Riesgo de mortalidad en infecciones invasivas por Mucor SPP. en niños con enfermedades hemato-oncológicas: revisión sistemática / Mortality risk of invasive Mucor spp. infections in children with cancer: A systematic review

Los estudios sobre la infección fúngica invasiva (IFI) por Mucor spp. en pacientes pediátricos con patología hematooncológica, son de baja solidez científica, lo que dificulta conocer en profundidad sus características y evolución. Con el objetivo de analizar la evolución fatal de esos pacientes, se llevó a cabo esta revisión sistemática (RS). Material y métodos: La búsqueda bibliográfica se realizó con fecha 23 de marzo de 2023, en las principales bases de datos (Medline (a través de Pubmed), Embase (a través de Embase-Elsevier), The Cochrane Library (a través de Wiley), Cinahl (a través de Ebsco HOST), SCI-EXPANDED, SciELO (a través de la WOS) y Scopus (a través de Scopus-Elsevier), libre (mediante el motor Google) y revisando las citas de los artículos incluidos. Resultados: Se rescataron 1393 artículos, de los cuales se descartaron 1386 por diversas razones. Mediante el análisis de los textos completos, finalmente se incluyeron 7 estudios. Todos los estudios eran series de casos (nivel 4). La mediana de la frecuencia de muerte observada fue de 36,6% (Q1 20% - Q347%). Conclusiones: Esta RS mostró en niños con patología hemato-oncológica, que la mortalidad por IFI por Mucor spp. alcanzó a casi un tercio de los pacientes (AU)

Studies on invasive fungal infection (IFI) by Mucor spp. in pediatric patients with cancer have a low level of evidence, which makes it difficult to elucidate its characteristics and progression. To analyze the fatal outcome of these patients, this systematic review (SR) was conducted. Material and methods: A literature search was carried out on March 23, 2023, in the following main databases (Medline (via Pubmed), Embase (via Embase-Elsevier), The Cochrane Library (via Wiley), Cinahl (via Ebsco HOST), SCI-EXPANDED, SciELO (via the WOS) and Scopus (via Scopus-Elsevier). Additionally, a complementary search was carried out using free search engines (such as Google) and by reviewing the references of the included articles. Results: A total of 1393 articles were retrieved, of which 1386 were excluded for various reasons. After a thorough analysis of the full-text articles, 7 studies were ultimately included in the review. All studies were case series (level 4). The median observed death rate was 36.6% (IQR, 20% - 47%). Conclusions: This SR showed that in children with hematological-oncological disease, mortality due to IFI by Mucor spp. affected almost one third of the patients (AU)

La neutropenia: Una revisión narrativa / Neutropenia: A narrative review

Introducción: La Neutropenia constituye una de las complicaciones más comunes en pacientes que reciben tratamiento sistémico con quimioterapia, siendo esta una población heterogénea; por lo tanto su presentación clínica es inespecífica, pudiendo presentarse de manera asintomática o inclusive evidenciar cuadros muy severos con signos de sepsis grave. Ante lo referido, en la actualidad los grupos de trabajo requieren determinar de manera consistente los diferentes factores de riesgo que contribuyen a la presentación de neutropenia, con el objetivo de estratificar de manera óptima al paciente y así disminuir complicaciones. Puntos importantes: Este trabajo se enfatiza en analizar los factores de riesgo; tanto del paciente, la enfermedad y el tratamiento; de acuerdo a los sistemas de estratificación como MASCC, CISNE. Además se evaluaron los fundamentos clínicos y microbiológicos para categorizar al paciente e incluir medidas de soporte profiláctico a los grupos con mayor fragilidad, disminuyendo el alto riesgo de complicaciones severas. Conclusión: La neutropenia es un evento adverso indeseable en el manejo del tratamiento oncohematológico. Los sistemas de estratificación de riesgos MASCC y CISNE son herramientas útiles para seleccionar pacientes de bajo riesgo. Sin embargo, otros factores, como el tipo de tumor y el tipo de infección, pueden influir en la estratificación. Por lo tanto, es importante manejar a cada paciente de forma individualizada.El inicio de la profilaxis antimicrobiana y el uso de FECG pueden ayudar a reducir la morbimortalidad.

Introduction: Neutropenia is one of the most common complications in patients receiving systemic treatment with chemotherapy; this is a heterogeneous population; therefore, its clinical presentation is nonspecific, presenting asymptomatically or even showing very severe symptoms with signs of severe sepsis. Given those above, currently, the working groups need to consistently determine the different risk factors contributing to the presentation of neutropenia to stratify the patient and thus optimally reduce complications. Important points: This work emphasizes the analysis of risk factors, including the patient, the disease, and the treatment, according to stratification systems such as MASCC and CISNE. In addition, the clinical and microbiological foundations were evaluated to categorize the patient and include prophylactic support measures for the most frail groups, reducing the high risk of severe complications. Conclusion: Neutropenia is an undesirable adverse event in managing oncohaematological treatment. The MASCC and CISNE risk stratification systems are valuable tools for selecting low-risk patients. However, other factors, such as the type of tumor and infection, may influence the stratification. Therefore, it is essential to manage each patient individually. The initiation of antimicrobial prophylaxis and the use of FECG can help reduce morbidity and mortality.

Reações adversas medicamentosas em pacientes em quimioterapia e estratégias de intervenções / Adverse drug reactions in chemotherapy patients and intervention strategies / Reacciones adversas a medicamentos en pacientes quimioterápicos y estrategias de intervención

A quimioterapia do câncer pode ocasionar reações adversas medicamentosas (RAM), podendo resultar de interações medicamentosas (IM) e impactar na adesão. O presente estudo relatou as RAM apresentadas por pacientes em quimioterapia (QT) e propôs estratégias de intervenções. Este trabalho foi aprovado em comité de ética (5.160.503), sendo incluídos 23 pacientes em quimioterapia (oral- VO e/ou endovenosa- EV) e todos foram entrevistados. Recebiam apenas o QTEV, 20 pacientes e 2 QTEV e VO, a maioria em tratamento paliativo (50%), predomínio de estadiamento IV, sendo as doenças mais presentes de pâncreas (27,3%), estômago (22,7%) e mama (18,2%) e esquema mais usado foi Carboplatina + Paclitaxel. As principais comorbidades foram diabetes e hipertensão arterial. As interações medicamentosas foram classificadas em graves (45%), moderadas (55%) e intencional (75%), sendo necessário introdução de medicamentos de suporte (61%). Houve RAM de maior gravidade, neutropenia, sendo necessário a suspensão temporária, e de menor gravidade náuseas. Houve um óbito relacionado a evolução de doença e, talvez, o tratamento possa ter contribuído. Ao final, foram feitas as intervenções para cada caso e validado o formulário para a consulta farmacêutica a pacientes oncológicos.

Cancer chemotherapy can cause adverse drug reactions (ADRs), which can result from drug interactions (IM) and impact adherence. The present study reported the ADRs presented by patients undergoing chemotherapy (CT) and proposed intervention strategies. This work was approved by the ethics committee (5,160,503), and 23 patients on chemotherapy (oral-VO and/or intravenous-IV) were included and all were interviewed. Only received CTIV, 20 patients and 2 CTIV and VO, most in palliative treatment (50%), predominance of stage IV, being the most common diseases of pancreas (27.3%), stomach (22.7%) and breast (18.2%) and the most used regimen was Carboplatin + Paclitaxel. The main comorbidities were diabetes and arterial hypertension. Drug interactions were classified as severe (45%), moderate (55%) and intentional (75%), requiring the introduction of supportive drugs (61%). There were more severe ADRs, neutropenia, requiring temporary suspension, and less severe nausea. There was one death related to the evolution of the disease and, perhaps, the treatment may have contributed. At the end, interventions were made for each case and the form for the pharmaceutical consultation to cancer patients was validated.

La quimioterapia contra el cáncer puede causar reacciones adversas a los medicamentos (RAM), que pueden ser consecuencia de interacciones farmacológicas (IM) y repercutir en la adherencia. El presente estudio reportó las RAM presentadas por pacientes en quimioterapia (QT) y propuso estrategias de intervención. Este trabajo fue aprobado en comité de ética (5.160.503), se incluyeron 23 pacientes en quimioterapia (oral- VO y/o endovenosa-EV) y todos fueron entrevistados. Recibieron sólo QTEV, 20 pacientes y 2 QTEV y VO, la mayoría en tratamiento paliativo (50%), predominio de estadiaje IV, siendo las enfermedades más presentes las de páncreas (27,3%), estómago (22,7%) y mama (18,2%) y el esquema más utilizado fue Carboplatino + Paclitaxel. Las principales comorbilidades fueron la diabetes y la hipertensión arterial. Las interacciones farmacológicas se clasificaron como graves (45%), moderadas (55%) e intencionadas (75%), requiriendo la introducción de fármacos de apoyo (61%). La RAM más grave fue la neutropenia, que requirió la suspensión temporal, y la menos grave las náuseas. Hubo una muerte relacionada con la evolución de la enfermedad y, tal vez, el tratamiento pudo haber contribuido. Al final, se realizaron intervenciones para cada caso y se validó el formulario de consulta farmacéutica a pacientes oncológicos.

Cuidados a la persona con cáncer y neutropenia / Caring for the person with cancer and neutropenia

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.

Clinical tolerability and pharmacokinetics of troxacitabine / 中华肿瘤杂志

Objective: To investigate the safety and efficacy of troxatabine in advanced or relapsed malignant tumors resistant to standard therapy in China. Methods: This is a phase Ⅰ prospective study. During dose escalation, patients in Cancer Hospital, Chinese Academy of Medical Sciences received a single-dose intravenous infusion of troxacitabine. The planned dosing groups were 1.8, 3.6, 4.8, 6.4 and 8.0 mg/m(2) on days 1 and 8 every 3 weeks. The data of all patients were collected for safety analyses. Safety and tolerability were evaluated by monitoring adverse events. Results: Nineteen patients were enrolled from April 2018 to May 2019. The major adverse events were fatigue (89.5%, 17/19), leukopenia (84.2%, 16/19) and neutropenia (78.9%, 15/19). The dose limiting toxicity was neutropenia. The maximum tolerated dose was 6.4 mg/m(2). The best effect was stable disease (43.8%). The half-life of elimination phase from 15.91 hours to 76.63 hours in each dose group. Conclusions: The toxicity of troxacitabine is well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 6.4 mg/m(2).

Consensus on clinical diagnosis, treatment, and prevention of chemotherapy-induced neutropenia in China (2023 edition) / 中华肿瘤杂志

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.

Short-term efficacy of empagliflozin in children with glycogen storage disease type Ⅰb / 中华儿科杂志

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×109, 0.50×109, 0.48×109, 0.48×109/L to 1.48×109, 3.04×109, 1.10×109, 0.73×109/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.

Neutropenia congénita de tipo IV: reporte de un caso / Congenital neutropenia type IV: case report

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.

Prevalencia de gérmenes con multi resistencia antibiótica en bacteriemia asociada a neutropenia febril en pacientes oncológicos hospitalizados. Un estudio de centro único / Prevalence of germs with multi antibiotic resistance in bacteremia associated with febrile neutropenia in hospitalized cancer patients. A single-center study

Introducción: El cáncer en el año 2020 provoco 1,4 millones de muertes, el 47% en personas menores de 65 años de edad,la neutropenia febril en el paciente oncológico aumenta los casos de infecciones graves, incrementando la morbimortalidad cuando no se ha empezado un tratamiento de oportuno. El objetivo del presente estudio fue describir una población con esta patología en un centro de referencia regional. Metodología: Este estudio transversal, se realizó en el Instituto Oncológico Nacional "Dr. Juan Tanca Marengo", Sociedad de Lucha contra el Cáncer, Solca Guayaquil, período enero 2020-junio 2021, con una muestra no probabilística, de pacientes con neoplasias, neutropenias y cultivos positivos. Se registraron variables demográficas, clínicas, de laboratorio. Se utiliza estadística descriptiva invariada. Resultados: Se analizan 126casos, de edad promedio 55 años, el 50.8% fue de sexo femenino; el 88.1 % ingresó con neutropenia febril; la estancia hospitalaria promedio fue de 7 días. La Escherichia coli fue el microorganismo más frecuente con el 17.5 %, seguido por Klebsiella neumonía en el 9.5 %, Enterobacteria aerógenas y Pseudomonas eruginosa en el 4.8 %. El 70.2 % de las bacterias aisladas presentó resistencia bacteriana, el 47 % fueron bacterias betalactamasa de espectro ampliado (BLEA), el 40 % fue betalactamasa de espectro extendido (BLEE), y el 5 % productor de carbapenémicas (KPC), el 57.5 % con resistencia bacteriana tuvo una estancia hospitalaria mayor a 7 días Conclusión: El principal microorganismo fue Escherichia coli y la resistencia mayormente la tuvieron las bacterias betalactamasa de espectro ampliado positiva; permitiendo conocer la epidemiología local del perfil microbiológico y su relación con los pacientes oncológicos con neutropenia febril

In troduction:Cancer in 2020 caused 1.4 million deaths, 47% in people under 65 years of age, febrile neu-tropenia in cancer patientsincreases cases of serious infections, increasing morbidity and mortality when Timely treatment has not been started. The objective of the present study was to describe a pop-ulation with this pathology in a regional reference center.Met hodology: This cross-sectional study was conducted at the National Oncology Institute "Dr. Juan Tanca Marengo," Society for the Fight Against Cancer, Solca-Guayaquil, period January 2020-June 2021, with a non-probabilistic sample of patients with neoplasms, neutropenia, and positive cultures. Demo-graphic, clinical, and laboratory variables were recorded. Univariate descriptive statistics are used.R esults: 126 cases were analyzed, with an average age of 55 years; 50.8% were female; 88.1% were admitted with febrile neutropenia; the average hospital stay was seven days. Escherichia coli was the most frequent microorganism with 17.5%, followed by Klebsiella pneumoniae in 9.5%, Enterobacter aerogenes, and Pseudomonas aureginosa in 4.8%. 70.2% of the isolated bacteria presented bacterial resistance, 47% were extendedspectrum beta-lactamase bacteria (ESBL), 40% were extended-spectrum betalactamase (ESBL), and 5% produced carbapenemases (KPC), 57.5% with bacterial resistance had a hospital stay greater than seven days.C o nclusion: The main microorganism was Escherichia coli, and resistance was primarily found in ex-tended-spectrum beta-lactamase-positive bacteria, allowing us to know the local epidemiology of the microbiological profile and its relationship with cancer patients with febrile neutropenia

Neutropenia al diagnóstico de lupus eritematoso sistémico: prevalencia y correlaciones clínicas y serológicas. Nuestra cohorte / Neutropenia at diagnosis of systemic lupus erythematosus: prevalence and clinical and serological correlations. Our cohort

Introducción: las manifestaciones hematológicas en el lupus eritematoso sistémico (LES) son frecuentes. La leucopenia se presenta del 50 al 60% de los casos, pero solo el 17% tiene un recuento leucocitario <1.000/mm3. La neutropenia en pacientes con leucopenia ocurre entre un 20-40% (según el valor de corte del laboratorio). Los mecanismos posibles de neutropenia descriptos son: aumento en la destrucción de granulocitos periféricos por anticuerpos antineutrófilos, opsonización y destrucción por monocitos; cambios en el pool esplénico y marginal; y disminución en la producción medular. La formación de trampas extracelulares de neutrófilos (neutrophil extracellular traps, NETs) contribuye en la producción de interferón tipo 1 (IFN-1) a partir de plasmocitos y células dendríticas causando daño endotelial y cambios protrombóticos. La NETosis y el clearence anormal de material apoptótico promueven mayor liberación de antígenos y la consiguiente formación de autoanticuerpos. Las consecuencias infecciosas de la neutropenia al diagnóstico de LES se desconocen. Los objetivos del presente estudio fueron conocer la prevalencia de la neutropenia al diagnóstico de LES, determinar su correlación con otras variables de la patología, y estudiar su relación con una mayor probabilidad de actividad, daño, infecciones y mortalidad. Materiales y métodos: estudio descriptivo, retrospectivo. Se incluyeron pacientes con diagnóstico de LES (Systemic Lupus International Collaborating Clinics, SLICC 2012) de la cohorte del Sanatorio, desde enero de 2010 a diciembre de 2020. Se consignaron variables demográficas y asociadas a la enfermedad (criterios clínicos y de laboratorio). Escala de actividad: Systemic Lupus Erythematosus Disease Activity Index 2k (SLEDAI-2k). Se dividieron en dos grupos según la presencia de neutropenia (<1.500/mm3). Se definió un subgrupo de neutropenia severa: <500/mm3. En pacientes con neutropenia se evaluó la presencia de infección viral, bacteriana y tratamiento con factor de crecimiento de colonias de granulocitos y monocitos (GM-GSF). Análisis estadístico: los datos descriptivos se presentaron como medias y sus desvíos estándar (±DS) (variables continuas) y porcentajes (variables categóricas). Se compararon variables independientes de acuerdo con su distribución con test Mann Whitney. Se utilizó prueba t de Student para comparación de medias, y chi cuadrado (X2) para variables cualitativas. Se consideró como estadísticamente una p≤0,05. Resultados: se incluyeron 70 pacientes. Mujeres 59 (84%), edad media 38,6 años (18-72). Leucopenia 24 (34%), linfopenia 30 (42,8%), neutropenia 12 (17%), neutropenia severa 2 (2,8%) y plaquetopenia 7 (10%). Grupo con neutropenia (n=12): Sicca 12 (100%). Media índice neutrófilo/linfocito (INL) 1,33 (DS 0,69), infecciones: virus de Epstein-Barr (VEB) IgM (+) uno, parvovirus y CMV solicitados y negativos dos. PAMO realizada una: normal. Pacientes en tratamiento con GM-GSF: dos, sin eventos adversos. Dos infecciones urinarias. Conclusiones: en nuestro estudio se observó correlación entre neutropenia con síntomas Sicca, leucopenia y linfopenia, y un INL menor. Se desconoce si se relacionó a peor evolución. La presencia de infección fue baja (16%). Dos pacientes requirieron GM-GSF (con neutropenia severa), sin haber presentado eventos adversos.

Introduction: hematological manifestations are frequent in systemic erythematosus lupus (SLE). Leukopenia is seen in between 50 to 60% of cases, but only 17% has a leukocyte count <1,000/mm3. Neutropenia in patients with leukopenia occurs between 20-40% of cases, depending on the cut-off value used. Possible described mechanisms for neutropenia are: an increase in destruction of granulocytes by anti-neutrophil antibodies, opsonization and destruction by monocytes; change in the splenic and marginal neutrophil pool; a diminished production in the bone marrow. The formation of NETs contributes to the production of INF-1 from plasmocytes and dendritic cells, causing endothelial damage and pro-thrombotic changes. NETosis and apoptotic abnormal clearence promote the formation of antigens and subsequent autoantibodies. Infectious consequences of neutropenia in SLE are still unknown. The objectives of this article were to know the prevalence of neutropenia at diagnosis of SLE in our hospital, and secondly to determine its correlation with other variables of the disease and to investigate whether it's related with a greater probability of infections. Materials and methods: descriptive, retrospective study. Patients with diagnosis of SLE (SLICC 2012) from our cohort were included. Demographic and related to disease variables were stated. Activity scale: SLEDAI-2k. Patients were divided into two groups according to the presence or absence of neutropenia (<1.500/mm3 ) and multivariate analysis was performed to clinical and analytical variables. A subgroup with severe neutropenia (<500/mm3) was evaluated. Multivariate analysis was performed to detect correlations between a diminished neutrophil count and clinical manifestations, disease severity, autoantibodies profile, infections, and associated diseases. In neutropenic patients, the presence of viral or bacterial infection and the use of GM-GSF were evaluated. Statistical analysis was performed as mean +/-SD for continuous variables and percentage for categorical variables. T-Test or Mann-Whitney were used to compare independent variables according to distribution. Student's T and Chi-Square for qualitative variables. Statistical significance: p<0.05. Results: 70 patients were included. Female 59 (84%), mean age 38.6 years (18- 72). Leukopenia 24 (34%), lymphopenia 30 (42.8%), neutropenia 12 (17%), severe 2 (2.8%), thrombocytopenia 7 (10%). Neutropenic group: Sicca 12 (100%), neutrophil/lymphocyte index (NLI) 1.33 (DS 0.69), infections: EBV IgM+1/12, parvovirus and CMV negative 2/12. BMA 1/12, without pathologic findings. GM-GSF 2/12. Infections: 2/12 (urinary). Conclusions: we observed a correlation between Sicca symptoms, leuko and lymphopenia, and a lower NLI. The clinical significance of these findings was uncertain. The presence of infection was low (16%). Two required GM-GSF, having not presented adverse events.

Riesgo de infección en pacientes oncológicos colonizados por bacterias productoras de p-lactamasas de espectro extendido y enterobacterias productoras de carbapenemasas / Risk of infection in cancer patients colonized by extended expectrum p-lactamases and carbapenem producing Enterobacteriaceae

INTRODUCCIÓN: La prevalencia de microorganismos multirresistentes es un problema de salud pública que continúa creciendo a lo largo del mundo. Existe una población principalmente susceptible de ser colonizada y posteriormente infectarse, son los pacientes oncológicos. OBJETIVO: Identificar las características clínicas y patológicas de los pacientes oncológicos y su relación con la infección con microorganismos productores de BLEE y EPC. PACIENTES Y MÉTODOS: Se condujo un estudio retrospectivo y de carácter analítico entre el primero de enero de 2019 y el 30 de junio de 2020 en tres unidades hemato-oncológicas. RESULTADOS: Incluyó a 3.315 pacientes, de los cuales 217 (6,5%) se encontraban colonizados por microorganismos productores de BLEE y EPC; de éstos, 106/217 (48,8%) presentaron al menos un episodio de infección. El microorganismo más frecuentemente aislado fue Klebsiella pneumoniae, en 29/106 (27,4%). De los infectados, 18/106 (17%) presentaron infección por el mismo microorganismo colonizador. La mucositis (p = 0,002), edad mayor a 65 años (p = 0,041), hipoalbuminemia (p < 0,01), neutropenia (p < 0,01) y la presencia dispositivos invasivos (p < 0,01) demostraron una relación con el desarrollo de infección. CONCLUSIÓN: La presencia de hipoalbuminemia (OR 3,3, IC 1,5-7,1, p < 0,01), dispositivos invasivos (OR 5,8, IC 3.0-11,4, p < 0,01) y neutropenia (OR 4,1, IC 1,5-11,4, p < 0,01) predicen el desarrollo de infecciones.

BACKGROUND: The prevalence of multi-resistant microorganisms is a public health problem that continues to grow globally. There is a population that is mainly susceptible to being colonized and subsequently infected, and these are cancer patients. AIM: To identify the clinical and pathological characteristics of cancer patients and their relationship with infection with ESBL and CPE producing microorganisms. METHODS: A retrospective and analytical study was conducted between January 1, 2019 and June 30, 2020 in three hematooncological units. RESULTS: We included 3315 patients of which 217 (6.5%) were colonized by microorganisms producing ESBL and CPE. Of these, 106/217 (48.8%) had at least one episode of infection. The most frequently isolated microorganism was Klebsiella pneumoniae 29/106 (27.4%). Of those infected, 18/106 (17%) presented infection by the same colonizing microorganism. Mucositis (p = 0.002), age over 65 years (p = 0.041), hypoalbuminemia (p < 0.01), neutropenia (p < 0.01) and the presence of invasive devices (p < 0.01) demonstrated a relationship with development of infection. The presence of hypoalbuminemia (OR 3.3, CI 1.5-7.1, P < 0.01), invasive devices (OR 5.8, CI 3.0-11.4, p < 0.01) and neutropenia (OR 4.1, CI 1.5-11.4, p < 0.01) predict the development of infections.

Enterocolitis neutropénica en el paciente oncológico pediátrico / Neutropenic enterocolitis in the pediatric cancer patient

Resumen La enterocolitis neutropénica (ECN) es una enfermedad heterogénea de foco digestivo, pero afectación sistémica, que corresponde a una condición clínica grave que amenaza la vida de pacientes inmunocomprometidos, particularmente oncológicos pediátricos. De patogenia aún poco definida y aunque de causa multifactorial, la ECN se asocia a los efectos citotóxicos de la quimioterapia empleada y se caracteriza por la triada clásica que incluye fiebre, neutropenia y dolor abdominal, donde la principal injuria se localiza en la mucosa intestinal, provocando su alteración como barrera y facilitando la invasión bacteriana intramural. La ECN constituye un reto diagnóstico para el equipo tratante, que requiere ser oportuno y contar con apoyo de un óptimo laboratorio general e imagenológico, para iniciar un completo manejo multidisciplinario en unidades y centros de alta complejidad. Se presenta una revisión actualizada del tema incorporando aspectos epidemiológicos, factores de riesgo, elementos de apoyo diagnóstico, consideraciones terapéuticas y medidas de prevención a fin de aportar en el conocimiento de esta patología, y reducir morbimortalidad en estos pacientes.

Abstract Neutropenic enterocolitis (NEC) is a heterogeneous disease of the gastrointestinal tract with systemic response, that corresponds to a severe and life-threatening clinical condition in immunocompromised patients, especially in childhood cancer. The pathologic features are poorly understood, although its multifactorial cause of NEC is well established and it is associated with the cytotoxic effects of the chemotherapy agents used and recognized by the classic triad of fever, neutropenia, and abdominal pain, secondary to gastrointestinal injuries that alters mucosal permeability and helps intramural bacterial invasion. NEC is truly a clinical challenge that requires an early diagnosis and a multidisciplinary approach including basic laboratory and imagological tests in high complexity centers. We present a current review, adding epidemiological aspects, risks factors, diagnostic support elements, therapeutic considerations, and preventive measures in order to provide knowledge of this disease and help to reduce morbidity and mortality associated with it.

Cuidados no uso do dispositivo Pegfilgrastim On-body injector na profilaxia de neutropenia induzida por quimioterapia: revisão de escopo / Cautions in the use of the Pegfilgrastim On-body injector device in the prophylaxis of chemotherapy-induced neutropenia: a scoping review

Introdução: A neutropenia febril induzida por quimioterapia é um fator de risco predisponente para infecção grave e aumenta a mortalidade do paciente com câncer. O uso de G-CSF é recomendado quando o risco de desenvolver neutropenia febril, decorrente do protocolo quimioterápico, é maior ou igual a 20%. Foi recentemente aprovado pela ANVISA uma nova apresentação de G-CSF, o Pegfilgrastim OBI. Dispositivo que conta com um sistema de aplicação automático que é ativado 27 horas após o término da quimioterapia. Objetivo: Mapear os cuidados em saúde para o uso do dispositivo "Pegfilgrastim OBI", na prevenção de neutropenia em pacientes adultos com câncer em assistência domiciliar após quimioterapia ambulatorial. Métodos: A revisão de escopo foi conduzida de acordo com a metodologia da Joanna Briggs Institute. A questão norteadora foi formulada a partir da estratégia PCC. Foram incluídos estudos com pacientes adultos com câncer submetidos à quimioterapia ambulatorial e excluídos estudos com pacientes internados. O protocolo da revisão de escopo foi registrado na organização Open Science Framework. A estratégia de busca foi desenvolvida a partir de descritores controlados e não controlados e foi realizada em 03 de junho de 2022 nas seguintes bases de dados: CENTRAL, CINAHL, EMBASE, LILACS, PubMed, Scopus, LIVIVO e Web of Science. A busca também foi realizada na literatura cinzenta, incluindo Google Scholar, Open Grey, bula do medicamento e websites. Todos os estudos identificados nas bases de dados foram exportados para o gerenciador de referências bibliográficas (EndNote Desktop) para remoção das duplicadas e importados para o aplicativo web Rayyan para realização da seleção das fontes de evidências por pares e às cegas. Resultados: A busca nas bases de dados resultou em 301 artigos que após o processo de seleção resultaram em 11 artigos incluídos. Os resultados foram subdivididos em 4 categorias: adesão do paciente, opinião da equipe de saúde, carga de trabalho do paciente em tratamento oncológico e o uso do dispositivo na prática clínica. O dispositivo apresenta poucas falhas e é aceito pela equipe de saúde e pacientes na maioria dos estudos. O principal benefício do uso do Pegfilgrastim OBI foi o paciente não precisar retornar na clínica no dia seguinte. Já a segunda parte dos resultados foi proveniente das buscas em sites, bulas e manuais e os dados foram exibidos por meio de dois mapas conceituais detalhados. O primeiro mapa conceitual resumiu as informações ao paciente em uso de PegFilgrastim OBI, descrevendo sobre o que é o dispositivo, como é colocado na clínica, os cuidados que o paciente precisa ter em casa e como é realizado a retirada e descarte após aplicação. Já o segundo mapa conceitual resumiu os cuidados que a equipe de enfermagem precisa ter na aplicação e contém informações de como avaliar o local de aplicação, como preparar o dispositivo, etapas da aplicação e o monitoramento do paciente em casa. Conclusão: Compreender os cuidados em saúde no uso do dispositivo Pegfilgrastim OBI otimiza o trabalho da equipe de saúde, favorece melhorias na prática clínica e inclui o paciente com câncer no centro do cuidado

Introduction: Chemotherapy-induced febrile neutropenia is a predisposing risk factor for severe incidence and increased cancer patient mortality. The use of G-CSF is recommended when the risk of developing febrile neutropenia, resulting from the chemotherapy protocol, is greater than or equal to 20%. A new presentation of G-CSF, Pegfilgrastim OBI, was recently approved by ANVISA. Device that has an automatic application system that is activated 27 hours after the end of chemotherapy. Objective: Mapping health care for the use of the "Pegfilgrastim OBI" device in the prevention of neutropenia in adult cancer patients receiving home care after outpatient chemotherapy. Methods: The scoping review was conducted according to the Joanna Briggs Institute methodology. The guiding question was formulated from the PCC strategy. Studies with adult cancer patients undergoing outpatient chemotherapy were included and studies with inpatients were excluded. The scope review protocol was registered with the Open Science Framework organization. The search strategy was developed from controlled and uncontrolled descriptors and was performed on June 3, 2022 in the following databases: CENTRAL, CINAHL, EMBASE, LILACS, PubMed, Scopus, LIVIVO and Web of Science. The search was also performed in the gray literature, including Google Scholar, Open Grey, drug leaflet and websites. All studies identified in the databases were exported to the bibliographic reference manager (EndNote Desktop) to remove duplicates and imported into the Rayyan web application to carry out the selection of evidence sources by peers and blindly. Results: The search in the databases resulted in 301 articles which, after the selection process, resulted in 11 articles included. The results were subdivided into 4 categories: patient adherence, opinion of the health team, workload of the patient undergoing cancer treatment and the use of the device in clinical practice. The device has few flaws and is accepted by the healthcare team and patients in most studies. The main benefit of using Pegfilgrastim OBI was that the patient did not have to return to the clinic the next day. The second part of the results came from searches on websites, package inserts and manuals and the data were displayed through two detailed concept maps. The first concept map summarized the information for the patient using PegFilgrastim OBI, describing what the device is about, how it is placed in the clinic, the care that the patient needs to have at home and how the removal and disposal is performed after application. The second conceptual map summarized the care that the nursing team needs to take in the application and contains information on how to assess the application site, how to prepare the device, application steps and patient monitoring at home. Conclusion: Understanding health care in the use of the Pegfilgrastim OBI device optimizes the work of the health team, favors improvements in clinical practice and includes the cancer patient at the center of care

Analysis of the Efficacy of Pemetrexed Maintenance Therapy in Patients with Malignant Pleural Mesothelioma / 中国肺癌杂志

BACKGROUND@#Malignant pleural mesothelioma (MPM) is a highly aggressive disease arising from pleural mesothelial cells. Advanced pleural mesothelioma has a poor prognosis, with a median survival of no more than 15 months. First line standard chemotherapy regimen recommended is Pemetrexed based chemotherapy regimen, with or without bevacizumab. There is no consensus on whether patients who have received first-line standard chemotherapy can benefit from pemetrexed maintenance chemotherapy. The study aimed to investigate the efficacy and safety of pemetrexed maintenance therapy (PMT) after treatment with a pemetrexed and platinum regimen for patients with MPM.@*METHODS@#A total of 40 MPM patients were collected from Cancer Hospital Chinese Academy of Medical Sciences from January 2013 to January 2018, eligible patients were unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum, including pemetrexed maintenance therapy group (22 cases) and observation group (18 cases). The last follow-up was conducted in January 2020. The primary endpoint were progression free survival (PFS), and the secondary end points were overall survival (OS), the efficacy, adverse reactions of PMT.@*RESULTS@#The median PFS in the PMT arm was longer than that in the observation arm (8.5 mon vs 3 mon, P=0.008), but there was no significant difference in median OS (26.4 mon vs 15.7 mon, P=0.177). Objective response rate (ORR) of two group were 22.7% and 0%, respectively. The grade 3-4 toxicity in PMT group included grade 4 neutropenia in 1 patient (4.5%), grade 3 neutropenia in 1 patient (4.5%), grade 4 anemia in 1 patient (4.5%) and grade 3 nausea and anorexia in 1 patient (4.5%).@*CONCLUSIONS@#Pemetrexed maintenance therapy following initial pemetrexed and platinum chemotherapy improve PFS in patients with MPM, and is well tolerated.

Effect of Age on the Time of Neutropenia after Initial Induction Therapy for Patients with Newly Diagnosed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of age on the time of neutropenia after initial induction therapy for newly diagnosed acute myeloid leukemia (AML) patients.@*METHODS@#Data of 18-65 years old AML patients treated in our hospital from Junuary 2015 to July 2020 were retrospectively analyzed. The clinical characteristics, time of neutropenia after initial induction treatment, early responses, and related influencing factors for the time of neutropenia were analyzed and compared between 18-40 years old group and 41-65 years old group.@*RESULTS@#There were 112 patients enrolled in this study, including 66 (58.9%) males, and their median age was 46 years old. Compared with 18-40 years old group, the incidence of FLT3-ITD gene mutation increased (P=0.039) but core binding factor (CBF) decreased (P=0.003) significantly in 41-65 years old group. The incidence of neutropenia was 97.3%, and the average time was (18.70±1.192) days. The time of neutropenia was (21.43±1.736) days in 41-65 years old group, which was longer than (14.91±1.356) days in 18-40 years old group (P=0.006). The time of neutropenia in CBF positive group was shorter than that in negative group (P=0.012), as well as in patients with remission (CR+CRi) (≤ 2 courses) than those with non-remission (NR) (P=0.024), while in high-risk group was longer than that in low-risk group (P=0.040). Multivariate analysis showed that age, FLT3-ITD gene mutation positive, and non-remission (NR) after two courses of treatment were independent risk factors for the time of neutropenia.@*CONCLUSION@#In non-elderly patients with newly diagnosed AML, age is an influencing factor for the time of neutropenia. Key words　　;

Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study / 中华血液学杂志

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

Síndrome de Evans y desregulación inmune: complejidades moleculares y etiopatogénicas / Evans syndrome and immune dysregulation: molecular and etiopathogenic complexities

Introducción: El síndrome de Evans se define como la presencia de citopenias inmunes que afectan dos o más líneas celulares simultánea o secuencialmente. Generalmente se refiere a la combinación de anemia hemolítica autoinmune con trombocitopenia inmune primaria, pero puede incluir también neutropenia autoinmune. Su etiología se atribuye a la producción de autoanticuerpos patológicos contra las células sanguíneas pero su causa real se desconoce. Objetivo: Explicar la relación del síndrome de Evans con la desregulación del sistema inmune. Método: Se realizó una revisión de la literatura en inglés y español a través del sitio web PubMed y el motor de búsqueda Google académico, de artículos publicados sobre el tema. El 69,73 por ciento correspondieron a los últimos 5 años. Conclusiones: La inmunopatología del síndrome de Evans se puede atribuir a una alteración en el desarrollo o la función de los linfocitos, de manera que el equilibrio inmunológico se inclina hacia la autorreactividad(AU)

Introduction: Evans syndrome is defined as the presence of autoimmune cytopenias affecting two or more blood cell lines, either simultaneously or sequentially. Most often, this refers to the combination of autoimmune hemolytic anemia and immune thrombocytopenia but can include autoimmune neutropenia as well. The etiology of Evans syndrome has been attributed to pathologic autoantibody production against the blood cells, but the true underlying cause remaining unknown. Objective: to explain the relationship of Evans syndrome with dysregulation of the immune system. Method: a review of the literature in English and Spanish was carried out through the PubMed website and the academic Google search engine for articles published on the subject. 69,73 percent corresponded to the last 5 years. Conclusions: the immunopathology of Evans syndrome can be attributed to an alteration in the development or function of lymphocytes, such that the immune balance is inclined towards self-reactivity(AU)

Duffy phenotyping and FY*B-67T/C genotyping as screening test for benign constitutional neutropenia

ABSTRACT Objective: Low levels of neutrophils can be an intrinsic condition, with no clinical consequences or immunity impairment. This condition is the benign constitutional neutropenia (BCN), defined as an absolute neutrophils count (ANC) ≤2000 cells/mm. Diagnosis of BCN is of exclusion where patients are submitted to blood tests and possibly to invasive diagnostic search until secondary causes of neutropenia are ruled out. The natural history of the disease suggests benign evolution and Brazilian study showed an overall frequency of 2.59%. The main mechanisms include reduced neutrophil production, increased marginalization, extravasation to the tissues and immune destruction. Genetic studies showed strong association between the single nucleotide variant rs2814778 located on chromosome 1q23.2 in the promoter region of the atypical chemokine receptor 1 (Duffy blood group system) gene (ACKR1, also termed DARC) and BCN. The aim of this study is to evaluate FY phenotypes and genotypes including the analysis of the rs2814778 SNP in Brazilian patients with BCN in order to determine an effective diagnostic tool, allowing reassurance of the patient and cost reduction in their care. Methods: Case control study, with 94 individuals (18 patients and 76 controls). Phenotyping was performed by gel test and genotyping was performed by PCR-RFLP. Results: White blood cell (WBC) and absolute neutrophils (AN) counts showed lower levels in patients compared to controls. In the patient group 83.3% were genotyped as FY*B/FY*B. The SNP rs2814778 (-67T > C) was identified in 77.8% of the patients genotyped as FY*B-67C/FY*B-67C. In the control group, 72.7% were homozygous for the wild type and 23.3% were heterozygous. Conclusion: This study reinforces that FY phenotyping and genotyping can be used to detect most people with BCN, avoiding excessive diagnostic investigation. Besides, this procedure may reduce health costs and be reproductible in clinical practice.