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1.
BMC Med Genet ; 21(1): 35, 2020 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-32066420

RESUMEN

BACKGROUND: We report a large family with four successive generations, presenting with a complex phenotype of severe congenital neutropenia (SCN), partially penetrant monocytosis, and hearing loss of varying severity. METHODS: We performed whole exome sequencing to identify the causative variants. Sanger sequencing was used to perform segregation analyses on remaining family members. RESULTS: We identified and classified a pathogenic GFI1 variant and a likely pathogenic variant in MYO6 which together explain the complex phenotypes seen in this family. CONCLUSIONS: We present a case illustrating the benefits of a broad screening approach that allows identification of oligogenic determinants of complex human phenotypes which may have been missed if the screening was limited to a targeted gene panel with the assumption of a syndromic disorder. This is important for correct genetic diagnosis of families and disentangling the range and severity of phenotypes associated with high impact variants.


Asunto(s)
/genética , Proteínas de Unión al ADN/genética , Pérdida Auditiva Sensorineural/genética , Cadenas Pesadas de Miosina/genética , Neutropenia/congénito , Factores de Transcripción/genética , Adulto , Anciano , /diagnóstico , Exoma/genética , Femenino , Enfermedades Genéticas Congénitas/complicaciones , Enfermedades Genéticas Congénitas/diagnóstico , Enfermedades Genéticas Congénitas/genética , Enfermedades Genéticas Congénitas/fisiopatología , Pérdida Auditiva Sensorineural/complicaciones , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/patología , Humanos , Masculino , Persona de Mediana Edad , Mutación/genética , Neutropenia/complicaciones , Neutropenia/diagnóstico , Neutropenia/genética , Neutropenia/fisiopatología , Linaje , Fenotipo , Secuenciación del Exoma Completo
2.
Acta otorrinolaringol. esp ; 70(6): 348-357, nov.-dic. 2019. tab, graf, ilus
Artículo en Español | IBECS | ID: ibc-184880

RESUMEN

Antecedentes y objetivo: El objetivo del estudio ha sido describir los resultados del tratamiento de sinusitis fúngica invasiva con cirugía endoscópica nasal en una población oncológica pediátrica con inmunosupresión e informar sobre la seguridad, la eficacia y las complicaciones del procedimiento. Métodos: Se realizó un estudio retrospectivo de la totalidad de los pacientes con diagnóstico de sinusitis fúngica invasiva operados en la Unidad Nacional de Oncología Pediátrica entre los años 2012 y 2016. Los datos tomados de su historial médico incluyeron: características epidemiológicas, diagnóstico oncológico, datos hematológicos, síntomas, estudios tomográficos, intervenciones quirúrgicas, resultados de enfermedad y cultivos, medicamentos recibidos, complicaciones, evolución y supervivencia. Los datos fueron analizados utilizando estadística descriptiva, las variables continuas con medidas de tendencia central y las variables categóricas de forma porcentual. Resultados: Se identificó a 18 pacientes, 7 de sexo masculino y 11 de sexo femenino. El promedio de edad fue de 12 años, 13 tuvieron diagnóstico de leucemia linfoide aguda y 5 de leucemia mieloide aguda; 17 pacientes presentaron neutropenia severa en el momento del diagnóstico. El agente etiológico más frecuentemente identificado fue Aspergillus en 13 pacientes. En 16 pacientes (89%) se controló la enfermedad con cirugía endoscópica nasal. Diez pacientes fallecieron por causas no relacionadas a lo largo del estudio. Discusión y conclusiones: La sinusitis fúngica invasiva es una enfermedad cuya incidencia va en aumento entre pacientes con inmunosupresión y debe de considerarse una urgencia médica debido a su alta mortalidad. El diagnóstico se basa en un alto índice de sospecha en pacientes con factores predisponentes (leucemia, neutropenia, fiebre persistente, sonda nasogástrica) y la evaluación endoscópica nasal. El tratamiento médico antifúngico y cirugía endoscópica nasal agresiva está indicado independientemente del estado del paciente para disminuir la carga fúngica y la alta mortalidad asociada. El tratamiento debe de ser suministrado por un equipo multidisciplinario que incluye pediatría, hemato-oncología, infectología y otorrinolaringología


Background and objective: to describe the results of the treatment of invasive fungal sinusitis with nasal endoscopic surgery in an immunocompromised paediatric oncological population. Methods: retrospective study of all patients diagnosed with invasive fungal sinusitis operated in the National Paediatric Oncology Unit between 2012 and 2016. Data taken from their medical history included: epidemiological characteristics, oncological diagnosis, haematological data, symptoms, tomographic studies, surgical interventions, results of pathology and cultures, medications received, complications, evolution and survival. Results: 18 patients were identified, 7 male and 11 female. The average age was 12 years, 13 had a diagnosis of acute lymphocytic leukemia and 5 of acute myeloid leukemia. Seventeen patients presented severe neutropenia at the time of diagnosis. The most frequently identified aetiological agent was Aspergillus in 13 patients. In 16 patients (89%) the disease was controlled with nasal endoscopic surgery. Ten patients died due to unrelated causes throughout the study. Discussion and conclusions: Invasive fungal sinusitis should be considered a medical emergency due to its high mortality. The diagnosis is based on a high index of suspicion in patients with predisposing factors (leukaemia, neutropenia, persistent fever, nasogastric tube) and endoscopic nasal evaluation. Antifungal medical treatment and aggressive nasal endoscopic surgery is indicated regardless of the patient's condition to reduce the fungal burden and associated high mortality. The treatment must be provided by a multidisciplinary team that includes paediatrics, haemato-oncology, infectology and otorhinolaryngology


Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Sinusitis/diagnóstico , Sinusitis/cirugía , Inmunosupresión , Endoscopía/métodos , Evaluación de Resultados de Intervenciones Terapéuticas , Estudios Retrospectivos , Neutropenia/complicaciones , Aspergillus/aislamiento & purificación , Micosis/complicaciones , Fiebre/etiología , Senos Paranasales/diagnóstico por imagen , Complicaciones Posoperatorias
3.
JAMA ; 322(17): 1673-1681, 2019 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-31688884

RESUMEN

Importance: Children, adolescents, and young adults with acute myeloid leukemia are at high risk of life-threatening invasive fungal disease with both yeasts and molds. Objective: To compare the efficacy of caspofungin vs fluconazole prophylaxis against proven or probable invasive fungal disease and invasive aspergillosis during neutropenia following acute myeloid leukemia chemotherapy. Design, Setting, and Participants: This multicenter, randomized, open-label, clinical trial enrolled patients aged 3 months to 30 years with newly diagnosed de novo, relapsed, or secondary acute myeloid leukemia being treated at 115 US and Canadian institutions (April 2011-November 2016; last follow-up June 30, 2018). Interventions: Participants were randomly assigned during the first chemotherapy cycle to prophylaxis with caspofungin (n = 257) or fluconazole (n = 260). Prophylaxis was administered during the neutropenic period following each chemotherapy cycle. Main Outcomes and Measures: The primary outcome was proven or probable invasive fungal disease as adjudicated by blinded central review. Secondary outcomes were invasive aspergillosis, empirical antifungal therapy, and overall survival. Results: The second interim efficacy analysis and an unplanned futility analysis based on 394 patients appeared to have suggested futility, so the study was closed to accrual. Among the 517 participants who were randomized (median age, 9 years [range, 0-26 years]; 44% female), 508 (98%) completed the trial. The 23 proven or probable invasive fungal disease events (6 caspofungin vs 17 fluconazole) included 14 molds, 7 yeasts, and 2 fungi not further categorized. The 5-month cumulative incidence of proven or probable invasive fungal disease was 3.1% (95% CI, 1.3%-7.0%) in the caspofungin group vs 7.2% (95% CI, 4.4%-11.8%) in the fluconazole group (overall P = .03 by log-rank test) and for cumulative incidence of proven or probable invasive aspergillosis was 0.5% (95% CI, 0.1%-3.5%) with caspofungin vs 3.1% (95% CI, 1.4%-6.9%) with fluconazole (overall P = .046 by log-rank test). No statistically significant differences in empirical antifungal therapy (71.9% caspofungin vs 69.5% fluconazole, overall P = .78 by log-rank test) or 2-year overall survival (68.8% caspofungin vs 70.8% fluconazole, overall P = .66 by log-rank test) were observed. The most common toxicities were hypokalemia (22 caspofungin vs 13 fluconazole), respiratory failure (6 caspofungin vs 9 fluconazole), and elevated alanine transaminase (4 caspofungin vs 8 fluconazole). Conclusions and Relevance: Among children, adolescents, and young adults with acute myeloid leukemia, prophylaxis with caspofungin compared with fluconazole resulted in significantly lower incidence of invasive fungal disease. The findings suggest that caspofungin may be considered for prophylaxis against invasive fungal disease, although study interpretation is limited by early termination due to an unplanned interim analysis that appeared to have suggested futility. Trial Registration: ClinicalTrials.gov Identifier: NCT01307579.


Asunto(s)
Antifúngicos/uso terapéutico , Caspofungina/uso terapéutico , Fluconazol/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Micosis/prevención & control , Adolescente , Adulto , Antifúngicos/efectos adversos , Aspergilosis/epidemiología , Aspergilosis/prevención & control , Caspofungina/efectos adversos , Niño , Preescolar , Terminación Anticipada de los Ensayos Clínicos , Femenino , Fluconazol/efectos adversos , Humanos , Lactante , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/complicaciones , Masculino , Neutropenia/complicaciones , Adulto Joven
4.
BMC Med Genet ; 20(1): 182, 2019 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-31727123

RESUMEN

BACKGROUND: Majeed syndrome is a rare, autosomal recessive autoinflammatory disorder first described in 1989. The syndrome starts during infancy with recurrent relapses of osteomyelitis typically associated with fever, congenital dyserythropoietic anemia (CDA), and often neutrophilic dermatosis. Mutations in the LPIN2 gene located on the short arm of chromosome 18 have been identified as being responsible for Majeed syndrome. CASE PRESENTATION: We report an 8-month-old boy, who presented with recurrent fever, mild to moderate anemia, and severe neutropenia. Erythrocyte sedimentation rate and C-reactive protein were elevated. Molecular testing identified a paternal splicing donor site variant c.2327 + 1G > C and a maternal frameshift variant c.1691_1694delGAGA (Arg564Lysfs*3) in LPIN2. CONCLUSIONS: Only a few cases with LPIN2 mutation have been reported, mainly in the Middle East with homozygous variants. Our patient exhibited a mild clinical phenotype and severe neutropenia, different from previous reports.


Asunto(s)
Anemia Diseritropoyética Congénita/genética , Fiebre/complicaciones , Síndromes de Inmunodeficiencia/genética , Mutación , Neutropenia/complicaciones , Proteínas Nucleares/genética , Osteomielitis/genética , Anemia Diseritropoyética Congénita/complicaciones , Femenino , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Lactante , Masculino , Osteomielitis/complicaciones , Linaje , Recurrencia , Índice de Severidad de la Enfermedad
5.
Medicine (Baltimore) ; 98(39): e17372, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31574885

RESUMEN

INTRODUCTION: Cyclic neutropenia (CyN) is a rare hematological disease, and patients with CyN often experience an early onset of severe periodontitis and are forced to undergo tooth extraction. Here, we report a case of a patient with CyN who showed different periodicity and oscillations of neutrophil count compared with her mother, despite sharing the same novel genetic mutation. PATIENT CONCERNS: A 17-year-old Japanese girl who had been diagnosed with CyN shortly after birth presented to our hospital with a complaint of mobility of her teeth and gingivitis. Upon presentation, an intraoral examination was performed and revealed redness and swelling of the marginal and attached gingiva. Radiographs revealed extreme resorption of the alveolar bone and apical lesions in her mandibular lateral incisors. The patient's hematologic data demonstrated a lack of blood neutrophils (0/µL). The patient had no history of dental extraction, and her mother also had a history of CyN. DIAGNOSES: The patient was diagnosed with severe periodontitis that was associated with CyN. Gene testing showed a novel heterozygous mutation in exon 4 of the ELANE gene (c.538delC, p.Leu180Ser fsX11). INTERVENTIONS: Based on the clinical findings, we planned to extract the patient's mandibular lateral incisors. Although the tooth extraction was scheduled considering the cyclic variation in neutrophil count, the patient's neutrophil count was 0/µL on the day before the planned extraction. Therefore, granulocyte-colony stimulating factor (G-CSF) was administered to increase the patient's neutrophil count. On the day of the patient's admission for the tooth extraction, she presented with fever (body temperature, 38.5°C), tonsillitis, and stomatitis. The extraction was subsequently delayed, and the patient was administered antibiotics and G-CSF for 4 days. At this time, the neutrophil count increased to 750/µL, and the tooth extraction was carried out safely. OUTCOMES: The postoperative course was uneventful, and the healing process at the extraction site was excellent. CONCLUSION: There is a possibility that the periodicity and oscillations of neutrophil count may change with growth in patients with CyN. Therefore, it is important to frequently examine and treat patients with fluctuating neutrophil levels for the management of invasive dental treatment in patients with CyN.


Asunto(s)
Elastasa de Leucocito/genética , Neutropenia/genética , Periodontitis/genética , Periodontitis/cirugía , Extracción Dental/efectos adversos , Adolescente , Exones , Femenino , Humanos , Recuento de Leucocitos , Mutación , Neutropenia/sangre , Neutropenia/complicaciones , Neutrófilos , Periodontitis/sangre
6.
Anticancer Res ; 39(9): 4925-4931, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31519597

RESUMEN

BACKGROUND/AIM: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy where antioxidant enzyme peroxiredoxin 6 (Prx6) has previously been associated with adverse outcomes. Its systemic effects in DLBCL are unknown. MATERIALS AND METHODS: This study included 53 patients with DLBCL, five patients with primary central nervous system lymphoma (PCNSL) and 20 healthy controls. The expression of Prx6 was evaluated immunohistochemically in DLBCL tissue samples and compared to its expression in blood serum. RESULTS: Prx6 expression was the highest in healthy controls, followed by DLBCL patients and PCNSL patients. Febrile neutropenic infection after the first treatment course was associated with low pre-treatment Prx6 serum levels (<14 ng/ml) (p=0.025, OR=8.615, 95% confidence interval=1.032-71.933). Serum levels of Prx6 recovered after treatment (p=0.006). CONCLUSION: Patients with low Prx6 levels might be more prone to treatment-related adverse effects through elevated levels of oxidative stress.


Asunto(s)
/etiología , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/complicaciones , Neutropenia/complicaciones , Neutropenia/etiología , Peroxiredoxina VI/sangre , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Medición de Riesgo , Factores de Riesgo
7.
Ann Hematol ; 98(10): 2311-2318, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31432214

RESUMEN

The role of adjunctive corticosteroid in septic shock remains debatable, and its role has not been assessed in neutropenic patients. We evaluated whether hydrocortisone reduces 28-day mortality in neutropenic patients with septic shock. We conducted a retrospective cohort study between January 2012 and May 2017 at a tertiary care center in South Korea. Patients who developed septic shock treated with at least one vasopressor and whose absolute neutrophil count was < 1000 cells/µL were included. Patients were classified into a steroid and a no-steroid group. The primary outcome of the study was 28-day mortality. Propensity score matching was used to adjust baseline characteristics and disease severity between the groups. Of the 287 patients analyzed, 189 were classified in the no-steroid group and 98 in the steroid group. Fifty propensity score-matched pairs were compared for the study outcomes. We found no significant difference in 28-day mortality between patients treated with and without steroid after propensity score matching (38.0% and 42.0%, respectively; p = 0.838). Incidences of pneumonia and gastrointestinal bleeding were more frequent in the steroid group, but it was not statistically significant after matching. In conclusion, adjunctive hydrocortisone was not associated with reduced 28-day mortality in neutropenic patients with septic shock.


Asunto(s)
Hidrocortisona/administración & dosificación , Neutropenia , Choque Séptico , Adulto , Anciano , Femenino , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/mortalidad , Humanos , Hidrocortisona/efectos adversos , Incidencia , Masculino , Persona de Mediana Edad , Mortalidad , Neutropenia/complicaciones , Neutropenia/tratamiento farmacológico , Neutropenia/mortalidad , Neumonía/etiología , Neumonía/mortalidad , Estudios Retrospectivos , Choque Séptico/complicaciones , Choque Séptico/tratamiento farmacológico , Choque Séptico/mortalidad , Factores de Tiempo
8.
BMC Res Notes ; 12(1): 464, 2019 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-31362783

RESUMEN

OBJECTIVE: The aim of this study was to determine the predominant bacterial species causing bacteremia among febrile cancer patients, and their antibacterial resistance profiles at the Uganda Cancer Institute. RESULTS: We enrolled in-patients with a documented fever (≥ 37.5 °C). Bacteria from positive blood cultures were identified using standard methods biochemically. Antibacterial susceptibility testing was performed with the Kirby-Bauer disc diffusion method. From a total of 170 febrile episodes, positive blood cultures were obtained from 24 (14.1%). A positive culture was more likely to be obtained from a patient with neutropenia (P = 0.017). Of 22 (66.7%) Gram-negative bacteria isolated, half were E. coli (n = 11). Gram-negative compared to Gram-positive bacteria were most likely to be isolated from patients with a hematologic malignancy (P = 0.02) or patients with neutropenia (P = 0.006). Of the isolated Enterobacteriaceae 85% (n = 20) were resistant to three or more classes of antibiotic and 41% (n = 7) had extended spectrum beta-lactamases. Of the 11 Gram-positive bacteria isolated, the S. aureus isolate was methicillin resistant but susceptible to vancomycin. Multidrug resistant Gram-negative bacteria are the main cause of bacteremia in febrile cancer patients at the Uganda Cancer Institute. There is need for ongoing microbial surveillance, infection prevention and control, and antibiotic stewardship programs.


Asunto(s)
Bacteriemia/microbiología , Fiebre/microbiología , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Grampositivas/microbiología , Neoplasias/microbiología , Neutropenia/microbiología , Adulto , Antibacterianos/uso terapéutico , Bacteriemia/complicaciones , Bacteriemia/tratamiento farmacológico , Bacteriemia/patología , Cultivo de Sangre , Niño , Estudios Transversales , Farmacorresistencia Bacteriana Múltiple/genética , Femenino , Fiebre/complicaciones , Fiebre/tratamiento farmacológico , Fiebre/patología , Expresión Génica , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/enzimología , Bacterias Gramnegativas/genética , Infecciones por Bacterias Gramnegativas/complicaciones , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/patología , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/enzimología , Bacterias Grampositivas/genética , Infecciones por Bacterias Grampositivas/complicaciones , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/patología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neutropenia/complicaciones , Neutropenia/tratamiento farmacológico , Neutropenia/patología , Uganda , beta-Lactamasas/genética , beta-Lactamasas/metabolismo
9.
Medicine (Baltimore) ; 98(35): e16993, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31464949

RESUMEN

RATIONALE: Parvovirus B19 (PV) infection is usually symptomless and can cause benign, short-lived conditions. Anemia associated with PRCA is the most representative hematologic manifestation, but neutropenia and thrombocytopenia have been rarely reported. PATIENT CONCERNS: Three patients were admitted to the hospital with neutropenia and thrombocytopenia. The accompanying symptoms were fever, myalgia, rash, or arthralgia, and all patients were previously healthy. DIAGNOSIS: Patients were positive for PV PCR and diagnosed with PV infection. Before the diagnosis of PV infection, 2 patients underwent BM study and almost absence of erythroid progenitor cells in BM aspiration were a clue for the PV infection. Other BM findings were hypocellular marrow and a few hemophagocytic histiocytes. INTERVENTIONS: Patients received supportive care with follow-up of CBC. OUTCOMES: All 3 patients spontaneously recovered from neutropenia and thrombocytopenia within 3 weeks without severe complications. LESSONS: The evaluation of PV infection should be considered in situations where there is neutropenia and thrombocytopenia in healthy individuals even without anemia as a differential diagnosis.


Asunto(s)
Neutropenia/complicaciones , Infecciones por Parvoviridae/complicaciones , Infecciones por Parvoviridae/diagnóstico , Trombocitopenia/complicaciones , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Parvoviridae/virología , Parvovirus B19 Humano , Reacción en Cadena de la Polimerasa
10.
Am J Case Rep ; 20: 1027-1034, 2019 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-31308356

RESUMEN

BACKGROUND Theranostics is a combined diagnostic and treatment approach to individualized patient care. Kostmann syndrome, or severe congenital neutropenia, is an autosomal recessive disease that affects the production of neutrophils. Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy associated with gene alterations, including in the mitogen-activated protein kinase (MAPK) signaling pathway gene. Translocation of the ETS variant 6/neurotrophic receptor tyrosine kinase 3 (ETV6/NTRK3) gene has been implicated in radiation-induced and pediatric forms of thyroid carcinoma but has rarely been described in sporadic PTC. This report is of a case of PTC in a patient with Kostmann syndrome associated with ETV6/NTRK3 gene translocation. CASE REPORT A 32-year-old woman with a history of Kostmann syndrome, acute myeloid leukemia (AML), and chronic graft versus host disease (GVHD) was diagnosed with PTC with cervical lymph node metastases and soft tissue invasion following total thyroidectomy and bilateral modified radical neck dissection. Her postoperative radioactive iodine (RAI) scan confirmed lymph node metastasis. Gene expression studies identified increased expression of iodine-handling genes and ETV6/NTRK3 gene fusion. Because of the bone marrow compromise due to Kostmann syndrome and AML, a careful genomic and molecular analysis was performed to guide therapy. CONCLUSIONS This is the first reported case of the association between PTC, Kostmann syndrome, and ETV6/NTRK3 gene translocation in which multimodality treatment planning was optimized by genomic profiling.


Asunto(s)
/terapia , Neutropenia/congénito , Nanomedicina Teranóstica , Cáncer Papilar Tiroideo/terapia , Neoplasias de la Tiroides/terapia , Adulto , /genética , Femenino , Fusión Génica/genética , Humanos , Neutropenia/complicaciones , Neutropenia/genética , Neutropenia/terapia , Proteínas Proto-Oncogénicas c-ets/genética , Receptor trkC/genética , Proteínas Represoras/genética , Cáncer Papilar Tiroideo/complicaciones , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/genética
11.
J Mycol Med ; 29(3): 278-281, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31202517

RESUMEN

Saprochaete clavata and Saprochaete capitata are closely related fungal species (family Dipodascaceae, order Saccharomycetales) that are rarely involved in the etiology of systemic infections in humans. In recent years, these yeasts are emerging as cause of life-threatening infections in patients with severe neutropenia and haematological malignancies. Infections by these fungi have been reported mostly from Mediterranean countries. To the best of our knowledge, only 2 cases of infection due to S. capitata have been reported in solid organ transplant recipients and none due to S. clavata. Herein we report a fatal case of S. clavata disseminated infection occurring in a patient with recent kidney transplantation and severe neutropenia. Patient was receiving antifungal echinocandin prophylaxis and the yeast was isolated from the blood and multiple non contiguous sites. Saprochaete spp. should be considered in the differential diagnosis of invasive mycoses in transplant recipients, especially if they are neutropenic and living or travelling in Mediterranean countries.


Asunto(s)
Infecciones Fúngicas Invasoras/diagnóstico , Trasplante de Riñón , Saccharomycetales/aislamiento & purificación , Receptores de Trasplantes , Antifúngicos/administración & dosificación , Diagnóstico Diferencial , Equinocandinas/administración & dosificación , Resultado Fatal , Femenino , Fungemia , Humanos , Infecciones Fúngicas Invasoras/sangre , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neutropenia/complicaciones , Neutropenia/microbiología
12.
Mycoses ; 62(9): 847-853, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31166627

RESUMEN

Fungal cholecystitis is an uncommon entity, and no cases of cholecystitis associated with mould infection have been reported. We present a case of acute Fusarium cholecystitis in a cytopenic patient with leukaemia who had disseminated fusariosis. We also review the published cases of fungal cholecystitis, which is most often caused by Candida species. Although it is rare, fungal cholecystitis should be part of the differential diagnosis of acute cholecystitis in high-risk patients with predisposing factors for opportunistic fungal infections.


Asunto(s)
Colecistitis Alitiásica/diagnóstico , Colecistitis Alitiásica/microbiología , Colecistitis Aguda/microbiología , Infecciones Oportunistas/diagnóstico , Abdomen/diagnóstico por imagen , Colecistitis Alitiásica/tratamiento farmacológico , Adulto , Antifúngicos/uso terapéutico , Biopsia , Diagnóstico Diferencial , Femenino , Fusariosis/tratamiento farmacológico , Fusariosis/microbiología , Fusarium/patogenicidad , Humanos , Pulmón/diagnóstico por imagen , Neutropenia/complicaciones , Neutropenia/microbiología , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/microbiología , Piel/microbiología , Piel/patología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
13.
Infection ; 47(5): 837-845, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31187401

RESUMEN

PURPOSE: The length of neutropenia has a significant impact on the incidence of bloodstream infection (BSI) in cancer patients, but limited information is available about the pathogen distribution in late BSI. METHODS: Between 2002 and 2014, BSI episodes in patients with neutropenia receiving chemotherapy for hematologic malignancies were prospectively identified by multicenter, active surveillance in Germany, Switzerland and Austria. The incidence of first BSI episodes, their microbiology and time to BSI onset during the first episode of neutropenia of 15,988 patients are described. RESULTS: The incidence rate of BSI episodes was 14.7, 8.7, and 4.7 per 1000 patient-days in the first, second, and third week of neutropenia, respectively. BSI developed after a median of 5 days of neutropenia (interquartile range [IQR] 3-10 days). The medium duration of neutropenia to BSI onset was 4 days in Escherichia coli (IQR 3-7 days), Klebsiella spp. (2-8 days), and Staphylococcus aureus (3-6 days). In contrast, BSI due to Enterococcus faecium occurred after a median of 9 days (IQR 6-14 days; p < 0.001 vs. other BSI). Late onset of BSI (occurring after the first week of neutropenia) was also observed for Stenotrophomonas maltophilia (12 days, IQR 7-17 days; p < 0.001), and non-albicans Candida spp. (13 days, IQR 8-19 days; p < 0.001). CONCLUSIONS: Over the course of neutropenia, the proportion of difficult to treat pathogens such as E. faecium, S. maltophilia, and Candida spp. increased. Among other factors, prior duration of neutropenia may help to guide empiric antimicrobial treatment in febrile neutropenia.


Asunto(s)
Antineoplásicos/efectos adversos , Bacteriemia/tratamiento farmacológico , Bacteriemia/etiología , Infección Hospitalaria/epidemiología , Neoplasias Hematológicas/complicaciones , Neutropenia/complicaciones , Adulto , Antibacterianos/uso terapéutico , Antineoplásicos/uso terapéutico , Austria/epidemiología , Bacteriemia/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Monitoreo Epidemiológico , Femenino , Alemania/epidemiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/epidemiología , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Estudios Retrospectivos , Infecciones Estafilocócicas/tratamiento farmacológico , Suiza/epidemiología
14.
Breast Cancer ; 26(5): 637-650, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31127500

RESUMEN

BACKGROUND: The cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib, in combination with endocrine therapy (ET), significantly prolonged progression-free survival in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC) in PALOMA-2 and PALOMA-3. Neutropenia and palbociclib dose reductions/interruptions occurred more frequently in the Japanese versus overall populations. We evaluated neutropenia patterns, palbociclib dose management, and clinical responses after dose reduction in Japanese patients in PALOMA-2 and PALOMA-3 and a single-arm Japanese phase 2 study. METHODS: PALOMA-2 and the Japanese phase 2 study enrolled postmenopausal women with estrogen receptor-positive, HER2- ABC who had not received prior systemic therapy for advanced disease; PALOMA-3 enrolled women with HR+/HER2- ABC, regardless of menopausal status, whose disease had progressed after prior ET. Palbociclib (125 mg/day) was administered 3 weeks on/1 week off. Dose reduction/interruption, cycle delay, tumor response, and laboratory-assessed neutropenia were analyzed in Japanese patients who received palbociclib. RESULTS: A total of 101 Japanese patients received palbociclib + ET. Among Japanese patients in the 3 studies, the frequency of all-grade/grade 3/grade 4 neutropenia was 94%/53%/34%, 100%/69%/21%, and 100%/67%/26%, respectively. Twenty (63%), 28 (67%), and 15 (56%) patients required palbociclib dose reduction. Dose interruption or reduction did not affect palbociclib treatment duration, and durable tumor response was observed despite dose reduction. CONCLUSION: Neutropenia was manageable with dose modifications, without affecting palbociclib treatment duration or efficacy. TRIAL REGISTRATION: Pfizer (NCT01740427, NCT01684215, NCT01942135).


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neutropenia/tratamiento farmacológico , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/uso terapéutico , Receptor ErbB-2/metabolismo , Receptores Estrogénicos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/complicaciones , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Japón , Menopausia , Persona de Mediana Edad , Neutropenia/complicaciones , Neutrófilos/metabolismo , Piperazinas/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Piridinas/administración & dosificación , Resultado del Tratamiento
15.
Mycoses ; 62(8): 651-658, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31066092

RESUMEN

Invasive aspergillosis (IA) is a serious hazard to haematological and critical care patients. Impactful risk factors for developing IA have been characterised; however, systematic analysis of baseline prognostic factors for treatment course of IA is missing. To understand prognostic variables, we analysed original articles identifying baseline factors that predict treatment outcome in patients with IA. PubMed database was searched for publications since database inception until May 2018. Inclusion criteria were published baseline prognostic factors present at the diagnosis of IA. In total, 58 studies from 267 centres reported 7320 patients with IA and 40 different predictors. Unfavourable predictors in medical history were kidney (7.4%, 10/136) and liver failure (3.7%, 5/136), ICU admission (3.7%, 5/136) and uncontrolled underlying disease (3.7%, 5/136). Regarding state of immunosuppression, negative outcome predictors were prolonged neutropenia (12.5%, 17/136), corticosteroid treatment (8.1%, 11/136) and graft-vs-host disease (3.7%, 5/136). On the pathogen side, relevant predictors were galactomannan positivity (8.1%, 11/136), Aspergillus terreus infection (2.2%, 3/136) and lack of amphotericin B susceptibility (1.5%, 2/136). IA-specific predictors were disseminated disease (5.1%, 7/136) and CNS involvement (2.9%, 4/136). Imaging results associated with negative outcome were multiple consolidations (2.9%, 4/136), bipulmonary lesions (2.2%, 3/136) and pleural effusion (2.2%, 3/136). At diagnosis of IA, most frequently identified predictors of outcome were neutropenia, corticosteroid use, elevated galactomannan, renal failure and disseminated disease. The predictors may be used to identify patients at high risk for treatment failure and to stratify neglected patient groups for clinical trials.


Asunto(s)
Aspergillus/patogenicidad , Aspergilosis Pulmonar Invasiva/diagnóstico , Adulto , Antifúngicos/uso terapéutico , Enfermedad Injerto contra Huésped/complicaciones , Humanos , Inmunosupresión/efectos adversos , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , Mananos/metabolismo , Neutropenia/complicaciones , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del Tratamiento , Resultado del Tratamiento
16.
Pediatr Rheumatol Online J ; 17(1): 19, 2019 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-31046790

RESUMEN

BACKGROUND: CANDLE syndrome (an acronym for Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature) is a recently described rare autosomal recessive disorder charaterized by systemic autoinflammation. Clinical manifestations include presentation in the first year of life, episodes of fever accompanied by erythematous skin lesions, progressive lipodystrophy, violaceous periorbital swelling and failure to thrive. This syndrome is caused by loss of function mutations and malfunction of the immunoproteasome complex. Most patients have biallelic mutations in the PSMB8 gene that encodes the ß5i catalytic subunit of the immunoproteasome. Examples of digenic inheritance have been also described in CANDLE. CANDLE patients have strong type I interferon gene expression signature and they are responsive to treatment with JAK inhibitors. However, possible serious side-effects remain a concern. Here, we report another patient with CANDLE whose disease activity was well controlled by the treatment with baricitinib. CASE PRESENTATION: We report a Bulgarian patient of the Turkish ancestry who carries biallelic mutations in the PSMB8 gene: p.Ala92Val and p.Lys105Gln. The pathogenic variant p.Ala92Val has not been previously described in patients with CANDLE. We also comment on the unusual feature in this patient, nephrolithiasis, that has not been described in other patients, however it might be related to the positive family history for kidney stones. We have treated the patient with the JAK inhibitor baricitinib for the past year and we observed a significant amelioration of his inflammatory episodes, skin and joint manifestations, and improvements in physical activities and growth. The treatment with glucocorticoids (GC) was completely discontinued. No side effects have been observed, however they remain in consideration for a life-long therapy of this disease. CONCLUSIONS: CANDLE should be suspected in patients with early-onset systemic inflammatory disease and prominent skin manifestations. Molecular testing can confirm the clinical diagnosis and is very important in guiding therapies. Treatment with JAK inhibitors is highly efficacious and appears to be safe in children with CANDLE and other intereforonopathies.


Asunto(s)
Azetidinas/uso terapéutico , Dermatitis/tratamiento farmacológico , Fiebre/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Lipodistrofia/tratamiento farmacológico , Neutropenia/tratamiento farmacológico , Sulfonamidas/uso terapéutico , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/tratamiento farmacológico , Niño , Enfermedad Crónica , Dermatitis/complicaciones , Fiebre/complicaciones , Humanos , Lipodistrofia/complicaciones , Masculino , Neutropenia/complicaciones , Complejo de la Endopetidasa Proteasomal/inmunología , Síndrome , Resultado del Tratamiento
17.
BMJ Support Palliat Care ; 9(4): 425-433, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30948447

RESUMEN

INTRODUCTION: Multiple studies have questioned the benefit of neutropenic diets in decreasing infections in patients with cancer, but recent surveys showed that such diets are still prescribed. In this study, we sought to evaluate the effectiveness of neutropenic diet in decreasing infection and mortality in neutropenic patients with cancer with neutropenia. This review is an update of a previously published systematic review. MATERIALS AND METHODS: We searched different databases to identify comparative studies that investigated the effect of neutropenic diet compared with regular diet in neutropenic adults and children with cancer. We conducted random-effects meta-analyses using the Der-Simonian and Laird method to pool treatment effects from included studies. Outcomes of interest were mortality, bacteremia/fungemia, major infections, quality of life, and the composite outcome for neutropenic fever and/or infection. RESULTS: We included six studies (five randomised) with 1116 patients, with 772 (69.1%) having underwent haematopoietic cell transplant. There was no statistically significant difference between neutropenic diet and regular diet in the rates of major infections (relative risk [RR] 1.16; 95% CI 0.94 to 1.42) or bacteremia/fungemia (RR 0.96; 95% CI 0.60 to 1.53). In haematopoietic cell transplant patients, neutropenic diet was associated with a slightly higher risk of infections (RR 1.25; 95% CI 1.02 to 1.54). No difference in mortality was seen between neutropenic diet and regular diet (RR 1.08, 95% CI 0.78 to 1.50). CONCLUSION: There is currently no evidence to support the use of neutropenic diet or other food restrictions in neutropenic patients with cancer. Patients and clinicians should continue to follow the safe food-handling guidelines as recommended by the U.S. Food and Drug Administration.


Asunto(s)
Infecciones Bacterianas/prevención & control , Neoplasias/complicaciones , Neutropenia/dietoterapia , Adulto , Niño , Dieta , Humanos , Neutropenia/complicaciones
18.
Infect Dis (Lond) ; 51(6): 425-434, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31010380

RESUMEN

BACKGROUND: In Norway, the epidemiological situation of candidemia is followed closely. We have previously demonstrated the highest incidence of candidemia in elderly >65 years of age. However, knowledge of other aspects of this infection is lacking. OBJECTIVE: The aim of this nationwide, retrospective study was to examine risk factors, therapeutic practice and outcome in adult candidemia patients according to age. METHODS: We retrieved data from medical records from patients who developed candidemia in Norway between 1 January 2008 and 31 December 2012. Data were analyzed according to age, younger patients being between 18 and 65 years, elderly being ≥65 years of age. RESULTS: From 771 eligible patients, 738 patients (95.7%) were included (58% men, mean age 65.2 years, 58.1% being ≥65 years). Exposure to health-care related risk factors for candidemia were significantly more common in the younger patients (neutropenia, central venous catheter, mechanical ventilation and chemotherapy) who received empirical treatment more often than the elderly (29.8% vs. 21.7%, p = .01). More elderly did not received any antifungal therapy (27.3% vs 16.8%, p < 0001) and had higher mortality compared to younger patients (45.5% vs 23.9%, p < .0001). In the study population, mortality was higher with age (per 10-years increase, OR 1.43;1.28-1.59, p < 0.0001), in patients not receiving targeted therapy (OR 2.5; CI 1.82-3.36, p < .0001) or any therapy at all (OR 4.64; 3.23-6.68, p < .0001). CONCLUSIONS: Risk factors for candidemia, treatment and outcome differed significantly according to age. Given the increasing numbers of elderly, scrutiny on our clinical practice is warranted.


Asunto(s)
Factores de Edad , Antifúngicos/uso terapéutico , Candidemia/tratamiento farmacológico , Candidemia/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Candidemia/mortalidad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neutropenia/complicaciones , Noruega/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
19.
J Pediatr Hematol Oncol ; 41(5): 345-354, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30973485

RESUMEN

Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in children with cancer. An overview of studies on the frequency and determinants of IFI in pediatric oncology patients in nonallogeneic stem cell transplantation settings is lacking. We performed a literature review in Pubmed and Embase, and included 13 prospective and 23 retrospective studies. The IFI frequency (proven/probable based on EORTC criteria) in nonallogeneic stem cell transplantation pediatric cancer patients ranged between 1.0% and 38.0%, with the highest frequencies reported in hematologic malignancies. The most common fungal species seen in the studied population was Candida, followed by Aspergillus. IFI are not well investigated in solid tumor patients. Significant recurrent determinants from univariate analysis were the diagnosis acute myeloid leukemia, (prolonged) neutropenia and an older age (above 10 years). The only 2 significant determinants based on multivariate analysis were the preceding number of days of broad-spectrum antibiotics (odds ratio, 1.05; 95% confidence interval, 1.02-1.07; P=0.0006) and the number of days of corticosteroids (odds ratio, 1.05; 95% confidence interval, 1.02-1.09; P=0.005), that were both based on a group of acute myeloid leukemia patients only. Future studies are necessary to determine the frequency and determinants of IFI in pediatric oncology including a representative number of solid tumor patients.


Asunto(s)
Neoplasias Hematológicas/complicaciones , Trasplante de Células Madre Hematopoyéticas/métodos , Infecciones Fúngicas Invasoras/etiología , Neoplasias/complicaciones , Adolescente , Corticoesteroides/efectos adversos , Factores de Edad , Antibacterianos/efectos adversos , Aspergillus/patogenicidad , Candida/patogenicidad , Niño , Neoplasias Hematológicas/microbiología , Humanos , Infecciones Fúngicas Invasoras/epidemiología , Leucemia Mieloide Aguda/complicaciones , Neoplasias/microbiología , Neutropenia/complicaciones , Factores de Riesgo
20.
J Med Microbiol ; 68(4): 609-615, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30875283

RESUMEN

PURPOSE: The oral microbiome is maintained by host- and microbe-derived factors. A shift in microbial composition, as a result of diseases related to the immune system, is the most important step in the development of oral and dental diseases. The aim of this study was to investigate the oral microbial composition of patients with Kostmann syndrome, who have severe neutropenia, compared with healthy children. METHODOLOGY: A group of nine Kostmann syndrome patients and a group of nine healthy controls participated. After clinical investigation, DNA from stimulated saliva specimens was examined by high-throughput sequencing of the V3-V4 hypervariable region of the 16S rRNA gene using Illumina sequencing. The QIIME software package was used for 16 S rRNA amplicon analysis, while the Greengenes database was used for taxonomic classification. RESULTS: The periodontal pocket depths, plaque indices and bleeding-on-probing percentages and caries status on the deciduous teeth of the patients with Kostmann syndrome were statistically higher than those for the healthy controls. Patients with Kostmann syndrome had significantly lower bacterial diversity as compared to the controls. The presence of Firmicutes was statistically higher in patients with Kostmann syndrome, while that for Proteobacteria was higher in samples from the healthy controls (P<0.05). Streptococcus, Rothia, Granulicatella, Actinomyces, and genera from the family Gemellaceae were present as the core microbiome (abundance >1 % in at least 75  % of samples) in all groups, whereas the genus Porphyromonas was only detected as a member of the core microbiome in Kostmann patients. CONCLUSIONS: The evidence of lower bacterial diversity and differences in microbial profile for patients with Kostmann syndrome not only shows the impact of immune system-related diseases on oral microbiota, but also endorses the ecological plaque hypothesis proposed for the aetiology of oral diseases such as dental caries and periodontitis.


Asunto(s)
Disbiosis/complicaciones , Microbiota , Boca/microbiología , Neutropenia/congénito , Saliva/microbiología , Adolescente , Bacterias/clasificación , Bacterias/aislamiento & purificación , Estudios de Casos y Controles , Niño , Preescolar , ADN Bacteriano/genética , Disbiosis/inmunología , Femenino , Variación Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Boca/patología , Neutropenia/complicaciones , Neutropenia/microbiología , Periodontitis/microbiología , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Adulto Joven
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