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4.
Cancer ; 125(2): 185-193, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30480777

RESUMO

High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are established components in the treatment of multiple myeloma; however, undergoing transplantation usually requires hematopoietic support, which poses a challenge among patients who are unwilling to receive blood products. Most transplant centers decline HDT/ASCT to these patients because of safety concerns. Here, the authors' institutional data on safety, engraftment parameters, and survival outcomes after bloodless ASCT (BL-ASCT) are examined among patients with myeloma. This retrospective case-control study included patients who underwent BL-ASCT and Transfusion-supported ASCT (TS-ASCT) at Emory University Hospital between August 2006 and August 2016. In total, 24 patients who underwent BL-ASCT and 70 who underwent TS-ASCT were included. The median time for neutrophil engraftment, platelet engraftment and the median length of hospital stay all were equivalent for both groups. There were no transplant-related cardiovascular complications or mortality in either the BL-ASCT group or the TS-ASCT group. The median progression-free survival was 36 months and 44 months in the BL-ASCT and TS-ASCT groups, respectively (P = .277), and the median OS was not reached in either group at a median follow-up of 59 months after ASCT (P = .627). There was no transplant-related mortality at the 100-day or 1-year mark in either group. BL-ASCT is safe and feasible; transplant-related mortality, cardiovascular and hematologic complications are similar to those associated with TS-ASCT. Furthermore, BL-ASCT can yield similar engraftment and survival parameters comparable to those observed with TS-ASCT.


Assuntos
Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Transplante de Células-Tronco/métodos , Adulto , Idoso , Amiloidose/mortalidade , Amiloidose/terapia , Transfusão de Sangue , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Análise de Sobrevida , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos , Transplante Autólogo/mortalidade , Resultado do Tratamento
6.
Intern Med ; 58(4): 557-561, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30333399

RESUMO

We herein report a case involving a 64-year-old Japanese woman with a pulmonary Mycobacterium abscessus infection complicated by reactive AA amyloidosis, which, to our knowledge, has not been reported to date. The patient underwent gastrointestinal endoscopy for diarrhea during the treatment of pulmonary M. abscessus infection and was diagnosed with AA amyloidosis according to the histopathological findings from the endoscopic specimen. She died four months later. The prognosis of AA amyloidosis associated with pulmonary M. abscessus infection may be very poor, and physicians should pay attention to this rare condition when difficult-to-treat diarrhea occurs in patients with pulmonary M. abscessus infection.


Assuntos
Amiloidose/etiologia , Amiloidose/mortalidade , Infecções por Micobactéria não Tuberculosa/complicações , Infecções por Micobactéria não Tuberculosa/mortalidade , Infecções Respiratórias/complicações , Infecções Respiratórias/mortalidade , Amiloidose/complicações , Amiloidose/terapia , Grupo com Ancestrais do Continente Asiático , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Micobactéria não Tuberculosa/terapia , Infecções Respiratórias/terapia
7.
Kidney Int ; 95(2): 405-411, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30580886

RESUMO

Therapies for AL amyloidosis have dramatically improved, leading to longer patient survival; however, more AL amyloidosis patients are reaching end-stage renal disease (ESRD). There are no clear guidelines regarding eligibility for kidney transplantation in patients with AL amyloidosis, and data on outcomes are limited. We evaluated the clinical and laboratory data of 49 patients who were followed in the Amyloidosis Center at Boston University and underwent kidney transplantation at a center in the United States between 1987-2017. During a median follow-up of 7.2 years (range 0-19), the median patient survival from diagnosis was 15.4 years, and from kidney transplantation was 10.5 years. One, three, and five-year graft survival were 94%, 89%, and 81%, respectively. Patients with hematologic complete response or very good partial response prior to kidney transplantation had significantly better patient survival than patients with partial response or no response, and the median time to graft loss was 10.4 years versus 5.5 years, respectively. This is the largest published series of kidney transplantation in patients with AL amyloidosis, suggesting that kidney transplantation can have a good outcome in carefully selected patients, particularly in those who have achieved a complete response or very good partial response at the time of kidney transplantation.


Assuntos
Amiloidose/complicações , Falência Renal Crônica/cirurgia , Transplante de Rim/estatística & dados numéricos , Seleção de Pacientes , Adulto , Idoso , Amiloidose/mortalidade , Amiloidose/cirurgia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Transplante de Rim/normas , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Recidiva , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
8.
Amyloid ; 25(3): 167-173, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30193539

RESUMO

INTRODUCTION: Cardiopulmonary exercise testing (CPET) has repeatedly been reported to reliably predict adverse outcomes in different forms of heart failure. However, it has not been elucidated in detail in cardiac amyloidosis (CA). Therefore, we evaluated the predictive value of CPET parameters in patients with CA regarding disease severity and prediction of mortality. METHODS: Twenty-seven consecutive patients with CA were assessed noninvasively, including electrocardiography, echocardiography, CPET, and laboratory tests. Clinical data were correlated with CPET findings. Univariate and multivariate analyses were performed to evaluate predictors of mortality. RESULTS: Within median follow-up period of 38 (IQR 43) months 19 (70%) deaths occurred. Patient initially presented with signs and symptoms of congestive heart failure NYHA 3 (IQR 1), reduced exercise capacity (peak V'O2 15.2 mL/kg body weight) and inefficient ventilation in CPET (V'E/V'CO2 slope (30 (IQR 3)), markedly elevated cardiac biomarkers (NT-proBNP 1791 (IQR 3249) ng/mL) and echocardiographic signs of morphological (septum thickness 18 (IQR 6) mm) and functional cardiac involvement (TAPSE 19 (IQR 8) mm). Patients with peak V'O2 below median value presented with significantly longer QTc interval when compared to patients with peak V'O2 above the median. Further these patients tend to have more pronounced impairment of longitudinal function as indicated by lower MAPSE, TAPSE, and elevation of cardiac biomarkers. Multivariate analysis revealed peak V'O2 slope as the only independent predictor of survival. CONCLUSIONS: We identified reduced peak V'O2 as an independent predictor of mortality in patients with cardiac involvement in different forms of systemic amyloidosis.


Assuntos
Amiloidose/mortalidade , Amiloidose/fisiopatologia , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Consumo de Oxigênio/fisiologia , Ecocardiografia , Humanos
9.
JAMA Cardiol ; 3(9): 865-870, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30046835

RESUMO

Importance: Cardiac amyloidosis is an underdiagnosed disease and is highly fatal when untreated. Early diagnosis and treatment with the emerging novel therapies significantly improve survival. A comprehensive analysis of amyloidosis-related mortality is critical to appreciate the nature and distribution of underdiagnosis and improve disease detection. Objective: To evaluate the temporal and regional trends in age-adjusted amyloidosis-related mortality among men and women of various races/ethnicities in the United States. Design, Setting, and Participants: In this observational cohort study, death certificate information from the Centers for Disease Control and Prevention's Wide-ranging ONline Data for Epidemiologic Research database and the National Vital Statistics System from 1979 to 2015 was analyzed. A total of 30 764 individuals in the United States with amyloidosis listed as the underlying cause of death and 26 591 individuals with amyloidosis listed as a contributing cause of death were analyzed. Exposures: Region of residence. Main Outcomes and Measures: Age-adjusted mortality rate from amyloidosis per 1 000 000 population stratified by year, sex, race/ethnicity, and state and county of residence. Results: Of the 30 764 individuals with amyloidosis listed as the underlying cause of death, 17 421 (56.6%) were men and 27 312 (88.8%) were 55 years or older. From 1979 to 2015, the reported overall mean age-adjusted mortality rate from amyloidosis as the underlying cause of death doubled from 1.77 to 3.96 per 1 000 000 population (2.32 to 5.43 in men and 1.35 to 2.80 in women). Black men had the highest mortality rate (12.36 per 1 000 000), followed by black women (6.48 per 1 000 000). Amyloidosis contributed to age-adjusted mortality rates as high as 31.73 per 1 000 000 in certain counties. Most southern states reported the lowest US mortality rates despite having the highest proportions of black individuals. Conclusions and Relevance: The increased reported mortality over time and in proximity to amyloidosis centers more likely reflects an overall increase in disease diagnosis rather than increased lethality. The reported amyloidosis mortality is highly variable in different US regions. The lack of higher reported mortality rates in states with a greater proportion of black residents suggests underdiagnosis of amyloidosis, including cardiac forms of the disease, in many areas of the United States. Better understanding of the determinants of geographic and racial disparity in the reporting of amyloidosis deaths are warranted.


Assuntos
Amiloidose/etnologia , Amiloidose/mortalidade , Cardiopatias/mortalidade , Adulto , Afro-Americanos/estatística & dados numéricos , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Estudos de Coortes , Atestado de Óbito , Feminino , Disparidades nos Níveis de Saúde , Cardiopatias/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos , Adulto Jovem
10.
J Am Coll Cardiol ; 71(25): 2919-2931, 2018 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-29929616

RESUMO

BACKGROUND: Prognosis in light-chain (AL) and transthyretin (ATTR) amyloidosis is influenced by cardiac involvement. ATTR amyloidosis has better prognosis than AL amyloidosis despite more amyloid infiltration, suggesting additional mechanisms of damage in AL amyloidosis. OBJECTIVES: The aim of the study was to assess the presence and prognostic significance of myocardial edema in patients with amyloidosis. METHODS: The study recruited 286 patients: 100 with systemic AL amyloidosis, 163 with cardiac ATTR amyloidosis, 12 with suspected cardiac ATTR amyloidosis (grade 1 on 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid), 11 asymptomatic individuals with amyloidogenic TTR gene mutations, and 30 healthy volunteers. All subjects underwent cardiovascular magnetic resonance with T1 and T2 mapping and 16 underwent endomyocardial biopsy. RESULTS: Myocardial T2 was increased in amyloidosis with the degree of elevation being highest in untreated AL patients (untreated AL amyloidosis 56.6 ± 5.1 ms; treated AL amyloidosis 53.6 ± 3.9 ms; ATTR amyloidosis 54.2 ± 4.1 ms; each p < 0.01 compared with control subjects: 48.9 ± 2.0 ms). Left ventricular (LV) mass and extracellular volume fraction were higher in ATTR amyloidosis compared with AL amyloidosis while LV ejection fraction was lower (p < 0.001). Histological evidence of edema was present in 87.5% of biopsy samples ranging from 5% to 40% myocardial involvement. Using Cox regression models, myocardial T2 predicted death in AL amyloidosis (hazard ratio: 1.48; 95% confidence interval: 1.20 to 1.82) and remained significant after adjusting for extracellular volume fraction and N-terminal pro-B-type natriuretic peptide (hazard ratio: 1.32; 95% confidence interval: 1.05 to 1.67). CONCLUSIONS: Myocardial edema is present in cardiac amyloidosis by histology and cardiovascular magnetic resonance T2 mapping. T2 is higher in untreated AL amyloidosis compared with treated AL and ATTR amyloidosis, and is a predictor of prognosis in AL amyloidosis. This suggests mechanisms additional to amyloid infiltration contributing to mortality in amyloidosis.


Assuntos
Amiloidose/diagnóstico por imagem , Cardiomiopatias/diagnóstico por imagem , Edema/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/genética , Amiloidose/mortalidade , Amiloidose/patologia , Cardiomiopatias/genética , Cardiomiopatias/mortalidade , Cardiomiopatias/patologia , Edema/mortalidade , Edema/patologia , Feminino , Humanos , Londres/epidemiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Pré-Albumina/genética
11.
Arch Cardiovasc Dis ; 111(10): 582-590, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29709420

RESUMO

BACKGROUND: The outcome of cardiac amyloidosis (CA) has been reported mainly in stable populations; limited data are available in patients referred for acute heart failure (AHF) to an intensive cardiac care unit (ICCU). AIMS: To address the characteristics and outcomes of patients with confirmed CA admitted to an ICCU for AHF and then to identify the predictors of evolution to cardiogenic shock. METHODS: All patients with CA referred to an ICCU for AHF between 2009 and 2015 were included. The clinical endpoint was 3-month death. Data from the population with cardiogenic shock, obtained in a stable haemodynamic state, were matched with data from a control group to determine predictors of evolution to cardiogenic shock. RESULTS: Among the 421 patients followed for CA in our expert centre, 46 patients (mean age: 64±14 years; 65% light-chain [AL] CA) were referred to the ICCU for AHF (n=26 with cardiogenic shock). At 3 months, death occurred in 24 (52%) patients, mostly in the cardiogenic shock group (n=21/26, 81%). Most deaths occurred 5 days [interquartile range 3-9 days] after catecholamine infusion and 50% occurred in patients aged<65 years. The majority of deaths were reported in patients with AL CA (n=19/24, 79%). Independent variables associated with in-hospital mortality were cardiogenic shock and uraemia level. N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) concentration obtained in a stable haemodynamic state was the only predictor of short-term evolution to cardiogenic shock (odds ratio: 8.7, 95% confidence interval: 2.2-34.6), with an optimal cut-off of 4040pg/mL (sensitivity=92%; specificity=81%). CONCLUSIONS: The study confirms the dramatic mortality associated with CA when presenting as cardiogenic shock and underlines the limited efficiency of conventional treatments. Given the rapid occurrence of death in a young population, an alternative strategy to dobutamine support should be investigated in patients with elevated NT-proBNP concentration.


Assuntos
Amiloidose/complicações , Cardiomiopatias/complicações , Insuficiência Cardíaca/etiologia , Unidades de Terapia Intensiva , Admissão do Paciente , Choque Cardiogênico/etiologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Amiloidose/diagnóstico , Amiloidose/mortalidade , Amiloidose/terapia , Biomarcadores/sangue , Cardiomiopatias/diagnóstico , Cardiomiopatias/mortalidade , Cardiomiopatias/terapia , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Hemodinâmica , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Peptídeo Natriurético Encefálico/sangue , Razão de Chances , Fragmentos de Peptídeos/sangue , Sistema de Registros , Fatores de Risco , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/mortalidade , Choque Cardiogênico/terapia , Fatores de Tempo , Resultado do Tratamento
12.
J Thorac Cardiovasc Surg ; 156(1): 98-103, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29397971

RESUMO

BACKGROUND: Outcome data on aortic valve replacement in patients with amyloidosis are limited. To address this issue, we reviewed our experience of patients with amyloidosis who underwent aortic valve replacement. METHODS: We retrospectively reviewed the records of 16 patients with amyloidosis who underwent aortic valve replacement between May 2000 and February 2017. RESULTS: The cohort comprised 11 males (69%) and 5 females (31%). The median patient age was 76 years (interquartile range [IQR], 71-82 years), and Society of Thoracic Surgeons predicted rate of mortality was 5.0% (IQR, 2.4%-8.7%). Amyloidosis type was immunoglobulin light chain in 6 patients (38%), age-related in 6 (38%), and localized in 4 (25%). The operation was surgical aortic valve replacement in 11 patients (69%) and balloon-expandable transfemoral transcatheter aortic valve insertion in the other 5. There was no procedure-related stroke, need for new-onset dialysis or pacemaker, or death within 30 days of surgery. The median length of hospital stay was 1 day (IQR, 1-2 days) in the transcatheter valve insertion group and 6 days (IQR, 6-8 days) in the surgical group (P = .002). Follow-up was available for all patients at a median of 1.9 years (IQR, 1.2-4.8 years). During the follow-up period, there were 4 deaths, all occurring >1 year after surgery. CONCLUSIONS: Aortic valve replacement can be performed with low risk of operative morbidity and mortality in patients with amyloidosis. Transcatheter valve insertion has the advantage of reduced hospital length of stay. The 1-year survival is excellent.


Assuntos
Amiloidose/complicações , Valva Aórtica/cirurgia , Implante de Prótese Vascular , Cardiomiopatias/complicações , Doenças das Valvas Cardíacas/cirurgia , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Amiloidose/mortalidade , Amiloidose/patologia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Cardiomiopatias/mortalidade , Cardiomiopatias/patologia , Feminino , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/mortalidade , Hemodinâmica , Humanos , Tempo de Internação , Masculino , Miocárdio/patologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Resultado do Tratamento
13.
Amyloid ; 25(2): 79-85, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29482381

RESUMO

OBJECTIVES: Prognosis of immunoglobulin light-chain (AL) amyloidosis depends mainly on the presence of cardiac involvement and the disease burden. A higher bone marrow plasma cell (BMPC) burden has been recognized as an adverse prognostic factor. The aim of our study was to analyze the correlation between the BMPC infiltration, clinical features and outcomes in patients with AL amyloidosis. METHODS: The clinical records of 79 patients with AL amyloidosis treated at a single institution. RESULTS: Median BMPC infiltration at diagnosis was 11% and significantly correlated with the serum free light-chain difference (p < .001). Patients with more than 10% BMPCs had more frequent cardiac involvement (86 vs. 63%; p = .015), a trend towards a higher early mortality (27 vs. 11%; p = .08) and a significantly shorter progression-free survival (PFS) (median of 18 vs. 48 months, p = .02) and overall survival (median of 33 months vs. not reached; p = .046). In the multivariate analysis, a BMPC infiltration over 10% retained its adverse prognostic value for PFS (HR = 2.26; 95% CI, 1.048-4.866; p = .038). The use of new drugs seemed to overcome the negative prognostic impact of a higher BMPC infiltration. CONCLUSION: Higher BMPC infiltration in AL amyloidosis might be associated with increased systemic organ damage, particularly cardiac involvement and is rarely related to the development of myeloma features.


Assuntos
Amiloidose/patologia , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Plasmócitos/patologia , Idoso , Amiloidose/diagnóstico , Amiloidose/mortalidade , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Nephrol Dial Transplant ; 33(2): 241-247, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29401357

RESUMO

Introduction: Renal biopsy series from North America suggest that leucocyte chemotactic factor 2 (ALECT2) amyloid is the third most common type of renal amyloid. We report the first case series from a European Centre of prevalence, clinical presentation and diagnostic findings in ALECT2 amyloidosis and report long-term patient and renal outcomes for the first time. Methods: We studied the clinical features, diagnostic investigations and the outcome of all patients with ALECT2 amyloidosis followed systematically at the UK National Amyloidosis Centre (NAC) between 1994 and 2015. Results: Twenty-four patients, all non-Caucasian, were diagnosed with ALECT2 amyloidosis representing 1.3% of all patients referred to the NAC with biopsy-proved renal amyloid. Diagnosis was made at median age of 62 years, usually from renal histology; immunohistochemical staining was definitive for ALECT2 fibril type. Median estimated glomerular filtration rate (GFR) at diagnosis was 33 mL/min/1.73 m2 and median proteinuria was 0.5 g/24 h. Hepatic amyloid was evident on serum amyloid P component (SAP) scintigraphy in 11/24 cases but was not associated with significant derangement of liver function. No patient had evidence of cardiac amyloidosis or amyloid neuropathy. Median follow-up was 4.8 (range 0.5-15.2) years, during which four patients died and four progressed to end-stage renal disease. The mean rate of GFR loss was 4.2 (range 0.5-9.6) mL/min/year and median estimated renal survival from diagnosis was 8.2 years. Serial SAP scans revealed little or no change in total body amyloid burden. Conclusions: ALECT2 amyloidosis is a relatively benign type of renal amyloid, associated with a slow GFR decline, which is reliably diagnosed on renal histology. Neither the molecular basis nor the factors underlying the apparent restriction of ALECT2 amyloidosis to non-Caucasian populations have been determined.


Assuntos
Amiloidose/diagnóstico , Amiloidose/mortalidade , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Falência Renal Crônica/patologia , Nefrectomia/mortalidade , Proteinúria/patologia , Adulto , Idoso , Amiloidose/metabolismo , Amiloidose/cirurgia , Feminino , Humanos , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteinúria/etiologia , Proteinúria/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida
15.
J Clin Pathol ; 71(5): 425-435, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28970295

RESUMO

BACKGROUND: Primary immunodeficiency disorders (PID) include a wide spectrum of inherited disorders characterised by functional abnormalities of one or more components of the immune system. Recent updates from the genomic data have contributed significantly to its better understanding with identification of new entities. Diagnosis is always challenging due to their variable clinical presentation. With the evolution of molecular diagnosis, many of these children are being diagnosed early and offered appropriate therapy. However, in developing countries, early diagnosis is still not being made: as a result these patients succumb to their disease. Autopsy data on PID is notably lacking in the literature with histopathological evaluation of PID being limited to rare case reports. OBJECTIVE: To analyse the clinical, immunologic (including mutational) and morphologic features at autopsy in 10 proven and suspected cases of primary immunodeficiency disorders diagnosed at our Institute over the past decade. METHODS: Study includes a detailed clinico-pathological analysis of 10 proven and suspected cases of primary immunodeficiency disorders. RESULTS: A varied spectrum of infectious and non-infectious complications were identified in these cases of which fungal infections were found to be more frequent compared with viral or bacterial infections. Rare and novel morphological findings, like granulomatous involvement of the heart in a patient with chronic granulomatous disease, systemic amyloidosis in a teenage girl with X-linked agammaglobulinemia, are highlighted which is distinctly lacking in the literature. CONCLUSIONS: The present study is perhaps the first autopsy series on PID. Even in the molecular era, such analysis is still important, as correlation of pathological features with clinical symptoms provides clues for a timely diagnosis and appropriate therapeutic intervention.


Assuntos
Amiloidose/patologia , Doença Granulomatosa Crônica/patologia , Hospedeiro Imunocomprometido , Síndromes de Imunodeficiência/patologia , Infecções Oportunistas/patologia , Amiloidose/genética , Amiloidose/imunologia , Amiloidose/mortalidade , Autopsia , Biópsia , Causas de Morte , Criança , Pré-Escolar , Análise Mutacional de DNA , Países em Desenvolvimento , Diagnóstico Precoce , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/mortalidade , Humanos , Imuno-Histoquímica , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/mortalidade , Índia , Lactente , Recém-Nascido , Masculino , Mutação , Infecções Oportunistas/genética , Infecções Oportunistas/imunologia , Infecções Oportunistas/mortalidade , Fenótipo , Valor Preditivo dos Testes , Prognóstico
16.
J Heart Lung Transplant ; 37(5): 611-618, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29217108

RESUMO

BACKGROUND: Cardiac amyloidosis, caused most commonly by deposition of light chain (AL) or transthyretin (ATTR) type fibrils, has an extremely poor prognosis. In this retrospective single-center study, we evaluated temporal trends in survival after heart transplantation for cardiac amyloidosis. METHODS: We analyzed 48 patients with cardiac amyloidosis (AL, n = 32; familial ATTR, n = 16) who underwent heart transplantation from May 2002 to March 2017. Patients were analysed in 2 periods, Era 1 (2002- 2007) and Era 2 (2008- 2017), separated by altered patient selection in both, AL and ATTR amyloidosis, and changed chemotherapy regimens for AL amyloidosis. RESULTS: The modern era was characterized by a lower number of extracardiac organ involvement for AL (94% isolated cardiac amyloidosis in Era 2 vs 56% in Era 1; p = 0.0221), and more frequent treatment for AL with the proteasome inhibitor bortezomib (94% in Era 2 vs 6% in Era 1; p < 0.0001). AL patients had significantly lower survival than patients with non-amyloid cardiomyopathy after heart transplantation in Era 1, and ATTR patients had numerically lower survival. However, survival in the modern era was comparable to non-amyloid transplants in both cohorts, possibly reflecting a shift in chemotherapy strategies and patient selection, respectively. CONCLUSIONS: In the current era, use of enhanced chemotherapy regimens for isolated advanced AL cardiac amyloidosis was associated with outcomes comparable to non-amyloid cardiomyopathy. We conclude that heart transplantation in highly selected patients with isolated non-systemic advanced cardiac amyloidosis may be a feasible approach.


Assuntos
Amiloidose/mortalidade , Amiloidose/cirurgia , Cardiopatias/mortalidade , Cardiopatias/cirurgia , Transplante de Coração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
17.
Heart Vessels ; 33(2): 170-179, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28840397

RESUMO

Few studies have focused on right ventricular (RV) involvement in cardiac amyloidosis (CA). We investigated the prognostic value of RV assessment by cardiovascular magnetic resonance (CMR) in CA. In 2011-2014, consecutive patients with suspected CA referred for CMR were retrospectively evaluated. Demographic and baseline clinical characteristics were collected. Healthy volunteers were matched for sex and age and served as controls. All subjects underwent a contrast-enhanced CMR examination. RV size, function, and late gadolinium enhancement (LGE) were analyzed. All deaths during follow-up were recorded. Sixty-one patients [37 males (60.7%), age 60 ± 11 years] were included; CA was diagnosed in 47 (77.0%) patients. CA patients displayed decreased biventricular ejection fraction, elevated left ventricular mass index, and increased biventricular end-systolic volume index (ESVi) compared with controls. A total of 27 deaths (57.4%) occurred in the CA group at 21-month median follow-up. Multivariable analysis demonstrated that RVESVi (HR 1.033, 95% CI 1.004-1.063, P = 0.026) and RV-LGE (HR 2.814, 95% CI 1.063-7.450, P = 0.037) were independent predictors of mortality in CA. For all amyloid patients, log NT-proBNP (HR 3.412; 95% CI 1.484-7.845; P = 0.004) and RV-LGE (HR 4.149; 95% CI 1.623-10.607; P = 0.003) were identified as independent predictors. RVESVi and RV-LGE are independent predictors of survival and evaluation of RV by CMR enables risk stratification in patients with CA.


Assuntos
Amiloidose/diagnóstico , Ventrículos do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Volume Sistólico/fisiologia , Disfunção Ventricular Direita/diagnóstico , Função Ventricular Direita/fisiologia , Idoso , Amiloidose/complicações , Amiloidose/mortalidade , China/epidemiologia , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Disfunção Ventricular Direita/etiologia , Disfunção Ventricular Direita/fisiopatologia
18.
J Cardiovasc Magn Reson ; 19(1): 98, 2017 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-29212513

RESUMO

BACKGROUND: Non-invasive cardiac imaging allows detection of cardiac amyloidosis (CA) in patients with aortic stenosis (AS). Our objective was to estimate the prevalence of clinically suspected CA in patients with moderate and severe AS referred for cardiovascular magnetic resonance (CMR) in age and gender categories, and assess associations between AS-CA and all-cause mortality. METHODS: We retrospectively identified consecutive AS patients defined by echocardiography referred for further CMR assessment of valvular, myocardial, and aortic disease. CMR identified CA based on typical late-gadolinium enhancement (LGE) patterns, and ancillary clinical evaluation identified suspected CA. Survival analysis with the Log rank test and Cox regression compared associations between CA and mortality. RESULTS: There were 113 patients (median age 74 years, Q1-Q3: 62-82 years), 96 (85%) with severe AS. Suspected CA was present in 9 patients (8%) all > 80 years. Among those over the median age of 74 years, the prevalence of CA was 9/57 (16%), and excluding women, the prevalence was 8/25 (32%). Low-flow, low-gradient physiology was very common in CA (7/9 patients or 78%). Over a median follow-up of 18 months, 40 deaths (35%) occurred. Mortality in AS + CA patients was higher than AS alone (56% vs. 20% at 1-year, log rank 15.0, P < 0.0001). Adjusting for aortic valve replacement modeled as a time-dependent covariate, Society of Thoracic Surgery predicted risk of mortality, left ventricular ejection fraction, CA remained associated with all-cause mortality (HR = 2.92, 95% CI = 1.09-7.86, P = 0.03). CONCLUSIONS: Suspected CA appears prevalent among older male patients with AS, especially with low flow, low gradient AS, and associates with all-cause mortality. The importance of screening for CA in older AS patients and optimal treatment strategies in those with CA warrant further investigation, especially in the era of transcatheter aortic valve implantation.


Assuntos
Amiloidose/epidemiologia , Estenose da Valva Aórtica/epidemiologia , Cardiomiopatias/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Amiloidose/diagnóstico por imagem , Amiloidose/mortalidade , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/mortalidade , Estenose da Valva Aórtica/cirurgia , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/mortalidade , Distribuição de Qui-Quadrado , Comorbidade , Meios de Contraste/administração & dosagem , Ecocardiografia Doppler , Feminino , Gadolínio/administração & dosagem , Implante de Prótese de Valva Cardíaca , Compostos Heterocíclicos/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Compostos Organometálicos/administração & dosagem , Pennsylvania/epidemiologia , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fatores de Tempo
19.
Rev Bras Reumatol Engl Ed ; 57(6): 535-544, 2017.
Artigo em Inglês, Português | MEDLINE | ID: mdl-29173691

RESUMO

AIM: Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. METHODS: A total of 81 patients (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. RESULTS: Most of the patients (55.6%) had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good outcome group and malignancy (20%) in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively). Median duration of renal survival was 65±3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p=0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p=0.006) and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p=0.027) were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3±16 months. CONCLUSION: Our study indicated that familial Mediterranean fever constituted a large proportion of cases and increased number of patients with idiopathic amyloid A amyloidosis. Additionally, it was observed that patient survival was not affected by different etiological causes in amyloid A amyloidosis.


Assuntos
Amiloidose/mortalidade , Febre Familiar do Mediterrâneo/mortalidade , Insuficiência Renal Crônica/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/complicações , Amiloidose/fisiopatologia , Creatinina/sangue , Febre Familiar do Mediterrâneo/complicações , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteinúria/urina , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Estudos Retrospectivos , Adulto Jovem
20.
J Med Invest ; 64(3.4): 217-221, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28954985

RESUMO

Amyloidosis is often overlooked because its clinical manifestations can mimic those of more-common diseases. It is important to get a precise diagnosis as early as possible for the prevention of further organ damages. Amyloidosis is a disorder caused by deposition of insoluble abnormal amyloid. The kidney is a frequent site of amyloid deposition. The amyloid fibrils have a characteristic appearance and generate birefringence under polarized light when stained with the Congo red dye. Classification of amyloidosis is based on the precursor protein that forms the amyloid fibrils and the distribution of amyloid deposits as either systemic or localized. Involvement of amyloid fibrils in kidneys mainly occurs as amyloid light-chain (AL) or amyloid A (AA) amyloidosis. The potassium permanganate method with Congo red staining was once used widely to discriminate AL and AA amyloidoses, but this method has a problem of false positive results. We found that extracellular and cytoplasmic glomerular 4', 6-diamidino-2-phenylindole (DAPI)-positive areas were clearly consistent with amyloid deposition in AL amyloidosis. In contrast, the overlapping staining was not seen in AA amyloidosis. Therefore, we propose that DAPI staining readily distinguishes AL renal amyloidosis from AA renal amyloidosis as a simple and reproducible histochemical method. J. Med. Invest. 64: 217-221, August, 2017.


Assuntos
Amiloidose/diagnóstico , Indóis/análise , Nefropatias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Amiloidose/metabolismo , Amiloidose/mortalidade , Diagnóstico Diferencial , Feminino , Humanos , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Proteína Amiloide A Sérica/análise , Coloração e Rotulagem
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