Combined Subcutaneous Fat Aspirate and Skin Tru-Cut Biopsy for Amyloid Screening in Patients with Suspected Systemic Amyloidosis.
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ABSTRACT:
SUBMITTER: Hansen CT
PROVIDER: S-EPMC8232664 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveDisease-modifying therapies are available for amyloidosis but are ineffective if end-organ damage is severe. As small fiber neuropathy is an early and common feature of amyloidosis, we assessed detection and typing yield of skin biopsy for amyloid in patients with confirmed systemic amyloidosis and neuropathic symptoms.MethodsIn this case-control study, patients with transthyretin and light chain amyloidosis (ATTRv, ATTRwt, and AL) were consecutively recruited. They were sex and age-matched to three control groups (1) non-neuropathic controls (NNC), (2) monoclonal gammopathy of undetermined significance (MGUS), and (3) other neuropathic disease controls (ONC). Patients underwent a double 3 mm skin biopsy in proximal and distal leg. Amyloid index and burden, protein typing by immuno-electron microscopy, intraepidermal nerve fiber density, electroneuromyography, and clinical characteristics were analyzed.ResultsWe studied 15 subjects with confirmed systemic amyloidosis, 20 NNC, 18 MGUS, and 20 ONC. Amyloid was detected in 100% of patients with amyloidosis (87% in ankle and 73% in thigh). It was not detected in any of the control groups. A small fiber neuropathy was encountered in 100% of amyloidosis patients, in 80% of MGUS, and in 78% of ONC. Amyloid burden was higher in ATTRv, followed by AL and ATTRwt. The ultrastructural examination allowed the identification of the precursor protein by immunotyping in most of the cases.InterpretationSkin biopsy is a minimally invasive test with optimal sensitivity for amyloid. It allows amyloid typing by electron microscope to identify the precursor protein. The diagnostic work up of systemic amyloidosis should include a skin biopsy.
| S-EPMC10723241 | biostudies-literature
Project description:PurposeConventional Abrams biopsy shows low sensitivity in suspected malignant pleural disease. There are limited data on the improvement in sensitivity by adding in image guidance. This retrospective study compares the diagnostic sensitivity of Abrams biopsy using ultrasound guidance with CT-guided Tru-Cut biopsy in suspected malignant pleural disease.MethodsData were collected from 2006 to 2012 of patients who underwent image-guided biopsies for suspected non-tuberculous pleural disease. Data were collected on the result of the initial biopsy and final patient diagnosis as of June 2015.ResultsSixty-three patients underwent image-guided Abrams biopsy and 29 underwent CT-guided Tru-Cut biopsies. The sensitivity of Abrams was 71.43 % compared to 75 % in the CT-guided Tru-Cut group. Specificity was 100 % in both groups.ConclusionsImage-guided Abrams biopsies demonstrate comparable diagnostic sensitivity in malignant pleural disease to CT-guided Tru-Cut biopsy.
| S-EPMC5093211 | biostudies-literature
Project description:Subcutaneous fat biopsy is useful for the evaluation of amyloidosis, environmental contaminants, lipid metabolism, genetic studies and diabetes research. The present study examined new technologies for fat biopsy.Subcutaneous fat biopsy in 10 high-risk individuals was randomized to (i) a 10 ml reciprocating procedure device (RPD) mechanical syringe or (ii) a 60 ml vacuum syringe. Outcome measures included pain by the 10 cm Visual Analogue Pain Scale (VAS), adequacy of biopsied tissue, complications and diagnosis. The operator's ability to control syringes was quantitatively measured by the linear displacement method.Both syringes permitted facile aspiration of subcutaneous fat with adequate sample without complications. The mechanical and the vacuum syringes enhanced control of the needle compared to conventional syringes, reducing unintended forward penetration by 75% (3.6 ± 0.5 mm) and 87% (12.0 ± 1.4 mm), respectively (p < 0.0001). Free adipose cells were obtained in abundance as well as columnar biopsies containing intact blood vessels and connective tissue septa permitting precise microhistological examination. One case of primary AL amyloidosis (? light chain disease) was diagnosed in each group.Subcutaneous fat biopsy by needle aspiration can be facilely achieved with new aspiration syringe technologies with improved needle control and enhanced patient safety.
| S-EPMC3638025 | biostudies-literature
Project description:Fat pad aspiration is a commonly used method for detecting amyloid in tissue. Amyloid is detected in the small blood vessels of the aspirated adipose tissue. Optimum evaluation of amyloid with electron microscopy requires at least 15 blood vessels in the fat pad aspirate. The presence of a significant proportion of adipocytes in the aspirate dilutes the fibrovascular portion. This may compromise the evaluation for amyloid with electron microscopy and in FFPE with proteomic studies by mass spectroscopy for confirmation of the amyloid subtype. This video article describes the updated protocol for processing the anterior fat pad aspirate. It demonstrates how to remove the interference of blood and fatty component in the fat pad aspirate performed by the previously reported procedure.
| S-EPMC7568089 | biostudies-literature
Project description:BACKGROUND:The diagnostic accuracy of histopathological detection of transthyretin amyloid (ATTR) by Congo red staining of abdominal fat samples has been questioned since low sensitivity has been reported, especially for patients with ATTR cardiomyopathy. However, the outcome of surgically obtained fat pad biopsies has not yet been evaluated. The aim was to evaluate the diagnostic accuracy of skin punch biopsies from abdominal fat in patients with suspected ATTR amyloidosis. MATERIAL AND METHODS:Data were evaluated from patients who had undergone abdominal fat pad biopsies using a skin punch due to suspected amyloidosis from 2006 to 2015. The biopsies had been analysed using Congo red staining to determine the presence of amyloid, and immunohistochemistry or Western blot to determine the type of amyloidosis. The final diagnosis was based on the clinical picture, biopsy results and DNA sequencing. Minimum follow-up after the initial biopsy was 3 years. RESULTS:Two hundred seventy-four patients (61% males) were identified, and in 132 (48%), a final diagnosis of amyloidosis had been settled. The majority (93%) had been diagnosed with hereditary transthyretin (ATTRv) amyloidosis, and therefore subsequent analyses were focused on these patients. Overall, our data showed a test specificity of 99% and a sensitivity of 91%. Ninety-eight (94%) of the patients had neuropathic symptoms at diagnosis, whereas 57 (55%) had signs of amyloid cardiomyopathy. Subgroup analyses showed that patients with merely neuropathic symptoms displayed the highest test sensitivity of 91%, whereas patients with pure cardiomyopathy displayed the lowest sensitivity of 83%. However, no significant differences in sensitivity were found between patients with or without cardiomyopathy or between the sexes. CONCLUSIONS:Abdominal fat pad biopsies exhibit good diagnostic accuracy in patients with suspect ATTRv amyloidosis, including patients presenting with cardiomyopathy. In addition, the method enables typing not only of the precursor protein but also of the amyloid fibril type, which is related to the phenotype and to the outcome of the disease.
| S-EPMC7545559 | biostudies-literature
Project description:Current diagnosis of Transthyretin-related Amyloidosis (ATTR) using bone scintigraphy is primarily based on visual scoring and semi-quantitative indices. With the introduction of new potential life-prolonging drugs for ATTR, a more precise quantification of myocardial amyloid burden is desirable for improved response prediction and therapy monitoring. At first, quantification experiments using an anthropomorphic thorax phantom were performed. Second, 32 patients underwent both planar whole body [99mTc]- 3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD)-scintigraphy and quantitative Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) of the thorax. SPECT/CT standardized myocardial uptake values SUVpeak and SUVpeak normalized to bone uptake (nSUVpeak) were determined. Phantom measurements showed a strong linear relationship between the activity in the myocardial insert and the measured activity (r = 0.9998, p = 0.01), but the measured activity was systematically underestimated by approximately 30%. Receiver operating characteristics (ROC) analysis revealed a 100% sensitivity and specificity at a cut-off of 3.1 for SUVpeak for the differentiation of both patient groups. SUV quantification of ATTR amyloid burden is feasible using novel SPECT/CT technology. With a SUVpeak cut-off of 3.1, patients with Perugini grade 2 and 3 could be clearly separated from those with Perugini grade 0 and 1. Besides ATTR diagnostics, quantification of amyloid deposits could potentially be used for therapy monitoring and prognostication in patients with cardiac ATTR.
| S-EPMC7693120 | biostudies-literature
Project description:AL amyloidosis is caused by the misfolding of immunoglobulin light chains leading to an impaired function of tissues and organs in which they accumulate. Due to the paucity of -omics profiles from undissected samples, few studies have addressed amyloid-related damage system wide. To fill this gap, we evaluated proteome changes in the abdominal subcutaneous adipose tissue of patients affected by the AL isotypes κ and λ. Through our retrospective analysis based on graph theory, we have herein deduced new insights representing a step forward from the pioneering proteomic investigations previously published by our group. ECM/cytoskeleton, oxidative stress and proteostasis were confirmed as leading processes. In this scenario, some proteins, including glutathione peroxidase 1 (GPX1), tubulins and the TRiC complex, were classified as biologically and topologically relevant. These and other results overlap with those already reported for other amyloidoses, supporting the hypothesis that amyloidogenic proteins could induce similar mechanisms independently of the main fibril precursor and of the target tissues/organs. Of course, further studies based on larger patient cohorts and different tissues/organs will be essential, which would be a key point that would allow for a more robust selection of the main molecular players and a more accurate correlation with clinical aspects.
| S-EPMC10000381 | biostudies-literature
Project description:Background The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined. Methods and Results We included all patients diagnosed with amyloid light-chain (AL) or transthyretin cardiac amyloidosis at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular endomyocardial biopsy. Patients (n=37) were more often men (92%), with a median age of 72 years (interquartile range, 68-81). Lambda-positive AL was found in 14 of 19 AL cases (38%) and kappa-positive AL in 5 of 19 (14%), while transthyretin was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10%-30%), without significant differences between AL and transthyretin amyloidosis. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10%-23%; range, 5%-60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between transthyretin amyloidosis and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance, the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (r=0.661, P=0.001). The combined amyloid and fibrosis extent correlated with high-sensitivity troponin T (P=0.035) and N-terminal pro-B-type natriuretic peptide (P=0.002) serum levels. Conclusions Extracellular spaces in cardiac amyloidosis are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased extracellular volume at cardiac magnetic resonance and circulating biomarkers than amyloid extent alone.
| S-EPMC8751897 | biostudies-literature
Project description:ObjectiveTo assess the relationship between bone marrow (BM) biopsy operator experience and both specimen quality and ancillary testing utilization.Patients and methodsWe evaluated all referred and in-house (IH) BM biopsy specimens obtained over a contiguous 6-week period from April 3, 2017, to May 19, 2017. The BM specimens were assessed for the length of interpretable marrow, and aspirates were assessed for the presence of spicules. Subgroup comparisons included IH BM obtained by a trained team of nurses within our institution, patients clinically referred (CR) to our institution with outside-obtained BM specimens, and outside pathologist-referred (PR) consultation cases. Ancillary study usage was compared between the first 100 cases of each group.ResultsA total of 1191 BM specimens were analyzed, including 600 IH, 288 CR, and 303 PR cases with biopsies and/or aspirates. The average interpretable biopsy lengths of IH, CR, and PR cases were 16.0 mm, 10.0 mm, and 7.0 mm, respectively (P<.001). World Health Organization-recommended length of 15 mm or more was achieved in 61.4%, 26.6%, and 19.1%, respectively (P<.001). Of the aspirates analyzed among IH, CR, and PR cases, 93%, 71.3%, and 73.5% contained spicules, respectively (P<.001). Use of immunohistochemistry, flow cytometry, karyotype, and fluorescence in situ hybridization was higher in CR and PR cases than in IH cases (all P<.05). The IH, CR, and PR cases used on average 1.5, 2.8, and 4.8 immunohistochemistry stains per case (P<.001).ConclusionHaving a dedicated team of BM biopsy operators is likely one factor contributing to improved BM biopsy quality and a reduced need for ancillary testing.
| S-EPMC6132213 | biostudies-literature
Project description:PURPOSE:Nipple secretions are protein-rich and a potential source of breast cancer biomarkers for breast cancer screening. Previous studies of specific proteins have shown limited correlation with clinicopathological features. Our aim, in this pilot study, was to investigate the intra- and interpatient protein composition of nipple secretions and the implications for their use as liquid biopsies. EXPERIMENTAL DESIGN:Matched pairs of nipple discharge/nipple aspirate fluid (NAF, n = 15) were characterized for physicochemical properties and SDS-PAGE. Four pairs were selected for semiquantitative proteomic profiling and trypsin-digested peptides analyzed using 2D-LC Orbitrap Fusion MS. The resulting data were subject to bioinformatics analysis and statistical evaluation for functional significance. RESULTS:A total of 1990 unique proteins were identified many of which are established cancer-associated markers. Matched pairs shared the greatest similarity (average Pearson correlation coefficient of 0.94), but significant variations between individuals were observed. CONCLUSIONS AND CLINICAL RELEVANCE:This was the most complete proteomic study of nipple discharge/nipple aspirate fluid to date providing a valuable source for biomarker discovery. The high level of milk proteins in healthy volunteer samples compared to the cancer patients was associated with galactorrhoea. Using matched pairs increased confidence in patient-specific protein levels but changes relating to cancer stage require investigation of a larger cohort.
| S-EPMC5638085 | biostudies-literature