scholarly journals The Systematic Effect of Mesenchymal Stem Cell Therapy in Critical COVID-19 Patients: A Prospective Double Controlled Trial

2021 ◽  
Vol 30 ◽  
pp. 096368972110249
Author(s):  
G Adas ◽  
Z Cukurova ◽  
K Kart Yasar ◽  
R Yilmaz ◽  
N Isiksacan ◽  
...  

The aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 106 cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFNγ, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-β, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.


2021 ◽  
Vol 74 (7) ◽  
pp. 1575-1580
Author(s):  
Serhii V. Pylypenko ◽  
Andrii A. Koval ◽  
Makarchuk V. Viktoria ◽  
Kostiantyn F. Chub

The aim: Of the work was to determine the content of pro- and anti-inflammatory cytokines in the blood serum of the control group rats and after 28 days of inhibiting HCl secretion in the stomach by proton pump blockers “Omeprazole” and “Pantoprazole”. Materials and methods: The studies were performed on 30 white non-linear male rats weighing 160-180 g, divided into three groups with 10 animals in each. The control (group 1) were injected intraperitoneally with water for injections within 28 days once a day. Group 2 was administered omeprazole. Group 3 was administered pantoprazole. The concentration of cytokines in the blood serum of rats was determined by the enzyme immunoassay method. For statistic data processing, Student’s t-criterion for independent samples was applied. Results: After prolonged administration of omeprazole and pantoprazole, the blood serum concentrations of IFNγ, TNFα, IL-1 in rats increased by 58.5% and 3.41%, 73.3% and 48.4%, 80.2% and 40.8%, respectively, and IL-12B 40p decreased by 36.6% when using omeprazole and was almost indistinguishable from the control values when pantoprazole was administered. With administration of omeprazole, IL-4 concentration decreased by 39.8% and that of pantoprazole increased by 3.86% compared to the control. Administration of omeprazole and pantoprazole did not affect IL-6 concentration. Conclusion: Inhibition of hydrochloric acid secretion in the stomach of rats for 28 days using omeprazole and pantoprazole led to an imbalance between pro- and anti-inflammatory cytokines. The adverse effect of pantoprazole was less pronounced than that of omeprazole.



2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina Scharf ◽  
Ines Schroeder ◽  
Michael Paal ◽  
Martin Winkels ◽  
Michael Irlbeck ◽  
...  

Abstract Background A cytokine storm is life threatening for critically ill patients and is mainly caused by sepsis or severe trauma. In combination with supportive therapy, the cytokine adsorber Cytosorb® (CS) is increasingly used for the treatment of cytokine storm. However, it is questionable whether its use is actually beneficial in these patients. Methods Patients with an interleukin-6 (IL-6) > 10,000 pg/ml were retrospectively included between October 2014 and May 2020 and were divided into two groups (group 1: CS therapy; group 2: no CS therapy). Inclusion criteria were a regularly measured IL-6 and, for patients allocated to group 1, CS therapy for at least 90 min. A propensity score (PS) matching analysis with significant baseline differences as predictors (Simplified Acute Physiology Score (SAPS) II, extracorporeal membrane oxygenation, renal replacement therapy, IL-6, lactate and norepinephrine demand) was performed to compare both groups (adjustment tolerance: < 0.05; standardization tolerance: < 10%). U-test and Fisher’s-test were used for independent variables and the Wilcoxon test was used for dependent variables. Results In total, 143 patients were included in the initial evaluation (group 1: 38; group 2: 105). Nineteen comparable pairings could be formed (mean initial IL-6: 58,385 vs. 59,812 pg/ml; mean SAPS II: 77 vs. 75). There was a significant reduction in IL-6 in patients with (p < 0.001) and without CS treatment (p = 0.005). However, there was no significant difference (p = 0.708) in the median relative reduction in both groups (89% vs. 80%). Furthermore, there was no significant difference in the relative change in C-reactive protein, lactate, or norepinephrine demand in either group and the in-hospital mortality was similar between groups (73.7%). Conclusion Our study showed no difference in IL-6 reduction, hemodynamic stabilization, or mortality in patients with Cytosorb® treatment compared to a matched patient population.



2019 ◽  
Vol 19 (1S) ◽  
pp. 111-112
Author(s):  
I V Stagniyeva ◽  
P A Stateshnaya

Purpose: to determine the role of a pain symptom in the diagnosis of rhinosinusitis on the background of immune deficiency. 240 patients with rhinosinusitis without pain symptom were divided into 3 groups: group 1 - patients with acute viral rhinosinusitis (AVRS), group 2 - patients with acute bacterial sinusitis (ABRS), group 3 (n = 32) - control. All patients underwent a complete otorhinolaryngological examination, assessment of the pain symptom, an immunogram, the level of SP in the blood serum. At SP > 100 pg/ml in group 1, the change in indicators was typical for viral infection, in group 2, for bacterial infection. With an SP < 100 pg/ml, the cytokine balance is predominantly biased towards anti-inflammatory cytokines, and the direction of differentiation of Th-1/Th-2 lymphocytes towards the Th-2 pathway, which is manifested by immune deficiency, which leads to severe or prolonged course of the disease, which may indicate impaired neuro-immune interactions.



2021 ◽  
pp. 22-27
Author(s):  
Vita Skoryk

The aim of the study. To compare the effectiveness of methylprednisolone, dexamethasone and tocilizumab in patients with severe coronavirus disease. Identify the most appropriate treatment option. Materials and methods. Patients of group 1 (n=20) received for anti-inflammatory purposes tocilizumab at a dose of 600–800 mg. Patients in group 2 (n=82) received pulse therapy with methylprednisolone. Patients in group 3 (n=20) received dexamethasone 6 mg / day. Data are presented as M [25–75]. Statistical analysis of the results was performed using the program "Statistica 10". Significance of differences in indicators was assessed using the nonparametric Wilcoxon test. The results were considered reliable at values of p <0.05. Results. The severe course of coronavirus disease with the development of cytokine storm and respiratory distress syndrome is characterized by an increase in markers of inflammation: in group 1 the median CRP was 89.2 g / l, in group 2 – 64.2 g / l, and in 3 – 76.2 g / l, and did not differ significantly between groups (p> 0.05). The level of IL-6 in group 1 was 61.8 pg / ml, in group 2 – 64.6 pg / ml, and in group 3 – 46.5 pg / ml without significant differences between groups (p> 0.05). The level of ferritin in all groups exceeded normal values. Conclusions The most favourable result was obtained when using methylprednisolone: it was possible to reduce the mortality rate to 59.8 %. The relative risk of developing VTE was significantly higher in groups 1 and 3 (RR12 6.8 [2.7–16.8] p12 <0.0001, RR23 0.15 [0.06–0.35] p23 <0.0001), which gives grounds to confirm the presence of anticoagulant activity in methylprednisolone



2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Christina Scharf ◽  
Uwe Liebchen ◽  
Michael Paal ◽  
Max Taubert ◽  
Michael Vogeser ◽  
...  

Abstract Objectives Beta-lactam antibiotics are often subject to therapeutic drug monitoring, but breakpoints of target attainment are mostly based on expert opinions. Studies that show a correlation between target attainment and infection resolution are missing. This analysis investigated whether there is a difference in infection resolution based on two breakpoints of target attainment. Methods An outcome group out of 1392 critically ill patients treated with meropenem or piperacillin-tazobactam was formed due to different selection criteria. Afterwards, three groups were created: group 1=free drug concentration (f) was < 100% of the time (T) above the minimal inhibitory concentration (MIC) (< 100% fT >MIC), group 2=100% fT >MIC<4xMIC, and group 3=100% fT >4xMIC. Parameters for infection control, renal and liver function, and estimated and observed in-hospital mortality were compared between those groups. Statistical analysis was performed with one-way analysis of variance, Tukey post hoc test, U test, and bivariate logistic regression. Results The outcome group consisted of 55 patients (groups 1–3, 17, 24, and 14 patients, respectively). Patients allocated to group 2 or 3 had a significantly faster reduction of the C-reactive protein in contrast to patients allocated to group 1 (p = 0.033 and p = 0.026). Patients allocated to group 3 had a worse renal function, a higher Acute Physiology and Chronic Health Evaluation (APACHE II) score, were older, and had a significantly higher in-hospital mortality compared to group 1 (p = 0.017) and group 2 (p = 0.001). The higher mortality was significantly influenced by worse liver function, higher APACHE II, and higher Sequential Organ Failure Assessment (SOFA) score and norepinephrine therapy. Conclusion Achieving the target 100% fT >MIC leads to faster infection resolution in the critically ill. However, there was no benefit for patients who reached the highest target of 100% fT >4xMIC, although the mortality rate was higher possibly due to confounding effects. In conclusion, we recommend the target 100% fT >MIC<4xMIC for critically ill patients. Trial registration NCT03985605



Author(s):  
Дмитрий Валериевич Судаков ◽  
Евгений Владимирович Белов ◽  
Олег Валериевич Судаков ◽  
Ольга Игоревна Гордеева ◽  
Оксана Александровна Андросова

В статье рассматриваются особенности своевременного выявления новой короновирусной инфекцией (НКИ) у пациентов хирургического профиля на уровне приемного отделения областной клинической больницы. Представленная работа является в настоящее время крайне актуальной, в виду продолжающейся в мире пандемии НКИ - Covid-19. Важное значение данному исследованию придает то, что оно направлено на как можно более раннюю диагностику Covid-19, уже на уровне нахождения в приемном отделении при поступлении в многопрофильный стационар. Подобные меры могут существенно помочь в сохранении здоровья медицинских работников и могут оказать положительное влияние на эпидемиологическую обстановку в целом. Интересной составляющей данного исследования является и то, что диагностика Covid-19 основывается лишь на тех лабораторных анализах, которые можно быстро определить в условиях приемного отделения. Объектами исследования послужило 200 пациентов, поступающих в приемное отделение БУЗ ВО ВОКБ №1 исключительно с хирургической патологией. Все больные были подразделены на 4 группы по 50 человек, всем им был поставлен сопутствующий диагноз Covid-19. В 1 группу вошли пациенты, поступающие в приемное отделение без сознания, сбор анамнеза и сбор жалоб у которых был невозможен. 2 группу составили пациенты, у которых НКИ была диагностирована непосредственно после оперативного вмешательства. В 3 группу вошли пациенты, у которых была выявлена НКИ, но объем оперативного вмешательства и объем поражения легких позволял им дальнейшее амбулаторное лечение. 4 группу составили пациенты, у которых Covid-19 выявлялся в течение 3 дней после оперативного вмешательства. У всех больных подробно собирался анамнез жизни и эпидемиологический анамнез (за исключением 1 группы), анализировались наиболее частые клинические проявления и показатели общего и биохимического анализа крови, обрабатывались данные КТ легких. Были определены основные клинические симптомы НКИ, такие как: повышенная температура тела, кашель, слабость и утомляемость. Наиболее важными лабораторными показателями стало определение уровня лейкоцитоза, с уровнем нейтрофилов и лимфоцитов, а также СОЭ, D-димера, С-реактивного белка. Представленная статья представляет большой интерес для врачей, работающих в условиях приемных отделений многопрофильных стационаров. По результатам работы планируется продолжение исследования с большей выборкой пациентов и большим количеством изучаемых параметров The article discusses the features of the timely detection of a new coronavirus infection (NCI) in surgical patients at the level of the admission department of a regional clinical hospital. The presented work is currently extremely relevant, in view of the ongoing NСI pandemic in the world - Covid-19. The importance of this study is attached to the fact that it is aimed at the earliest possible diagnosis of Covid-19, already at the level of being in the admission department upon admission to a multidisciplinary hospital. Such measures can significantly help preserve the health of medical workers and can have a positive impact on the epidemiological situation in general. An interesting component of this study is the fact that the diagnosis of Covid-19 is based only on those laboratory tests that can be quickly determined in the conditions of the admission department. The objects of the study were 200 patients admitted to the admission department of BUZ VO VOKB № 1 exclusively with surgical pathology. All patients were divided into 4 groups of 50 people, all of them were diagnosed with a concomitant Covid-19 diagnosis. Group 1 consisted of patients admitted to the emergency department unconscious, and it was impossible to collect anamnesis and collect complaints. Group 2 consisted of patients in whom NCI was diagnosed immediately after surgery. Group 3 included patients who had NCI, but the volume of surgery and the volume of lung lesions allowed them further outpatient treatment. Group 4 consisted of patients in whom Covid-19 was detected within 3 days after surgery. In all patients, a detailed life history and epidemiological history were collected (except for group 1), the most frequent clinical manifestations and indicators of general and biochemical blood tests were analyzed, and CT data of the lungs were processed. The main clinical symptoms of NCI were identified, such as: fever, cough, weakness and fatigue. The most important laboratory indicators were the determination of the level of leukocytosis, with the level of neutrophils and lymphocytes, as well as ESR, D-dimer, C-reactive protein. The presented article is of great interest to doctors working in the admission departments of multidisciplinary hospitals. Based on the results of the work, it is planned to continue the study with a larger sample of patients and a large number of studied parameters



2018 ◽  
Vol 21 (1) ◽  
pp. 4-10 ◽  
Author(s):  
Melissa M. Stamates ◽  
David M. Frim ◽  
Carina W. Yang ◽  
Gregory L. Katzman ◽  
Saad Ali

OBJECTIVETethered cord syndrome (TCS) is a neurosurgical disorder with varied clinical manifestations believed to result from vascular compromise due to stretch forces on the spinal cord. Conventional supine MRI findings may include a low-lying conus medullaris, thickened or fat-infiltrated filum terminale, or lipoma; however, imaging sensitivity and specificity for tethered cord can be low. The purpose of this study was to evaluate the utility of prone MRI in the diagnosis of tethered and retethered spinal cord.METHODSMedical records were reviewed in 41 patients who underwent surgical release of tethered cord and in whom preoperative prone MRI sequences were available. Patients were divided into Group 1 (new TCS diagnosis) and Group 2 (recurrent TCS after previous untethering). Absolute conus ventral motion and motion as a percentage of canal width between supine and prone positions was measured in these 2 groups via sagittal T2-weighted sequences; these groups were compared with 30 consecutive patients (Group 3) who were classified as the normal control group.RESULTSThe mean ventral motion was as follows: Group 1 (absolute: 0.5 ± 0.5 mm [range 0–2.4 mm]; canal percentage: 3.7% ± 3.9% [range 0%–16.3%]); Group 2 (absolute: 0.4 ± 0.7 mm [range 0–2.6 mm]; canal percentage: 2.2% ± 3.7% [range 0%–14.0%]); and Group 3 (absolute: 3.4 ± 1.3 mm [range 1.4–5.6 mm]; canal percentage: 22.0% ± 7.2% [range 10.5%–36.1%]). Whereas 38/41 surgically treated patients with TCS had diminished (< 10% canal width) ventral motion on preoperative MRI, 30/30 controls had > 10% canal width motion. Sensitivity and specificity were thereby calculated as 92.7% and 100%, respectively.CONCLUSIONSIn the present series, prone imaging is found to be a sensitive and specific tool, and the authors believe it may have a role as supportive evidence in the diagnosis of tethered and retethered spinal cord.



2020 ◽  
pp. 112067212096205
Author(s):  
Mehmet Cem Sabaner ◽  
Muberra Akdogan ◽  
Mustafa Doğan ◽  
Ayse Yesim Oral ◽  
Resat Duman ◽  
...  

Purpose: To determine the levels of serum oxidative, antioxidative markers and inflammatory cytokines in patients diagnosed with diabetic macular edema (DME) whose hyperreflective spots (HRS) were detected by optical coherence tomography (OCT). Methods: In this prospective cross-sectional clinical study included a total of 88 patients; 31 patients (group-1) with DME and HRS detected by OCT, 29 patients (group-2) with DME without HRS, and 28 patients (group-3) diagnosed with diabetes mellitus (DM) without any diabetic retinopathy findings. The main outcomes were best-corrected visual acuity (BCVA), CMT (central macular thickness), CMV (central macular volume), TMV (total macular volume), CT (choroidal thickness), serum TAS (total antioxidant status), TOS (total oxidant status), VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor) and IL-1b levels. OCT parameters and biochemical measurements were compared statistically between the three groups. Results: A total of 88 patients (43 females (48.9%) and 45 males (51.1%)) were included in the study. The mean age was 56.29 ± 9.23 years. There was no difference between the three groups in age-and-sex. In group-1 and 2, BCVA(LogMAR) was statistically higher than group 3. CMT, CMV, TMV, TAS, TOS, VEGF and FGF were significantly higher in group-1 than in group-3. CMT, CMV, TMV, VEGF and FGF were significantly higher in group-2 than group 3. TOS and VEGF were significantly higher in group-1 than group-2. Conclusions: This study demonstrates that in patients with DME and HRS, TOS and VEGF levels were higher than those without HRS. Hence, hyperreflective spots may be an inflammatory biomarker.



2021 ◽  
pp. 1-8
Author(s):  
Goichiro Tamura ◽  
Takayuki Inagaki

<b><i>Background and Objective:</i></b> Acute encephalopathy is a life-threatening brain dysfunction in children, often associated with a preceding infection and diffuse noninflammatory brain edema. At present, the role of decompressive craniectomy (DC) over the swollen area of the brain is unclear. The risk factors for predicting clinical deterioration also need clarification. <b><i>Methods:</i></b> A retrospective study of pediatric patients admitted between 2015 and 2019 with acute cerebral encephalopathy was carried out. Patients were classified according to: (1) the preceding pathogens, (2) the syndromic classification, and (3) the extent of brain edema. The syndromic classification is a relatively new classification of acute encephalopathy proposed in 2016 and divides patients into 3 groups: those with systemic inflammatory reactions or “cytokine storms” (group 1), those with status epilepticus but no cytokine storm (group 2), and others (group 3). Glasgow Outcome Scale (GOS) scores of 1–3 were defined as unfavorable, while a GOS score of 4 or 5 was defined as a favorable outcome in this study. DC was performed for select patients with life-threatening signs of brainstem compression. <b><i>Results:</i></b> Nineteen patients (mean age: 23.3 months) were included in the study, 8 (42.1%) of whom had an unfavorable outcome. There was no significant correlation between the types of pathogens and outcome. Unfavorable outcomes were observed in significantly more patients in group 1 (87.5%) than group 2 (14.3%) and group 3 (0%). There was a significant association between diffuse brain edema and unfavorable outcomes (72.7%). Neurosurgical DC was performed in 2 patients to alleviate life-threatening brainstem compression: one with a cytokine storm and diffuse bilateral brain edema, and the other with prolonged status epilepticus causing diffuse right-sided brain edema. The GOS score was 3 and 4, respectively. <b><i>Conclusion:</i></b> The risk factors for clinical deterioration in pediatric acute encephalopathy were evaluated based on a variety of classifications, including the new syndromic classification. Laboratory features of cytokine storms and radiological evidence of diffuse brain edema were associated with unfavorable outcomes. The role of surgical decompression is still controversial and should be assessed on a case-by-case basis.



2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1803.1-1804
Author(s):  
O. Egorova ◽  
B. Belov

Background:Panniculitis is a group of heterogeneous inflammatory diseases that occur with damage to the subcutaneous fat (SCF), musculoskeletal system, and often internal organsObjectives:to evaluate the course and outcome in patients with panniculitisMethods:the course of the disease was monitored in 193 patients treated at the V.A. Nasonova Research Institute of Rheumatology for 3-5 years (142 women, 51 men) aged 19 to 77 with the referral diagnosis of erythema nodosum (EN) and undifferentiated panniculitis and with the disease duration of 1 week to 13 years. In addition to general clinical study, serum concentrations of α-1 antitrypsin, amylase, lipase, ferritin, creatinephosphokinase were determined, computed tomography of the chest organs, immunological, ultrasound scanning of the skin and SCF of the node area, tuberculosis tests and pathomorphological study of skin biopsy from the node area were performed.Results:: as a result of laboratory and instrumental examination, the following diagnoses were made: EN associated with infection (72 people – group 1), lipodermatosclerosis (LDS) (40 –group 2), idiopathic lobular panniculitis (ILP) (32 – group 3), Löfgren’s syndrome (SL) (49 –group 4). During the follow-up period, 6 deaths occurred (3.1%): in a patient with LDS due to acute heart failure and in 5 patients with ILP due to the activity of the disease which led to the development of cardiopulmonary pathology and disseminated intravascular coagulation (DIC) syndrome. In group 1, during the observation period, UE recurred in 18 people (25%), the probable causes were: hypothermia (6), exacerbation of chronic tonsillitis (6), acute respiratory viral infections (ARVI) (4), stress (1), a rapid decrease in the dose of glucocorticoids (GC) (1), the cause is unknown (2). In group 2, recurrence occurred in 19 patients (47.5%) due to the lack of anti-inflammatory therapy (plaquenil) (10), trauma (4), stress (3), and weight lifting (2). There was no recurrence in 7 patients in this group, however, nodes would not disappear completely, which is obviously due to the absence of plaquenil. In group 3, recurrence was registered in 24 cases (75%) and it was associated with insufficient effect of the ongoing anti-inflammatory therapy (9), a decrease in blood glucose to minimal doses (6), hypothermia (6) and the absence/cancellation of anti-inflammatory therapy (3). In group 4, recurrence of nodes was registered in 14 cases (28.5%), possible causes: cancellation of GC (9) and cooling/ARVI(5).Conclusion:in the observed group of patients with panniculitis mortality was 3.1%. The main causes of recurrence in EN were viral-bacterial infections, and in case of ILP, LDS and SL it was insufficient effect/absence of anti-inflammatory therapy.Disclosure of Interests:None declared



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