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Rheumatology (Oxford, England) Jul 2024Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine...
INTRODUCTION
Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as interleukin-1β (IL-1β), TNF-α, and interleukin-6 (IL-6) inhibitors, have been considered. However, the accessibility and cost of IL-1β inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented.
OBJECTIVE
To evaluate the efficacy and safety of tocilizumab in the treatment of FMF.
METHODS
Following PRISMA guidelines, we identified 237 articles on the use of TCZ in FMF.
RESULTS
After selection, 14 articles were included: 2 double-blind RCTs, 2 retrospective studies, and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in pediatric FMF.
CONCLUSION
This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1β inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.
PubMed: 38950176
DOI: 10.1093/rheumatology/keae338 -
Frontiers in Immunology 2024Leukocyte cell-derived chemotaxin-2 (LECT2) is an important cytokine synthesized by liver. Significant research interest is stimulated by its crucial involvement in... (Review)
Review
Leukocyte cell-derived chemotaxin-2 (LECT2) is an important cytokine synthesized by liver. Significant research interest is stimulated by its crucial involvement in inflammatory response, immune regulation, disease occurrence and development. However, bibliometric study on LECT2 is lacking. In order to comprehend the function and operation of LECT2 in human illnesses, we examined pertinent studies on LECT2 investigation in the Web of Science database, followed by utilizing CiteSpace, VOSview, and Scimago Graphica for assessing the yearly quantity of papers, countries/regions involved, establishments, authors, publications, citations, and key terms. Then we summarized the current research hotspots in this field. Our study found that the literature related to LECT2 has a fluctuating upward trend. "Angiogenesis", "ALECT2", "diagnosis", and "biliary atresia" are the current investigative frontiers. Our findings indicated that liver diseases (e.g. liver fibrosis and hepatic cell carcinoma), systemic inflammatory disease, and amyloidosis are the current research focus of LECT2. The current LECT2 research outcomes are not exceptional. We hope to promote the scientific research of LECT2 and exploit its potential for clinical diagnosis and treatment of related diseases through a comprehensive bibliometric review.
Topics: Humans; Bibliometrics; Intercellular Signaling Peptides and Proteins; Animals; Biomedical Research
PubMed: 38881894
DOI: 10.3389/fimmu.2024.1413466 -
Journal of Comparative Effectiveness... Jun 2024The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy... (Review)
Review
The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy (CM) trials, including transthyretin-mediated amyloidosis with CM (ATTR-CM), are often limited to hospitalization and mortality. To investigate the relationship between the 6MWT and hospitalization or mortality in CM, including ATTR-CM. A PRISMA-guided systematic literature review was conducted using search terms for CM, 6MWT, hospitalization and mortality. Forty-one studies were identified that reported 6MWT data and hospitalization or mortality data for patients with CM. The data suggest that a greater 6MWT distance is associated with a reduced risk of hospitalization or mortality in CM. The 6MWT is an accepted alternative end point in CM trials, including ATTR-CM.
PubMed: 38869839
DOI: 10.57264/cer-2023-0158 -
Rheumatology International Jul 2024We aimed to review the literature on the clinical presentation, renal pathology, treatment, and outcome of renal manifestations in adult-onset Still's disease (AOSD).
OBJECTIVE
We aimed to review the literature on the clinical presentation, renal pathology, treatment, and outcome of renal manifestations in adult-onset Still's disease (AOSD).
METHODS
We used PRISMA guidelines for our systematic review and included all English-language original articles from inception till September 15, 2023, on AOSD and kidney involvement in any form. Data on patient demographics, diagnostic criteria, clinical presentation, renal pathology, treatment employed including dialysis, outcome, cause of death were collected and analyzed.
RESULTS
The median age at the diagnosis of renal issues was 37, with a higher prevalence among females (58.1%). Among the cases, 28 experienced renal problems after being diagnosed with AOSD, 12 had simultaneous diagnoses of renal issues and AOSD, and in 4 cases, renal problems appeared before AOSD diagnosis. Out of the 44 cases, 36 underwent renal biopsy, revealing various pathology findings including AA amyloidosis (25%), collapsing glomerulopathy (11.4%), thrombotic microangiopathy (TMA) (11.4%), IgA nephropathy (9.1%), minimal change disease (6.8%), and others. Some cases were clinically diagnosed with TMA, proximal tubular dysfunction, or macrophage activation syndrome-related acute kidney injury. Treatment approaches varied, but glucocorticoids were commonly used. Renal involvement was associated with increased mortality and morbidity, with 6 out of 44 patients passing away, 4 progressing to end-stage renal disease (ESRD), and data on 2 cases' outcomes not available.
CONCLUSION
Renal manifestations in AOSD are diverse but rarely studied owing to the rarity of the disease. Studies with larger data would be essential to study further on the pathogenesis and implications.
Topics: Humans; Still's Disease, Adult-Onset; Kidney Diseases; Adult; Nephrosis, Lipoid; Kidney; Thrombotic Microangiopathies; Female; Amyloidosis; Glomerulonephritis, IGA; Glucocorticoids
PubMed: 38625385
DOI: 10.1007/s00296-024-05578-5 -
Minimal residual disease in systemic light chain amyloidosis: a systematic review and meta-analysis.Journal of Cancer Research and Clinical... Apr 2024Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains... (Meta-Analysis)
Meta-Analysis
PURPOSE
Minimal residual disease (MRD) is a validated prognostic factor in several hematological malignancies. However, its role in systemic light chain (AL) amyloidosis remains controversial, and this systematic review and meta-analysis aims to fill this gap.
METHODS
We searched for relevant studies on Pubmed, Embase, and Cochrane Controlled Register of Trials, nine studies involving 451 patients were included and meta-analyzed. This systematic review has been registered in PROSPERO (CRD42023494169).
RESULTS
Our study found that in the group of patients who achieved very good partial response (VGPR) or better, MRD negativity was correlated with higher cardiac and renal response rates [pooled risk ratio (RR) = 0.74 (95% CI 0.62-0.89), 0.74 (95% CI 0.64-0.87), respectively]. Patients with MRD positivity had a higher hematologic progression rate within two years after MRD detection [pooled RR = 10.31 (95% CI 2.02-52.68)]; and a higher risk of hematologic + organ progression in the first year [pooled RR = 12.57 (95% CI 1.73-91.04)]. Moreover, MRD negativity was correlated with a better progression-free survival (PFS) [pooled hazard ratio (HR) = 0.27 (95% CI 0.17-0.45)]; but it did not significantly improve the overall survival (OS) [pooled HR = 0.34 (95% CI 0.11-1.07)].
CONCLUSION
In AL amyloidosis, our study supports that MRD negativity correlates with higher cardiac or renal response rates and indicates a better PFS in the follow-up. However, the correlation between OS and the status of MRD is not significant.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Neoplasm, Residual; Amyloidosis; Hematologic Neoplasms; Kidney
PubMed: 38619663
DOI: 10.1007/s00432-024-05733-2 -
International Journal of Molecular... Mar 2024Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is... (Review)
Review
Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (v) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 v carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis.
Topics: Humans; Prealbumin; Intermediate Filaments; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Polyneuropathies; Biomarkers
PubMed: 38612579
DOI: 10.3390/ijms25073770 -
Current Cardiology Reviews Mar 2024Pericardial effusion is associated with amyloidosis, specifically amyloid light chain (AL) and transthyretin (ATTR) subtypes. However, the patients might present with...
BACKGROUND
Pericardial effusion is associated with amyloidosis, specifically amyloid light chain (AL) and transthyretin (ATTR) subtypes. However, the patients might present with different clinical symptoms.
OBJECTIVE
To determine the characteristics and associations of patients with pericardial effusion owing to either AL or ATTR amyloidosis.
METHODS
This study reviewed 26 studies from databases such as PubMed, MEDLINE, Web of Science, Google Scholar and CINAHL databases after protocol registration. The data were analyzed in IBM SPSS 21. Many statistical tests, such as Student t- and the Mann-Whitney U tests, were used. Multivariate logistic regression analysis was also performed. A p-value< 0.05 was considered significant.
RESULTS
A total of 531 patients with pericardial effusion secondary to amyloidosis were included. The mean age was 58.4±24.5 years. Most of the patients were male (72.9%). Common co-morbid conditions included hypertension (16.8%) and active smoking (12.9%). The most common time from symptom onset to the clinical presentation was less than 1 week (45%). ATTR amyloidosis was more common in older patients (p<0.05). Abdominal and chest discomfort were commonly associated with AL and ATTR amyloidosis, respectively (p<0.05). Patients with AL amyloidosis had a higher association with interventricular septal thickening and increased posterior wall thickness (p<0.05). First-degree atrioventricular block, left bundle branch block (LBBB), and atrial fibrillation (AF) were more associated with ATTR amyloidosis (p<0.05).
CONCLUSION
Pericardial effusion in patients with AL amyloidosis was associated with hypertrophic remodeling, while conduction abnormalities were associated with ATTR amyloidosis.
PubMed: 38465427
DOI: 10.2174/011573403X280737240221060630 -
Neurological Sciences : Official... Jul 2024To review the current data on cognitive and psychological characteristics of patients with CAA and on the instruments used for their evaluation. (Review)
Review
AIM
To review the current data on cognitive and psychological characteristics of patients with CAA and on the instruments used for their evaluation.
METHODS
A systematic search was performed in Embase, Scopus and PubMed with terms related to "cerebral amyloid angiopathy", "neuropsychological measures" and "patient-reported outcome measures" from January 2001 to December 2021.
RESULTS
Out of 2851 records, 18 articles were selected. The cognitive evaluation was present in all of which, while the psychological one only in five articles. The MMSE (Mini Mental State Examination), TMT (Trail Making Test), fluency test, verbal learning test, digit span, digit symbol and Rey figure tests were the most used cognitive tests, while executive function, memory, processing speed, visuospatial function, attention and language were the most frequent impaired cognitive functions. Depression was the most considered psychological factor usually measured with BDI (Beck Depression Inventory) and GDS (Geriatric Depression Scale).
CONCLUSIONS
The results of this study might be used in clinical practice as a guide to choose cognitive and psychological instruments and integrate them in the clinical evaluation. The results might also be used in the research field for studies investigating the impact of cognitive and psychological variables on the disease course and for consensus studies aimed at define a standardized evaluation of these aspects.
Topics: Humans; Cerebral Amyloid Angiopathy; Neuropsychological Tests; Cognitive Dysfunction; Depression
PubMed: 38388894
DOI: 10.1007/s10072-024-07399-7 -
International Journal of Cardiology May 2024Cardiac amyloidosis is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality. With the emergence of novel therapies, there is a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiac amyloidosis is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality. With the emergence of novel therapies, there is a growing interest in prognostication of patients with cardiac amyloidosis using cardiac magnetic resonance imaging (CMR). In this systematic review and meta-analysis, we aimed to examine the prognostic significance of myocardial native T1 and T2, and extracellular volume (ECV).
METHODS
Observational cohort studies or single arms of clinical trials were eligible. MEDLINE, EMBASE and CENTRAL were systematically searched from their respective dates of inception to January 2023. No exclusions were made based on date of publication, study outcomes, or study language. The study populations composed of adult patients (≥18 years old) with amyloid cardiomyopathy. All studies included the use of CMR with and without intravenous gadolinium contrast administration to assess myocardial native T1 mapping, T2 mapping, and ECV in association with the pre-specified primary outcome of all-cause mortality. Data were extracted from eligible primary studies by two independent reviewers and pooled via the inverse variance method using random effects models for meta-analysis.
RESULTS
A total of 3852 citations were reviewed. A final nine studies including a total of 955 patients (mean age 65 ± 10 years old, 32% female, mean left ventricular ejection fraction (LVEF) 59 ± 12% and 24% had NYHA class III or IV symptoms) with cardiac amyloidosis [light chain amyloidosis (AL) 50%, transthyretin amyloidosis (ATTR) 49%, other 1%] were eligible for inclusion and suitable for data extraction. All included studies were single centered (seven with 1.5 T MRI scanners, two with 3.0 T MRI scanners) and non-randomized in design, with follow-up spanning from 8 to 64 months (median follow-up = 25 months); 320 patients died during follow-up, rendering a weighted mortality rate of 33% across studies. Compared with patients with AL amyloid, patients with ATTR amyloid had significantly higher mean left ventricular mass index (LVMi) (102 ± 34 g/m vs 127 ± 37 g/m, p = 0.02). N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin T levels, mean native T1 values, ECV and T2 values did not differ between patients with ATTR amyloid and AL amyloid (all p > 0.25). Overall, the hazard ratios for mortality were 1.33 (95% CI = [1.10, 1.60]; p = 0.003; I = 29%) for every 60 ms higher T1 time, 1.16 (95% CI = [1.09, 1.23], p < 0.0001; I = 76%) for every 3% higher ECV, and 5.23 (95% CI = [2.27, 12.02]; p < 0.0001; I = 0%) for myocardial-to-skeletal T2 ratio below the mean (vs above the mean).
CONCLUSION
Higher native T1 time and ECV, and lower myocardial to skeletal T2 ratio, on CMR are associated with worse mortality in patients with cardiac amyloidosis. Therefore, tissue mapping using CMR may offer a useful non-invasive technique to monitor disease progression and determine prognosis in patients with cardiac amyloidosis.
Topics: Adult; Humans; Female; Middle Aged; Aged; Adolescent; Male; Cardiomyopathies; Stroke Volume; Ventricular Function, Left; Magnetic Resonance Imaging; Myocardium; Amyloid Neuropathies, Familial; Disease Progression; Magnetic Resonance Imaging, Cine; Predictive Value of Tests; Contrast Media; Observational Studies as Topic
PubMed: 38382853
DOI: 10.1016/j.ijcard.2024.131892 -
Journal of the Neurological Sciences Mar 2024Iatrogenic cerebral amyloid angiopathy (iCAA) is a rare form of CAA. Imaging features are overlapping with spontaneous CAA. However, in iCAA imaging features have not... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Iatrogenic cerebral amyloid angiopathy (iCAA) is a rare form of CAA. Imaging features are overlapping with spontaneous CAA. However, in iCAA imaging features have not been systematically described so far. The aim of this metaanalysis was to evaluate if any of the described imaging features showed colocalization with the initial site of surgery.
MATERIAL AND METHODS
A systematic review of the medical literature was performed. Patients with probable iCAA were included if the route of potential entry of amyloid into the CNS was unambiguous.
RESULTS
24 patients from 19 reports could be included. 84 ICHs were reported. 11 of the first ever ICH (69%, p = 0.0498, Fisher's exact test) occurred ipsilateral to the site of the initial surgery, whereas 59% of all ICH (n = 63, p = 0.126, Fisher's exact test) occurred ipsilateral to the site of the initial surgery. No cerebellar hemorrhages (0%) were reported. In 5 of 8 patients, ipsilateral hemorrhagic and non-hemorrhagic manifestations were present before symptom onset and/or occurrence of ICH.
DISCUSSION
This metananalysis of the imaging markers of iCAA revealed a spatial colocalization of first ICH with the site of the surgery. Imaging studies with patients at risk for iCAA after exposure to lyophilized dura should be conducted.
Topics: Humans; Cerebral Amyloid Angiopathy; Cerebral Hemorrhage; Iatrogenic Disease; Magnetic Resonance Imaging
PubMed: 38382149
DOI: 10.1016/j.jns.2024.122931