UNASSIGNED: We present a case with systemic amyloidosis secondary to ankylosing spondylitis (AA amyloidosis), whose 99mTc PYP scintigraphy revealed amyloid deposition in the thyroid gland (amyloid goiter). Amyloidosis is characterized by extracellular accumulation of amyloid fibril proteins leading to organ malfunction. Even though AA amyloidosis can be observed in patients with systemic inflammatory diseases, it is a very rare complication in ankylosing spondylitis. SPECT/CT images showed diffuse tracer uptake in enlarged thyroid gland containing fat density areas.

Amyloidosis is a disease characterized by local and systemic extracellular deposition of amyloid protein fibrils where its excessive accumulation in tissues and resistance to degradation can lead to organ failure. Diagnosis is challenging because of approximately 36 different amyloid protein subtypes. Imaging methods like immunohistochemistry and the use of Congo red staining of amyloid proteins for laser capture microdissection combined with liquid chromatography tandem mass spectrometry (LMD/LC-MS/MS) are two diagnostic methods currently used depending on the expertise of the pathology laboratory. Here, we demonstrate a streamlined in situ amyloid peptide spatial mapping by Matrix Assisted Laser Desorption Ionization-Mass Spectrometry Imaging (MALDI-MSI) combined with Trapped Ion Mobility Spectrometry for potential transthyretin (ATTR) amyloidosis subtyping. While we utilized the standard LMD/LC-MS/MS workflow for amyloid subtyping of 31 specimens from different organs, we also evaluated the potential introduction in the MS workflow variations in data acquisition parameters like dynamic exclusion, or testing Data Dependent Acquisition combined with High-Field Asymmetric Waveform Ion Mobility Spectrometry (DDA FAIMS) versus Data Independent Acquisition (DIA) for enhanced amyloid protein identification at shorter acquisition times. We also demonstrate the use of Mascot\'s Error Tolerant Search and PEAKS de novo sequencing for the sequence variant analysis of amyloidosis specimens.

BACKGROUND: Congo red staining of fat pad fine needle aspiration specimens is a method utilized for evaluation of amyloid deposition. However, these specimens can pose diagnostic challenges for cytopathologists. As part of ongoing internal quality improvement measures, the objective of this study was to evaluate the intradepartmental interobserver agreement of these specimens and to identify factors that affect the variability of the interpretations.
METHODS: There were 7 participants, which included 3 trainees, 3 cytopathologists, and 1 cytotechnologist. Each participant reviewed 50 Congo red stained fat pad fine needle aspiration slides. The interpretations were categorized into 3 groups: negative, indeterminate/suspicious, and positive. The participants also noted any interpretation challenges they encountered for each case.
RESULTS: There was only slight interobserver agreement among all participants (κ = 0.133). Stratified by participant group, the interobserver agreement among the trainees was slight bordering on poor (κ = 0.028) and among cytopathologists was fair (κ = 0.249). The highest agreement between 2 observers was between 2 cytopathologists and the level of agreement was moderate bordering on fair (κ = 0.426). There were only 3 cases (6.0%) with full agreement among observers, while in 25 cases (50.0%), there were 2 category differences in interpretations. The primary diagnostic challenge reported by participants was when weak or focal birefringence was encountered as well as cases complicated by poor stain quality and overstaining.
CONCLUSIONS: We found only slight interobserver agreement among all study participants. A major area of challenge was cases with weak birefringence resulting in high variance of interpretation among participants.

Amyloid A (AA) amyloidosis is induced by administering amyloid fibrils to animals under inflammatory conditions. Silk fibroin (SF), the main component of silk threads, forms amyloid-like fibrils and has been previously reported to induce AA amyloidosis in mice. In this study, SF was cultured in ethanol solution, and after confirming fibril formation through Thioflavin T assay, Congo red assay, and observation under electron microscopy, cultured SF ethanol solutions were administered to mice via various routes to investigate the induction of target organs and amyloidosis. As a result, cultured SF ethanol solutions were confirmed to reach the lungs and spleen, but no amyloid deposition was observed. While SF forms amyloid-like fibril structures through cultivation in ethanol solution, its amyloid-enhancing factor (AEF) activity is considered low in mice.

The relationship between amyloidosis and vasculature in cognitive impairment and Alzheimer\'s disease (AD) pathogenesis is increasingly acknowledged. We conducted a quantitative and topographic assessment of retinal perivascular amyloid plaque (AP) distribution in individuals with both normal and impaired cognition. Using a retrospective dataset of scanning laser ophthalmoscopy fluorescence images from twenty-eight subjects with varying cognitive states, we developed a novel image processing method to examine retinal peri-arteriolar and peri-venular curcumin-positive AP burden. We further correlated retinal perivascular amyloidosis with neuroimaging measures and neurocognitive scores. Our study unveiled that peri-arteriolar AP counts surpassed peri-venular counts throughout the entire cohort (P < 0.0001), irrespective of the primary, secondary, or tertiary vascular branch location, with a notable increase among cognitively impaired individuals. Moreover, secondary branch peri-venular AP count was elevated in the cognitively impaired (P < 0.01). Significantly, peri-venular AP count, particularly in secondary and tertiary venules, exhibited a strong correlation with clinical dementia rating, Montreal cognitive assessment score, hippocampal volume, and white matter hyperintensity count. In conclusion, our exploratory analysis detected greater peri-arteriolar versus peri-venular amyloidosis and a marked elevation of amyloid deposition in secondary branch peri-venular regions among cognitively impaired subjects. These findings underscore the potential feasibility of retinal perivascular amyloid imaging in predicting cognitive decline and AD progression. Larger longitudinal studies encompassing diverse populations and AD-biomarker confirmation are warranted to delineate the temporal-spatial dynamics of retinal perivascular amyloid deposition in cognitive impairment and the AD continuum.

Systemic diseases can cause heart block owing to the involvement of the myocardium and thereby the conduction system. Younger patients (<60) with heart block should be evaluated for an underlying systemic disease. These disorders are classified into infiltrative, rheumatologic, endocrine, and hereditary neuromuscular degenerative diseases. Cardiac amyloidosis owing to amyloid fibrils and cardiac sarcoidosis owing to noncaseating granulomas can infiltrate the conduction system leading to heart block. Accelerated atherosclerosis, vasculitis, myocarditis, and interstitial inflammation contribute to heart block in rheumatologic disorders. Myotonic, Becker, and Duchenne muscular dystrophies are neuromuscular diseases involving the myocardium skeletal muscles and can cause heart block.

UNASSIGNED: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a fatal disease. Tafamidis was approved to treat patients with ATTR-CM based on findings from the ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial).
UNASSIGNED: This post hoc analysis examined the proportion of patients who experienced improved efficacy measures through 30 months of treatment with tafamidis or placebo in ATTR-ACT.
UNASSIGNED: Patients with ATTR-CM were randomized to tafamidis (80 mg or 20 mg) or placebo. Change from baseline in 6-minute walk test distance, Kansas City Cardiomyopathy Questionnaire Overall Summary score, N-terminal pro-B-type natriuretic peptide concentration, patient global assessment of overall health, and New York Heart Association functional class were assessed at regular time points. The proportion of patients with improvement was summarized for each time point with odds ratio. Missing data were imputed as deterioration.
UNASSIGNED: Higher proportions of tafamidis-treated patients (n = 264) than placebo-treated patients (n = 177) showed improvement in all assessments. The odds ratio for improvement favored tafamidis for all measures and at all time points. It was significant (P < 0.001) at month 30 for 6-minute walk test distance (4.9; 95% CI: 2.28-10.69), Kansas City Cardiomyopathy Questionnaire Overall Summary score (3.3; 95% CI: 1.85-5.78), N-terminal pro-B-type natriuretic peptide concentration (5.3; 95% CI: 2.66-10.73), and patient global assessment of overall health (2.9; 95% CI: 1.69-4.95).
UNASSIGNED: This analysis found that higher proportions of patients treated with tafamidis experienced improvement from baseline in measures of heart failure, functional capacity, and health-related quality of life than those treated with placebo during ATTR-ACT. These data provide further evidence of the clinical benefits of tafamidis in patients with ATTR-CM. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT]; NCT01994889).

UNASSIGNED: Cardiac amyloidosis can coexist in patients with severe aortic stenosis. There are limited outcomes data on whether this impacts the risk of transcatheter aortic valve replacement (TAVR).
UNASSIGNED: The authors aimed to investigate the effect of amyloidosis on outcomes of TAVR.
UNASSIGNED: We used the Nationwide Readmissions Database to identify hospitalizations for TAVR between 2016 and 2019. The presence of a diagnosis of amyloidosis was identified. Propensity score-weighted regression analysis was used to identify the association of amyloidosis with in-hospital mortality, acute ischemic stroke, and 30-day readmission rate after TAVR.
UNASSIGNED: We identified 245,020 hospitalizations for TAVR, including 273 in patients with amyloidosis. The mean age was 79.4 ± 8.4 years. There was no difference in in-hospital mortality or 30-day readmission rate in patients with and without amyloidosis (1.8% vs 1.5%, P = 0.622; and 12.9% vs 12.5%, P = 0.858; respectively). However, there was a higher rate of acute ischemic stroke in patients with amyloidosis (6.2% vs 1.8%, P < 0.001). Propensity score-weighted logistic regression analysis showed the presence of amyloidosis was associated with greater odds of acute ischemic stroke (odds ratio: 3.08, 95% CI: 1.41-6.71, P = 0.005), but no difference in mortality (odds ratio: 0.79, 95% CI: 0.28-2.27, P = 0.666) or 30-day readmission rate after TAVR (HR: 0.72, 95% CI: 0.41-1.25, P = 0.241).
UNASSIGNED: This analysis suggests amyloidosis may be associated with a higher thromboembolic risk after TAVR that merits further investigation.

暂无摘要。

OBJECTIVE: Our purpose was to compare differences in the incidence of amyloid deposition in tenosynovium (TS) versus transverse carpal ligament (TCL) biopsies obtained during open carpal tunnel release. We hypothesized that the incidence of amyloid would be similar between TCL and TS when obtaining both specimens from the same patient.
METHODS: All primary, elective open carpal tunnel release cases that underwent biopsy for amyloid between January 2022 and September 2023 were reviewed. Tenosynovial and TCL specimens were independently evaluated by a pathologist to assess for amyloid. Demographic data were collected, and incidence of amyloid deposition was compared between the two samples. Agreement statistics, sensitivity, and specificity were calculated for TCL, using TS as the reference standard.
RESULTS: A total of 196 cases met either Tier 1 (n=180) or Tier 2 (n=16) biopsy criteria. Forty-eight cases were excluded for missed biopsies or laboratory processing errors, leaving 148 cases available for analysis. Amyloid deposition was present in 31 out of 148 (21%) TS specimens and 33 out of 148 (22%) TCL specimens. Overall, the results of the TS biopsy agreed with TCL biopsy in 138 out of 148 cases (93%). In the 10 cases for which the results of the TCL and TS biopsy differed, six cases had (+) TCL and (-) TS, and four cases had amyloid deposition in TS without evidence of deposition in the TCL. Sensitivity and specificity values for the TCL specimen were 87% and 95%, respectively. Positive and negative predictive values were 82% and 97%, respectively.
CONCLUSIONS: For cases of open carpal tunnel release undergoing biopsy, amyloid deposition was noted in 21% of TS specimens and 22% of TCL specimens. Results of TS and TCL biopsies obtained from the same patient agreed in 93% of cases. Single-source biopsy for amyloid represents a reasonable diagnostic approach. Future cost analyses should be performed to determine whether the addition of two biopsy sources to improve diagnostic accuracy is justified.
METHODS: Prognostic II.