889 results on '"immunomodulatory therapy"'
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2. Evaluating the Efficacy and Safety of Baricitinib in Reducing COVID-19 Mortality: A Comprehensive Review of Clinical Evidence and Pharmacological Strategies.
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Kwaśniewska, Paulina, Graczyk, Patryk, Wilewska, Anna, Borowiec, Kinga, Borowiec, Agnieszka, Biernikiewicz, Julia, Alabrudziński, Konstanty, Biernikiewicz, Milena, Pomirski, Bartosz, and Pomirska, Agata more...
- Abstract
Introduction: COVID-19 manifests with symptoms ranging from mild to severe, including respiratory and cardiovascular complications. Severe cases are often marked by a cytokine storm, causing pulmonary damage and multi-organ dysfunction. Current treatments lack a specific antiviral, though several pharmacological options, including immunomodulatory and antiviral drugs, are under investigation. Purpose: The purpose of this article is to provide an evaluation of the efficacy and safety of baricitinib, a JAK inhibitor, combined with standard care for hospitalized adults with COVID-19. By reviewing recent literature, it aims to assess baricitinib's effectiveness in improving patient outcomes. Material and methods: A systematic review of clinical trials and case studies was conducted to analyze baricitinib's impact on COVID-19 mortality. Data includes treatment-emergent adverse events and patient outcomes in moderate to severe cases. Discussion: Baricitinib has demonstrated potential in managing hyperinflammation in severe COVID-19 by inhibiting multiple proinflammatory cytokines and enhancing immune response. Clinical trials show that baricitinib, particularly in combination with corticosteroids, reduces mortality and serious infections compared to standard care alone. Due to potential adverse events, continuous monitoring of hematological and lipid levels is essential. These findings highlight baricitinib's dual role as an immunomodulatory and antiviral agent, suggesting its importance in treating severe COVID-19. Future research should focus on optimizing treatment regimens and further exploring the long-term implications of baricitinib therapy. [ABSTRACT FROM AUTHOR] more...
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- 2024
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3. Risk of Intestinal Complications, Extraintestinal Morbidity, and Mortality in Patients with Crohn's Disease and Ocular Involvement.
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Alsoudi, Amer F., Wai, Karen M., Koo, Euna, McConnell, Ryan A., Pham, Nathan H., Do, Brian K., Ludwig, Cassie A., Kossler, Andrea L., Mruthyunjaya, Prithvi, and Rahimy, Ehsan
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CROHN'S disease , *IRON deficiency anemia , *INFLAMMATORY bowel diseases , *PROPENSITY score matching , *ELECTRONIC health records , *CHOLANGITIS - Abstract
Purpose: Patients with Crohn's disease (CD) and subsequent ocular manifestations may have worse outcomes when compared to matched patients with CD without ocular disease. Methods: In this retrospective cohort study, an aggregated electronic health records research network, TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with CD stratified by the presence or absence of ocular involvement with at least 1 year of follow-up. Propensity score matching (PSM) was performed to control for baseline demographics and medical comorbidities. Results: Patients with CD with ocular disease showed a greater risk of undergoing bowel resections (RR: 2.06, 95% CI: 1.48–2.85, p < 0.001), developing other CD-related gastrointestinal complications (RR: 1.31, CI: 1.15–1.49, p < 0.001), or acquiring Clostridioides difficile infections (RR: 2.19, CI: 1.89–2.54, p < 0.001). Further, patients with CD with ocular sequelae had a greater risk of developing NASH (RR: 1.43, CI: 1.31–1.56, p < 0.001), CD-related nutrient deficiencies (RR: 1.38, CI: 1.29–1.49, p < 0.001), iron deficiency anemia (RR: 1.41, CI: 1.33–1.50, p < 0.001), CD-related dermatological disease (RR: 1.84, CI: 1.65–2.05, p < 0.001), osteoporosis (RR: 1.49, CI: 1.37–1.64, p < 0.001) and primary sclerosing cholangitis (RR: 1.63, CI: 1.11–2.38, p = 0.011). Among patients with CD with ocular involvement, there was an elevated risk of MI (RR: 1.36, CI: 1.14–1.63, p < 0.001), stroke (RR: 1.42, CI: 1.18–1.70, p < 0.001), VTE (RR: 1.37, CI: 1.22–1.54, p < 0.001), and sepsis (RR: 1.53, CI: 1.37–1.71, p < 0.001). Conclusions: Patients who have CD and subsequent ocular involvement have an increased risk of local intestinal complications, extraintestinal morbidity, and cardiovascular complications when compared to patients with CD without ocular involvement. [ABSTRACT FROM AUTHOR] more...
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- 2024
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4. Autoimmune Retinopathy Following COVID-19: A Case Report.
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Fekri, Sahba, Mahmoudimehr, Parisa, Oliya, Behrooz, Abtahi, Seyed-Hossein, and Nouri, Hosein
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VISUAL acuity , *COVID-19 , *VISUAL fields , *OPTICAL coherence tomography , *COVID-19 pandemic - Abstract
Purpose: To present a presumed case of non-paraneoplastic autoimmune retinopathy (nPAIR) following COVID-19 in a healthy woman. Methods: A single case was evaluated and followed for 32 months. Results: A healthy 32-year-old woman presented with photopsia and paracentral scotoma (OU) after a recent COVID-19 infection. Past medical history and family history were unremarkable. Her visual acuity was normal (OU). Retinal atrophy, mild disc pallor, and foveal reflex attenuation were observed (OU). Optical coherence tomography (OCT) scans showed outer nuclear layer thinning and ellipsoid zone disruption (OU). The visual field test showed blind spot enlargement and arcuate scotomas (OU). Uveitis workup and underlying malignancy investigations were negative. A diagnosis of nPAIR was presumed. At the time, she refused therapy, and 20 months later, her visual acuity was stable, but there were progressive retinal atrophic changes and visual field constriction. After initiation of glucocorticoids and immunosuppressive therapy, flashing lights completely disappeared, her visual field was stabilized without progression, and OCT scans showed partial recovery of ellipsoid zone. Conclusion: SARS-CoV-2 infection may be a trigger for nPAIR in susceptible individuals, but further research is needed to determine this association. [ABSTRACT FROM AUTHOR] more...
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- 2024
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5. T cells and macrophages jointly modulate osteogenesis of mesenchymal stromal cells.
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Murayama, Masatoshi, Shinohara, Issei, Toya, Masakazu, Susuki, Yosuke, Lee, Max L., Young, Bill, Gao, Qi, Chow, Simon Kwoon‐Ho, and Goodman, Stuart B.
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Approximately 5%–10% of fractures go on to delayed healing and nonunion, posing significant clinical, economic, and social challenges. Current treatment methods involving open bone harvesting and grafting are associated with considerable pain and potential morbidity at the donor site. Hence, there is growing interest in minimally invasive approaches such as bone marrow aspirate concentrate (BMAC), which contains mesenchymal stromal cells (MSCs), macrophages (Mφ), and T cells. However, the use of cultured or activated cells for treatment is not yet FDA‐approved in the United States, necessitating further exploration of optimal cell types and proportions for effective bone formation. As our understanding of osteoimmunology advances, it has become apparent that factors from anti‐inflammatory Mφ (M2) promote bone formation by MSCs. Additionally, M2 Mφ promote T helper 2 (Th2) cells and Treg cells, both of which enhance bone formation. In this study, we investigated the interactions among MSCs, Mφ, and T cells in bone formation and explored the potential of subsets of BMAC. Coculture experiments were conducted using primary MSCs, Mφ, and CD4+ T cells at specific ratios. Our results indicate that nonactivated T cells had no direct influence on osteogenesis by MSCs, while coculturing MSCs with Mφ and T cells at a ratio of 1:5:10 positively impacted bone formation. Furthermore, higher numbers of T cells led to increased M2 polarization and a higher proportion of Th2 cells in the early stages of coculture. These findings suggest the potential for enhancing bone formation by adjusting immune and mesenchymal cell ratios in BMAC. By understanding the interactions and effects of immune cells on bone formation, we can develop more effective strategies and protocols for treating bone defects and nonunions. Further studies are needed to investigate these interactions in vivo and explore additional factors influencing MSC‐based therapies. [ABSTRACT FROM AUTHOR] more...
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- 2024
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6. Lupus nephritis napjainkban.
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GABRIELLA, SZŰCS, ZSÓFIA, PETHŐ, and SZILVIA, SZAMOSI
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Copyright of Immunology Quarterly / Immunológiai Szemle is the property of Medicina Konyvkiado Zrt. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...
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- 2024
7. Barriers to Adherence with Immunosuppressive Therapy in Patients with Uveitis.
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Sun, Karen, Marshall, Rayna, Frankland, Michael, Taylor, Amal, Montana, Cynthia, Crowell, Eric, Armbrust, Karen R., Kopplin, Laura, and Berkenstock, Meghan
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PATIENT compliance , *CHILD patients , *IMMUNOSUPPRESSIVE agents , *THERAPEUTICS , *ACADEMIC degrees - Abstract
PurposeMethodsResultsConclusionTo evaluate the barriers to adherence with immunomodulatory therapy (IMT) for patients with uveitis across multiple regions of the United States.A multi-center survey of adult and pediatric patients with ocular inflammatory diseases undergoing treatment with IMT was conducted between September 2021 and August 2022. Participating sites included Johns Hopkins Wilmer Eye Institute, Wong Eye Institute of the University of Texas at Austin, University of Wisconsin-Madison, University of Minnesota, Veterans Affairs Hospital of Minneapolis, and Washington University of St. Louis. Each patient completed a self-reporting survey to identify barriers to adherence.The survey was completed by 98 subjects, of whom were 71% white, 67% female, and 61% had a college or advanced degree. Nearly half (49%) were on two or more IMTs of which the most common were methotrexate (38%), mycophenolate (36%), or adalimumab (36%). Nearly half (52%) of patients required reminders to take their medications and 20% found it difficult to take IMT regularly, with 12% struggling to take medications multiple times a day. A lack of refills resulted in 15% of patients missing doses. Limitations to completing laboratory studies to monitor for drug-related side-effects included finding time (10%) and cost (22%).Barriers to IMT treatment include laboratory study cost, difficulty with medication administration, and adhering to medication schedules. Monthly cost of medication was high for some, but no patients were unable to take IMT due to insurance loss. Addressing these barriers may improve IMT adherence for uveitis patients and better clinical outcomes. [ABSTRACT FROM AUTHOR] more...
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- 2024
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8. Long-Term Outcomes of Pediatric Pars Planitis: Retrospective Cohort from a Single Tertiary Center in Turkey.
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Yılmaz Çebi, Aslıhan, Kılıçarslan, Oğuzhan, and Uçar, Didar
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OPTIC disc edema , *BIOLOGICALS , *VISUAL acuity , *MACULAR edema , *SUMMATIVE tests - Abstract
PurposeMethodsResultsConclusionTo retrospectively analyze long-term outcomes of pediatric pars planitis (PP).PP was defined as vitreal inflammation with snowbank or snowball formation in the absence of a related disease. Eighty-five eyes of 44 patients were included in this study. Demographic and clinical characteristics were obtained from medical records.Approximately 70% of the patients were males; the mean patient age was 10.4 ± 3.6 years at presentation, and the mean follow-up time was 42.8 ± 27.9 months. At presentation, the mean best corrected visual acuity (BCVA, logMAR) was 0.17 ± 0.27 in the right eyes and 0.27 ± 0.33 in the left eyes. Common symptoms included blurry vision (29 eyes, 65%), redness (17, 38%), pain (8, 18%), and floaters (5, 11%). Sight-threatening complications included optic disc edema/hyperemia (26, 30%), cataracts (16, 18%), macular edema (16, 18%), and glaucoma (15, 17%). All 38 patients who initially required systemic treatment received corticosteroids. During the follow-up, 24 patients were treated with azathioprine, 20 with methotrexate, 11 with cyclosporine, 20 with adalimumab, and 8 with infliximab. At the final examination, the mean BCVA of the right and left eyes improved significantly (0.08 ± 0.23 and 0.06 ± 0.17,
p = 0.006 andp < 0.001, respectively). The severities of vitritis, anterior chamber inflammation, snowbank/snowball formation, and endotheliitis decreased (allp < 0.001). Thirty-one patients remained on systemic treatment, with only four patients still receiving corticosteroids. No life-threatening adverse effects were reported.Despite pediatric PP’s mild course, severe vision-threatening complications can occur. Immunomodulatory or biologic agents are important for controlling inflammation and tapering corticosteroids. Further research could enhance understanding of optimal treatments. [ABSTRACT FROM AUTHOR] more...- Published
- 2024
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9. Immunohistochemical Expression of Immune Regulatory Proteins in Interface Dermatoses.
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McAlpine, Sarah Grace, Culton, Donna, Duplisea, Michael, Liu, Zhi, Lim, Si On, and Googe, Paul
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LUPUS erythematosus , *ORAL lichen planus , *BIOMARKERS , *TOXIC epidermal necrolysis , *CELL death - Abstract
ABSTRACT Cutaneous immune‐related adverse events (irAEs) of immunotherapies, such as anti‐programmed cell death protein‐1 (PD‐1), suggest that immune checkpoint factors may contribute to the pathobiology of lichenoid interface dermatitis in immunotherapy‐naïve patients. Our study aimed to describe innate and adaptive immune markers via immunohistochemical (IHC) staining of lichenoid interface dermatoses. We studied the staining patterns of PD‐L1, STING, IL‐36 gamma, CD8, PD‐1, and LAG‐3 in five interface dermatoses: oral lichen planus (LP) (
n = 10), cutaneous LP (n = 10), chronic cutaneous lupus erythematosus (CLE) (n = 11), erythema multiforme (EM) (n = 11), and toxic epidermal necrolysis (TEN) (n = 13), by immunohistochemistry (IHC) analysis. Expression was evaluated semi‐quantitively according to the percentage of keratinocytes and dermal lymphocytes stained compared to keratinocytes and resident pericapillary lymphocytes in normal human skin. All interface dermatoses evaluated showed increased expression of PD‐L1 on keratinocytes and LAG‐3 in lymphocytes. STING was increased on the keratinocytes of most specimens. Expression of IL‐36 gamma, in basal layer keratinocytes was more extensive in oral LP and cutaneous LP and varied in CLE, EM, and TEN. Lymphocytic infiltration expressing PD‐1 was elevated in oral LP, cutaneous LP, and CLE. Current thinking is that interface dermatitis is the result of a cell‐mediated immune reaction involving cytotoxic CD8+ T‐cell‐mediated apoptosis of keratinocytes. The findings of this study suggest that in addition to cell‐mediated immunity, innate immune factors may contribute to pathobiology. [ABSTRACT FROM AUTHOR] more...- Published
- 2024
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10. Serum inflammatory biomarkers associated with disease severity and response to dupilumab treatment in bullous pemphigoid: A cluster analysis.
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Li, Jiaqi, Chen, Xixue, Zhu, Xuejun, Shang, Panpan, and Wang, Mingyue
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IMMUNOGLOBULIN G , *SEROTHERAPY , *B cells , *DUPILUMAB , *BLOOD serum analysis - Abstract
Dupilumab, a novel therapy targeting the T helper (Th) 2-mediated inflammation, is showing clinical benefits in treating bullous pemphigoid (BP). However, limited research investigated the serum biomarkers that reflect the inflammation alterations throughout the disease course. To explore the changes of the serum inflammatory biomarkers under dupilumab therapy in BP and establish their correlations with disease severity and clinical outcomes. This exploratory study evaluated serum samples from 40 patients with BP at baseline, 30 of these patients following 16-week dupilumab therapy, and 20 senior healthy controls. Serum levels of 29 cytokines and chemokines were quantified using the Magnetic Luminex Assay. Two distinct clusters based on serum inflammatory profiles were identified. The first cluster, characterized by elevated levels of inflammatory activation, exhibited worse disease severity and poorer remission outcomes. Following the 16-week dupilumab therapy regimen, a significant suppression of Th2-mediated inflammation in the serum was observed, alongside a relative upregulation of Th1 responses. Patients treated with adjuvant systemic steroids exhibited an enhanced suppression of B cell activating factor compared to those receiving dupilumab alone. Significant correlations were unveiled between Th2 biomarkers and clinical scores, eosinophil counts, and anti-BP180 immunoglobulin G levels. Baseline levels of CCL18, Periostin, interleukin (IL)-6, and IL-16 constitute an optimal combination to distinguish between inflammatory clusters. Cluster analysis of serum inflammatory biomarkers provided novel insights into the heterogeneity of the inflammation profiles in BP. Baseline levels of CCL18, Periostin, IL-6, IL-16 emerged as effective predictors for disease severity and therapy response to dupilumab. • Dupilumab, a therapy targeting the interleukin-4 / 13 signaling pathway, has emerged as an effective treatment for bullous pemphigoid. • Dupilumab therapy demonstrated effectiveness in the suppression of serum Type II inflammation. • Serum biomarkers of the Type II inflammation significantly correlated with clinical disease severity of bullous pemphigoid. • Patients with highly activated serum inflammation demonstrated worse disease severity and less favorable clinical outcomes. [ABSTRACT FROM AUTHOR] more...
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- 2024
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11. The Role of Corticosteroids and Immunomodulatory Therapy in the Management of Infectious Uveitis.
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Akhavanrezayat, Amir, Uludag Kirimli, Gunay, Matsumiya, Wataru, Khojasteh, Hassan, Or, Christopher, Karaca, Irmak, Pham, Brandon, Ongpalakorn, Prapatsorn, Lajevardi, Sherin, Lam, Brandon, Hwang, Jaclyn Joyce, Than, Ngoc Trong Tuong, Park, SungWho, Yavari, Negin, Bazojoo, Vahid, Mobasserian, Azadeh, Khatri, Anadi, Halim, Muhammad Sohail, Thng, Zheng Xian, and Ghoraba, Hashem more...
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LITERATURE reviews , *UVEITIS , *CORTICOSTEROIDS , *MEDICAL personnel , *TUBERCULOSIS - Abstract
Purpose: The index review aims to provide an update on the role of corticosteroids and steroid-sparing immunomodulatory therapy (IMT) in managing patients with infectious uveitis. Method: Narrative literature review. Results: Corticosteroids and immunomodulatory therapy (IMT) focus on the host defense system instead of the pathogen, adjusting exaggerated inflammatory reactions to reduce potential harm to ocular tissues. Systemic or local corticosteroids are primarily selected as adjunctive medication for infectious uveitis. Concomitant corticosteroids have also been used in cases of paradoxical worsening in ocular tuberculosis and immune recovery uveitis in cytomegalovirus (CMV) retinitis. While there is no well-established evidence to support the use of IMT in infectious uveitis, it is occasionally used in clinical settings to treat persistent inflammation following resolution of infection such as cases of ocular tuberculosis and ocular syphilis where an insufficient response is observed with corticosteroids. Conclusion: There is no consensus on the position of immunomodulatory therapy in the management of infectious uveitis with different etiologies. The index review provides an overview of available adjunctive corticosteroids and IMT options to assist clinicians in managing such disease entities more efficiently. [ABSTRACT FROM AUTHOR] more...
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- 2024
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12. Dramatic Improvement of Acute Fulminant Lymphocytic Myocarditis with Short-course Intravenous Pulse Corticosteroids: A Case Study
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Abdelfatah Elasfar, Salma Suliman, Mohammed Ahmad Al Hijji, Amr Badr, Issam Al-Bozom, and Ashfaq Patel
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fulminant myocarditis ,immunomodulatory therapy ,intravenous pulse corticosteroids ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
We report a 31-year-old patient with acute fulminant myocarditis, resulting in cardiogenic shock that necessitated mechanical circulatory support, who improved dramatically after treatment with intravenous (IV) pulse steroids. A coordinated multidisciplinary team was the key secret in the cure of this critical patient. In this case study, we focus on the role of IV pulse steroids in the treatment of fulminant lymphocytic myocarditis. more...
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- 2024
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13. The interactions of macrophages, lymphocytes, and mesenchymal stem cells during bone regeneration
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Masatoshi Murayama, Simon K. Chow, Max L. Lee, Bill Young, Yasemin S. Ergul, Issei Shinohara, Yosuke Susuki, Masakazu Toya, Qi Gao, and Stuart B. Goodman
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bone regeneration ,bone marrow aspirate concentrate therapy ,cell-based therapy ,immunomodulatory therapy ,stem cells ,lymphocytes ,macrophages ,mesenchymal stem cells (mscs) ,cytokines ,osteogenesis ,bone marrow aspirate concentrate (bmac) ,secretion ,inflammation ,nonunion of fractures ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes – the main cellular components in BMAC – interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes. Cite this article: Bone Joint Res 2024;13(9):462–473. more...
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- 2024
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14. Risk Factors for Cardiac Involvement in Children with Severe Acute Respiratory Syndrome Coronavirus 2-related Multisystem Inflammatory Syndrome in Children: A Prospective Observational Study
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R. V. Chinchilu, Kiran Narayanan, Susy Joseph, and A. S. Ajith Krishnan
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cardiac manifestations ,immunomodulatory therapy ,multisystem inflammatory syndrome in children ,severe acute respiratory syndrome coronavirus 2 ,Medicine ,Surgery ,RD1-811 ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Introduction: Our study aims to investigate the association between cardiac involvement in multisystem inflammatory syndrome in children (MIS-C) and the patient’s epidemiological, clinical, and investigative profile. Identifying such associations could facilitate the early detection and management of cardiac complications, potentially leading to improved patient outcomes. Materials and Methods: The study was conducted as a prospective observational study at SAT Hospital, Government Medical College, Thiruvananthapuram. It included all children aged 0–12 years admitted during the study period who met the criteria for the diagnosis of MIS-C as per the guidelines provided by the World Health Organization. Exclusion criteria comprised children with a confirmed alternative diagnosis, preexisting heart disease, and those whose parents declined consent for participation. Despite aiming for a sample size of 55 based on previous studies, only 50 samples were obtained within the study period. Ethical considerations were met and no funding was involved in our study. A well-structured pro forma was used for data collection. Results: Our study included 50 children aged under 12 years, with a median age of 7 years, and an interquartile range of 4.6 years. Of these participants, 54% were male, and the remaining 46% were female. According to the operational definition utilized in our study, 62% of the children exhibited cardiac involvement, while 38% had a normal cardiac status. In our investigation, the median values for C-reactive protein and erythrocyte sedimentation rate were found to be 10 mg/dl and 60 mm/h, respectively. Furthermore, the median platelet count was observed to be 1.87 lakhs/mm3, while the median absolute lymphocyte count was recorded as 1472 cells/mm3. Serum albumin and NT-pro BNP were identified to have a statistically significant association with cardiac involvement, exhibiting significance at the 1% level. Conclusion: Our findings suggest that serum albumin and NT-pro BNP have a statistically significant association with cardiac involvement in MIS-C. Furthermore, hemodynamic instability in MIS-C may result primarily from vasculopathy rather than cardiac dysfunction. more...
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- 2024
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15. Synthetic thymic hexapeptide in the correction of alterations of antibacterial immune defense and normalization of the profile of proinflammatory cytokines in immunocompromized Children with local unlimited acute peritonitis
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Svetlana V. Kovaleva, V. N. Chapurina, L. V. Lomtatidze, D. E. Lyagusha, Yu. V. Teterin, N. K. Barova, and K. I. Melkonyan
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acute peritonitis ,immunocompromise ,children ,immunomodulatory therapy ,hexapeptide ,cytokines ,Infectious and parasitic diseases ,RC109-216 - Abstract
The study of dysregulatory disorders of the immune system underlying the immunopathogenesis of severe purulent-inflammatory diseases (PIDs) is important for development of new therapeutic tactics of restoring antibacterial defense. Acute peritonitis (AP) is a severe PID of the abdominal cavity, the course of which are dependent on the treatment, cytokine balance and adequate functioning of the immunity. Objective: to evaluate the modulating effects on the immune system and the levels of proinflammatory cytokines of the synthetic thymic hexapeptide, active substance of Imunofan, included in the complex postoperative treatment (CPOT) of immunocompromised children with local AP. Clinical and immunological examination of 20 immunocompromised children aged 5–12 years with local AP was carried out before (study group 1, SG1) and after (study group 1a, SG1a) CPOT including synthetic thymic hexapeptide (Arginyl-alpha-AspartylLysyl-Valyl-Tyrosyl-Arginine, НР), alongside 20 conditionally healthy children (comparison group, SG). The content of T and B lymphocytes, natural killer cells (NK), levels of serum pro-inflammatory cytokines IL-1β, IL-6, TNFα, IL-8, IL-18, phagocytic and microbicidal activity of neutrophils (NG) were assessed. In SG1, before treatment, a decrease in the number of T lymphocytes, T helpers, CTL-lymphocytes, NK and an increase in the level of B lymphocytes was revealed. Defects in the effector functions of NG were determined: impaired bacterial antigen killing and decreased NADPH oxidase activity. It was established that in case of AP in immunocompromised children, the cytokine profile is characterized by overproduction of studied proinflammatory and neutrophil-associated cytokines. After complex treatment including immunomodulatory therapy, there was a restoration of the content of T lymphocytes, T helper cells, TCTL lymphocytes, an increase in the number of NK and decrease in the level of B lymphocytes. In addition, regression of the levels of inflammatory, including neutrophil-associated, cytokines and emergence of effector functions of NG due to restoration of NADPH oxidases activity, was noted. Thus, the restoration of immunological parameters in AP leads to earlier regression of the purulent-inflammatory process in the abdominal cavity and to the absence of postoperative complications. The clinical and immunological effects of the immunomodulatory therapy program with inclusion of the drug based on HP determines the feasibility of its use in the postoperative period in immunocompromised children with local AP. more...
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- 2024
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16. Intestinal pseudo-obstruction in a myasthenia gravis patient after thymectomy: A case report and literature review.
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Yun Qian and Congguo Yin
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RECEPTOR antibodies , *ANTIBODY titer , *PARENTERAL feeding , *THYMECTOMY , *INTESTINES , *MYASTHENIA gravis - Abstract
Intestinal pseudo-obstruction in patients with myasthenia gravis is a rare and poorly understood phenomenon. We report a case coexisting with intestinal pseudo-obstruction and myasthenia gravis. The patient was diagnosed to have myasthenia gravis and underwent thymectomy seven years ago. He was tested positive for anti-acetylcholine receptor antibody and was free of thymoma recurrence during the current illness. Despite being given gastrointestinal decompression and parenteral nutrition, the patient’s gastrointestinal symptoms did not improve. Symptoms were rectified effectively by immunomodulatory therapy. This case adds intestinal pseudo-obstruction to the phenotypic profile of post-thymectomy myasthenia gravis. High titer of AChR antibody might play a role in the pathogenesis of myasthenia gravis with intestinal pseudo-obstruction [ABSTRACT FROM AUTHOR] more...
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- 2024
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17. Subcutaneous Histaglobulin as an Emerging Therapy in Refractory Chronic Urticaria: A Clinical Evaluation.
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Bunker, Abhishek, Koushal, Paras, Kumawat, Harish Kumar, and Khan Pathan, Mohammad Shahid
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WILCOXON signed-rank test , *VISUAL analog scale , *QUALITY of life , *REFRACTORY materials , *SYMPTOMS - Abstract
Background: Chronic urticaria (CU) is a persistent condition characterized by recurrent hives and itching, often resistant to standard treatments. Subcutaneous Histaglobulin, an immunomodulatory agent, has emerged as a potential therapeutic option for refractory CU. This study aims to evaluate the efficacy and safety of SC Histaglobulin in managing patients with refractory chronic urticaria. Methods: A clinical evaluation was conducted with 50 patients diagnosed with refractory CU. Participants received SC Histaglobulin (2 mL weekly) for 8 weeks. Outcomes were assessed using the Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and visual analog scale (VAS) for pruritus. Data were collected at baseline, during treatment, and at 4 weeks post-treatment. Statistical analyses included paired t-tests and Wilcoxon signed-rank tests. Results: The mean UAS7 score decreased significantly from 31.4 ± 6.2 at baseline to 12.1 ± 5.4 at the end of the treatment (p < 0.001), with 40% of patients achieving complete symptom resolution. DLQI scores improved from 15.8 ± 4.3 to 6.4 ± 3.1 (p < 0.001), and VAS scores for pruritus reduced from 7.6 ± 1.4 to 2.5 ± 1.1 (p < 0.001). SC Histaglobulin was well-tolerated, with mild adverse events reported. Conclusion: SC Histaglobulin is an effective and well-tolerated treatment for refractory chronic urticaria, significantly improving symptoms and quality of life. The study supports the use of SC Histaglobulin as a viable therapeutic option in this challenging patient population, although further research is needed to confirm these findings and explore long-term outcomes. [ABSTRACT FROM AUTHOR] more...
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- 2024
18. Das deutsche COVID-19-Rheumaregister.
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Hasseli, Rebecca, Regierer, Anne C., Strangfeld, Anja, and Pfeil, Alexander
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Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...
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- 2024
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19. Natalizumab in Multiple Sclerosis: A Single Centre Real-World Study.
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Onder, Ayşen, Sen, Sedat, and Terzi, Murat
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NATALIZUMAB ,MULTIPLE sclerosis ,PATIENT safety ,DISEASE duration ,IMMUNOTHERAPY ,DESCRIPTIVE statistics ,SEVERITY of illness index ,MAGNETIC resonance imaging ,DRUG efficacy ,IMMUNOSUPPRESSION ,DISEASE progression - Abstract
Objective: Natalizumab (NTZ) is an effective immunomodulator therapy (IMT) employed for multiple sclerosis (MS) therapy. This study aimed to investigate the efficacy and safety of NTZ treatment in MS patients. Materials and Methods: Patients with clinically definite MS who received NTZ treatment were included in the study, and their data were derived from the iMed database. Patient demographics such as age, sex, and disease duration were assessed. The results pertaining to the annual number of attacks, expanded disability status scale (EDSS) results, magnetic resonance data, and no evidence of disease activity-3 (NEDA-3) were obtained. Results: This study included 153 patients (108 female and 43 male). The patients' ages ranged from 21.63 to 67.60 years, with a mean age of 44.50 years. Prior to undergoing NTZ treatment, 54.3% of the patients had received at least two other IMTs. The mean annual number of assaults was 1.19, and the number of attacks in the year prior to treatment ranged from 0 to 6. The mean number of attacks in the first year following treatment was 0.07, 0.13 in the second year, and 0.09 in the third year. The baseline EDSS values of the patients varied between 0 and 5.5, and the mean baseline EDSS value was 3.08. During the initial year of treatment, the patient's mean EDSS value was 2.58, the second year was 2.32, and the third year was 2.34. Recurrence with increased severity of disease activity or rebound development was observed in 14.6% of the patients whose NTZ treatment was terminated for any reason. The NEDA-3 value decreased from 82.8% (n=145) in the first year to 77.3% (n=132) in the second year and 79.0% (n=81) in the third year. Conclusion: Patients received NTZ for three years on average. 14.6% of the patients exhibit a recurrence or rebound of disease activity. Anti-John Cunningham virus antibody was detected in 5% of patients during the course of treatment. Approximately 80% of patient achieved NEDA-3 while receiving NTZ over the three-year period. [ABSTRACT FROM AUTHOR] more...
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- 2024
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20. Protein-based biomarkers in pulmonary malignancies.
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Haragan, Alexander K.
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Targeted therapies have revolutionised the management of patients with lung cancer over the last 20 years. A crucial role for pulmonary pathologists is to provide high quality and timely analysis of predictive biomarkers that guide the use of these targeted treatments. Protein-based biomarkers, alongside nucleic acid analyses, are mostly used to predict response to therapies that inhibit oncogenic stimulation or utilise immune checkpoint inhibition. Despite the protein-based mechanism of action of targeted therapies, development of biomarkers for lung cancers have been chiefly focused on genomics. With ongoing expansion of targeted treatments, including novel classes of therapeutics such as antibody drug conjugates, and an increasing requirement for effective biomarkers, however, immunochemistry and related techniques may still continue to play a valuable and crucial role in predictive profiling. This review will focus on current and future protein-based biomarkers in pulmonary malignancies alongside the assays, underlying biology and appropriate clinical context required to effectively utilise them. This will provide an overview of the role of the pathologist in effectively guiding targeted treatments for lung cancer patients. [ABSTRACT FROM AUTHOR] more...
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- 2024
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21. Evaluating the Efficacy and Safety of Baricitinib in Reducing COVID-19 Mortality: A Comprehensive Review of Clinical Evidence and Pharmacological Strategies
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Paulina Klaudia Kwaśniewska, Patryk Graczyk, Anna Wilewska, Kinga Borowiec, Agnieszka Borowiec, Julia Biernikiewicz, Konstanty Alabrudziński, Milena Biernikiewicz, Bartosz Pomirski, and Agata Pomirska more...
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COVID-19 ,baricitinib ,JAK inhibitors ,immunomodulatory therapy ,SARS-CoV ,Education ,Sports ,GV557-1198.995 ,Medicine - Abstract
Introduction: COVID-19 manifests with symptoms ranging from mild to severe, including respiratory and cardiovascular complications. Severe cases are often marked by a cytokine storm, causing pulmonary damage and multi-organ dysfunction. Current treatments lack a specific antiviral, though several pharmacological options, including immunomodulatory and antiviral drugs, are under investigation. Purpose: The purpose of this article is to provide an evaluation of the efficacy and safety of baricitinib, a JAK inhibitor, combined with standard care for hospitalized adults with COVID-19. By reviewing recent literature, it aims to assess baricitinib's effectiveness in improving patient outcomes. Material and methods: A systematic review of clinical trials and case studies was conducted to analyze baricitinib’s impact on COVID-19 mortality. Data includes treatment-emergent adverse events and patient outcomes in moderate to severe cases. Discussion: Baricitinib has demonstrated potential in managing hyperinflammation in severe COVID-19 by inhibiting multiple proinflammatory cytokines and enhancing immune response. Clinical trials show that baricitinib, particularly in combination with corticosteroids, reduces mortality and serious infections compared to standard care alone. Due to potential adverse events, continuous monitoring of hematological and lipid levels is essential. These findings highlight baricitinib's dual role as an immunomodulatory and antiviral agent, suggesting its importance in treating severe COVID-19. Future research should focus on optimizing treatment regimens and further exploring the long-term implications of baricitinib therapy. more...
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- 2024
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22. Network meta-analysis of four common immunomodulatory therapies for the treatment of patients with thin endometrium
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Lifei Li, Zhijian Kou, Fei Zhao, Yan Wang, and Xuehong Zhang
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Thin endometrium ,immunomodulatory therapy ,granulocyte colony-stimulating factor ,platelet-rich plasma ,network meta-analysis ,Gynecology and obstetrics ,RG1-991 ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Obejective To compare the effectiveness of endometrial receptivity and pregnancy outcomes of four common immunomodulatory therapies for patients with thin endometrium.Method This systematic review and network meta-analysis using a literature search up to January 2024, to identify relevant trials comparing endometrial receptivity and pregnancy outcomes of human chorionic gonadotropin (hCG), platelet-rich plasma (PRP), infusion of granulocyte colony-stimulating factor (IG-CSF), and peripheral blood mononuclear cell (PBMC) for patients with thin endometrium. We used surface under the cumulative ranking (SUCRA) to ranked four common immunomodulatory therapies on endometrium thickness, implantation rate (IR), clinical pregnancy rate (CPR), and live birth rate (LBR). RoB2 and ROBINS-I were used to assess the certainty of evidence.Results The pooled results of 22 studies showed that hCG (mean difference [MD]: 3.05, 95% confidence interval [CI]: 1.46–4.64) and PRP (MD: 0.98, 95% CI: 0.20–1.76) significantly increase endometrium thickness. The hCG was the best among the IG-CSF (MD = −2.56, 95% CI = −4.30 to −0.82), PBMC (MD = −2.75, 95% CI = −5.49 to −0.01), and PRP (MD = −2.07, 95% CI = −3.84 to −0.30) in increasing endometrium thickness. However, IG-CSF and PRP significantly improved IR (IG-CSF: risk ratio (RR; IG-CSF: RR = 1.33, 95% CI = 1.06–1.67; PRP: RR = 1.63, 95% CI = 1.19–2.23), and LBR (IG-CSF: RR = 1.53, 95% CI = 1.16–2.02; PRP: RR = 1.59, 95% CI = 1.08–2.36).Conclusions Available evidence reveals that hCG and subcutaneous or intrauterine CSF (SG-CSF) may be the best treatment options for current thin endometrium patients. However, future high-quality and large-scale studies are necessary to validate our findings. more...
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- 2024
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23. Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial.
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Reddy, Amit K, Miller, D Claire, Sura, Amol A, Rathinam, SR, Gonzales, John A, Thundikandy, Radhika, Kanakath, Anuradha, Murugan, Bala, Vedhanayaki, Rajesh, Lim, Lyndell L, Suhler, Eric B, Doan, Thuy, Al-Dhibi, Hassan A, Goldstein, Debra A, Arellanes-Garcia, Lourdes, and Acharya, Nisha R more...
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Immunomodulatory therapy ,Methotrexate ,Mycophenolate mofetil ,Non-infectious uveitis ,Retinal vasculitis ,Clinical Research ,Patient Safety ,Eye Disease and Disorders of Vision ,Comparative Effectiveness Research ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Good Health and Well Being - Abstract
BackgroundThe antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis.Main bodyThis is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF.ConclusionRetinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics. more...
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- 2023
24. INNOVATIONS IN THE TREATMENT OF PEDIATRIC CONJUNCTIVITIS: MODERN SOLUTIONS FOR SMALL PATIENTS
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Iulian Catalin Bratu, Irina Ruxandra Strambu, Iulia Alecsandra Salcianu, Marius Vacaru Carnaru, Olimpia Dumitriu-Buzia, Nicolae Sarbu, Ion Ciuca, Alina Mihaela Calin, Norin Forna, and Simona Parvu
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conjunctivitis ,therapeutic innovations ,nanoparticles ,led light therapy ,immunomodulatory therapy ,health education ,Dentistry ,RK1-715 - Abstract
Conjunctivitis, a common inflammation of the conjunctiva, commonly affects children and can be caused by bacterial, viral infections or allergic reactions. This condition, manifested by redness, itching, and eye discharge, can negatively influence children’s quality of life and lead to school absenteeism. In addition, the rapid spread of infection in communities such as schools and kindergartens underlines the need for effective and safe treatment solutions. This article explores recent innovations in the treatment of pediatric conjunctivitis, highlighting modern methods and advanced technologies that promise to improve the management of this condition. These innovations include state-of-the-art antibiotic and antiviral therapies, nanoparticle use, probiotics and LED light therapy applications, and new immunomodulatory strategies for allergic conjunctivitis. It also discusses the psychological impact of conjunctivitis on children and the importance of education and prevention in the management of this condition. By presenting these modern solutions, the article emphasizes the need for prompt and adequate treatment to prevent long-term complications and ensure a better quality of life for small patients. At the same time, the importance of continuous development of research and innovation in pediatric ophthalmology is emphasized. more...
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- 2024
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25. Treatment of severe perinuclear antineutrophil cytoplasmic antibody–associated vasculitis with efgartigimod
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Afsoon Ghafari-Saravi, BS, Alana Haussmann, MD, Jessica Wu, MD, and Kyle Cheng, MD
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autoimmune disease ,efgartigimod ,immunomodulatory therapy ,P-ANCA vasculitis ,perinuclear anti-neutrophil cytoplasmic antibodies ,vasculitis ,Dermatology ,RL1-803 - Published
- 2024
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26. Efficacy and Safety of PEGylated Interferons for Relapsing-Remitting Multiple Sclerosis in Adult Patients: Results of Matching-Adjusted Indirect Comparison
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Taras O. Simaniv, Maria N. Zakharova, Kirill V. Sapozhnikov, Daria G. Tolkacheva, Valeria D. Sokolova, Natalia A. Sableva, Olga N. Mironenko, and Taras V. Khimich
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multiple sclerosis ,immunomodulatory therapy ,dmds ,pegylated interferons ,peg-ifn-β1a ,sampeg-ifn-β1a ,indirect comparison ,efficacy ,safety ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Introduction. Beta interferons are effective and safe agents for the treatment of relapsing-remitting multiple sclerosis (RRMS). PEGylated interferons have been developed in order to increase patient adherence. Direct comparisons of the efficacy and safety of PEGylated interferons have not yet been conducted. Our objective was to evaluate the efficacy and safety of SamPEG-IFN-β1a versus PEG-IFN-β1a in adult patients with RRMS. Materials and methods. We conducted a systematic search of randomized clinical trials (RCTs) using the PubMed, Embase and eLIBRARY.RU databases. Efficacy was assessed based on the proportion of patients with disease relapses and the annualized relapse rate (ARR) during the 1st and the 2nd years of treatment. Safety was assessed by the number of patients with adverse events (AEs), serious AEs (SAEs), and any AEs that led to the treatment discontinuation. We conducted pairwise matching-adjusted indirect comparison (MAIC) to assess comparative efficacy of PEGylated IFNs. To evaluate the efficacy, hypotheses of non-inferiority of SamPEG-IFN-β1a to PEG-IFN-β1a and superiority of SamPEG-IFN-β1a over PEG-IFN-β1a were tested. Results. Based on results of the systematic review, four articles were selected wherein the results of phase 3 clinical trial of PEG-IFN-β1a and phase 2–3 clinical trial of SamPEG-IFN-β1a were described. In PEG-IFN-β1a group (n = 512) the agent was administered once every 2 weeks, in SamPEGIFN-β1a group (n = 114) the agent was administered at a dose of 240 μg. The analysis results confirmed the hypothesis of SamPEG-IFN-β1a non-inferiority to PEG-IFN-β1a in efficacy, while SamPEG-IFN-β1a superiority over PEG-IFN-β1a in efficacy was not confirmed. The hypothesis of SamPEG-IFN-β1a superiority over PEG-IFN-β1a in safety was also confirmed based on a significantly lower incidence of SAEs and any AEs that led to treatment discontinuation. Conclusions. The proportion of patients with relapses and the ARR in 1 year and in 2 years of therapy indicates that SamPEG-IFN-β1a is non-inferior to PEG-IFN-β1a in efficacy. SamPEG-IFN-B1a demonstrated a more favourable safety profile than PEG-IFN-B1a as showing less odds of SAEs and AEs leading to treatment discontinuation. more...
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- 2024
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27. Preliminary evaluation of safety and migration of immune activated mesenchymal stromal cells administered by subconjunctival injection for equine recurrent uveitis.
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Cassano, Jennifer, Leonard, Brian, Martins, Bianca, Vapniarsky, Natalia, Morgan, Joshua, Dow, Steven, Wotman, Kathryn, and Pezzanite, Lynn
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equine ,equine recurrent uveitis (ERU) ,immunomodulatory therapy ,mesenchymal stromal (stem) cell (MSC) ,regenerative medicine ,subconjunctival therapy - Abstract
INTRODUCTION: Equine recurrent uveitis (ERU), an immune mediated disease characterized by repeated episodes of intra-ocular inflammation, affects 25% of horses in the USA and is the most common cause of glaucoma, cataracts, and blindness. Mesenchymal stromal cells (MSCs) have immunomodulatory properties, which are upregulated by preconditioning with toll-like receptor agonists. The objective was to evaluate safety and migration of TLR-3 agonist polyinosinic, polycytidylic acid (pIC)-activated MSCs injected subconjunctivally in healthy horses prior to clinical application in horses with ERU. We hypothesized that activated allogeneic MSCs injected subconjunctivally would not induce ocular or systemic inflammation and would remain in the conjunctiva for >14 days. METHODS: Bulbar subconjunctiva of two horses was injected with 10 × 106 pIC-activated (10 μg/mL, 2 h) GFP-labeled MSCs from one donor three times at two-week intervals. Vehicle (saline) control was injected in the contralateral conjunctiva. Horses received physical and ophthalmic exams [slit lamp biomicroscopy, rebound tonometry, fundic examination, and semiquantitative preclinical ocular toxicology scoring (SPOTS)] every 1-3 days. Systemic inflammation was assessed via CBC, fibrinogen, and serum amyloid A (SAA). Horses were euthanized 14 days following final injection. Full necropsy and histopathology were performed to examine ocular tissues and 36 systemic organs for MSC presence via IVIS Spectrum. Anti-GFP immunohistochemistry was performed on ocular tissues. RESULTS: No change in physical examinations was noted. Bloodwork revealed fibrinogen 100-300 mg/dL (ref 100-400) and SAA 0-25 μg/mL (ref 0-20). Ocular effects of the subjconjucntival injection were similar between MSC and control eyes on SPOTS grading system, with conjunctival hypermia, chemosis and ocular discharge noted bilaterally, which improved without intervention within 14 days. All other ocular parameters were unaffected throughout the study. Necropsy and histopathology revealed no evidence of systemic inflammation. Ocular histopathology was similar between MSC and control eyes. Fluorescent imaging analysis did not locate MSCs. Immunohistochemistry did not identify intact MSCs in the conjunctiva, but GFP-labeled cellular components were present in conjunctival phagocytic cells. DISCUSSION: Allogeneic pIC-activated conjunctival MSC injections were well tolerated. GFP-labeled tracking identified MSC components phagocytosed by immune cells subconjunctivally. This preliminary safety and tracking information is critical towards advancing immune conditioned cellular therapies to clinical trials in horses. more...
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- 2023
28. Spatial transcriptomic brain imaging reveals the effects of immunomodulation therapy on specific regional brain cells in a mouse dementia model.
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Lee, Eun Ji, Suh, Minseok, Choi, Hongyoon, Choi, Yoori, Hwang, Do Won, Bae, Sungwoo, and Lee, Dong Soo
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- *
BRAIN imaging , *TRANSCRIPTOMES , *LABORATORY mice , *ALZHEIMER'S disease , *KILLER cells , *IMMUNOGLOBULINS - Abstract
Increasing evidence of brain-immune crosstalk raises expectations for the efficacy of novel immunotherapies in Alzheimer's disease (AD), but the lack of methods to examine brain tissues makes it difficult to evaluate therapeutics. Here, we investigated the changes in spatial transcriptomic signatures and brain cell types using the 10x Genomics Visium platform in immune-modulated AD models after various treatments. To proceed with an analysis suitable for barcode-based spatial transcriptomics, we first organized a workflow for segmentation of neuroanatomical regions, establishment of appropriate gene combinations, and comprehensive review of altered brain cell signatures. Ultimately, we investigated spatial transcriptomic changes following administration of immunomodulators, NK cell supplements and an anti-CD4 antibody, which ameliorated behavior impairment, and designated brain cells and regions showing probable associations with behavior changes. We provided the customized analytic pipeline into an application named STquantool. Thus, we anticipate that our approach can help researchers interpret the real action of drug candidates by simultaneously investigating the dynamics of all transcripts for the development of novel AD therapeutics. [ABSTRACT FROM AUTHOR] more...
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- 2024
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29. Dramatic Improvement of Acute Fulminant Lymphocytic Myocarditis with Short-course Intravenous Pulse Corticosteroids: A Case Study.
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Elasfar, Abdelfatah, Suliman, Salma, Al Hijji, Mohammed Ahmad, Badr, Amr, Al-Bozom, Issam, and Patel, Ashfaq
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- *
ARTIFICIAL blood circulation , *CARDIOGENIC shock , *INTRAVENOUS therapy , *MYOCARDITIS , *CORTICOSTEROIDS - Abstract
We report a 31-year-old patient with acute fulminant myocarditis, resulting in cardiogenic shock that necessitated mechanical circulatory support, who improved dramatically after treatment with intravenous (IV) pulse steroids. A coordinated multidisciplinary team was the key secret in the cure of this critical patient. In this case study, we focus on the role of IV pulse steroids in the treatment of fulminant lymphocytic myocarditis. [ABSTRACT FROM AUTHOR] more...
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- 2024
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30. Schwangerschaft und Stillzeit bei Frauen mit Multipler Sklerose.
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Witt, Laura, Thiel, Sandra, and Hellwig, Kerstin
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The diagnosis of multiple sclerosis (MS) in women of reproductive age is associated with many uncertainties regarding childbearing and lactation. Pregnancies of MS patients are not usually considered high-risk pregnancies per se. The likelihood of pregnancy complications or adverse pregnancy outcomes is not increased by the disease; however, a careful planning of pregnancy is important in order to choose the treatment option with the greatest benefit for the mother and the least possible risk for the baby. For highly active courses of the disease, anti-CD20 antibodies, cladribine, or continued administration of natalizumab show the best data. Patients with MS can be supported in their desire to breastfeed. If women have had a very active disease course, it is recommended that treatment should be started as soon as possible postpartum. Interferon-beta preparations, glatiramer acetate and ofatumumab are also approved for use during breastfeeding but off-label breastfeeding is also possible with other monoclonal antibodies. [ABSTRACT FROM AUTHOR] more...
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- 2024
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31. INNOVATIONS IN THE TREATMENT OF PEDIATRIC CONJUNCTIVITIS: MODERN SOLUTIONS FOR SMALL PATIENTS.
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Bratu, Iulian Catalin, Strambu, Irina Ruxandra, Salcianu, Iulia Alecsandra, Carnaru, Marius Vacaru, Dumitriu-Buzia, Olimpia, Sarbu, Nicolae, Ciuca, Ion, Calin, Alina Mihaela, Forna, Norin, and Parvu, Simona more...
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MEDICAL personnel ,ALLERGIC conjunctivitis ,TEA tree oil ,MEDICAL education ,EYE infections - Abstract
This article provides an overview of the diagnosis and treatment of pediatric conjunctivitis, focusing on modern advancements and technologies. It discusses different types of conjunctivitis, their symptoms, and specific treatment approaches. The article emphasizes the importance of education, prevention, and prompt treatment to prevent complications and improve the quality of life for children. It also highlights the psychological and educational aspects of managing conjunctivitis. Additionally, a document of references from various scientific articles on conjunctivitis in pediatric patients is provided, offering a diverse perspective on the subject. [Extracted from the article] more...
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- 2024
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32. Complete response of metastatic cutaneous squamous cell carcinoma and multiple locally advanced basal cell carcinomas with concomitant pembrolizumab and sonidegib therapy
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Carlos González-Cruz, MD, Eva Muñoz-Couselo, MD, PhD, Carolina Ortiz-Velez, MD, Berta Ferrer, MD, Vicente García-Patos, MD, PhD, and Carla Ferrándiz-Pulido, MD, PhD
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basal cell carcinoma ,hedgehog ,immunomodulatory therapy ,squamous cell carcinoma ,Dermatology ,RL1-803 - Published
- 2024
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33. Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies
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Irmak Karaca, Elaine M. Tran, SungWho Park, Albert Bromeo, Hassan Khojasteh, Anh Ngọc Tram Tran, Negin Yavari, Amir Akhavanrezayat, Cigdem Yasar, Gunay Uludag Kirimli, Ngoc Tuong Trong Than, Muhammad Hassan, Christopher Or, Hashem Ghoraba, Diana V. Do, and Quan Dong Nguyen more...
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Cyclophosphamide ,Scleritis ,Uveitis ,Severe ,Refractory ,Immunomodulatory therapy ,Ophthalmology ,RE1-994 - Abstract
Abstract Background Ocular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such strategy includes conventional therapies (antimetabolites, alkylating agents, and calcineurin inhibitors) as well as biologic agents like adalimumab, infliximab, rituximab, and tocilizumab. Cyclophosphamide (CP) is an alkylating agent and mainly inhibits the functioning of both T and B cells. Though known to have potential adverse events, including bone marrow suppression, hemorrhagic cystitis, and sterility, CP has been shown to be efficacious, especially in recalcitrant cases and when used intravenous (IV) for a limited period. Main findings We conducted a retrospective case-series to assess the safety and efficacy of CP therapy for patients with severe ocular inflammatory diseases who failed other IMTs. Medical records of 1295 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were reviewed. Seven patients (10 eyes) who received CP therapy for ocular inflammatory diseases with at least one year of follow-up were included. The mean age of the patients (4 males, 3 females) was 61.6 ± 14.9 (43.0–89.0) years. Clinical diagnoses included necrotizing scleritis (5 eyes), peripheral ulcerative keratitis (2 eyes), orbital pseudotumor (1 eye), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes). Ocular disease was idiopathic in 3 patients, and was associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All the patients had history of previous IMT use including methotrexate (5), mycophenolate mofetil (3), azathioprine (1), tacrolimus (1), adalimumab (2), infliximab (4), and rituximab (1). The mean follow-up time was 34.4 ± 11.0 (13–45) months, and mean duration of CP therapy was 11.9 ± 8.8 (5–28) months. Remission was achieved in 5 patients (71.4%). Four patients (57.1%) experienced transient leukopenia (white blood cell count more...
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- 2024
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34. Intravitreal Fluocinolone Acetonide 0.19 mg Implant in a Patient with Resistant Blau Syndrome: A Case Report
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Khushi Saigal and Arash Maleki
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blau syndrome ,choroiditis ,fluocinolone acetonide implant ,immunomodulatory therapy ,uveitis ,Ophthalmology ,RE1-994 - Abstract
Introduction: Blau syndrome is a progressive disease with an unknown etiology and pathogenesis. It can cause severe damage, especially in the eye with severe involvement. Case Presentation: A six-year-old female was referred to us complaining about blurry vision and floaters in both eyes for 1 year. She had been diagnosed with Blau syndrome and Blau syndrome-associated anterior uveitis. Her best-corrected visual acuity in the right and left eyes was 20/70 and 20/80, respectively. Slit-lamp exam revealed faint bilateral band keratopathy along with 1+ anterior chamber cells and posterior synechia 360° in both eyes. During dilated fundoscopy, 2+ haze in the media was observed, along with swollen and hyperemic disc OU. Based on changes in optical coherence tomography, fluorescein angiography, and indocyanine green angiography, she was diagnosed with panuveitis and retinal vasculitis. Given her complicated history, we decided to proceed with an intravitreal fluocinolone acetonide 0.19 mg implant implantation in both eyes. During the 1-month follow-up visit, vitreous haze, retinal vasculitis, and active choroiditis were resolved. At 6-month follow-up visit, no changes were observed compared to the 1-month follow-up visit. Conclusion: In cases of Blau syndrome that display resistance to systemic immunomodulatory therapies, the inclusion of local treatments, such as the intravitreal fluocinolone acetonide 0.19 mg implant, should be considered as an adjunctive therapeutic option. more...
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- 2024
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35. Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies
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Karaca, Irmak, Tran, Elaine M., Park, SungWho, Bromeo, Albert, Khojasteh, Hassan, Tran, Anh Ngọc Tram, Yavari, Negin, Akhavanrezayat, Amir, Yasar, Cigdem, Uludag Kirimli, Gunay, Than, Ngoc Tuong Trong, Hassan, Muhammad, Or, Christopher, Ghoraba, Hashem, Do, Diana V., and Nguyen, Quan Dong more...
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- 2024
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36. Intravitreal Fluocinolone Acetonide 0.19 mg Implant in a Patient with Resistant Blau Syndrome: A Case Report.
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Saigal, Khushi and Maleki, Arash
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- *
IRIDOCYCLITIS , *FLUORESCENCE angiography , *OPTICAL coherence tomography , *INDOCYANINE green , *VISUAL acuity , *SYNDROMES - Abstract
Introduction: Blau syndrome is a progressive disease with an unknown etiology and pathogenesis. It can cause severe damage, especially in the eye with severe involvement. Case Presentation: A six-year-old female was referred to us complaining about blurry vision and floaters in both eyes for 1 year. She had been diagnosed with Blau syndrome and Blau syndrome-associated anterior uveitis. Her best-corrected visual acuity in the right and left eyes was 20/70 and 20/80, respectively. Slit-lamp exam revealed faint bilateral band keratopathy along with 1+ anterior chamber cells and posterior synechia 360° in both eyes. During dilated fundoscopy, 2+ haze in the media was observed, along with swollen and hyperemic disc OU. Based on changes in optical coherence tomography, fluorescein angiography, and indocyanine green angiography, she was diagnosed with panuveitis and retinal vasculitis. Given her complicated history, we decided to proceed with an intravitreal fluocinolone acetonide 0.19 mg implant implantation in both eyes. During the 1-month follow-up visit, vitreous haze, retinal vasculitis, and active choroiditis were resolved. At 6-month follow-up visit, no changes were observed compared to the 1-month follow-up visit. Conclusion: In cases of Blau syndrome that display resistance to systemic immunomodulatory therapies, the inclusion of local treatments, such as the intravitreal fluocinolone acetonide 0.19 mg implant, should be considered as an adjunctive therapeutic option. [ABSTRACT FROM AUTHOR] more...
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- 2024
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37. A Rare Presentation: Bilateral Necrotizing Scleritis in Primary Sjögren’s Syndrome.
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Narain, Shishir, Pyare, Richa, and Rath, P. D.
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PurposeMethodsResultsConclusionWe report a rare and challenging case of bilateral necrotizing scleritis in primary Sjögren’s syndrome (pSS).Retrospective case report.A 72-year-old diabetic, hypertensive female patient presented with sudden onset of painful red left eye and was noted to have a corneal ulcer with severe thinning. She was managed with topical fortified antibiotics and tissue glue and bandage contact lens. During subsequent follow-ups, she developed necrotizing scleral melts in both eyes. On investigations, antinuclear antibodies were positive in a dilution of 1:160 with 2+ speckled pattern, with antinuclear antibody line immunoassay showing anti SS-A/ Ro52 positive. In view of rapidly developing scleral thinning and impending perforation, she was started on intravenous methylprednisolone 1 g/day for 3 days, along with steroid-sparing immunomodulatory therapy (mycophenolate mofetil 500 mg twice a day). She showed a rapid response to therapy and is currently stable on tapering oral steroids and mycophenolate mofetil.This case underscores the unique presentation of pSS, characterized by bilateral necrotizing scleritis. The favorable outcome was attained through prompt immunosuppressive intervention and a collaborative, multidisciplinary approach. Further, this case report addresses a gap in the existing literature concerning pSS-related scleritis. It also emphasizes the crucial role of a rheumatologist in the comprehensive management of this condition. [ABSTRACT FROM AUTHOR] more...
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- 2024
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38. Treatment of Neurological Disorders
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Kondziella, Daniel, Waldemar, Gunhild, Kondziella, Daniel, and Waldemar, Gunhild
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- 2023
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39. Clinical Characteristics and Outcomes of Coronavirus Disease 2019 Patients Who Received Compassionate-Use Leronlimab
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Yang, Bryant, Fulcher, Jennifer A, Ahn, Jenny, Berro, Marlene, Goodman-Meza, David, Dhody, Kush, Sacha, Jonah B, Naeim, Arash, and Yang, Otto O
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Clinical Research ,Inflammatory and immune system ,Aged ,Aged ,80 and over ,Antibodies ,Monoclonal ,Humanized ,COVID-19 ,HIV Antibodies ,Humans ,Immunization ,Passive ,Middle Aged ,SARS-CoV-2 ,Treatment Outcome ,COVID-19 Serotherapy ,leronlimab ,immunomodulatory therapy ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundLeronlimab, a monoclonal antibody blocker of C-C chemokine receptor type 5 originally developed to treat human immunodeficiency virus infection, was administered as an open-label compassionate-use therapeutic for coronavirus disease 2019 (COVID-19).MethodsTwenty-three hospitalized severe/critical COVID-19 patients received 700 mg leronlimab subcutaneously, repeated after 7 days in 17 of 23 patients still hospitalized. Eighteen of 23 received other experimental treatments, including convalescent plasma, hydroxychloroquine, steroids, and/or tocilizumab. Five of 23 received leronlimab after blinded, placebo-controlled trials of remdesivir, sarilumab, selinexor, or tocilizumab. Outcomes and results were extracted from medical records.ResultsMean age was 69.5 ± 14.9 years; 20 had significant comorbidities. At baseline, 22 were receiving supplemental oxygen (3 high flow, 7 mechanical ventilation). Blood showed markedly elevated inflammatory markers (ferritin, D-dimer, C-reactive protein) and an elevated neutrophil-to-lymphocyte ratio. By day 30 after initial dosing, 17 were recovered, 2 were still hospitalized, and 4 had died. Of the 7 intubated at baseline, 4 were fully recovered off oxygen, 2 were still hospitalized, and 1 had died.ConclusionsLeronlimab appeared safe and well tolerated. The high recovery rate suggested benefit, and those with lower inflammatory markers had better outcomes. Some, but not all, patients appeared to have dramatic clinical responses, indicating that unknown factors may determine responsiveness to leronlimab. Routine inflammatory and cell prognostic markers did not markedly change immediately after treatment, although interleukin-6 tended to fall. In some persons, C-reactive protein clearly dropped only after the second leronlimab dose, suggesting that a higher loading dose might be more effective. Future controlled trials will be informative. more...
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- 2021
40. Epidemiology and Clinical Course of Pediatric Uveitis in a Tertiary Referral Center in Northeastern Iran.
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Khazaei, Sahel, Bakhtiari, Elham, Ansari Astaneh, Mohammad Reza, and Hosseini, Seyedeh Maryam
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IRIDOCYCLITIS , *BEHCET'S disease , *UVEITIS , *CLINICAL epidemiology , *JUVENILE idiopathic arthritis , *VISUAL acuity - Abstract
To describe the distribution, clinical findings, treatment, complications, and visual outcomes of pediatric uveitis at a tertiary referral ophthalmic center. The medical records of all patients ≤18 years diagnosed with and managed as uveitis from August 2016 to August 2021 were reviewed retrospectively. Of the 97 patients, 52.6% were female, and the mean age at the onset was 10.5 ± 4.6 years (6 months to 18 years). Uveitis cases were predominantly anterior (33 [34%]), chronic (59 [60.8%]), bilateral (63 [64.9%]), and non-infectious (80 [82.5%]). A total of 36.1% (35 patients) of cases were idiopathic, and the most frequent systemic associations were juvenile idiopathic arthritis (JIA), 16 [16.5%]) and Behcet's disease (15 [15.5%]). Most patients (74 [76.3%]) experienced ocular complications, including vasculitis (29 [29.9%]), posterior synechiae (23 [23.7%]), and cataracts (22 [22.7%]). Patients with uveitis of all anatomic locations experienced an improvement in best-corrected visual acuity during the follow-up period (p < 0.01). The most prevalent systemic associations were JIA and Behcet's disease. Ocular Behcet is a common etiology of pediatric uveitis in northeastern Iran. A timely and appropriate treatment could result in satisfactory visual outcomes. [ABSTRACT FROM AUTHOR] more...
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- 2023
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41. Hantavirus Pulmonary Syndrome Caused by Puumala Orthohantavirus—A Case Report and Literature Review.
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Santini, Marija, Ljubić, Jelena, Šoštar, Nikola, Vilibić-Čavlek, Tatjana, Bogdanić, Maja, Zakotnik, Samo, Avšič-Županc, Tatjana, Korva, Miša, Kurolt, Ivan Christian, Radmanić, Leona, Šimičić, Petra, Krznarić, Juraj, Gjurašin, Branimir, Kutleša, Marko, Višković, Klaudija, Balent, Nataša Cetinić, Žunec, Renata, Margeta Marić, Ivana, Ribarović, Ana, and Židovec-Lepej, Snjezana more...
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FEVER ,LITERATURE reviews ,HEMORRHAGIC fever with renal syndrome ,ADULT respiratory distress syndrome ,HANTAVIRUS diseases ,INTENSIVE care units - Abstract
In this article, we report on a rare case of acute respiratory distress syndrome (ARDS) caused by the Puumala orthohantavirus (PUUV), which is typically associated with hemorrhagic fever with renal syndrome (HFRS). This is the first documented case of PUUV-associated ARDS in Southeast Europe. The diagnosis was confirmed by serum RT-PCR and serology and corroborated by phylogenetic analysis and chemokine profiling. The patient was a 23-year-old male from Zagreb, Croatia, who had recently traveled throughout Europe. He presented with fever, headache, abdominal pain, and sudden onset of ARDS. Treatment involved high-flow nasal cannula oxygen therapy and glucocorticoids, which resulted in a full recovery. A systematic literature review identified 10 cases of hantavirus pulmonary syndrome (HPS) caused by PUUV in various European countries and Turkey between 2002 and 2023. The median age of patients was 53 years (range 24–73), and six of the patients were male. Most patients were treated in intensive care units, but none received antiviral therapy targeting PUUV. Eight patients survived hospitalization. The presented case highlights the importance of considering HPS in the differential diagnosis of ARDS, even in areas where HFRS is the dominant form of hantavirus infection. [ABSTRACT FROM AUTHOR] more...
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- 2023
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42. Diferenciální diagnostika a možnosti léčby recidivujících infekcí dolních dýchacích cest.
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Džingozovová, M.
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Copyright of Studia Pneumologica et Phthiseologica is the property of TRIOS, spol. sr.o. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) more...
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- 2023
43. Decoding Sepsis-Induced Disseminated Intravascular Coagulation: A Comprehensive Review of Existing and Emerging Therapies.
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Unar, Ahsanullah, Bertolino, Lorenzo, Patauner, Fabian, Gallo, Raffaella, and Durante-Mangoni, Emanuele
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DISSEMINATED intravascular coagulation , *PULMONARY alveolar proteinosis , *MEDICAL personnel , *BLOOD coagulation , *GRANULOCYTE-colony stimulating factor , *GRANULOCYTE-macrophage colony-stimulating factor - Abstract
Disseminated intravascular coagulation (DIC) is a recurrent complication of sepsis. Since DIC not only promotes organ dysfunction but also represents a strong prognostic factor, it is important to diagnose DIC as early as possible. When coagulation is activated, fibrinolysis is inhibited, blood thinners are consumed, and a condition is created that promotes blood clotting, making it more difficult for the body to remove fibrin or prevent it from being deposited in the blood vessels. This leads to microvascular thrombosis, which plays a role in organ dysfunction. Despite efforts to understand the underlying mechanisms of sepsis-induced DIC, healthcare providers worldwide still face challenges in effectively treating this condition. In this review, we provide an in-depth analysis of the available strategies for sepsis-induced DIC, considering their effectiveness, limitations, and potential for future advances. Corticosteroids (CS), recombinant thrombomodulin (rTM), vitamin C, fibrinolytic therapy, and platelet transfusion are among the treatments discussed in the review. In addition, we are specifically addressing immunomodulatory therapy (IMT) by investigating treatments such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), and mesenchymal stem cell therapy (MSC). Finally, we also examined how these therapies might affect COVID-19 cases, which often present with sepsis-induced DIC. The review suggests that targeted experiments with randomization are needed to verify the effectiveness of these treatments and to discover novel approaches to treat sepsis-induced DIC. By increasing our knowledge of sepsis-induced DIC, we can develop targeted treatments that have the potential to save lives and improve outcomes. [ABSTRACT FROM AUTHOR] more...
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- 2023
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44. B Cell Depletion Therapy as a Cutting-Edge Treatment of Demyelinating Diseases of the Central Nervous System
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Taras O. Simaniv, Anna A. Belkina, and Maria N. Zakharova
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multiple sclerosis ,pathogenesis ,immunomodulatory therapy ,b cells ,demyelinating diseases ,central nervous system ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Demyelinating diseases of the central nervous system and multiple sclerosis in particular are a pressing issue for medical community and society as a whole. Deve- lopment and implementation of highly effective specific therapy significantly slow the disease progression and help maintain patients' quality of life and social participation. We analyzed pathogenic mechanisms of multiple sclerosis and other B cell-mediated diseases and reviewed therapeutic options for main disease stages. more...
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- 2023
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45. Dynamics of cellular immunity indicators in the complex treatment of acute optic neuritis
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D. A. Storozhilova, O. V. Kolenko, L. P. Danilova, L. P. Emanova, and I. V. Vasilieva
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optic neuritis ,herpes virus infection ,corticosteroid therapy ,immunomodulatory therapy ,indicators of cellular immunity ,imunofan ,Immunologic diseases. Allergy ,RC581-607 - Abstract
An increase in the incidence of optic neuritis among the working-age population, as well as an unpromising prognosis for vision due to the development of optic nerve atrophy, determines the high social significance of this problem. The aim of the work is to analyze the effect of Imunofan at the parameters of cellular immunity and clinical symptoms of the disease in the complex treatment of optic neuritis associated with herpes virus infection. The study involved 37 people (37 eyes) with acute optic neuritis associated with herpes infection. The treatment regimen included the appointment of a dexamethasone solution according to a decreasing scheme, a 1% solution of the drug Emoxipin 0.5 mL and a 12.5% solution of the drug Dicynone 0.5 mL through an irrigation system implanted in the retrobulbar space, in combination with the neuroprotection drugs (Pikamilon and Semax) for 10 days. All patients were divided into 2 groups. The main group consisted of 20 patients who received Imunofan to the treatment regimen in addition. The comparison group included 17 patients who were treated only according to the method described above. The course of treatment lasted 10 days. The analysis of the data showed a more significant positive dynamics of cellular immunity parameters in those who received immunotherapy. Our studies showed the effectiveness of this drug in the complex treatment of optic neuritis associated with herpes infection, what is confirmed by the acceleration of inflammation relief, a more significant increase in visual functions of patients treated with Imunofan, and a lower percentage of optic nerve atrophy. In this group of patients, changes in the parameters of the cellular link of immunity occurred earlier and remained stable throughout the entire period of observation. According to our data, an intergroup assessment of the immunoregulatory index showed its faster increase in patients of the comparison group who received Imunofan, and reached normal values already 6 months after treatment. The clinical effectiveness of Imunofan in the complex therapy of optic neuritis associated with herpes infection was characterized by a reduction in the period of relief of signs of inflammation in the optic nerve by 2 times or more, by an increase in the maximum corrected visual acuity by 4.5 times, and by a decrease in the incidence of recurrence of optic neuritis by 2 times over a 12 months observation period. more...
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- 2023
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46. Risk of failing both methotrexate and mycophenolate mofetil from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial
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Amit K. Reddy, D. Claire Miller, Amol A. Sura, SR Rathinam, John A Gonzales, Radhika Thundikandy, Anuradha Kanakath, Bala Murugan, Rajesh Vedhanayaki, Lyndell L. Lim, Eric B. Suhler, Thuy Doan, Hassan A. Al-Dhibi, Debra A. Goldstein, Lourdes Arellanes-Garcia, and Nisha R Acharya more...
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Non-infectious uveitis ,Immunomodulatory therapy ,Methotrexate ,Mycophenolate mofetil ,Retinal vasculitis ,Ophthalmology ,RE1-994 - Abstract
Abstract Background The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis. Main body This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF. Conclusion Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics. more...
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- 2023
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47. Hyperinflammatory Syndrome in Patients with COVID-19
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Mehmet UZUNLULU, Hatice Şeyma MARAŞLI, Erhan EKEN, Onur İNCEALTIN, and Haluk VAHABOĞLU
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covid-19 ,hyperinflammatory syndrome ,risk score ,immunomodulatory therapy ,prognosis ,Medicine (General) ,R5-920 - Abstract
Objective:The aim of this study was to investigate the relationship between the initial hyperinflammatory syndrome (HIS) risk score, calculated according to the clinical criteria recommended in the literature, and clinical outcomes in hospitalized patients with the diagnosis of coronavirus disease 2019-(COVID-19).Methods:A total of 169 patients (93 females, 76 males, mean age: 65.10±14.74 years) who were hospitalized with a polymerase chain reaction-confirmed COVID-19 diagnosis at the time of hospitalization were consecutively enrolled in this retrospective, observational and clinical study. Those with two or more of the characteristics of fever, macrophage activation, haematological dysfunction, hepatic injury, coagulopathy, and cytokinemia constituted the group with high risk of HIS, and those with more...
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- 2023
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48. Preliminary evaluation of safety and migration of immune activated mesenchymal stromal cells administered by subconjunctival injection for equine recurrent uveitis
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Jennifer M. Cassano, Brian C. Leonard, Bianca C. Martins, Natalia Vapniarsky, Joshua T. Morgan, Steven W. Dow, Kathryn L. Wotman, and Lynn M. Pezzanite
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regenerative medicine ,mesenchymal stromal (stem) cell (MSC) ,equine ,subconjunctival therapy ,equine recurrent uveitis (ERU) ,immunomodulatory therapy ,Veterinary medicine ,SF600-1100 - Abstract
IntroductionEquine recurrent uveitis (ERU), an immune mediated disease characterized by repeated episodes of intra-ocular inflammation, affects 25% of horses in the USA and is the most common cause of glaucoma, cataracts, and blindness. Mesenchymal stromal cells (MSCs) have immunomodulatory properties, which are upregulated by preconditioning with toll-like receptor agonists. The objective was to evaluate safety and migration of TLR-3 agonist polyinosinic, polycytidylic acid (pIC)-activated MSCs injected subconjunctivally in healthy horses prior to clinical application in horses with ERU. We hypothesized that activated allogeneic MSCs injected subconjunctivally would not induce ocular or systemic inflammation and would remain in the conjunctiva for >14 days.MethodsBulbar subconjunctiva of two horses was injected with 10 × 106 pIC-activated (10 μg/mL, 2 h) GFP-labeled MSCs from one donor three times at two-week intervals. Vehicle (saline) control was injected in the contralateral conjunctiva. Horses received physical and ophthalmic exams [slit lamp biomicroscopy, rebound tonometry, fundic examination, and semiquantitative preclinical ocular toxicology scoring (SPOTS)] every 1–3 days. Systemic inflammation was assessed via CBC, fibrinogen, and serum amyloid A (SAA). Horses were euthanized 14 days following final injection. Full necropsy and histopathology were performed to examine ocular tissues and 36 systemic organs for MSC presence via IVIS Spectrum. Anti-GFP immunohistochemistry was performed on ocular tissues.ResultsNo change in physical examinations was noted. Bloodwork revealed fibrinogen 100-300 mg/dL (ref 100–400) and SAA 0–25 μg/mL (ref 0–20). Ocular effects of the subjconjucntival injection were similar between MSC and control eyes on SPOTS grading system, with conjunctival hypermia, chemosis and ocular discharge noted bilaterally, which improved without intervention within 14 days. All other ocular parameters were unaffected throughout the study. Necropsy and histopathology revealed no evidence of systemic inflammation. Ocular histopathology was similar between MSC and control eyes. Fluorescent imaging analysis did not locate MSCs. Immunohistochemistry did not identify intact MSCs in the conjunctiva, but GFP-labeled cellular components were present in conjunctival phagocytic cells.DiscussionAllogeneic pIC-activated conjunctival MSC injections were well tolerated. GFP-labeled tracking identified MSC components phagocytosed by immune cells subconjunctivally. This preliminary safety and tracking information is critical towards advancing immune conditioned cellular therapies to clinical trials in horses. more...
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- 2023
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49. Juvenile idiopathic arthritis and its associated uveitis.
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Maleki, Arash, Patel, Priya D., and Foster, C. Steven
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JUVENILE idiopathic arthritis ,IRIDOCYCLITIS ,UVEITIS ,CLINICAL trials ,DISEASE progression ,SYMPTOMS - Abstract
Juvenile idiopathic arthritis is the most common chronic rheumatologic disease in children. Uveitis is the most common extra-articular manifestation of JIA, and it can be a sight-threatening condition. In this review article, we discussed epidemiology, risk factors, clinical presentation, supportive laboratory tests, treatment options, and complications of Juvenile idiopathic arthritis and Juvenile idiopathic arthritis associated uveitis. We covered conventional immunomodulatory therapy and biologic response modifiers agents for different types of Juvenile idiopathic arthritis and their associated uveitis. Finally, we discussed the course of disease, functional outcome, and the quality of life of Juvenile idiopathic arthritis and Juvenile idiopathic arthritis-associated uveitis. Although clinical outcomes of Juvenile idiopathic arthritis and its associated uveitis have been improved over the past three decades by biologic response modifier agents, a significant proportion of patients require active treatment into adult life therefore screening and monitoring of these patients is required during the patient's entire life. The limited number of food and drug administration approved biologic response modifier agents for the treatment of Juvenile idiopathic arthritis associated uveitis justify more randomized clinical trials with new medications in this field. [ABSTRACT FROM AUTHOR] more...
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- 2023
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50. Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss.
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Banjar, Shorooq, Kadour, Einav, Khoudja, Rabea, Ton‐leclerc, Shaonie, Beauchamp, Coralie, Beltempo, Marc, Dahan, Michael H., Gold, Phil, Jacques Kadoch, Isaac, Jamal, Wael, Laskin, Carl, Mahutte, Neal, Reinblatt, Shauna Leigh, Sylvestre, Camille, Buckett, William, and Genest, Genevieve more...
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RECURRENT miscarriage , *BODY mass index - Abstract
Problem: Recurrent pregnancy loss (RPL) affects up to 4% of couples attempting to conceive. RPL is unexplained in over 50% of cases and no effective treatments exist. Due to the immune system's pivotal role during implantation and pregnancy, immune‐mediated RPL may be suspected and immunomodulatory treatments like intravenous immunoglobulin (IVIg) have been administered but remain controversial. The goal of our study was to evaluate our center's 6 year‐outcomes and to develop a framework for IVIg use in RPL. Method of the study: Retrospective, single‐center cohort study. All patients having received IVIg for unexplained RPL at the McGill Reproductive Immunology Clinic (MRIC) from January 2014 to December 2020 were included if maternal age was <42 years, body mass index (BMI) < 35 kg/m2, non‐smoker and having had ≥3 consecutive RPL despite previous treatment with aspirin and progesterone. IVIg 0.6–0.8 g/kg was given prior to conception and monthly during pregnancy until 16–20 weeks' gestation. We compared IVIg treated patient's outcomes to a separate "natural history cohort". This cohort was composed of patients consulting at the McGill recurrent pregnancy loss clinic and the MRIC over a 2‐year period (January 2020 to December 2021) with similar inclusion criteria as the treatment cohort but did not receive IVIg or other immunomodulatory treatments. The association of IVIg with outcomes (compared to no IVIg) was evaluated among the groups of patients with primary RPL and secondary RPL. The primary outcome was live birth rate (LBR), secondary outcomes included IVIg safety, obstetrical, and neonatal complications. Results: Among 169 patients with unexplained RPL that were included in the study, 111 had primary RPL (38 exposed to IVIg and 83 controls) and 58 had secondary RPL (nine exposed to IVIG and 49 controls). Among patients with primary RPL (n = 111), the LBR was 64.3% (18/28) among patient exposed to IVIg compared to 43.4% (36/83) in controls (p = 0.079); regression analysis adjusting for BMI and number of previous miscarriages showed benefit favoring the use of IVIg (OR = 3.27, CI 95% (1.15–10.2), p = 0.03) when evaluating for live birth. In the subgroup of patients with ≥5 previous RPL and primary RPL (n = 31), IVIg was associated with higher LBR compared to control (10/15 (66.7%) vs. 3/16 (18.8%); p = 0.0113) but not the in the sub‐group of patients with <5 miscarriages and primary RPL (8/13 (61.5%) vs. 33/67 (49.3%); p = 0.548). IVIG treatment did not improve LBR in patients with secondary RPL in our study (3/9 (33.3%) vs. 23/49 (47%); p = 0.495). There were no serious adverse events in the IVIg treatment group, obstetrical/neonatal complications were similar between groups. Conclusion: IVIg may be an effective treatment for patients with RPL if appropriately used in specific groups of patients. IVIg is a blood product and subject to shortages especially with unrestricted off‐label use. We propose considering IVIg in well‐selected patients with high order RPL who have failed standard medical therapy. Further mechanistic studies are needed to understand immune‐mediated RPL and IVIg's mode of action. This will enable further refinement of treatment criteria and the development of standardized protocol for its use in RPL. [ABSTRACT FROM AUTHOR] more...
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- 2023
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