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Transplant Infectious Disease : An... Dec 2022The role of culturing the graft preservation fluid (PF) is controversial and its impact on graft arteritis development remains unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of culturing the graft preservation fluid (PF) is controversial and its impact on graft arteritis development remains unclear.
METHODS
Systematic literature search retrieving observational studies comparing solid organ transplant (SOT) recipients with culture-positive PF versus culture-negative PF. The quality of included studies was independently assessed according to the ROBINS-I tool for observational studies. Meta-analysis was performed using Mantel-Haenszel random-effect models. Graft site arteritis within 180 days from transplant was selected as the primary outcome.
RESULTS
Twenty-one observational studies (N = 2208 positive PF vs. 4458 negative) were included. Among positive PF, 857 (38.8%) were classified as high-risk group pathogens and 1351 (61.2%) as low-risk pathogens. Low-risk and negative PF showed similar odds ratios. A significant higher risk of graft arteritis was found in SOT recipients with a PF yielding a high-risk pathogen (odds ratio [OR] 18.43, 95% confidence interval [CI] 7.83-43.40) compared to low-risk and negative PF, with low heterogeneity (I = 2.24%). Similar results were found considering separately high-risk bacteria (OR 12.02, 95%CI 4.88-29.60) and fungi (OR 71.00, 95%CI 28.07-179.56), with no heterogeneity (I = 0%), and in the subgroup analyses of the liver (OR 16.78, 95%CI 2.95-95.47) and kidney (OR 19.90, 95%CI 4.78-82.79) recipients. However, data about diagnostic features of graft arteritis were very limited, indeed for only 11 of the 93 events histological or microbiological results were reported.
CONCLUSIONS
Our results may support the performance of PF culturing and a preemptive diagnostic or therapeutic management upon isolation of high-risk pathogens. Further studies based on a reliable diagnosis of graft arteritis are needed.
Topics: Humans; Liver; Fungi; Bacteria; Arteritis
PubMed: 36271646
DOI: 10.1111/tid.13979 -
RMD Open Sep 2022Informing an international task force updating the consensus statement on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) selectively...
A systematic literature review informing the consensus statement on efficacy and safety of pharmacological treatment with interleukin-6 pathway inhibition with biological DMARDs in immune-mediated inflammatory diseases.
OBJECTIVES
Informing an international task force updating the consensus statement on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) selectively targeting interleukin-6 (IL-6) pathway in the context of immune-mediated inflammatory diseases.
METHODS
A systematic literature research of all publications on IL-6 axis inhibition with bDMARDs published between January 2012 and December 2020 was performed using MEDLINE, EMBASE and Cochrane CENTRAL databases. Efficacy and safety outcomes were assessed in clinical trials including their long-term extensions and observational studies. Meeting abstracts from ACR, EULAR conferences and results on clinicaltrials.gov were taken into consideration.
RESULTS
187 articles fulfilled the inclusion criteria. Evidence for positive effect of IL-6 inhibition was available in various inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, cytokine release syndrome due to chimeric antigen receptor T cell therapy and systemic sclerosis-associated interstitial lung disease. Newcomers like satralizumab and anti-IL-6 ligand antibody siltuximab have expanded therapeutic approaches for Castleman's disease and neuromyelitis optica, respectively. IL-6 inhibition did not provide therapeutic benefits in psoriatic arthritis, ankylosing spondylitis and certain connective tissue diseases. In COVID-19, tocilizumab (TCZ) has proven to be therapeutic in advanced disease. Safety outcomes did not differ from other bDMARDs, except higher risks of diverticulitis and lower gastrointestinal perforations. Inconsistent results were observed in several studies investigating the risk for infections when comparing TCZ to TNF-inhibitors.
CONCLUSION
IL-6 inhibition is effective for treatment of several inflammatory diseases with a safety profile that is widely comparable to other bDMARDs.
Topics: Adult; Humans; Antirheumatic Agents; Interleukin-6; Ligands; Receptors, Chimeric Antigen; COVID-19 Drug Treatment
PubMed: 36260501
DOI: 10.1136/rmdopen-2022-002359 -
Open Forum Infectious Diseases Aug 2022Diagnostic outcomes for fever of unknown origin (FUO) remain with notable numbers of undiagnosed cases. A recent systemic review and meta-analysis of studies reported...
BACKGROUND
Diagnostic outcomes for fever of unknown origin (FUO) remain with notable numbers of undiagnosed cases. A recent systemic review and meta-analysis of studies reported geographic variation in FUO-related infectious diseases. Whether geography influences types of FUO noninfectious diagnoses deserves examination.
METHODS
We systematically searched Medline (PubMed), Embase, Scopus, and Web of Science databases using medical subject headings published from January 1, 1997 to March 31, 2021. Prospective clinical studies investigating participants meeting adult FUO defining criteria were selected if they assessed final diagnoses. Meta-analyses were based on the random-effects model according to World Health Organization (WHO) geographical regions.
RESULTS
Nineteen studies with significant heterogeneity were analyzed, totaling 2667 participants. Noninfectious inflammatory disorders had a pooled estimate at 20.0% (95% confidence interval [CI], 17.0%-23.0%). Undiagnosed illness had a pooled estimate of 20.0% (95% CI, 14.0%-26.0%). The pooled estimate for cancer was 15.0% (95% CI, 12.0%-18.0%). Miscellaneous conditions had a pooled estimate of 6.0% (95% CI, 4.0%-8.0%). Noninfectious inflammatory disorders and miscellaneous conditions were most prevalent in the Western Pacific region with a 27.0% pooled estimate (95% CI, 20.0%-34.0%) and 9.0% (95% CI, 7.0%-11.0%), respectively. The highest pooled estimated for cancer was in the Eastern Mediterranean region at 25.0% (95% CI, 18.0%-32.0%). Adult-onset Still's disease (114 [58.5%]), systemic lupus (52 [26.7%]), and giant-cell arteritis (40 [68.9%]) predominated among the noninfectious inflammatory group. Lymphoma (164 [70.1%]) was the most common diagnosis in the cancer group.
CONCLUSIONS
In this systematic review and meta-analysis, noninfectious disease diagnostic outcomes varied among WHO-defined geographies. Evaluations for FUO should include local variations in disease prevalence.
PubMed: 36004312
DOI: 10.1093/ofid/ofac396 -
Frontiers in Immunology 2022To evaluate the randomized controlled trials (RCTs) of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the randomized controlled trials (RCTs) of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases.
METHODS
Databases such as Embase, Web of Science, PubMed and The Cochrane Library were searched from the database establishment to February 2022 to collect RCTs of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. Then the literature was screened and the data were extracted. Meta-analysis was performed using RevMan 5.3 software.
RESULTS
A total of 34 records were included, involving 31 RCTs and 10 types of autoimmune disease. Among them, ankylosing spondylitis (AS) involves one RCT, Behcet 's disease (BD) involves one RCT, Crohn 's disease involves two RCTs, multiple sclerosis (MS) involves two RCTs, oral lichen planus involves six RCTs, psoriasis involves two RCTs, rheumatoid arthritis (RA) involves five RCTs, systemic lupus erythematosus (SLE) involves two RCTs, arteritis involves one RCT, ulcerative colitis (UC) involves nine RCTs. Among them, most of the RCTs of ulcerative colitis (UC), oral lichen planus, RA showed that curcumin and curcumin extracts improved clinical or laboratory results. Crohn ' s disease, MS, SLE, psoriasis included two RCTs; they all showed improvements (at least one RCT reported improvements in clinical outcomes). AS, BD and arteritis included only one RCT, and the clinical results showed improvement. However, due to the small number of RCTs and the small number of patients involved in each disease, there is still a need for more high-quality RCTs.
CONCLUSION
Curcumin and Curcuma longa Extract had good clinical efficacy in the treatment of Psoriasis, UC and RA, so Curcumin and Curcuma longa Extract could be used in the treatment of the above diseases in the future. The results of Meta-analysis showed that Curcumin and Curcuma longa Extract did not show efficacy in the treatment of oral lichen planus, while Takayasu arteritis, SLE, MS, AS, BD and CD did not report sufficient clinical data for meta-analysis. Therefore, large-sample, multi-center clinical trials are still needed for revision or validation.
Topics: Arteritis; Arthritis, Rheumatoid; Colitis, Ulcerative; Crohn Disease; Curcuma; Curcumin; Humans; Lichen Planus, Oral; Lupus Erythematosus, Systemic; Plant Extracts; Psoriasis; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing
PubMed: 35979355
DOI: 10.3389/fimmu.2022.896476 -
The Permanente Journal Sep 2022IntroductionTakayasu's arteritis (TA) is an inflammatory condition that affects large vessels and frequently involves the aortic valve causing valve regurgitation.... (Review)
Review
IntroductionTakayasu's arteritis (TA) is an inflammatory condition that affects large vessels and frequently involves the aortic valve causing valve regurgitation. Surgical management is recommended for symptomatic severe aortic regurgitation (AR); however, the optimal surgical approach is yet unclear. This study aims to review surgical treatment options for AR in TA and determine which procedure has a lower chance of late postoperative events and/or mortality. MethodsAn electronic database search was performed within PubMed, EMBASE, Web of Science, and SCOPUS to identify articles from 1975 to 2016 focusing on surgical management of the AR in TA. ResultsTwenty seven studies encompassing a total of 194 cases (77% females) were included. Isolated aortic valve replacement (AVR) was performed in 105/194 cases (54%) (Group A), while combined aortic valve and root replacement (CAVRR) was performed in 87/194 (45%) (Group B). Prosthetic valve detachment was reported in 10/105 cases (9.5%) in group A and 1/87 cases (1.2%) in group B (p = 0.02). Dilation of the residual aorta was reported in 10/105 cases (9.5%) in group A and 1/87 cases (1.2%) in group B (p = 0.02). Any late (≥ 30 d) postoperative cardiac event was reported in 26/105 cases (24.8%) in group A, and in 7/87 cases (8.1%) in group B (p = 0.003). ConclusionsAlthough CAVRR is a more complex procedure, it might offer a better outcome in terms of late postoperative cardiac events compared to isolated AVR procedure. Future prospective studies are required to help determine the best surgical approach in such a population.
Topics: Aortic Valve; Aortic Valve Insufficiency; Female; Heart Valve Prosthesis Implantation; Humans; Male; Takayasu Arteritis
PubMed: 35939573
DOI: 10.7812/TPP/21.017 -
Seminars in Arthritis and Rheumatism Oct 2022Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) can be concurrent diseases. We aimed to estimate the point-prevalence of concurrent GCA and PMR.... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) can be concurrent diseases. We aimed to estimate the point-prevalence of concurrent GCA and PMR. Additionally, an incidence rate (IR) of GCA presenting after PMR diagnosis in patients was estimated.
METHODS
Two authors performed a systematic literature search, data extraction and risk of bias assessment independently. Studies assessing cohorts of patients presenting with both GCA and PMR were included. The outcomes were point-prevalence of concurrent GCA and PMR and IR for development of GCA after PMR diagnosis. A meta-analysis was performed to calculate a pooled prevalence of concurrent PMR and GCA.
RESULTS
We identified 29 studies investigating concurrent GCA and PMR. Only two studies applied imaging systematically to diagnose GCA and none to diagnose PMR. GCA presenting after PMR diagnosis was assessed in 12 studies but imaging was not applied systematically. The point-prevalence of concurrent GCA present at PMR diagnosis ranged from 6%-66%. The pooled estimate of the point-prevalence from the meta-analysis was 22%. The point-prevalence of PMR present at GCA diagnosis ranged from 16%-65%. The pooled estimate of the point-prevalence from the meta-analysis was 42%. The IR ranged between 2-78 cases of GCA presenting after PMR per 1000 person-years.
CONCLUSION
This review and meta-analysis support that concurrent GCA and PMR is frequently present at the time of diagnosis. Additionally, we present the current evidence of GCA presenting in patients after PMR diagnosis. These results emphasize the need for studies applying imaging modalities to diagnose GCA.
Topics: Diagnostic Imaging; Giant Cell Arteritis; Humans; Incidence; Polymyalgia Rheumatica; Prevalence
PubMed: 35858507
DOI: 10.1016/j.semarthrit.2022.152069 -
Frontiers in Medicine 2022Chronic inflammation represents the cornerstone of the raised cardiovascular (CV) risk in patients with inflammatory rheumatic diseases (IRD), including vasculitis....
Chronic inflammation represents the cornerstone of the raised cardiovascular (CV) risk in patients with inflammatory rheumatic diseases (IRD), including vasculitis. Standardized mortality ratios in these patients are higher as compared to the general population, and the excess of premature mortality is due to early atherosclerotic events. Thus, IRD patients need appropriate CV risk assessment and management according to this CV disease (CVD) burden. Adequate control of CV risk is still lacking in usual care, but early diagnosis of silent and subclinical CVD is crucial to improve the long-term prognosis of these patients. Increased arterial stiffness may provide a pathophysiological link between inflammation and increased cardiovascular risk. Several noninvasive methods are now available to estimate artery stiffness in the clinical setting, including pulse wave velocity assessment. The independent predictive value of arterial stiffness for cardiovascular events has been demonstrated in general as well as in selected populations, and reference values adjusted for age and blood pressure have been suggested. Thus, arterial stiffness is an interesting biomarker for cardiovascular risk stratification. This systematic review summarizes the additional value that PWV measurement can provide in the setting of vasculitis, with a focus in the different clinical stages and CV risk prevention. This systematic review is registered with registration number: Prospero CRD42021259603.
PubMed: 35646970
DOI: 10.3389/fmed.2022.824630 -
Plastic and Reconstructive Surgery.... May 2022Temporal artery biopsy (TAB) is currently the gold standard procedure to diagnose giant cell arteritis. Despite low sensitivity, TAB is routinely performed even if a...
UNLABELLED
Temporal artery biopsy (TAB) is currently the gold standard procedure to diagnose giant cell arteritis. Despite low sensitivity, TAB is routinely performed even if a clinical diagnosis has already been made. The objective of this study was to determine the usefulness of TAB for giant cell arteritis management.
METHODS
We performed a systematic review to identify studies that compared steroid treatment between TAB+ and TAB- patients. EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched from inception until April 4, 2020. Titles, abstracts, and full texts were reviewed by two independent reviewers and conflicts resolved by consensus. Studies reporting TAB result and steroid treatment were included. Information pertaining to steroid treatment was compared between TAB+ and TAB- groups. Steroid duration was compared by grouping patients in a less than 6 month group, a 6-24 month group, and a more than 24 month group.
RESULTS
An estimated 5288 abstracts were screened and 13 studies involving 1355 patients were included. Rate of prebiopsy steroid treatment was higher in TAB+ patients compared with TAB- patients [93% versus 63% ( < 0.001)]. The TAB+ group was more likely to be started on steroids prebiopsy [28% versus 8% ( < 0.001)]. TAB+ and TAB- patients had similar steroid duration for all groups [<6-month group 17% versus 19% (-0.596), the 6-24-month group 16% versus 19% (-0.596), and the >24-month group 66% versus 63% (-0.642)].
CONCLUSION
TAB results have minimal impact on treatment, and the utility should be reconsidered when a clinical diagnosis of giant cell arteritis is possible.
PubMed: 35620490
DOI: 10.1097/GOX.0000000000004185 -
The Cochrane Database of Systematic... May 2022Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to... (Review)
Review
BACKGROUND
Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to large-sized vessels. Tocilizumab is a recombinant monoclonal antibody directed against interleukin-6 receptors (IL-6R).
OBJECTIVES
To assess the effectiveness and safety of tocilizumab, given alone or with corticosteroids, compared with therapy without tocilizumab for treatment of GCA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Science Information database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). There were no date or language restrictions in the electronic search for trials. We last searched the electronic databases on 3 January 2020.
SELECTION CRITERIA
We included only randomized controlled trials (RCTs) that compared tocilizumab of any dosage regimen (alone or with corticosteroids) with therapy without tocilizumab that had a minimum follow-up of six months. Participants were at least 50 years of age, with biopsy-proven GCA or by large-vessel vasculitis by angiography, and met the American College of Rheumatology 1990 guidelines for GCA.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
Main results We included two RCTs in the review. The studies were conducted in the USA, Canada, and Europe and enrolled a total of 281 participants with GCA, of whom 74% were women. The mean age of participants was 70 years, with new-onset or relapsing GCA, and fulfilled the 1990 American College of Rheumatology criteria with no uncontrolled comorbidities. Both studies were funded by F. Hoffmann-La Roche AG, the manufacturer of tocilizumab. Findings One RCT (30 participants) compared tocilizumab administered every four weeks versus placebo. Point estimates at 12 months and beyond favored tocilizumab over placebo in terms of sustained remission (risk ratio (RR) 4.25, 95% confidence interval (CI) 1.21 to 14.88; moderate-certainty evidence). Point estimates suggest no evidence of a difference for all-cause mortality at 12 months or more (RR 0.17, 95% CI 0.01 to 3.94; moderate-certainty evidence). At 12 months, mean time to first relapse after induction of remission was 25 weeks in favor of participants receiving tocilizumab compared to placebo (mean difference (MD) 25, 95% CI 11.4 to 38.6; moderate-certainty evidence). The second RCT (250 participants) randomized participants into two intervention and two comparator groups to receive tocilizumab weekly (100 participants), bi-weekly (49 participants), weekly placebo + 26-week taper (50 participants), or weekly placebo + 52-week taper (51 participants). At 12 months, point estimates from this study on proportion of participants with sustained remission favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 3.17, 95% CI 1.71 to 5.89; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 4.00, 95% CI 1.97 to 8.12; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 3.01, 95% CI 1.57 to 5.75; 100 participants); tocilizumab every other week versus placebo + 26-week taper (RR 3.79, 95% CI 1.82 to 7.91; 99 participants) (moderate-certainty evidence). Point estimates on proportion of participants who did not need escape therapy (defined by the study as the inability to keep to the protocol-defined prednisone taper) favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 1.71, 95% CI 1.24 to 2.35; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 2.96, 95% CI 1.83 to 4.78; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 1.49, 95% CI 1.04 to 2.14; 100 participants) but not tocilizumab every other week versus placebo + 26-week taper (RR 0.65, 95% CI 0.27 to 1.54; 99 participants) (moderate-certainty evidence). This study did not report mean time to first relapse after induction of remission or all-cause mortality. Across comparison groups, the same study found no evidence of a difference in vision changes and inconsistent evidence with regard to quality of life. Evidence on quality of life as assessed by the physical (MD 8.17, 95% CI 4.44 to 11.90) and mental (MD 5.61, 95% CI 0.06 to 11.16) component score of the 36-Item Short Form Health Survey (SF-36) favored weekly tocilizumab versus placebo + 52-week taper but not bi-weekly tocillizumab versus placebo + 26-week taper (moderate-certainty evidence). Adverse events One RCT reported a lower percentage of participants who experienced serious adverse events when receiving tocilizumab every four weeks versus placebo. The second RCT reported no evidence of a difference among groups with regard to adverse events; however, fewer participants reported serious adverse events in the tocilizumab weekly and tocilizumab biweekly interventions compared with the placebo + 26-week taper and placebo + 52-week taper comparators. Investigators in both studies reported that infection was the most frequently reported adverse event.
AUTHORS' CONCLUSIONS
This review indicates that tocilizumab therapy may be beneficial in terms of proportion of participants with sustained remission, relapse-free survival, and the need for escape therapy. While the evidence was of moderate certainty, only two studies were included in the review, suggesting that further research is required to corroborate these findings. Future trials should address issues related to the required duration of therapy, patient-reported outcomes such as quality of life and economic outcomes, as well as the clinical outcomes evaluated in this review.
Topics: Adrenal Cortex Hormones; Aged; Antibodies, Monoclonal, Humanized; Female; Giant Cell Arteritis; Humans; Male; Recurrence
PubMed: 35560150
DOI: 10.1002/14651858.CD013484.pub3 -
Seminars in Arthritis and Rheumatism Aug 2022To determine the prevalence and predictors of subclinical giant cell arteritis (GCA) in patients with newly diagnosed polymyalgia rheumatica (PMR). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine the prevalence and predictors of subclinical giant cell arteritis (GCA) in patients with newly diagnosed polymyalgia rheumatica (PMR).
METHODS
PubMed, Embase, and Web of Science Core Collection were systematically searched (date of last search July 14, 2021) for any published information on any consecutively recruited cohort reporting the prevalence of GCA in steroid-naïve patients with PMR without cranial or ischemic symptoms. We combined prevalences across populations in a random-effect meta-analysis. Potential predictors of subclinical GCA were identified by mixed-effect logistic regression using individual patient data (IPD) from cohorts screened with PET/(CT).
RESULTS
We included 13 cohorts with 566 patients from studies published between 1965 to 2020. Subclinical GCA was diagnosed by temporal artery biopsy in three studies, ultrasound in three studies, and PET/(CT) in seven studies. The pooled prevalence of subclinical GCA across all studies was 23% (95% CI 14%-36%, I=84%) for any screening method and 29% in the studies using PET/(CT) (95% CI 13%-53%, I=85%) (n=266 patients). For seven cohorts we obtained IPD for 243 patients screened with PET/(CT). Inflammatory back pain (OR 2.73, 1.32-5.64), absence of lower limb pain (OR 2.35, 1.05-5.26), female sex (OR 2.31, 1.17-4.58), temperature >37° (OR 1.83, 0.90-3.71), weight loss (OR 1.83, 0.96-3.51), thrombocyte count (OR 1.51, 1.05-2.18), and haemoglobin level (OR 0.80, 0.64-1.00) were most strongly associated with subclinical GCA in the univariable analysis but not C-reactive protein (OR 1.00, 1.00-1.01) or erythrocyte sedimentation rate (OR 1.01, 1.00-1.02). A prediction model calculated from these variables had an area under the curve of 0.66 (95% CI 0.55-0.75).
CONCLUSION
More than a quarter of patients with PMR may have subclinical GCA. The prediction model from the most extensive IPD set has only modest diagnostic accuracy. Hence, a paradigm shift in the assessment of PMR patients in favour of implementing imaging studies should be discussed.
Topics: Biopsy; Female; Giant Cell Arteritis; Humans; Polymyalgia Rheumatica; Positron Emission Tomography Computed Tomography; Prevalence
PubMed: 35537222
DOI: 10.1016/j.semarthrit.2022.152017