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OBJECTIVE: To determine the rate of different amputation levels in diabetic foot patients and the incidence of repetitive foot surgeries and evaluate the factors causing a delay in hospital stay and amputation of patients. METHODOLOGY: This prospective cohort study was conducted in Dr. Ruth K.M. Pfau, Civil Hospital Karachi, Pakistan. The study selected 375 participants from the clinic's daily patient inflow from October 2021 to March 2022 using a non-probability consecutive sampling technique. Those who had a delay in hospital stay and amputation were further followed up from May-October 2022. The chi-square test and Kruskal Wallis test (p-value <0.05) were used to correlate the effect of the level of lower limb amputation and the cause of delay in amputation using SPSS version 24.0. RESULT(S): Total 246(65.60%) were males and 129(34.40%) were females. Toe amputation was the most commonly seen amputation in 173(46.1%) participants. About 168(44.8%) patients had some in-hospital delay stay during their treatment. Preoperative hurdles (Uncontrolled RBS, Osteomyelitis, etc.) were the most common factor causing an in-hospital delay in 92(24.5%) patients. The level of amputation performed was found to be statistically significant with factors causing a delay in hospital stay through chi-square (p=0.003*) and Kruskal Wallis test H (2) statistic= 13.3, df = 3, H (2), P=0.004*). CONCLUSION(S): Diabetic foot is a frequent cause of amputation globally, majorly in developing countries like Pakistan. On-time provision of treatment to these patients can decline the global amputation rate due to diabetic foot ulcers.Copyright © 2023 Syeda Anjala Tahir.
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Background: Tixagevimab(Txg)/cilgavimab (Cgv) was given emergency use authorization (EUA) to provide passive immunity against COVID-19(CoV) for immunocompromised (IC) pts who may not mount an adequate response to CoV vaccination [1]. Recipients of allogeneic hematopoietic cell transplant (Allo-HCT) are amongst the most IC. Due to high risk of mortality and complications of CoV in this population, Txg/ Cgv was used as pre-exposure prophylaxis (PrEP) under EUA without prior study. Our study aims to assess efficacy and adverse events (AE) of Txg/Cgv administration in this cohort of patients to help guide future practice. Method(s): We retrospectively investigated Allo-HCT recipients who received Txg/Cgv as PrEP. Data were gathered including changes in blood counts, incidence of graft-vs-host-disease (GVHD), history of prior CoV infection and vaccination status. Pts who developed CoV infection after PrEP were assessed for supplemental oxygen(O2) need and hospitalization. Data cutoff date was 9/30/2022. Result(s): A total of 18 Allo-HCT recipients received Txg/Cgv. Table 1 summarizes patient and transplant characteristics. Thirteen (72.2%) pts received 2 doses of 150mg of Txg / Cgv, while 4 pts received 1 dose of 300mg, and one patient received one dose of 150mg. Median time to first dose was 213 days [range 22-3660] post-transplant. Two pts had lab confirmed CoV, one at 24 days post dosing and the 2nd patient at 22 days post dose. Neither required supplemental O2;one was hospitalized for fever. Prior to dosing, 44.4% (8/18) of pts had GVHD. (Table Presented) (Figure Presented) (Figure Presented) Of these, 62.5% (5/8) had no changes in the severity of their GVHD. Two of 8 (25%) pts with pre-existing chronic GVHD had a flare of symptoms. Two (25%) had improvement of GVHD. Two pts developed new onset acute GVHD following Txg/Cgv administration, one requiring 1mg/kg prednisone and the other topical steroids (2/18, 11%). Figure 1 summarizes GVHD patterns observed. Hematologic parameters did not change significantly, see Figure 2. None of the pts reported any subjective AE following dosing. Summary: Txg/Cgv was found to be safe and effective for Allo-HCT pts, without significant toxicity. Two patients had new onset GVHD and 2 patients had progressive GVHD. Whether there is a true association between Txg/Cgv and development of GVHD should be investigated in a larger cohort and then investigated for possible underlying mechanisms.Copyright © 2023 American Society for Transplantation and Cellular Therapy
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Introduction: Since March 2020, a number of SARS-CoV-2 patients have frequently required intensive care unit (ICU) admission, associated with moderate survival outcomes and an increasing economic burden. Elderly patients are among the most numerous, due to previous comorbidities and complications they develop during hospitalization [1]. For this reason, a reliable early risk stratification tool could help estimate an early prognosis and allow for an appropriate resources allocation in favour of the most vulnerable and critically ill patients. Method(s): This retrospective study includes data from two Spanish hospitals, HU12O (Madrid) and HCUV (Valencia), from 193 patients aged > 64 with COVID-19 between February and November 2020 who were admitted to the ICU. Variables include demographics, full-blood-count (FBC) tests and clinical outcomes. Machine learning applied a non-linear dimensionality reduction by t-distributed stochastic neighbor embedding (t-SNE) [2];then hierarchical clustering on the t-SNE output was performed. The number of clinically relevant subphenotypes was chosen by combining silhouette and elbow coefficients, and validated through exploratory analysis. Result(s): We identified five subphenotypes with heterogeneous interclustering age and FBC patterns (Fig. 1). Cluster 1 was the 'healthiest' phenotype, with 2% 30-day mortality and characterized by moderate leukocytes and eosinophils. Cluster 5, the severe phenotype, showed 44% 30-day mortality and was characterized by the highest leukocyte, neutrophil and platelet count and minimal monocytes and lymphocyte count. Clusters 2-4 displayed intermediate mortality rates (20-28%). Conclusion(s): The findings of this preliminary report of Eld-ICUCOV19 patients suggest the patient's FBC and age can display discriminative patterns associated with disparate 30-day ICU mortality rates.
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Corona Virus disease 2019 (COVID-19) pandemic has presented a huge challenge to the health care system in terms of magnitude of cases and to pediatric oncology units with varied clinical presentations. Acute myeloid leukemia(AML) is a rare heterogenous cancer of childhood with an induction mortality around 15% in our country due to neutropenic sepsis. Multisystem inflammatory syndrome in children(MIS-C) is an hyperinflammatory syndrome seen 4–6 weeks after COVID-19 infection. COVID infection in some of these children would have gone unnoticed. Here we report a two year eight months old boy diagnosed with AML on induction chemotherapy developed post COVID MIS-C. © 2022
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Objective. To assess the impact of obesity and overweight on the course of COVID-19. Patients and methods. This prospective study included 218 patients with SARS-CoV-2 infection aged 18 to 94 years hospitalized between June 2020 and March 2021. We evaluated their clinical and laboratory parameters and their association with body weight. All patients were divided into 3 groups depending on their body mass index (BMI). Group 1 included 81 patients with grade 1-3 obesity (BMI >=30);group 2 comprised 71 overweight patients (BMI >=25 and <30);group 3 included 66 patients with normal body weight (BMI >=18.5 and <25). We analyzed clinical symptoms (including shortness of breath, fever, myalgia, headache, fatigue, changes in the oropharynx, cough, rhinorrhea, sore throat, anosmia, and diarrhea), prevalence of concomitant disorders and complications, findings of computed tomography and pulse oximetry, and findings of instrumental and laboratory examinations (complete blood count, urine test, electrocardiography, echo cardiography, biochemical assays, including C-reactive protein, procalcitonin, alanine aminotransferase, aspartate aminotransferase, lactate, lactate dehydrogenase, activated partial thromboplastin time, prothrombin index, D-dimer, ferritin). Data analysis was performed using the Statistica 6.0 software. Results. We found that overweight and obese patients were more likely to have the main COVID-19 symptoms and comorbidities than those with normal weight. Overweight and obese patients also required respiratory support more frequently than patients with normal weight. Obese and overweight patients had more severe systemic inflammation (CRP, procalcitonin), cytolysis (ALT, AST), and thrombosis (D-dimer). Conclusion. Our findings suggest that obesity and overweight are the factors associated with a more severe SARS-CoV-2 infection, which should be considered when planning their treatment and developing resource strategies.Copyright © 2022, Dynasty Publishing House. All rights reserved.
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Introduction: The coronavirus disease 2019 (COVID-19) mainly causes pulmonary disease. However, extrapulmonary manifesta-tions, which affect the gastrointestinal tract and hepatobiliary system, have been reported. Case Presentation: Here we reported a 4-year-old boy with acute lymphoblastic leukemia and abdominal pain who had acute necrotic pancreatitis secondary to COVID-19. Conclusion(s): According to the COVID-19 epidemic, if drug-induced pancreatitis is ruled out, viral causes, especially COVID-19, should be considered.Copyright © 2023, Author(s).
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Aim: To study the characterization of the CT Brain in COVID 19. Material(s) and Method(s): Patients of COVID 19 who had neurological signs either before they were admitted or while they were in the hospital had a CT brain plain once during their time in the hospital. CT Brain plain presentations were shown to correspond with CNS symptoms, progression throughout the patients' hospital stays, and outcomes. Several tests, such as RT-PCR for COVID 19, CT Brain plain, complete blood count, liver function tests, renal function tests with electrolytes, and others were performed. Result(s): In the current investigation, there were a total of 50 patients, 46 (92%) of whom were male, while just 4 (8%), on the other hand, were female. The patients' ages ranged anywhere from 35 to 82 years old, with a mean of 65.85+/-8.69 years. NLR was 14.98+/-2.69 (range 1.31-47.5), mean LDH 992.17+/-25.69 (range 221-5125), and Hs-CRP was 171.22+/-22.69 (range 2.9-321.5). Mean haemoglobin of the patients was 11.12+/-1.85 (range 4-15 g/dl), total leukocyte count was 16580.63+/-5896.45, mean platelet count was 2.11+/-1.02 / lacs (0. 27 patients, or 54%, were discovered to have had an ischemic stroke, whereas 5 patients, or 10%, were found to have had a hemorrhagic stroke. The CT brain results were found to be abnormal in 30 individuals (or 60%), whereas in 20 patients (or 40%), they were determined to be normal. 11 (22%) of the patients required the assistance of a ventilator, 6 (12%), of the patients used a BiPAP, 2 (4%), of the patients used a Hudson mask, and 10 (20%) of the patients had NRM. Conclusion(s): In conclusion, we were surprised to find that the proportion of patients with severe COVID-19 infection who had abnormal brain CT scans was rather significant. Ischemic stroke was the most common kind of stroke that occurred in conjunction with aberrant CT results. We believe that the connection between aberrant brain CT and the fate of patients warrants further validation in a wider patient population.Copyright ©2022Int. J. Life Sci. Biotechnol. Pharma. Res.
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Background ACE is a potent pro-inflammatory modulator that controls chemokines and adhesion molecules, and elevated ACE activity associated with immunoinflammatory conditions, including cardiovascular diseases (CVD) and diabetes. The ACE inhibitors are recommended as primary treatment for these illnesses. ACE is a peptidyl-dipeptidase that catalyses Angiotensin I to Angiotensin II, whilst inactivating bradykinin during blood pressure regulation via the Renin-Angiotensin System. The purpose of this study is to establish a reference interval (RI) for ACE in the Irish population after COVID, and to examine if there is an underlying correlation between ACE concentrations and a range of biomarkers. Methods Serum samples of 200 randomly selected patients were obtained from several Irish hospitals in March 2022 (in compliance withGuidance on Anonymisation and Pseudonymisation, June 2019). We analysed for ACE (Buhlmann reagents), HBA1C, 25OHD and other biomarkers on the Abbott Architect ci8200. Full Blood Count was measured on Sysmex CS-2500. The statistical analysis used the EP Evaluator 11.3.0.23 and SPSS 22.0 software. Results The RI based on the central 95% of data was 8-78 U/L. This is higher than the RI proposed by the manufacturer (20-70 U/L) but is very close to our RI (5-79 U/L) from 2019. We found a significant positive correlation between ACE concentration and HBA1c, Urea, Creatinine, White Blood Cells (p<0.0001), Glucose (p=0.02), LDL (p=0.03), Neutrophils (p=0.003), Lymphocytes (p=0.001). A significant negative correlation was observed with 25OHD (p<0.0001). Conclusions This study did not show any notable change in the RI for ACE after COVID in Ireland. The significant positive correlations with HBA1c and other biomarkers may indicate the importance for ACE testing for diabetic management and progression, but further studies will be needed. Patients' overall health and medical history should always be considered when evaluating ACE results, including Vitamin D levels.
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The new coronavirus infection COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2, has posed scientific and public health challenges. The problem of treating COVID-19 still remains, and the pathogenesis of COVID-19 needs to be studied in detail, including the involvement of mast cells (MCs) and their specific proteases. The aim of this study was to characterize the role of mast cell proteases chymase, tryptase, and carboxypeptidase A3 (CPA3) in the lung damage associated with COVID-19. Methods. The study included postmortem lung biopsies from 30 patients who died of severe COVID-19, and biopsies from 9 control group patients. Histological preparations were made and protease profile and degranulation activity of MCs were analyzed. In addition, some demographic, clinical, and laboratory parameters were analyzed. Results. The average number of tryptase-positive MCs without evidence of degranulation and the total number of CPA3-positive MCs were statistically significantly higher in patients with COVID-19, and the number of tryptase-positive and CPA3-positive MCs fragments was lower compared with controls. Negative correlations were established between the numbers of tryptase-positive MCs and red blood cell count. Negative correlations were found between non-granulating tryptase-positive MCs and hemoglobin levels. Positive correlations were noted between tryptase-positive MCs and the leukocytes and eosinophils counts, and negative correlations were noted between the number of CPA3-positive cells and the platelet count. A positive correlation was found between the number of adjoining MCs, as well as fragments of tryptase-positive MCs, and the erythrocyte sedimentation rate (ESR). A negative correlation was also observed between the number of non-degranulated CPA3-positive MCs and the blood level of C-reactive protein. In patients with COVID-19, reduced degranulation activity of tryptase-positive MCs was found along with increased representation of CPA3-positive MCs. Several trends and associations with laboratory test results were noted. The potential involvement of MCs in the development of anemia and thrombocytopenia is considered. Associations were established between tryptase-positive MCs and the peripheral blood counts of leukocytes and eosinophils, as well as ESR. Conclusion. The results obtained are highly contradictory. Since many aspects of the involvement of MCs and their proteases in COVID-19 pathogenesis are still unknown, studies with larger cohorts of patients are needed.Copyright © Budnevsky A.V. et al., 2023.
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The relevance of research on a novel coronavirus infection is associated with an increase in the incidence among children since 2021, which may be due to the accumulation of mutations in the virus genome and its evolution towards increased contagiousness, replicative ability, and evasion of immune protection. While there are many studies in adults, data analyzing the clinical course of the disease in pediatric patients infected with SARS-CoV-2 are limited, particularly regarding adolescents. Objective. To study the clinical and laboratory features of the course of a novel coronavirus infection in hospitalized adolescents in Novosibirsk during the first, second and third waves of the pandemic. Materials and methods. A retrospective analysis of case histories of 125 children treated at Novosibirsk Children's Clinical Hospital No 6 with a confirmed diagnosis of coronavirus infection during three pandemic waves was carried out (June- August 2020, October-December 2020, June-August 2021). Based on these time intervals, three groups of adolescents admitted to the hospital during the first, second, and third waves of coronavirus infection were formed. SARS-CoV-2 RNA in nasopharyngeal and oropharyngeal scrapings was determined using the PCR-RT method. Biochemical and general clinical studies were performed in accordance with the guidelines of the Ministry of Health of the Russian Federation. Statistical processing was carried out using the Satistika 7.0 software package (StatSoft, USA). Differences between the groups were assessed using the Z-test and the Mann-Whitney U test. Differences between the compared series were considered statistically significant with a probability level of 95%. Results. It was shown that during three pandemic waves (June 2020 - August 2021), more than half of the hospitalized children were adolescents. At the same time, regardless of the pandemic wave, intoxication, catarrhal and intestinal syndromes predominated in hospitalized adolescents. CNS injury symptoms were significantly less frequent in the first wave, as were skin rashes. Cough in the third wave was observed in 100% of hospitalized adolescents. The average values of the parameters of complete blood count, as well as CRP, D-dimer and ferritin had no statistically significant differences in different pandemic waves, but there was a significant variation in individual values within the groups in each wave.Copyright © 2022, Dynasty Publishing House. All rights reserved.
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Background: A single-stranded mRNA virus SARS-CoV- 2 is associated with severe acute respiratory syndrome in the predisposed individuals such as elderly, obese, chronic cardiovascular or pulmonary diseases. Higher risk for severe course was also reported in inborn errors of immunity (IEI). While restriction measures play important role from the short-term perspective, vaccination may provide long-term protection. However, only limited data are available on safety and efficacy in immunocompromised patients with IEI such as Common variable immunodeficiency (CVID). Method(s): We assessed humoral and cellular responses, safety and efficacy in a cohort of 20 CVID patients after 2 doses of anti-SARS- CoV- 2 vaccine BNT162b. The humoral reponse was evaluated using ELISA and western blot methods, the T cell response measured by IFNg secretion functional assay. Adverse events were reported by Patient Clinical Questionnaire. Blood count, biochemical, coagulation and immunological parameters were checked before and after vaccination. The patients were followed for 6 months. Result(s): Despite severely impaired antibody production hunoral response was detected in 48% (n = 10/21) of patients at month 1. However, the response persisted in only 33% (n = 6/18) at month 3 and further decreaed to 13% (n = 2/15) at month 6. The T cell response was measurable in 5 patients (28%) at month 1. In total, 4 out of 20 (20%) patients got infected within the study period. None of them required oxygenotherapy or hospital admission. We did not observe any severe adverse effects beyond local pain, fatigue, headche, fever, arthralgia and myalgia. Conclusion(s): Vaccination with mRNA vaccine BNT162b provides safe and effective protection for a subgroup of CVID patients. However, the immunogenicity is lower compared to the general population.
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Background: Vaccination is considered the most effective preventive strategy to fight COVID-19. The aim of this study was to evaluate two critical concerns about: 1) the kinetic response of IgG and IgM, and: 2) the hematological abnormalities in a longitudinal cohort of health-care workers (HCW) who had received 2 doses of BNT162b2 mRNA-based vaccine. Method(s): Blood and nasopharyngeal swabs were collected from 46 volunteers' participants, previous written consensus, with presumable no symptoms of COVID-19. Anti-SARS-CoV-2 serum immunoglobulin G (IgG) and M (IgM) and hematological parameters were examined. Multivariable mixed-effects models for repeated measure analysis were adopted to evaluate time changes in IgG, IgM and hematological parameters, and to investigate associations with vaccination response. Result(s): Forty-six subjects (N.=46;31.8% men;68.2% women;mean age near 36 years-old) were enrolled among healthcare workers of IRCCS MultiMedica (Milan, Italy). Overall, increase in serological IgG concentration appeared mainly between 21-28 days after the 1st dose, whereas IgM did not reach positivity in all cases. Mean blood cells counts were in normal range but we observed a significant reduction of total white blood cells and absolute lymphocyte counts after the 1st dose, persisting until the day 28. The increase of monocytes and neutrophils the day after the 1st dose subsequently decayed significantly. Eosinophils concentration showed a tendency to increase over time. Peripheral blood smear showed a growing frequency of atypical lymphocytes (lympho-variants), and of plasmacytoid forms, whereas no difference was found in large granular lymphocytes (LGL), although a decay after the boost was evident. The stratification of subjects, relative to the timing of IgG increase, showed the occurrence of 3 different patterns after vaccination, namely early-responders (R+), late-responders (R-) and pauci-responders (PR) with a peculiar kinetics of hematological parameters. Lymphocytes were significantly associated with total IgG: lower in R+ and PR compared to R- (P=0.0193 and P=00054, respectively). Conclusion(s): In healthy subjects, anti SARS-CoV-2 vaccination induced a variety of non-pathologic abnormalities. The response to vaccination was not equal in the groups examined. In PR group a major difference occurred with respect to R- and R+. This work adds novel insight into the puzzle of changes induced by SARS-CoV-2 virus.Copyright © 2022 EDIZIONI MINERVA MEDICA.
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Objective: This study included participants from Hacettepe University 4th, 5th, and 6th-grade students of Medical School and 4th and 5th-grade students of Dental School;and aimed to evaluate the general health status, COVID-19 history, vaccination status, and SARS-CoV-2 antibody levels of the participants to support their physical and social health, during the pandemic period. Method(s): A prospective cohort study was conducted with an integrated, matched, nested case-control study. Sociode-mographic characteristics, life habits, COVID-19 history, vaccination status, compliance with mask-distance-hygiene rules, and risks (if any) for COVID-19 were inquired via online questionnaires. Physical examinations, complete blood count, biochemistry tests, and anti-SARS-CoV-2 anti-spike antibody tests were conducted for all consenting partici-pants. All analyses were established using depersonalized data. Result(s): Of the 778 participants completing the baseline visit in June-July 2021, the percentages of those vaccinated with at least one, two, and three/more doses of COVID-19 vaccine were 99.1%, 98.0%, and 11.7%, respectively;one had four doses. The median (minimum-maximum) time since the last vaccination was 134 (34-166) days for those vaccinated with two doses [CoronaVac (Sinovac Life Sciences, Beijing, China)] and 25 (14-56) days for those vaccinated with three doses [two doses of CoronaVac and a last dose of Pfizer-BioNTech mRNA vaccine (Comirnaty). The third dose was applied at a median of 164 (151-202) days after the second dose, and all were heterologous in type. The median (minimum-maximum) antibody level for the overall group was 53.55(0-5680) BAU/mL: 47.19 BAU/mL in those who received two doses, with a more than 100 times increase after a third dose (4943.64 BAU/mL). Of the 522 participants followed up to October 1, 2021, 6 PCR-positive symptomatic participants were diagnosed with COVID-19: the incidence rate was 4/1000 person-months. Conclusion(s): A 100-fold neutralizing antibody level following the third dose demonstrated the importance of a booster dose. Given the time lag between doses, antibody measurements of BioNTech recipients should be repeated in the upcoming months. Booster selection should involve antibody level, variant sensitivity of the vaccine, and individual characteristics of the recipient.Copyright © 2023, DOC Design and Informatics Co. Ltd.. All rights reserved.
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Background: In the context of the COVID-19 pandemic it is very important to achieve collective immunity. Allergic reactions to vaccines are rare -up to 30 per 100 000, but 4-8 may have anaphylaxis. The aim of this study was to develop safe COVID-19 vaccination algorithm for patients with allergic diseases (AD). Method(s): Patients with the history of AD were invited for vacination to the Regional Allergy Center in Dnipro (Ukraine). Before vaccination all patients underwent: serum tryptase, whole blood count (WBC), D-dimer, blood biochemistry, electrocardiogram (ECG) and spirometry (for patients with asthma (A) only). 126 patients with AD 19-85 (53.2+/-1.5) years old (50, 39.68% men) were included into the study. 25.39% of them had seasonal allergic rhinitis (SAR);15.07% -A;10.32% -A+ SAR;35.71% -urticaria;11.11% -drug allergy;2.38% -history of anaphylaxis. Result(s): There were not any clinically significant changes found in WBC, blood biochemistry and ECG. At the same time in 4 patients (3.2%) high tryptase level was detected. Mastocytosis was diagnosed by sternal puncture in 3 of them. During 12 weeks they were treated by monoclonal antibodies and after that vaccinated with two doses of mRNA vaccine without adverse reactions. For 1 patient with high tryptase level and a history of 3 anaphylaxis with hospitalization vacination was postponed. 1 patient had elevated D-dimer (PTA was diagnosed by CT) -vaccination was temporarily delayed. In 10 patients uncontrolled A with FEV1 below 70% (36-65%) was found. After the correction of basic therapy, within 2 weeks vaccination was carried out. All patients were given a 4-fold dose of desloratadine 30 minutes before vaccination. Conclusion(s): 1. AD are not a contraindication for vacciantion against COVID-19. 2. Before vacciantion all patients with a history of AD should be examined by an allergist. 3. For patients with severe AD level of serum tryptase should be detected before vacciantion. 4. Patients with AD should be vaccinated in an allergy center with premedication of H1-blocker in a 4-fold dose.
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Case report Introduction: Toxic epidermal necrolysis (TEN), is an immune-mediated disease characterized by severe mucocutaneous symptoms and is the result of an inflammatory response that leads to keratinocyte necrosis and perivascular lymphocyte infiltration, mostly drug-related. Case report: A 35-year- old male, with a history of recently diagnosed systemic lupus under treatment with prednisone, hydroxychloroquine, mycophenolate and cotrimoxazole forte evolves with persistent proteinuria, it is decided to add losartan, chlorthalidone and atorvastatin. Nevertheless despite immunosuppression, proteinuria and skin involvement persisted, so mycophenolate was suspended and a bolus of cyclophosphamide 1 g was administered. Eight weeks after adjusting treatment, the patient went to the emergency department due to a confluent, pruritic, maculopapular rash with blistering lesions on the trunk, upper limbs, face, and oral mucosa, associated with fever over 38degreeC, that evolved during one week. On admission, the following was confirmed: confluent erythematous macular exanthem associated with multiple flaccid blisters on the chest, upper limbs and neck, Nikolsky's sign (+), keratoconjunctivitis and dryness on the lips. Admission tests included complete blood count with no leukocytosis or eosinophilia, ESR 29 mm/hr, C-RP 19.8 mg/L, no liver profile abnormalities, creatinine 0.8 mg/dl, and urine test with proteinuria 300 mg/dl. Negative infectious study for mycoplasma, herpes 6 virus, cytomegalovirus, Epstein barr virus, hepatitis A, B, C, E and SARS-COV2 virus. Due to severe mucosal skin involvement, TEN/SJS was suspected v/s (TEN)-like Lupus presentation, drugs used prior to admission (chlorthalidone, losartan, atorvastatin) were discontinued, and treatment was started with Hydrocortisone 100 mg every 8 hours IV, Immunoglobulin 2 g/kg daily IV for 4 days, plus skin and mucous membrane care. Patient had a favorable evolution, with resolution of skin and mucosal lesions and no signs of infection. Skin biopsy showed necrotic epidermis, necrotic basal keratinocytes, and sparse lymphocytic inflammatory infiltrate in the papillary dermis, consistent with erythema multiforme/toxic epidermal necrolysis. Conclusion(s): Extensive mucosal involvement is one of the cardinal signs of the presentation of SJS/ETN and given its severity, a high index of suspicion is important with the consequent suspension of suspected drugs and support management for a favorable evolution. In this case the suspected culprit drug was the combination of cyclophosphamide and chlorthalidone, due to reports of increased toxicity of cyclophosphamide in combination with diuretic drugs.
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Background. Environmental factors such as infections and vaccines are known to trigger dermatomyositis (DM), and during the recent SARS-CoV-2 pandemic this has become even clearer. SARS-CoV-2 infection may share features with anti-MDA5 DM, such as rapidly progressive lung involvement, cutaneous lesions and cytokine release syndrome. A few case reports of DM following SARSCoV-2 vaccination have been published, suggesting the onset of an aberrant immune response leading to DM with specific autoantibody signatures and severe organ impairment. Methods. Clinical and laboratory data of the 2 case reports were obtained from electronic clinical charts in Humanitas Research Hospital (Rozzano, Milan, Italy). Autoantibody analysis was performed by protein-immunoprecipitation for anti-MDA5 and immunoblot for anti-Ro52 and TIF1gamma antibodies as per protocol. Results. Case report 1 is a 71-year-old woman who developed fever, cough, and anosmia, which resolved spontaneously in two weeks, but did not undergo a nasopharyngeal swab, while her relatives were diagnosed with SARS-CoV-2 infection. When symptoms improved, she developed arthralgia and skin lesions on her face, chest, and hands for which she started topical treatment, with negative SARSCoV-2 nasopharyngeal swab and positive serum test for IgG against SARS-CoV-2 spike protein. For the persistence of the skin rash and arthralgia, she was admitted to our Department in March 2021. Blood tests showed mild elevation of C reactive protein (2.1 mg/L -normal value NV<5), aspartate (84 UI/L) and alanine aminotransferase (133 UI/L -NV<35), ferritin (595 ng/ml -NV<306), troponin I (19 ng/L -NV<14), and BNP (251 pg/ml -NV<100) with normal complete blood cell count, creatine kinase, C3 and C4. IgG antibodies for SARS-CoV-2 spike protein were confirmed to be elevated (96 AU/ml -NV<15). Autoantibodies associated with connective tissue diseases were tested and only anti-MDA5 antibodies were positive at immunoprecipitation. A punch biopsy of a Gottron-like lesion on the left hand showed leukocytoclastic vasculitis. We observed reduced capillary density with neoangiogenesis and ectasic capillaries at the nailfold capillaroscopy. EKG and ecocardiography were normal, while cardiac magnetic resonance detected abnormalities in the parametric sequences, consistent with signs of previous myocarditis. A lung CT scan revealed pulmonary emphysema while respiratory function tests demonstrated reduced volumes (FVC 82%, FEV1 64%, inadequate compliance CO diffusion test). Based on the biochemical and clinical findings, a diagnosis of anti-MDA5-associated DM with skin and heart involvement was made and treatment with low-dose methylprednisolone (0.25 mg/kg daily) and azathioprine 100 mg was started, then switched to mycophenolate because not effective on skin lesions. Case report 2 is an 84-year-old woman with history of colon cancer (surgical treatment) and oral lichen treated with low doses steroids in the last 2 years. After the 2nd dose of SARS-CoV-2 mRNA vaccination, in March 2021 she developed skin rash with V-sign, Gottron's papules, periungueal ulcers, muscle weakness and fatigue, thus she performed a rheumatologic evaluation. Blood tests showed mild elevation of creatine kinase (484 UI/L, NV <167), CK-MB (9.6ng/ml, NV <3.4), BNP (215 pg/ml -NV<100) with normal values of complete blood cell count, C3 and C4. Anti-Ro52kDa and TIF1gamma were positive at immunoblot, thus we confirmed a diagnosis of DM. The clinical evaluation also showed active scleroderma pattern at nailfold capillaroscopy, normal echocardiography, bronchiectasia but not interstitial lung disease at lung CT, and normal respiratory function tests (FVC 99%, FEV1 99%, DLCO 63%, DLCO/VA 81%). A PET-CT scan was performed to exclude paraneoplastic DM, and treatment with steroids and mycophenolate was started. Conclusions. SARS-CoV-2 may induce mechanisms for escaping the innate immunity surveillance and causing autoimmune diseases, but more clinical and functional studies are needed to demonstrate this possible association.
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Background: COVID-19 is a viral disease affecting mostly respiratory system with variable severity of the clinical course. Several clinical and laboratory parameters are associated with poor outcome. Progression of the clinical stage is associated with the exaggerated immune response and the cytokine storm. Method(s): We focused on the search of potential prognostic markers of fatal outcome among immune parameters. To this end, we examined the immune profile in 823 COVID-19 patients hospitalized in University Teaching Hospital in Martin (Slovakia) on admission and its changes over time during the first week of hospitalization. The examined immune profile consisted of the differential blood cell counts, serum concentration of immunoglobulins and basic complement compounds C4 and C3, flow cytometric lymphocyte subsets phenotyping and the measurement of selected activation and inhibition markers. Result(s): Although none of examined parameters alone had sufficient AUC value to be considered as a marker of (un)favourable outcome, we found several significant differences among different severity groups of patients, as well as between survivors and non-survivors. Severity of COVID-19 correlated with the severity of neutrophilia, thrombocytopenia, depletion of leukocyte (except for neutrophils) and lymphocyte subsets. In comparison to the fatal outcome, survival was associated with higher concentration of C3 and IgM, lower proportion of CD8+CD38+ cells, higher proportion of CD8+NKG2A+ and NK NKG2A+ cells on admission and with the significant increase in the expression on HLA-DR on both CD3+ and CD8+ cells over the first week. Conclusion(s): Our results point out to the dysregulated functional status of depleted CD8+ cells with their over-activation and possibly insufficient compensatory inhibition in COVID-19 non-survivors. Based on our results, the increase in HLA-DR expression on CD3+ and CD8+ cells is necessary for recovery.
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Introduction (contexte de la recherche): Erythema nodosum (EN) is a type IV delayed hypersensitivity reaction to a variety of antigens stimuli. In fact, EN is commonly caused by a range of conditions, including infections and vaccines. EN induced by COVID-19 vaccines is rarely reported. Objectif: Herein, we report an original clinical observation of EN occurring after the first dose of AstraZeneca COVID-19 vaccine (vaxzevria), a viral vector vaccine, without recurrence after the second dose. Methodes: This case was notified on August 2021 to Tunisian National Centre of Pharmacovigilance and was analyzed according to the French updated method for the causality assessment of adverse drug reactions. Resultats: A 46-year-old woman with no medical history, presented with diffuse erythematous painful and nodular lesions, located symmetrically over her legs. Eleven days before, she had received the first dose of vaxzevria which was followed by a sudden asthenia, and oedema over her lower limbs. The patient reported no recent infectious episodes. She had no known drug allergy. Skin examination showed multiple, tender, erythematous nodules, which ranged from 3 to 4 cm in diameter located over the tibial area. Some were regressive according to biligenesis shades. Laboratory tests including a complete blood count, renal and hepatic tests and antistreptolysin O titer were carried out and were negative except an elevated c-reactive protein of 45 mg/dL. The dermatological examination found lesions on both legs to be consistent with EN and started therapy with prednisone 40 mg daily for one week, subsequently gradually tapered and suspended, with complete regression of lower limb skin lesions within 10 days. No skin biopsy was performed due to the typical clinical presentation, color evolution and a complete response to steroid therapy. The patient subsequently received the second dose after two months without the reappearance of EN. Conclusion(s): In this case the role of vaccine was suspected in front of a temporal association between the first dose of vaccine and the onset of EN and the absence of another etiology. However, the good evolution of this skin manifestation will help reassure patients in the safety of vaccine administration.Copyright © 2023
ABSTRACT
Case report In May 2021, the European Medicines Agency (EMA) approved the administration of the mRNA BNT162b2 vaccine (Pfizer/BioNTech) in adolescents aged 12-15 years, in the form of a two-doses-primary course three weeks apart, with a booster dose after five months. Few adverse events have been observed in vaccinated children -mainly fever, myalgia, or local edema at the injection site. Conversely, delayed cutaneous reactions are little reported in adults and even rarer in pediatric age. A 12-year-old boy, with no previous cutaneous or autoimmune diseases nor allergic reactions to previous vaccines or drugs, came to our attention because of a cutaneous rash, which started on his right arm two days after his first dose of Pfizer/BioNTech vaccine. The rash was flat, erythematous, and purpuric, with subsequent bruise appearance and spontaneous resolution. Lesions took over on the front side of his arms and shoulders until a month after the vaccine. Urine and blood tests -including blood cell count, flow cytometry, plasma biochemistry, inflammatory index, autoantibodies, coagulation, and platelets aggregation test -did not show significant alterations. Grass pollen monosensitization was detected. Biopsy of the lesions showed 'modest perivascular lymphohistiocytic infiltrate and focal infiltration of vascular walls with swollen endothelium' with 'occasional eosinophils, scattered neutrophil granulocytes, and erythrocytes in interstitial areas,' compatible with leukocytoclastic vasculitis. Epidermidis was undamaged, and the direct immunofluorescence showed fibrinogen deposits in superficial-to-middle dermis vessels. Further tests highlighted a high immune response to the vaccine without previous Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. No therapies were needed, and the boy experienced no other side effects undergoing his second dose. Few leukocytoclastic vasculitis cases after SARS-CoV-2-vaccination have been reported in adults, primarily flares of previously known vasculitis. A role for induced spike glycoprotein as a pseudovirion docking to specific vascular receptors has been suggested, too. To our knowledge, no similar cases were described currently, neither in such young patients nor with such atypical, focal lesions. Further studies are needed to identify the pathogenesis and possibly prevent the onset of this adverse reaction.
ABSTRACT
Background: Large-scale vaccination against the novel coronavirus (COVID-19) occurred globally at an unprecedented pace. Sporadic cases of autoimmune encephalitis (AE) have been reported following COVID-19 vaccination, mainly in adults. Case report: A 14-year-old girl developed altered mental status and was brought to our emergency department because of a seizure 19 days after receiving the third dose of COVID-19 vaccination. She was treated with steroid pulse therapy and fully recovered. The diagnosis of probable autoantibody-negative AE was finally made. Conclusion(s): This case met the criteria for probable autoantibody-negative AE in children, as well as adults. Because of the temporal association and absence of another identifiable cause, her conditions may have been triggered by the COVID-19 vaccination. To our knowledge, this is the first published pediatric case of autoantibody-negative but probable AE following COVID-19 vaccination.Copyright © 2023 The Authors