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PURPOSE: Malignant otitis externa (MOE) is a rare form of invasive osteomyelitis of the external ear canal. It is typically caused by Pseudomonas aeruginosa in immunocompromised patients. The diagnosis is clinical, and the initial treatment involves systemic antibiotics or antifungal therapy. Surgery is usually only considered when medical treatment has failed. Although hyperbaric oxygen therapy (HBOT) is recommended for refractory osteomyelitis, there are no specific guidelines for MOE. METHODS: This is a retrospective study that evaluates clinical data, treatment, and results obtained in patients diagnosed with MOE treated with HBOT at the Pedro Hispano Hospital between 2007 and 2022. RESULTS: During the study period, fifteen patients diagnosed with MOE were admitted for treatment with HBOT. All patients received antibiotic and/or antifungal therapy, and three required surgical intervention before starting HBOT. The pathology was successfully managed on all patients. CONCLUSIONS: HBOT may be an effective adjuvant treatment option in patients with MOE but it lacks robust scientific evidence. However, its therapeutic value should not be underestimated due to the good results and few adverse effects reported in recent retrospective studies and case reports.
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Acute myeloid leukaemia (AML) management remains a significant challenge in oncology due to its low survival rates and high post-treatment relapse rates, mainly attributed to treatment-resistant leukaemic stem cells (LSCs) residing in bone marrow (BM) niches. This review offers an in-depth analysis of AML progression, highlighting the pivotal role of extracellular vesicles (EVs) in the dynamic remodelling of BM niche intercellular communication. We explore recent advancements elucidating the mechanisms through which EVs facilitate complex crosstalk, effectively promoting AML hallmarks and drug resistance. Adopting a temporal view, we chart the evolving landscape of EV-mediated interactions within the AML niche, underscoring the transformative potential of these insights for therapeutic intervention. Furthermore, the review discusses the emerging understanding of endothelial cell subsets' impact across BM niches in shaping AML disease progression, adding another layer of complexity to the disease progression and treatment resistance. We highlight the potential of cutting-edge methodologies, such as organ-on-chip (OoC) and single-EV analysis technologies, to provide unprecedented insights into AML-niche interactions in a human setting. Leveraging accumulated insights into AML EV signalling to reconfigure BM niches and pioneer novel approaches to decipher the EV signalling networks that fuel AML within the human context could revolutionise the development of niche-targeted therapy for leukaemia eradication.
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Progressão da Doença , Vesículas Extracelulares , Leucemia Mieloide Aguda , Nicho de Células-Tronco , Humanos , Vesículas Extracelulares/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Microambiente Tumoral , Animais , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Medula Óssea/patologia , Medula Óssea/metabolismo , Comunicação Celular , Transdução de Sinais , Resistencia a Medicamentos AntineoplásicosRESUMO
It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment, rather than specific bone marrow stroma, to combat the invasion by and survival of chemo-resistant T-ALL cells.
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Células da Medula Óssea/citologia , Leucemia-Linfoma de Células T do Adulto/patologia , Transplante de Neoplasias , Microambiente Tumoral , Animais , Movimento Celular , Progressão da Doença , Feminino , Células-Tronco Hematopoéticas/citologia , Humanos , Microscopia Intravital , Masculino , Camundongos , Osteoblastos/citologia , Análise de Célula ÚnicaRESUMO
The interplay of cancer cells and surrounding stroma is critical in disease progression. This is particularly evident in hematological malignancies that infiltrate the bone marrow and peripheral lymphoid organs. Despite clear evidence for the existence of these interactions, the precise repercussions on the growth of leukemic cells are poorly understood. Recent development of novel imaging technology and preclinical disease models has advanced our comprehension of leukemia-microenvironment crosstalk and has potential implications for development of novel treatment options.
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Medula Óssea/metabolismo , Neoplasias Hematológicas/metabolismo , Leucemia/metabolismo , Neoplasias Experimentais/metabolismo , Microambiente Tumoral , Animais , Medula Óssea/patologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Leucemia/patologia , Leucemia/terapia , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapiaRESUMO
PURPOSE: Tonsillectomy is one of the most common surgical procedures in otorhinolaryngology. Hemorrhage in the postoperative period has an incidence of up to 20% and is a potentially fatal complication. We aim to assess the incidence of hemorrhage after tonsillectomy in our institution, and to evaluate and identify the possible associated risk factors. METHODS: This retrospective study included 897 patients who underwent tonsillectomy between January 2015 and December 2018, 50.7% women and 49.3% men, aged between 2 and 83 years. No coagulopathies were identified. Comparison of age, gender, surgical indication, coagulation profile, concomitant adenoidectomy, surgical technique, surgeon's experience and hemostasis method between groups with and without post-operative bleeding was made. RESULTS: Our incidence of post-tonsillectomy hemorrhage was 6%. Most patients (83.3%) had secondary bleeding (> 24 h after surgery). In 22.2% of the bleeding cases, it was necessary to revise the hemostasis in the operating room. Adulthood (age ≥ 18 years) (p < 0.001), INR values ≥ 1.2 (p = 0.014), aPTT values ≥ 35 s (p = 0.001), as well as concomitant adenoidectomy (p < 0.001) were the predictors of post-tonsillectomy bleeding. CONCLUSION: Recognition of adult age, INR ≥ 1.2, aPTT ≥ 35 s and concomitant adenoidectomy as risk factors can be useful in identifying the patients at higher risk for bleeding complications.
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Tonsilectomia , Adenoidectomia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/cirurgia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Tonsilectomia/efeitos adversos , Adulto JovemRESUMO
The majority of acute myeloid leukemia (AML) patients have a poor response to conventional chemotherapy. The survival of chemoresistant cells is thought to depend on leukemia-bone marrow (BM) microenvironment interactions, which are not well understood. The CXCL12/CXCR4 axis has been proposed to support AML growth but was not studied at the single AML cell level. We recently showed that T-cell acute lymphoblastic leukemia (T-ALL) cells are highly motile in the BM; however, the characteristics of AML cell migration within the BM remain undefined. Here, we characterize the in vivo migratory behavior of AML cells and their response to chemotherapy and CXCR4 antagonism, using high-resolution 2-photon and confocal intravital microscopy of mouse calvarium BM and the well-established MLL-AF9-driven AML mouse model. We used the Notch1-driven T-ALL model as a benchmark comparison and AMD3100 for CXCR4 antagonism experiments. We show that AML cells are migratory, and in contrast with T-ALL, chemoresistant AML cells become less motile. Moreover, and in contrast with T-ALL, the in vivo exploratory behavior of expanding and chemoresistant AML cells is unaffected by AMD3100. These results expand our understanding of AML cells-BM microenvironment interactions, highlighting unique traits of leukemia of different lineages.
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Movimento Celular , Quimiocina CXCL12/metabolismo , Compostos Heterocíclicos/antagonistas & inibidores , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Receptores CXCR4/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Benzilaminas , Medula Óssea/metabolismo , Medula Óssea/patologia , Linhagem Celular Tumoral , Ciclamos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos Heterocíclicos/metabolismo , Microscopia Intravital , Leucemia Mieloide Aguda/metabolismo , Camundongos , Microscopia Confocal , Microscopia de Fluorescência por Excitação Multifotônica , Microambiente TumoralRESUMO
Heme is essential for a variety of proteins involved in vital physiological functions in the body, such as oxygen transport, drug metabolism, biosynthesis of steroids, signal transduction, antioxidant defense and mitochondrial respiration. However, free heme is potentially cytotoxic due to the capacity of heme iron to promote the oxidation of cellular molecules. The liver plays a central role in heme metabolism by significantly contributing to heme synthesis, heme detoxification, and recycling of heme iron. Conversely, enzymatic defects in the heme biosynthetic pathway originate multisystemic diseases (porphyrias) that are highly associated with liver damage. In addition, there is growing evidence that heme contributes to the outcomes of inflammatory, metabolic and malignant liver diseases. In this review, we summarize the contribution of the liver to heme metabolism and the association of heme dyshomeostasis with liver disease.
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Neurotoxicity associated with cephalosporins is an increasingly recognized complication, although among cephalosporins, ceftazidime is rarely reported for such an adverse reaction. Moreover, subacute, rather than acute, presentation of neurotoxicity associated with cephalosporins is rare. A 77-year-old female patient with stage 4 chronic renal disease was admitted due to cellulitis in her right lower limb, multiorgan dysfunction complicated by oliguric acute kidney injury, and a need for hemodialysis via a central venous catheter. On the 13th day after admission, she became febrile, and bacteremia associated with a central venous catheter was identified, which prompted the initiation of empirical antibiotic therapy with vancomycin and ceftazidime. After 13 days of antibiotic therapy with vancomycin and ceftazidime, the patient became confused, with temporal-spatial disorientation and myoclonus, especially in the upper limbs, with worsening renal function. Ceftazidime was discontinued, and the patient's condition improved with complete remission of symptoms on the 8th day after symptom onset. Neurotoxicity associated with ceftazidime is a rare but probably underdiagnosed adverse reaction. It is more frequent in elderly patients with previous neurological dysfunction and end-stage kidney disease and/or acute kidney injury, and it usually manifests soon after starting treatment. Early identification and monitoring of risk factors and symptoms should lead the physician to a rapid withdrawal of the offending drug.
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Antibacterianos , Ceftazidima , Síndromes Neurotóxicas , Humanos , Idoso , Feminino , Ceftazidima/efeitos adversos , Ceftazidima/uso terapêutico , Antibacterianos/efeitos adversos , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/diagnóstico , Vancomicina/efeitos adversos , Diálise Renal , Resultado do Tratamento , Injúria Renal Aguda/induzido quimicamenteRESUMO
More effective approaches are needed in the treatment of blood cancers, in particular acute myeloid leukemia (AML), that are able to eliminate resistant leukemia stem cells (LSCs) at the bone marrow (BM), after a chemotherapy session, and then enhance hematopoietic stem cell (HSC) engraftment for the re-establishment of the HSC compartment. Here, we investigate whether light-activatable nanoparticles (NPs) encapsulating all-trans-retinoic acid (RA+NPs) could solve both problems. Our in vitro results show that mouse AML cells transfected with RA+NPs differentiate towards antitumoral M1 macrophages through RIG.1 and OASL gene expression. Our in vivo results further show that mouse AML cells transfected with RA+NPs home at the BM after transplantation in an AML mouse model. The photo-disassembly of the NPs within the grafted cells by a blue laser enables their differentiation towards a macrophage lineage. This macrophage activation seems to have systemic anti-leukemic effect within the BM, with a significant reduction of leukemic cells in all BM compartments, of animals treated with RA+NPs, when compared with animals treated with empty NPs. In a separate group of experiments, we show for the first time that normal HSCs transfected with RA+NPs show superior engraftment at the BM niche than cells without treatment or treated with empty NPs. This is the first time that the activity of RA is tested in terms of long-term hematopoietic reconstitution after transplant using an in situ activation approach without any exogenous priming or genetic conditioning of the transplanted cells. Overall, the approach documented here has the potential to improve consolidation therapy in AML since it allows a dual intervention in the BM niche: to tackle resistant leukemia and improve HSC engraftment at the same time.
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Iron overload (IOL) is hypothesized to contribute to dysplastic erythropoiesis. Several conditions, including myelodysplastic syndrome, thalassemia and sickle cell anemia, are characterized by ineffective erythropoiesis and IOL. Iron is pro-oxidant and may participate in the pathophysiology of these conditions by increasing genomic instability and altering the microenvironment. There is, however, lack of in vivo evidence demonstrating a role of IOL and oxidative damage in dysplastic erythropoiesis. NRF2 transcription factor is the master regulator of antioxidant defenses, playing a crucial role in the cellular response to IOL in the liver. Here, we crossed Nrf2-/- with hemochromatosis (Hfe-/-) or hepcidin-null (Hamp1-/-) mice. Double-knockout mice developed features of ineffective erythropoiesis and myelodysplasia including macrocytic anemia, splenomegaly, and accumulation of immature dysplastic bone marrow (BM) cells. BM cells from Nrf2/Hamp1-/- mice showed increased in vitro clonogenic potential and, upon serial transplantation, recipients disclosed cytopenias, despite normal engraftment, suggesting defective differentiation. Unstimulated karyotype analysis showed increased chromosome instability and aneuploidy in Nrf2/Hamp1-/- BM cells. In HFE-related hemochromatosis patients, NRF2 promoter SNP rs35652124 genotype TT (predicted to decrease NRF2 expression) associated with increased MCV, consistent with erythroid dysplasia. Our results suggest that IOL induces ineffective erythropoiesis and dysplastic hematologic features through oxidative damage in Nrf2-deficient cells.
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Anemia , Hemocromatose , Sobrecarga de Ferro , Síndromes Mielodisplásicas , Animais , Humanos , Camundongos , Anemia/metabolismo , Eritropoese/genética , Hemocromatose/genética , Hemocromatose/metabolismo , Sobrecarga de Ferro/genética , Sobrecarga de Ferro/metabolismo , Camundongos Knockout , Síndromes Mielodisplásicas/genética , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismoRESUMO
Type 1 diabetes mellitus is responsible for metabolic dysfunction, accompanied by chronic inflammation, oxidative stress, and endothelium dysfunction, and is often associated with impaired wound healing. Phenol-rich food improves vascular function, contributing to diabetes prevention. This study has evaluated the effect of phenol-rich beverage consumption in diabetic rats on wound healing, through angiogenesis, inflammation, and oxidative stress modulation. A wound-healing assay was performed in streptozotocin-induced diabetic Wistar rats drinking water, 5% ethanol, and stout beer with and without 10 mg/L xanthohumol (1), for a five-week period. Wounded skin microvessel density was reduced to normal values upon consumption of 1 in diabetic rats, being accompanied by decreased serum VEGF-A and inflammatory markers (IL-1ß, NO, N-acetylglucosaminidase). Systemic glutathione and kidney and liver H2O2, 3-nitrotyrosine, and protein carbonylation also decreased to healthy levels after treatment with 1, implying an improvement in oxidative stress status. These findings suggest that consumption of xanthohumol (1) by diabetic animals consistently decreases inflammation and oxidative stress, allowing neovascularization control and improving diabetic wound healing.
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Indutores da Angiogênese/metabolismo , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Propiofenonas/farmacologia , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Flavonoides/química , Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Inflamação/complicações , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Fígado/metabolismo , Masculino , Neovascularização Patológica/metabolismo , Fenóis/farmacologia , Propiofenonas/química , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Tirosina/análogos & derivados , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
INTRODUCTION: Artery of Percheron (AOP) is an uncommon anatomic variant of the arterial supply of the medial thalami. Owing to variable clinical presentation, challenging imaging diagnosis, and its rarity, it is difficult to diagnose AOP infarctions. We present a clinical case of a unique presentation of AOP infarction associated with paradoxical embolism and highlight the atypical clinical manifestations and challenging diagnosis of this stroke syndrome. CASE REPORT: A 58-year-old White female with chronic renal insufficiency on hemodialysis was admitted to our center with a 10-hour course of hypersomnolence and right-sided ataxia. She had normal body temperature, blood pressure, peripheral oxygen saturation, and heart rate and scored 11 points in the Glasgow Coma Scale and 12 points in National Institutes of Health Stroke Scale. Initial brain computerized tomography scan, electrocardiogram, and thoracic radiography were normal; transcranial Doppler ultrasound showed >50% stenosis at the P2 segment of the right posterior cerebral artery, and transthoracic echocardiogram, a patent foramen ovale and thrombus adherent to the hemodialysis catheter. On day 3, she underwent brain magnetic resonance that showed acute ischemic lesions at the paramedian thalami and the superior cerebral peduncles. AOP infarction due to a paradoxical embolism from a patent foramen ovale with a right atrial thrombus was the final diagnosis. CONCLUSIONS: AOP infarctions are a rare type of stroke with elusive clinical presentations and frequently, initial imaging assessment is normal. Early recognition is crucial, and a high index of suspicion is needed to suspect this diagnosis.
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Distúrbios do Sono por Sonolência Excessiva , Embolia Paradoxal , Forame Oval Patente , Acidente Vascular Cerebral , Trombose , Humanos , Feminino , Pessoa de Meia-Idade , Forame Oval Patente/complicações , Embolia Paradoxal/complicações , Embolia Paradoxal/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Artérias/patologia , Trombose/complicações , Infarto/complicações , Distúrbios do Sono por Sonolência Excessiva/complicaçõesRESUMO
Angiogenesis and inflammation are two intermingled processes that play a role in wound healing. Nevertheless, whenever exacerbated, these processes result in nonhealing wounds. Xanthohumol (XN), a beer-derived polyphenol, inhibits these processes in many physiopathological situations. This study aimed at examining whether XN ingestion affects wound healing. Wistar rats drinking water, 5% ethanol, stout beer (SB) or stout beer supplemented with 10 mg/L XN (Suppl SB) for 4 weeks, were subjected to a 1.5 cm full skin-thickness longitudinal incision, and further maintained under the same beverage conditions for another week. No differences in beverage consumption or body weight were found throughout the study but food intake decreased in every group relative to controls. Consumption of Suppl SB resulted in decreased serum VEGF levels (18.42%), N-acetylglucosaminidase activity (27.77%), IL1ß concentration (9.07%), and NO released (77.06%), accompanied by a reduced redox state as observed by increased GSH/GSSG ratio (to 198.80%). Also, the number of blood vessels within the wound granulation tissue seems to reduce in animals drinking Suppl SB (23.08%). Interestingly, SB and primarily Suppl SB showed a tendency to increase adipocyte number (to 194.26% and 156.68%, respectively) and reduce adipocyte size (4.60% and 24.64%, respectively) within the granuloma. Liver function and metabolism did not change among the animal groups as analyzed by plasma biochemical parameters, indicating no beverage toxicity. This study shows that XN intake in its natural beer context reduced inflammation, oxidative stress, and angiogenesis, ameliorating the wound healing process, suggesting that this polyphenol may exert beneficial effect as a nutritional supplement.
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Adipócitos/efeitos dos fármacos , Cerveja , Flavonoides/farmacologia , Inflamação/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Propiofenonas/farmacologia , Cicatrização/efeitos dos fármacos , Acetilglucosaminidase/metabolismo , Animais , Suplementos Nutricionais , Glutationa/sangue , Granuloma/metabolismo , Interleucina-1beta/metabolismo , Óxido Nítrico/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/lesões , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
The bone marrow (BM) is the soft tissue found within bones where hematopoiesis, the process by which new blood cells are generated, primarily occurs. As such, it contains hematopoietic stem and progenitor cells (HSPCs), as well as supporting stromal cells that contribute to the maintenance and regulation of HSPCs. Hematological and other BM disorders disrupt hematopoiesis by affecting hematopoietic cells directly and/or through the alteration of the BM niche. Here, we describe a method to study hematopoiesis in health and malignancy through the phenotypic analysis of murine BM HSPCs and stromal niche populations by flow cytometry. Our method details the required steps to enrich BM cells in endosteal and central BM fractions, as well as the appropriate gating strategies to identify the two key niche cell types involved in HSPC regulation, endothelial cells and mesenchymal stem cells. The phenotypic analysis proposed here may be combined with mouse mutants, disease models, and functional assays to characterize the HSPC compartment and its niche.
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Medula Óssea , Nicho de Células-Tronco , Camundongos , Animais , Medula Óssea/metabolismo , Nicho de Células-Tronco/fisiologia , Citometria de Fluxo , Células Endoteliais , Células-Tronco Hematopoéticas/metabolismo , Hematopoese , Células da Medula Óssea/metabolismo , Células Estromais/metabolismoRESUMO
OBJECTIVE: To ascertain the cumulative incidence of acute organ failure and intensive care unit admission in cancer patients. METHODS: This was a single-center prospective cohort study of adult cancer patients admitted for unscheduled inpatient care while on systemic cancer treatment. RESULTS: Between August 2018 and February 2019, 10,392 patients were on systemic treatment, 358 had unscheduled inpatient care and were eligible for inclusion, and 285 were included. The mean age was 60.9 years, 50.9% were male, and 17.9% of patients had hematologic cancers. The cumulative risk of acute organ failure was 39.6% (95%CI: 35 - 44), and that of intensive care unit admission among patients with acute organ failure was 15.0% (95%CI: 12 - 18). On admission, 62.1% of patients were considered not eligible for artificial organ replacement therapy. The median follow-up time was 9.5 months. Inpatient mortality was 17.5%, with an intensive care unit mortality rate of 58.8% and a median cohort survival of 134 days (95%CI: 106 - 162). In multivariate analysis, acute organ failure was associated with 6-month postdischarge mortality (HR 1.6; 95%CI: 1.2 - 2.2). CONCLUSION: The risk of acute organ failure in cancer patients admitted for unscheduled inpatient care while on systemic treatment was 39.6%, and the risk of intensive care unit admission was 15.0%. Acute organ failure in cancer patients was an independent poor prognostic factor for inpatient hospital mortality and 6-month survival.
OBJETIVO: Determinar a incidência cumulativa de falência aguda de órgão e internamento em unidade de terapia intensiva em pacientes oncológicos. MÉTODOS: Estudo de coorte prospectivo de pacientes oncológicos adultos em tratamento sistêmico antineoplásico, internados de forma não programada. RESULTADOS: Entre agosto de 2018 e fevereiro de 2019, 10.392 pacientes foram submetidos a tratamento sistêmico antineoplásico, sendo que 358 necessitaram de internamento hospitalar não programado e foram elegíveis para inclusão; por fim, 258 desses pacientes foram incluídos. A média de idade foi de 60,9 anos, e 50,9% eram do sexo masculino; 17,9% dos pacientes tinham câncer hematológico. O risco acumulado de falência de órgãos foi de 39,6% (IC95% 35 - 44) e o risco de internamento na unidade de terapia intensiva em pacientes com falência aguda de órgão foi de 15,0% (IC95% 12 - 18). À admissão em internamento, 62,1% dos pacientes foram considerados não elegíveis para terapia de substituição artificial de órgãos. O tempo mediano de seguimento foi de 9,5 meses. A mortalidade hospitalar foi de 17,5%, na unidade de terapia intensiva de 58,8%. A mediana de sobrevivência da coorte foi de 134 dias (IC95% 106 - 162). Na análise multivariada, a falência aguda de órgão se associou com a mortalidade aos 6 meses após a alta (hazard ratio: 1,6; IC95% 1,2 - 2,2). CONCLUSÃO: O risco de falência aguda de órgão em pacientes oncológicos admitidos para tratamento hospitalar não programado durante o tratamento sistémico foi de 39,6% e o risco de internamento em unidade de terapia intensiva foi de 15,0%. A falência aguda de órgão em pacientes oncológicos foi um fator de prognóstico independente para maior mortalidade intra-hospitalar e menor sobrevivência aos 6 meses após a alta.
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Assistência ao Convalescente , Neoplasias , Adulto , Estudos de Coortes , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/terapia , Alta do Paciente , Prognóstico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Acute myeloid leukemia (AML) is a blood cancer of the myeloid lineage. Its prognosis remains poor, highlighting the need for new therapeutic and precision medicine approaches. AML symptoms often include cytopenias linked to loss of healthy hematopoietic stem and progenitor cells (HSPCs). The mechanisms behind HSPC decline are complex and still poorly understood. Here, intravital microscopy (IVM) of a well-established experimental model of AML allows direct observation of the interactions between healthy and malignant cells in the bone marrow (BM), suggesting that physical dislodgment of healthy cells by AML through damaged vasculature may play an important role. Multiple matrix metalloproteinases (MMPs), known to remodel extracellular matrix, are expressed by AML cells and the BM microenvironment. We reason MMPs could be involved in cell displacement and vascular leakiness; therefore, we evaluate the therapeutic potential of MMP pharmacological inhibition using the broad-spectrum inhibitor prinomastat. IVM analyses of prinomastat-treated mice reveal reduced vascular permeability and healthy cell clusters in circulation and lower AML infiltration, proliferation, and cell migration. Furthermore, treated mice have increased retention of healthy HSPCs in the BM and increased survival following chemotherapy. Analysis of a human AML transcriptomic database reveals widespread MMP deregulation, and human AML cells show susceptibility to MMP inhibition. Overall, our results suggest that MMP inhibition could be a promising complementary therapy to reduce AML growth and limit HSPC loss and BM vascular damage caused by MLL-AF9 and possibly other AML subtypes.
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Leucemia Mieloide Aguda , Animais , Medula Óssea/patologia , Células-Tronco Hematopoéticas/patologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Metaloproteases , Camundongos , Prognóstico , Microambiente TumoralRESUMO
Foreign bodies in the external ear are very common. The same cannot be said about foreign bodies in the Eustachian tube (ET). We report the case of a 63-year-old woman with a history of painless left side otorrhea and hearing loss. She reported a left ear surgery when she was 30-year-old but she did not know the diagnosis that was made at that time neither the kind of surgery performed. Otoscopic examination revealed an inferior perforation of the eardrum. Audiologic evaluation demonstrated a unilateral, moderate-severe mixed hearing loss. Computed tomography scan showed, in left ear, a soft tissue density filling the middle ear cavity and a foreign body in ET. The patient underwent middle ear exploration which required endoscopic assistance to visualize and remove the foreign body. It appeared to be a stapes prothesis of Robinson type. The displacement of a stapes prosthesis to the ET has not been reported in the literature. Surgeries in this region are challenging. This case highlights the importance of the integration of endoscopy into otologic surgery.
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INTRODUCTION: The performance of pediatric tympanoplasty is a matter of controversy in the literature, varying from 35 to 94%. Several authors argue that the performance of tympanoplasty should be delayed until 6-8 years old or even after 10 years old. OBJECTIVES: To analyze the results of type I tympanoplasty in pediatric age and to identify possible prognostic factors. MATERIAL AND METHODS: Retrospective study of children undergoing type I tympanoplasty (Portmann's classification) between January 2012 and December 2018 in our hospital. The following variables were analyzed: age, gender, etiology, size and location of the perforation, operated ear, season of the surgery, experience of the surgeon, condition of the contralateral ear, previous otologic surgery, previous adenoidectomy, presence of tympanosclerosis, surgical approach, type of graft, tympanoplasty technique, pre and postoperative audiometric results and follow-up time. The integrity of tympanic membrane (TM) was defined as anatomical success at 6 months postoperatively and as functional success we defined a pure tone average < 20 dB (mean of 0.5-4 KHz) in postoperative tonal audiometry, performed between 3 and 6 months after surgery. RESULTS: A total of 48 ears operated on 38 patients, aged between 8 and 17 years. Anatomical and functional success rates of 81.3% and 87.5%, respectively, were obtained. The only statistically significant poor prognostic factor was the presence of tympanosclerosis plaques in the middle ear, negatively affecting anatomical success (p = 0.007) and functional success (p = 0.008). There was an anatomical failure rate of 25% in the anterior and lower TM perforations, 14.3% in central and 7.7% in posterior perforations (p = 0.603). Perforations >50% of the TM surface showed a functional failure rate of 25% vs. 10% in perforations <50% of the TM (p = 0.242) and anatomical failure rates of 12.5% vs. 20%, respectively (p = 0.620). Regarding age, the group <12 years had an anatomical success rate of 85.7%, while the group ≥12 years had a rate of 79.4% (p = 0.611). As for the functional success rates, this was 92.9% and 85.3%, respectively (p = 0.471). Apart from the presence of tympanosclerosis, no other variable was statistically significantly associated with surgical success. CONCLUSIONS: Our study shows that type I tympanoplasty in pediatric age is a procedure with a high rate of anatomical and functional success. The presence of tympanosclerosis plaques in the middle ear was the only factor associated with poor anatomical and functional prognosis. Contrary to what has been described in some articles in the literature, in this study, the functional and anatomical success rates did not vary according to the age group.