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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
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Introduction: The Covid-19 pandemic has led to an uncomfortable and often recurrent situation in foot care services in the UK which frequently manifests in the older, White British, overweight, lone male population who often are manual workers. Result(s): These patients are unaware of local or national health promotion campaigns (e.g. iDEAL group's ACT NOW campaign, Diabetes UK's Putting Feet First) so have little awareness and education regarding potential foot problems. They are not aware of 5-to drive, eat 5 portions of fruit and vegetables a day, check your feet every day or walk 10,000 steps initiatives. They do not access public health materials and do not follow social media platforms, magazines, or newspapers. Therefore when they present in clinic, often after an emergency appointment with their GP, or an attendance at A&E, they present with significant soft tissue damage or systemic infection, frequently catastrophic tissue loss and serious co-morbidity (often in the form of renal or cardiac failure). Many require immediate hospital admission, intra-venous antibiotics, surgical debridement, vascular intervention and/or amputation. Unfortunately for some early mortality (often from an overwhelming cardio-vascular event) is the reality before they get as far as a major amputation. Discussion(s): Patients with more long-term conditions have increased risk of missing GP appointments (after controlling for number of appointments made) and are at increased risk of all-cause mortality, with those with long-term mental-health conditions who miss >2 appointments per year having >8x risk of all-cause mortality compared with those similar diagnoses who missed no appointments (McQueenie et al. 2019).
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Globally, hepatitis C (26%), alcohol (24%), and hepatitis B (23%) contribute almost equally to the global burden of cirrhosis. The contribution from nonalcoholic fatty liver disease (8%) is small but increasing. Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acuteon-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure, Cardiovascular alterations including portal hypertension trigger the formation of portocaval shunts and varices. Systemic under filling and arterial hypotension is compensated by vasoconstriction but might decline into a state of aggravated portal hypertension and cirrhotic cardiomyopathy, leading to a hyperdynamic state, microvascular dysfunction and reduced organ perfusion culminating in decompensation. The immune system is dysfunctional showing a contrary co-existence of immune paralysis and immune overstimulation leading to secondary infections and inflammatory response syndrome aggravating cardiovascular alterations but also initiating tissue injury and metabolic alteration. This transition from compensated to decompensated cirrhosis is characterised by the occurrence of ascites, variceal bleeding and/or hepatic encephalopathy or organ failures (in the case of ACLF. Precipitating events for ACLF vary between Western countries (bacterial infection, alcohol intake) and Eastern countries (flare of HBV, superimposed HAV or HEV). In the majority of patients, systemic inflammation is a major driver of progression from compensated to decompensated cirrhosis. Once the first episode of AD develops, systemic inflammation follows a chronic course, with transient periods of aggravation due to proinflammatory precipitants or bursts of bacterial translocation resulting in repeated episodes of AD. The multistate model describing the clinical outcomes of decompensated cirrhosis has been well validated. State 3 is defined by the occurrence of variceal bleeding alone, state 4 by any single non-bleeding event, state 5 by any 2 or more events and the late decompensate state by any event with organ failures either with or without ACLF. 5-year mortality across states from 3 to 5 is in the order of, respectively: 20%, 30%, 88%. With late decompensation mortality ranges between 60 and 80% at 1 year. Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes. Aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, management of hepatic encephalopathy (HE), ascites, hepatorenal syndrome, non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue, and reduce the risk of hepatocellular carcinoma. New disease-modifying agents are expected to be identified in the next few years by systematic drug repurposing and the development of novel molecules currently undergoing pre-clinical or early clinical testing. COVID-19 continues to pose a significant healthcare challenge throughout the world. Comorbidities including diabetes and hypertension are associated with a significantly higher mortality risk. Cirrhosis is associated with an increased risk of all-cause mortality in COVID-19 infection compared to non-cirrhotic patients. Patients with cirrhosis should be considered for targeted public health interventions to prevent COVID-19 infection, such as shielding and prioritisation of vaccination.
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Objective: assessment of the efficacy and safety of the use of anticoagulant, glucocorticosteroid, metabolic therapy in patients with COVID-19 at the inpatient stage of treatment. Material and methods. In February 2021, a prospective, randomized, single-center, continuous comparative study was organized on the basis of the Gomel City Clinical Hospital No. 3, which included 827 patients with moderate and severe clinical course of COVID-19. Results. Stratification of the risks of an unfavorable outcome in patients with moderate and severe clinical course of COVID-19 made it possible to optimize treatment, with the selection of optimal doses of anticoagulant and glucocorticosteroid therapy, which led to an increase in patient survival. A high level of blood lactate reflects the degree of damage to the lung tissue, the severity of the course of the disease and requires an increase in the dose of anticoagulant therapy. The use of thiotriazoline effectively reduces the level of lactate, which makes it possible to restore the energy balance of the cell. Conclusion. The use of therapeutic (intermediate) doses of anticoagulant and optimal glucorticosteroid therapy in patients at high risk of poor outcomes with moderate and severe clinical course of COVID-19, can increase the survival rate from 82.1 to 96.8%, p<0.0001. The appointment of anticoagulant therapy was complicated by "minor" bleeding in 2.13% in the main group, in 2.11% in the control group, p>0.05, and the use of glucocorticosteroids was complicated by newly diagnosed diabetes mellitus (2.13% in the main group, 1.81% in the control group, p>0.05), which allows us to consider the therapy used is safe. The use of the metabolic, antioxidant agent thiotriazoline in patients with an LDH level of more than 800 U/L and with a high risk of an unfavorable outcome led to a decrease in LDH within five days of treatment by 447.9 U/L in the main group compared with the control group by 124.0 U/L (p=0.0001), which was accompanied by an improvement in the general condition, increased physical activity, and an earlier start of rehabilitation.Copyright © 2022 by the authors.
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The COVID-19 pandemic continues to spread despite all the efforts of the medical community. The aim of the study - to identify the features of a new coronavirus infection (COVID-19) with lung tissue damage in men and women receiving inpatient treatment. Material and methods. The method of continuous sampling selected 225 patients admitted to inpatient treatment. The patients were divided in 2 groups: the 1st group - men (n=85), the 2nd group - women (n=140). Statistical processing was carried out using the IBM SPSS Statistics 22.0 program. Results. In a comprehensive study of the features of lung tissue damage by the new coronavirus infection SARS-CoV-2 in men and women was found that women received inpatient treatment more often, after ineffective outpatient treatment, the general serious condition at admission was more typical for women who had a positive result of a PCR-test for the detection of SARS-CoV-2 (p=0.038). In the presence of general clinical manifestations complaints of loss of sense of smell were more often presented by women (p=0.020). According to laboratory studies in the indicators of general clinical and biochemical blood tests, on average men often have higher levels of creatinine (p<0.001), women more often have elevated levels of ESR (p=0.003), erythrocytes (p<0.001), CRP (p=0.042) and decreased hemoglobin (p=0.029). Conclusion. In the first wave of the Wuhan pandemic of the SARS-CoV-2 virus strain women prevailed among patients admitted to inpatient treatment with lung tissue damage after ineffective outpatient treatment (p=0.038). There was a commonality in age and clinical manifestations, of the complaints in women, only loss of sense of smell was more common (p=0.020). The erythrocytosis detected in women, increased ESR and CRP, lower hemoglobin and creatinine levels are not specific for COVID-19. There were no statistically significant differences in the terms of hospitalization and the fatal outcome of the disease between men and women.Copyright © Eco-Vector, 2022.
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Aim. An online survey among social network users was conducted to assess the frequency of COVID-19 cases, the spectrum of medications used for treatment, and the subjective assessment of clinical manifestations of the disease. Material and methods. An anonymous online survey was conducted among users of various social networks using a questionnaire created on the SurveyMonkey survey and research platform. During the first month of December 2021, the survey included 23 questions regarding the clinical and demographic characteristics of respondents, the number of COVID-19 cases, clinical manifestations, and severity, as well as the need for medical help and medication. Results. 752 respondents took part in the online survey, more than 70% of them are under 50 years old. Among the respondents 59.73% had a new coronavirus infection (COVID-19). More than 40% of the participants had COVID-19 in the period from September 2020 to April 2021 (2nd wave in Russia). In 79.2% of people, the presence of a new coronavirus infection was confirmed by one of the diagnostic methods: polymerase chain reaction (PCR test), radiography, the presence of antibodies to Ig G/M, and took into account the presence of contact with infected SARS-CoV-2. 411 participants observed any clinical manifestations of the disease. Most often respondents who had COVID-19 indicated weakness, cough, dyspnea, disappearance or decrease in the acuity of smell and taste. The volume of lung tissue damage in 36.5% of cases was less than 25%. The disappearance of any clinical manifestations of the disease immediately after recovery was noted by 32.0% of respondents. Most of the patients (59.2%) sought medical help at the polyclinic, 38.9% had to self-medicate. 71.9% respondents indicated they had been vaccinated against COVID-19, but without specifying the timing and completeness of the course. Side effects after immunization (fever, weakness, soreness, and redness at the injection site) were subjectively assessed by 41.9% of respondents. Conclusion. Among the surveyed respondents, 62.7% of the disease symptoms were mild. The highest number of cases occurred in the 2nd and 4th waves of COVID-19 morbidity in Russia. Most often respondents indicated symptoms of acute respiratory infection. The complete disappearance of clinical manifestations of the disease immediately after recovery was noted by 32.0 % of respondents, and the persistence of symptoms for up to a year - 7.5. More than 70% of the participants in the online survey reported vaccination against COVID-19, but the questionnaire did not include questions about the timing of vaccinations (before or after COVID-19) and the completeness of the course.Copyright © Eco-Vector, 2023. All rights reserved.
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It is now widely accepted that SARS-CoV-2 infection can affect long-term health and quality of life. Long COVID, a type of post-acute sequelae of SARS-CoV-2 infection (PASC) characterized by persistent unexplained symptoms, has a major impact on the health of many COVID-19 survivors. Although many individuals (up to 30%) experience some limited symptoms in the weeks and months following COVID-19, the prevalence of severe disabling Long COVID is less common (perhaps <5%). Long COVID syndromes are variable and include general (e.g., fatigue) and organ-system specific symptoms (e.g., shortness of breath, palpitations, neurocognitive symptoms), as well as symptoms resembling other medically unexplained syndromes (e.g., myalgic encephalomyelitis/chronic fatigue syndrome, dysautonomia, post-exertional malaise). For reasons not yet understood, female sex is a strong predictor of Long COVID, as is the presence of certain comorbidities, particularly obesity. Mechanisms that might plausibly contribute to Long COVID include irreversible tissue damage associated with acute infection, persistence of SARS-CoV-2 antigen or possibly a viral reservoir, residual or ongoing immune activation and inflammation, reactivation of other latent human viruses, microvascular dysregulation and thrombotic events, microbial translocation, dysbiosis, and autoimmune phenomena. These mechanisms may act in isolation or in combination to drive Long COVID syndromes. Notably, many if not all of these pathways have been implicated as possible mechanisms for the excess rate of cardiovascular disease and other comorbidities in people living with HIV. Industry engagement in Long COVID research is growing, and NIH funding for clinical trials is emerging through programs such as the RECOVER Initiative. As a result, we are entering an era of experimental medicine, in which potential interventions will be used as tools to probe the biology of the disease. This presentation will provide an overview of the proposed biological mechanisms contributing to Long COVID, with a focus on the current state of evidence, human and animal models, and the emerging therapeutic agenda.
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Home accidents can cause serious injuries, disabilities, and deaths. Approximately 40 million people were treated in hospitals annually because of injuries occurring in homes, and these injuries were responsible for approximately 76% of preventable deaths. The aims of this study are to compare the home accidents in the one-year period during the pandemic and the home accidents in the one-year period before the pandemic, and to reveal how the home accidents are affected in which part of the home and in which types of injuries. A retrospective study was made of the records of patients injured in home accidents between pre-pandemic and pandemic one-year periods. The patients were classified according to age groups, gender, season, day and time of the home accident, accident type, part of the home, trauma localization and type, and severity of injuries. While 46.5% of the 581 injured patients were before the pandemic, 53.5% were in the pandemic period. The injuries increased as the number of households staying at home increased compared to the pre-pandemic period. Likewise, there was a significant increase in the number of falls from balconies and windows during the pandemic period. It is still not possible to make a definite prediction about the course of the pandemic. In this context, it is of great importance to provide information on prevention from home accidents, especially in television programs and distance education activities.Copyright © 2023, Yuzuncu Yil Universitesi Tip Fakultesi. All rights reserved.
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Outbreaks of chilblains, a hallmark sign of type I interferonopathies, have been reported during the COVID-19 pandemic. These cases occurred mostly in patients who were asymptomatic and showed negative results from PCR and serology tests for SARS-CoV-2. We hypothesized that chilblain patients are predisposed to mount a robust innate immunity against the virus, which clinically manifests as chilblains and promotes early viral clearance, thereby preventing pulmonary disease and precluding adaptive responses. By profiling skin lesions in the early stage following chilblain onset, we uncover a transient IRF7-dependent type I interferon (IFN) signature that is driven by the acral infiltration of systemically activated plasmacytoid dendritic cells (pDCs). Patients' peripheral blood mononuclear cells (PBMCs) demonstrate increased production of IFNalpha when exposed to SARS-CoV-2 and influenza A, but not herpes simplex virus 1 (HSV-1), indicating a heightened ability to detect RNA -but not DNA- viruses. Further investigations revealed enhanced responsiveness of pDCs in chilblain patients to the RNA sensor TLR7, but not the DNA sensor TLR9. Collectively, our study establishes a two-step model for the immunopathology of SARS-CoV-2-related chilblains: enhanced TLR7 immunity in pDCs, likely triggered by SARS-CoV-2 exposure at the mucosal site, leads to prompt viral clearance, which explains the lack of infection markers in most cases. Subsequently, systemic spread of activated pDCs and infiltration of the toes in response to mechanical stress or acral coldness, may result in IFN-mediated tissue damage with development of chilblains.Copyright © 2023
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Coronavirus disease 2019 (COVID-19) predominantly manifests with signs of respiratory system injury;however, multi-systemic manifestations may occur. Renal pathology develops in up to 80% of patients with COVID-19. The aim of the study was to describe the case of isolated massive polyuria of unknown etiology in the patient with severe COVID-19-related pneumonia complicated by pulmonary embolism (PE). A 54-year-old male with bilateral pneumonia, related to COVID-19, developed PE. The next day after successful thrombolysis with alteplase (90 mg) the diuresis of the patient began to increase and fluctuated between 5000 mL and 8000 mL. The diuresis returned to normal ranges two weeks after PE episode. The rise of the diuresis was not accompanied by electrolyte disorders and elevation of serum creatinine. Changes in the urine tests were minimal, only once the urine protein was detected (0.25 g/L). The highest urine excretion was observed in evening hours (16.00-24.00). Chest CT on the day 14 after the patient's admission revealed 90% of lung tissue injury, cranial CT showed no brain abnormalities, including hypothalamus and pituitary gland. The patient's condition met neither diagnostic criteria of acute kidney injury, nor acute interstitial nephritis, nor pituitary gland damage. The course of the polyuria in the presented case was benign (self-limiting, no blood electrolyte abnormalities, compensated by oral rehydration only). Polyuria in patients with COVID-19 may not be a life-threatening condition that does not require active treatment.Copyright © 2021 EDIZIONI MINERVA MEDICA.
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Introduction: Covid-19 is associated with elevated proinflammatory cytokines that are associated with increased severity and mortality. There is controversy about the true role of cytokine storm (CS) in the pathophysiology of COVID-19. Method(s): Prospective, observational, longitudinal study of 91 hospitalized patients with different severity. It included Viral phase(1-9 days from clinical onset), early inflammatory (10-16 days), and late (>17 days). Clinical data, immune cell counts, proinflammatory cytokine levels (TNF-alpha,IL-1beta,IL-8,IL-6,INF-gamma,IL-17A andG-CSF), serum inflammatory markers (CRP,PCT,D-dimer,ferritin) and tissue damage markers (LDH and cfDNA) were included. Result(s): TNF- alpha, IL-8,IL-6 and G-CSF, were elevated in the most severe patients. IL-6, IL-8 and G-CSF were already elevated in the first admission sample in those who died. Only IL-6 remained elevated in all 3 phases of the disease in deceased patients. IL-1beta, INF-gamma and IL-17A were not related to severity. We found increased levels of cytokines from the viral phase to the early inflammatory phase, significant in moderate Covid-19, but stable in severe and decreasing in critically ill patients. Only IL-6 showed increasing levels in the evolution of critically ill patients. IL-6 correlated with the tissue damage markers studied and with length of stay, especially in critical patients (r=0.598). Conclusion(s): Only IL-6, TNF-alpha,IL-8 and G-CSF were associated with severity. IL-6 was the cytokine that best expressed hyperactivation of the innate immune response and cellular damage in critically ill. There was no significant and sustained increase in cytokines in late inflammation, as would be expected in major CS.
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Introduction: LDH is released by cytokine-mediated tissue damage, reflecting injury and possible organ dysfunction. It is associated with severity and mortality in patients with Covid-19. Circulating free DNA (cfDNA) is a marker of tissue damage, released by the nucleus and mitochondria after cell destruction. Recent studies have showed its possible role as a marker of tissue damage in Covid-19. Method(s): Prospective, observational, longitudinal study of 91 hospitalized patients with different degrees of severity. The evolution distinguished viral, early inflammatory and late inflammatory phases. Clinical data, immune cells, proinflammatory cytokine levels(TNF-alpha,IL-1beta,IL-8,IL-6,INF-gamma,IL-17A andG-CSF),serum inflammatory markers (CRP,PCT,D-dimer,ferritin) and tissue damage markers (LDH and cfDNA) were included. Result(s): LDH levels increased in parallel with severity, but did not discriminate mortality in the first sample and only showed significantly higher levels in critically ill patients. The IL-6/LDH correlation was close and significant in all degrees of severity and at all stages of the disease. The cfDNA value was higher in more severe and patients who died, and was the only biomarker that remained higher in these patients during the 3 phases of the disease. The multivariate study showed that cfDNA, and not IL-6, was an independent risk factor for critical status and ICU admission. Conclusion(s): cfDNA is an excellent marker of tissue damage, severity and mortality in Covid-19 disease, better than LDH. The IL-6/LDH association seems to reflect better timely inflammation, and cfDNA probably reflects better the extent of tissue damage.
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Despite the rapid accumulation of facts about the humoral immune response in COVID-19, there are still no evidence-based answers to questions about the factors influencing the level and duration of the detection period of antibodies to SARS-CoV-2 in the blood. Objective(s): To assess the prevalence, clinical and demographic associations of IgG antibodies to RBD of the SARSCoV-2 spike protein at different times after COVID-19. Materials and methods. Residents of the Altai region of Russia, Caucasians aged 20-93 years, who had COVID-19 from May 2020 to February 2021 (n = 314), took part in a onetime observational study. The level of antibodies in the blood was measured by enzyme-linked immunosorbent assay 1-14 months after the onset of the clinical manifestation of CO-VID-19. Results. Anti-RBD IgG antibodies of the SARS-CoV-2 spike protein were detected in 86.9% of the study participants. The dependence of the antibody titer on the duration of the period after COVID-19 was not revealed. The antibody titer was positively correlated with the complication of CO-VID-19 pneumonia and the volume of lung tissue lesions. The presence of pneumonia COVID-19 and the volume of lung tissue lesions are positively associated with age. Age positively correlated with antibody titer regardless of the pneumonia COVID-19 in the anamnesis. Conclusion. IgG antibodies to RBD of the SARS-CoV-2 spike protein are present in most of the COVID-19 patients. The titer of these antibodies in adults depends on age, complications of pneumonia COVID-19, and probably persists up to 14 months after the first symptoms of infection appear.Copyright © 2022 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved.
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Objective In 2021, accumulated coronavirus disease 2019 (COVID-19) confirmed cases exceeded 100 million worldwide. We sought the long term sequale on COVID-19. Design and Method Although there is a hope for vaccination, continuous infection is observed with case fatality rate over 2%. Patients with cardiovascular disease are more susceptible to COVID-19 and show more severe clinical course after the infection. COVID-19 related myocardial injury evidenced by increased troponin plasma levels occur in at least 10% of hospitalized patients and 25% to 35% or more, of critically ill patients. Patients with SARS-CoV-2 infection related cardiac complications are heart failure, arrhythmia, acute thrombosis, and stress induced cardiomyopathy. Results Myocardial injury is an important entity that cause long term sequale. The extent of the local tissue damage and cytokine storm triggered by the host immune response both contribute to the severity of the myocarditis. An exaggerated inflammatory response can be extremely fatal, and immunomodulators such as corticosteroids are considered in selected cases even though the efficacy and safety is questionable. Combined with these mechanisms related to a host immune response, multiple factors are responsible for the cardiac consequence of COVID-19, such as an oxygen supply and demand imbalance (with or without coronary artery disease), increased right ventricular afterload due to respiratory acidosis, hypoxemia and positive pressure ventilation. Even though it is difficult to discriminate all the possible mechanisms related to myocarditis, accordingly the effort to identify the dominant cause is necessary for the selection of the proper target treatment. Conclusions Substantial evidence has suggested a non-negligible incidence of cardiac injury related to COVID-19. Although the clinical significance and exact mechanisms are under investigation, we should be aware of the potentially fatal cardiac manifestations when dealing with patients with COVID-19. Long-term complications are also noticed from the recent publications and need further attention.
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Background: Neurodivergence has been established as associated with a significant number of co-occurring physical conditions, particularly for autistic individuals who are at risk for increased pain, hypermobility (including Ehlers-Danlos Syndrome) and gastrointestinal problems. However, data, so far, has been focused on adults and generally limited to discussions of condition prevalence alone. Method(s): The following article will present a topical review of the literature considering evidence for increased physical health concerns within neurodivergent populations, particularly autistic individuals, with a focus on the impact that these physical health concerns may have in an educational setting. Results and discussion: The impact of physical health concerns within neurodivergent populations in an educational setting may be concerning. Such populations may face a range of challenges in obtaining appropriate support for physical conditions. We discuss a number of said challenges including;communication challenges, misattributing physical health symptoms as a part of neurodivergence, and a history of not being believed, which limits symptomatic reporting. We further consider the potential impact these physical health concerns may have on scholastic and social development, such as impacts for attainment and attendance. Furthermore, we provide recommendations for teachers, parents/carers and other allied professionals in young people's lives, on supporting young neurodivergent people with physical health concerns.Copyright © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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Introduction: The persistence of the SARS-CoV-2 virus is related to inflammation and lymphopenia in severe Covid19. Longitudinal follow-up of patients is scarce and would be of help to determine if the different immune responses lead to different clinical presentations Methods: Longitudinal prospective observational study of 91 patients. They were classified into viral phase, early inflammatory, and late inflammatory. We included clinical data, immune cell count, proinflammatory cytokine levels, serum inflammatory markers and tissue damage. Result(s): Lymphocyte count was lower with greater severity, and double in survivors. It remained stable during evolution, but with variations depending on the level of severity: critical and deceased patients, had a very low initial count (500/mm3) that did not increase;severe patients the initial lymphopenia (900/mm3) normalized during hospitalization;and moderate, showed a normal and stable count. The correlation of the initial innate immune response cytokine TNF-a with the T-cell-derived (CD4+) cytokines, IFN-g and IL-17A, was significant at all severity levels, although this correlation decreased in the late inflammatory phase. Furthermore, in patients who reached critical status or died, there was not the sustained increase in IFN-g levels observed in less severe Covid-19 (p<0.001), coinciding with the persistent lymphopenia in those patients. Conclusion(s): Our results confirm a drop in lymphocyte counts and decreased production of effector T-cell cytokines in the most severe patients, especially in the late phase of evolution, in line with the lymphocyte depletion described in critical and fatal Covid-19 disease.
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Introduction: Persistence of SARS-Cov-2 leads to immunosuppression and lack of viral control. Better understanding of the immune response throughout the course of evolution is important for a better patient management. Method(s): Prospective observational longitudinal study of 91 hospitalised patients with different degrees of severity (moderate, severe, critical). In 72 we obtained >=2 blood samples and classified them into viral phase (1-9 days after clinical onset), early inflammatory (10-16), and late inflammatory (>17). We included clinical data, immune cell counts, proinflammatory cytokine levels, serum inflammatory markers, and tissue damage. Result(s): We observed higher serum IL-6 levels in the more severe groups, from the first sample. In inflammatory phases, we found a significant decrease in IL-6 and LDH in moderate, severe and survivors, and high persistence in critical and deceased patients. The biphasic behavior of IL-6 described, first neutrophil recruitment, epithelial and endothelial damage and then, after achieving viral control, CD4 differentiation, Th cells response and potentiation of Ac response, could explain these differences between those who do not achieve viral control (critical, deceased) and those who do. Conclusion(s): - IL-6 levels at 10-16 days may indicate whether or not viral control is achieved and whether there may be progression to critical stage/death.
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Rational: Evidence of neutrophil dysfunction in COVID-19 is based on transcriptomics. Cell functions are interwoven pathways, so understanding the effect of COVID-19 across neutrophil function may identify therapeutic targets. We examined neutrophil phenotype and function in 41 hospitalised, non-ICU COVID-19 patients versus 23 age-matched controls (AMC) and 26 community acquired pneumonia (CAP) patients. Method(s): Isolated neutrophils underwent ex vivo analyses for migration, phagocytosis and NETosis, and the effect of PI3K inhibition. Circulating DNAse 1 activity and levels of cfDNA were measured. Result(s): Compared to AMC and CAP, COVID-19 neutrophils demonstrated elevated transmigration (p=0.0397, A) and NETosis (p=0.0366, B), but impaired phagocytosis (p=0.0236, C) associated with impaired ROS generation (p<0.0001). COVID-19 and CAP patients showed increased systemic markers of NETosis including increased cfDNA (p=0.0153) and impaired DNAse activity (p<0.0.001, D). Ex vivo inhibition of PI3K gamma and delta reduced NET release by COVID-19 neutrophils (p=0.0156). Conclusion(s): COVID-19 is associated with neutrophil dysfunction across all main effector functions, with elevated migration, impaired antimicrobial responses and elevated NETosis. These changes represent a clear mechanism for tissue damage and highlight that targeting neutrophil function via PI3k may help modulate COVID-19 severity. (Figure Presented).
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Aim: Our study aims to evaluate the upper extremity trauma that admitted to our hospital from April 11, 2020, to June 1, 2020, the days when the restrictions were applied in Turkey, and to investigate the effect of COVID-19 on upper extremity trauma by comparing with the data of a year ago between the same dates. Material(s) and Method(s): Demographic information, trauma details, and region, and the treatment method of patients with any upper extremity trauma who were over the age of 18 and admitted to the hospital between April 11, 2019, and June 1, 2019 (2019-Before Restrictions) and between April 11, 2020, and June 1, 2020 (2020-Lockdown) were examined retrospectively. Result(s): In 2019-Before Restrictions, 218 patients and in the 2020-Lockdown, 163 patients were admitted to the hospital due to upper extremity trauma. The number of hospital admissions with upper extremity trauma during the 2020-Lockdown was 25.22% less than that of those in 2019-Before Restrictions, (p<0.05). While the number of patients admitted to the hospital due to fractures in the upper extremity during 2019-Before Restrictions, was 89 (Open Fracture=32, Closed Fracture=57), this number was observed to decrease to 48 (Open Fracture=11, Closed Fracture=37) in the 2020-Lockdown (p<0.05). Discussion(s): It was determined that there was a decrease in upper extremity trauma during 2020-Lockdown compared to the same dates of the previous year. It is possible to state that quarantine practices applied to prevent the spread of COVID-19 affect the decrease in upper extremity trauma.Copyright © 2022, Derman Medical Publishing. All rights reserved.
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Feline Infectious Peritonitis (FIP)is a fatal disease caused by Feline coronaviruses. The causative agent is Feline Infectious Peritonitis Virus, a mutation of Feline Enteric Coronavirus. Feline Corona Virusinfection is very common in the cat population.In Feline Corona Virus infected cats, the development of FIP depends on the cat's immune response. FIP disease is more common in young and old cats because young and old animals have a weaker immune system. The acute phase response is a complex systemic reaction that occurs as a response to acute or chronic inflammatory processes such as infection, neoplasia or immunological disorders, tissue damage, trauma, and surgery. The study material was composed of15 cats with FIP (study group) and 10 healthy cats (control group). Serum amyloid A (SAA), haptoglobin (Hp), alpha1-acid glycoprotein (AGP), albumin, interleukin-6 (IL-6), hepcidin, alanine-amino transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen(BUN), and creatinine levels were measured in the serum collected from both groups. There was no difference between the wet and dry FIP in albumin values (p<0.05).Haptoglobin, alpha1-acid glycoprotein, SAA, IL-6, and hepcidin values were significantly different between the two groups (P<0.001). It was also concluded that hepcidinhas a potential for use as a biomarker in Feline Infectious Peritonitis disease like other acute phase proteins.Copyright © 2023, Sima Sahinduran, Metin Koray Albay, Mehmet Karaca, Mehmet Cagri Karakurum, Reyda Kiyici