RESUMO
INTRODUCTION: Hodgkin Lymphoma (HL) is a prevalent hematological cancer in the world and Chile. OBJECTIVES: Show the experience of 10 years treating HL in a Chilean academic center. Additionally, it exposes the diagnostic performance of PET CT and Bone Marrow Biopsy. MATERIAL AND METHODS: We conducted a retrospective cohort study to collect data and outcomes of patients treated in our center. RESULTS: 82 patients were analyzed (Average age, 35 years old; the ratio between men and women was 1.9:1). Progression-free survival was 88.6% and 66.4% for localized and advanced stages, respectively. PET as a staging strategy had better sensitivity than Marrow Biopsy. CONCLUSIONS: The clinical results of the patients treated in this Chilean teaching center were comparable to the international literature. Additionally, PET CT proved to be a superior tool in diagnosis and staging compared to biopsy in our patients.
Assuntos
Doença de Hodgkin , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Chile , Biópsia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Idoso , Sensibilidade e Especificidade , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologiaRESUMO
BACKGROUND: Acute myeloid leukemia (AML) is the most common leukemia in adults. AIM: To Describe our population of patients with AML and report the outcomes of our treatments. MATERIAL AND METHODS: Review of electronic clinical records of 114 patients with AML with a median age of 57 years (59% men). RESULTS: Seventeen percent of patients were classified as low risk, 38% as intermediate risk and 33% as high risk. Seventy-six percent of patients were treated with intensive chemotherapy. Five years overall survival according to cytogenetic risk was 59, 41, and 12% in low, intermediate, and high-risk patients, respectively. The outcomes were better in patients under 60 years. The median survival of patients treated with intensive chemotherapy aged less than 60 years and 60 years and above was 3.4 and 1 year, respectively. CONCLUSIONS: Our results are comparable to those reported in developed countries. Improving the survival of patients 60 years and older is our main challenge.
Assuntos
Leucemia Mieloide Aguda , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Resultado do TratamentoRESUMO
COVID-19 has rapidly become a major concern for the health systems worldwide. Its high contagiousness and associated mortality demand the discovery of helpful interventions with promising safety profile. Here, we report 3 severe COVID-19 cases, which achieved rapid and sustained improvement in outcome with the use of ruxolitinib, a JAK/STAT pathway inhibitor.
Assuntos
COVID-19/patologia , Doenças Hematológicas/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Adulto , Proteína C-Reativa/análise , COVID-19/complicações , COVID-19/virologia , Ferritinas/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Doenças Hematológicas/etiologia , Humanos , Inibidores de Janus Quinases/farmacologia , Masculino , Pessoa de Meia-Idade , Nitrilas , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Pirimidinas , SARS-CoV-2/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Currently, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is a major public health problem worldwide. Although most patients present a mild infection, effective strategies are required for patients who develop the severe disease. Anti-inflammatory treatment with JAK inhibitors has been considered in SARS-CoV-2. METHODS: In this study, we presented our experience in a group of severe SARS-CoV-2 Chilean patients. This prospective study was performed on consecutive patients presenting severe respiratory failure owing to COVID-19 or high-risk clinical condition associated with SARS-CoV-2, and who were treated with ruxolitinib for management of associated inflammation. Overall, 18 patients presenting SARS-CoV-2 viral-induced hyperinflammation were treated with ruxolitinib, with 16 patients previously treated with steroids, 4 with tocilizumab, and 3 with both treatments. RESULTS: Ten patients evolved with favorable response, including 7 patients admitted with severe respiratory failure (PaFi less than 200 mm Hg in high-flow nasal cannula), presenting complete regression of hyperinflammation, regression of the lung lesions, and subsequent discharge. In the remaining 8 patients, 25% showed reduced inflammation, but early discharge was not achieved owing to the slow evolution of respiratory failure. Unfortunately, 3 patients demonstrated a severe respiratory failure. The early initiation of ruxolitinib was found to be associated with better clinical evolution (p < 0.005). CONCLUSION: In this study, ruxolitinib resolved hyperinflammatory state in 55% of the patients, regardless of the previous steroid or tocilizumab therapy. Unfortunately, few patients demonstrated severe evolution despite ruxolitinib therapy. Notably, the treatment starting time appears to play an important role in achieving good outcomes. Further validation in randomized controlled trials is crucial.
Assuntos
COVID-19/complicações , Inflamação/tratamento farmacológico , Nitrilas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/patologia , COVID-19/virologia , Chile , Feminino , Humanos , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/etiologia , SARS-CoV-2/isolamento & purificação , Esteroides/uso terapêutico , Trombocitopenia/etiologia , Resultado do TratamentoRESUMO
Monoclonal gammopathies of uncertain significance (MGUS) correspond to pre-malignant hematological disorders characterized by the production of a monoclonal protein and infiltration of less than 10% of the bone marrow by plasma cells. Its importance lies in the risk of progression to malignant disorders and in the association with different renal, neurological and skin manifestations. There are pathophysiological mechanisms that support a causal relationship between monoclonal gammopathies (MGs) and different skin diseases, such as type I cryoglobulinemia (CG), primary systemic amyloidosis (PSA) or necrobiotic xanthogranuloma (NXG). However, there is a group of skin diseases associated with MGs whose pathogenesis has not been elucidated. In this context, the role of the dermatologist is crucial in the suspicion of different haematological disorders based on skin manifestations and in the multidisciplinary treatment of these patients. In this article, we carry out an exhaustive review of the literature published in this area and propose a screening algorithm for MGs in patients with specific skin diseases.
Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Dermatopatias , Medula Óssea , Humanos , Paraproteinemias/complicações , Dermatopatias/etiologiaRESUMO
BACKGROUND: In our country, transplantation centers differ in the age limit for allogeneic hematopoietic transplantation (ALOHT). In our program, transplants with age- adjusted conditioning are performed in patients until 70 years old. Currently more than 60% of ALOHT reported to the Center for International Bone Marrow Transplantation Research (CIBMTR) are performed in patients older than 40 years. AIM: To report our experience with ALOHT in acute myelogenous leukemia (AML), analyzing patient age at transplantation in different periods and transplant results in different age groups. MATERIAL AND METHODS: A retrospective analysis of the database of adult hematopoietic transplants in AML patients was performed. Demographic data, disease characteristics, transplant data, survival and relapse times, and mortality were collected. RESULTS: In our program, 1030 transplants were performed in adults and 119 ALOHT were performed in AML patients, between 1990 and 2020. The median age of patients in all periods was 41 years, (range 16-69). The median age was 33 and 45 years, in the periods 1990-2000 and 2000-2020 respectively (p < 0.01). Seventy-eight patients received myeloablative conditioning (median age 44 years) and 41 reduced intensity conditioning (median age 53 years). Five-year overall survival was 44.6% (confidence intervals (CI) 41-48). Non relapse mortality of all periods was 19% (CI 17 - 40%) and relapse rate was 17 % (CI 16-22). No difference in five years overall survival among patients younger than 40, 41 to 50 and over 51 years was observed. CONCLUSIONS: Overall Survival, non-relapse mortality and relapse rate were similar in younger and older patients in our program and similar to those previously reported in other centers.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adolescente , Adulto , Idoso , Humanos , Leucemia Mieloide Aguda/terapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
The pathophysiology of the inflammatory profile induced by SARS-COV2 infection has similarities with conditions of immune system activation with cytokine release such as hemophagocytic syndrome and some cases of acute graft-versus-host disease. There are encouraging results of clinical studies, performed with increasingly better methodological quality, supporting the use of targeted and specific anti-inflammatory therapy in selected groups of patients with COVID-19 with severe inflammation. In this review we describe the inflammatory pathophysiology of the disease and the recent findings about its treatment.
Assuntos
COVID-19 , RNA Viral , Anti-Inflamatórios/uso terapêutico , Citocinas , Humanos , SARS-CoV-2RESUMO
Due to blood derivative requirements, many patients with hemophilia were exposed to Hepatitis C virus infection (HCV) before the availability of HCV testing. We report a 46-year-old male with Hemophilia A with a hepatitis virus C infection since 2004 causing a cirrhosis. Due to a hepatopulmonary syndrome, he received a liver allograph using a factor VIII replacement protocol, after eradicating the virus C. He had a good postoperative evolution, and no more factor VIII was required after transplantation until his last assessment.
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Hemofilia A/complicações , Hepatite C/complicações , Cirrose Hepática/cirurgia , Transplante de Fígado/métodos , Fator IX/administração & dosagem , Fator VIII/administração & dosagem , Hemofilia A/terapia , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-IdadeRESUMO
GABA is a widely distributed inhibitory neurotransmitter. GABA-A receptors are hetero-pentameric channels assembled in multiple combinations from 19 available subunits; this diversity mediates phasic and tonic inhibitory synaptic potentials. Whereas GABA-A phasic receptors are located within the synaptic cleft, GABA-A tonic receptors are found peri- or extra-synaptically, where they are activated by diffusion of synaptic GABA release. In the neostriatum, GABA-A tonic subunits are present in the D2 medium-size spiny neurons. Since early impairment of these neurons is observed in Huntington's disease, we determined the ultrastructural localization of GABA-A-α5, -ß3, -δ, -ρ2 and, for the first time, of GABA-A-ρ3 subunits, in the D2 pathway of the YAC128 murine model of Huntington's disease at various stages of disease progression. We report mislocalization of all five subunits from peri- and extra-synaptic spaces into the synaptic clefts of YAC128 mice, present in diseased mice as early as 6 months-old. The synaptic localization of GABA-A tonic receptors correlated with increased sensitivity to pharmacologic antagonists during extracellular electrophysiological recordings in neostriatal slices. Finally, the association of GABA-A tonic receptors with the D2 pathway in 6-month-old mice was largely lost at 12 months of age.
Assuntos
Neurônios GABAérgicos/metabolismo , Doença de Huntington/metabolismo , Receptores de GABA-A/metabolismo , Animais , Neurônios GABAérgicos/patologia , Neurônios GABAérgicos/ultraestrutura , Humanos , Doença de Huntington/patologia , Camundongos , Camundongos Transgênicos , Neostriado/metabolismo , Neostriado/patologia , Sinapses/metabolismoRESUMO
The microtubule-associated protein 1B (MAP1B) plays critical roles in neurite growth and synapse maturation during brain development. This protein is well expressed in the adult brain. However, its function in mature neurons remains unknown. We have used a genetically modified mouse model and shRNA techniques to assess the role of MAP1B at established synapses, bypassing MAP1B functions during neuronal development. Under these conditions, we found that MAP1B deficiency alters synaptic plasticity by specifically impairing long-term depression (LTD) expression. Interestingly, this is due to a failure to trigger AMPA receptor endocytosis and spine shrinkage during LTD. These defects are accompanied by an impaired targeting of the Rac1 activator Tiam1 at synaptic compartments. Accordingly, LTD and AMPA receptor endocytosis are restored in MAP1B-deficient neurons by providing additional Rac1. Therefore, these results indicate that the MAP1B-Tiam1-Rac1 relay is essential for spine structural plasticity and removal of AMPA receptors from synapses during LTD. This work highlights the importance of MAPs as signalling hubs controlling the actin cytoskeleton and receptor trafficking during plasticity in mature neurons.
Assuntos
Endocitose/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Proteínas Associadas aos Microtúbulos/metabolismo , Plasticidade Neuronal/fisiologia , Receptores de AMPA/metabolismo , Sinapses/fisiologia , Animais , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Hipocampo/citologia , Camundongos , Camundongos Transgênicos , Microscopia de Fluorescência , Proteínas Associadas aos Microtúbulos/deficiência , Neuropeptídeos , Técnicas de Patch-Clamp , RNA Interferente Pequeno/genética , Coluna Vertebral/citologia , Estatísticas não Paramétricas , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T , Proteínas rac1 de Ligação ao GTPRESUMO
BACKGROUND: Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk of developing osteoporosis. AIM: To determine the frequency and severity of Vitamin D deficiency, secondary hyperparathyroidism and low bone mass in patients undergoing HCT. PATIENTS AND METHODS: Analysis of the database of patients undergoing HCT in our institution in the 2010-2015 period. We searched for patients with measurements of 25-OH vitamin D (25OHD), parathyroid hormone (PTH) and bone densitometry by double beam X ray absorptiometry (DXA) prior and up to one year after HCT. RESULTS: Ninety patients were included, 53 were evaluated prior to HCT and 37 after HCT. They represent 73% of all patients undergoing HCT in the period. Median 25OHD was 12 ng/ml (range 4-41.4). Ninety seven percent of patients had levels considered insufficient and 85% compatible with deficiency. Median PTH was 60.5 pg/ml (range 21-186). Forty five percent of patients had secondary hyperparathyroidism. DXA was performed in 65 patients (prior to HCT in 54 and after HCT in 11). Of these, 11% had had a low bone mineral density. CONCLUSIONS: Patients undergoing HCT have a high risk of vitamin D deficiency, secondary hyperparathyroidism and low bone mineral density.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hiperparatireoidismo Secundário/etiologia , Hormônio Paratireóideo/análise , Deficiência de Vitamina D/etiologia , Vitamina D/análise , Adolescente , Adulto , Idoso , Densidade Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Estudos Retrospectivos , Adulto JovemRESUMO
Patients undergoing hematopoietic cell transplantation (HCT) can have complications that require management in the intensive care unit (ICU). We conducted a retrospective study of patients undergoing HCT between 2007 and 2011 with admission to the ICU. We analyzed 97 patients, with an average age of 37 (range, 15 to 68). The main indications for HCT were hematologic malignancies (84%, n = 82). Ninety percent (n = 87) received myeloablative conditioning. Thirty-one percent were admitted (autologous transplant recipients 15%, allogeneic transplant recipients 34%, and umbilical cord blood [UCB] transplant recipients 48%) with an average length of stay of 19 days (range, 1 to 73 days). The average time between transplantation and transfer was 15 days. The main causes of admission were acute respiratory failure (63%) and septic shock (20%). ICU mortality was 20% for autologous transplantations and 64% for allogeneic transplantations (adult donor and UCB combined). On average, patients died 108 days after the transplantation (range, 4 to 320 days). One-year overall survival, comparing patients entering the ICU with those never admitted, was 16% versus 82% (P < .0001) for allogeneic transplantations (adult donor and UCB combined) and 80% versus 89% (P = not significant) for autologous transplantations. Acute graft-versus-host disease was significantly associated with death in ICU after UCB HCT. ICU support is satisfactory in about one half of patients admitted, characterized by a short and medium term prognosis not as unfavorable as has been previously reported.
Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Agonistas Mieloablativos/uso terapêutico , Admissão do Paciente/estatística & dados numéricos , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Chile , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Hospitais Universitários , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Recidiva , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/patologia , Estudos Retrospectivos , Choque Séptico/tratamento farmacológico , Choque Séptico/etiologia , Choque Séptico/mortalidade , Choque Séptico/patologia , Análise de Sobrevida , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento , Doadores não RelacionadosRESUMO
BACKGROUND: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, emphasizing its high recurrence rate despite hematopoietic cell transplantation (HCT). AIM: To report the results of AML treatment at the Catholic University of Chile Clinical Hospital. PATIENTS AND METHODS: Review of medical records of patients with AML. RESULTS: 63 patients, median age 55.4 years (range:16-89), treated between 2010 and 2014. Admission laboratory values showed (median values): leukocytes 45.989/mm³, hemoglobin 9.1 g/dl, platelets 75.548/mm³, peripheral blood blasts 38% and bone marrow blasts 74%. According to cytogenetic risk classification we observed the following groups: favorable 8% (n = 5), intermediate 51% (n = 32), unfavorable 13% (n = 8) and unknown 28% (n = 17). Seventy five percent of patients received induction chemotherapy and 25% palliative care. Median survival of treated and palliative care patients was 27.3 and 1 month respectively. Induction chemotherapy (IC) mortality (ICM) was 4.2%. Seventy percent (n = 33) of patients who received IC had complete response (CR) with a 3-year relapse free survival (RFS) of 25% and overall survival (OS) of 31%. Multivariate analysis demonstrated that achievement of CR, cytogenetic risk group and receiving consolidation chemotherapy were significantly associated with better RFS and OS. CONCLUSIONS: AML treatment with standard chemotherapy in our center achieves similar results to what has been described in international series regarding induction rates and ICM, however RFS and OS are still very low, especially in intermediate and high cytogenetic risk groups.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Chile , Intervalo Livre de Doença , Feminino , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival. Currently, clinically used c-Abl inhibitors are non-selective and have poor brain penetration. The allosteric c-Abl inhibitor, neurotinib, used here has favorable potency, selectivity, pharmacokinetics, and vastly improved brain penetration. Neurotinib-administered mice have fewer seizures and improved survival following pilocarpine-SE induction. Our findings reveal c-Abl kinase activation as a key factor in ictogenesis and highlight the impact of its inhibition in preventing the insurgence of epileptic-like seizures in rodents and humans.
Assuntos
Pilocarpina , Proteínas Proto-Oncogênicas c-abl , Convulsões , Animais , Masculino , Camundongos , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/patologia , Neurônios/metabolismo , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-abl/metabolismo , Proteínas Proto-Oncogênicas c-abl/antagonistas & inibidores , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/patologia , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/patologiaRESUMO
Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and degeneration of motoneurons starting in adulthood. Recent studies using cell or animal models document that astrocytes expressing disease-causing mutations of human superoxide dismutase 1 (hSOD1) contribute to the pathogenesis of ALS by releasing a neurotoxic factor(s). Neither the mechanism by which this neurotoxic factor induces motoneuron death nor its cellular site of action has been elucidated. Here we show that acute exposure of primary wild-type spinal cord cultures to conditioned medium derived from astrocytes expressing mutant SOD1 (ACM-hSOD1(G93A)) increases persistent sodium inward currents (PC(Na)), repetitive firing, and intracellular calcium transients, leading to specific motoneuron death days later. In contrast to TTX, which paradoxically increased twofold the amplitude of calcium transients and killed motoneurons, reduction of hyperexcitability by other specific (mexiletine) and nonspecific (spermidine and riluzole) blockers of voltage-sensitive sodium (Na(v)) channels restored basal calcium transients and prevented motoneuron death induced by ACM-hSOD1(G93A). These findings suggest that riluzole, the only FDA-approved drug with known benefits for ALS patients, acts by inhibiting hyperexcitability. Together, our data document that a critical element mediating the non-cell-autonomous toxicity of ACM-hSOD1(G93A) on motoneurons is increased excitability, an observation with direct implications for therapy of ALS.
Assuntos
Potenciais de Ação , Astrócitos/metabolismo , Neurônios Motores/efeitos dos fármacos , Mutação , Superóxido Dismutase/genética , Animais , Cálcio/metabolismo , Sinalização do Cálcio , Morte Celular , Células Cultivadas , Meios de Cultivo Condicionados/toxicidade , Humanos , Camundongos , Camundongos Transgênicos , Neurônios Motores/fisiologia , Ratos , Ratos Sprague-Dawley , Sódio/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologiaRESUMO
BACKGROUND: Hematopoietic autologous stem cell transplantation (ASCT) is a validated therapeutic strategy for lymphoma treatment and precise well-tolerated conditioning. Several conditioning methods are available, but the most commonly used are CVB, BEAM, and ICE, which are conventionally administered in 6 to 7 days. Since 2015, our program has moved toward noncryopreserved platforms that require concise times; therefore, we have modified the conditioning by reducing it to 4 to 5 days. In this study, we show our experience. METHODS: We compared ASCT performed in our program before and after 2015 in lymphoma patients. Between 2000 and 2014 and from 2015 to 2022, we performed 46 and 61 ASCT procedures, respectively. RESULTS: Since 2015, we observed a greater number of infused stem cells, fewer episodes of febrile neutropenia (60% vs. 37% P = .008), shorter hospitalizations (30 vs. 18 days P = .001), faster engraftment (20 vs. 14 days P = .001) and better progression-free survival (72 vs. 44 months P = .002). Additionally, a prolonged overall survival was observed at these results, and this prolonged survival is difficult to interpret due to the short follow-up. CONCLUSION: In conclusion, conditioning adjusted for a noncryopreserved strategy offers at least similar or even better results than the cryopreserved strategy. Prospective studies are warranted.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante Autólogo/métodos , Transplante de Células-Tronco , Linfoma/terapia , Intervalo Livre de Progressão , Condicionamento Pré-Transplante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos RetrospectivosRESUMO
Introduction: As the SARS-CoV-2 continues to evolve, new variants pose a significant threat by potentially overriding the immunity conferred by vaccination and natural infection. This scenario can lead to an upswing in reinfections, amplified baseline epidemic activity, and localized outbreaks. In various global regions, estimates of breakthrough cases associated with the currently circulating viral variants, such as Omicron, have been reported. Nonetheless, specific data on the reinfection rate in Chile still needs to be included. Methods: Our study has focused on estimating COVID-19 reinfections per wave based on a sample of 578,670 RT-qPCR tests conducted at the University of Santiago of Chile (USACH) from April 2020 to July 2022, encompassing 345,997 individuals. Results: The analysis reveals that the highest rate of reinfections transpired during the fourth and fifth COVID-19 waves, primarily driven by the Omicron variant. These findings hold despite 80% of the Chilean population receiving complete vaccination under the primary scheme and 60% receiving at least one booster dose. On average, the interval between initial infection and reinfection was found to be 372 days. Interestingly, reinfection incidence was higher in women aged between 30 and 55. Additionally, the viral load during the second infection episode was lower, likely attributed to Chile's high vaccination rate. Discussion: This study demonstrates that the Omicron variant is behind Chile's highest number of reinfection cases, underscoring its potential for immune evasion. This vital epidemiological information contributes to developing and implementing effective public health policies.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/epidemiologia , Chile/epidemiologia , Reinfecção/epidemiologiaRESUMO
Amiloride-sensitive epithelial Na(+) channels (ENaCs) can be formed by different combinations of four homologous subunits, named α, ß, γ, and δ. In addition to providing an apical entry pathway for transepithelial Na(+) reabsorption in tight epithelia such as the kidney distal tubule and collecting duct, ENaCs are also expressed in nonepithelial cells, where they may play different functional roles. The δ-subunit of ENaC was originally identified in humans and is able to form amiloride-sensitive Na(+) channels alone or in combination with ß and γ, generally resembling the canonical kidney ENaC formed by α, ß, and γ. However, δ differs from α in its tissue distribution and channel properties. Despite the low sequence conservation between α and δ (37% identity), their similar functional characteristics provide an excellent model for exploring structural correlates of specific ENaC biophysical and pharmacological properties. Moreover, the study of cellular mechanisms modulating the activity of different ENaC subunit combinations provides an opportunity to gain insight into the regulation of the channel. In this review, we examine the evolution of ENaC genes, channel subunit composition, the distinct functional and pharmacological features that δ confers to ENaC, and how this can be exploited to better understand this ion channel. Finally, we briefly consider possible functional roles of the ENaC δ-subunit.
Assuntos
Canais Epiteliais de Sódio/metabolismo , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Quimotripsina/farmacologia , Canais Epiteliais de Sódio/efeitos dos fármacos , Canais Epiteliais de Sódio/genética , Epitélio/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Túbulos Renais Coletores/efeitos dos fármacos , Túbulos Renais Coletores/metabolismo , Túbulos Renais Distais/efeitos dos fármacos , Túbulos Renais Distais/metabolismo , Camundongos , Sódio/metabolismo , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To study the impact of non-psychiatric medical visits by patients with Major Depressive Disorder (MDD) and their family members, compared to healthy people and their relatives in Primary Care. DESIGN: Retrospective cohort observational study. LOCATION: San Alberto Hurtado Primary Care Clinic, Santiago-Chile. PARTICIPANTS: Patients diagnosed with MDD during 2008 were paired by gender, age, and educational level with 2 healthy controls. We followed-up 206 patients with 310 family members and 412 controls with 588 relatives. MAIN MEASUREMENTS: During 1 year after the diagnosis, all health visits were assessed in patients and their family members and compared with healthy controls and their relatives. For statistical analysis we used U-Mann-Whitney, considering statistical significance with p values ≤0.05. RESULTS: The relative risk of making a non-psychiatric medical visit in depressed patients was 1.43 (95% CI: 1.19-1.67) and in their family members was 1.37 (95% CI: 1.16-1.58). The most frequent health complaints in patients were trauma, respiratory, and neurological problems. Family members visited physicians due trauma, psychiatric and endocrinological complaints. CONCLUSIONS: The patients with MDD and their family members have a higher rate of medical visits in Primary Care. A family-oriented treatment of these patients could improve clinical outcomes and reduce the patient overload in this setting.