Asunto(s)
Humanos , Masculino , Anciano de 80 o más Años , Carcinoma Medular , Hepatitis C , Sofosbuvir , Anemia Ferropénica , Gastroscopía , BiopsiaAsunto(s)
Humanos , Femenino , Adulto , Hernia Hiatal/cirugía , Cirugía Bariátrica , Estómago/cirugía , GastrectomíaRESUMEN
BACKGROUND: Chest CT has been proposed as a screening test to rule out SARS-CoV-2 lung infection in acute stroke. Our objectives are to analyze the predictive value of neck CT angiography (CTA) source images compared with conventional chest CT, the interobserver concordance and the reliability of the diagnosis using a mobile app. METHODS: A retrospective observational study that included acute stroke patients admitted to a stroke center. Two raters blinded to the clinical data evaluated and classified the pulmonary findings in chest CT and neck CTA source images according to the COVID-19 Reporting and Data System (CO-RADS). CTA findings were evaluated using a conventional workstation and the JOIN mobile app. Scores of 3-5 were grouped as appearing typical or indeterminate for COVID-19 lung involvement and 0-2 as appearing atypical or negative for pneumonia. SARS-CoV-2 infection was confirmed by polymerase chain reaction (PCR). RESULTS: A total of 242 patients were included (42 with PCR-confirmed COVID-19). In the cohort of 43 patients with both neck CTA and chest CT, the predictive value for COVID-19 was equivalent (sensitivity, 53.8%; specificity, 92.9%). The interobserver agreement in the classification into CO-RADS 3-5 or 1-2 in CTA was good (K = 0.694; standard error, 0.107). In the cohort of 242 patients with neck CTA, the intraobserver agreement between the workstation and the JOIN app was perfect (K = 1.000; standard error 0.000). CONCLUSIONS: Neck CTA enables the accurate identification of COVID-19-associated lung abnormalities in acute stroke. CO-RADS evaluations through mobile applications have a predictive value similar to the usual platforms.
Asunto(s)
COVID-19 , Accidente Cerebrovascular , Telemedicina , Humanos , Angiografía por Tomografía Computarizada , SARS-CoV-2 , Reproducibilidad de los Resultados , Pulmón , Tomografía Computarizada por Rayos X/métodos , Estudios RetrospectivosAsunto(s)
Derivación Gástrica , Hernia Hiatal , Laparoscopía , Humanos , Hernia Hiatal/cirugía , Gastrectomía , Estómago/cirugíaRESUMEN
Drug hypersensitivity reactions (DHRs) to intravenous drugs can be severe and might leave patients and doctors in a difficult position where an essential treatment or intervention has to be suspended. Even if virtually any intravenous medication can potentially trigger a life-threatening DHR, chemotherapeutics, biologics, and antibiotics are amongst the intravenous drugs most frequently involved in these reactions. Admittedly, suspending such treatments may negatively impact the survival outcomes or the quality of life of affected patients. Delabeling pathways and rapid drug desensitization (RDD) can help reactive patients stay on first-choice therapies instead of turning to less efficacious, less cost-effective, or more toxic alternatives. However, these are high-complexity and high-risk techniques, which usually need expert teams and allergy-specific techniques (skin testing, in vitro testing, drug provocation testing) to ensure safety, an accurate diagnosis, and personalized management. Unfortunately, there are significant inequalities within and among countries in access to allergy departments with the necessary expertise and resources to offer these techniques and tackle these DHRs optimally. The main objective of this consensus document is to create a great benefit for patients worldwide by aiding allergists to expand the scope of their practice and support them with evidence, data, and experience from leading groups from around the globe. This statement of the Drug Hypersensitivity Committee of the World Allergy Organization (WAO) aims to be a comprehensive practical guide on the technical aspects of implementing acute-onset intravenous hypersensitivity delabeling and RDD for a wide range of drugs. Thus, the manuscript does not only focus on clinical pathways. Instead, it also provides guidance on topics usually left unaddressed, namely, internal validation, continuous quality improvement, creating a healthy multidisciplinary environment, and redesigning care (including a specific supplemental section on a real-life example of how to design a dedicated space that can combine basic and complex diagnostic and therapeutic techniques in allergy).
RESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic hereditary renal disease, promoting end-stage renal disease (ESRD). Klinefelter syndrome (KS) is a consequence of an extra copy of the X chromosome in males. Main symptoms in KS include hypogonadism, tall stature, azoospermia, and a risk of cardiovascular diseases, among others. Gitelman syndrome (GS) is an autosomal recessive disorder caused by SLC12A3 variants, and is associated with hypokalemia, hypomagnesemia, hypocalciuria, normal or low blood pressure, and salt loss. The three disorders have distinct and well-delineated clinical, biochemical, and genetic findings. We here report a male patient with ADPKD who developed early chronic renal failure leading to ESRD, presenting with an intracranial aneurysm and infertility. NGS identified two de novo PKD1 variants, one known (likely pathogenic), and a previously unreported variant of uncertain significance, together with two SLC12A3 pathogenic variants. In addition, cytogenetic analysis showed a 47, XXY karyotype. We investigated the putative impact of this rare association by analyzing possible clinical, biochemical, and/or genetic interactions and by comparing the evolution of renal size and function in the proband with three age-matched ADPKD (by variants in PKD1) cohorts. We hypothesize that the coexistence of these three genetic disorders may act as modifiers with possible synergistic actions that could lead, in our patient, to a rapid ADPKD progression.
Asunto(s)
Síndrome de Gitelman , Fallo Renal Crónico , Riñón Poliquístico Autosómico Dominante , Insuficiencia Renal Crónica , Síndrome de Gitelman/complicaciones , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/genética , Humanos , Riñón/patología , Fallo Renal Crónico/genética , Masculino , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/patología , Miembro 3 de la Familia de Transportadores de Soluto 12/genéticaRESUMEN
PURPOSE OF REVIEW: Drug desensitization is the only therapeutic option for patients with drug allergies who need to receive the drugs they are allergic to, and it is especially critical in patients with an urgent need for chemotherapy, biologics, or antibiotics, where equally effective alternatives might not be available. However, drug desensitization is not a cookbook where anyone with no experience or specific training can find a general recipe. This review article will approach the singularities that make personalized and highly specialized care essential in this field. RECENT FINDINGS: Drug desensitization needs to be personalized for each individual patient bearing in mind countless factors. Recent articles have tried to define the optimal resources and the most important factors to account for in personalization. However, drug desensitization is only a tool within the wider management pathway, and we will discuss recent findings in allergy delabelling in chemotherapy, biologics, and antibiotics. SUMMARY: Risk-assessment, delabelling, and desensitization protocols, as a part of wider management pathways, can be adapted locally along with comprehensive and multifactorial risk-management strategies. These high-complexity and high-risk procedures, such as drug desensitization, need to be managed by expert allergists who can provide personalization, innovation, continuous improvement, research, and teaching in expert centres.
Asunto(s)
Productos Biológicos , Hipersensibilidad a las Drogas , Antibacterianos/efectos adversos , Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/terapia , HumanosRESUMEN
Biologicals are crucial targeted therapeutic agents in oncological, immunological, and inflammatory diseases, and their use in clinical practice is broadening. In recent years, the spread of Personalized Precision Medicine has facilitated a proliferation of new treatment options, especially biologicals. Consequently, biologicals are now among the drugs that most frequently cause hypersensitivity reactions (HSRs). Patients can develop HSRs to these agents during the first-lifetime exposure or after repeated exposure, and these HSRs can be potentially life-threatening or limit therapeutic options. Despite the relatively high prevalence, the underlying mechanisms of these HSRs remain obscure, and the optimal management pathways are still a matter of discussion. In this Position Paper, the authors will provide evidence-based recommendations for diagnosing and managing HSRs to biologicals. Additionally, the document defines unmet needs as an opportunity to shape future research.
Asunto(s)
Antineoplásicos , Productos Biológicos , Hipersensibilidad a las Drogas , Antineoplásicos/uso terapéutico , Productos Biológicos/efectos adversos , Desensibilización Inmunológica/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/epidemiología , Hipersensibilidad a las Drogas/etiología , Humanos , Medicina de PrecisiónRESUMEN
Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section.
Asunto(s)
Anafilaxia , Antineoplásicos , Hipersensibilidad a las Drogas , Neoplasias , Anafilaxia/tratamiento farmacológico , Antineoplásicos/efectos adversos , Desensibilización Inmunológica/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/epidemiología , Hipersensibilidad a las Drogas/etiología , Humanos , Neoplasias/complicaciones , Pruebas Cutáneas/efectos adversosRESUMEN
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) and neurofibromatosis type 1 (NF1) are both autosomal dominant disorders with a high rate of novel mutations. However, the two disorders have distinct and well-delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and NF1 in a single individual have been reported, but the possible implications of this association are unknown. METHODS: We report an ADPKD male belonging to a family of several affected members in three generations associated with NF1 and optic pathway gliomas. The clinical diagnosis of ADPKD and NF1 was performed by several image techniques. RESULTS: Linkage analysis of ADPKD family was consistent to the PKD2 locus by a nonsense mutation, yielding a truncated polycystin-2 by means of next-generation sequencing. The diagnosis of NF1 was confirmed by mutational analysis of this gene showing a 4-bp deletion, resulting in a truncated neurofibromin, as well. The impact of this association was investigated by analyzing putative genetic interactions and by comparing the evolution of renal size and function in the proband with his older brother with ADPKD without NF1 and with ADPKD cohorts. CONCLUSION: Despite the presence of both conditions there was not additive effect of NF1 and PKD2 in terms of the severity of tumor development and/or ADPKD progression.
Asunto(s)
Neurofibromatosis 1/genética , Glioma del Nervio Óptico/genética , Fenotipo , Riñón Poliquístico Autosómico Dominante/genética , Adolescente , Adulto , Codón sin Sentido , Humanos , Masculino , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/patología , Neurofibromina 1/genética , Glioma del Nervio Óptico/complicaciones , Glioma del Nervio Óptico/patología , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/patología , Canales Catiónicos TRPP/genéticaRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous inherited disease characterized by renal and extrarenal manifestations with progressive fluid-filled cyst development leading to end-stage renal disease. The rate of disease progression in ADPKD exhibits high inter- and intrafamilial variability suggesting involvement of modifier genes and/or environmental factors. Renal hypouricemia (RHUC) is an inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and chronic kidney disease (CKD). However, the two disorders have distinct and well-delineated genetic, biochemical, and clinical findings. Only a few cases of coexistence of ADPKD and RHUC (type 1) in a single individual have been reported. We report a family with two members: an ADPKD 24-year-old female which presented bilateral renal cysts in utero and hypouricemia since age 5, and her mother with isolated hypouricemia. Next-generation sequencing identified two mutations in two genes PKD1 and SLC2A9 in this patient and one isolated SLC2A9 mutation in her mother, showing RHUC type 2, associated to CKD. The coexistence of these two disorders provides evidence of SLC2A9 variant could act as a modifier change, with synergistic actions, that could promote cystogenesis and rapid ADPKD progression. This is the first case of coexistence of PKD1 and SLC2A9 mutations treated with tolvaptan.
Asunto(s)
Proteínas Facilitadoras del Transporte de la Glucosa/genética , Enfermedades Renales Poliquísticas/genética , Defectos Congénitos del Transporte Tubular Renal/genética , Canales Catiónicos TRPP/genética , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/genética , Lesión Renal Aguda/patología , Adulto , Preescolar , Femenino , Humanos , Mutación/genética , Enfermedades Renales Poliquísticas/complicaciones , Enfermedades Renales Poliquísticas/diagnóstico , Enfermedades Renales Poliquísticas/patología , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/diagnóstico , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/patología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/patología , Defectos Congénitos del Transporte Tubular Renal/complicaciones , Defectos Congénitos del Transporte Tubular Renal/diagnóstico , Defectos Congénitos del Transporte Tubular Renal/patología , Adulto JovenRESUMEN
Introducción: La Poliquistosis Renal Autosómica Dominante es una enfermedad renal crónica responsable del 10% de los casos de insuficiencia renal terminal. La participación y los grupos de apoyo entre iguales son herramientas que mejoran el bienestar, evitando complicaciones y retrasando el avance de la enfermedad. Objetivos: Detectar necesidades informativas, así como recursos de apoyo, en este grupo de pacientes mediante la puesta en marcha de una Escuela de Pacientes con poliquistosis renal autosómica dominante. Material y Método: Se utilizó un diseño mixto (cuantitativo y cualitativo). El estudio se desarrolló mediante cuatro fases: 1) Grupo focal: pacientes con poliquistosis renal y sus cuidadores; 2) Selección de los pacientes expertos; 3) Elaboración de los contenidos del programa de la Escuela de pacientes con poliquitstosis renal autosómica dominante; 4) Pilotaje del programa. Resultados: Se detectaron necesidades de información referentes al tratamiento oral y al afrontamiento de la poliquistosis renal que no están cubiertas por los equipos de nefrología. Conclusiones: La Escuela de Pacientes ha demostrado ser una herramienta útil para detectar necesidades y recursos en pacientes con poliquistosis renal autosómica dominante que han de enfrentarse a una enfermedad crónica donde se requiere la participación del paciente para garantizar la adhesión al tratamiento
Introduction: Autosomal Dominant Polycystic Kidney Disease is a chronic kidney disease responsible for 10% of cases of end-stage renal failure. Participation and peer support groups are tools that improve well-being, avoiding complications and delaying disease progression. Objectives: To detect information needs, as well as support resources, in patients with autosomal dominant polycystic kidney disease trough a Patient School. Material and Method: A mixed design (quantitative and qualitative) was used. The study was developed through four phases: 1) Focus group: patients with autosomal dominant polycystic kidney disease and their caregivers; 2) Selection of expert patients; 3) Preparation of the contents of the program of the Patient School with autosomal dominant polycystic kidney disease; 4) Piloting the program. Results: Information needs regarding oral treatment and coping with autosomal dominant polycystic kidney disease were detected, which are not covered by nephrology teams. Conclusions: Patients School has proven to be a useful tool to detect needs and resources in patients with autosomal dominant polycystic kidney disease who have to face a chronic disease where patient participation is required to ensure adherence to treatment
Asunto(s)
Humanos , Automanejo/educación , Riñón Poliquístico Autosómico Dominante/enfermería , Grupos de Entrenamiento Sensitivo/organización & administración , Evaluación de Eficacia-Efectividad de Intervenciones , Educación del Paciente como Asunto/estadística & datos numéricos , Progresión de la Enfermedad , Información de Salud al Consumidor/organización & administraciónRESUMEN
BACKGROUND: Large-scale studies of drug provocation testing (DPT) or rapid drug desensitization (RDD) for hypersensitivity to antineoplastics and biologicals are scarce and limited to a few institutions. OBJECTIVE: Our aim was to review our experience with DPT and RDD in a large number of patients with a history of hypersensitivity to antineoplastics and biologicals and summarize the practical implications of that experience. METHODS: This was a 7-year prospective, observational, longitudinal study with reactive patients referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were selected after following our systematic and validated diagnostic approach (clinical history, skin test, risk assessment, specific IgE, DPT) before RDD. Candidate patients underwent RDD using the RCUH protocol. Cetuximab reactors underwent 1-bag RDDs. RESULTS: A total of 1027 intravenous RDDs were performed using the RCUH protocol (399 platins, 395 taxanes, 178 biologicals, 55 other drugs), and 1026 were successfully accomplished in the 186 patients (of 515 referred patients) who met inclusion criteria for RDD. No breakthrough reactions occurred in 88% of RDDs. Most breakthrough reactions were mild. A total of 341 DPTs were performed, and 229 results were negative (67%). DPTs helped exclude hypersensitivity in 44% (229 of 515) of referred patients. In addition, 77 one-bag RDDs were performed in 6 cetuximab-reactive patients. CONCLUSIONS: This experience allows us to describe general management plans, as well as specific patient phenotypic patterns, predictors for reactions, and risk considerations that need a tailored approach (taking into account the 3 prominent drug categories: platins, taxanes, and biologicals).