scholarly journals Efek Obat Imunosupresan Pada Pasien Autoimun dengan COVID-19 (A Scoping Review of The Clinical Evidence)

2022 ◽  
Vol 6 (2) ◽  
pp. 88-94
Oki Nugraha Putra ◽  
Mia Arum Anggraini ◽  
Hardiyono Hardiyono

The main modality in autoimmune disease is a long-term immunosuppressant treatment aiming to control disease progression and increase patient life expectancy. This scoping review aims to evaluate the effect of immunosuppressant treatment in autoimmune patients with COVID-19 on clinical outcomes and disease progression. This scoping review was conducted following the PRISMA extension for scoping review (PRISMA-ScR) guidelines. The Pubmed and Science Direct databases are used to find articles that match the study objectives. Thirteen articles met the inclusion criteria, and all of them were classified as observational studies. Most immunosuppressant treatments are the disease-modifying anti-rheumatic drugs (DMARD) and glucocorticoids. The highest number of autoimmune patients with rheumatoid arthritis (RA) was 43.4%, systemic lupus erythematosus (SLE) 13.6%, and others was 43%. Autoimmune patients with COVID-19 taking immunosuppressant medications, particularly glucocorticoids, significantly increased the risk of hospitalization and the use of ventilators.  However, there was no mention of the dosage and duration of immunosuppressant therapy in most of the studies.  In general, the use of immunosuppressant drugs was not associated with an increased risk of COVID-19 infection and mortality compared with the general population. Increasing age and comorbidities were associated with poor clinical outcomes. In conclusion, autoimmune patients with COVID-19 who are taking immunosuppressant therapy particularly glucocorticoid exacerbate clinical outcomes.  Periodic clinical monitoring and appropriate pharmacological interventions are required in autoimmune patients with COVID-19 to improve clinical outcomes and prevent death.Keywords: Autoimmune, COVID-19, Immunosuppressant, Clinical outcome.

2021 ◽  
Vol 21 (1) ◽  
Yuki Abe ◽  
Masaru Suzuki ◽  
Hironi Makita ◽  
Hirokazu Kimura ◽  
Kaoruko Shimizu ◽  

Abstract Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with a complex progression of many clinical presentations, and clinically important deterioration (CID) has been proposed in the Western studies as a composite endpoint of disease progression. The aim of this study was to investigate the relationships between 1-year CID and the following long-term clinical outcomes in Japanese patients with COPD who have been reported to have different characteristics compared to the Westerners. Methods Among Japanese patients with COPD enrolled in the Hokkaido COPD cohort study, 259 patients who did not drop out within the first year were analyzed in this study. Two definitions of CID were used. Definition 1 comprised ≥ 100 mL decrease in forced expiratory volume in 1 s (FEV1), ≥ 4-unit increase in St George’s Respiratory Questionnaire (SGRQ) score from baseline, or moderate or severe exacerbation. For Definition 2, the thresholds for the FEV1 and SGRQ score components were doubled. The presence of CID was evaluated within the first year from enrollment, and analyzed the association of the presence of CID with following 4-year risk of exacerbations and 9-year mortality. Results Patients with CID using Definition 1, but not any single CID component, during the first year had a significantly worse mortality compared with those without CID. Patients with CID using Definition 2 showed a similar trend on mortality, and had a shorter exacerbation-free survival compared with those without CID. Conclusions Adoption of CID is a beneficial and useful way for the assessment of long-term disease progression and clinical outcomes even in Japanese population with COPD. The definition of CID might be optimized according to the characteristics of COPD population and the observation period for CID.

2000 ◽  
Vol 11 (11) ◽  
pp. 2114-2121

Abstract. Proinflammatory cytokines have been implicated in the short- and long-term morbidity experienced by hemodialysis (HD) patients. The present study, which is based on long-term follow-up of a cohort of 37 patients, relates peripheral blood mononuclear cell (PBMC) interleukin-1 receptor antagonist (IL-1Ra) synthesis (a reliable marker of IL-1β synthesis in HD patients) and plasma levels of an acute phase reactant, lipopolysaccharide binding protein (LBP), to clinical outcomes. In July 1993, predialysis blood samples from these patients were collected and IL-1Ra synthesis by PBMC and plasma LBP was measured. Hospital records were reviewed and patient follow-up data were obtained until December 1997 (54 mo) or death, whichever occurred earlier. The effect of age, diabetes, endotoxin- and IgG-stimulated IL-1Ra synthesis, and plasma LBP levels on mortality was assessed using the Cox proportional hazard regression model. Poisson regression was used to determine potential relationships between the number of outcome events and each continuous risk factor. Twenty-two patients (59%) died during the follow-up period. Mortality was unrelated to IL-1Ra synthesis but did increase with age (relative risk, 1.05/yr; P = 0.01) and diabetes (relative risk, 3.00/yr; P = 0.03). Cardiovascular event rates were higher among older individuals and in those with higher endotoxin-stimulated PBMC IL-1Ra synthesis. Cardiovascular events increased with plasma LBP levels in the range of 9,000 to 12,000 pg/ml but then seemed to decrease. In contrast, older age and low IgG-stimulated IL-1Ra synthesis were associated with an increased risk of infectious events. The results of this study demonstrate an interesting link between stimulus-dependent variability in IL-1Ra synthesis by PBMC and clinical outcomes among patients on chronic HD and provide interesting targets for therapeutic interventions in this vulnerable patient population.

Hisashi Ogawa ◽  
Yoshimori An ◽  
Kenjiro Ishigami ◽  
Syuhei Ikeda ◽  
Kosuke Doi ◽  

Abstract Aims Oral anticoagulants reduce the risk of ischaemic stroke but may increase the risk of major bleeding in atrial fibrillation (AF) patients. Little is known about the clinical outcomes of patients after a major bleeding event. This study assessed the outcomes of AF patients after major bleeding. Methods and results The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Analyses were performed on 4304 AF patients registered by 81 institutions participating in the Fushimi AF Registry. We investigated the demographics and outcomes of AF patients who experienced major bleeding during follow-up period. During the median follow-up of 1307 days, major bleeding occurred in 297 patients (6.9%). Patients with major bleeding were older than those without (75.6 vs. 73.4 years; P < 0.01). They were more likely to have pre-existing heart failure (33.7% vs. 26.7%; P < 0.01), history of major bleeding (7.7% vs. 4.0%; P < 0.01), and higher mean HAS-BLED score (2.05 vs.1.73; P < 0.01). On landmark analysis, ischaemic stroke or systemic embolism occurred in 17 patients (3.6/100 person-years) after major bleeding and 227 patients (1.7/100 person-years) without major bleeding, with an adjusted hazard ratio (HR) of 1.93 [95% confidence interval (CI), 1.06–3.23; P = 0.03]. All-cause mortality occurred in 97 patients with major bleeding (20.0/100 person-years) and 709 (5.1/100 person-years) patients without major bleeding [HR 2.73 (95% CI, 2.16–3.41; P < 0.01)]. Conclusion In this community-based cohort, major bleeding is associated with increased risk of subsequent all-cause mortality and thromboembolism in the long-term amongst AF patients. Trial registration Unique identifier: UMIN000005834. (last accessed 22 October 2020)

Nobutake Ozeki ◽  
Romain Seil ◽  
Aaron J Krych ◽  
Hideyuki Koga

The meniscus is important for load distribution, shock absorption and stability of the knee joint. Meniscus injury or meniscectomy results in decreased function of the meniscus and increased risk of knee osteoarthritis. To preserve the meniscal functions, meniscal repair should be considered as the first option for meniscus injury. Although reoperation rates are higher after meniscal repair compared with arthroscopic partial meniscectomy, long-term follow-up of meniscal repair demonstrated better clinical outcomes and less severe degenerative changes of osteoarthritis compared with partial meniscectomy. In the past, the indication of a meniscal repair was limited both because of technical reasons and due to the localised vascularity of the meniscus. Meanwhile, it spreads today as the development of the concept to preserve the meniscus and the improvement of meniscal repair techniques. Longitudinal vertical tears in the peripheral third are considered the ‘gold standard’ indication in terms of meniscus healing. Techniques for meniscal repair include ‘inside-out’, ‘outside-in’ and ‘all-inside’ strategies. Surgical decision-making depends on the type, size and location of the meniscus injury. Meniscal root tears substantially affect meniscal hoop function and accelerate cartilage degeneration; therefore, meniscus root repair is necessary to prevent the progression of osteoarthritis change. For symptomatic meniscus defects after meniscectomy, transplantation of allograft or collagen meniscus implant may be indicated, and acceptable clinical results have been obtained. Recently, meniscus extrusion has attracted attention due to increased interest in early osteoarthritis. The centralisation techniques have been proposed to reduce the meniscus extrusion by suturing the meniscus-capsule complex to the edge of the tibial plateau. Long-term clinical outcomes of this procedure may change the strategy of treating meniscus extrusion. When malalignment of the lower leg is accompanied with meniscus pathologies, knee osteotomies are a reasonable option to protect the repaired meniscus by unloading the pathological compartment. Advancements in biological augmentation such as bone marrow stimulation, fibrin clot, platelet-rich plasma, stem cell therapy and scaffolds have also expanded the indications for meniscus surgery. In summary, improved repair techniques and biological augmentation have made meniscus repair more appealing to treat that had previously been considered irreparable. However, further research would be necessary to validate the efficacy of these specialised technique.

2016 ◽  
Vol 6 (1) ◽  
Duy Vu ◽  
Srini Reddy ◽  
Lynn Day ◽  
Nail Aydin ◽  
Subhasis Misra

Kikuchi-Fujimoto disease (KFD) is a rare, benign disorder that typically follows a selflimiting natural course and was initially described in young females of Asian descent. Its clinical presentation may mimic lymphoproliferative disorders, connective tissue disorders, and chronic infections. This often leads to misdiagnosis and inappropriate treatment. The exact cause of this condition remains unknown although autoimmune processes and certain infectious agents have been associated with the disease. The diagnosis of KFD is made histopathologically. Treatment is supportive and long-term follow-up is recommended due to increased risk of future development of systemic lupus erythematosus. Here we are presenting a case of a patient with an unusual presentation of KFD.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3022-3022 ◽  
Rahul Raj Aggarwal ◽  
Scott Thomas ◽  
Nela Pawlowska ◽  
Jennifer A. Grabowsky ◽  
Susan Calabrese ◽  

3022 Background: We previously reported the initial phase 1b study results of PAZ + ABX, a potent pan-HDAC inhibitor, demonstrating acceptable toxicity profile and encouraging anti-tumor activity (Aggarwal et al. JCO 2017). We report the long-term follow up of exceptional responders and additional correlative analyses associated with clinical outcomes. Methods: Key efficacy endpoints included objective response rate and duration of response. Peripheral blood histone acetylation, HDAC expression, and plasma VEGF levels were analyzed and associated with clinical outcomes. Results: 51 pts (RCC subset; N = 22) were enrolled between June 2012 and October 2015. 10 pts (20%) had experienced disease progression on prior PAZ; 59% had received any prior VEGF-targeting therapy. 9 evaluable pts (18%) (N = 6 RCC; 2 thyroid; 1 mesothelioma) achieved partial tumor response (PR), of which 6 had prior progression on VEGF-targeting therapy. 7/10 (70%) of pts with prior disease progression on PAZ monotherapy had reduction in tumor burden on study. The median duration of response was 9.1 months (range 1.2 to 70+), and clinical benefit rate (PR or stable disease > 6 months) was 33%. Five treatment-refractory pts achieved durable PRs lasting for > 2 years duration, and one previously PAZ-refractory patient with RCC remains on treatment with ongoing PR for > 6 years. Higher HDAC2 expression was associated with prolonged progression-free survival (median PFS 5.9 vs. 3.5 months, log-rank p = 0.02). Induction of histone acetylation on ABX lead-in treatment was associated with subsequent time to progression (p = 0.002). On-treatment plasma VEGF levels were inversely correlated with PBMC histone acetylation (p = 0.02). Conclusions: Markedly durable responses with PAZ + ABX are achievable, including in pts with PAZ- and VEGF-refractory RCC and other solid tumor malignancies. Host factors including HDAC expression and acetylation status may identify those most likely to benefit. A randomized phase 3 study is underway of PAZ + ABX as a first- or second-line therapy in pts with locally advanced or metastatic RCC (RENAVIV; NCT03592472). Clinical trial information: NCT01543763.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 360.3-360
T. Goulenok ◽  
A. L. Gerard ◽  
M. Bahuaud ◽  
P. Aucouturier ◽  
H. Moins ◽  

Background:Systemic lupus erythematosus (SLE) patients are at increased risk forStreptococcus pneumoniaeinfection. Although pneumococcal vaccination is an attractive method to prevent invasive pneumococcal infection, vaccination coverage remains dramatically low in SLE. Moreover, the efficacy of vaccination may be reduced in SLE patients and sequential pneumococcal vaccination using new conjugated pneumococcal vaccines in combination with 23-valent pneumococcal polysaccharide vaccine (PPV23) is now advocated. However, limited study directly addressed the immune efficacy of such prime-and-boost strategy in SLEObjectives:We aimed to measure the immunological efficacy of the sequential pneumococcal vaccination using PCV13 in combination with PPV23 and identify factors associated with long-term immune protection following vaccination in SLE.Methods:SLE patients received PCV13 vaccine followed by PPSV23 vaccine 8 weeks later. Immune protection, defined by an antigen-specific IgG concentration ≥ 1.3 µg/mL for at least 70% of 7 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F), was assessed at baseline, 2 months, 12 months, and 36 months, defining very long-term protection.Results:21 (40[25-75] years; 85.7% female) SLE patients received the sequential PCV13/PPV23 vaccines. Only 10 (47.6%) showed a sustained immune protection against pneumococcal infection 36 months after PCV13 shot (very long-term protected, VLTP). Eleven patients had no long-term protection (NLTP) with a seroconversion that never (n=6) or only transiently (n=5) occurred. SLE disease features, treatment received and immunological characteristic did not differ between VLTP and NLTP patients except for a lower serum IgG2 levels in NLTP (1.45 [1.30, 1.82] vs 3.30 [2.92, 4.44] g/L, p<0.001). Noteworthy the ROC curve showed that the serum IgG2 level before vaccination (AUC 0.95 [95% CI: 0.84-1]; p=0.004) was predictive for very long-term protection. A baseline serum IgG2 level of 2.125µg/ml or more showed a sensitivity of 100% and a specificity of 90.9% for very long-term protectionConclusion:The benefit of sequential PCV13/PPV23 vaccination in SLE is limited. Baseline IgG2 serum level before vaccination is strongly indicative of very long term protection following vaccinationDisclosure of Interests:None declared

2021 ◽  
Vol 21 (1) ◽  
Haley J. Appaneal ◽  
Theresa I. Shireman ◽  
Vrishali V. Lopes ◽  
Vincent Mor ◽  
David M. Dosa ◽  

Abstract Background Antibiotic use is associated with several antibiotic-related harms in vulnerable, older long-term care (LTC) residents. Suboptimal antibiotic use may also be associated with harms but has not yet been investigated. The aim of this work was to compare rates of poor clinical outcomes among LTC residents with UTI receiving suboptimal versus optimal antibiotic treatment. Methods We conducted a retrospective cohort study among residents with an incident urinary tract infection (UTI) treated in Veterans Affairs LTC units (2013–2018). Potentially suboptimal antibiotic treatment was defined as use of a suboptimal initial antibiotic drug choice, dose frequency, and/or excessive treatment duration. The primary outcome was time to a composite measure of poor clinical outcome, defined as UTI recurrence, acute care hospitalization/emergency department visit, adverse drug event, Clostridioides difficile infection (CDI), or death within 30 days of antibiotic discontinuation. Shared frailty Cox proportional hazard regression models were used to compare the time-to-event between suboptimal and optimal treatment. Results Among 19,701 LTC residents with an incident UTI, 64.6% received potentially suboptimal antibiotic treatment and 35.4% experienced a poor clinical outcome. In adjusted analyses, potentially suboptimal antibiotic treatment was associated with a small increased hazard of poor clinical outcome (aHR 1.06, 95% CI 1.01–1.11) as compared with optimal treatment, driven by an increased hazard of CDI (aHR 1.94, 95% CI 1.54–2.44). Conclusion In this national cohort study, suboptimal antibiotic treatment was associated with a 6% increased risk of the composite measure of poor clinical outcomes, in particular, a 94% increased risk of CDI. Beyond the decision to use antibiotics, clinicians should also consider the potential harms of suboptimal treatment choices with regards to drug type, dose frequency, and duration used.

2020 ◽  
Vol 13 (7) ◽  
pp. 143 ◽  
Franz Geisslinger ◽  
Angelika M. Vollmar ◽  
Karin Bartel

The world is currently suffering from a pandemic which has claimed the lives of over 230,000 people to date. The responsible virus is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causes the coronavirus disease 2019 (COVID-19), which is mainly characterized by fever, cough and shortness of breath. In severe cases, the disease can lead to respiratory distress syndrome and septic shock, which are mostly fatal for the patient. The severity of disease progression was hypothesized to be related to an overshooting immune response and was correlated with age and comorbidities, including cancer. A lot of research has lately been focused on the pathogenesis and acute consequences of COVID-19. However, the possibility of long-term consequences caused by viral infections which has been shown for other viruses are not to be neglected. In this regard, this opinion discusses the interplay of SARS-CoV-2 infection and cancer with special focus on the inflammatory immune response and tissue damage caused by infection. We summarize the available literature on COVID-19 suggesting an increased risk for severe disease progression in cancer patients, and we discuss the possibility that SARS-CoV-2 could contribute to cancer development. We offer lines of thought to provide ideas for urgently needed studies on the potential long-term effects of SARS-CoV-2 infection.

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