Marked progress in AL amyloidosis survival: a 40-year longitudinal natural history study.
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ABSTRACT:
SUBMITTER: Staron A
PROVIDER: S-EPMC8338947 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe world's most catastrophic epidemic thunderstorm asthma event (ETSA) affected Melbourne in 2016. Little is known about the natural history of individuals affected by such extreme events.ObjectiveIn this single center prospective 3-year longitudinal study, symptomatology and behaviors of individuals affected by ETSA were assessed.MethodsStandardized telephone questionnaire was used to evaluate frequency of asthma symptoms, inhaled corticosteroid preventer use, asthma action plan ownership, and healthcare utilization. Questionnaires were administered at 12, 24, and 36 months after 2016 ETSA. Subgroup analyses of the 'current', 'past', 'possible,' and 'no asthma' subgroups were also conducted.ResultsTwo hundred and eight, 164, and 112 completed questionnaires were analyzed in 2017, 2018, and 2019, respectively. Seventy to eighty five percent of respondents reported ongoing asthma symptoms in any given year, of which 20%-28% experienced weekly symptoms. Nearly 50% of respondents were prescribed preventers, with approximately 45% adherent at least 5 days a week. Less than 40% had an asthma action plan and 15%-20% sought urgent medical attention for asthma over the follow-up period. Among 106 individuals with 3 consecutive years of completed questionnaires, those with no prior doctor diagnosis of asthma were significantly more likely to be asymptomatic on follow-up than those with a prior doctor diagnosis of asthma (p = 0.02). Subgroup analyses suggest that large proportions of respondents with 'past' and 'no asthma' continue to remain symptomatic throughout the 36-month period.ConclusionIn individuals affected by ETSA, we found evidence of ongoing loss of asthma control in those with previously well controlled asthma, and the persistence of symptoms suggestive of asthma in those with no history or symptoms suggestive of prior asthma, even after 36 months from initial ETSA. Low rates of inhaler adherence and asthma action plan ownership may contribute to increased morbidity and mortality from future ETSA events. Further research is required to confirm these findings.
| S-EPMC7402954 | biostudies-literature
Project description:AimsTransthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly diagnosed at an early stage of the disease natural history, defined as National Amyloidosis Centre (NAC) ATTR Stage I. The natural history of early-stage ATTR-CM remains poorly characterized.Methods and resultsA retrospective multi-centre observational study of 879 patients with ATTR-CM, either wild-type TTR genotype or carrying the p.V142I TTR variant, and NAC ATTR Stage I biomarkers at the time of diagnosis who did not receive disease-modifying therapy for amyloidosis. Disease characteristics at diagnosis that were independently associated with mortality by Cox regression analysis were N-terminal pro-B-type natriuretic peptide (NT-proBNP), TTR genotype, and troponin T. Patients were categorized into NAC ATTR Stage Ia, defined as a furosemide equivalent diuretic requirement of <0.75 mg/kg and an NT-proBNP ≤500 ng/L or ≤1000 ng/L in the presence of atrial fibrillation, and NAC ATTR Stage Ib comprising all remaining Stage I patients. Median estimated survival among the 88% NAC ATTR Stage Ib patients was 75 (95% CI 57-93) months compared with >100 months in the 12% with Stage Ia disease [hazard ratio for death 5.06 (95% confidence interval 1.23-20.87); P = 0.025] despite significant cardiovascular morbidity at the time of diagnosis which increased during follow-up, including among patients diagnosed in NAC ATTR Stage Ia. Estimated survival among UK NAC ATTR Stage Ia patients was comparable to UK general population controls (P = 0.297).ConclusionPatients with NAC ATTR Stage I ATTR-CM can be further stratified according to NT-proBNP concentration and diuretic requirement at diagnosis. Patients with Stage Ia ATTR-CM have significant cardiovascular morbidity despite good short- and mid-term survival.
| S-EPMC9279112 | biostudies-literature
Project description:ObjectiveNatural history of cardiac amyloidosis (CA) is poorly understood. We aimed to examine the changing mortality of different types of CA over a 30-year period.Patients and methodsConsecutive patients included in the "Trieste CA Registry" from January 1, 1990 through December 31, 2021 were divided into a historical cohort (diagnosed before 2016) and a contemporary cohort (diagnosed after 2016). Light chain (AL), transthyretin (ATTR) and other forms of CA were defined according to international recommendations. The primary and secondary outcome measures were all-cause mortality and cardiac death, respectively.ResultsWe enrolled 182 patients: 47.3% AL-CA, 44.5% ATTR-CA, 8.2% other etiologies. The number of patients diagnosed with AL and ATTR-CA progressively increased over time, mostly ATTR-CA patients (from 21% before 2016 to 67% after 2016) diagnosed non-invasively. The more consistent increase in event-rate was observed in the long-term (after 50 months) in ATTR-CA compared to the early increase in mortality in AL-CA. In the contemporary cohort, during a median follow up of 16 [4-30] months, ATTR-CA was associated with improved overall and cardiac survival compared to AL-CA. At multivariable analysis, ATTR-CA (HR 0.42, p = 0.03), eGFR (HR 0.98, p = 0.033) and ACE-inhibitor therapy (HR 0.24, p < 0.001) predicted overall survival in the contemporary cohort.ConclusionIncidence and prevalence rates of ATTR-CA and, to a less extent, of AL-CA have been increasing over time, with significant improvements in 2-year survival of ATTR-CA patients from the contemporary cohort. Reaching an early diagnosis and starting disease-modifying treatments will improve long-term survival in CA.
| S-EPMC9677956 | biostudies-literature
Project description:Specimens and associated data in natural history collections (NHCs) foster substantial scientific progress. In this paper, we explore recent contributions of NHCs to the study of systematics and biogeography, genomics, morphology, stable isotope ecology, and parasites and pathogens of mammals. To begin to assess the magnitude and scope of these contributions, we analyzed publications in the Journal of Mammalogy over the last decade, as well as recent research supported by a single university mammal collection (Museum of Southwestern Biology, Division of Mammals). Using these datasets, we also identify weak links that may be hindering the development of crucial NHC infrastructure. Maintaining the vitality and growth of this foundation of mammalogy depends on broader engagement and support from across the scientific community and is both an ethical and scientific imperative given the rapidly changing environmental conditions on our planet.
| S-EPMC4794611 | biostudies-literature
Project description:Systemic light chain (AL) amyloidosis is a protein misfolding disorder characterized by the deposition of abnormal immunoglobulin light chains in fibrillary aggregates, resulting in end-organ damage. Several unique challenges face treating physicians, including delayed diagnosis, advanced vital organ involvement, and morbidity with treatment. Aggressive supportive care and risk-adapted application of plasma cell-directed therapies are the cornerstones of management. The therapeutic revolution in multiple myeloma will likely further expand the arsenal against plasma cells. Careful investigation of these agents will be critical to establish their role in this fragile population. The promise of fibril-directed therapies to restore organ function remains despite early disappointments. In this review, we discuss new therapies to tackle AL amyloidosis using a case-based approach.
| S-EPMC8791171 | biostudies-literature
Project description:CD138-selected marrow plasma cells from newly diagnosed AL patients were studied for cyclin D1 expression. We identified patients whose plasma cells overexpressed cyclin D1 and compared them to those whose cells did not.
2010-09-15 | GSE24128 | GEO
Project description:Alpha-Mannosidosis is a rare lysosomal storage disorder, caused by the deficiency of the enzyme alpha-Mannosidase. Clinically it is characterized by hearing impairment, skeletal and neurological abnormalities and mental retardation. In order to characterize the clinical features and disease progression of patients affected by alpha-Mannosidosis, a survey study was conducted. 43 patients from 4 European countries participated in this longitudinal study. Age range of the participants was 3 to 42 years. For each patient a medical history, complete physical and neurological examination, joint range of motion and assessment of physical endurance and of lung function were completed. In addition, serum and urinary oligosaccharide levels were analysed.In this multicenter longitudinal study clinical data of 43 alpha-Mannosidosis patients were collected. In addition to objective clinical measurements biochemical assays were performed.Data analysis revealed a wide spectrum of clinical presentation regarding the severity and disease progression. Most clinical abnormalities were observed in the musculoskeletal and neurological system. All patients showed mental retardation and hearing loss from early childhood. An impairment in physical endurance was revealed by the 6-minute walk and 3-minute stair stair climb tests. There was only slight progression of a few clinical findings: Psychiatric troubles in both groups essentially, and respiratory dysfunction under 18 years. The serum and urinary oligosaccharide levels were increased in all affected individuals and correlated well with the 6-minute walk and 3-minute stair climb test results.This study confirms that alpha-Mannosidosis is a very heterogeneous disorder regarding both, disease severity and progression. As it has been shown that Mannosidosis patients are able to perform lung function tests and the 6MWT and stair-climb test, these clinical parameters apparently can be used as clinical endpoints for clinical trials. Oligosaccharide levels appeared correlated with functional testing and may serve as biomarkers of disease severity, progression and response to treatment.ClinicalTrials.gov Identifier = NCT00498420 and EuropeanCommission FP VI contract LHSM-CT-2006-018692.
| S-EPMC3691585 | biostudies-literature
Project description:In amyloid light chain (AL) amyloidosis, a small B-cell clone, most commonly a plasma cell clone, produces monoclonal light chains that exert organ toxicity and deposit in tissue in the form of amyloid fibrils. Organ involvement determines the clinical manifestations, but symptoms are usually recognized late. Patients with disease diagnosed at advanced stages, particularly when heart involvement is present, are at high risk of death within a few months. However, symptoms are always preceded by a detectable monoclonal gammopathy and by elevated biomarkers of organ involvement, and hematologists can screen subjects who have known monoclonal gammopathy for amyloid organ dysfunction and damage, allowing for a presymptomatic diagnosis. Discriminating patients with other forms of amyloidosis is difficult but necessary, and tissue typing with adequate technology available at referral centers, is mandatory to confirm AL amyloidosis. Treatment targets the underlying clone and should be risk adapted to rapidly administer the most effective therapy patients can safely tolerate. In approximately one-fifth of patients, autologous stem cell transplantation can be considered up front or after bortezomib-based conditioning. Bortezomib can improve the depth of response after transplantation and is the backbone of treatment of patients who are not eligible for transplantation. The daratumumab+bortezomib combination is emerging as a novel standard of care in AL amyloidosis. Treatment should be aimed at achieving early and profound hematologic response and organ response in the long term. Close monitoring of hematologic response is vital to shifting nonresponders to rescue treatments. Patients with relapsed/refractory disease are generally treated with immune-modulatory drugs, but daratumumab is also an effective option.
| S-EPMC7727541 | biostudies-literature
Project description:BackgroundSystemic light chain (AL) amyloidosis is a clonal plasma-cell neoplasm that carries a poor prognosis. Although AL amyloidosis and Multiple Myeloma (MM) can co-exist and share various cytogenetic chromosomal abnormalities, little is known about Fluorescent in situ hybridization (FISH) and its prognostic relevance in AL amyloidosis.AimThe study aims to evaluate the most prevalent FISH cytogenetic abnormalities in AL patients as independent prognostic factors, and assess the impact of cytogenetics on the survival of high-risk cardiac AL patients.Materials & methodsThis retrospective study reviewed 113 consecutive AL patients treated at The Ohio State University (OSU). Patients were divided into subgroups based on FISH data obtained within 90 days of diagnosis. Hyperdiploidy was defined as trisomies of at least 2 chromosomal loci. Primary endpoints were progression free survival (PFS) and overall survival (OS). Kaplan Meier curves were used to calculate PFS and OS. The log-rank test and Cox proportional hazard models were used to test the equality of survival functions and further evaluate the differences between groups.ResultsFISH abnormalities were detected in 76% of patients. Patients with abnormal FISH trended toward lower overall survival (OS) (p=0.06) and progression free survival (PFS) (p=0.06). The two most prevalent aberrations were translocation t(11;14) (39%) and hyperdiploidy-overall (38%). Hyperdiploidy-overall was associated with worsening PFS (p=0.018) and OS (p=0.03), confirmed in multivariable analysis. Patients with del 13q most frequently had cardiac involvement (p=0.006) and was associated with increased bone marrow plasmacytosis (p=0.02). Cardiac AL patients with no FISH abnormalities had much improved OS (p=0.012) and PFS (p=0.018) CONCLUSIONS: Our findings ultimately reveal the association of hyperdiploidy on survival in AL amyloidosis patients, including the high-risk cardiac AL population.
| S-EPMC7897960 | biostudies-literature
Project description:CD138-selected marrow plasma cells from newly diagnosed AL patients were studied for cyclin D1 expression. We identified patients whose plasma cells overexpressed cyclin D1 and compared them to those whose cells did not. We compared two groups of AL patients based cyclin D1 expression being high or low.
2010-09-15 | E-GEOD-24128 | biostudies-arrayexpress