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1.
Transplantation ; 104(8): 1703-1711, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732850

RESUMO

BACKGROUND: There are limited data on the outcome of transplant recipients with familial Mediterranean fever (FMF)-associated AA amyloidosis. The aim of the present study is to evaluate demographic, clinical, laboratory, and prognostic characteristics and outcome measures of these patients. METHODS: Eighty-one renal transplant recipients with FMF-associated AA amyloidosis (group 1) and propensity score-matched transplant recipients (group 2, n = 81) with nonamyloidosis etiologies were evaluated in this retrospective, multicenter study. Recurrence of AA amyloidosis was diagnosed in 21 patients (group 1a), and their features were compared with 21 propensity score-matched recipients with FMF amyloidosis with no laboratory signs of recurrence (group 1b). RESULTS: The risk of overall allograft loss was higher in group 1 compared with group 2 (25 [30.9%] versus 12 [14.8%]; P = 0.015 [hazard ratio, 2.083; 95% confidence interval, 1.126-3.856]). Patients in group 1 were characterized by an increased risk of mortality compared with group 2 (11 [13.6%] versus 0%; P = 0.001 [hazard ratio, 1.136; 95% confidence interval, 1.058-1.207]). Kaplan-Meier analysis revealed that 5- and 10-year patient survival rates in group 1 (92.5% and 70.4%) were significantly lower than in group 2 (100% and 100%; P = 0.026 and P = 0.023, respectively). Although not reaching significance, overall, 5- and 10-year graft survival rates (57.1%, 94.7%, and 53.8%, respectively) in group 1a were worse than in group 1b (76.2%, 95%, and 77.8%, respectively; P = 0.19, P = 0.95, and P = 0.27, respectively). CONCLUSIONS: AA amyloidosis is associated with higher risk of mortality after kidney transplantation. Inflammatory indicators should be monitored closely, and persistent high levels of acute-phase reactants should raise concerns about amyloid recurrence in allograft.


Assuntos
Amiloidose/cirurgia , Febre Familiar do Mediterrâneo/complicações , Rejeição de Enxerto/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Aloenxertos/imunologia , Aloenxertos/patologia , Amiloidose/imunologia , Amiloidose/mortalidade , Amiloidose/patologia , Biópsia , Febre Familiar do Mediterrâneo/imunologia , Febre Familiar do Mediterrâneo/mortalidade , Febre Familiar do Mediterrâneo/cirurgia , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Humanos , Estimativa de Kaplan-Meier , Rim/imunologia , Rim/patologia , Falência Renal Crônica/imunologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Proteína Amiloide A Sérica/imunologia , Proteína Amiloide A Sérica/metabolismo , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
2.
Clin Nucl Med ; 45(10): 838-839, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32796236

RESUMO

Amyloid deposition can lead to Alzheimer disease and cerebral amyloid angiopathy. Rarely, it presents as a solitary focal deposition, primary cerebral amyloidoma, which can be misinterpreted as a neoplasm because of the "tumor-like" appearances. We present the case of a 54-year-old woman where MRI revealed a T2-hyperintense mass periventricular in the white matter with moderate contrast enhancement. Pathological investigation revealed AL (lambda) amyloidoma. F-florbetapir PET/CT was used to support the diagnosis and in follow-up. This case highlights that F-florbetapir PET/CT might play a role in the diagnostic workup of patients suggestive of cerebral amyloidoma, especially in cases where biopsy is not feasible.


Assuntos
Amiloidose/diagnóstico por imagem , Compostos de Anilina , Etilenoglicóis , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Idoso , Amiloidose/patologia , Biópsia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
3.
Neurology ; 95(7): e815-e826, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32690787

RESUMO

OBJECTIVES: To investigate the relationships of serum albumin with in vivo Alzheimer disease (AD) pathologies, including cerebral ß-amyloid (Aß) protein deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMH), in the human brain. METHODS: A total of 396 older adults without dementia underwent comprehensive clinical assessments, measurement of serum albumin level, and multimodal brain imaging, including [11C] Pittsburgh compound B-PET, 18F-fluorodeoxyglucose-PET, and MRI. Serum albumin was categorized as follows: <4.4 g/dL (low albumin), 4.4 to 4.5 g/dL (middle albumin), and >4.5 g/dL (high albumin; used as a reference category). Aß positivity, AD-signature region cerebral glucose metabolism (AD-CM), AD-signature region cortical thickness (AD-CT), and WMH volume were used as outcome measures. RESULTS: Serum albumin level (as a continuous variable) was inversely associated with Aß deposition and Aß positivity. The low albumin group showed a significantly higher Aß positivity rate compared to the high albumin group (odds ratio 3.40, 95% confidence interval 1.67-6.92, p = 0.001), while the middle albumin group showed no difference (odds ratio 1.74, 95% confidence interval 0.80-3.77, p = 0.162). Neither serum albumin level (as a continuous variable) nor albumin categories were related to AD-CM, AD-CT, or WMH volume. CONCLUSIONS: Low serum albumin may increase the risk of AD dementia by elevating amyloid accumulation. In terms of AD prevention, more attention needs to be paid to avoid a low serum albumin level, even within the clinical normal range, by clinicians.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/sangue , Encéfalo/metabolismo , Albumina Sérica/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Amiloide/metabolismo , Amiloidose/patologia , Encéfalo/patologia , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos
4.
PLoS One ; 15(7): e0235143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609750

RESUMO

To clarify the significance of quantitative analyses of amyloid proteins in clinical practice and in research relating to systemic amyloidoses, we applied mass spectrometry-based quantification by isotope-labeled cell-free products (MS-QBIC) to formalin-fixed, paraffin-embedded (FFPE) tissues. The technique was applied to amyloid tissues collected by laser microdissection of Congo red-stained lesions of FFPE specimens. Twelve of 13 amyloid precursor proteins were successfully quantified, including serum amyloid A (SAA), transthyretin (TTR), immunoglobulin kappa light chain (IGK), immunoglobulin lambda light chain (IGL), beta-2-microglobulin (B2M), apolipoprotein (Apo) A1, Apo A4, Apo E, lysozyme, Apo A2, gelsolin, and fibrinogen alpha chain; leukocyte cell-derived chemotaxin-2 was not detected. The quantification of SAA, TTR, IGK, IGL, and B2M confirmed the responsible proteins, even when the immunohistochemical results were not decisive. Considerable amounts of Apo A1, Apo A4, and Apo E were deposited in parallel amounts with the responsible proteins. Quantification of amyloid protein by MS-QBIC is feasible and useful for the classification of and research on systemic amyloidoses.


Assuntos
Proteínas Amiloidogênicas/análise , Amiloidose/patologia , Espectrometria de Massas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade
5.
Clin Nucl Med ; 45(9): 705-706, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32604112

RESUMO

Amyloidosis is a disorder resulting from the deposition of fibrillary protein in the extracellular tissue and can be classified into primary, secondary, familial, and senile types. Isolated lymph node amyloidosis without any other organ involvement is very rarely seen in clinical parlance, and diagnosis remains very challenging owing to nonspecific imaging findings. We present a case of 50-year-old man with lymphadenopathy, which was later confirmed to be amyloidosis on biopsy and serum-free light chain assay with efficacious use of F-FDG PET/CT for response assessment to bortezomib, cyclophosphamide, and dexamethasone.


Assuntos
Amiloidose/diagnóstico por imagem , Amiloidose/tratamento farmacológico , Fluordesoxiglucose F18 , Linfonodos/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Amiloidose/patologia , Biópsia , Bortezomib/uso terapêutico , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
6.
Muscle Nerve ; 62(4): 445-454, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32478919

RESUMO

Muscle disorders are characterized by differential involvement of various muscle groups. Among these, weakness predominantly affecting finger flexors is an uncommon pattern, most frequently found in sporadic inclusion-body myositis. This finding is particularly significant when the full range of histopathological findings of inclusion-body myositis is not found on muscle biopsy. Prominent finger flexor weakness, however, is also observed in other myopathies. It occurs commonly in myotonic dystrophy types 1 and 2. In addition, individual reports and small case series have documented finger flexor weakness in sarcoid and amyloid myopathy, and in inherited myopathies caused by ACTA1, CRYAB, DMD, DYSF, FLNC, GAA, GNE, HNRNPDL, LAMA2, MYH7, and VCP mutations. Therefore, the finding of finger flexor weakness requires consideration of clinical, myopathological, genetic, electrodiagnostic, and sometimes muscle imaging findings to establish a diagnosis.


Assuntos
Dedos/fisiopatologia , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Doenças Musculares/fisiopatologia , Amiloidose/patologia , Amiloidose/fisiopatologia , Miopatias Distais/patologia , Miopatias Distais/fisiopatologia , Doença de Depósito de Glicogênio Tipo II/patologia , Doença de Depósito de Glicogênio Tipo II/fisiopatologia , Humanos , Músculo Esquelético/patologia , Doenças Musculares/patologia , Distrofias Musculares/patologia , Distrofias Musculares/fisiopatologia , Distrofia Muscular do Cíngulo dos Membros/patologia , Distrofia Muscular do Cíngulo dos Membros/fisiopatologia , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular de Duchenne/fisiopatologia , Miosite de Corpos de Inclusão/patologia , Miosite de Corpos de Inclusão/fisiopatologia , Distrofia Miotônica/patologia , Distrofia Miotônica/fisiopatologia , Sarcoidose/patologia , Sarcoidose/fisiopatologia
7.
Lancet ; 395(10242): 1988-1997, 2020 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-32593336

RESUMO

BACKGROUND: Alzheimer's disease and its complications are the leading cause of death in adults with Down syndrome. Studies have assessed Alzheimer's disease in individuals with Down syndrome, but the natural history of biomarker changes in Down syndrome has not been established. We characterised the order and timing of changes in biomarkers of Alzheimer's disease in a population of adults with Down syndrome. METHODS: We did a dual-centre cross-sectional study of adults with Down syndrome recruited through a population-based health plan in Barcelona (Spain) and through services for people with intellectual disabilities in Cambridge (UK). Cognitive impairment in participants with Down syndrome was classified with the Cambridge Cognitive Examination for Older Adults with Down Syndrome (CAMCOG-DS). Only participants with mild or moderate disability were included who had at least one of the following Alzheimer's disease measures: apolipoprotein E allele carrier status; plasma concentrations of amyloid ß peptides 1-42 and 1-40 and their ratio (Aß1-42/1-40), total tau protein, and neurofilament light chain (NFL); tau phosphorylated at threonine 181 (p-tau), and NFL in cerebrospinal fluid (CSF); and one or more of PET with 18F-fluorodeoxyglucose, PET with amyloid tracers, and MRI. Cognitively healthy euploid controls aged up to 75 years who had no biomarker abnormalities were recruited from the Sant Pau Initiative on Neurodegeneration. We used a first-order locally estimated scatterplot smoothing curve to determine the order and age at onset of the biomarker changes, and the lowest ages at the divergence with 95% CIs are also reported where appropriate. FINDINGS: Between Feb 1, 2013, and June 28, 2019 (Barcelona), and between June 1, 2009, and Dec 31, 2014 (Cambridge), we included 388 participants with Down syndrome (257 [66%] asymptomatic, 48 [12%] with prodromal Alzheimer's disease, and 83 [21%] with Alzheimer's disease dementia) and 242 euploid controls. CSF Aß1-42/1-40 and plasma NFL values changed in individuals with Down syndrome as early as the third decade of life, and amyloid PET uptake changed in the fourth decade. 18F-fluorodeoxyglucose PET and CSF p-tau changes occurred later in the fourth decade of life, followed by hippocampal atrophy and changes in cognition in the fifth decade of life. Prodromal Alzheimer's disease was diagnosed at a median age of 50·2 years (IQR 47·5-54·1), and Alzheimer's disease dementia at 53·7 years (49·5-57·2). Symptomatic Alzheimer's disease prevalence increased with age in individuals with Down syndrome, reaching 90-100% in the seventh decade of life. INTERPRETATION: Alzheimer's disease in individuals with Down syndrome has a long preclinical phase in which biomarkers follow a predictable order of changes over more than two decades. The similarities with sporadic and autosomal dominant Alzheimer's disease and the prevalence of Down syndrome make this population a suitable target for Alzheimer's disease preventive treatments. FUNDING: Instituto de Salud Carlos III, Fundació Bancaria La Caixa, Fundació La Marató de TV3, Medical Research Council, and National Institutes of Health.


Assuntos
Doença de Alzheimer/metabolismo , Biomarcadores/sangue , Síndrome de Down/complicações , Adulto , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/epidemiologia , Peptídeos beta-Amiloides/metabolismo , Amiloidose/diagnóstico por imagem , Amiloidose/patologia , Apolipoproteínas E/metabolismo , Estudos de Casos e Controles , Disfunção Cognitiva/psicologia , Estudos Transversais , Síndrome de Down/epidemiologia , Síndrome de Down/mortalidade , Síndrome de Down/psicologia , Fluordesoxiglucose F18/administração & dosagem , Humanos , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Tomografia por Emissão de Pósitrons/métodos , Prevalência , Espanha/epidemiologia , Reino Unido/epidemiologia , Proteínas tau/metabolismo
8.
Proc Natl Acad Sci U S A ; 117(22): 12050-12061, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32414928

RESUMO

Amyloidoses (misfolded polypeptide accumulation) are among the most debilitating diseases our aging societies face. Amyloidogenesis can be catalyzed by hydrophobic-hydrophilic interfaces (e.g., air-water interface in vitro [AWI]). We recently demonstrated hydrogelation of the amyloidogenic type II diabetes-associated islet amyloid polypeptide (IAPP), a hydrophobic-hydrophilic interface-dependent process with complex kinetics. We demonstrate that human IAPP undergoes AWI-catalyzed liquid-liquid phase separation (LLPS), which initiates hydrogelation and aggregation. Insulin modulates these processes but does not prevent them. Using nonamyloidogenic rat IAPP, we show that, whereas LLPS does not require the amyloidogenic sequence, hydrogelation and aggregation do. Interestingly, both insulin and rat sequence delayed IAPP LLPS, which may reflect physiology. By developing an experimental setup and analysis tools, we show that, within the whole system (beyond the droplet stage), macroscopic interconnected aggregate clusters form, grow, fuse, and evolve via internal rearrangement, leading to overall hydrogelation. As the AWI-adsorbed gelled layer matures, its microviscosity increases. LLPS-driven aggregation may be a common amyloid feature and integral to pathology.


Assuntos
Amiloidose/patologia , Diabetes Mellitus Tipo 2/patologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Amiloide/fisiologia , Proteínas Amiloidogênicas/metabolismo , Animais , Hidrogéis , Interações Hidrofóbicas e Hidrofílicas , Insulina/metabolismo , Agregados Proteicos/fisiologia , Ratos
9.
Braz J Med Biol Res ; 53(6): e8625, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428129

RESUMO

Amyloidosis comprises a group of disorders that accumulate modified autologous proteins in organs, mainly the kidneys. Few studies have addressed the amyloid compartmental distribution and associated clinical outcomes. The aim of this study was to present a case series of renal amyloidosis correlating histopathological data with glomerular filtration rate (GFR) during kidney biopsy. We studied 53 cases reviewed by nephropathologists from 2000 to 2018 in a single kidney biopsy center in Brazil. GFR was estimated using the CKD-EPI formula. Cases were divided into Group A ≥60 and Group B <60 mL·min-1·(1.73 m2)-1 using the estimated GFR during kidney biopsy. Semiquantitative histopathological study was performed, including extension and distribution of amyloid deposits by compartments (glomeruli, tubulointerstitial tissue, and vessels). Statistical analyses were made to understand associations with lower GFR. No difference was seen for age, gender, proteinuria, hematuria, subtype of amyloid protein, arteriosclerosis, interstitial fibrosis/infiltrate, or glomerular and interstitial amyloid deposits. After a previous P value <0.1 in the descriptive analysis, the following variables were selected: globally sclerotic glomeruli, high blood pressure, and the extension of vascular amyloid deposition. A binary logistic regression model with GFR as the dependent variable showed history of hypertension and vascular amyloid to be robust and independent predictors of Group B <60 mL·min-1·(1.73 m2)-1. Beyond the histopathologic diagnosis of amyloidosis, a semiquantitative approach on renal biopsy could provide new insights. Vascular amyloid is an independent predictor of renal dysfunction in cases of renal amyloidosis.


Assuntos
Amiloide/fisiologia , Amiloidose/patologia , Taxa de Filtração Glomerular , Nefropatias/patologia , Rim/patologia , Adulto , Idoso , Amiloidose/fisiopatologia , Biópsia , Feminino , Humanos , Rim/fisiopatologia , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
PLoS One ; 15(5): e0232785, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469871

RESUMO

BACKGROUND: Alzheimer's disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) Aß42 (A) and tau (T) ratio. METHODS: As part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression. RESULTS: Mean age (± standard deviation) in the CH-PAT group (n = 27; 75.2 ± 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 ± 7.9 years). Mean RNFL (standard error) was thinner in the CH-PAT group by 9.8 (2.7) µm; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity. CONCLUSIONS: Our retinal data predict which individuals have CSF biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity. Such results from easy-to-acquire, objective and non-invasive measurements of the RNFL merit further study of OCT technology to monitor or screen for early AD pathology.


Assuntos
Doença de Alzheimer/genética , Peptídeos beta-Amiloides/genética , Disfunção Cognitiva/genética , Proteínas tau/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Amiloidose/líquido cefalorraquidiano , Amiloidose/diagnóstico por imagem , Amiloidose/genética , Amiloidose/patologia , Biomarcadores/líquido cefalorraquidiano , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/metabolismo , Fibras Nervosas/patologia , Disco Óptico/diagnóstico por imagem , Disco Óptico/metabolismo , Disco Óptico/patologia , Retina/diagnóstico por imagem , Retina/metabolismo , Retina/patologia , Células Ganglionares da Retina/metabolismo , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Proteínas tau/líquido cefalorraquidiano
11.
World Neurosurg ; 140: 325-331, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32461181

RESUMO

BACKGROUND: Solitary spinal amyloidoma (SSA) is a rare and poorly characterized disease. There are few cases described, and the knowledge of this neoplasm is limited. A more accurate description of demographics, clinical findings, and outcomes may be useful for a better understanding of this pathology, as well as therapeutic intervention, adding value to the research of localized amyloidosis. METHODS: A systematic search was carried out from when registries began until February 2020. We also include a case diagnosed and treated in our department. Descriptive statistics were used to evaluate data, demographics, clinical findings, diagnostic modalities, therapeutics, and finally neurologic outcomes. The Kaplan-Meier method was used to assess overall survival and progression-free survival. RESULTS: The final cohort comprises 35 patients. The mean age at diagnosis was 61.97 years, and 68.60% of the patients were male. SSA developed more frequently in the thoracic spine (48.60%), followed by the cervical spine (17.10%). Intradural lesions were rare, and the average neoplastic score for spinal instability was 9.5 points. The most common symptoms were impaired motor function (74.29%) and axial back pain (65.70%). After surgery, neurologic recovery was reported in 82.90% of cases. Mean progression-free survival and mean overall survival were 47.26 and 156.66 months. CONCLUSIONS: SSA is a rare subgroup of localized amyloidosis, usually being diagnosed in male patients between the sixth and eighth decades. The gold standard treatment seems to be surgical resection. SSA patients have excellent long-term survival and a low rate of local recurrence.


Assuntos
Amiloidose/cirurgia , Coluna Vertebral/cirurgia , Amiloidose/patologia , Feminino , Humanos , Masculino , Doenças da Coluna Vertebral/patologia , Doenças da Coluna Vertebral/cirurgia , Coluna Vertebral/patologia , Resultado do Tratamento
12.
Cardiovasc Pathol ; 48: 107218, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32388447

RESUMO

Cardiac amyloid A (AA) amyloidosis is rare. We present the case of a 72-year-old woman with obstructive hypertrophic cardiomyopathy (HCM) and biopsy-proven renal AA amyloidosis whose dyspnea and exercise intolerance had worsened over the previous year. Her AA amyloidosis was suspected to be secondary to chronic diverticulitis for which she had undergone hemicolectomy and sigmoidectomy 3 years prior. Echocardiographic findings were consistent with worsening left ventricular outflow tract obstruction at rest. Cardiac magnetic resonance imaging revealed patchy areas of midwall late gadolinium enhancement. Right ventricular endomyocardial biopsy did not reveal amyloid deposition, and cardiac technetium-99m pyrophosphate scintigraphy did not suggest transthyretin amyloidosis. The patient underwent septal myectomy with resection of an accessory papillary muscle. Pathological examination of the myectomy specimen was consistent with HCM. In addition, there was a thick layer of diffuse endocardial and vascular amyloid deposition that was identified as AA type by laser-microdissection with liquid chromatography-coupled tandem-mass spectrometry. This case report highlights the presence of 2 distinct disease processes occurring simultaneously and the importance of tissue diagnosis of AA amyloidosis, a condition that is not commonly associated with HCM.


Assuntos
Amiloidose/complicações , Cardiomiopatia Hipertrófica/complicações , Insuficiência Cardíaca/etiologia , Nefropatias/complicações , Miocárdio/patologia , Obstrução do Fluxo Ventricular Externo/etiologia , Idoso , Amiloidose/metabolismo , Amiloidose/patologia , Amiloidose/fisiopatologia , Procedimentos Cirúrgicos Cardíacos , Cardiomiopatia Hipertrófica/metabolismo , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Feminino , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Nefropatias/metabolismo , Nefropatias/patologia , Miocárdio/metabolismo , Proteína Amiloide A Sérica/metabolismo , Resultado do Tratamento , Função Ventricular Esquerda , Obstrução do Fluxo Ventricular Externo/metabolismo , Obstrução do Fluxo Ventricular Externo/patologia , Obstrução do Fluxo Ventricular Externo/fisiopatologia
13.
Am J Kidney Dis ; 76(2): 295-297, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32362418
14.
Prostate ; 80(9): 687-697, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32271960

RESUMO

BACKGROUND: Corpora amylacea (CAM), in benign prostatic acini, contain acute-phase proteins. Do CAM coincide with carcinoma? METHODS: Within 270 biopsies, 83 prostatectomies, and 33 transurethral resections (TURs), CAM absence was designated CAM 0; corpora in less than 5% of benign acini: CAM 1; in 5% to 25%: CAM 2; in more than 25%: CAM 3. CAM were compared against carcinoma presence, clinicopathologic findings, and grade groups (GG) 1 to 2 vs 3 to 5. The frequency of CAM according to anatomic zone was counted. A pilot study was conducted using paired initial benign and repeat biopsies (33 benign, 24 carcinoma). RESULTS: A total of 68.9% of biopsies, 96.4% of prostatectomies, and 66.7% of TURs disclosed CAM. CAM ≥1 was common at an older age (P = .019). In biopsies, 204 cases (75%) had carcinoma; and CAM of 2 to 3 (compared to 0-1) were recorded in 25.0% of carcinomas but only 7.4% of benign biopsies (P = .005; odds ratio [OR] = 5.1). CAM correlated with high percent Gleason pattern 3, low GG (P = .035), and chronic inflammation (CI). CI correlated inversely with carcinoma (P = .003). CAM disclosed no association with race, body mass index, serum prostate specific antigen (PSA), acute inflammation (in biopsies), atrophy, or carcinoma volume. With CAM 1, the odds of GG 3 to 5 carcinoma, by comparison to CAM 0, decreased more than 2× (OR = 0.48; P = .032), with CAM 2, more than 3× (OR = 0.33; P = .005), and with CAM 3, almost 3× (OR = 0.39, P = .086). For men aged less than 65, carcinoma predictive model was: Score = (2 × age) + (5 × PSA) - (20 × degree of CAM); using our data, area under the ROC curve was 78.17%. When the transition zone was involved by cancer, it showed more CAM than in cases where it was uninvolved (P = .012); otherwise zonal distributions were similar. In the pilot study, CAM ≥1 predicted carcinoma on repeat biopsy (P < .05; OR = 8), as did CAM 2 to 3 (P < .0001; OR = 30). CI was not significant, and CAM retained significance after adjusting for CI. CONCLUSION: CAM correlate with carcinoma. Whether abundant CAM in benign biopsies adds value amidst high clinical suspicion, warrants further study.


Assuntos
Próstata/citologia , Neoplasias da Próstata/patologia , Proteínas da Fase Aguda/metabolismo , Idoso , Amiloide/metabolismo , Amiloidose/metabolismo , Amiloidose/patologia , Biópsia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/metabolismo , Próstata/patologia , Próstata/cirurgia , Prostatectomia , Neoplasia Prostática Intraepitelial/metabolismo , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/cirurgia
15.
J Neuropathol Exp Neurol ; 79(4): 355-364, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32167544

RESUMO

Peripheral neuropathy is a common disorder with many possible etiologies including metabolic diseases, inflammatory conditions, infections, malignancy, inherited diseases, drugs, and toxins. In most instances, diagnosis and treatment plan can be established based on clinical presentation, family history, laboratory results, genetic testing, and electrophysiological studies. But in some situations, a peripheral nerve biopsy remains a valuable tool. This is especially true in patients with rapidly progressive disease, with atypical presentation or for whom other approaches fail to yield a definitive diagnosis. The pathologic examination starts with basic decisions about specimen triage. A few basic questions help to provide an initial framework for the assessment of a nerve biopsy-is the specimen adequate; are there inflammatory changes; are there vascular changes; is there amyloid; are there changes to axonal density and the Schwann cell-myelin-axon unit. In the appropriate context and with such an approach peripheral nerve biopsies can still represent a clinically helpful test.


Assuntos
Biópsia/métodos , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/patologia , Amiloidose/diagnóstico , Amiloidose/patologia , Axônios/ultraestrutura , Humanos , Neuropatologia , Células de Schwann/patologia , Vasculite/diagnóstico , Vasculite/patologia
16.
Cardiovasc Pathol ; 47: 107210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32142924

RESUMO

Nonbacterial thrombotic endocarditis is a form of a thrombotic angiopathy involving the endothelial lined endocardial surfaces of the heart which includes valves and the chamber walls. Underlying etiologies for nonbacterial thrombotic endocarditis include autoimmune diseases, hypercoagulable states, in the setting of certain malignant neoplasms, and physical injury. The pathogenesis for these processes is that of primary endothelial injury resulting in a thrombotic angiopathy. We present a patient with heart failure being evaluated before hematopoietic stem cell transplantation who had previously been provided with chemotherapy and whose cardiac magnetic resonance imaging reveals findings suggestive of amyloidosis. A subsequent endomyocardial biopsy instead showed nonbacterial thrombotic endocarditis characterized by the endocardium with fibromyxoid thickening and overlying fresh fibrin. This case highlights histopathologic findings of chemotherapy-associated nonbacterial thrombotic endocarditis involving the right ventricle wall of the endocardium, therefore expanding the radiological differential in patients with cardiac magnetic resonance imaging findings suggestive of amyloidosis.


Assuntos
Amiloidose/patologia , Antineoplásicos/efeitos adversos , Endocardite não Infecciosa/induzido quimicamente , Cardiopatias/patologia , Valvas Cardíacas/efeitos dos fármacos , Trombose/induzido quimicamente , Amiloidose/diagnóstico por imagem , Biópsia , Cardiotoxicidade , Diagnóstico Diferencial , Endocardite não Infecciosa/diagnóstico por imagem , Endocardite não Infecciosa/patologia , Cardiopatias/diagnóstico por imagem , Valvas Cardíacas/diagnóstico por imagem , Valvas Cardíacas/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Trombose/diagnóstico por imagem , Trombose/patologia
17.
J Clin Ultrasound ; 48(3): 168-173, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32003472

RESUMO

We describe the case of a 41-year-old woman with primary Sjögren's syndrome (SS) who presented multiple recurrences of breast amyloidosis. Each recurrence of breast amyloidosis showed different sonographic features, potentially mimicking malignancy. We briefly discuss the possible cause of this variability in imaging features based on the radiologic-histologic correlation.


Assuntos
Amiloidose/complicações , Amiloidose/diagnóstico por imagem , Doenças Mamárias/complicações , Doenças Mamárias/diagnóstico por imagem , Síndrome de Sjogren/complicações , Adulto , Amiloidose/patologia , Amiloidose/cirurgia , Doenças Mamárias/patologia , Doenças Mamárias/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva , Ultrassonografia/métodos
18.
Virchows Arch ; 477(1): 157-163, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31932919

RESUMO

An 84-year-old woman with a history of haemodialysis for renal failure from approximately 1 year before death. Autopsy revealed numerous spheroid-type amyloid deposits in the kidney that were observed mainly in the interstitium but not the glomeruli and vessels. In addition, intracytoplasmic small globular amyloid deposits in the proximal tubules in addition to amyloid casts were identified. Immunohistochemistry and proteomic analyses indicated these deposits were composed of λ light chains. Amyloid deposition was also found in the lung and heart. λ-type monoclonal protein was detected in her serum and increased numbers of CD138-positive cells with λ-restriction was observed in the bone marrow. The case was diagnosed as amyloid tubulopathy (AT) associated with systemic ALλ amyloidosis related to plasma cell neoplasm. This case indicates that AT is associated with ALλ amyloidosis, which developed systemically with characteristic amyloid deposition forms. These pathological features may be associated with her rapid progressive renal failure.


Assuntos
Amiloide/metabolismo , Amiloidose/patologia , Autopsia , Idoso de 80 Anos ou mais , Amiloidose/diagnóstico , Autopsia/métodos , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/metabolismo , Cadeias lambda de Imunoglobulina/metabolismo , Proteínas do Mieloma/metabolismo , Proteômica
19.
PLoS One ; 15(1): e0227227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978114

RESUMO

Many conflicting reports about the involvement of serum amyloid P component (SAP) in amyloid diseases have been presented over the years; SAP is known to be a universal component of amyloid aggregates but it has been suggested that it can both induce and suppress amyloid formation. By using our Drosophila model of systemic lysozyme amyloidosis, SAP has previously been shown to reduce the toxicity induced by the expression of the disease-associated lysozyme variant, F57I, in the Drosophila central nervous system. This study further investigates the involvement of SAP in modulating lysozyme toxicity using histochemistry and spectral analyses on the double transgenic WT and F57I lysozyme flies to probe; i) formation of aggregates, ii) morphological differences of the aggregated lysozyme species formed in the presence or absence of SAP, iii) location of lysozyme and iv) co-localisation of lysozyme and SAP in the fly brain. We found that SAP can counteract the toxicity (measured by the reduction in the median survival time) induced by F57I lysozyme by converting toxic F57I species into less toxic amyloid-like structures, as reflected by the spectral changes that p-FTAA undergoes when bound to lysozyme deposits in F57I-F57I-SAP flies as compared to F57I-F57I flies. Indeed, when SAP was introduced to in vitro lysozyme fibril formation, the endpoint fibrils had enhanced ThT fluorescence intensity as compared to lysozyme fibrils alone. This suggests that a general mechanism for SAP's role in amyloid diseases may be to promote the formation of stable, amyloid-like fibrils, thus decreasing the impact of toxic species formed along the aggregation pathway.


Assuntos
Amiloidose/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Muramidase/metabolismo , Componente Amiloide P Sérico/metabolismo , Amiloide/genética , Amiloide/metabolismo , Amiloide/ultraestrutura , Amiloidose/genética , Amiloidose/patologia , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Humanos , Muramidase/genética , Agregados Proteicos , Agregação Patológica de Proteínas/genética , Agregação Patológica de Proteínas/metabolismo , Agregação Patológica de Proteínas/patologia
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