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Introducción: La neutropenia febril (NF) constituye una complicación frecuente, considerada una urgencia infectológica en los pacientes con cáncer que reciben tratamiento mielosupresor. Metodología: Se realizó un estudio retrospectivo descriptivo a través de la revisión de los expedientes de todos los episodios de NF secundarios a quimioterapia ingresados en el Hospital del Niño - Dr. José Renán Esquivel durante el periodo de enero a diciembre de 2017. Resultados: El estudio consistió en la evaluación de características epidemiológicas e identificación de agentes infecciosos en 49 casos de NF, y 104 eventos febriles. Se observó que el 51% de los casos eran varones, con una edad promedio de 7 años, y recuperación de NF en los primeros 7 días del 68%. La mayoría de las hospitalizaciones (53,8%) duraron de 1 a 7 días, con una relación directa con los días de fiebre y la presencia de neutropenia. La letalidad registrada fue de 6.1%. Los agentes etiológicos más frecuentes fueron la Pseudomonas aeruginosa, los Estafilococos coagulasa negativos y Staphylococcus aureus meticilino sensible. Conclusión: Los hallazgos permiten conocer la epidemiología actual de los pacientes con NF que se admiten al hospital, con el fin de optimizar el tratamiento para reducir la tasa de letalidad. (provisto por Infomedic International)
Introduction: Febrile neutropenia (NF) constitutes a frequent complication, considered an infectious emergency in cancer patients receiving myelosuppressive treatment. Methodology: A descriptive retrospective study was conducted by reviewing the records of all episodes of NF secondary to chemotherapy admitted to the Hospital del Niño - Dr. José Renán Esquivel during the period from January to December 2017. Results: The study consisted of the evaluation of epidemiological characteristics and identification of infectious agents in 49 cases of NF, and 104 febrile events. It was observed that 51% of the cases were male, with a mean age of 7 years, and recovery from NF in the first 7 days of 68%. Most hospitalizations (53.8%) lasted from 1 to 7 days, with a direct relationship with the number of days of fever and the presence of neutropenia. The case fatality rate was 6.1%. The most frequent etiological agents were Pseudomonas aeruginosa, coagulase-negative Staphylococci and methicillin-sensitive Staphylococcus aureus. Conclusion: The findings provide insight into the current epidemiology of patients with NF admitted to the hospital, in order to optimize treatment to reduce the case-fatality rate. (provided by Infomedic International)
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Introducción: La infección fúngica invasora (IFI) es una causa importante de morbilidad y mortalidad en pacientes oncológicos pediátricos y portadores de aplasia medular (AM) severa. Objetivo: Describir la epidemiología de la IFI desde el año 2016 al 2020 en niños con cáncer y AM para evaluar la necesidad de profilaxis antifúngica. Métodos: Estudio retrospectivo, multicéntrico, en pacientes pediátricos con cáncer y AM severa. Se incluyeron IFI probables y probadas. Resultados: Se diagnosticaron 57 casos de IFI, mediana de edad 9 años, 70% probadas y 30% probables. Hubo 42% de infecciones por levaduras y 56% por hongos filamentosos. Los sitios de infección más frecuentes fueron pulmón 38%, sangre 36% y rinosinusal 21%. La frecuencia global fue 5,4%; de ellas 21% en AM severa, 10% en leucemia mieloide aguda (LMA), 6,9% en recaída de LMA, 5,4% en recaída de leucemia linfática aguda (LLA), 3,8% en LLA. Las infecciones por hongos filamentosos predominaron en LMA, recaída de LMA. y AM severa. La mortalidad en pacientes con IFI fue de 11%. Conclusión: La frecuencia de IFI concuerda con la literatura médica. Recomendamos profilaxis antifúngica contra hongos filamentosos en pacientes con AM severa, LMA y recaída de LMA. Considerar en recaída de LLA de alto riesgo en etapa de inducción.
Background: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in pediatric oncology patients and severe aplastic anemia (SAA). Aim: To describe the epidemiology of IFI from 2016 to 2020 in children with cancer and SAA to assess the indication of antifungal prophylaxis. Methods: Multicenter, retrospective study of IFIs in pediatric oncology patients and SAA. Probable and proven IFIs were included. Results: Over the 5-year period, 57 IFIs were found, median age 9 years, 70% were proven and 30% were probable. Yeast infections were 42% and mold infections 56%. The most frequent infection sites were lung 38%, blood 36% and rhinosinusal 21%. The total IFI frequency was 5.4%, 21% in SAA, 10% in acute myeloid leukemia (AML), 6.9% in relapsed AML, 5.4% in relapsed acute lymphoblastic leukemia (ALL), 3.8% in ALL. Mold infections were predominant in AML, relapsed AML, and SAA. IFIs mortality was 11%. Conclusion: Frequency of IFI was consistent with the literature. We strongly recommend antifungal prophylaxis against mold infections in patients with SAA, AML, and relapsed AML. Would consider in high risk ALL relapse in induction chemotherapy.
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El Comité de Infecciones en Inmunocomprometidos de la Sociedad Chilena de Infectología presenta aquí una actualización en el Manejo de episodios de neutropenia febril en adultos y niños con cáncer, derivado de los grandes cambios ocurridos en los últimos años en el enfrentamiento de estos pacientes. Para estos efectos, un grupo multidisciplinario desarrolló recomendaciones en relación a: su enfrentamiento inicial, exámenes de laboratorio requeridos, el tratamiento antimicrobiano inicial empírico y frente a focos infecciosos conocidos, las infecciones fúngicas invasoras y profilaxis antimicrobiana.
The Committee of Infections in Immunocompromised Patients of the Chilean Society of Infectious Diseases presents an update in the Management of febrile neutropenia in adults and children with cancer. It comes from the significant changes that occurred in recent years in the confrontation of these patients. For which a multidisciplinary task force group developed recommendations in relation to their initial handling, laboratory exams required, the initial empirical antimicrobial treatment and in front of known infectious focus, invasive fungal infections and antimicrobial prophylaxis.
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Abstract Background: Mucormycosis is a rare infection caused by ubiquitous fungi of the Mucorales order that mainly affects immunocompromised patients. These fungi have an important tropism for blood vessels that allows them to spread rapidly and cause thromboembolic events. Case report: We present a case of an 8-year-old male patient diagnosed with acute lymphoblastic leukemia treated with chemotherapy. He presented icteric syndrome, hepato-splenomegaly, and data of intestinal obstruction. Although he underwent intestinal resection, he did not improve and died. The autopsy identified disseminated mucormycosis involving the brain, lungs, esophagus, small intestine, colon, and pancreas. Conclusions: Hematological neoplastic diseases and their treatment are important risk factors for developing infections by opportunistic microorganisms such as mucormycosis. Early diagnosis and adequate treatment are essential due to their intrinsic difficulty and the high mortality rate of these cases.
Resumen Introducción: La mucormicosis es una infección poco frecuente causada por hongos ubicuos del orden de los Mucorales que afecta principalmente a pacientes inmunocomprometidos. Estos hongos poseen un importante tropismo por vasos sanguíneos que les permite diseminarse rápidamente y provocar lesiones trombo-embólicas. Caso clínico: Se presenta el caso de un paciente de sexo masculino de 8 años con diagnóstico de leucemia linfoblástica aguda tratada con quimioterapia. Presentó síndrome ictérico, hepato-esplenomegalia y datos de obstrucción intestinal. A pesar de que fue sometido a resección intestinal, no presentó mejoría y falleció. En la autopsia se identificó mucormicosis diseminada con afección de cerebro, pulmones, esófago, intestino delgado, colon y páncreas. Conclusiones: Las enfermedades neoplásicas hematológicas y su tratamiento son importantes factores de riesgo para el desarrollo de infecciones por microorganismos oportunistas como la mucormicosis. El diagnóstico temprano y adecuado tratamiento son importantes debido a la dificultad intrínseca de los mismos y la alta tasa de mortalidad de estos casos.
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ABSTRACT Objective. The DoTT (Decreasing Time to Therapy) project aimed to minimize the interval between fever onset and medical interventions for children with febrile neutropenia. The objective of this study was to determine the effect of implementing the DoTT project on the hospital time to antibiotic (TTA) and patient time to arrival (PTA) at the hospital in children with febrile neutropenia admitted to the emergency department. Methods. The DoTT project was implemented at a Peruvian hospital and followed the World Health Organization (WHO) multimodal improvement strategy model. Components included creating a healthcare delivery bundle and antibiotic selection pathways, training users of the bundle and pathways, monitoring patient outcomes and obtaining user feedback, encouraging use of the new system, and promoting the integration of DoTT into the institutional culture. Emergency room providers were trained in the care delivery for children with cancer and fever and taught to use the bundle and pathways. DoTT was promoted via pamphlets and posters, with a view to institutionalizing the concept and disseminating it to other hospital services. Results. Admission data for 129 eligible patients in our registry were analyzed. The TTA and PTA were compared before and after the DoTT intervention. The median TTA was 146 minutes (interquartile range [IQR] 97-265 minutes) before the intervention in 99 patients, and 69 minutes (IQR 50-120 minutes) afterwards in 30 patients (p < 0.01). The median PTA was reduced from 1 483 minutes at baseline to 660 minutes after the intervention (p < 0.01). Conclusions. Applying the WHO multimodal improvement strategy model to the care of children with febrile neutropenia arriving at the hospital had a positive impact on the PTA and TTA, thus potentially increasing the survival of these patients.
RESUMEN Objetivo. El proyecto DoTT (Disminuyendo el tiempo a la terapia, sigla en inglés) busca minimizar el intervalo entre el inicio de la fiebre y las intervenciones médicas en la población infantil con neutropenia febril. El objetivo de este estudio fue determinar el efecto de la implementación del proyecto DoTT sobre el tiempo transcurrido desde el inicio de la fiebre hasta la llegada del paciente (TLP) al hospital y el tiempo transcurrido en el hospital hasta la administración del antibiótico (TAA) en niños con neutropenia febril ingresados en el servicio de urgencias. Métodos. El proyecto DoTT se puso en marcha en un hospital peruano, según el modelo de estrategia multimodal de mejora de la Organización Mundial de la Salud (OMS). Entre sus componentes se encontraban crear un conjunto de servicios de atención de salud y de algoritmos para la selección de antibióticos; capacitar a los usuarios en la utilización del conjunto de servicios y de los algoritmos; realizar un seguimiento de los resultados de los pacientes y recabar la opinión de los usuarios; fomentar el uso del nuevo sistema; y promover la integración del proyecto en la cultura institucional. Se capacitó al personal de la sala de urgencias en la atención de pacientes pediátricos con cáncer y fiebre, y en el uso del conjunto de servicios y de los algoritmos. Se informó sobre el proyecto DoTT mediante folletos y carteles, con vistas a institucionalizar el concepto y difundirlo a otros servicios hospitalarios. Resultados. Se analizaron los datos de ingreso de 129 pacientes de nuestro registro que cumplían con los requisitos. Se compararon el TAA y el TLP al hospital antes y después de la intervención con las pautas del proyecto DoTT. La mediana del TAA fue de 146 minutos (intervalo intercuartílico [II]: 97-265 minutos) en 99 pacientes antes de la intervención y de 69 minutos (II: 50-120 minutos) en 30 pacientes después de ella (p <0,01). La mediana del TLP disminuyó de 1 483 minutos en el momento de la evaluación inicial a 660 minutos después de la intervención (p <0,01). Conclusiones. La aplicación del modelo de estrategia multimodal de mejora de la OMS a la atención de la población infantil con neutropenia febril que acude al hospital tuvo un efecto positivo sobre el TLP y el TAA, lo que podría aumentar la supervivencia de estos pacientes.
RESUMO Objetivo. O projeto DoTT (Redução do Tempo para o Tratamento, na sigla em inglês) tem como objetivo reduzir ao máximo o intervalo entre o início da febre e as intervenções médicas em crianças com neutropenia febril. O objetivo deste estudo foi determinar o efeito da implementação do projeto DoTT no tempo desde o início da febre até a chegada do paciente (TCP) ao hospital e no tempo no hospital até a administração de antibióticos (TAA) em crianças com neutropenia febril admitidas no departamento de emergência. Métodos. O projeto DoTT foi implementado em um hospital do Peru e seguiu o modelo de estratégia de melhoria multimodal da Organização Mundial da Saúde (OMS). Os componentes incluíram a criação de um pacote de prestação de serviços de saúde e de protocolos de seleção de antibióticos, o treinamento de usuários no pacote e nos protocolos de seleção, o monitoramento da evolução dos pacientes e obtenção de feedback dos usuários, o incentivo ao uso do novo sistema e a promoção da integração do DoTT à cultura institucional. Os profissionais do pronto-socorro foram capacitados na prestação de cuidados a crianças com câncer e febre e no uso do pacote e dos protocolos de seleção. O DoTT foi divulgado por meio de panfletos e pôsteres, com o objetivo de institucionalizar o conceito e disseminá-lo para outros serviços hospitalares. Resultados. Foram analisados os dados de internação de 129 pacientes elegíveis em nosso registro. O TAA e o TCP foram comparados antes e depois da intervenção DoTT. O TAA mediano era de 146 minutos (intervalo interquartil: 97-265 minutos) antes da intervenção em 99 pacientes e de 69 minutos (intervalo interquartil: 50-120 minutos) depois da intervenção em 30 pacientes (p < 0,01). O TCP mediano diminuiu de 1483 minutos na linha de base para 660 minutos após a intervenção (p < 0,01). Conclusão. A aplicação do modelo de estratégia multimodal de melhoria da OMS ao atendimento de crianças com neutropenia febril que chegam ao hospital teve um impacto positivo no TCP e no TAA, potencialmente aumentando a sobrevida desses pacientes.
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ABSTRACT Objective To assess the incidence of febrile neutropenia without primary granulocyte colony-stimulating factor prophylaxis in patients undergoing chemotherapy with adjuvant docetaxel and cyclophosphamide, and to evaluate the toxicity profile of brand-name docetaxel (Taxotere ® ) and the generic formulation. Methods This retrospective study was conducted using data obtained from electronic medical records of patients treated at a Brazilian cancer center. Patients with breast cancer who underwent adjuvant treatment between January 2016 and June 2019 were selected. Data were analyzed using chi-square and Fisher correlation of variables, and multivariate analyses were adjusted for propensity score. Results A total of 231 patients with a mean age of 55.9 years at the time of treatment were included in the study. The majority (93.9%) had luminal histology, 84.8% were at clinical stage I, and 98.2% had a good performance status. The overall incidence of febrile neutropenia in the study population was 13.4% (31 cases). The use of brand-name docetaxel (Taxotere ® ) was the only factor associated with febrile neutropenia occurrence (OR= 3.55, 95%CI= 1.58-7.94, p=0.002). Conclusion In patients with breast cancer who require treatment with adjuvant docetaxel and cyclophosphamide regimen, the toxicity profile differs between brand-name and generic docetaxel. Regardless of the formulation used, the incidence of febrile neutropenia was less than 20%, which may allow for the omission of primary prophylactic granulocyte colony-stimulating factor use in this setting.
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La vancomicina es un antibiótico de uso común en pacientes hospitalizados. Se han descrito múltiples efectos adversos relacionados a este fármaco, de los cuales la agranulocitosis es una entidad poco frecuente pero potencial mente grave. Este caso muestra una consecuencia médica secundaria al uso prolongado de este antibiótico, generando una neutropenia profunda posterior a 24 días de tratamiento, presentándose clínicamente con un pico febril aislado. Se asume que esta situación es consecuencia de una respuesta inmunológica inadecuada del huésped, por lo que la suspensión del agente etiológico es la clave del tratamiento. Existen pocos reportes de estos casos en la población pediátrica y debe considerarse un efecto secundario que requiere vigilancia estrecha para evitar repercusiones clínicas.
Vancomycin is a commonly used antibiotic in hospitalized patients. Multiple adverse effects related to this drug have been described, of which agranulocytosis is a rare but potentially serious entity. This case shows a medical consequence secondary to the prolonged use of this antibiotic, generating profound neutropenia after 24 days of treatment, presenting clinically with an isolated feverish peak. It is assumed that this situation is the consequence of an inadequate immunological response of the host, for which reason the suspension of the etiological agent is the key to treatment. There are few reports of these effects in the pediatric population and should be considered a side effect that requires close monitoring to avoid clinical repercussions.
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Este trabajo se realizó como respuesta a un problema de la practica en enfermería al haberse realizado en el marco de un producto requerido desde la formación posgradual de la maestría en enfermería con profundización en oncología, buscando aportar y transferir el conocimiento a la sociedad. El trabajo está orientado a la educación que requieren los cuidadores de pacientes adultos con Leucemia linfoblástica aguda de células B CD 19 positivo con cromosoma Philadelphia negativo en situación de recaída o refractariedad al tratamiento o con enfermedad mínima residual positiva y que requieran tratamiento con Blinatumomab. El objetivo fue elaborar una guía práctica de cuidado dirigida a los cuidadores de estos pacientes con la intención de brindar herramientas desde el conocimiento que permitan conocer sobre la enfermedad, el tratamiento, la identificación de los signos y síntomas asociados a eventos adversos por la administración del Blinatumomab descritos en la misma guía, para prevenir o disminuir la ocurrencia de desenlaces fatales en esta población de pacientes. Se contó con la participación de enfermeros profesionales y de cuidadores de pacientes que han administrado y recibido terapia con Blinatumomab respectivamente para identificar las necesidades en educación desde la práctica profesional y el desarrollo de los cuidados. Se diseño un material educativo basado en las orientaciones dadas por la Organización Panamericana de la Salud para la elaboración de material educativo, obteniendo como producto una guía comprensible y útil como instrumento para el desarrollo de procesos educativos con cuidadores de adultos con LLA de células B CD 19 positivo PH negativo R/R o con EMR positiva.
The present work was carried out in response to a problem in nursing practice because it was carried out within the framework of a product required from the postgraduate training of the master's degree in nursing with a deepening in oncology, seeking to contribute and transfer knowledge to society. The work is oriented towards the education required by caregivers of adult patients with Philadelphia chromosome negative CD 19 positive B-cell acute lymphoblastic leukemia in a situation of relapse or refractory to treatment or with positive minimal residual disease and who require treatment with Blinatumomab. The objective was to develop a practical care guide aimed at the caregivers of these patients with the intention of providing tools based on knowledge that allow them to know about the disease, treatment, identification of signs and symptoms associated with adverse events due to the administration of the Blinatumomab described in the same guidelines, to prevent or reduce the occurrence of fatal outcomes in this patient population. Professional nurses and caregivers of patients who have administered and received Blinatumomab therapy, respectively, participated to identify educational needs from professional practice and care development. An educational material was designed based on the guidelines given by the Pan American Health Organization for the elaboration of educational material, obtaining as a product an understandable and useful primer as an instrument for the development of educational processes with caregivers of adults with CD B-cell ALL. 19 positive PH negative R/R or with positive EMR.
Subject(s)
Humans , Male , Female , Caregivers/education , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Neutropenia , Practice GuidelineABSTRACT
Abstract Introduction Febrile neutropenia (FN) is a serious complication of cancer chemotherapy. The present study aimed to identify risk factors for documented infection in pediatric patients with FN and cancer. Methods This prospective cohort study included patients under 18 years from 2016 to 2018. Infection was defined according to the Centers for Disease Control and Prevention criteria. Results A total of 172 febrile neutropenic episodes were evaluated. From univariate analysis, the risk factors were: female gender; monocyte count < 100 cell/mm³, platelets < 50,000, C-reactive protein (CRP) > 90 mg/dl and hemoglobin < 7mg/dl at the onset of an episode; two or more episodes of FN, and; fever onset; positive blood culture at the fever onset. Independent risk factors according to the multivariate analysis were: CRP at the onset of a febrile episode > 90mg/dl, fever onset and first blood culture with a positive result. The lowest probability of infection was related to first episode and to platelets > 50,000 at the onset of fever. Conclusion A CRP > 90 at the onset of a febrile episode, platelets < 50,000, second episode or more, first fever episode during hospitalization and positive first blood culture were found to be associated with a higher risk of infection and they could be useful for the establishment of risk scores for infection in neutropenic children.
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Sepsis , Febrile Neutropenia , Risk Factors , Bacteremia , Drug Therapy , NeoplasmsABSTRACT
Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Subject(s)
Humans , Polymyxin B/adverse effects , Retrospective Studies , Gram-Negative Bacterial Infections/complications , Fever/drug therapy , Sepsis/drug therapy , Anti-Bacterial Agents/therapeutic use , Bacteremia/complicationsABSTRACT
Objective: To determine whether the adenine base editor (ABE7.10) can be used to fix harmful mutations in the human G6PC3 gene. Methods: To investigate the safety of base-edited embryos, off-target analysis by deep sequencing was used to examine the feasibility and editing efficiency of various sgRNA expression vectors. The human HEK293T mutation models and human embryos were also used to test the feasibility and editing efficiency of correction. Results: ①The G6PC3(C295T) mutant cell model was successfully created. ②In the G6PC3(C295T) mutant cell model, three distinct Re-sgRNAs were created and corrected, with base correction efficiency ranging from 8.79% to 19.56% . ③ ABE7.10 could successfully fix mutant bases in the human pathogenic embryo test; however, base editing events had also happened in other locations. ④ With the exception of one noncoding site, which had a high safety rate, deep sequencing analysis revealed that the detection of 32 probable off-target sites was <0.5% . Conclusion: This study proposes a new base correction strategy based on human pathogenic embryos; however, it also produces a certain nontarget site editing, which needs to be further analyzed on the PAM site or editor window.
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Humans , Gene Editing , CRISPR-Cas Systems , Adenine , HEK293 Cells , Mutation , Glucose-6-Phosphatase/metabolismABSTRACT
@#During chemotherapy of malignant tumors,neutropenia is the most important adverse event caused by myelosuppressive chemotherapeutics,of which the degree and duration are closely related to the risk of infection and even death.Granulocyte-colony stimulating factor(G-CSF) is an endogenous hematopoietic growth factor that can stimulate the proliferation and differentiation of neutrophil precursors,and increase the survival rate and activity of mature neutrophils.Recombinant human granulocyte-colony stimulating factor(rhG-CSF) is an artificially synthesized cytokine with G-CSF biological activity.It is used clinically for the prevention and treatment of neutropenia after treatment with cytotoxic chemotherapeutics,requiring multiple medications and repeated injections during application for its short half-life.Pegylated recombinant human granulocyte-colony stimulating factor(PEG-rhG-CSF) is its long-acting dosage form,and patients only need to be administered once per cycle of chemotherapy,which has been widely used in clinical practice because of its stability and convenience.This paper systematically described the clinical application value of PEG-rhG-CSF in neutropenia after chemotherapy,aiming to provide a reference for its further clinical application.
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Chemotherapy-induced neutropenia (CIN) is a common hematological adverse events and dose-limiting toxicities of chemotherapy. CIN may lead to dose reduction and delay of chemotherapeutic agents, febrile neutropenia and severe infection, which results in increased treatment cost, reduced efficacy of chemotherapy, and even life-threatening morbidities. Assessment of risk of CIN, early detection of FN and infection, and proper prevention and treatment play a crucial role in reducing the occurrence of CIN-related morbidities, improving patient treatment safety and anticancer efficacy. Based on evidence and expert opinion, the expert committee of Chinese Anti-Cancer Association issued "the consensus on diagnosis and treatment of chemotherapy-induced neutropenia in China (2023 edition)", which is an update version of the 2019 edition, aiming to provide reference for the diagnosis and treatment of CIN for Chinese oncologists.
Subject(s)
Humans , Granulocyte Colony-Stimulating Factor , Consensus , Neutropenia/prevention & control , Neoplasms/drug therapy , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
ABSTRACT Background: Carbapenem-Resistant Gram-Negative (CRGN) Bloodstream Infections (BSI) represent a therapeutic challenge, especially in the context of Febrile Neutropenia (FN) in cancer patients. Methods: We characterized pathogens causing BSI in patients aged ≥18 years who had undergone systemic chemotherapy for solid or hematological cancers between 2012 and 2021 in Porto Alegre, Brazil. Predictors of CRGN were evaluated through a case-control analysis. Each case was matched to two controls from whom CRGN were not isolated and had the same sex and year of inclusion in the study. Results: From 6094 blood cultures evaluated, 1512 (24.8%) showed positive results. Gram-negative bacteria accounted for 537 (35.5%) of the isolated bacteria, of which 93 (17.3%) were carbapenem-resistant. From 105 patients included in the case-control analysis, all cases had baseline hematological malignancies (60% acute myeloid leukemia). Variables related to CRGN BSI in Cox regression analysis were the first chemotherapy session (p<0.01), chemotherapy performed in the hospital setting (p = 0.03), intensive care unit admission (p<0.01), and CRGN isolation in the previous year (p<0.01). Patients with CRGN BSI received 75% less empirical active antibiotics and had 27.2% higher 30-day mortality rates than controls. Conclusions: A CRGN risk-guided approach should be considered for empirical antibiotic therapy in patients with FN.
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ABSTRACT Background: Despite high cure rates, treatment-related mortality in children with acute lymphoblastic leukemia (ALL) remains significant. About 4% of patients die during remission induction therapy and approximately two-thirds of treatment-related deaths are due to infectious complications. Methods: From May 2021 to June 2022, children aged one through 18 years, with a recent diagnosis of ALL, admitted to three pediatric oncology centers in Brazil, were enrolled in this multicenter, open-label, randomized, phase 3 clinical trial. Eligible patients were randomly divided into two groups, based on a 1:1 allocation ratio, to receive, or not, levofloxacin as a prophylactic agent during the induction phase. All patients were treated according to the IC-BFM 2009 chemotherapy protocol. Primary endpoints were carbapenemase-producing Enterobacteriaceae (CPE) colonization, Clostridioides difficile diarrhea, and other adverse events related to the use of levofloxacin. The secondary endpoint was febrile neutropenia during induction. The median follow-up was 289 days. Results: Twenty patients were included in this trial, 10 in each group (control and levofloxacin). Mild adverse reactions related to levofloxacin were observed in three patients (30%). Three patients had Clostridioides difficile diarrhea, two in the levofloxacin group and one in the control group (p > 0.99). Only one patient presented colonization by CPE. This patient belonged to the levofloxacin group (p > 0.99). Nine patients presented febrile neutropenia, five in the control group and four in the levofloxacin intervention group (p > 0.99), one patient died due to febrile neutropenia. Conclusion: The use of levofloxacin was shown to be safe in the induction phase in children with de novo ALL. The use of this medication did not increase the rate of colonization by CPE nor the rate of diarrhea by C. difficile. All adverse reactions were mild and remitted either spontaneously or after switching medicine administration from oral to intravenous route.
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Resumo Objetivo Mapear os cuidados em saúde do dispositivo Pegfilgrastim on-body injector na prevenção de neutropenia em adultos com câncer em assistência domiciliar após quimioterapia ambulatorial. Métodos Revisão de escopo baseada na metodologia do Joanna Briggs Institute . Foram incluídos somente estudos com adultos com câncer submetidos à quimioterapia ambulatorial. A busca foi realizada nas bases de dados Cochrane, CINAHL, EMBASE, LILACS , PubMed, Scopus, LIVIVO e Web of Science, além da literatura cinzenta ProQuest, Scielo, Banco de Dados em Enfermagem, Google Scholar, Open Grey, bula do medicamento e websites . Foram esgotadas as buscas nas referências dos estudos elegidos. Todos os estudos identificados foram exportados para o gerenciador de referências EndNote para organização e remoção das duplicadas. Utilizou-se o aplicativo web Rayyan para seleção das evidências. Os estudos foram selecionados por pares e de forma independente, sendo os conflitos solucionados por um terceiro pesquisador. Resultados Foram incluídos 10 artigos cujos resultados foram subdivididos nas categorias: adesão do paciente, opinião da equipe de saúde, carga de trabalho do paciente em tratamento do câncer e uso do dispositivo na prática clínica. O dispositivo apresenta poucas falhas e foi aceito pelas equipes de saúde e pacientes na maioria dos estudos. Conclusão Os principais cuidados em saúde para o uso do dispositivo Pegfilgrastim on-body injector estão relacionados à técnica de preparo da pele onde o dispositivo será aplicado, o preparo e a administração do dispositivo. Além disso, salienta-se a importância da avaliação do conhecimento do paciente e seu familiar sobre o dispositivo, o fornecimento de todas as orientações necessárias, verbalmente e por escrito, de forma clara e objetiva, e a validação dessas informações, certificando-se que o paciente compreendeu todas elas e está seguro.
Resumen Objetivo Mapear los cuidados de la salud al utilizar el dispositivo Pegfilgrastim on-body injector para prevenir la neutropenia en adultos con cáncer en atención domiciliaria después de quimioterapia ambulatoria. Métodos Revisión de alcance basada en la metodología del Joanna Briggs Institute . Se incluyeron solamente estudios con adultos con cáncer sometidos a quimioterapia ambulatoria. La búsqueda se realizó en las bases de datos Cochrane, CINAHL, EMBASE, LILACS , PubMed, Scopus, LIVIVO y Web of Science, además de la literatura gris ProQuest, Scielo, Banco de Datos de Enfermería, Google Scholar, Open Grey, prospecto del medicamento y sitios web. Se concluyeron las búsquedas en las referencias de los estudios seleccionados. Todos los estudios identificados se exportaron al programa de gestión de referencias EndNote para organizarlas y remover las duplicadas. Se utilizó la aplicación web Rayyan para seleccionar las evidencias. Se seleccionaron los estudios por pares y de forma independiente, y los conflictos se solucionaron mediante un tercer investigador. Resultados Se incluyeron diez artículos cuyos resultados fueron subdivididos en las siguientes categorías: adhesión del paciente, opinión del equipo de salud, carga de trabajo del paciente en tratamiento de cáncer y uso del dispositivo en la práctica clínica. El dispositivo presenta pocas fallas y fue aceptado por los equipos de salud y por los pacientes en la mayoría de los estudios. Conclusión Los principales cuidados de la salud para el uso del dispositivo Pegfilgrastim on-body injector se relacionan con la técnica de preparación de la piel donde se aplicará el dispositivo, la preparación y la administración del dispositivo. Además, se destaca la importancia de la evaluación de conocimientos del paciente y su familiar sobre el dispositivo, la entrega de todas las instrucciones necesarias, verbalmente y por escrito, de forma clara y objetiva, la validación de la información y la verificación de que el paciente haya comprendido todo y esté seguro.
Abstract Objective To map the health care of Pegfilgrastim On-body Injector in neutropenia prevention in adults with cancer in home care after outpatient chemotherapy. Methods This is a scoping review based on the JBI methodology. Only studies with adults with cancer undergoing outpatient chemotherapy were included. The search was carried out in the Cochrane, CINAHL, EMBASE, LILACS, PubMed, Scopus, LIVIVO and Web of Science databases, in addition to gray literature ProQuest, SciELO, Database in Nursing, Google Scholar, Open Grey, drug leaflet and websites. The searches in the references of selected studies were exhausted. All identified studies were exported to the EndNote reference manager for organization and removal of duplicates. The Rayyan web application was used for evidence selection. The studies were selected by pairs independently, with conflicts resolved by a third researcher. Results A total of 10 articles were included, whose results were subdivided into categories: patient compliance, health team opinion, patient workload in cancer treatment and device use in clinical practice. The device has few flaws and was accepted by health care teams and patients in most studies. Conclusion The main health care for Pegfilgrastim On-body Injector use is related to the skin preparation technique where the device will be applied, in addition to device preparation and administration. Moreover, the importance of assessing the knowledge of patients and their family about the device is highlighted, providing all the necessary guidelines, verbally and in writing, clearly and objectively, and validating this information, making sure that patients have understood all of them and are safe.
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ABSTRACT Background: Severe congenital neutropenia type 4 (SCN4) is a rare autosomal recessive granulopoiesis disorder caused by G6PC3 gene pathogenic variants. The estimated prevalence is 1/10,000,000 people. Over 90% of patients present a syndromic form with variable multisystemic involvement, including congenital heart defects, increased visibility of superficial veins (IVSV), inflammatory bowel disease, and congenital urogenital defects as prominent symptoms. Objectives: The objective of the study was to study non-hematological phenotypic findings that suggest a clinical diagnosis of SCN4. Methods: We examined medical records of patients diagnosed with neutropenia from January 2000 to December 2020, selecting cases with non-hematologic manifestations for phenotypic description and G6PC3 gene sequencing. Results: We found 11 cases with non-hematologic features: congenital heart defects in 8, IVSV in 6, inflammatory bowel disease in 4, urogenital defects in 4, and similar facial appearance. In addition, Sanger sequencing confirmed 3 homozygous cases for the c.210delC variant, a compound heterozygous harboring this variant, and a c.199_218+1 deletion. Conclusions: Our findings of the c.210delC variant in very close geographical settings, to date, have only been reported among Mexicans, and a mutual uncommon surname in two families strongly supports a founder effect for the variant in the studied population. Furthermore, the described non-hematologic symptoms in patients with severe primary neutropenia should be explored, confirming SCN4 by investigating G6PC3 gene mutations.
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Tratamientos intensificados se asocian con neutropenia severa, identificada como factor de riesgo de complicaciones infecciosas en pacientes con enfermedades neoplásicas. Objetivo: Evaluar la importancia del momento de inicio del tratamiento antibiótico en la evolución y pronóstico de pacientes con neutropenia febril (NF) por Cáncer ingresados al Hospital de Niños "J.M. de los Ríos" entre febrero 2020 febrero 2022. Métodos: Estudio descriptivo, prospectivo, transversal, analítico, se registró formulario de recolección de datos y base de datos Google Drive para análisis estadístico por distribución de frecuencias y porcentajes. Se entregó Consentimiento y Asentimiento Informado a padres y pacientes, ambos aprobados por Comisión de Bioética, capacitándose en manejo de fiebre neutropénica. Incluyó pacientes con fiebre durante la primera hora después de recibir quimioterapia, indicándoseles antibióticos. Resultados: Sexo masculino 63,2 % (36/57) de los casos de NF y preescolares 43,9 % (25/57) fueron los más afectados. Leucemia Linfocítica Aguda fue el cáncer más frecuente 68,4 % (39/57) y Bacteriemia 40,4 % (23/57) la patología infecciosa predominante. Evolucionaron satisfactoriamente en la mayoría de los casos; la Media de la estancia hospitalaria fue 14,56 días, más prolongada en pacientes con Leucemia Linfocítica Aguda en fase de inducción. Gramnegativos los aislamientos predominantes 35,1 % (20/57), representados por Pseudomonas aeruginosa. El tiempo de cumplimiento de antibióticos fue 4 - 12 horas desde el inicio de fiebre. Mortalidad ocurrió por enfermedad de base mal controlada. Conclusiones: Cumplimiento de antibióticos durante la primera hora de fiebre neutropénica en pacientes pediátricos con cáncer disminuye complicaciones infecciosas, estancia hospitalaria y mortalidad.
Intensified treatments are associated with severe neutropenia, identified as a risk factor for infectious complications in patients with neoplastic diseases. Objective: To evaluate the importance of the moment of initiation of antibiotic treatment in the evolution and prognosis of patients with febrile neutropenia (NF) due to Cancer admitted to the Hospital de Niños J.M. de los Ríos between February 2020 - February 2022. Methods: Descriptive, prospective, cross-sectional, analytical study, a data collection form and Google Drive database were registered for statistical analysis by distribution of frequencies and percentages. Consent and Informed Assent were given to parents and patients, both approved by the Bioethics Commission, training in the management of neutropenic fever. It included patients with fever during the first hour after receiving chemotherapy, indicating antibiotics. Results: Male sex 63.2 % (36/57) of the cases of NF and preschoolers 43.9 % (25/57) were the most affected. Acute Lymphocytic Leukemia was the most frequent cancer 68.4 % (39/57) and Bacteremia 40.4 % (23/57) the predominant infectious pathology. They evolved satisfactorily in most cases; Mean hospital stay was 14.56 days, longer in patients with Acute Lymphocytic Leukemia in the induction phase. Gram-negative the predominant isolates 35.1 % (20/57), represented by Pseudomonas aeruginosa. Antibiotic compliance time was 4 - 12 hours from the onset of fever. Mortality occurred due to poorly controlled underlying disease. Conclusions: Antibiotic compliance during the first hour of neutropenic fever in pediatric patients with cancer reduces infectious complications, hospital stay and mortality.
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Introducción: Las inmunodeficiencias primarias son enfermedades de origen genético causadas por alteraciones cuantitativas o funcionales del sistema inmune. La incidencia de las neutropenias es de 3,4 casos por millón de personas por año Son enfermedadess heterogéneas en cuanto a la etiología, la fisiopatología, la clínica y la respuesta al tratamiento. Muchos casos presentan manifestaciones graves y mal pronóstico aún con diagnóstico y tratamiento oportunos. Objetivo: Presentar a la comunidad científico-médica un caso de neutropenia congénita con evolución desfavorable. Presentación de caso: Lactante femenina de siete meses con antecedentes de múltiples ingresos por infecciones respiratorias altas y bajas complicadas, asociadas a cuadros diarreicos, infecciones de piel y partes blandas (abscesos en región glútea y pabellones auriculares). Valorada por las especialidades de Inmunología y Hematología, las que diagnosticaron una neutropenia congénita (infecciones por Estafilococo aureus, Pseudomona sp y Cándida albicans). Recuento absoluto de neutrófilos en varias ocasiones con valores en 108 mm3; ausencia de elementos del gránulo en sistema granulopoyético en medulograma y estudios inmunológicos (ausencia de área tímica e IgA en 0,14 g/L). Se inició tratamiento con antimicrobianos de amplio espectro, inmunomoduladores (Hebertrans, Leukocin, Prednisona) y concentrado de granulocitos de donación paterna con escasa respuesta al tratamiento. Evolucionó desfavorablemente y falleció por shock séptico. El informe de necropsia confirmó el diagnóstico. Conclusiones: La neutropenia congénita se sospecha en pacientes con antecedentes de infecciones recurrentes con evolución tórpida y valores disminuidos de neutrófilos, es de gran importancia establecer un diagnóstico de certeza y conducta terapéutica temprana que favorezcan la disminución de la morbilidad y mortalidad(AU)
Introduction: Primary immunodeficiencies are diseases of genetic origin caused by quantitative and/or functional alterations of the immune system. The incidence of neutropenia is 3.4 cases per million people per year; it is a heterogeneous entity in terms of etiology, pathophysiology, clinic and response to treatment. It presents with severe manifestations and poor prognosis even with timely diagnosis and treatment. Objective: To present to scientific and medical community a case of Congenital Neutropenia with unfavorable evolution. Case presentation: Seven-month-old female infant with a history of multiple admissions for complicated upper and lower respiratory tract infections, associated with diarrhea and skin and soft tissue infections (abscesses in the gluteal region and ear pinnae). He was evaluated by Immunology and Hematology and Congenital Neutropenia was diagnosed (Staphylococcus aureus, Pseudomonas sp and Candida albicans infections), absolute neutrophil count on several occasions with values in 108 mm3, absence of granule elements in granulopoietic system in medullogram and studies immunological (absence of thymic area and IgA at 0.14 g/L). Treatment was started with broad-spectrum antimicrobials, immunomodulators (Hebertrans, Leukocin, Prednisone) and paternally donated granulocyte concentrate with little response to treatment. He evolved unfavorably and died of septic shock. The autopsy report confirmed the diagnosis. Conclusions: Congenital Neutropenia is suspected in patients with a history of recurrent infections with torpid evolution and neuthopenia, it is of great importance to establish an accurate diagnosis and early therapeutic behavior that favor the reduction of morbidity and mortality(AU)
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HumansABSTRACT
La neutropenia congénita grave (NCG) es una entidad heterogénea cuya característica común es un recuento absoluto de neutrófilos inferior a 0,5 x 10 9/l. Presenta gran heterogeneidad genética, las mutaciones más frecuentes son las del gen de la elastasa 2 (ELA 2). El tratamiento de primera elección es la administración de factor estimulador de colonias de granulocitos. Los pacientes con NCG presentan infecciones graves en etapas tempranas de la vida. Se presenta una paciente con NCG asociada a fenotipo peculiar con facies triangular, retromicrognatia, patrón venoso prominente en miembros inferiores, comunicación interauricular y mal progreso ponderal, en quien se diagnosticó déficit de la enzima glucosa 6 fosfato deshidrogenasa, subunidad catalítica 3 (G6PC3). A pesar de lo infrecuente de esta mutación como causa de NCG (2 %), su conocimiento cobra importancia porque la coexistencia del fenotipo característico con una NCG orienta en la solicitud del estudio genético que permite arribar al diagnóstico.
Severe congenital neutropenia (SCN) is a heterogeneous disease whose more common feature is an absolute neutrophil count less than 0.5 x 10 9/l. It presents great genetic heterogeneity. Autosomal dominant inherited mutations of the elastase 2 gene (ELA2) represent the most common etiology. The first choice treatment is the administration of granulocyte colony stimulating factor. Patients with SCN develop severe infections early in life. We present a patient who associated SCN to a peculiar phenotype, characterized by triangular facies, retromicrognathia, prominent venous pattern in the lower limbs, atrial septal defect and poor weight progress, in whom a deficiency of the enzyme glucose 6 phosphate dehydrogenase, a catalytic subunit 3 (G6PC3), was diagnosed. Despite the infrequency of this mutation as the origin of SCN (2%), its knowledge becomes important because the coexistence of the characteristic phenotype and SCN guides the request for the genetic study that allows reaching the diagnosis.