Minimal/Measurable Residual Disease Monitoring in NPM1-Mutated Acute Myeloid Leukemia: A Clinical Viewpoint and Perspectives

Acute myeloid leukemia (AML) with NPM1 gene mutations is currently recognized as a distinct entity, due to its unique biological and clinical features. We summarize here the results of published studies investigating the clinical application of minimal/measurable residual disease (MRD) in patients with NPM1-mutated AML, receiving either intensive chemotherapy or hematopoietic stem cell transplantation. Several clinical trials have so far demonstrated a significant independent prognostic impact of molecular MRD monitoring in NPM1-mutated AML and, accordingly, the Consensus Document from the European Leukemia Net MRD Working Party has recently recommended that NPM1-mutated AML patients have MRD assessment at informative clinical timepoints during treatment and follow-up. However, several controversies remain, mainly with regard to the most clinically significant timepoints and the MRD thresholds to be considered, but also with respect to the optimal source to be analyzed, namely bone marrow or peripheral blood samples, and the correlation of MRD with other known prognostic indicators. Moreover, we discuss potential advantages, as well as drawbacks, of newer molecular technologies such as digital droplet PCR and next-generation sequencing in comparison to conventional RQ-PCR to quantify NPM1-mutated MRD. In conclusion, further prospective clinical trials are warranted to standardize MRD monitoring strategies and to optimize MRD-guided therapeutic interventions in NPM1-mutated AML patients

Multi-response optimization of a green solid-phase extraction for the analysis of heterocyclic aromatic amines in environmental samples

A multi-response optimization of a green and efficient solid phase extraction (SPE) sample treatment using non-modified multi-walled carbon nanotubes combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the quantification of ten heterocyclic aromatic amines (HAAs) in river and reservoir surface water samples. The proposed methodology was evaluated with the employment of experimental designs, which provided to greening the approach. Ultra-trace amounts of HAAs were retained into the SPE cartridge. Then, these analytes were removed from the carbon nanotubes with 0.8 mL of a mixture of acetonitrile/water with 0.1 % of formic acid. Under the optimal conditions, linearity was achieved for concentration levels ranging from 0.20 µg L-1 to 500 µg L-1, with regression coefficients (R2) from 0.990 to 0.998. Limits of detection varying from 0.06 µg L-1 and 0.23 µg L-1 were attained, the relative standard deviations (n=3) varied from 1.7 to 6.4, and extraction recoveries ranged from 90.6 % to 106.0 % for all the analytes. Results of the presence of HAAs found in the river samples demonstrated levels from 0.16 µg L-1 to 0.53 µg L-1; meanwhile, in the reservoir, the levels were higher, from 0.37 µg L-1 to 0.93 µg L-1. Finally, a comparative discussion was applied in order to assess the greenness of approaches for the determination of heterocyclic aromatic amines in surface water using the available metrics.Fil: Canales, Maria Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Marino Repizo, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Reta, Mario Roberto. Universidad Nacional de La Plata; ArgentinaFil: Cerutti, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; Argentin

Diagnóstico imagenológico en el Síndrome de Abernethy

El shunt portosistémico congénito (SPSC) o Síndrome de Abernethy es una patología muy poco frecuente, descrita por primera vez en 1793 por John Abernethy. Existen dos tipos de SPSC: tipo I (shunt terminolateral) en el que existe ausencia total de flujo portal intrahepático y tipo II (shunt laterolateral) con flujo portal parcialmente conservado. Los SPSC tipo I se presentan predominantemente en el sexo femenino y se asocian con múltiples malformaciones como poliesplenia, malrotación y cardiopatía. Los tipo II, aún más raros, afectan a ambos sexos y no suelen presentar malformaciones asociadas. La encefalopatía hepática es una complicación posible en ambos tipos de SPSC en la edad adulta. El trasplante hepático es el único tratamiento descrito para el SPSC tipo I cuando se vuelve sintomático, mientras que la ligadura del shunt es una opción quirúrgica para el tipo II. Objetivo: Presentar el diagnóstico imagenológico en un paciente adulto con Síndrome de Abernethy tipo 1B.Congenital portosystemic shunt (CEPS) or Abernethy Syndrome is a rare condition that was first reported by John Abernethy in 1793. Two types of CEPS are described: type I (side to end anastomosis) or congenital absence of the portal vein, and type II (side to side anastomosis) with portal vein supply partially conserved. Type I CEPS is usually seen in girls and associates multiple malformations as polysplenia, malrotation, and cardiac anomalies. Type II is even rarer with no sex preference and no malformations associated. Hepatic encephalopathy is a common complication of both types in adulthood. Liver transplantation is the only effective treatment for symptomatic type I CEPS. A therapeutic approach for type II could be surgical closure of the shunt. Objective: To present the imagenological diagnosis an adult patient with Abernethy Syndrome type 1B.Fil: Pérez Monteleone, Leonardo E.. Hospital Luis Lagomaggiore (Mendoza, Argentina). Servicio de Cirugía General.Fil: Manzino, Ricardo. Hospital Luis Lagomaggiore (Mendoza, Argentina). Servicio de Cirugía General.Fil: Gutierrez, Mario. Hospital Luis Lagomaggiore (Mendoza, Argentina). Servicio de Cirugía General.Fil: Bufaliza, Jorge. Hospital Luis Lagomaggiore (Mendoza, Argentina). Servicio de Cirugía General.Fil: Correa, Roberto. Hospital Luis Lagomaggiore (Mendoza, Argentina). Servicio de Cirugía General

Targeting neoplastic B cells and harnessing microenvironment: the “double face” of ibrutinib and idelalisib

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not suitable for high dose chemotherapy with autologous stem cell transplantation (ASCT) has a dismal prognosis and no standard therapy. We designed an Italian multicenter retrospective study aimed at evaluating the safety and efficacy of rituximab plus bendamustine (R–B) as salvage treatment in patients not eligible for ASCT because of age and/or comorbidity or in patients with post-ASCT recurrence. Fifty-five patients with a median age of 76 years were included. The overall response rate was 50%, including 28% complete remission and 22% partial remission. The median overall survival (OS) was 10.8 months. The median progression free survival (PFS) was 8.8 months. Eleven patients are still alive and in complete remission at last follow-up (12–71 months). Toxicity was moderate, mainly grades 1 and 2. R–B showed promising efficacy results with an acceptable toxicity profile and should be further investigated, possibly in combination with novel drugs

Efficacy of imatinib mesylate as maintenance therapy in adults with acute lymphoblastic leukemia in first complete remission

Seven Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients in first complete remission received maintenance therapy with imatinib alone. Two-year progression-free survival was 75%. Quantitative polymerase-chain-reaction (qPCR) monitoring of BCR-ABL showed that: (i) persisting molecular complete response (CR) was associated with long-lasting CR; (ii) molecular relapse did not invariably mean hematologic relapse; (iii) only the wide and rapid increment of BCR-ABL values was predictive of leukemia relapse

A importância da endotoxina bacteriana (LPS) na endodontia atual

New knowledge of the structure and biological activity of endotoxins (LPS) has revolutionized concepts concerning their mechanisms of action and forms of inactivation. Since the 1980's, technological advances in microbiological culture and identification have shown that anaerobic microorganisms, especially Gram-negative, predominate in root canals of teeth with pulp necrosis and radiographically visible chronic periapical lesions. Gram-negative bacteria not only have different factors of virulence and generate sub-products that are toxic to apical and periapical tissues, as also contain endotoxin (LPS) on their cell wall. This is especially important because endotoxin is released during multiplication or bacterial death, causing a series of biological effects that lead to an inflammatory reaction and resorption of mineralized tissues. Thus, due to the role of endotoxin in the pathogenesis of periapical lesions, we reviewed the literature concerning the biological activity of endotoxin and the relevance of its inactivation during treatment of teeth with pulp necrosis and chronic periapical lesion.O conhecimento mais aprofundado sobre a estrutura e atividade biológica das endotoxinas (LPS) revolucionou os conceitos sobre seu mecanismo de ação e formas de inativação. A partir da década de 80, os avanços tecnológicos na cultura e identificação microbiológica demonstraram que, em canais radiculares de dentes portadores de necrose pulpar e lesão periapical crônica, visível radiograficamente, predominam microrganismos anaeróbios, particularmente os gram-negativos. Como se sabe, os microrganismos gram-negativos, além de possuírem diferentes fatores de virulência e gerarem produtos e sub-produtos tóxicos aos tecidos apicais e periapicais, contêm endotoxina em sua parede celular. Esse conhecimento é particularmente importante, uma vez que a endotoxina é liberada durante a multiplicação ou morte bacteriana, exercendo uma série de efeitos biológicos relevantes, que conduzem a uma reação inflamatória e à reabsorção dos tecidos mineralizados. Tendo em vista o papel da endotoxina na patogênese das lesões periapicais, os autores realizaram uma revisão da literatura específica, abordando suas atividades biológicas e a importância de sua inativação durante o tratamento de dentes portadores de necrose pulpar e lesão periapical

Periapical repair after root canal filling with different root canal sealers

The aim of this study was to evaluate periapical repair after root canal filling with different endodontic sealers. Sixty-four root canals from dog&acute;s teeth were filled, divided into 4 groups (n=16). Root canals were instrumented with K-type files and irrigated with 1% sodium hypochlorite solution. Root canals were filled in the same session by active lateral condensation of the cones and sealers: Intrafill, AH Plus, Roeko Seal and Resilon/Epiphany System. After 90 days, the animals were euthanized and the tissues to be evaluated were processed and stained with hematoxylin and eosin. For histopathological analysis, the following parameters were evaluated: inflammatory process, mineralized tissue resorption, and apical mineralized tissue deposition. Histopathological analysis demonstrated that Intrafill had less favorable results in terms of apical and periapical repair, compared to the other sealers (p<0.05). AH Plus, Roeko Seal, and Epiphany sealers had similar and satisfactory results (p>0.05). In conclusion, AH Plus and the materials Roeko Seal and Epiphany are good options for clinical use in Endodontics.O objetivo deste estudo foi avaliar o reparo periapical após obturação de canal radicular usando os cimentos Roeko Seal e Epiphany. Sessenta e quatro canais radiculares de dentes de cães foram obturados, divididos em 4 grupos (n=16). Os canais radiculares foram instrumentados com limas tipo K e irrigados com solução de hipoclorito de sódio a 1%. Os canais radiculares foram obturados na mesma sessão usando condensação lateral ativa dos cones e os cimentos: Grupo I - Intra Fill; Grupo II - AH Plus; Grupo III - Roeko Seal e Grupo IV - Sistema Resilon/Epiphany. Após 90 dias, os animais foram mortos e os tecidos a serem avaliados foram processados e corados por hematoxilina e eosina. Para análise histopatológica, os seguintes parâmetros foram avaliados: processo inflamatório, reabsorção dos tecidos mineralizados e deposição de tecido mineralizado apical. A análise histopatológica demonstrou que o Intrafill teve resultados menos favoráveis em relação ao reparo apical e periapical comparado aos outros cimentos (p<0,05). AH Plus, Roeko Seal e Epiphany demonstraram resultados similares e satisfatórios (p>0,05). Conclui-se que o AH Plus e os materiais Roeko Seal e Epiphany são boas opções para uso clínico em endodontia.(FAPESP) São Paulo Research Foundatio

Periapical repair after root canal filling with different root canal sealers

The aim of this study was to evaluate periapical repair after root canal filling with different endodontic sealers. Sixty-four root canals from dog&acute;s teeth were filled, divided into 4 groups (n=16). Root canals were instrumented with K-type files and irrigated with 1% sodium hypochlorite solution. Root canals were filled in the same session by active lateral condensation of the cones and sealers: Intrafill, AH Plus, Roeko Seal and Resilon/Epiphany System. After 90 days, the animals were euthanized and the tissues to be evaluated were processed and stained with hematoxylin and eosin. For histopathological analysis, the following parameters were evaluated: inflammatory process, mineralized tissue resorption, and apical mineralized tissue deposition. Histopathological analysis demonstrated that Intrafill had less favorable results in terms of apical and periapical repair, compared to the other sealers (p<0.05). AH Plus, Roeko Seal, and Epiphany sealers had similar and satisfactory results (p>0.05). In conclusion, AH Plus and the materials Roeko Seal and Epiphany are good options for clinical use in Endodontics.O objetivo deste estudo foi avaliar o reparo periapical após obturação de canal radicular usando os cimentos Roeko Seal e Epiphany. Sessenta e quatro canais radiculares de dentes de cães foram obturados, divididos em 4 grupos (n=16). Os canais radiculares foram instrumentados com limas tipo K e irrigados com solução de hipoclorito de sódio a 1%. Os canais radiculares foram obturados na mesma sessão usando condensação lateral ativa dos cones e os cimentos: Grupo I - Intra Fill; Grupo II - AH Plus; Grupo III - Roeko Seal e Grupo IV - Sistema Resilon/Epiphany. Após 90 dias, os animais foram mortos e os tecidos a serem avaliados foram processados e corados por hematoxilina e eosina. Para análise histopatológica, os seguintes parâmetros foram avaliados: processo inflamatório, reabsorção dos tecidos mineralizados e deposição de tecido mineralizado apical. A análise histopatológica demonstrou que o Intrafill teve resultados menos favoráveis em relação ao reparo apical e periapical comparado aos outros cimentos (p<0,05). AH Plus, Roeko Seal e Epiphany demonstraram resultados similares e satisfatórios (p>0,05). Conclui-se que o AH Plus e os materiais Roeko Seal e Epiphany são boas opções para uso clínico em endodontia.(FAPESP) São Paulo Research Foundatio

Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura

Treatment of severe, chronic idiopathic thrombocytopenic purpura (ITP) refractory to most usual therapies is a difficult challenge. Little information exists on the clinical use of cyclosporin A (CyA) in the treatment of ITP. This report describes long-term treatment with CyA (median, 40 months) and follow-up (median, 36.8 months) in 12 adult patients with resistant ITP. CyA used in relatively low doses (2.5-3 mg/kg of body weight per day) led to a clinical improvement in 10 patients (83.3%). Five had a complete response (41.1%), 4 a complete response to maintenance therapy (33.3%), and one a partial response (8.3%). Two patients had no response. Most patients with a response (60%) had a long-term remission (mean, 28.6 months) after discontinuation of CyA. One patient had a relapse of ITP 4 years after CyA therapy was stopped. Side effects were moderate and transient, even in patients dependent on continued CyA treatment. CyA seems to represent reasonable salvage treatment in severe, potentially life-threatening, refractory ITP

Efeito de diferentes técnicas de instrumentação rotatória e obturação termoplástica no selamento apical

The aim of this study was to evaluate apical sealing after root canal treatment using two different rotary instrumentation techniques and two thermoplastic root canal filling techniques. The study was performed in 115 human extracted mandibular premolars. After coronary access the apical foramen was opened with a # 15 K file 1 mm beyond the apex. Cleaning and shaping was subsequently carried out at the working length, 1 mm from the apex, with ProFile .04/.06 system (Dentsply/Maillefer), Quantec (Analytic Endodontics/Kerr) or by the step-back technique with 1% sodium hypochlorite solution as irrigating solution. The root canals were filled with Thermafil (Dentsply/Maillefer) or Microseal (Analytic Endodontics/Kerr) or by lateral condensation technique using AH Plus sealer (epoxy type). The teeth were immersed in 2% methylene blue under vacuum. Then, they were longitudinally sectioned. The results showed that the association of Profile and Thermafil Plus provide the best results (pO objetivo deste estudo foi avaliar o selamento apical após obturação de canal radicular usando duas diferentes técnicas de instrumentação rotatória e duas técnicas termoplásticas de obturação de canal radicular. O estudo foi realizado em 115 pré-molares extraídos de humanos. Após abertura coronária, o forame apical foi dilatado com lima tipo K 15, 1 mm além do ápice. Em seguida, o preparo biomecânico foi conduzido no comprimento de trabalho, 1 mm aquém do ápice, utilizando o Sistema ProFile 0,04/0,06 (Dentsply/Maillefer), Quantec (Analytic Endodontics/Kerr) ou técnica escalonada com hipoclorito de sódio como solução irrigadora. Os canais radiculares foram obturados com Thermafil (Dentsply/Maillefer) ou Microseal (Analytic Endodontics/Kerr) ou condensação lateral ativa usando o cimento AH Plus. Os dentes foram imersos em solução de azul de metileno a 2% em ambiente de vácuo. Depois, eles foram seccionados longitudinalmente. Os resultados demonstraram que a associação do Profile e Thermafil promoveu os melhores resultados (