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In a randomized trial of bortezomib, cyclophosphamide, and dexamethasone as compared with the same therapy plus daratumumab, patients with light-chain amyloidosis who received daratumumab had a higher frequency of hematologic complete response than those who did not (53.3% vs. 18.1%). Deaths were most commonly due to cardiac failure.

Aims We aim to determine if our previously validated, diagnostic artificial intelligence (AI) electrocardiogram (ECG) model is prognostic for survival among patients with cardiac amyloidosis (CA). Methods A total of 2533 patients with CA (1834 with light chain amyloidosis (AL), 530 with wild‐type transthyretin amyloid protein (ATTRwt) and 169 with hereditary transthyretin amyloid (ATTRv)] were included. An amyloid AI ECG (A2E) score was calculated for each patient reflecting the likelihood of CA. CA stage was calculated using the European modification of the Mayo 2004 criteria for AL and Mayo stage for transthyretin amyloid (ATTR). Risk of death was modelled using Cox proportional hazards, and Kaplan–Meier was used to estimate survival. Results Median age of the cohort was 67 [inter‐quartile ratio (IQR) 59, 74], and 71.6% were male. The median overall survival for the cohort was 35.6 months [95% confidence interval (CI) 32.3, 39.5]. For AL, ATTRwt and ATTRv, respectively, median survival was 22.9 (95% CI 19.2, 28.2), 47.2 (95% CI 43.4, 52.3) and 61.4 (95% CI 48.7, 75.9) months. On univariate analysis, an increasing A2E score was associated with more than a two‐fold risk of all‐cause death. On multivariable analysis, the A2E score retained its importance with a risk ratio of 2.0 (95% CI 1.58, 2.55) in the AL group and 2.7 (95% CI 1.81, 4.24) in the ATTR group. Conclusions Among patients with AL and ATTR amyloidosis, the A2E model helps to stratify risk of CA and adds another dimension of prognostication.

Background Although the use of bortezomib alone and in combination with steroids has shown efficacy in AL amyloidosis, its role in combination with high-dose melphalan and autologous stem cell transplantation (HDM/SCT) is unknown. In this study, we evaluated bortezomib in combination with dexamethasone (BD) for induction chemotherapy prior to HDM/SCT. Methods This was a single-center, prospective, randomized controlled trial comparing induction therapy consisting of two BD cycles followed by HDM/SCT (BD + HDM/SCT) with HDM/SCT alone in the treatment of patients with newly diagnosed AL amyloidosis. The hematological and organ responses of the patients were assessed every three months post HDM/SCT. Results Fifty-six patients newly diagnosed with renal (100%), cardiac (57.1%), liver (7.1%), or nervous system (8.9%) AL amyloidosis were enrolled in this study; 28 patients were assigned to each arm. Two patients died within 100 days of HDM/SCT (3.6% treatment-related mortality). The overall hematologic response rates in the BD + HDM/SCT arm and HDM/SCT arm at three, six and twelve months were 78.5% versus 50%, 82.1% versus 53.5% and 85.7% versus 53.5%, respectively. In the BD + HDM/SCT arm, 15 (53.5%) patients achieved a hematologic response after BD and before HDM/SCT. An intention-to-treat analysis revealed a higher rate of complete remission in the BD + HDM/SCT arm at both 12 and 24 months (67.9% and 70%, respectively) than with the HDM/SCT-only therapy (35.7% and 35%, respectively, P  = 0.03). After a median follow-up of 28 months, the survival rates at 24 months post-treatment start were 95.0% in the BD + HDM/SCT group and 69.4% in the HDM/SCT alone group ( P  = 0.03). Conclusions Our preliminary data suggest that the outcome of treating AL amyloidosis with BD induction and HDM/SCT was superior to the outcome of the HDM/SCT treatment alone. Trial registration This trial has been registered at clinicaltrials.gov with the number NCT01998503 .

Introduction Cardiac amyloidosis is frequently overlooked, leading to delayed diagnosis and underestimation of its true impact on cardiac mortality. Methods Using CDC WONDER (1999–2020), we identified U.S. decedents aged ≥ 25 years with amyloidosis (ICD-10 E85) as the underlying cause of death and at least one cardiac-related condition as a contributing cause. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated, and trends were analyzed using Joinpoint regression and autoregressive integrated moving average (ARIMA) forecasting through 2040. Results Among 16,673 deaths, the AAMR rose from 0.261 in 1999 to 0.608 in 2020, with inflection points in 2012 and 2017 and an overall annual increase of 3.96%. Mortality was higher in men (0.537 vs. 0.210) and Black individuals (0.83 vs. 0.32), with a sharp post-2017 rise, especially among Black decedents. Geographic disparities were also observed, with the highest rates in the Northeast and urban areas. Most deaths occurred in hospitals (43.2%) or at home (31.4%), and mortality rates peaked in those aged 85 and older. Forecasting models project continued increases in AAMR through 2040, reaching approximately 2.0 overall, with especially elevated rates among Black (≈ 5.9) and male (≈ 3.8) decedents. Conclusion Cardiac mortality in amyloidosis has risen sharply since 2017, likely driven by improved ATTR-CM detection through non-biopsy imaging and guideline adoption. Disparities by sex, race, and geography persist, reflecting uneven diagnostic capacity concentrated in urban and Northeastern centers. Forecasts project continued increases, particularly among Black and male individuals, underscoring the need for more equitable access to diagnosis and treatment.

Malnutrition is associated with mortality and impaired quality of life (QoL) in systemic immunoglobulin light-chain (AL) amyloidosis. The aim of this study was to determine whether nutritional counseling is beneficial to patients with AL. In this intervention study (ClinicalTrials.gov Identifier: NCT02055534), 144 treatment-naïve outpatients with AL were randomized to usual care (UC; n = 72) and nutritional counseling (NC; n = 72). In the randomized population, although patients in the NC group maintained a stable body weight (weight loss [WL] = 0.6 kg; 95% confidence interval [CI], −1.0 to 2.1; P = 0.214), those in the UC group demonstrated a significant decrease (WL = 2.1 kg; 95% CI, 0.2–4.1; P = 0.003). However, the difference in weight between groups was not significant (mean WL difference = 1.6 kg; 95% CI, −0.7 to 3.9; P = 0.179). Patients in the NC group demonstrated more satisfactory energy intake (≥75% of estimated requirements, odds ratio, 2.18; 95% CI, 1.04–4.57; P = 0.048) and a significant increase in the mental component summary of QoL (Short form-36) at 12 mo (mean difference, 8.1; 95% CI, 2.3–13.9; P = 0.007), which was restored to a mean score of 53 (95% CI, 50–53), over the healthy population norms. NC was also associated with better survival (crude hazard ratio, 0.57; 95% CI, 0.35–0.94; P = 0.028). In outpatients with AL, NC was helpful in preserving body weight, effective in improving mental QoL, and associated with better survival. •We investigated whether nutritional counseling is beneficial to patients with systemic immunoglobulin light-chain amyloidosis.•Nutritional counseling was helpful in preserving body weight in these patients.•Nutritional counseling was effective in improving the mental quality of life of these patients.•Nutritional counseling was associated with better survival in patients with systemic immunoglobulin light-chain amyloidosis.

Amyloid A (AA) amyloidosis, a complication of chronic inflammatory conditions, develops when proteolytic fragments of serum amyloid A protein are deposited in tissues as amyloid fibrils. This placebo-controlled trial investigated the effect of eprodisate, a small molecule that inhibits amyloid fibril polymerization and tissue deposition in patients with renal AA amyloidosis. As compared with placebo, the drug slowed a decline in renal function. Eprodisate is a member of a new class of compounds that interfere with interactions between amyloidogenic proteins and glycosaminoglycans. This trial investigated the effect of eprodisate, a small molecule that inhibits amyloid fibril polymerization and tissue deposition in patients with renal AA amyloidosis. As compared with placebo, the drug slowed a decline in renal function. The amyloidoses constitute a group of diseases in which proteins are deposited extracellularly in the tissues as insoluble fibrils, causing progressive organ dysfunction and death. 1 Amyloid A (AA) amyloidosis, also referred to as secondary amyloidosis, is a rare but serious complication of chronic inflammatory diseases and chronic infections. The amyloidogenic protein in AA amyloidosis is a proteolytic fragment of serum amyloid A protein (SAA), an acute-phase reactant produced by the liver. The kidney is the organ most frequently affected in AA amyloidosis. 2 Ongoing deposition of amyloid in the kidney results in proteinuria and progressive loss of renal function. The gastrointestinal . . .

High-dose melphalan and autologous stem cell transplantation (HDM/ASCT) is widely used in immunoglobulin light chain (AL) amyloidosis, but the benefit is debated mainly because of the high treatment-related mortality (24% in a randomised study comparing HDM/ASCT with oral melphalan/dexamethasone). We report here on the long-term outcome of all patients treated with HDM/ASCT for AL amyloidosis in Sweden between 1994 and 2009. Seventy-two patients were treated at eight Swedish centres. Median follow-up was 67.5 months. At least partial response (organ or haematological) was seen in 64% of the patients. Median overall survival was 98 months or 8.2 years, with 5-year survival 63.9% and 10-year survival 43.4%. In patients with cardiac involvement or multiple organ involvement, survival was significantly shorter, median overall survival 49 and 56 months, respectively. All mortality within 100 days from ASCT was 12.5% for all patients and 17.2% in the patients with cardiac involvement. For patients treated in the earlier time period (1994–2001), 100-day mortality was 23.8% compared with 7.8% in the later period (2002–2009). In conclusion, long survival times can be achieved in patients with AL amyloidosis treated with HDM/ASCT, also in smaller centres. Early mortality is high, but with a decreasing trend over time.

Background Hereditary gelsolin (AGel) amyloidosis is an autosomal dominantly inherited systemic amyloidosis that manifests with the characteristic triad of progressive ophthalmological, neurological and dermatological signs and symptoms. The National Finnish Gelsolin Amyloidosis Registry (FIN-GAR) was founded in 2013 to collect clinical data on patients with AGel amyloidosis, including altogether approximately one third of the Finnish patients. We aim to deepen knowledge on the disease burden and life span of the patients using data from the updated FIN-GAR registry. We sent an updated questionnaire concerning the symptoms and signs, symptomatic treatments and subjective perception on disease progression to 240 members of the Finnish Amyloidosis Association (SAMY). We analyzed the lifespan of 478 patients using the relative survival (RS) framework. Results The updated FIN-GAR registry includes 261 patients. Symptoms and signs corresponding to the classical triad of ophthalmological (dry eyes in 93%; corneal lattice amyloidosis in 89%), neurological (numbness, tingling and other paresthesias in 75%; facial paresis in 67%), and dermatological (drooping eyelids in 86%; cutis laxa in 84%) manifestations were highly prevalent. Cardiac arrhythmias were reported by 15% of the patients and 5% had a cardiac pacemaker installed. Proteinuria was reported by 13% and renal failure by 5% of the patients. A total of 65% of the patients had undergone a skin or soft tissue surgery, 26% carpal tunnel surgery and 24% at least unilateral cataract surgery. As regards life span, relative survival estimates exceeded 1 for males and females until the age group of 70–74 years, for which it was 0.96. Conclusions AGel amyloidosis causes a wide variety of ophthalmological, neurological, cutaneous, and oral symptoms that together with repeated surgeries cause a clinically significant disease burden. Severe renal and cardiac manifestations are rare as compared to other systemic amyloidoses, explaining in part the finding that AGel amyloidosis does not shorten the life span of the patients at least for the first 75 years.

Background Few studies have been conducted on the long-term prognosis of patients with amyloid light chain (AL) and amyloid A (AA) renal amyloidosis in the same cohort. Methods We retrospectively examined 68 patients with biopsy-proven renal amyloidosis (38 AL and 30 AA). Clinicopathological findings at the diagnosis and follow-up data were evaluated in each patient. We analyzed the relationship between clinicopathological parameters and survival data. Results Significant differences were observed in several clinicopathological features, such as proteinuria levels, between the AL and AA groups. Among all patients, 84.2 % of the AL group and 93.3 % of the AA group received treatments for the underlying diseases of amyloidosis. During the follow-up period (median 18 months in AL and 61 months in AA), 36.8 % of the AL group and 36.7 % of the AA group developed end-stage renal failure requiring dialysis, while 71.1 % of the AL group and 56.7 % of the AA group died. Patient and renal survivals were significantly longer in the AA group than in the AL group. eGFR of >60 mL/min/1.73 m 2 at biopsy and an early histological stage of glomerular amyloid deposition were identified as low-risk factors. A multivariate analysis showed that cardiac amyloidosis and steroid therapy significantly influenced patient and renal survivals. Conclusions Our results showed that heart involvement was the major predictor of poor outcomes in renal amyloidosis, and that the prognosis of AA renal amyloidosis was markedly better than that in previously reported cohorts. Therapeutic advances in inflammatory diseases are expected to improve the prognosis of AA amyloidosis.

Myeloablative doses of melphalan with rescue by autologous hematopoietic stem cells are currently used in the treatment of immunoglobulin-light-chain (AL) amyloidosis, but the efficacy of the therapy is unproven. This randomized trial compared a regimen of high-dose melphalan with standard doses of melphalan plus high doses of dexamethasone. The aggressive treatment had no survival advantage as compared with conventional treatment with standard-dose melphalan. This trial compared a regimen of high-dose melphalan with standard doses of melphalan plus high doses of dexamethasone. The aggressive treatment had no survival advantage as compared with conventional treatment. The origin of amyloid in systemic immunoglobulin-light-chain (AL) amyloidosis is a clone of plasma cells in the bone marrow that synthesizes monoclonal immunoglobulin light chains. In tissues, these light chains aggregate into amyloid fibrils. The accumulation of amyloid deposits in vital organs leads to progressive disability and death. Life expectancy depends on the degree of organ involvement and ranges from a few years to less than 6 months for patients with severe cardiomyopathy. 1 In the mid-1990s, two randomized trials showed that standard-dose chemotherapy with melphalan and prednisone could prolong survival in patients with AL amyloidosis, 1 , 2 but clinical responses were . . .