scholarly journals Proactive anti-inflammatory and anticoagulant therapy in the treatment of advanced stages of novel coronavirus infection (COVID-19). Case Series and Study Design: COLchicine versus ruxolitinib and secukinumab in open prospective randomIzed trial (COLORIT)

Kardiologiia ◽  
2020 ◽  
Vol 60 (9) ◽  
pp. 4-21
Author(s):  
V. Yu. Mareev ◽  
Ya. A. Orlova ◽  
E. P. Pavlikova ◽  
Z. A. Akopyan ◽  
S. T. Matskeplishvili ◽  
...  

The article is devoted to the treatment of the new coronavirus infection (COVID-19) in the advanced stages of the disease. The types of response of the immune system to the viral load of SARS-CoV-2 with the start of the inflammation process are considered. The situation is analyzed in detail in which the growing autoimmune inflammation (up to the development of a "cytokine storm") affects not only the pulmonary parenchyma, but also the endothelium of the small vessels of the lungs. Simultaneous damage to the alveoli and microthrombosis of the pulmonary vessels are accompanied by a progressive impairment of gas exchange, the development of acute respiratory distress syndrome, the treatment of which, even with the use of invasive ventilation, is ineffective and does not really change the prognosis of patients with COVID-19. In order to interrupt the pathological process at the earliest stages of the disease, the necessity of proactive anti-inflammatory therapy in combination with active anticoagulation treatment is substantiated. The results of the first randomized studies on the use of inhibitors of pro-inflammatory cytokines and chemokines (interleukin-6 (tocilizumab), interleukin-17 (secukinumab), Janus kinase blockers, through which the signal is transmitted to cells (ruxolitinib)), which have potential in the early treatment of COVID- 19. The use of a well-known anti-inflammatory drug colchicine (which is used for gout treatment) in patients with COVID-19 is considered. The design of the original COLORIT comparative study on the use of colchicine, ruxolitinib and secukinumab in the treatment of COVID-19 is presented. Clinical series presented, illustrated early anti-inflammatory therapy together with anticoagulants in patients with COVID-19 and the dangers associated with refusing to initiate such therapy on time.

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3094 ◽  
Author(s):  
Jun Yin ◽  
Han Hyuk Kim ◽  
In Hyeok Hwang ◽  
Dong Hee Kim ◽  
Min Won Lee

Quercus mongolica Fisch. ex Ledeb. (QM) has been used as an oriental traditional medicine to relieve hemorrhoids, fever, and enteritis. We screened the inhibitory activities of the extracts and compounds (1–6) isolated from QM on the production of inflammatory cytokines and chemokines to evaluate their anti-inflammatory activities. Further, we evaluated the expression levels of cytokines, chemokines, and immune factors on pedunculagin (PC, 1), which was selected from isolated compounds (1–6) because of its potential anti-inflammation effect. Additionally, we evaluated whether the inflammation mitigation effects of PC (1) following UVB exposure in keratinocytes occurred because of nuclear factor (NF)-κB and signal transducer and activator of transcription (STAT)/Janus kinase (JAK) activation. PC (1) remarkably suppressed interleukin (IL)-6, IL-10, IL-13, and monocyte chemoattractant protein-1 (MCP-1) mRNA expression and reduced the mRNA expression level of Cyclooxygenase-2 (COX-2) and also reduced the phosphorylation of p38 mitogen-activated protein kinases (p38), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in a concentration-dependent manner.


2022 ◽  
Author(s):  
Shumin Li ◽  
Siying Liu ◽  
Rui Ai Chen ◽  
Mei Huang ◽  
To Sing Fung ◽  
...  

Coronavirus infections induce the expression of multiple proinflammatory cytokines and chemokines. We have previously shown that in cells infected with gammacoronavirus infectious bronchitis virus (IBV), interleukin 6 (IL-6) and IL-8 were drastically upregulated, and the MAP kinase p38 and the integrated stress response pathways were implicated in this process. In this study, we report that coronavirus infection activates a negative regulatory loop that restricts the upregulation of a number of proinflammatory genes. As revealed by the initial transcriptomic and subsequent validation analyses, the anti-inflammatory adenine-uridine (AU)-rich element (ARE)-binding protein, Zinc finger protein 36 (ZFP36) and its related family members were upregulated in cells infected with IBV and three other coronaviruses, alphacoronaviruses porcine epidemic diarrhea virus (PEDV) and human coronavirus 229E (HCoV-229E), and betacoronavirus HCoV-OC43, respectively. Characterization of the functional roles of ZFP36 during IBV infection demonstrated that ZFP36 promoted the degradation of transcripts coding for IL-6, IL-8, dual-specificity phosphatase 1 (DUSP1), prostaglandin-endoperoxide synthase 2 (PTGS2) and TNF-α-induced protein 3 (TNFAIP3), through binding to AREs in these transcripts. Consistently, knockdown and inhibition of JNK and p38 kinase activities reduced the expression of ZFP36, as well as the expression of IL-6 and IL-8. On the contrary, overexpression of mitogen-activated protein kinase kinase 3 (MKK3) and MAPKAP kinase-2 (MK2), the upstream and downstream kinases of p38, respectively, increased the expression of ZFP36 and decreased the expression of IL-8. Taken together, this study reveals an important regulatory role of the MKK3-p38-MK2-ZFP36 axis in coronavirus infection-induced proinflammatory response. Importance Excessive and uncontrolled induction and release of proinflammatory cytokines and chemokines, the so-called cytokine release syndrome (CRS), would cause life-threatening complications and multiple organ failure in severe coronavirus infections, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and COVID-19. This study reveals that coronavirus infection also induces the expression of ZFP36, an anti-inflammatory ARE-binding protein, promoting the degradation of ARE-containing transcripts coding for IL-6 and IL-8 as well as a number of other proteins related to inflammatory response. Furthermore, the p38 MAP kinase, its upstream kinase MKK3 and downstream kinase MK2 were shown to play a regulatory role in upregulation of ZFP36 during coronavirus infection cycles. This MKK3-p38-MK2-ZFP36 axis would constitute a potential therapeutic target for severe coronavirus infections.


2021 ◽  
Vol 64 (2) ◽  
pp. 116-123
Author(s):  
Soo Min Ahn ◽  
Yong-Gil Kim

Ankylosing spondylitis (AS) is a chronic inflammatory disease predominantly affecting the axial skeleton. AS treatment aims to reduce pain and inflammation and maintain functional capacity. Nonsteroidal anti-inflammatory drugs are the first-line treatment for those with active AS. While for peripheral arthritis, sulfasalazine or local glucocorticoid injection can be used, these are not recommended for axial symptoms. Twenty years ago, biological products that target the tumor necrosis factor (TNF) were developed. These have been approved for use in rheumatoid arthritis and AS. Since the introduction of these TNF inhibitors, the control of disease activity in AS has improved markedly. TNF inhibitors, including both anti-TNF-alpha monoclonal antibodies and recombinant TNF soluble receptors, can be considered for patients with persistently active disease despite nonsteroidal anti-inflammatory drug treatment. Recently, interleukin-17 inhibitors have also been approved for use in AS patients with insufficient responses to TNF inhibitors. Ongoing clinical trials are exploring the effect of Janus kinase inhibitors against AS. This review summarizes the current pharmaceutical treatment for AS, focusing on the biological products. Recommendations for AS management are also discussed in this review.


Author(s):  
Jacob J Glaser ◽  
Adam Czerwinski ◽  
Ashley Alley ◽  
Michael Keyes ◽  
Valentino Piacentino ◽  
...  

Background: REBOA has become an established adjunct to hemorrhage control. Prospective data sets are being collected, primarily from large, high volume trauma centers. There are limited data, and guidelines, to guide implementation and use outside of highly resourced environments. Smaller centers interested in adopting a REBOA program could benefit from closing this knowledge gap. Methods: A clinical series of cases utilizing REBOA from Grand Strand Medical Center, Myrtle Beach, South Carolina were reviewed. This represents early data from a busy community trauma center (ACS Level 2), from January 2017 to May 2018. Seven cases are identified and reported on, including outcomes. Considerations and ‘lessons learned’ from this early institutional experience are commented on.   Results: REBOA was performed by trauma and acute care surgeons for hemorrhage and shock (blunt trauma n=3, penetrating trauma n=2, no- trauma n=2). All were placed in Zone 1 (one initially was placed in zone 3 then advanced). Mean (SD) systolic pressure (mmHg) before REBOA was 43 (30); post REBOA pressure was 104 (19). N=4 were placed via an open approach, n=3 percutaneous (n=2 with ultrasound). All with arrest before placement expired (n=3) and all others survived. Complications are described.   Conclusions: REBOA can be a feasible adjunct for shock treatment in the community hospital environment, with outcomes comparable to large centers, and can be implemented by acute care and trauma surgeons. A rigorous process improvement program and critical appraisal process are critical in maximizing benefit in these centers.


2020 ◽  

Ibuprofen is a long lasting non-steroidal anti-inflammatory drugs (NSAIDs) and still represents one of the most diffused analgesics around the world. It has an interesting story started over 50 years ago. In this short comment to an already published paper, the authors try to focus some specific important point. On top, they illustrate the recent, confusing and fake assertion on the potentially dangerous influence that ibuprofen could have, increasing the risk of Coronavirus infection. This is also better illustrated in a previously published paper, where the readers could find more clear responses to eventual doubts.


2021 ◽  
pp. 221049172098698
Author(s):  
Wai-Him Lam ◽  
Chi-Yin Tso ◽  
Ning Tang ◽  
Wing-Hoi Cheung ◽  
Ling Qin ◽  
...  

Biodegradable magnesium-based implants are innovative alternatives that potentially eliminate the need for implant removal. Recent studies have demonstrated the osteogenic properties and bacterial inhibition potentials of magnesium screws. We reported a clinical series of three elbow fracture cases, where magnesium screws were used in the treatment of one radial head and two capitellum fractures. Postoperative clinical courses were uneventful, and fracture healing occurred within 3 months. In all cases, radiolucencies were observed around implants especially in the screw head region at 2 months post-operation, but disappeared with consolidation at 1 year post-operation. All patients achieved near normal range of motion, minimal symptoms and good functional outcomes. No complication such as failure of fixation, loss of reduction, malunion or infection was seen. No implant revision or removal was necessary. Magnesium bioabsorbable screws are shown to be a viable option for these fractures.


Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 918
Author(s):  
Adéla Holubová ◽  
Lucie Chlupáčová ◽  
Lada Cetlová ◽  
Niels A. J. Cremers ◽  
Andrea Pokorná

Non-healing wounds are usually colonised by various types of bacteria. An alternative to antibiotic treatment in patients with infected wounds with local signs of inflammation may be medical-grade honey (MGH), which favourably affects the healing process with its antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory properties. The objective of this study was to evaluate the effect of MGH therapy on the healing process of non-healing wounds of various aetiologies and different wound colonisations. Prospective, observation–intervention case studies (n = 9) of patients with wounds of various aetiologies (venous leg ulcers, diabetic foot ulcers, surgical wound dehiscence) are presented. All wounds were treated with MGH and the healing trajectory was rigorously and objectively monitored. In all cases, pain, odour, and exudation were quickly resolved, which led to an improvement in the quality of life of patients. Despite the proven bacterial microflora in wounds, antibiotic treatment was not necessary. The effects of MGH alleviated the signs of local infection until their complete elimination. In eight out of nine cases, the non-healing wound was completely healed. MGH has antimicrobial, anti-inflammatory, and antioxidant effects in wounds of various aetiologies and forms an effective alternative for the use of antibiotics for treating locally infected wounds.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Vana Vukić ◽  
Ana Smajo ◽  
Mandica Vidović ◽  
Rudolf Vukojević ◽  
Miroslav Harjaček ◽  
...  

Abstract Background The last two decades brought new treatment options and high quality guidelines into the paediatric rheumatologic practice. Nevertheless, a number of patients still present a diagnostic and therapeutic challenge due to combination of vague symptoms and unresponsiveness to available treatment modalities. Case presentation We report a case of sixteen years old girl suffering from polyarticular type of juvenile idiopathic arthritis refractory to multiple treatment options. She first presented at the age of 4 with swelling and contractures of both knees. Her symptoms were initially unresponsive to nonsteroidal anti-inflammatory drugs and progressed despite treatment with intraarticular and systemic glucocorticoids and methotrexate. Throughout the years, she received several biologics together with continuous administration of nonsteroidal anti-inflammatory drugs and disease modifying anti-rheumatic drugs as well as intraarticular and systemic glucocorticoids in disease flares. However, none of this options  provided a permanent remission, so various other modalities, as well as other possible diagnoses were constantly being considered. Eventually she became dependent on a daily dose of systemic glucocorticoids. In 2018, the treatment with Janus kinase inhibitor tofacitinib was initiated, which led to gradual amelioration of musculoskeletal symptoms, improvement of inflammatory markers and overall well-being, as well as to the weaning of systemic glucocorticoids. As the swelling of the wrists subsided for the first time in many years, Madelung’s deformity was noticed, first clinically, and later radiographically as well. Genetic analysis revealed short-stature homeobox gene deficiency and confirmed the diagnosis of Leri Weill syndrome. Conclusions This case report emphasizes the need for reporting refractory, complicated cases from everyday clinical practice in order to build-up the overall knowledge and share experience which is complementary to available guidelines. Individual reports of difficult to treat cases, especially when additional diagnoses are involved, can be helpful for physicians treating patients with common rheumatological diseases such as juvenile idiopathic arthritis.


Oral ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 159-167
Author(s):  
Lucio Lo Russo ◽  
Eleonora Lo Muzio ◽  
Giuseppe Colella ◽  
Maria Eleonora Bizzoca ◽  
Vera Panzarella ◽  
...  

(1) Background: Gingival cancer has a significant incidence and is often diagnosed at advanced stages. The aim of this paper is to highlight its clinical aspects on the basis of a case series analysis in order to promote awareness and improve the diagnosis process. (2) Methods: Oral cancers diagnosed and treated at three Italian University Hospitals over ten years were retrospectively investigated. Cancer location on the gingiva, edentulous ridge, and retromolar pad was addressed. Data regarding clinical features, stage at the diagnosis, and time from presenting symptoms to first medical consultation were retrieved. (3) Results: Thirty-three cancers located on the gingiva, edentulous ridge, and retromolar pad were retrieved from 276 total oral cancer cases (11.9%). A median of 50 days (range 2–300) passed for the patient to seek for a medical evaluation. At the time of diagnosis, 63.3% were advanced stage cancers, mainly located at the mandible (91%), especially in the retromolar pad (48.5%) and the edentulous alveolar ridge (24.2%). Lesions were red (45.5%), red and white (45.4%), or white (9.1%), appearing as an ulcer (69.7%), exophytic mass (12.1%) or flat lesion (12.1%). Sixty-six percent of cancers were completely asymptomatic, regardless their clinical appearance. A statistically significant association between the time from the presentation of symptoms to the first medical consultation and the cancers stage was found. (4) Conclusions: The clinical appearance of gingival cancer is very polymorphous; its understanding may be significant to improve patient education and early medical consultation.


2015 ◽  
Vol 86 (11) ◽  
pp. e4.158-e4
Author(s):  
Catherine Morgan ◽  
Benjamin Wakerley ◽  
Geraint Fuller

Guillain Barré syndrome (GBS) varies both in terms of clinical phenotype and underlying pathology. Serial assessments allow greater understanding of the pathophysiology. The evolution of neurophysiological changes is particularly helpful in distinguishing between demyelination and reversible axonal conduction failure.Bilateral facial weakness with distal paraesthesias is a rare subtype of GBS. In the largest case series 64% had abnormalities in motor and 27% in sensory conduction on single neurophysiological assessments; this was interpreted as a demyelinating neuropathy.We report an 18-year-old male with bilateral lower motor neurone facial weakness preceded by distal paraesthesias following a ‘flu-like illness. Examination of power and sensation was normal. Deep tendon reflexes were present. Cerebrospinal fluid showed albuminocytologic dissociation. By 6 weeks his facial weakness had almost completely resolved without treatment.Serial nerve conduction studies were performed. The first study (day 4) found prolonged distal motor latency and delayed F waves in posterior tibial and common peroneal nerves; normal sensory studies. Second study (day 18) found distal motor latencies and F waves had increased in upper and lower limb nerves. Third study (day 60) found improvement but abnormalities remained with changes similar to the first study.The neurophysiological changes became more marked while he improved clinically. These serial studies confirmed the primary pathological process of this GBS variant to be demyelination.


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