different disciplines and sectors, and could be applied across the preparedness phases at national and international level. We discuss here gaps and needs in preparedness strategies, which can benefit from the OH approach, and a set of actionable recommendations, as shared with the G20-2021 with a dedicated Policy Brief. The discussion adds to the current debate about OH operationalization and promotes a paradigm shift towards coordinated prevention and preparedness strategies for early assessment and management of global health threats.
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The article aims to analyze the Peruvian educational system through the context of a pandemic, highlighting the influence of the neoliberal economic model on the policies proposed in the face of the health emergency. This is why the need to identify current educational gaps in order to recognize perennial inequalities as a result of poor government management capacity to guarantee quality education. From this perspective, an assessment of capitalist influence and its impact on the conduct of competitive demands in digital education is also carried out, as well as the limited response and prevention capacity in the face of the eventual crisis that afflicts not only Peru, but also to the entire Latin American region. In this sense, this research is developed from a qualitative approach under the methodology of theory based on an exploratory and descriptive framework of the previously described phenomenal situation. © 2022 Universidad Nacional Experimental Rafael Maria Baralt. All Rights Reserved.
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Introduction & Objectives: Indwelling ureteric stents are valuable devices used in emergency drainage of upper urinary tract obstruction due to ureteric stones. However, stents can cause significant morbidity with infections, encrustations and blockages. In the study we look at the outcomes of pre-operative stent dwell time on infectious complications following ureteroscopy and laser fragmentation (URSL). Materials & Methods: Data was retrospectively collected for outcomes of URSL from 3 European endourology centres for patients with preoperative indwelling ureteric stents. We included data for patient details, stone demographics, operative details, stone free rate (SFR), outcomes and complications between 2011 and 2020. Patients were divided into two groups based on the stent dwell time: group 1 (<6 months) and group 2 (≥6 months). Descriptive statistics were used to determine the rate of early post-operative infectious complications (defined as the presence of fever?) and ICU access. Binomial logistic regression analysis were used to explore the relationship between stent dwelling time and post-operative early infectious complications. (SPSS v.24). Results: There were 501 patients undergoing URSL in the study period, with 429 and 72 patients in groups 1 and 2 respectively (Table 1). The mean age and operative time in groups 1 and 2 were 71±30 years and 64±22 years, and 51±28 minutes and 59±31 minutes respectively. Infectious complications and ICU admissions were seen in 32 (8%) and 3 (0.7%), and 22 (31%) and 1 (1.4%) in groups 1 and 2 respectively. Stent dwell time of ≥6 months carried significantly higher risk for febrile UTI post URSL (RR=5.45, 95% CI: 2.94-10.10, p<0.001). (Table Presented) Conclusions: Although the overall risk of infectious complication rates from URSL were low, longer indwelling stent time significantly increases the risk of post-operative infections, of which a small proportion of patients end up in ICU. We would recommend having the stent dwell time as short as possible and not to exceed a 6 months’ time period, and our findings will help prioritise these patients in the post-COVID era.
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Background: The COVID-19 pandemic modified the way of practicing medicine, causing a changes in medical actions in the health professional and in their habits in relation to daily practices. Accelerated changes have taken place, which have led to the development and implementation of telemedicine as a very useful tool that allows professional contact with their patients, and on the other hand, access to up-to-date scientific training. Objetive: Evaluate the impact of the COVID-19 pandemic on the activity of the allergist in Argentina during phase 1 of preventive and mandatory social isolation (april and may 2020). Determine the impact of the pandemic on allergic diseases. Analyze the use of telemedicine in daily practice. Method: It is a prospective, observational and cross-sectional study. A questionnaire was made to specialist doctors in Allergy and Immunology during april and may 2020 of preventive and compulsory social isolation, for subsequent statistical study. Results: 113 surveys were carried out, 72.9% showed a decrease in work practice by 50%, 20.7% between 25-50% and 6.3% less than 25%. The most frequent consultations were request for prescriptions in 67%, medical history certificates in 48%, rhinitis and urticaria in 46%, atopic dermatitis and asthma attack in 23%, and contact dermatitis in 5.3%. 94% implemented telemedicine, the most used tools were whatsapp/webcam (61%) followed by telephone assistance (38%). Conclusion: The COVID-19 pandemic affected the practice of the specialty in terms of the decrease in medical consultation, the way of working, interacting with patients, the need for protective equipment, with an emotional and economic cost. On the other hand, it gave the possibility of having other care alternatives such as telemedicine.
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Introduction: Indwelling ureteric stents, usually inserted for emergency drainage of an obstructed system, can cause significant morbidity with infections. We aimed to assess pre-operative stent dwell time on infectious complications following ureteroscopy and laser fragmentation (URSL). Material and Methods: Data was retrospectively collected for outcomes of URSL from 3 European endourology centres for patients with pre-operative indwelling ureteric stents. We included data for patient details, stone demographics, operative details, stone free rate (SFR), outcomes and complications between 2011 and 2020. Patients divided into group 1 (<6 months stent dwell time) and group 2 (6 months). Primary outcomes were early post-operative infectious complications (febrile UTI) and ICU access. Analysis with binomial logistic regression (SPSS v.24). Results: 501 patients were included (group 1, n=429;group 2, n=72) [Table 1]. Mean age and operative time in groups 1/2 were 71-30 years and 64-22 years, and 51-28 minutes and 59-31 minutes. Febrile UTI and ICU admissions were seen in 32(8%) and 3(0.7%), and 22(31%) and 1(1.4%) in groups 1/2 respectively. Stent dwell time of 6 months carried significantly higher risk for febrile UTI post URSL (RR=5.45, 95% CI: 2.94-10.10, p<0.001) [see fig 1]. Conclusion: Although the overall risk of infectious complication rates from URSL were low, longer indwelling stent time significantly increases the risk of post-operative infections. We would recommend having the stent dwell time as short as possible and not to exceed 6 months. Our findings will help prioritise these patients in the post-COVID era.
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Syndrome coronavirus 2 (SARS-CoV-2) pandemic is causing a second outbreak significantly delaying the hope for the virus' complete eradication. In the absence of effective vaccines, we need effective treatments with low adverse effects that can treat hospitalized patients with COVID-19 disease. In this study, we determined the existence of SARS-CoV-2-specific T cells within CD45RA- memory T cells in the blood of convalescent donors. Memory T cells can respond quickly to infection and provide long-term immune protection to reduce the severity of COVID-19 symptoms. Also, CD45RA- memory T cells confer protection from other pathogens encountered by the donors throughout their life. It is of vital importance to resolve other secondary infections that usually develop in patients hospitalized with COVID-19. We found SARS-CoV-2-specific memory T cells in all of the CD45RA- subsets (CD3+, CD4+, and CD8+) and in the central memory and effector memory subpopulations. The procedure for obtaining these cells is feasible, easy to implement for small-scale manufacture, quick and cost-effective, involves minimal manipulation, and has no GMP requirements. This biobank of specific SARS-CoV-2 memory T cells would be immediately available "off-the-shelf" to treat moderate/severe cases of COVID-19, thereby increasing the therapeutic options available for these patients.
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Introduction: SARS-CoV-2 causing COVID-19 has rapidly spread around the world with the first German cluster emerging in the area around Heinsberg. Mortality rates are reported to vary between 1-14%. While end-stage renal disease is a putative risk factor for adverse outcomes of COVID-19, the impact of carrying a renal transplant (KTX) versus being on chronic hemodialysis (HD) is not well defined. Methods: We describe a cohort of 21 patients on renal replacement therapy (7 KTX and 11 HD treated for COVID-19 plus 3 asymptomatic HD carriers of SARS-CoV-2) in the Heinsberg area. Data were collected systematically via the two local dialysis care providers specifically serving the area as well as the local tertiary care hospital and renal transplant center at the University Hospital Aachen. All patients were followed for the entire course of the disease over a median of 66 days (40-71 IQR). Medication, comorbidities and clinical outcome were recorded. Results: Of the seven KTX patients four were hospitalized with an acute respiratory distress syndrome (ARDS), three of which died;two of fulminant multiorgan failure and one of multiple complications of intensive care medicine after prolonged weaning and viral encephalitis. These three patients also developed acute kidney injury requiring renal replacement therapy. In all hospitalized KTX recipients MPA was stopped directly upon admission while CNIs were held only as a more severe clinical course ensued. Of the 11 HD patients with COVID-19 six were hospitalized. Three developed ARDS, two of them died. While requirement for hospitalization and duration of viral RNAshedding were similar in KTX versus HD patients, the duration of illness and of hospitalization were longer in the KTX group by 8 and 14 days, respectively. Conclusion: COVID-19 has a variable course in renal transplant recipients as well as patients on chronic hemodialysis ranging from (almost) asymptomatic infection to severe ARDS with lethal outcome. Patients on renal replacement therapy seem to have a more favorable outcome than patients after kidney transplantation (mortality 18% vs. 43% following KTX). Early reduction of immunosuppression did not seem to prevent mortality.