Scintigraphic and Echocardiographic Study of Patients with Pathogenic or Probably Pathogenic Variants of the TTR Gene without Overt Cardiac Involvement. / Avaliação Cintilográfica e Ecocardiográfica em Portadores de Variantes Patogênicas ou Provavelmente Patogênicas do Gene TTR sem Envolvimento Cardíaco Manifesto.

BACKGROUND: Transthyretin amyloidosis (ATTR) is an infiltrative disease caused by abnormal protein deposition mainly in the heart and peripheral nervous system. When it affects the heart, the disease presents as restrictive cardiomyopathy; when it affects the peripheral and autonomic nervous system, it manifests as polyneuropathy, and is called familial amyloid polyneuropathy (FAP). There are two ATTR subtypes: wild-type ATTR, where there is no mutation, and mutant ATTR (ATTRm), which is characterized by a mutation in the gene encoding the transthyretin protein (TTR). In both subtypes, cardiac involvement is the major marker of poor prognosis. OBJECTIVES: To assess the prevalence of subclinical cardiac involvement in a sample of patients with TTR gene mutation by using pyrophosphate scintigraphy and strain echocardiography; to compare scintigraphy and strain findings; to evaluate the association between neurological manifestations (FAP) and subclinical cardiac involvement; and to analyze whether there is an association between any specific mutation and cardiac involvement. METHODS: This is a cross-sectional study with carriers of the TTR gene mutation, without cardiovascular symptoms or changes in electrocardiographic or conventional echocardiographic parameters. All patients underwent pyrophosphate scintigraphy and strain echocardiography. Subclinical cardiac involvement was defined as a Perugini score ≥ 2, heart-to-contralateral lung (H/CL) ratio ≥ 1.5 at 1 h, H/CL ≥1.3 at 3 h, or global longitudinal strain (GLS) ≤ -17%. Descriptive and analytical analyses were performed and Fisher's exact test and Mann-Whitney test were applied. A value of p < 0.05 was considered significant. RESULTS: The 23 patients evaluated had a median age of 51 years (IQR 37-57 years), 15 (65.2%) were female, 12 (52.2%) were Pardo, nine (39.1%) had systemic arterial hypertension, and nine (39.1%) had a previous diagnosis of FAP. Of the nine patients with FAP, 8 (34.8%) were on tafamidis. The associated mutations were Val142IIe, Val50Met, and IIe127Val. The median GLS in the sample was -19% (-16% to -20%). Of the 23 patients, nine (39.1%; 95% CI = 29-49%) met criteria for cardiac involvement, six (26%) by the GLS-based criteria only. There was no association between having FAP and being an asymptomatic carrier, as assessed by strain echocardiography and pyrophosphate scintigraphy (p = 0.19). The prevalence of systemic arterial hypertension, diabetes mellitus, dyslipidemia, smoking, and reduced GLS did not differ between groups. Septal e' wave velocity was the only variable that significantly differed between individuals with and without reduced GLS, with an area under the ROC curve of 0.80 (95% CI = 0.61-0.98, p = 0.027). The best diagnostic accuracy was achieved with a septal e' velocity ≤ 8.5 cm/s. There was no association between mutation type and preclinical cardiac involvement, nor between tafamidis use and lower degree of cardiac involvement (37.5% versus 40.0%, p = 0.90). CONCLUSION: Subclinical cardiac involvement was common in a sample of TTR mutation carriers without cardiac involvement. Reduced left ventricular GLS was the most frequent finding. There was no association between the presence of amyloid polyneuropathy and subclinical cardiac involvement. Type of mutation was not associated with early cardiac involvement. In this sample, the use of tafamidis 20 mg/day was not associated with a lower prevalence of subclinical cardiac involvement.

FUNDAMENTO: A amiloidose por transtirretina (ATTR) é uma doença infiltrativa causada pela deposição anormal de proteína principalmente no coração e no sistema nervoso periférico. Quando acomete o coração, a doença manifesta-se como uma cardiomiopatia restritiva e, quando afeta o sistema nervoso periférico e autônomo, apresenta-se como uma polineuropatia, podendo ser chamada de Polineuropatia Amiloidótica Familiar (PAF). Existem dois subtipos de ATTR, a ATTR selvagem, em que não há variantes genéticas, e a ATTR hereditária, caracterizada por uma variante no gene que codifica a proteína transtirretina (T\TR). Em ambos os subtipos, o envolvimento cardíaco é o principal marcador prognóstico. OBJETIVOS: Avaliar a prevalência do envolvimento cardíaco subclínico em uma amostra de pacientes com variantes genéticas no gene TTR usando a cintilografia com pirofosfato e o ecocardiograma com strain; comparar os achados cintilográficos e as medidas de strain; avaliar a associação entre PAF e o envolvimento subclínico; e analisar se existe uma associação entre uma variante genética específica e o envolvimento cardíaco. MÉTODOS: Estudo transversal com carreadores de variantes no gene TTR sem sintomas cardiovasculares e sem alterações nos parâmetros da eletrocardiografia ou do ecocardiograma convencional. Todos os pacientes foram submetidos à cintilografia com pirofosfato e à ecocardiografia com análise de strain. O envolvimento cardíaco subclínico, definido como um escore de Perugini ≥ 2, razão Coração (C)/ Hemitórax Contralateral (CL) ≥ 1,5 em uma hora, C/CL ≥ 1,3 na terceira hora, ou um strain longitudinal global (SGL) ≤ −17%. Realizadas análises descritiva e analítica, e aplicados o teste exato de Fisher e o teste de Mann-Whitney. Um valor de p<0,05 foi considerado significativo. RESULTADOS: Os 23 pacientes avaliados apresentavam uma idade mediana de 51 (37-57) anos, 15 (65,2%) eram do sexo feminino, 12 (52,2%) eram pardos, nove (39,1%) apresentavam hipertensão arterial sistêmica, e nove (39,1%) tinham um diagnóstico prévio de PAF. Dos nove pacientes com PAF, oito (34,8%) usavam tafamidis. As variantes genéticas identificadas foram Val142IIe, Val50Met e IIe127Val. O valor mediano do SGL foi −19% (-16% ­ −20%). Dos 23 pacientes, nove (39,1%; 95% CI = 29­49%) preencheram os critérios de envolvimento cardíaco, seis (26%) somente pelo critério do SGL. Não houve associação entre PAF e um carreador assintomático avaliado por ecocardiograma com análise de strain e pela cintilografia com pirofostato (p=0,19). A prevalência de hipertensão arterial sistêmica, diabetes mellitus, dislipidemia, tabagismo e SGL reduzido não foi diferente entre os grupos. A velocidade da onda e' septal foi a única variável que apresentou diferença significativa entre os indivíduos com e sem SGL reduzido, com uma área sob a curva ROC de 0,80 (IC95% = 0,61­0,98, p = 0,027). A melhor acurácia diagnóstica foi alcançada com uma velocidade e' septal ≤ 8,5 cm/s. Não houve associação entre o tipo de variante genética e o envolvimento cardíaco pré-clínico, nem entre o uso de tafamidis e este mesmo envolvimento (37,5% versus 40,0%, p = 0,90). CONCLUSÃO: O envolvimento cardíaco subclínico foi frequente em uma amostra de carreadores da variante genética do gene TTR. Um valor do SGL reduzido foi o achado mais comum. Não houve associação entre a presença de polineuropatia amiloidótica e o envolvimento subclínico. O tipo de variante genética não foi associado com envolvimento cardíaco precoce. Nesta amostra, o uso de tafamidis (20mg/dia) não foi associado com uma menor prevalência de envolvimento cardíaco subclínico.

Shear thickening fluid (STF) in engineering applications and the potential of cork in STF-based composites.

Shear thickening fluids (STFs) are a unique type of fluids that can quickly transform into a solid-like state when subjected to forces (rate dependent). These fluids are created by dispersing micro and nanoparticles within a medium. When the force is removed, they return to their original liquid state. Shear thickening fluids can absorb a significant amount of impact energy, making them useful for reducing vibrations and serving as a damper. This study provides a comprehensive and brief overview of existing literature on shear thickening fluids, including their properties, classification, and the rheological mechanisms behind the shear thickening behaviour. It also examines the use of these fluids in various applications, such as improving resistance to stabs and spikes, protecting against low- and high-velocity impacts, and as a new medium for energy dissipation in industries such as battery safety, vibration control and adaptive structures. Lastly, this work reviews the promising combination of STFs with cork. Given the sustainability of cork and its energy absorption capacity, cork-STF composites are a promising solution for various impact-absorbing applications. Overall, the paper underscores the versatility and potential of STFs, and advocates for further research and exploration.

Eco-Friendly Cork-Polyurethane Biocomposites for Enhanced Impact Performance: Experimental and Numerical Analysis.

Cork composites are byproducts from wine stopper production, resulting from the agglomeration of cork granules with a thermoset resin. The resulting compound is a versatile and durable material with numerous industrial applications. Due to its unique properties, such as low-density, high-strength, excellent energy absorption, and good thermal and acoustic insulators, cork composites find room for application in demanding industries such as automotive, construction, and aerospace. However, agglomerated cork typically has a polyurethane matrix derived from petrochemical sources. This study focuses on developing eco-friendly porous polyurethane biocomposites manufactured with the used cooking oil polyol modified with cork. Since cork and polyurethane foam are typically used for impact shock absorption, the manufactured samples were subjected to impact loading. The assessment of crashworthiness is performed through 100 J impact tests. A finite element numerical model was developed to simulate the compression of these new composites under impact, and the model validation was performed. The highest specific absorbed energy was obtained for petrochemical polyol composites with the 3% addition of natural or modified cork. The research conducted in this study showcased the feasibility of substituting certain petrochemical components used for the synthesis of the polyurethane matrix with ecological waste vegetable oil components.

Guidelines on the Diagnosis and Treatment of Hypertrophic Cardiomyopathy ­ 2024 / Diretriz sobre Diagnóstico e Tratamento da Cardiomiopatia Hipertrófica ­ 2024

Hypertrophic cardiomyopathy (HCM) is a form of genetically caused heart muscle disease, characterized by the thickening of the ventricular walls. Diagnosis requires detection through imaging methods (Echocardiogram or Cardiac Magnetic Resonance) showing any segment of the left ventricular wall with a thickness > 15 mm, without any other probable cause. Genetic analysis allows the identification of mutations in genes encoding different structures of the sarcomere responsible for the development of HCM in about 60% of cases, enabling screening of family members and genetic counseling, as an important part of patient and family management. Several concepts about HCM have recently been reviewed, including its prevalence of 1 in 250 individuals, hence not a rare but rather underdiagnosed disease. The vast majority of patients are asymptomatic. In symptomatic cases, obstruction of the left ventricular outflow tract (LVOT) is the primary disorder responsible for symptoms, and its presence should be investigated in all cases. In those where resting echocardiogram or Valsalva maneuver does not detect significant intraventricular gradient (> 30 mmHg), they should undergo stress echocardiography to detect LVOT obstruction. Patients with limiting symptoms and severe LVOT obstruction, refractory to beta-blockers and verapamil, should receive septal reduction therapies or use new drugs inhibiting cardiac myosin. Finally, appropriately identified patients at increased risk of sudden death may receive prophylactic measure with implantable cardioverter-defibrillator (ICD) implantation.

La miocardiopatía hipertrófica (MCH) es una forma de enfermedad cardíaca de origen genético, caracterizada por el engrosamiento de las paredes ventriculares. El diagnóstico requiere la detección mediante métodos de imagen (Ecocardiograma o Resonancia Magnética Cardíaca) que muestren algún segmento de la pared ventricular izquierda con un grosor > 15 mm, sin otra causa probable. El análisis genético permite identificar mutaciones en genes que codifican diferentes estructuras del sarcómero responsables del desarrollo de la MCH en aproximadamente el 60% de los casos, lo que permite el tamizaje de familiares y el asesoramiento genético, como parte importante del manejo de pacientes y familiares. Varios conceptos sobre la MCH han sido revisados recientemente, incluida su prevalencia de 1 entre 250 individuos, por lo tanto, no es una enfermedad rara, sino subdiagnosticada. La gran mayoría de los pacientes son asintomáticos. En los casos sintomáticos, la obstrucción del tracto de salida ventricular izquierdo (TSVI) es el trastorno principal responsable de los síntomas, y su presencia debe investigarse en todos los casos. En aquellos en los que el ecocardiograma en reposo o la maniobra de Valsalva no detecta un gradiente intraventricular significativo (> 30 mmHg), deben someterse a ecocardiografía de esfuerzo para detectar la obstrucción del TSVI. Los pacientes con síntomas limitantes y obstrucción grave del TSVI, refractarios al uso de betabloqueantes y verapamilo, deben recibir terapias de reducción septal o usar nuevos medicamentos inhibidores de la miosina cardíaca. Finalmente, los pacientes adecuadamente identificados con un riesgo aumentado de muerte súbita pueden recibir medidas profilácticas con el implante de un cardioversor-desfibrilador implantable (CDI).

A cardiomiopatia hipertrófica (CMH) é uma forma de doença do músculo cardíaco de causa genética, caracterizada pela hipertrofia das paredes ventriculares. O diagnóstico requer detecção por métodos de imagem (Ecocardiograma ou Ressonância Magnética Cardíaca) de qualquer segmento da parede do ventrículo esquerdo com espessura > 15 mm, sem outra causa provável. A análise genética permite identificar mutações de genes codificantes de diferentes estruturas do sarcômero responsáveis pelo desenvolvimento da CMH em cerca de 60% dos casos, permitindo o rastreio de familiares e aconselhamento genético, como parte importante do manejo dos pacientes e familiares. Vários conceitos sobre a CMH foram recentemente revistos, incluindo sua prevalência de 1 em 250 indivíduos, não sendo, portanto, uma doença rara, mas subdiagnosticada. A vasta maioria dos pacientes é assintomática. Naqueles sintomáticos, a obstrução do trato de saída do ventrículo esquerdo (OTSVE) é o principal distúrbio responsável pelos sintomas, devendo-se investigar a sua presença em todos os casos. Naqueles em que o ecocardiograma em repouso ou com Manobra de Valsalva não detecta gradiente intraventricular significativo (> 30 mmHg), devem ser submetidos à ecocardiografia com esforço físico para detecção da OTSVE.   Pacientes com sintomas limitantes e grave OTSVE, refratários ao uso de betabloqueadores e verapamil, devem receber terapias de redução septal ou uso de novas drogas inibidoras da miosina cardíaca. Por fim, os pacientes adequadamente identificados com risco aumentado de morta súbita podem receber medida profilática com implante de cardiodesfibrilador implantável (CDI).

Perfis clínicos e genéticos de pacientes com amiloidose transtiretina hereditária e do tipo selvagem: o registro de amiloidose cardíaca transtiretina no Estado de São Paulo, Brasil (REACT-SP) / Clinical and genetic profiles of patients with hereditary and wild-type transthyretin amyloidosis: the transthyretin cardiac amyloidosis registry in the State of São Paulo, Brazil (REACT-SP)

INTRODUÇÃO: A amiloidose transtiretina (ATTR) é uma doença multissistêmica causada pela deposição de proteína fibrilar em órgãos e tecidos. Os genótipos e fenótipos da ATTR são altamente heterogêneos. MÉTODOS: Apresentamos dados sobre sinais e sintomas físicos, avaliações cardíacas e neurológicas, e genética em pacientes incluídos no Registro de Amiloidose Cardíaca Transtiretina no Estado de São Paulo (REACT-SP), Brasil. RESULTADOS: Foram incluídos 644 pacientes, sendo 505 com a forma variante (ATTRv) e 139 com a forma selvagem (ATTRwt). Dezesseis mutações diferentes foram detectadas, sendo as mais comuns Val50Met (48,3%) e V142Ile (40,8%). No geral, mais da metade dos pacientes apresentou envolvimento cardíaco, e a diferença nessa proporção entre os grupos ATTRv e ATTRwt foi significativa (43,9 vs. 89,9%; p<0,001). O fenótipo neurológico também diferiu entre ATTRv e ATTRwt (56,8 vs. 31,7%; p<0,001). O fenótipo misto foi encontrado em 25,6% da população, sem diferença significativa entre as formas de amiloidose. Um grupo de pacientes permaneceu assintomático (10,4%), com uma proporção menor de pacientes assintomáticos no grupo ATTRwt. CONCLUSÕES: Este estudo detalha o espectro clínico e genético de pacientes com ATTR em São Paulo, Brasil. Esta análise preliminar destaca a considerável heterogeneidade fenotípica das manifestações neurológicas e cardíacas em pacientes com ATTR variante e ATTR do tipo selvagem.

Advanced Erosive Gouty Arthropathy of the Knee.

A 57-year-old male, with chronic bilateral knee pain and a history of poorly controlled hyperuricemia leading to gouty attacks, underwent orthopedic assessment. Radiographic and MRI findings confirmed chronic gouty arthropathy with erosive bony defects, the most significant on the right proximal tibia. Total knee arthroplasty (TKA) was performed without any complications, addressing the bony defect with cement and a semi-constrained prosthesis. However, a gouty attack led to prolonged wound discharge and periprosthetic infection postoperatively, prompting revision surgery with debridement, antibiotics, and implant retention (DAIR). Intraoperative cultures revealed methicillin-sensitive Staphylococcus aureus (MSSA). The treatment included vancomycin and rifampicin. Two years post-surgery, the patient walked pain-free with a knee range of motion of 0-90º. This report highlights the complexity of treating gout-related knee osteoarthritis, emphasizing early intervention to mitigate risks of extensive surgical procedures and infections.

Assessment of potential transthyretin amyloid cardiomyopathy cases in the Brazilian public health system using a machine learning model.

OBJECTIVES: To identify and describe the profile of potential transthyretin cardiac amyloidosis (ATTR-CM) cases in the Brazilian public health system (SUS), using a predictive machine learning (ML) model. METHODS: This was a retrospective descriptive database study that aimed to estimate the frequency of potential ATTR-CM cases in the Brazilian public health system using a supervised ML model, from January 2015 to December 2021. To build the model, a list of ICD-10 codes and procedures potentially related with ATTR-CM was created based on literature review and validated by experts. RESULTS: From 2015 to 2021, the ML model classified 262 hereditary ATTR-CM (hATTR-CM) and 1,581 wild-type ATTR-CM (wtATTR-CM) potential cases. Overall, the median age of hATTR-CM and wtATTR-CM patients was 66.8 and 59.9 years, respectively. The ICD-10 codes most presented as hATTR-CM and wtATTR-CM were related to heart failure and arrythmias. Regarding the therapeutic itinerary, 13% and 5% of hATTR-CM and wtATTR-CM received treatment with tafamidis meglumine, respectively, while 0% and 29% of hATTR-CM and wtATTR-CM were referred to heart transplant. CONCLUSION: Our findings may be useful to support the development of health guidelines and policies to improve diagnosis, treatment, and to cover unmet medical needs of patients with ATTR-CM in Brazil.

Assessment of potential transthyretin amyloid cardiomyopathy cases in the Brazilian public health system using a machine learning mode

OBJECTIVES: To identify and describe the profile of potential transthyretin cardiac amyloidosis (ATTR-CM) cases in the Brazilian public health system (SUS), using a predictive machine learning (ML) model. METHODS: This was a retrospective descriptive database study that aimed to estimate the frequency of potential ATTR-CM cases in the Brazilian public health system using a supervised ML model, from January 2015 to December 2021. To build the model, a list of ICD-10 codes and procedures potentially related with ATTR-CM was created based on literature review and validated by experts. RESULTS: From 2015 to 2021, the ML model classified 262 hereditary ATTR-CM (hATTR-CM) and 1,581 wild-type ATTR-CM (wtATTR-CM) potential cases. Overall, the median age of hATTR-CM and wtATTR-CM patients was 66.8 and 59.9 years, respectively. The ICD-10 codes most presented as hATTR-CM and wtATTR-CM were related to heart failure and arrythmias. Regarding the therapeutic itinerary, 13% and 5% of hATTR-CM and wtATTR-CM received treatment with tafamidis meglumine, respectively, while 0% and 29% of hATTR-CM and wtATTR-CM were referred to heart transplant. CONCLUSION: Our findings may be useful to support the development of health guidelines and policies to improve diagnosis, treatment, and to cover unmet medical needs of patients with ATTR-CM in Brazil.

Limitations of Apical Sparing Pattern in Cardiac Amyloidosis: A Multicenter Echocardiographic Study.

BACKGROUND: Although impaired left ventricular (LV) global longitudinal strain (GLS) with apical sparing is a feature of cardiac amyloidosis (CA), its diagnostic accuracy has varied across studies. We aimed to determine the ability of apical sparing ratio (ASR) and most common echocardiographic parameters to differentiate patients with confirmed CA from those with clinical and/or echocardiographic suspicion of CA, but with this diagnosis ruled out. METHODS: We identified 544 patients with confirmed CA and 200 controls as defined above (CTRL Patients). Measurements from transthoracic echocardiograms (TTE) were performed using artificial intelligence software (Us2.AI, Singapore) and audited by an experienced echocardiographer. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic performance and optimal cutoffs for the differentiation of CA patients from CTRL Patients. Additionally, a group of 174 healthy subjects (Healthy CTRL) was included to provide insight on how Patients and Healthy controls differed echocardiographically. RESULTS: LV GLS was more impaired (-13.9 ± 4.6% vs -15.9 ± 2.7%, p < 0.0005) and ASR was higher (2.4 ± 1.2 vs 1.7 ± 0.9, p < 0.0005) in the CA group vs. CTRL Patients. Relative wall thickness and ASR were the most accurate parameters for differentiating CA from CTRL Patients (AUC: 0.77 and 0.74, respectively). However, even with the optimal cutoff of 1.67, ASR was only 72% sensitive and 66% specific for CA, indicating presence of apical sparing in 32% of CTRL Patients and even in 6% Healthy CTRLs. CONCLUSIONS: Apical sparing did not prove to be a CA-specific biomarker for accurate identification of CA, when compared to clinically similar controls with no CA.

Effect of Tafamidis on Cardiac Function in Patients With Transthyretin Amyloid Cardiomyopathy: A Post Hoc Analysis of the ATTR-ACT Randomized Clinical Trial.

Importance: Tafamidis has been shown to improve survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with placebo. However, its effect on cardiac function has not been fully characterized. Objective: To examine the effect of tafamidis on cardiac function in patients with ATTR-CM. Design, Setting, and Participants: This was an exploratory, post hoc analysis of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), a multicenter, international, double-blind, placebo-controlled phase 3 randomized clinical trial conducted from December 2013 to February 2018. The ATTR-ACT included 48 sites in 13 counties and enrolled patients aged 18 to 90 years with ATTR-CM. Data were analyzed from July 2018 to September 2023. Intervention: Patients were randomized to tafamidis meglumine, 80 mg or 20 mg, or placebo for 30 months. Main Outcomes and Measures: Patients were categorized based on left ventricular (LV) ejection fraction at enrollment as having heart failure with preserved ejection fraction (≥50%), mildly reduced ejection fraction (41% to 49%), or reduced ejection fraction (≤40%). Changes from baseline to month 30 in LV ejection fraction, LV stroke volume, LV global longitudinal strain, and the ratio of early mitral inflow velocity to septal and lateral early diastolic mitral annular velocity (E/e') were compared in patients receiving tafamidis, 80 mg, vs placebo. Results: A total of 441 patients were randomized in ATTR-ACT, and 436 patients had available echocardiographic data. Of 436 included patients, 393 (90.1%) were male, and the mean (SD) age was 74 (7) years. A total of 220 (50.5%), 119 (27.3%), and 97 (22.2%) had heart failure with preserved, mildly reduced, and reduced LV ejection fraction, respectively. Over 30 months, there was less pronounced worsening in 4 of the echocardiographic measures in patients receiving tafamidis, 80 mg (n = 176), vs placebo (n = 177) (least squares mean difference: LV stroke volume, 7.02 mL; 95% CI, 2.55-11.49; P = .002; LV global longitudinal strain, -1.02%; 95% CI, -1.73 to -0.31; P = .005; septal E/e', -3.11; 95% CI, -5.50 to -0.72; P = .01; lateral E/e', -2.35; 95% CI, -4.01 to -0.69; P = .006). Conclusions and Relevance: Compared with placebo, tafamidis, 80 mg, attenuated the decline of LV systolic and diastolic function over 30 months in patients with ATTR-CM. Approximately half of patients had mildly reduced or reduced LV ejection fraction at enrollment, suggesting that ATTR-CM should be considered as a possible diagnosis in patients with heart failure regardless of underlying LV ejection fraction. Trial Registration: ClinicalTrials.gov Identifier: NCT01994889.

A Review of the Metal Additive Manufacturing Processes.

Metal additive manufacturing (AM) is a layer-by-layer process that makes the direct manufacturing of various industrial parts possible. This method facilitates the design and fabrication of complex industrial, advanced, and fine parts that are used in different industry sectors, such as aerospace, medicine, turbines, and jewelry, where the utilization of other fabrication techniques is difficult or impossible. This method is advantageous in terms of dimensional accuracy and fabrication speed. However, the parts fabricated by this method may suffer from faults such as anisotropy, micro-porosity, and defective joints. Metals like titanium, aluminum, stainless steels, superalloys, etc., have been used-in the form of powder or wire-as feed materials in the additive manufacturing of various parts. The main criterion that distinguishes different additive manufacturing processes from each other is the deposition method. With regard to this criterion, AM processes can be divided into four classes: local melting, sintering, sheet forming, and electrochemical methods. Parameters affecting the properties of the additive-manufactured part and the defects associated with an AM process determine the method by which a certain part should be manufactured. This study is a survey of different additive manufacturing processes, their mechanisms, capabilities, shortcomings, and the general properties of the parts manufactured by them.

Resource utilization and costs related to the management of obstructive hypertrophic cardiomyopathy under the Brazilian supplementary healthcare system´s perspective: results from a modified Delphi panel / Utilização de recursos e custos relacionados ao manejo da cardiomiopatia hipertrófica obstrutiva sob a perspectiva do sistema de saúde suplementar brasileiro: resultados de um painel Delphi modificado

Objective: To generate data on the costs associated with the diagnosis and treatment of obstructive ypertrophic cardiomyopathy (HCM) from the perspective of the private health system in Brazil. Methods: A modified Delphi panel including seven different specialists (three clinical cardiologists with experience in obstructive HCM, two hemodynamicists with experience in septal ablation and two cardiac surgeons with expertise in myectomy), from two Brazilian states (São Paulo and Pernambuco), was conducted between August and November 2022. Two rounds of questions about the use of healthcare resources according to the functional class (NYHA I-IV) and a panel in a virtual platform were conducted to obtain the final consensus. Micro-costing defined costs and unit values were determined based on official price lists. Results: The total diagnosis cost per patient was estimated at BRL 11,486.81. The obstructive HCM management costs analysis showed average annual costs per patient of BRL 17,026.74, BRL 19,401.46, BRL 73,310.07, and BRL 94,885.75 for the functional classes NYHA I, NYHA II, NYHA III, and NYHA IV, respectively. The average costs per patient related to procedures in a year were BRL 12,698.53, BRL 13,462.30, BRL 58,841.67, and BRL 75,595.90 for the functional classes NYHA I, II, III, and IV, respectively. Conclusions: The annual costs of HCM management increased according to the functional class, highlighting the need for safe and effective strategies to improve patient's NYHA functional class while promoting a decrease in the need for invasive therapies.

Objetivo: Gerar dados acerca dos custos associados ao diagnóstico e tratamento da cardiomiopatia hipertrófica (CMH) obstrutiva, sob a perspectiva do sistema de saúde privado no Brasil. Métodos: Um painel Delphi modificado incluindo sete especialistas (três cardiologistas clínicos com experiência em CMH obstrutiva, dois hemodinamicistas com experiência em ablação de septo e dois cirurgiões cardíacos com experiência em miectomia) de dois estados brasileiros (São Paulo e Pernambuco) foi conduzido entre agosto e novembro de 2022. Foram realizadas duas rodadas de perguntas acerca da utilização de recursos de acordo com a classe funcional (NYHA I-IV) e uma reunião virtual para obtenção do consenso final. Os custos foram definidos por meio de microcusteio, e os valores unitários foram definidos com base em listas de preço oficiais. Resultados: O custo total do diagnóstico por paciente foi estimado em R$ 11.486,81. A análise de custos de manejo da CMH obstrutiva mostrou custos médios anuais por paciente de R$ 17.026,74, R$ 19.401,46, R$ 73.310,07 e R$ 94.885,75 para as classes funcionais NYHA I, NYHA II, NYHA III e NYHA IV, respectivamente. Os custos médios por paciente relacionados a procedimentos em um ano foram de R$ 12.698,53, R$ 13.462,30, R$ 58.841,67 e R$ 75.595,90 para as classes NYHA I, II, III e IV, respectivamente. Conclusões: Os custos anuais com o manejo da CMH aumentam de acordo com a classe funcional, destacando a necessidade de estratégias seguras e eficazes capazes de melhorar a classe funcional NYHA do paciente, ao mesmo tempo que promove diminuição da necessidade de terapias invasivas.

Using machine learning to assess potential cases of transthyretin cardiac amyloidosis in Brazil: a retrospective database approach

INTRODUCTION: Amyloidosis is a group of protein misfolding disorders leading to organ damage due to insoluble amyloid fibril deposits • The two primary types of cardiac amyloidosis are light-chain amyloid (AL) and transthyretin (TTR) cardiac amyloidosis • TTR amyloidosis can be hereditary (hATTR) or age-related (wtATTR). It is an often-overlooked cause of heart failure in older adults • Recent studies reveal its prevalence in various patient groups: up to 13% in HFpEF, 16% in aortic stenosis patients undergoing valve replacement, 7-8% in carpal tunnel release surgery, and 17% in some other contexts • ATTR-CM is significant in the context of cardiovascular diseases, a leading global cause of death. OBJECTIVE: This study aimed to identify and describe the profile of potential transthyretin cardiac amyloidosis (ATTR-CM) cases in the Brazilian public health system (SUS), using a predictive machine learning (ML) model. MATERIALS AND METHODS: This was a retrospective descriptive database study that aimed to estimate the frequency of potential ATTR-CM cases in the Brazilian public health system (Figure 1) using a supervised machine learning (Figure 2) model, with data extracted from DATASUS outpatient and inpatient datasets from January 2015 to December 2021 • To build the model, a list of ICD-10 codes and procedures potentially related with ATTR-CM was created based on literature review and validated by experts (Figure 3). RESULTS: From 2015 to 2021, the ML model classified 262 hATTR-CM (213 reference hATTR-CIM and 49 hATTR-CM-like) and 1,581 wtATTR-CM (203 reference wtATTR-CM and 1,378 wtATTR-CM-like). Overall, the median age of hATTR-CM and wtATTR-CM patients was 66.8 and 59.9 years, respectively • The ICD-10 codes most presented as hATTR-CM and wtATTR-CM were related to heart failure and arrythmias, with similar procedures performed (Figure 4). Regarding healthcare utilization, hATTR-CM and hATTR-CM-like had similar profiles on proportion of patients with outpatient visits (hATTR-CM 98.0% vs. 92.0% hATTR-CM-like) and different profile related to proportion of hospitalized patients (hATTR-CM 94.4% vs. 32.7% hATTR-CM-like) (Figure 5) • In wtATTR-CM groups, although both proportions on outpatient visits and hospitalizations were similar, the length of stay (LOS) on hospitalizations was different in wtATTR-CM-like (wtATTR-CM median LOS 5.0 (IQR:2.0 - 10.0] vs. median LOS 7.0 [IQR:3.0 - 14.0]). CONCLUSIONS: Our findings may be useful to support decreasing the uncertainties on ATTR-CM population size in Health Technology Assessment appraisals and in the development of healthcare guidelines and policies to address patients' unmet needs and to improve early diagnosis and access to treatment for patients with ATTR-CM in Brazil This study puts a spotlight on the ATTR-CM underdiagnosis in Brazil using a machine learning approach, which can be used as an important tool to support diagnosis improvement.

Rare association between giant-cell aortitis and giant-cell aortic valvulitis.

Giant cell arteritis (GCA) is a type of chronic vasculitis that affects medium and large-caliber arteries, frequently related to aortic involvement and, consequently, to aneurysm formation. However, associated valvulitis with giant cells is uncommon. We describe the case of a 50-year-old female patient with aortic aneurysm and valvular insufficiency, whose anatomopathological examination revealed giant-cell aortic valvulitis associated with giant cell aortitis.

Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis.

BACKGROUND: Transthyretin amyloidosis, also called ATTR amyloidosis, is associated with accumulation of ATTR amyloid deposits in the heart and commonly manifests as progressive cardiomyopathy. Patisiran, an RNA interference therapeutic agent, inhibits the production of hepatic transthyretin. METHODS: In this phase 3, double-blind, randomized trial, we assigned patients with hereditary, also known as variant, or wild-type ATTR cardiac amyloidosis, in a 1:1 ratio, to receive patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks for 12 months. A hierarchical procedure was used to test the primary and three secondary end points. The primary end point was the change from baseline in the distance covered on the 6-minute walk test at 12 months. The first secondary end point was the change from baseline to month 12 in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score (with higher scores indicating better health status). The second secondary end point was a composite of death from any cause, cardiovascular events, and change from baseline in the 6-minute walk test distance over 12 months. The third secondary end point was a composite of death from any cause, hospitalizations for any cause, and urgent heart failure visits over 12 months. RESULTS: A total of 360 patients were randomly assigned to receive patisiran (181 patients) or placebo (179 patients). At month 12, the decline in the 6-minute walk distance was lower in the patisiran group than in the placebo group (Hodges-Lehmann estimate of median difference, 14.69 m; 95% confidence interval [CI], 0.69 to 28.69; P = 0.02); the KCCQ-OS score increased in the patisiran group and declined in the placebo group (least-squares mean difference, 3.7 points; 95% CI, 0.2 to 7.2; P = 0.04). Significant benefits were not observed for the second secondary end point. Infusion-related reactions, arthralgia, and muscle spasms occurred more often among patients in the patisiran group than among those in the placebo group. CONCLUSIONS: In this trial, administration of patisiran over a period of 12 months resulted in preserved functional capacity in patients with ATTR cardiac amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO-B ClinicalTrials.gov number, NCT03997383.).

The association of myocardial strain with cardiac magnetic resonance and clinical outcomes in patients with acute myocarditis.

Introduction: The role of myocardial strain in risk prediction for acute myocarditis (AMC) patients, measured by cardiac magnetic resonance (CMR), deserves further investigation. Our objective was to evaluate the association between myocardial strain measured by CMR and clinical events in AMC patients. Material and methods: This was a prospective single-center study of patients with AMC. We included 100 patients with AMC with CMR confirmation. The primary outcome was the composite of all-cause mortality, heart failure and AMC recurrence in 24 months. A subgroup analysis was performed on a sample of 36 patients who underwent a second CMR between 6 and 18 months. The association between strain measures and clinical events or an increase in left ventricular ejection fraction (LVEF) was explored using Cox regression analysis. Global peak radial, circumferential and longitudinal strain in the left and right ventricles was assessed. ROC curve analysis was performed to identify cutoff points for clinical event prediction. Results: The mean follow-up was 18.7 ± 2.3 months, and the composite primary outcome occurred in 26 patients. The median LVEF at CMR at baseline was 57.5% (14.6%). LV radial strain (HR = 0.918, 95% CI: 0.858-0.982, p = 0.012), LV circumferential strain (HR = 1.177, 95% CI: 1.046-1.325, p = 0.007) and LV longitudinal strain (HR = 1.173, 95% CI: 1.031-1.334, p = 0.015) were independently associated with clinical event occurrence. The areas under the ROC curve for clinical event prediction were 0.80, 0.79 and 0.80 for LV radial, circumferential, and longitudinal strain, respectively. LV longitudinal strain was independently correlated with prognosis (HR = 1.282, CI 95%: 1.022-1.524, p = 0.007), even when analyzed together with ejection fraction and delayed enhancement. LV and right ventricle (RV) strain were not associated with an increase in LVEF. Finally, when the initial CMR findings were compared with the follow-up CMR findings, improvements in the measures of LV and RV myocardial strain were observed. Conclusion: Measurement of myocardial strain by CMR can provide prognostic information on AMC patients. LV radial, circumferential and longitudinal strain were associated with long-term clinical events in these patients.

Detection of Early Diffuse Myocardial Fibrosis and Inflammation in Chagas Cardiomyopathy with T1 Mapping and Extracellular Volume.

Purpose: To evaluate myocardial T1 mapping and extracellular volume (ECV) parameters in different stages of Chagas cardiomyopathy and determine whether they are predictive of disease severity and prognosis. Materials and Methods: Prospectively enrolled participants (July 2013 to September 2016) underwent cine and late gadolinium enhancement (LGE) cardiac MRI and T1 mapping with a precontrast (native) or postcontrast modified Look-Locker sequence. The native T1 and ECV values were measured among subgroups that were based on disease severity (indeterminate, Chagas cardiomyopathy with preserved ejection fraction [CCpEF], Chagas cardiomyopathy with midrange ejection fraction [CCmrEF], and Chagas cardiomyopathy with reduced ejection fraction [CCrEF]). Cox proportional hazards regression and the Akaike information criterion were used to determine predictors of major cardiovascular events (cardioverter defibrillator implant, heart transplant, or death). Results: In 107 participants (90 participants with Chagas disease [mean age ± SD, 55 years ± 11; 49 men] and 17 age- and sex-matched control participants), the left ventricular (LV) ejection fraction and the extent of focal and diffuse or interstitial fibrosis were correlated with disease severity. Participants with CCmrEF and participants with CCrEF showed significantly higher global native T1 and ECV values than participants in the indeterminate, CCpEF, and control groups (T1: 1072 msec ± 34 and 1073 msec ± 63 vs 1010 msec ± 41, 1005 msec ± 69, and 999 msec ± 46; ECV: 35.5% ± 3.6 and 35.0% ± 5.4 vs 25.3% ± 3.5, 28.2% ± 4.9, and 25.2% ± 2.2; both P < .001). Remote (LGE-negative areas) native T1 and ECV values were also higher (T1: 1056 msec ± 32 and 1071 msec ± 55 vs 1008 msec ± 41, 989 msec ± 96, and 999 msec ± 46; ECV: 30.2% ± 4.7 and 30.8% ± 7.4 vs 25.1% ± 3.5, 25.1% ± 3.7, and 25.0% ± 2.2; both P < .001). Abnormal remote ECV values (>30%) occurred in 12% of participants in the indeterminate group, which increased with disease severity. Nineteen combined outcomes were observed (median follow-up time: 43 months), and a remote native T1 value greater than 1100 msec was independently predictive of combined outcomes (hazard ratio, 12 [95% CI: 4.1, 34.2]; P < .001). Conclusion: Myocardial native T1 and ECV values were correlated with Chagas disease severity and may serve as markers of myocardial involvement in Chagas cardiomyopathy that precede LGE and LV dysfunction.Keywords: MRI, Cardiac, Heart, Imaging Sequences, Chagas Cardiomyopathy Supplemental material is available for this article. © RSNA, 2023.

Assessment of child safety on bicycles in baby carriers - The importance of evaluating both head and neck injuries.

INTRODUCTION: The paper addresses an important accident type that involves children in bicycle seats - the bicycle fall over. It is a significant and common accident type and many parents have been reported to experience this type of "close call." The fall over occurs at low velocities and even while a bicycle is standing still, and may result from a split-second lack of attention on behalf of the accompanying adult (e.g. while loading groceries, i.e. while not being exposed to traffic per se). Moreover, irrespective of the low velocities involved, the trauma that may result to the head of the child is considerable and may be life-threatening, as shown in the study. METHOD: The paper presents two methods to address this accident scenario in a quantitative way: in-situ accelerometer-based measurement and numerical modeling approaches. It is shown that the methods produce consistent results under the prerequisites of the study. They are therefore promising methods to be used in the study of this type of accident. RESULTS: The importanance of the protective role of a child helmet is without discussion in everyday traffic.However, this study draws attention to one particular effect observed in this accident type: that the geometry of the helmet may at times expose the child's head to considerably larger forces, by having contact with the ground. The study also highlights the importance of neck bending injuries during bicycle fall over, which are often neglected in the safety assessment - not only for children in bicycle seats. The study concludes that considering only head acceleration may lead to biased conclusions about using helmets as protective devices.

Extracellular Vesicles and Infection: From Hijacked Machinery to Therapeutic Tools.

Extracellular vesicles (EVs) comprise a broad range of secreted cell-derived membrane vesicles. Beyond their more well-characterized role in cell communication, in recent years, EVs have also been shown to play important roles during infection. Viruses can hijack the biogenesis of exosomes (which are small EVs) to promote viral spreading. Additionally, these exosomes are also important mediators in inflammation and immune responses during both bacterial and viral infections. This review summarizes these mechanisms while also describing the impact of bacterial EVs in regulating immune responses. Finally, the review also focuses on the potential and challenges of using EVs, in particular, to tackle infectious diseases.

Cork Porous Biocomposites with Polyurethane Matrix Modified with Polyol Based on Used Cooking Oil.

Renewable materials are materials that are replenished naturally and can be used again and again. These materials include things such as bamboo, cork, hemp, and recycled plastic. The use of renewable components helps to reduce the dependence on petrochemical resources and reduce waste. Adopting these materials in various industries such as construction, packaging, and textiles can lead to a more sustainable future and decrease the carbon footprint. The presented research describes new porous polyurethane biocomposites based on used cooking oil polyol (50 per hundred polyol-php) modified with cork (3, 6, 9, and 12 php). The research described here demonstrated that it is possible to replace some petrochemical raw materials with raw materials of renewable origin. This was achieved by replacing one of the petrochemical components used for the synthesis of the polyurethane matrix with a waste vegetable oil component. The modified foams were analyzed in terms of their apparent density, coefficient of thermal conductivity, compressive strength at 10% of deformation, brittleness, short-term water absorption, thermal stability, and water vapor permeability, while their morphology was examined using scanning electron microscopy and the content of closed cells. After the successful introduction of a bio-filler, it was found that the thermal insulation properties of the modified biomaterials were comparable to those of the reference material. It was concluded that it is possible to replace some petrochemical raw materials with raw materials of renewable origin.