viernes, 15 de noviembre de 2024

 El chagas continúa siendo un padecimiento endémico en la region, y en nuestro país los datos son preocupantes. La importancia de utilizar Test Rápidos para su Diagnóstico.

Con 1,6 millones de personas infectadas, Argentina es el país con más casos de Chagas a nivel mundial. Lo inesperado: más de la mitad de estos casos están en la Ciudad y Provincia de Buenos Aires.

A pesar de estas cifras que ya encienden las alarmas, expertos consultados por diario Clarín declaran que existe un subregistro de casos: hay infectados que no lo saben y otros que, incluso enterados, no reciben el seguimiento médico adecuado.

Nuestro país está primero en números absolutos por “cuestiones ambientales y ecológicas” que propician que el vector se reproduzca pero también “por las condiciones de vulnerabilidad en las que vive parte de la población que no tiene acceso a la salud y, por lo tanto, no se testea ni se trata”, explica Marcelo Abril, biólogo y director ejecutivo de la Fundación Mundo Sano

Asociada a la pobreza extrema y endémica en 21 países de América Latina, la enfermedad de Chagas afecta aproximadamente a 8 millones de personas en el mundo, de las cuales 1,2 millones son mujeres en edad fértil. Según la Organización Mundial de la Salud, más del 95 por ciento de ellos desconocen su estado. 

Chagas-  Zonas afectadas en Argentina

Se la solía asociar con zonas rurales del norte del país y con la presencia de su vector: las vinchucas o chinches. Sin embargo, desde hace tiempo que dejó de ser así.  La mayoría de los infectados de Chagas están en las grandes ciudades: Ciudad de Buenos Aires, Gran Buenos Aires, Rosario y Córdoba.

En una serie de notas publicadas por Infobae, el biólogo Diego Weinberg integrante de la Fundación Mundo Sano, declara: “Seguir con la idea de que se trata de una enfermedad vinculada al rancho de adobe, la vinchuca y el monte chaqueño es una visión recortada. Es cierto que la transmisión vectorial se localiza en determinadas provincias –Chaco, Santiago del Estero, Formosa, San Juan, Catamarca–, pero los enfermos de chagas están distribuidos en todo el país y en el resto del mundo. El problema no es el vector, sino las personas enfermas.

También explicó que, “si bien, en general, se asocia la enfermedad con la presencia de vinchucas, en la actualidad y como consecuencia de los progresos en el control vectorial y transfusional, la transmisión de madre a hijo es uno de los modos de contagio más importante.”

Además, “existe la transmisión por donación sanguínea o de órganos, pero esto ya es poco probable. En consecuencia, aunque está clara la necesidad de control vectorial, sin dudas, lo fundamental es garantizar el acceso al diagnóstico y tratamiento de la mujer en edad fértil, tarea importante que no se está realizando de la mejor manera”, dijo.

*1Fuentes consultadas: Clarín, Infobae, Abbott. Droguería Dimat.

martes, 15 de octubre de 2024

Influenza tipo B

 

Abstract

Introduction: Since the 80s two lineages of type B viruses are co - circulating in the world. Antigenic differences between them are important and it leads to lack of cross-reactivity. The impact on the burden of disease due to influenza B virus, poor foresight in estimating which of the two lineages of B viruses circulate in the season, and the consequent lack of immunity in case of including the wrong strain make that the availability of the quadrivalent vaccine is very useful. The aim of this paper is to analyze the past influenza seasons in Spain to assess the burden of disease, divergence between the vaccine strain and the circulating B and viral characteristics associated with type B in each seasonal epidemic.


Material and methods: Review of all reports issued by the Influenza Surveillance System in Spain since the 2003-2004 season to 2012-2013.


Results: Over the past influenza seasons, although type A was present mostly, circulation of influenza B virus in each season was observed, even being co - dominant in some of them. In a high number of seasons the divergence between the vaccine strain and the circulating strain lineage has been observed


Conclusions: The protective effect of influenza vaccine has varied depending on the type / subtype of influenza virus studied. The vaccine effectiveness against influenza infection by influenza B virus has varied greatly depending on the season analyzed.*1


Abstract in English, Spanish

La miocarditis es una enfermedad inflamatoria del miocardio. Las infecciones virales son la causa más común, aunque también puede deberse a reacciones de hipersensibilidad y de etiología autoinmunitaria, entre otras. El espectro clínico de la enfermedad es variado y comprende desde un curso asintomático, seguido de dolor torácico, arritmias y falla cardiaca aguda, hasta un cuadro fulminante. El término 'fulminante' se refiere al desarrollo de un shock cardiogénico con necesidad de soporte vasopresor e inotrópico o dispositivos de asistencia circulatoria, ya sea oxigenación por membrana extracorpórea o balón de contrapulsación intraaórtico. Cerca del 10 % de los casos de falla cardiaca por miocarditis corresponde a miocarditis fulminante. La miocarditis por influenza se considera una condición infrecuente; no obstante, su incidencia ha aumentado desde el 2009 a raíz de la pandemia de influenza por el virus AH1N1. Por su parte, la miocarditis por influenza de tipo B sigue siendo una condición infrecuente. Se describen aquí dos casos confirmados de miocarditis fulminante por el virus de la influenza B atendidos en un centro cardiovascular, que requirieron dispositivos de asistencia circulatoria mecánica.


Keywords: Myocarditis; influenza B virus; adult; shock; cardiogenic; intra-aortic balloon pumping; extracorporeal membrane oxygenation; assisted circulation. *2


Abstract

Results of investigations carried out during an outbreak of influenza occurred in January 1981 in a School of Milan are reported and discussed. A total of 9 type A (H1N1) influenza virus strains, antigenically intermediate between A/USSR/90/77 and A/Brazil/11/78 variants, and 2 type B influenza virus strains, antigenically intermediate between B/Hong Kong/8/73 and B/Singapore/222/79 variants, have been isolated. In one case both epidemic strains have been simultaneously detected. From the results of type-specific complement-fixing antibody titration it appears that an influenza virus infection occurred in 64% of the 300 subjects serologically examined. In 43% of the cases type A strain was involved, in 12% type B strain and in 9% both serotypes. Judging from the data of school absenteeism it seems that infections by type A virus were more severe than those by type B virus. Finally, because a group of pupils attending the school had been vaccinated in December 1978, it has been demonstrated that the rate of type A presumptive infections was correlated to the hemagglutination-inhibiting antibody titers attained after vaccination.*3

Abstract

We report the case of a 6-year-old girl who presented with encephalitis during type B influenza. The clinical picture was characterized by an alteration of the state of consciousness associated with focal neurological signs with electroencephalographic changes and brain MRI. Clinical improvement was rapid and without neurological outcomes. The clinical characteristics, the pathogenic mechanisms, the prognosis and the therapy of neuroinfluenza cases are described.*4



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1*Burden of influenza virus type B and mismatch with the flu vaccine in Spain]

[Article in Spanish]

Jose Ma Eiros-Bouza et al. Rev Esp Quimioter. 2015 Feb.

*2Fulminant myocarditis due to the influenza B virus in adults: Report of two cases and literature review

[Article in English, Spanish]

Edwin Silva et al. Biomedica. 2019.

Free article

*3An influenza outbreak of type A and type B influenza viruses]

[Article in Italian]

M L Profeta et al. Boll Ist Sieroter Milan. 1983.

*4Encephalitis by type B influenza: a pediatric clinical case and literature review]

[Article in Italian]

Adriana Fumarola et al. Recenti Prog Med. 2019 Jan.


viernes, 16 de agosto de 2024

Oropouche virus

 Abstract

The Oropouche virus is an important arthropod-borne virus in the Peribunyaviridae family that can cause febrile illnesses, and it is widely distributed in tropical regions such as Central and South America. Since the virus was first identified, a large number of related cases are reported every year. No deaths have been reported to date, however, the virus can cause systemic infections, including the nervous and blood systems, leading to serious complications. The transmission of Oropouche virus occurs through both urban and sylvatic cycles, with the anthropophilic biting midge Culicoides paraensis serving as the primary vector in urban areas. Direct human-to-human transmission of Oropouche virus has not been observed. Oropouche virus consists of three segments, and the proteins encoded by the different segments enables the virus to replicate efficiently in the host and to resist the host's immune response. Phylogenetic analyses showed that Oropouche virus sequences are geographically distinct and have closer homologies with Iquitos virus and Perdoes virus, which belong to the family Peribunyaviridae. Despite the enormous threat it poses to public health, there are currently no licensed vaccines or specific antiviral treatments for the disease it causes. Recent studies have utilised imJatobal virusmunoinformatics approaches to develop epitope-based peptide vaccines, which have laid the groundwork for the clinical use of vaccines. The present review focuses on the structure, epidemiology, immunity and phylogeny of Oropouche virus, as well as the progress of vaccine development, thereby attracting wider attention and research, particularly with regard to potential vaccine programs.


Keywords: Epidemiology; Evolutionary; Immunity; Oropouche virus; Structure; Vaccine development.


Copyright © 2024. Published by Elsevier B.V.


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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.*1

Abstract

AbstractOropouche virus (OROV) is an important cause of arboviral illness in Latin American countries, more specifically in the Amazon region of Brazil, Venezuela and Peru, as well as in other countries such as Panama. In the past decades, the clinical, epidemiological, pathological, and molecular aspects of OROV have been published and provide the basis for a better understanding of this important human pathogen. Here, we describe the milestones in a comprehensive review of OROV epidemiology, pathogenesis, and molecular biology, including a description of the first isolation of the virus, the outbreaks during the past six decades, clinical aspects of OROV infection, diagnostic methods, genome and genetic traits, evolution, and viral dispersal.


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Conflict of interest statement

Disclosure: Jorge Fernando Travassos da Rosa is a Senior Researcher of the Department of Arboviruses and was the Director of the institution between 1988 and 2002. *2

Abstract

This perspective underscores the rising challenge posed by emerging diseases against the backdrop of modern advancements in global public health understanding. It particularly highlights the emergence of the Oropouche virus (OROV) as a significant global threat, detailing its transmission dynamics, symptoms, and epidemiological impact, with a focus on its historical and current manifestations. It further delves into the molecular aspects of OROV, elucidating its unique characteristics, lack of structural similarity with other arboviruses, and the limited progress in medicinal chemistry research. Still, it highlights notable studies on potential antiviral agents and the challenges in drug development, emphasizing the need for innovative approaches such as structure-based drug design (SBDD) and drug repurposing. Finally, it concludes with a call to action, urging increased attention and research focus on OROV to prevent potential future pandemics fueled by viral mutations.


Keywords: Drug design; Drug repurposing; Endonuclease; Medicinal chemistry; Oropouche.


Copyright © 2024 Elsevier Ltd. All rights reserved.


PubMed Disclaimer


Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.*3


Figures



*1Oropouche virus: A neglected global arboviral threat

Yuli Zhang et al. Virus Res. 2024 Mar.

*2Oropouche Virus: Clinical, Epidemiological, and Molecular Aspects of a Neglected Orthobunyavirus

Jorge Fernando Travassos da Rosa et al. Am J Trop Med Hyg. 2017 May.

*3Oropouche virus - The "Newest" invisible public enemy?

Edeildo Ferreira da Silva-Júnior. Bioorg Med Chem. 2024.


Viruela del Mono

 Viruela del Mono

Published online: July 2022.


Esta hoja trata de la exposición a la viruela del mono en el embarazo y durante la lactancia. Esta información no debe usarse como un sustituto de la atención médica o los consejos de su proveedor de atención de salud.


¿Qué es la viruela del mono (o viruela del simio o viruela símica)?


La viruela del mono es una enfermedad causada por un virus. El virus pertenece a un grupo de virus llamados orthopoxvirus.


Los síntomas de la viruela del mono pueden comenzar de 5 a 21 días después de haber estado expuesto al virus, pero la mayoría de las personas comienzan a tener síntomas en 7 a 14 días. Los primeros síntomas que aparecen pueden ser: fiebre, dolor de cabeza, dolores musculares, dolor de espalda, ganglios linfáticos ("glándulas") inflamados, escalofríos y agotamiento (estar muy cansado). En unos pocos días, aparece un sarpullido en el cuerpo, que a menudo comienza cerca de los genitales o en la cara. El sarpullido causa bultos y llagas que pueden causar picazón y dolor y que gradualmente se convierten en costras que se caen. En la mayoría de las personas, la enfermedad dura de 2 a 4 semanas antes de desaparecer por sí sola. En algunas personas, la viruela del mono puede causar enfermedad más grave e incluso la muerte. No hay cura para la viruela del mono, pero ciertos medicamentos (llamados antivirales) pueden ayudar a controlar los síntomas.


Hay dos tipos de vacunas disponibles contra la viruela del mono / viruela para las personas que han estado expuestas a un orthopoxvirus o para ciertas personas con mayor riesgo de exposición. Puede leer más sobre estas vacunas en las hojas informativas de MotherToBaby en https://mothertobaby.org/es/hojas-informativas/vacuna-contra-viruela-del-mono-viruela-jynneos/pdf/ y https://mothertobaby.org/es/hojas-informativas/vacuna-contra-viruela-del-mono-viruela-acam2000/pdf/.


¿Cómo se propaga la viruela del mono?


La viruela del mono se propaga de persona a persona a través de líquidos del cuerpo, incluido el contacto directo con las llagas o costras de la piel de una persona infectada, de los líquidos que salen de estas llagas (como en la ropa o la ropa de cama), o a través de la saliva y las gotitas respiratorias (como besarse o estar en contacto cercano con alguien con viruela del mono cuando respiran, hablan, tosen, o estornudan). El virus también puede pasar de una persona que está embarazada a su bebé en desarrollo. No se sabe en este momento si la viruela del mono puede propagarse a través del semen o los líquidos vaginales, pero el contacto cercano durante las relaciones sexuales puede propagar el virus..*1

Esta hoja trata de la exposición a la vacuna contra viruela de mono / viruela JYNNEOS™ en el embarazo y durante la lactancia. Esta información no debe usarse como un sustituto de la atención médica o los consejos de su proveedor de atención de salud.


¿Qué es mpox (viruela del mono)?


Mpox es una enfermedad causada por un virus. El virus pertenece a un grupo de virus llamados orthopoxvirus. El virus se propaga de persona a persona a través de los fluidos corporales. El virus también puede pasar de una persona que está embarazada a su bebé en desarrollo. Para obtener más información sobre mpox, consulte la hoja informativa de MotherToBaby en https://mothertobaby.org/es/hojas-informativas/viruela-del-mono/.


¿Qué es la vacuna contra viruela de mono / viruela JYNNEOS™?


La vacuna JYNNEOS™ (también conocida como Imvamune® o Imvanex®) ayuda a proteger contra mpox, la viruela, y otras enfermedades causadas por los ortopoxvirus. JYNNEOS™ no contiene virus vivo que pueda causar mpox o viruela. En cambio, contiene una forma debilitada de un virus relacionado, que no puede hacer copias de sí mismo (replicarse) en el cuerpo para causar enfermedades. Recibir JYNNEOS™ ayuda al sistema inmunológico del cuerpo a aprender cómo protegerse (producir anticuerpos) contra los ortorpoxvirus en general.


JYNNEOS™ se puede administrar antes o después de la exposición a un orthopoxvirus para ayudar a prevenir la enfermedad o reducir los síntomas. La mayoría de las personas requieren 2 dosis (inyecciones) administradas con 4 semanas de diferencia. Según los Centros para el Control y la Prevención de Enfermedades (CDC), JYNNEOS™ se puede administrar al mismo tiempo que otras vacunas. Cuando existe la posibilidad de estar expuesto al virus que causa mpox u otro orthopoxvirus, es importante continuar tomando otros pasos para evitar la exposición incluso después de ser vacunado. CDC tiene información de prevención aquí (en inglés): https://www.cdc.gov/poxvirus/monkeypox/prevention.html.


ACAM2000® es otro tipo de vacuna contra la viruela del mono/viruela disponible en los Estados Unidos. Puede leer más sobre ACAM2000® en la hoja informativa de MotherToBaby https://mothertobaby.org/es/hojas-informativas/vacuna-contra-viruela-del-mono-viruela-acam2000/.*2


*1Centers for Disease Control and Prevention. 2022. Clinical considerations for monkeypox in people who are pregnant or breastfeeding. Available at URL: https://www​.cdc.gov/poxvirus​/monkeypox/clinicians/pregnancy​.html

Centers for Disease Control and Prevention. 2022. Monkeypox. Available at URL: https://www​.cdc.gov/poxvirus​/monkeypox/index.html

Jamieson DJ, et al. 2004. The role of the obstetrician–gynecologist in emerging infectious diseases: monkeypox and pregnancy. Obstetrics & Gynecology 103(4):754-756. [PubMed]

Khalil A, et al. 2022. Monkeypox and pregnancy: what do obstetricians need to know? Ultrasound Obstet Gynecol. Published online June 2, 2022. DOI: https://doi​.org/10.1002/uog.24968. [PubMed]

Kisalu NK and Mokili JL. 2017. Toward understanding the outcomes of monkeypox infection in human pregnancy. J Infectious Diseases 216(7):795–797. [PMC free article] [PubMed]

Mbala PK, et al. 2017. Maternal and fetal outcomes among pregnant women with human monkeypox infection in the Democratic Republic of Congo. J Infectious Diseases 216(7):824-828. [PubMed]

Nishiura H. 2009. Maternal outcomes in pregnancy with smallpox: epidemiologic investigations of case fatality, miscarriage and premature birth based on previous outbreaks. In: Canfield RN, ed. Infectious Pregnancy Complications. Nova Science Publishers, Inc.; 2009:407-420.

*2Centers for Disease Control and Prevention. 2022. Clinical considerations for monkeypox in people who are pregnant or breastfeeding. Available at URL: https://www​.cdc.gov/poxvirus​/monkeypox/clinicians/pregnancy​.html

Centers for Disease Control and Prevention. 2022. Considerations for monkeypox vaccination. Available at URL: https://www​.cdc.gov/poxvirus​/monkeypox/considerations-for-monkeypox-vaccination​.html.

Vaccine Information Statement: Smallpox/monkeypox vaccine (JYNNEOS™): what you need to know. Revised 06/2022. Available at URL: https://www​.cdc.gov/vaccines​/hcp/vis/vis-statements​/smallpox-monkeypox.pdf.

JYNNEOS Package Insert. Revised 06/2021. Available at URL: https://www​.fda.gov/media​/131078/download.

Meaney-Delman, DM, et al. 2022. A primer on monkeypox virus for obstetrician–gynecologists, Obstetrics & Gynecology. Published online July 11, 2022. DOI: https://doi​.org/10.1097/AOG​.0000000000004909. [PMC free article] [PubMed]

Rao AK, et al. 2022. Use of JYNNEOS (smallpox and monkeypox vaccine, live, nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: recommendations of the advisory committee on immunization practices — United States, 2022. MMWR Morb Mortal Wkly Rep 2022;71:734–742. [PMC free article] [PubMed]





martes, 6 de agosto de 2024

Enfermedad de Fabry

 Abstract

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene leading to deficient α-galactosidase A activity, glycosphingolipid accumulation, and life-threatening complications. Phenotypes vary from the "classic" phenotype, with pediatric onset and multi-organ involvement, to later-onset, a predominantly cardiac phenotype. Manifestations are diverse in female patients in part due to variations in residual enzyme activity and X chromosome inactivation patterns. Enzyme replacement therapy (ERT) and adjunctive treatments can provide significant clinical benefit. However, much of the current literature reports outcomes after late initiation of ERT, once substantial organ damage has already occurred. Updated monitoring and treatment guidelines for pediatric patients with Fabry disease have recently been published. Expert physician panels were convened to develop updated, specific guidelines for adult patients. Management of adult patients depends on 1) a personalized approach to care, reflecting the natural history of the specific disease phenotype; 2) comprehensive evaluation of disease involvement prior to ERT initiation; 3) early ERT initiation; 4) thorough routine monitoring for evidence of organ involvement in non-classic asymptomatic patients and response to therapy in treated patients; 5) use of adjuvant treatments for specific disease manifestations; and 6) management by an experienced multidisciplinary team.


Keywords: Diagnosis; Fabry disease; Management; Mutation; Treatment.


Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.*1

Abstract

Background: Fabry disease, an X-linked lysosomal storage disorder, causes intracellular accumulation of glycosphingolipids leading to progressive renal, cardiovascular, and cerebrovascular disease, and premature death.


Methods: This longitudinal Fabry Registry study analyzed data from patients with Fabry disease to determine the incidence and type of severe clinical events following initiation of enzyme replacement therapy (ERT) with agalsidase beta, as well as risk factors associated with occurrence of these events. Severe events assessed included chronic dialysis, renal transplantation, cardiac events, stroke, and death.


Results: The analyses included 969 male and 442 female Fabry patients. The mean age at first agalsidase beta infusion was 35 and 44, and median treatment follow-up 4.3years and 3.2years, respectively. Among males, cardiac events were the most common on-ERT events, followed by renal, stroke, and non-cardiac death. Among females, cardiac events were also most common followed by stroke and renal events. Patients with on-ERT events had significantly more advanced cardiac and renal disease at baseline as compared with patients without on-ERT events. Severe events were also associated with older age at ERT initiation (males and females), a history of pre-ERT events (females; approaching statistical significance in males), and a higher urinary protein/creatinine ratio (females). Approximately 65% of patients with pre-ERT events did not experience subsequent on-ERT events. Of patients without pre-ERT events, most (84% of males, 92% of females) remained event-free.


Conclusions: Patients with on-ERT severe events had more advanced Fabry organ involvement at baseline than those without such events and patients who initiated ERT at a younger age had less residual risk of on-ERT events. The observed patterns of residual risk may aid clinicians in multidisciplinary monitoring of male and female patients with Fabry disease receiving ERT, and in determining the need for administration of adjunctive therapies.


Keywords: Agalsidase beta; Fabry disease; Risk factors; Severe clinical events.


Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.*2


Abstract

Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3-0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C-based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-β dose-reduction and switch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used.


Keywords: Fabry’s disease; chronic kidney disease; creatinine clearance; cystatin C clearance; enzyme; outcomes; replacement therapy.


Copyright © 2016 by the American Society of Nephrology. *3


Abstract

Because of the shortage of agalsidase-beta in 2009, many patients with Fabry disease were treated with lower doses or were switched to agalsidase-alfa. This observational study assessed end-organ damage and clinical symptoms during dose reduction or switch to agalsidase-alfa. A total of 105 adult patients with Fabry disease who had received agalsidase-beta (1.0 mg/kg body weight) for ≥1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=38), receive a reduced dose of 0.3-0.5 mg/kg (dose-reduction group, n=29), or switch to 0.2 mg/kg agalsidase-alfa (switch group) and were followed prospectively for 1 year. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD); changes in cardiac, renal, and neurologic function; and Fabry-related symptoms (neuropathic pain, hypohidrosis, diarrhea, and disease severity scores). Organ function and Fabry-related symptoms remained stable in the regular-dose group. In contrast, estimated GFR decreased by about 3 ml/min per 1.73 m(2) (P=0.01) in the dose-reduction group, and the median albumin-to-creatinine ratio increased from 114 (0-606) mg/g to 216 (0-2062) mg/g (P=0.03) in the switch group. Furthermore, mean Mainz Severity Score Index scores and frequencies of pain attacks, chronic pain, gastrointestinal pain, and diarrhea increased significantly in the dose-reduction and switch groups. In conclusion, patients receiving regular agalsidase-beta dose had a stable disease course, but dose reduction led to worsening of renal function and symptoms. Switching to agalsidase-alfa is safe, but microalbuminuria may progress and Fabry-related symptoms may deteriorate.*4

Abstract

Background: Fabry patients on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in estimated glomerular filtration rate (eGFR) and an increase of the Mainz Severity Score Index.


Methods: In this prospective observational study, we assessed end-organ damage and clinical symptoms in 112 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, who were (i) non-randomly assigned to continue this treatment regime (regular-dose group, n = 37); (ii) received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n = 38); or (iii) were re-switched to agalsidase-beta after receiving agalsidase-alfa for at least 12 months (re-switch group, n = 37) with a median follow-up of 53 (38-57) months.


Results: eGFR of patients in the regular-dose group remained stable. Patients in the switch group showed an annual eGFR loss of - 4.6 ± 9.1 mL/min/1.73 m2 (P < 0.05). Patients in the re-switch group also had an eGFR loss of - 2.2 ± 4.4 mL/min/1.73 m2 after re-switch to agalsidase-beta, but to a lower degree compared with the switch group (P < 0.05). Patients in the re-switch group suffered less frequently from diarrhoea (relative risk 0.42; 95% confidence interval 0.19-0.93; P = 0.02). Lyso-Gb3 remained stable in the switch (P = 0.97) and the regular-dose (P = 0.48) groups, but decreased in the re-switch group after change of the therapy regimen (P < 0.05).


Conclusions: After switch to agalsidase-alfa, Fabry patients experienced a continuous decline in eGFR, while this decline was attenuated in patients who were re-switched to agalsidase-beta. Decreasing lyso-Gb3 levels may indicate a better treatment response in the latter group.*5


Abstract

Background: Patients with Fabry disease (FD) on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in chronic kidney disease epidemiology collaboration-based estimated glomerular filtration rate (eGFR) and a worsened plasma lyso-Gb3 decrease. Hence, the most effective dose is still a matter of debate.


Methods: In this prospective observational study, we assessed end-organ damage and clinical symptoms in 78 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, which were assigned to continue this treatment (agalsidase-beta, regular-dose group, n=17); received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n=22); or were re-switched to agalsidase-beta after receiving agalsidase-alfa for 12 months (re-switch group, n=39) with a follow-up of 88±25 months.


Results: No differences for clinical events were observed for all groups. Patients within the re-switch group started with the worst eGFR values at baseline (p=0.0217). Overall, eGFR values remained stable in the regular-dose group (p=0.1052) and decreased significantly in the re-switch and switch groups (p<0.0001 and p=0.0052, respectively). However, in all groups males presented with an annual loss of eGFR by -2.9, -2.5 and -3.9 mL/min/1.73 m² (regular-dose, re-switch, switch groups, all p<0.05). In females, eGFR decreased significantly only in the re-switch group by -2.9 mL/min/1.73 m² per year (p<0.01). Lyso-Gb3 decreased in the re-switch group after a change back to agalsidase-beta (p<0.05).


Conclusions: Our data suggest that a re-switch to high dosage of agalsidase results in a better biochemical response, but not in a significant renal amelioration especially in classical males.


Keywords: genetics; renal medicine.


© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Conflict of interest statement

Competing interests: ML and TD received speaker honoraria from Amicus Theraputics, Sanofi Genzyme and Shire/Takeda. S-MB has received speaker honoraria from Shire/Takeda. CW, SC-K and EB received speaker and advisory board honoraria from Amicus Therapeutics, Greenovation, Sanofi Genzyme and Shire/Takeda. PN received speaker and advisory board honoraria from Amicus Therapeutics, Greenovation, Idorsia, Sanofi Genzyme and Shire/Takeda. CW is a member of the Fabry Registry European Board of Advisors and received travel assistance and speaker honoraria. Research grants were given to the institutions (Würzburg and Münster) by Amicus Therapeutics, Sanofi Genzyme and Shire/Takeda. *6


*1Fabry disease revisited: Management and treatment recommendations for adult patients

Alberto Ortiz et al. Mol Genet Metab. 2018 Apr.

Free article

*2Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry

Robert J Hopkin et al. Mol Genet Metab. 2016 Sep.

Free article

*3Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch-2-Year Follow-Up

Malte Lenders et al. J Am Soc Nephrol. 2016 Mar.

*4Patients with Fabry disease after enzyme replacement therapy dose reduction versus treatment switch

Frank Weidemann et al. J Am Soc Nephrol. 2014 Apr.

*5Fabry disease under enzyme replacement therapy-new insights in efficacy of different dosages

Johannes Krämer et al. Nephrol Dial Transplant. 2018.

*6Treatment switch in Fabry disease- a matter of dose?

Malte Lenders et al. J Med Genet. 2021 May.


jueves, 25 de julio de 2024

Bloqueo AV completo durante el ejercicio

 Abstract

Exercise-induced atrioventricular (AV) block in patients with normal electrocardiogram at rest is uncommon. We report the clinical features of two patients with AV block during treadmill test. The first patient was a woman of 54 years of age with presyncope on exercise. She developed complete AV block during exercise testing without evidence of ischemic myocardial disease. Electrophysiologic study documented distal AV block. The second patient was a man 31 years old who developed angina and third-degree AV block with depression of ST segment during treadmill test. Myocardial perfusion study suggested ischemic heart disease. He received anti-ischemic drugs with improvement of symptoms. A control exercise testing demonstrated normal AV conduction and electrophysiologic study was normal. In the first case, exercise AV block was probably due to abnormal His Purkinje conduction system refractoriness to autonomic modulation, while in second case AV block was secondary to ischemic heart disease. Third-degree AV block at exercise can be present in patients without conduction system abnormalities at rest. Exercise-induced infra-Hisian AV block must be treated with pacing until ischemic heart disease has been ruled out. *1

Abstract

In this report we describe the case of a 56-year-old woman with normal 1:1 AV conduction at rest who developed 2:1 AV block during treadmill exercise testing. Electrophysiological study documented 2:1 AV block proximal to the His bundle with reappearance of 1:1 AV conduction at a higher pacing atrial rate. A gap phenomenon involving a proximal and distal part of the AV node may be a likely explanation of paradoxical AV conduction in our case.*2


Abstract

Exercise-induced atrioventricular block in patients with normal atrioventricular conduction at rest is uncommon. Electrophysiologic studies have documented block distal to the atrioventricular node in these patients. Implantation of a permanent pacemaker is recommended because of a high incidence of subsequent symptomatic block. We report three symptomatic patients with exercise-induced atrioventricular block. Two patients showed a bundle branch block in the baseline electrocardiogram, suggesting a distal location of the block. In the remainder, with a normal QRS, the electrophysiologic study revealed AV block within the His bundle in response to atrial pacing.*3

Abstract

Three patients with 1:1 atrio-ventricular conduction at rest developed fixed 2nd or 3rd degree atrio-ventricular block during exercise testing. In all patients electrophysiologic study documented block distal to the atrioventricular node. The exercise induced block probably occurred because of increased atrial rate and abnormal refractoriness of the His-Purkinje conduction system. These findings suggest that high degree atrioventricular block appearing during exercise reflects conduction disease of the His-Purkinje system rather than of the atrio-ventricular node, even in absence of bundle branch block. These patients should be considered for permanent cardiac pacing.*4

Abstract

Four personal cases of exercise-induced conduction defects occurring during stress testing are reported. The significance of these changes is discussed in the light of the authors' observations and of the cases published in the literature. The development of atrioventricular block is usually related to pre-existing disease of the conduction system, whilst left anterior or posterior hemiblock is usually due to transient ischaemia related to significant stenosis of the coronary artery responsible for the vascularisation of the relevant bundle branch (usually a proximal stenosis of the left anterior descending artery). Complete left bundle branch block may be due to a number of conditions (including chronic ischaemic heart disease).*5


*1 A complete atrioventricular block during exertion]

[Article in Spanish]

A Medeiros et al. Arch Inst Cardiol Mex. 1999 May-Jun.

*2Exercise-induced second-degree atrioventricular block

Loukas K Pappas et al. Int J Cardiol. 2006.

*3Exercise-induced atrioventricular block

[Article in Spanish]

J M Barbero et al. Rev Esp Cardiol. 1993

*4 Intermittent atrio-ventricular block induced by exertion. Description of 3 cases]

[Article in Italian]

M Barra et al. G Ital Cardiol. 1985 Nov.

*5 Significance of exercise-induced arrhythmias]

[Article in French]

D M Marcadet et al. Arch Mal Coeur Vaiss. 1988 Aug.

lunes, 22 de julio de 2024

Nuevas indicaciones para marcapaseo

 Abstract

New indications have recently appeared for cardiac pacing with haemodynamic and antiarrhythmic objectives without any symptomatic bradycardia. The best documented indication, though relatively rare, is stimulation of obstructive hypertrophic cardiomyopathy; initially reserved for cases with favorable results of an acute haemodynamic test, it is now used in other cases without this criterion; hypertrophic cardiomyopathy without permanent obstruction, atrial fibrillation or left bundle branch block. The improvement observed during follow-up is always greater as a real remodeling of the myocardium seems to occur with ventricular dilatation and/or septal thinning. However, the position of the atrial, and above all, of the ventricular pacing catheters is critical as is regulation of the pacemaker which should allow complete ventricular capture with an AV delay allowing good filling. The follow-up of these patients must therefore be regular and the effects on longevity are unknown. DDD pacing has also been proposed in dilated cardiomyopathy. The results are contradictory and only very selected cases with left bundle branch block and long PR interval seem justified with, again, optimisation of the pacing sites with high septal or biventricular stimulation. Recurrent atrial tachycardia, special algorithms preventing extrasystoles have been tried with variable results. In cases with inter-atrial block, atrial resynchronisation by bi-atrial stimulation has been assessed with promising results but many technical problems remain unsolved.*1

Abstract

In view of the large number of inappropriate shocks observed in patients with implanted defibrillators, improved detection of ventricular arrhythmias has become a major objective. The addition of an atrial catheter has been proposed to improve discrimination between ventricular and non-ventricular arrhythmias. Besides this function, the additional catheter could be used for DDD pacing without risk of interaction between the pacemaker and defibrillator. The authors report their initial experience in 16 patients implanted with a DDD pacemaker. The indication was resuscitated sudden death (N = 5) or ventricular tachycardia (N = 11). The choice of a DDD defibrillator was justified by a bradycardia (N = 9), haemodynamic factors (N = 4) or supraventricular tachycardia (N = 3). The devices used were the Defender 9001 (ELA Medical SA, France, N = 3), the Ventak AV 1810 and the Ventak AV II DR 1821 (Guidant/CPI, Inc. USA, N = 11 and N = 2 respectively). There were three immediate complications. After 2 to 29 months' follow-up, 5 patients had received appropriate treatment by their devices. Five patients had inappropriate shocks : one patient received a shock triggered by electrical interference, two others had no active sensing algorithme when the shocks were delivered, and the other two had an activated algorithme with 1/1 conduction of a supraventricular arrhythmia. No recurrences were recorded after reprogramming the device. DDD or VDD pacing was permanent in 9 patients and intermittent in 3 others. Seven patients had dilated cardiomyopathy and severe cardiac failure and were clinically improved by dual chamber pacing. In many patients, candidates for a defibrillator, this new generation of devices has improved specificity of arrhythmia detection and cardiac pacing without risk of interaction. The authors propose a classification of the indications for a DDD defibrillator.*2

Abstract

T he Dual Chamber and VVI Implantable Defibrillator (DAVID) trial randomized 506 patients and tested the hypothesis that the dual-chamber pacing mode would produce improved hemodynamics and would in turn reduce congestive heart failure, heart failure hospitalizations, heart failure deaths, atrial fibrillation, strokes, ventricular arrhythmias, and total mortality compared to backup ventricular pacing in patients indicated for implantable defibrillator therapy. Patients had either primary prevention indications (47%) or secondary prevention indications (53%) for implantable defibrillator therapy but had no indications for bradycardia pacemaker support. All the patients had moderate to severe left ventricular dysfunction with a left ventricular ejection fraction of 40% or less (mean = 27%) and were consistently treated with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers (86%) and beta adrenergic blocking agents (85%). The primary combined endpoint of hospitalization for congestive heart failure or death was paradoxically increased and statistically significant ( p = 0.03) at one year in the patients paced in the dual chamber mode (22.6%) compared to patients randomized to ventricular backup pacing (13.3%). Both heart failure hospitalization and mortality contributed outcome. Another perspective would consider this a randomized controlled study of presence or absence of pacemaker therapy in patients with left ventricular dysfunction and indications for implantable defibrillator therapy. Ventricular backup pacing produced less than 3% ventricular and no atrial pacing, while dual chamber pacing produced approximately 60% atrial and ventricular paced heart beats. The poor outcome in the dual chamber paced group correlated with the percentage of right ventricular pacing and suggests that right ventricular pacing caused ventricular dyssynchrony. The poor outcome associated with right ventricular pacing compared to intrinsic activation in the control group of the DAVID trial is reminiscent of the poor outcome associated with prolonged intraventricular conduction activation in the control groups compared to biventricular pacing in the intervention groups of the cardiac resynchronization trials. The direct conclusion from these results are that patients with indications for implantable defibrillators and no indication for pacing should not be paced in the dual chamber pacing mode. It is not appropriate to conclude that only single chamber implantable defibrillators should be implanted. There are other potential advantages to having an implanted atrial lead including improved secondary outcomes. However the DAVID trial results suggest that the dual chamber paced mode was not associated with improved quality of life or decreased frequency of hospitalization, inappropriate shocks from the defibrillator or atrial fibrillation. The more important question is what is the optimal pacing mode in these patients? The AAIR mode is under investigation in the DAVID II study in an attempt to identify a pacing mode that preserves atrio-ventricular synchrony, normal atrio-ventricular timing, prevents bradycardia and also prevents right ventricular stimulation. Caution should be taken to not directly apply these results to patients with either an indication for pacemaker therapy or to patients with an indication for cardiac resynchronization therapy since patients from neither population were included. However, considering the large magnitude of the deleterious effects associated with dual chamber pacing in the DAVID trial future studies should explore the possibility that left ventricular stimulation may be the only pacing mode capable of preventing bradycardia without increasing death and congestive heart failure.*3

Abstract

We compared 2 studies of implantable cardiac defibrillators (ICDs) to determine the effects of device mode on outcomes. The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial (1993 to 1997) demonstrated improved survival with the ICD compared with antiarrhythmic drug therapy. The Dual-chamber And VVI Implantable Defibrillator (DAVID) trial (2000 to 2002) showed that VVI pacing at 40 beats/min in patients with ICDs reduced the combined end point of death and hospitalization for congestive heart failure compared with DDDR pacing at 70 beats/min. Patients in the AVID trial (631 of 1,016) and the DAVID trial (221 of 506) meeting common inclusion and all exclusion criteria were studied. The major end points were the time to death, and the composite end point of time to death or hospitalization for congestive heart failure. Patients in the AVID and DAVID trials were similar, but more AVID patients had coronary artery disease (p = 0.04), history of myocardial infarction (p = 0.005), and previous ventricular arrhythmias (p = 0.03). DAVID patients underwent more previous revascularization procedures (coronary artery bypass surgery, p = 0.03; percutaneous coronary intervention, p = 0.001), and were more often taking beta-blocking drugs at hospital discharge (p <0.001). The backup VVI ICD groups in both studies had similar outcomes (p = 0.4), even when corrected for the previous demographic differences. The time-to- composite end point was similar in AVID patients treated with antiarrhythmic drugs and DAVID patients treated with DDDR ICDs (p = 0.6). Despite improved pharmacologic therapy and revascularization, outcomes have not improved with backup VVI pacing ICDs. If DDDR ICDs had been used in the AVID trial, benefit from ICDs for patients with serious ventricular arrhythmias could have been missed.*4

Abstract

Context: Implantable cardioverter defibrillator (ICD) therapy with backup ventricular pacing increases survival in patients with life-threatening ventricular arrhythmias. Most currently implanted ICD devices provide dual-chamber pacing therapy. The most common comorbid cause for mortality in this population is congestive heart failure.


Objective: To determine the efficacy of dual-chamber pacing compared with backup ventricular pacing in patients with standard indications for ICD implantation but without indications for antibradycardia pacing.


Design: The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial, a single-blind, parallel-group, randomized clinical trial.


Setting and participants: A total of 506 patients with indications for ICD therapy were enrolled between October 2000 and September 2002 at 37 US centers. All patients had a left ventricular ejection fraction (LVEF) of 40% or less, no indication for antibradycardia pacemaker therapy, and no persistent atrial arrhythmias.


Interventions: All patients had an ICD with dual-chamber, rate-responsive pacing capability implanted. Patients were randomly assigned to have the ICDs programmed to ventricular backup pacing at 40/min (VVI-40; n = 256) or dual-chamber rate-responsive pacing at 70/min (DDDR-70; n = 250). Maximal tolerated medical therapy for left ventricular dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, was prescribed to all patients.


Main outcome measure: Composite end point of time to death or first hospitalization for congestive heart failure.


Results: One-year survival free of the composite end point was 83.9% for patients treated with VVI-40 compared with 73.3% for patients treated with DDDR-70 (relative hazard, 1.61; 95% confidence interval [CI], 1.06-2.44). The components of the composite end point, mortality of 6.5% for VVI-40 vs 10.1% for DDDR-70 (relative hazard, 1.61; 95% CI, 0.84-3.09) and hospitalization for congestive heart failure of 13.3% for VVI-40 vs 22.6% for DDDR-70 (relative hazard, 1.54; 95% CI, 0.97-2.46), also trended in favor of VVI-40 programming.


Conclusion: For patients with standard indications for ICD therapy, no indication for cardiac pacing, and an LVEF of 40% or less, dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure.*5

*1New indications for cardiac pacing

[Article in French]

J M Davy et al. Arch Mal Coeur Vaiss. 1995 Dec

*2Dual-chamber implantable automatic defibrillators. Experiences apropos of 16 cases]

[Article in French]

P Le Franc et al. Arch Mal Coeur Vaiss. 1998 Jun.

*3The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial: rationale, design, results, clinical implications and lessons for future trials

Bruce L Wilkoff et al. Card Electrophysiol Rev. 2003 Dec.

*4A comparison of the AVID and DAVID trials of implantable defibrillators.

Arjun Sharma et al. Am J Cardiol. 2005.

*5Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial

Bruce L Wilkoff et al. JAMA. 2002.