RESUMO
Multiple chemodrugs with nanotechnology have proven to be an effective cancer treatment technique. When taken combined, cabazitaxel (CTX) and cisplatin (PT) have more excellent cytotoxic effects than drugs used alone in the chemotherapy of several different cancers. However, several severe side effects are associated with using these chemotherapy drugs in cancer patients. Gold nanomaterials (AuNMs) are promising as drug carriers because of their small diameter, easy surface modifications, good biocompatibility, and strong cell penetration. This work aimed to determine the CTX and PT encapsulated with AuNMs against human glioma U87 cancer cells. The fabrication of the AuNMs achieved a negative surface charge, polydispersity index, and the mean sizes. The combined cytotoxic effect of CTX and PT bound to AuNMs was greater than that of either drug alone when tested on U87 cells. The half inhibitory concentration (IC50) values for free PT were 54.7 µg/mL (at 24 h) and 4.8 g µg/mL (at 72 h). Results acquired from the MTT assay show cell growth decreases time- and concentration-dependent AuNMs, free CTX, free PT, and AuNMs@CTX/PT-induced cytotoxicity and, ultimately, the cell death of U87 cells via apoptosis. The biochemical apoptosis staining techniques investigated the cells' morphological changes of the cells (acridine orange and ethidium bromide (AO-EB) and nuclear staining (DAPI) techniques). The AO-EB and nuclear staining results reveal that the NPs effectively killed cancer cells. Furthermore, the flow cytometry analysis examined the mode of cell death. Therefore, AuNMs@CTX/PT has excellent potential in the cancer therapy of different cancer cells.
Assuntos
Antineoplásicos , Erwinia , Hiperamonemia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Asparaginase/efeitos adversos , Hiperamonemia/induzido quimicamente , Antineoplásicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaçõesRESUMO
Objective: To improve the care for pediatric oncology patients with neutropenic fever who present to the emergency department (ED) by administering appropriate empiric antibiotics within 60 minutes of arrival. Patients and Methods: We focused on improving the care for pediatric oncology patients at risk of neutropenia who presented to the ED with concern for fever. Our baseline adherence to the administration of empiric antibiotics within 60 minutes for this population was 53% (76/144) from January 1, 2010, to December 21, 2014. During 2015, we reviewed data monthly, finding 73% adherence. We used the Lean methodology to identify the process waste, completed a value-stream map with input from multidisciplinary stakeholders, and convened a root cause analysis to identify causes for delay. The 4 causes were as follows: (1) lack of staff awareness; (2) missing patient information in electronic medical record; (3) practice variation; and 4) lack of clear prioritization of laboratory draws. We initiated Plan-Do-Study-Act cycles to achieve our goal of 80% of patients receiving appropriate empiric antibiotics within 60 minutes of arrival in the ED. Results: Five Plan-Do-Study-Act cycles were completed, focusing on the following: (1) timely identification of patients by utilizing the electronic medical record to initiate a page to the care team; (2) creation of a streamlined intravascular access process; (3) practice standardization; (4) convenient access to appropriate antibiotics; and (5) care team education. Timely antibiotic administration increased from 73%-95% of patients by 2018. More importantly, the adherence was sustained to greater than 90% through 2021. Conclusion: A structured and multifaceted approach using quality improvement methodologies can achieve and sustain improved patient care outcomes in the ED.
Assuntos
RNA/genética , Telomerase/genética , Homeostase do Telômero , Telômero/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Germline predisposition syndromes (GPS) result from constitutional aberrations in tumor suppressive and homeostatic genes, increasing risk for neoplasia in affected kindred. In this study, we present clinical and genomic data on 144 Mayo Clinic patients with GPS; 59 evaluated prospectively using an algorithm-based diagnostic approach in the setting of a dedicated GPS/ inherited bone marrow failure syndrome (IBMFS) clinic. Seventy-two (50%) patients had IBMFS (telomere biology disorders-32,Fanconi anemia-18, Diamond Blackfan Anemia - 11, congenital neutropenia-5, Schwachman-Diamond Syndrome-5 and Bloom Syndrome-1), 27 (19%) had GPS with antecedent thrombocytopenia (RUNX1-FPD-15, ANKRD26-6, ETV6-2, GATA1-1, MPL-3), 28 (19%) had GPS without antecedent thrombocytopenia (GATA2 haploinsufficiency-16, DDX41-10, CBL-1 and CEBPA-1) and 17 (12%) had general cancer predisposition syndromes (ataxia telangiectasia-7, heterozygous ATM variants-3, CHEK2-2, TP53-2, CDK2NA-1, NF1-1 and Nijmegen Breakage Syndrome-1). Homozygous and heterozygous ATM pathogenic variants were exclusively associated with lymphoproliferative disorders (LPD), while DDX41 GPS was associated with LPD and myeloid neoplasms. The use of somatic NGS-testing identified clonal evolution in GPS patients, with ASXL1, RAS pathway genes, SRSF2 and TET2 being most frequently mutated. Fifty-two (91%) of 59 prospectively identified GPS patients had a change in their management approach, including additional GPS-related screening in 42 (71%), referral for allogenic HSCT workup and screening of related donors in 16 (27%), medication initiation and selection of specific conditioning regimens in 14 (24%), and genetic counseling with specific intent of fertility preservation and preconceptual counseling in 10 (17%) patients; highlighting the importance of dedicated GPS screening, detection and management programs for patients with hematological neoplasms.
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Evolução Clonal , Neoplasias Hematológicas/genética , Adolescente , Adulto , Idoso , Anemia de Diamond-Blackfan/genética , Criança , Pré-Escolar , Síndrome Congênita de Insuficiência da Medula Óssea/genética , Anemia de Fanconi/genética , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
In this study, iron oxide (Fe2O3), tungsten oxide (WO3) and iron-tungstate oxide (FeWO4) nanoparticles (NPs) were synthesized by simple precipitation, acid precipitation, and hydrothermal method respectively. All the spectroscopic analysis reveals that as-synthesized NPs are crystalline with a z-average size of 342, 313 and 373 d.nm respectively. The element compositions, shape and size of the NPs were identified with the help of SEM with EDX analysis. FTIR analysis concluded that the presence of functional groups on the surface of NPs and which responsible for capping and formation of NPs. Besides, the as-synthesized NPs have been used as a photocatalyst for the degradation of Methyl Orange (MO) dye under visible irradiation. FeWO4 NPs (98%) show more effective in the degradation of MO as compared to other NPs. Moreover, the degraded MO and its by-products were used to assess their toxicity on Vigna radiata and RAW 264.7 cell line and which were confirmed that degraded by-products were non-hazardous.
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Compostos Azo/isolamento & purificação , Compostos Férricos/química , Nanopartículas/química , Óxidos/química , Fotólise , Tungstênio/química , Animais , Catálise , Compostos Férricos/toxicidade , Camundongos , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Óxidos/toxicidade , Células RAW 264.7 , Espectroscopia de Infravermelho com Transformada de Fourier , Tungstênio/toxicidade , Vigna/efeitos dos fármacosAssuntos
Proteínas de Fusão bcr-abl/genética , Hibridização in Situ Fluorescente , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Estudos RetrospectivosRESUMO
Short telomere syndromes (STSs) are accelerated aging syndromes with multisystemic manifestations that present complex management challenges. In this article, we discuss a single-institution experience in diagnosing and managing patients with inherited STSs. In total, we identified 17 patients with short telomeres, defined by flow-fluorescence in-situ hybridization telomere lengths of less than first centile in granulocytes/lymphocytes OR the presence of a characteristic germline pathogenic variant in the context of a highly suggestive clinical phenotype. Genetic variations in the telomere complex were identified in 6 (35%) patients, with 4 being known pathogenic variants involving TERT (n=2), TERC (n=1), and DKC1 (n=1) genes, while 2 were variants of uncertain significance in TERT and RTEL1 genes. Idiopathic interstitial pneumonia (IIP) (n=12 [71%]), unexplained cytopenias (n=5 [29%]), and cirrhosis (n=2 [12%]) were most frequent clinical phenotypes at diagnosis. At median follow-up of 48 (range, 0-316) months, Kaplan-Meier estimate of overall survival, median (95% CI), was 182 (113, not reached) months. Treatment modalities included lung transplantation for IIP (n=5 [29%]), with 3 patients developing signs of acute cellular rejection (2, grade A2; 1, grade A1); danazol therapy for cytopenias (n=4 [24%]), with only 1 out of 4 patients showing a partial hematologic response; and allogeneic hematopoietic stem cell transplant for progressive bone marrow failure (n=2), with 1 patient dying from transplant-related complications. In summary, patients with STSs present with diverse clinical manifestations and require a multidisciplinary approach to management, with organ-specific transplantation capable of providing clinical benefit.
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Encurtamento do Telômero , Adolescente , Idoso , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Síndrome , Resultado do TratamentoRESUMO
HSTCL is a highly aggressive malignancy with a poor prognosis. Case series and accounts have reported the use of different chemotherapy regimens with diverse patient outcomes. Most long-term survivors had undergone high-dose chemotherapy with autologous or allogeneic HCT. We describe two pediatric patients with HSTCL who were treated with chemotherapy followed by allogeneic HCT. Both patients are alive and in complete remission 2 and 8 years after therapy. Multiagent chemotherapy followed with allogeneic HCT seems to provide patients who have chemotherapy-sensitive disease a long-term disease-free survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Neoplasias Hepáticas/terapia , Linfoma de Células T/terapia , Neoplasias Esplênicas/terapia , Adolescente , Criança , Terapia Combinada , Humanos , Adulto JovemRESUMO
BACKGROUND: Overall incidence of hemostatic complications in pediatric recipients of Hematopoietic Stem Cell Transplant (HSCT) is scarcely studied. This retrospective review explored the incidence and underlying risk factors of bleeding and thrombotic complications in children. PROCEDURE: Clinical characteristics, hemorrhagic events (HE), thrombotic events (TE) and follow up data were abstracted from medical records on patients aged <21â¯years undergoing HSCT during January 2000-June 2015. RESULTS: From start of conditioning until last follow up, 238 pediatric patients were reviewed during this study. There were 16 symptomatic thrombotic complications in 15 patients, along with 13 major bleeding events. Incidence of HE or TE was higher in allogeneic HSCT compared to autologous HSCT (pâ¯=â¯0.02). Severe thrombocytopenia could not be identified as a major contributor to bleeding. All patients with HE had platelets between 20,000-50,000â¯×â¯109/L, except one patient, who had platelets <20,000â¯×â¯109/L. All patients with hemorrhagic cystitis (nâ¯=â¯7) had received cyclophosphamide (Cy). For patients with sinusoidal obstruction syndrome, conditioning included either busulfan (Bu)/Cy (nâ¯=â¯5), Cy with total body irradiation (nâ¯=â¯4), or thiotepa (nâ¯=â¯2). Among allogeneic HSCT recipients, 60% of HE and 92% with TE had underlying myeloid neoplasms. Graft versus Host disease contributed to both types of complications (pâ¯=â¯0.07), although not reaching statistical significance. CONCLUSIONS: Allogeneic pediatric HSCT patients had higher overall risk of hemorrhagic or thrombotic complications compared to autologous recipients in this study. HSCT for myeloid malignancies was a risk factor for higher complications.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Trombose/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Hemorragia/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Trombose/patologia , Adulto JovemRESUMO
Late-onset HC is a well-recognized complication associated with cyclophosphamide/acrolein-induced toxicity. It poses a management challenge when hyperhydration and bladder irrigation do not result in clinical improvement as desired. The data regarding use of hyperbaric oxygen therapy (HBO2) as an early treatment modality in this clinical setting are limited. We present 2 cases, that were refractory to hyperhydration and bladder irrigation but responded to HBO2. They were treated with 20-30 daily sessions over weekdays with 100% oxygen for 90 minutes at 2 atmospheric pressure units (2 atm). Both patients reported improved symptoms within the first 15 sessions, and hematuria diminished by 20 sessions. Hyperbaric oxygen is a less invasive, outpatient therapy that is effective for treatment of HC and is tolerated well by young patients.
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Ciclofosfamida/efeitos adversos , Cistite/terapia , Hematúria/terapia , Oxigenoterapia Hiperbárica , Imunossupressores/efeitos adversos , Adolescente , Adulto , Cistite/induzido quimicamente , Feminino , Hematúria/induzido quimicamente , Humanos , MasculinoRESUMO
Post-transplant lymphoproliferative disorder (PTLD) has rarely been associated with ocular manifestations. We report a case of bilateral ocular involvement by PTLD with histopathologic features of extranodal marginal zone (MALT) lymphoma in an 8-year-old boy following orthotopic heart transplantation. The anterior segment disease was treated successfully using a combination of intraocular and systemic injections of humanized anti-CD20 antibody (rituximab).
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Antineoplásicos Imunológicos/uso terapêutico , Transplante de Coração , Neoplasias da Íris/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Transtornos Linfoproliferativos/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Rituximab/uso terapêutico , Criança , Humanos , Imunossupressores/uso terapêutico , Injeções Intraoculares , Neoplasias da Íris/etiologia , Neoplasias da Íris/patologia , Linfoma de Zona Marginal Tipo Células B/etiologia , Linfoma de Zona Marginal Tipo Células B/patologia , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/patologia , MasculinoRESUMO
Standardised approaches to functional immune assessment after haematopoietic cell transplantation (HCT) are lacking. A 12-year-old girl with relapsed acute myelogenous leukaemia, 2 years post-unrelated HCT, underwent immunological evaluation prior to receiving live vaccinations. Assessment of standard immune parameters and T-cell proliferation to phytohaemagglutinin was reassuring. She was given Varicella vaccination based on usual post-transplant protocols but was hospitalised 10 days later with localised Varicella infection (vaccine strain). Following recovery, she underwent further assessment that showed reduced T-cell proliferation to an anti-CD3 stimulation panel (anti-CD3 alone, soluble anti-CD3+ anti-CD28 and soluble anti-CD3+ plus exogenous IL-2). On reassessment, 7 months later, T-cell responses to anti-CD3 stimulation were normal and she was revaccinated without further incident. Measurement of T-cell proliferation to anti-CD3 stimulants likely yields more useful information about global T-cell function and should be strongly considered prior to live vaccine administration post-allogeneic haematopoietic transplant.
Assuntos
Complexo CD3/imunologia , Vacina contra Varicela/efeitos adversos , Varicela/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfócitos T/imunologia , Varicela/prevenção & controle , Vacina contra Varicela/imunologia , Criança , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Medição de RiscoAssuntos
Evolução Clonal/genética , Mutação em Linhagem Germinativa , Síndromes Mielodisplásicas/genética , Adolescente , Adulto , Anemia Aplástica/genética , Doenças da Medula Óssea/genética , Transtornos da Insuficiência da Medula Óssea , Feminino , Predisposição Genética para Doença , Hemoglobinúria Paroxística/genética , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The aim of this study was to investigate whether prosthodontic residents' attitudes toward provider-client communication would be shaped by a tailor-made communications skills course. In 2016, the pre-intervention attitudes of all six second- and third-year prosthodontic residents in a three-year residency at an academic dental institution in India were assessed using the Communication Skills Attitude Scale (CSAS). The residents' performance was then video-recorded while they treated complete denture patients and was analyzed using the Kalamazoo scale, a validated scale for communication skills assessment. The residents' weaknesses were identified, and a custom-made generic module was designed along with individual guidance counseling for addressing aspects relevant to complete denture patients. The residents' attitudes were again assessed immediately after they completed the training using CSAS, as well as after two and four months using Balint sessions. Analysis of the recordings showed that few of the deficiencies during intraoral procedures were contextual, and the Kalamazoo scale did not address them: these were noted as being "beyond Kalamazoo." After the training, the residents reported awareness of their weaknesses and feeling motivated to practice their newly acquired skills. The Balint sessions showed that they had started valuing patients' agendas and the rapport-building process, and they reported transfer of skills when treating other types of prosthodontic patients. In this study, a customized communication skills module brought about a positive change in residents' attitudes, which was sustained over four months. Similar training could be implemented in other dental specialties.
Assuntos
Atitude do Pessoal de Saúde , Comunicação , Relações Dentista-Paciente , Internato e Residência , Arcada Edêntula , Prostodontia/educação , Humanos , Índia , Arcada Edêntula/terapia , Projetos PilotoRESUMO
Myocardial dysfunction after Fontan palliation for univentricular congenital heart disease is a challenging clinical problem. The medical treatment has a limited impact, with cardiac transplant being the ultimate management step. Cell-based therapies are evolving as a new treatment for heart failure. Phase 1 clinical trials using regenerative therapeutic strategies in congenital heart disease are ongoing. We report the first case of autologous bone marrow-derived mononuclear cell administration for ventricular dysfunction, 23 years after Fontan operation in a patient with hypoplastic left heart syndrome. The cells were delivered into the coronary circulation by cardiac catheterization. Ventricular size decreased and several parameters reflecting ventricular function improved, with maximum change noted 3 months after cell delivery. Such regenerative therapeutic options may help in delaying and preventing cardiac transplant.
RESUMO
IMPORTANCE: Bone marrow or peripheral blood from unrelated donors may be used for hematopoietic cell transplantation. Information about the relative success of transplantation with these 2 graft sources would help physicians and patients choose between them. OBJECTIVE: To compare patient-reported outcomes between patients randomized to receive 1 of 2 graft types for unrelated donor transplantation. DESIGN, SETTING, AND PARTICIPANTS: This follow-up of a randomized clinical trial included English- or Spanish-speaking patients 16 years or older participating in a multicenter randomized clinical trial of unrelated donor bone marrow (BM) vs peripheral blood (PB) (N = 551) in hematopoietic cell transplantation for hematologic neoplasms. Patient-reported outcomes were collected from patients at enrollment and 0.5, 1, 2, and 5 years after transplantation. INTERVENTIONS: Unrelated donor BM or PB hematopoietic cell transplantation. MAIN OUTCOMES AND MEASURES: Functional Assessment of Cancer Therapy-Bone Marrow Transplant, Mental Health Inventory, occupational functioning, Lee Chronic Graft-vs-Host Disease Symptom Scale. RESULTS: At 5 years after transplantation, 102 BM and 93 PB participants were alive and eligible for assessment (age ≥40 years or older: 104 [53.5%] male: 101 [51.8%]). The mean (SE) Mental Health Inventory Psychological Well-Being scores (78.9 [1.7] vs 72.2 [1.9]; P = .01; higher better) and Lee chronic graft-vs-host disease symptom scores (13.1 [1.5] vs 19.3 [1.6]; P = .004; lower better) were significantly better for BM recipients, adjusting for baseline scores and missing data. Recipients of BM were also more likely to be working full or part-time than recipients of PB (odds ratio, 1.5; 95% CI, 1.2-2.0; P = .002), adjusting for work status before transplantation. With a median follow-up of 73 months (range, 30-121 months) for survivors, no differences in survival (40% vs 39%; P = .84), relapse (32% vs 29%; P = .47), or treatment-related mortality (29% vs 32%; P = .44) between BM and PB were observed. CONCLUSIONS AND RELEVANCE: Recipients of unrelated donor BM had better psychological well-being, less burdensome chronic GVHD symptoms, and were more likely to return to work than recipients of PB at 5 years after transplantation. Bone marrow should be the standard of care for these types of transplant procedures. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00075816.
Assuntos
Transplante de Medula Óssea/métodos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Adolescente , Adulto , Idoso , Medula Óssea/imunologia , Feminino , Seguimentos , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Doadores não RelacionadosRESUMO
Neonatal renal vein thrombosis (NRVT) is a rare thromboembolic complication in the neonatal period, and sequelae from renal dysfunction can cause significant morbidity. The authors retrospectively reviewed 10 patients with NRVT treated at their institution. The majority of the cohort were male (n = 9), preterm (n = 6), and had unilateral NRVT (n = 6). Six patients received thrombolysis and/or anticoagulation, and 4 patients received supportive care only. Two of the 6 patients treated with anticoagulation who had bilateral NRVT and anuria received thrombolysis with low-dose tissue plasminogen activator. Thrombolysis was not associated with any major adverse events, and both patients had marked improvement of renal function. Eight patients subsequently developed renal atrophy (3 received anticoagulation, 2 received thrombolysis with anticoagulation, and 3 received supportive care). Anticoagulation/thrombolysis did not appear to prevent renal atrophy. The role of thrombolysis needs to be further studied and considered in the setting of bilateral NRVT and acute renal failure.