Optimal practices for the management of hereditary transthyretin amyloidosis: real-world experience from Japan, Brazil, and Portugal.

Hereditary transthyretin (ATTRv) amyloidosis is a rare and autosomal dominant disorder associated with mutations in the transthyretin gene. Patients present with diverse symptoms related to sensory, motor, and autonomic neuropathy, as well as gastrointestinal, ocular, cardiac, renal and orthopedic symptoms, resulting from the deposition of transthyretin amyloid fibrils in multiple organs. The progressive nature of ATTRv amyloidosis necessitates pre- and post-onset monitoring of the disease. This review article is primarily based on a collation of discussions from a medical advisory board meeting in August 2021. In this article, we summarize the best practices in amyloidosis centers in three major endemic countries for ATTRv amyloidosis (Japan, Brazil, and Portugal), where most patients carry the Val30Met mutation in the transthyretin gene and the patients' genetic background was proven to be the same. The discussions highlighted the similarities and differences in the management of asymptomatic gene mutation carriers among the three countries in terms of the use of noninvasive tests and tissue biopsies and timing of starting the investigations. In addition, this article discusses a set of practical tests and examinations for monitoring disease progression applicable to neurologists working in diverse medical settings and generalizable in non-endemic countries and areas. This set of assessments consists of periodic (every 6 to 12 months) evaluations of patients' nutritional status and autonomic, renal, cardiac, ophthalmologic, and neurological functions. Physical examinations and patient-reported outcome assessments should be also scheduled every 6 to 12 months. Programs for monitoring gene mutation carriers and robust referral networks can aid in appropriate patient management in pre- to post-onset stages. For pre- and post-symptom onset testing for ATTRv amyloidosis, various noninvasive techniques are available; however, their applicability differs depending on the medical setting in each country and region, and the optimal option should be selected in view of the clinical settings, medical environment, and available healthcare resources in each region.

Migrant and ethnic minority nurses' experience of working in European health services: a qualitative study.

OBJECTIVE: To analyze the perception of culture and experience of working in European health services of a purposive sample of qualified migrant and ethnic minority nurses currently living in Belgium, Portugal, Spain and Turkey. METHOD: A qualitative phenomenological method was chosen. Individual interviews took place with 8 qualified migrant and ethnic minority nurses currently living in four European countries. Thematic analysis was conducted using Braun and Clark's stages after qualitative data had been verbatim transcribed, translated into English, and analyzed. RESULTS: Four themes and 4 subthemes emerged from thematic analysis of the transcripts. CONCLUSION: Migrant and ethnic minority nurses working in the European Union experience and witness discrimination and prejudice from patients and colleagues due to cultural differences. European health services should closely monitor and address discrimination and prejudice towards migrant and ethnic minority staff and patients, and take initiatives to reduce and, eventually, eradicate them.

Characteristics of patients with autonomic dysfunction in the Transthyretin Amyloidosis Outcomes Survey (THAOS).

BACKGROUND: Autonomic dysfunction is common in transthyretin amyloidosis (ATTR amyloidosis), but its frequency, characteristics, and quality-of-life (QoL) impact are not well understood. METHODS: The Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing, global, longitudinal survey of patients with ATTR amyloidosis, including patients with inherited (ATTRv) and wild-type (ATTRwt) disease and asymptomatic patients with TTR mutations (ClinicalTrials.gov: NCT00628745). In a descriptive analysis, characteristics and Norfolk QoL-DN total (TQoL) scores at enrolment were compared in patients with vs without autonomic dysfunction (analysis cut-off: 1 August 2020). RESULTS: Autonomic dysfunction occurred in 1181/2922 (40.4%) symptomatic patients, and more commonly in ATTRv (1107/1181 [93.7%]) than ATTRwt (74/1181 [6.3%]) amyloidosis. Time (mean [SD]) from ATTR amyloidosis symptom onset to first autonomic dysfunction symptom was shorter in ATTRv (3.4 [5.7] years) than ATTRwt disease (9.7 [10.4]). In ATTRv disease, patients with vs without autonomic dysfunction had worse QoL (TQoL, 47.3 [33.2] vs 16.1 [18.1]); in ATTRwt disease, those with vs without autonomic dysfunction had similar QoL (23.0 [18.2] vs 19.9 [20.5]). CONCLUSIONS: Autonomic dysfunction was more common and presented earlier in symptomatic ATTRv than ATTRwt amyloidosis and adversely affected QoL in ATTRv disease. These THAOS findings may aid clinicians in diagnosing and treating patients with ATTR amyloidosis. Trial registration: ClinicalTrials.gov: NCT00628745.

Migrant and ethnic minority nurses' experience of working in European health services: a qualitative study / Experiência de enfermeiros migrantes e de minorias étnicas em trabalho em serviços de saúde europeus: estudo qualitativo / Experiencia de trabajo de enfermeras inmigrantes y de minorías étnicas en los servicios de salud europeos: un estudio cualitativo

ABSTRACT Objective: To analyze the perception of culture and experience of working in European health services of a purposive sample of qualified migrant and ethnic minority nurses currently living in Belgium, Portugal, Spain and Turkey. Method: A qualitative phenomenological method was chosen. Individual interviews took place with 8 qualified migrant and ethnic minority nurses currently living in four European countries. Thematic analysis was conducted using Braun and Clark's stages after qualitative data had been verbatim transcribed, translated into English, and analyzed Results: Four themes and 4 subthemes emerged from thematic analysis of the transcripts. Conclusion: Migrant and ethnic minority nurses working in the European Union experience and witness discrimination and prejudice from patients and colleagues due to cultural differences. European health services should closely monitor and address discrimination and prejudice towards migrant and ethnic minority staff and patients, and take initiatives to reduce and, eventually, eradicate them.

RESUMO Objetivo: Analisar a percepção da cultura e experiência de trabalho em serviços de saúde europeus de uma amostra intencional de enfermeiros qualificados migrantes e de minorias étnicas que moram atualmente na Bélgica, Portugal, Espanha e Turquia. Método: Optou-se pelo método fenomenológico qualitativo. Realizaram-se entrevistas individuais com 8 enfermeiros qualificados migrantes e de minorias étnicas que moram atualmente em quatro países europeus. A análise temática foi realizada por meio das etapas de Braun e Clark após os dados qualitativos terem sido transcritos na íntegra, traduzidos para o inglês e analisados. Resultados: Quatro temas e 4 subtemas emergiram da análise temática das transcrições. Conclusão: Enfermeiros migrantes e de minorias étnicas que trabalham na União Europeia vivenciam e testemunham discriminação e preconceito de pacientes e colegas devido a diferenças culturais. Os serviços de saúde europeus devem acompanhar de perto e combater a discriminação e o preconceito contra os trabalhadores e pacientes migrantes e de minorias étnicas, e tomar iniciativas para os reduzir e, em seguida, erradicá-los.

RESUMEN Objetivo: Analizar la percepción de la cultura y la experiencia de trabajar en los servicios de salud europeos de una muestra intencional de enfermeros calificados de minorías étnicas y migrantes que actualmente viven en Bélgica, Portugal, España y Turquía. Método: Se decidió utilizar un método cualitativo fenomenológico. Se realizaron entrevistas individuales con 8 enfermeros calificados inmigrantes y de minorías étnicas que actualmente viven en cuatro países europeos. El análisis temático se realizó utilizando las etapas de Braun y Clark después de que los datos cualitativos fueran transcritos palabra por palabra, traducidos al inglés y analizados. Resultados: Del análisis temático de las transcripciones surgieron 4 temas y 4 subtemas. Conclusión: Los enfermeros de minorías étnicas y migrantes que trabajan en la Unión Europea experimentan y son testigos de la discriminación y de los prejuicios de los pacientes y colegas sobre la base de la diferencia cultural. Los servicios de salud europeos deben monitorear de cerca y abordar la discriminación y los prejuicios hacia el personal y los pacientes de minorías étnicas y migrantes, y tomar iniciativas para reducirlos y, eventualmente, erradicarlos.

Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy.

Amyloid transthyretin (ATTR) amyloidosis with polyneuropathy (PN) is a progressive, debilitating, systemic disease wherein transthyretin protein misfolds to form amyloid, which is deposited in the endoneurium. ATTR amyloidosis with PN is the most serious hereditary polyneuropathy of adult onset. It arises from a hereditary mutation in the TTR gene and may involve the heart as well as other organs. It is critical to identify and diagnose the disease earlier because treatments are available to help slow the progression of neuropathy. Early diagnosis is complicated, however, because presentation may vary and family history is not always known. Symptoms may be mistakenly attributed to other diseases such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), idiopathic axonal polyneuropathy, lumbar spinal stenosis, and, more rarely, diabetic neuropathy and AL amyloidosis. In endemic countries (e.g., Portugal, Japan, Sweden, Brazil), ATTR amyloidosis with PN should be suspected in any patient who has length-dependent small-fiber PN with autonomic dysfunction and a family history of ATTR amyloidosis, unexplained weight loss, heart rhythm disorders, vitreous opacities, or renal abnormalities. In nonendemic countries, the disease may present as idiopathic rapidly progressive sensory motor axonal neuropathy or atypical CIDP with any of the above symptoms or with bilateral carpal tunnel syndrome, gait disorders, or cardiac hypertrophy. Diagnosis should include DNA testing, biopsy, and amyloid typing. Patients should be followed up every 6-12 months, depending on the severity of the disease and response to therapy. This review outlines detailed recommendations to improve the diagnosis of ATTR amyloidosis with PN.

Correction to: Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis.

The original version of this article unfortunately contained a mistake.

Analysis of autonomic outcomes in APOLLO, a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis.

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, - 7.5; 95% CI: - 11.9, - 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, - 1.1; - 1.8, - 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; - 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, - 0.3; - 0.5, - 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, - 5.3; 95% CI: - 7.9, - 2.7) and individual domains, orthostatic intolerance (- 4.6; - 6.3, - 2.9) and gastrointestinal symptoms (- 0.8; - 1.5, - 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.

Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial.

BACKGROUND: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations. OBJECTIVE: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis. METHODS: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial ( www.clinicaltrials.gov , NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed. RESULTS: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity. CONCLUSIONS: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems.

Corino de Andrade disease: mechanisms and impact on reproduction.

Familial amyloid polyneuropathy was first described by Corino de Andrade in 1952 in Northern Portugal. It is a fatal autosomal dominant neurodegenerative disorder characterized by a progression of neurologic symptoms, beginning early in the reproductive life. The Transthyretin gene mutation originates a mutated protein that precipitates in the connective tissue as amyloid deposits. This disease is presently named Transthyretin-related hereditary amyloidosis. We performed an extensive review on this disease based on searches in Medical databases and in paper references. In this review, we briefly summarize the epidemiology and the mechanisms involved on amyloid deposition; we detailed how to evaluate the mechanisms implicated on the development of the major signs and symptoms associated with reproductive dysfunction; and we discuss the mechanisms involved in secondary sexual dysfunction after psychological treatments. Treatment of the disease is directed towards relieving specific symptoms in association with liver transplant, and molecular and genetic therapeutics. Although the current clinical trials indicate symptoms relief, no data on the reproductive function was reported. Thus, preimplantation genetic diagnosis is presently the only available technique that eradicates the disease as it avoids the birth of new patients.

Litopédio abdominal. Um caso de rara evoluçao / Lithopaedion: case report

Os autores apresentam um caso de gravidez abdominal com feto mumificado e calcificado (litopédio) em paciente de 60 anos com antecedentes de suspeita de gravidez há 22 anos e menopausa há cerca de 10 anos. O diagnóstico foi confirmado após laparotomia exploradora. O seguimento pós operatório nÝo apresentou intercorrências

Influência da idade na morbidade e mortalidade da cirurgia arterial coronária / Influence of age on the morbidity and mortality of the coronary artery surgery

Para estudar os efeitos da idade nos resultados da cirurgia coronária, 250 pacientes, operados entre 1986 e 1989, foram divididos em dois grupos: 1) doentes apresentando menos de 65 anos de idade; 2) pacientes com idade igual ou superior a 65 anos. Os dados analisados no pré, trans e pós-operatório incluíram: sexo, tipo e classe de angina, doenças associadas, infarto do miocárdio prévio, cirurgia coronária prévia, aneurisma do ventrículo esquerdo, tempos de perfusäo e de clampeamento aórtico, número de artérias revascularizadas, necessidade de suporte inotrópico prolongado, complicaçöes pós-operatórias e mortalidade. Observou-se nos pacientes idosos uma maior incidência de angina instável (20,3% x 6,2%), angina pós-infarto (10,1% x 7,8%), angina em repouso (10,1 x 3,6%), doença vascular periférica (8,4% x 2,6%), necessidade de suporte inotrópico prolongado (18,6% x 3,1%), complicaçöes neurológicas (8,4% x 0,5%) e, por fim, infarto do miocárdio trans ou pós-operatório (5,0% x 0,5%). A mortalidade global foi de 3,6%, sendo, contudo, significativamente maior nos pacientes idosos (11,8% x 1,0%). Estes dados sugerem que os pacientes idosos apresentam um risco maior de complicaçöes neurológicas, cardíacas e de mortalidade, o que provavelmente deve-se a uma maior susceptibilidade desses doentes a complicaçöes pós-operatórias graves