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1.
Eur J Cancer ; 204: 114074, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38691877

RESUMO

Cancers of the skin are the most commonly occurring cancers in humans. In fair-skinned populations, up to 95% of keratinocyte skin cancers and 70-95% of cutaneous melanomas are caused by ultraviolet radiation and are thus theoretically preventable. Currently, however, there is no comprehensive global advice on practical steps to be taken to reduce the toll of skin cancer. To address this gap, an expert working group comprising clinicians and researchers from Africa, America, Asia, Australia, and Europe, together with learned societies (European Association of Dermato-Oncology, Euromelanoma, Euroskin, European Union of Medical Specialists, and the Melanoma World Society) reviewed the extant evidence and issued the following evidence-based recommendations for photoprotection as a strategy to prevent skin cancer. Fair skinned people, especially children, should minimise their exposure to ultraviolet radiation, and are advised to use protective measures when the UV index is forecast to reach 3 or higher. Protective measures include a combination of seeking shade, physical protection (e.g. clothing, hat, sunglasses), and applying broad-spectrum, SPF 30 + sunscreens to uncovered skin. Intentional exposure to solar ultraviolet radiation for the purpose of sunbathing and tanning is considered an unhealthy behaviour and should be avoided. Similarly, use of solaria and other artificial sources of ultraviolet radiation to encourage tanning should be strongly discouraged, through regulation if necessary. Primary prevention of skin cancer has a positive return on investment. We encourage policymakers to communicate these messages to the general public and promote their wider implementation.


Assuntos
Neoplasias Cutâneas , Raios Ultravioleta , Humanos , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/epidemiologia , Raios Ultravioleta/efeitos adversos , Pigmentação da Pele/efeitos da radiação , Protetores Solares/uso terapêutico , Melanoma/prevenção & controle , Melanoma/etiologia , Melanoma/epidemiologia , Neoplasias Induzidas por Radiação/prevenção & controle , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/epidemiologia , Fatores de Risco
2.
Hemasphere ; 8(5): e76, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38716147

RESUMO

The 2/20/20 International Myeloma Working Group (IMWG) score is the most employed risk score in clinical practice to evaluate the risk of progression from smoldering multiple myeloma (SMM) to symptomatic multiple myeloma. However, it faces a serious limitation: The risk score is applied at diagnosis and cannot be reapplied. Since a dynamic accurate patient risk assessment for progression is necessary, we aimed to investigate whether the detection of an evolving pattern in serum M-protein (SMP) improves the identification of high-risk patients. Eighty-three patients diagnosed with SMM between 2011 and 2020 were included. Patients were initially classified applying the 2/20/20 IMWG score at baseline and later reclassified depending on the presence of an SMP evolving pattern into six groups. We regrouped the patients into three final risk groups: low-risk, intermediate-risk, and high-risk. The risk of progression at two years for the high-risk group was 88% and all patients had progressed at 4 years. The performance measurements were superior for the new 2/20/20-Evolving score independently for the detection of high-risk patients. We show that the sequential measurement of the SMP is a noninvasive and widely available test that improves the 2/20/20 IMWG risk score.

3.
Clin Cancer Res ; 30(10): 2085-2096, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38466644

RESUMO

PURPOSE: B-cell maturation antigen (BCMA)-chimeric antigen receptor T-cells (CART) improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overcome these issues. Moreover, response biomarkers and resistance mechanisms need to be identified and addressed to improve efficacy and patient selection. Here, we present clinical and ancillary results of the 60 patients treated with the academic BCMA-CART, ARI0002h, in the CARTBCMA-HCB-01 trial. PATIENTS AND METHODS: We collected apheresis, final product, peripheral blood and bone marrow samples before and after infusion. We assessed BCMA, T-cell subsets, CART kinetics and antibodies, B-cell aplasia, cytokines, and measurable residual disease by next-generation flow cytometry, and correlated these to clinical outcomes. RESULTS: At cut-off date March 17, 2023, with a median follow-up of 23.1 months (95% CI, 9.2-37.1), overall response rate in the first 3 months was 95% [95% confidence interval (CI), 89.5-100]; cytokine release syndrome (CRS) was observed in 90% of patients (5% grades ≥3) and grade 1 immune effector cell-associated neurotoxicity syndrome was reported in 2 patients (3%). Median progression-free survival was 15.8 months (95% CI, 11.5-22.4). Surface BCMA was not predictive of response or survival, but soluble BCMA correlated with worse clinical outcomes and CRS severity. Activation marker HLA-DR in the apheresis was associated with longer progression-free survival and increased exhaustion markers correlated with poorer outcomes. ARI0002h kinetics and loss of B-cell aplasia were not predictive of relapse. CONCLUSIONS: Despite deep and sustained responses achieved with ARI0002h, we identified several biomarkers that correlate with poor outcomes.


Assuntos
Antígeno de Maturação de Linfócitos B , Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/tratamento farmacológico , Antígeno de Maturação de Linfócitos B/imunologia , Antígeno de Maturação de Linfócitos B/antagonistas & inibidores , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Adulto , Biomarcadores Tumorais , Receptores de Antígenos Quiméricos/imunologia , Resultado do Tratamento
4.
Rev. colomb. neumol ; 35(2): 28-34, 05/12/2023.
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1551148

RESUMO

El blastoma pulmonar es una neoplasia poco común y agresiva que se origina en el pulmón; está compuesto por tejido mesenquimal y epitelial inmaduro que imita la configuración pulmonar en etapas embrionarias. Tiene una baja incidencia y una alta tasa de mortalidad, con aproximadamente un 60 %. Este blastoma tiende a desarrollarse con mayor frecuencia entre la cuarta y quinta década de vida, siendo más prevalente en mujeres y generalmente asociado al tabaquismo. Se presenta el caso de una mujer de 23 años sin factores de riesgo conocidos, a quien se le diagnosticó incidentalmente un blastoma pulmonar primario. La paciente experimentaba dolor en la región costal izquierda, tos productiva, disnea y hemoptisis desde hace 30 días. Los hallazgos en las imágenes de rayos X y tomografías de tórax llevaron a la realización de una biopsia del pulmón izquierdo, que reveló fragmentos de tejido con una notable presencia de necrosis tumoral. Cinco días después, la paciente consultó nuevamente debido a un empeoramiento de los síntomas, incluyendo dolor torácico de tipo pleurítico. Se decidió realizar una lobectomía inferior izquierda, durante la cual se encontró un tumor sólido adherido a la pleura visceral, con masas tumorales en la pleura parietal. El estudio histopatológico final confirmó el diagnóstico de un tumor maligno de alto grado compatible con blastoma pulmonar. En conclusión, el blastoma pulmonar es una neoplasia rara que puede presentarse en diferentes etapas de la vida, aunque tiene mayor incidencia entre los 40 y 50 años. Es importante que los patólogos consideren esta enfermedad en sus diagnósticos diferenciales debido a los desafíos que implica su diagnóstico. Detectar el blastoma pulmonar en etapas tempranas es crucial para el tratamiento adecuado, aunque actualmente no se conocen marcadores predictivos confiables y el pronóstico de esta enfermedad es generalmente desfavorable.


Pulmonary blastoma is a rare and aggressive neoplasm that originates in the lung. It is composed of immature mesenchymal and epithelial tissue that mimics the embryonic configuration of the lung. It has a low incidence and a high mortality rate, of approximately 60%. Pulmonary blastoma tends to occur more frequently between the fourth and fifth decades of life, being more prevalent in women and generally associated with smoking. The case of a 23-year-old woman with no known risk factors is presented, who incidentally was diagnosed with a primary pulmonary blastoma. The patient experienced pain in the left costal region, productive cough, dyspnea, and hemoptysis for 30 days. Findings on X-ray and chest tomography led to a biopsy of the left lung, which revealed tissue fragments with significant tumor necrosis. Five days later, the patient consulted again due to worsened symptoms, including pleuritic chest pain. It was decided to perform a left lower lobectomy, during which a solid tumor attached to the visceral pleura with tumor masses in the parietal pleura was found. The final histopathological study confirmed the diagnosis of a high-grade malignant tumor compatible with pulmonary blastoma. In conclusion, pulmonary blastoma is a rare neoplasm that can occur at different stages of life, although it has a higher incidence between the ages of 40 and 50. Pathologists need to consider this disease in their differential diagnoses due to the challenges involved in its diagnosis. Detecting pulmonary blastoma at early stages is crucial for appropriate treatment, although currently there are no reliable predictive markers, and the prognosis of this disease is generally unfavorable.


Assuntos
Humanos
5.
Cancers (Basel) ; 15(21)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37958434

RESUMO

The proportion of non-transplant-eligible (NTE) newly diagnosed multiple myeloma (NDMM) patients excluded from clinical trials (CTs) and their prognosis is unknown. CT results may not be generalizable to real-world practice due to strict recruitment criteria. We analyzed causes of NTE-NDMM patient exclusion form CTs and their outcomes. A total of 211 NTE-NDMM patients were included. They were divided into three periods: 2003-2007, 2008-2012, and 2013-2017. Overall, 50% received non-trial treatment (NCT), while 50% participated in a CT (20% control group (CG) and 30% experimental group (EG)). Main causes for exclusion from CTs were comorbidities, ECOG > 2, and renal insufficiency. In the first two periods, the CR rate was similar regardless of treatment type, but in the last period, the EG group showed improved CR. Median PFS was similar in the first two periods, with a benefit seen only in the EG in the last period. The median OS was significantly longer in CT-included patients compared to NCT group in the last two periods. Conclusions: The presence of comorbidities and worsened ECOG were the main reasons for CT exclusion. Patients included in CTs had a longer OS than NCT. This OS benefit may be influenced by a selection bias, making it challenging to generalize CT results to real clinical practice.

6.
Microb Biotechnol ; 16(11): 2053-2071, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37804207

RESUMO

Iron is an essential element for all eukaryote organisms because of its redox properties, which are important for many biological processes such as DNA synthesis, mitochondrial respiration, oxygen transport, lipid, and carbon metabolism. For this reason, living organisms have developed different strategies and mechanisms to optimally regulate iron acquisition, transport, storage, and uptake in different environmental responses. Moreover, iron plays an essential role during microbial infections. Saccharomyces cerevisiae has been of key importance for decrypting iron homeostasis and regulation mechanisms in eukaryotes. Specifically, the transcription factors Aft1/Aft2 and Yap5 regulate the expression of genes to control iron metabolism in response to its deficiency or excess, adapting to the cell's iron requirements and its availability in the environment. We also review which iron-related virulence factors have the most common fungal human pathogens (Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans). These factors are essential for adaptation in different host niches during pathogenesis, including different fungal-specific iron-uptake mechanisms. While being necessary for virulence, they provide hope for developing novel antifungal treatments, which are currently scarce and usually toxic for patients. In this review, we provide a compilation of the current knowledge about the metabolic response to iron deficiency and excess in fungi.


Assuntos
Deficiências de Ferro , Proteínas de Saccharomyces cerevisiae , Humanos , Fatores de Transcrição/metabolismo , Ferro/metabolismo , Saccharomyces cerevisiae/genética , Transporte Biológico , Regulação Fúngica da Expressão Gênica , Transativadores/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo
7.
Dermatol Pract Concept ; 13(3)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37557116

RESUMO

INTRODUCTION: Melanoma is the deadliest of all the skin cancers and its incidence is increasing every year in Europe. Patients with melanoma often present late to the specialist and treatment is delayed for many reasons (delay in patient consultation, misdiagnosis by general practitioners, and/or limited access to dermatologists). Beyond this, there are significant inequalities in skin cancer between population groups within the same country and between countries across Europe. The emergence of the COVID-19 pandemic only aggravated these health deficiencies. OBJECTIVES: The aim was to create an expert opinion about the challenges in skin cancer management in Europe during the post COVID-19 acute pandemic and to identify and discuss the implementation of new technologies (including e-health and artificial intelligence defined as "Smart Skin Cancer Care") to overcome them. METHODS: For this purpose, an ad-hoc questionnaire with items addressing topics of skin cancer care was developed, answered independently and discussed by a multidisciplinary European panel of experts comprising dermatologists, dermato-oncologists, patient advocacy representatives, digital health technology experts, and health technology assessment experts. RESULTS: After all panel of experts discussions, a multidisciplinary expert opinion was created. CONCLUSIONS: As a conclusion, the access to dermatologists is difficult and will be aggravated in the near future. This fact, together with important differences in Skin Cancer Care in Europe, suggest the need of a new approach to skin health, prevention and disease management paradigm (focused on integration of new technologies) to minimize the impact of skin cancer and to ensure optimal quality and equity.

8.
Dermatol Pract Concept ; 13(3)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37403983

RESUMO

INTRODUCTION: Melanoma of the lentigo maligna (LM) type is challenging. There is lack of consensus on the optimal diagnosis, treatment, and follow-up. OBJECTIVES: To obtain general consensus on the diagnosis, treatment, and follow-up for LM. METHODS: A modified Delphi method was used. The invited participants were either members of the International Dermoscopy Society, academic experts, or authors of published articles relating to skin cancer and melanoma. Participants were required to respond across three rounds using a 4-point Likert scale). Consensus was defined as >75% of participants agreeing/strongly agreeing or disagreeing/strongly disagreeing. RESULTS: Of the 31 experts invited to participate in this Delphi study, 29 participants completed Round 1 (89.9% response rate), 25/31 completed Round 2 (77.5% response rate), and 25/31 completed Round 3 (77.5% response rate). Experts agreed that LM diagnosis should be based on a clinical and dermatoscopic approach (92%) followed by a biopsy. The most appropriate primary treatment of LM was deemed to be margin-controlled surgery (83.3%), although non-surgical modalities, especially imiquimod, were commonly used either as alternative off-label primary treatment in selected patients or as adjuvant therapy following surgery; 62% participants responded life-long clinical follow-up was needed for LM. CONCLUSIONS: Clinical and histological diagnosis of LM is challenging and should be based on macroscopic, dermatoscopic, and RCM examination followed by a biopsy. Different treatment modalities and follow-up should be carefully discussed with the patient.

9.
Cureus ; 15(5): e38480, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37273293

RESUMO

Tuberous sclerosis (TS) is a multisystem neurocutaneous disorder with an autosomal dominant pattern of inheritance. It is characterized by hamartomas that damage the skin, kidneys, lungs, heart, and central nervous system, among other organs. Rhabdomyomas, benign tumors of aberrant myocytes, are common in affected patients at birth. Depending on their size and location, these lesions might create valvopathies, which can cause heart failure or malignant arrhythmias, or they can cause obstruction of the outlet or inlet tract. Before making the diagnosis, a long time-even years-often passes. Early diagnosis can help prevent permanent irreversible complications. Differential diagnoses may include neurofibromatosis type 1, Sturge-Weber syndrome, and von Hippel-Lindau disease, among others. Diagnostic aids, such as MRI, CT scans, and genetic testing, can be useful in confirming a diagnosis of TS. Histological findings may include the presence of hamartomas, which are benign tumors composed of abnormal cells. Treatment for TS is mainly supportive and may involve medications to manage symptoms, and surgery to remove tumors. We present the case of a 23-year-old woman with TS who was admitted with macroscopic hematuria and fever, with further workup revealing tumor-like cardiac lesions associated with infective endocarditis.

10.
Hematol Oncol Clin North Am ; 37(4): 659-670, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37211494

RESUMO

With the increasing availability of sequencing techniques and new polymerase chain reaction-based methods, data regarding the genomic profile of Waldenström macroglobulinemia (WM) are being continuously analyzed and reproduced. MYD88 and CXCR4 mutations are highly prevalent in all the stages of WM, including the early IgM monoclonal gammopathy of undetermined significance or a more advanced stage, such as smoldering WM. Thus, there is a need to define genotypes before starting either standard treatment regimens or clinical trials. Here, we review the genomic profile of WM and its clinical implications while focusing on recent advances.


Assuntos
Linfoma de Células B , Gamopatia Monoclonal de Significância Indeterminada , Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/terapia , Gamopatia Monoclonal de Significância Indeterminada/genética , Mutação , Fator 88 de Diferenciação Mieloide/genética , Genômica
12.
J Dent ; 134: 104521, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37061118

RESUMO

OBJECTIVES: To assess the influence of different restorative materials and surface wetness on intraoral scanning accuracy. METHODS: Reference casts with an extracted second premolar and first and second molar were digitized (L2). Four groups were established according to the material of the first molar: natural tooth (control), zirconia (Z), lithium disilicate (LD), and nanoceramic resin crown (NC). Four subgroups were developed: dry, low-, mild-, and high-wetness subgroups (n = 15). All the scans were completed by using an intraoral scanner (TRIOS 3). In the control-dry subgroup, the reference cast was dry. In the control-low subgroup, artificial saliva was sprayed with a 1 mL/min volumetric flow for 4 s. In the control-mild and control-high subgroups, the same procedures as in the control-low subgroup were performed, but with a volumetric flow of 4 and of 8 mL/min, respectively. In the Z, LD and NC groups, each crown was fabricated with its respective material. Trueness was analyzed using 2-way ANOVA and Bonferroni tests. The Levene and Bonferroni tests were used to assess precision (α = 0.05). RESULTS: Material (P < .001) and wetness (P < .001) significantly influenced trueness and precision. The mild and high subgroups revealed lower trueness and precision compared with the dry and low subgroups. The control, Z, and LD groups under dry and low wetness conditions showed better trueness compared with the NC group, but the materials tested had no significant precision discrepancies. Under mild wetness conditions, all the materials showed no significant trueness discrepancies. Under high wetness conditions, the LD group demonstrated the best trueness and precision. CONCLUSIONS: The restorative materials and surface wetness tested influenced scanning trueness and precision of the IOS assessed. CLINICAL SIGNIFICANCE: Dried surfaces are recommended to maximize the scanning accuracy values of the IOS tested. Overall, the presence of saliva and dental restorations can reduce the performance of the IOS tested.


Assuntos
Técnica de Moldagem Odontológica , Imageamento Tridimensional , Modelos Dentários , Desenho Assistido por Computador , Materiais Dentários
13.
Br J Haematol ; 200(2): 187-196, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36210485

RESUMO

Waldenström macroglobulinaemia (WM) is characterized by recurrent somatic mutations in MYD88 and CXCR4 genes. However, limitations arise when analysing these mutations in IgM monoclonal gammopathy of undetermined significance (MGUS) or smouldering WM (SWM) given the lower tumour load. Here, we used droplet digital polymerase chain reaction (ddPCR) to analyse MYD88 L265P and CXCR4 S338* mutations (C1013G and C1013A) in unsorted bone marrow (BM) or cell-free DNA (cfDNA) samples from 101 IgM MGUS and 69 SWM patients. ddPCR was more sensitive to assess MYD88 L265P compared to allele-specific PCR, especially in IgM MGUS (64% vs 39%). MYD88 mutation burden correlated with other laboratory biomarkers, particularly BM infiltration (r = 0.8; p < 0.001). CXCR4 C1013G was analysed in MYD88-mutated samples with available genomic DNA and was detected in 19/54 (35%) and 18/42 (43%) IgM MGUS and SWM cases respectively, also showing correlation with BM involvement (r = 0.9; p < 0.001). ddPCR also detected 8 (38%) and 10 (63%) MYD88-mutated cfDNA samples in IgM MGUS and SWM respectively. Moreover, high BM mutation burden (≥8% MYD88 and ≥2% CXCR4) was associated with an increased risk of progression to symptomatic WM. We show the clinical applicability of ddPCR to assess MYD88 and CXCR4 in IgM MGUS and SWM and provide a molecular-based risk classification.


Assuntos
Ácidos Nucleicos Livres , Linfoma de Células B , Gamopatia Monoclonal de Significância Indeterminada , Macroglobulinemia de Waldenstrom , Humanos , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/genética , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/genética , Fator 88 de Diferenciação Mieloide/genética , Prognóstico , Mutação , Reação em Cadeia da Polimerase , Ácidos Nucleicos Livres/genética , Imunoglobulina M/genética , Receptores CXCR4/genética
14.
Blood Cancer J ; 12(9): 135, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114167

RESUMO

From January 1970 to December 2018, 1304 patients were diagnosed with multiple myeloma (MM) at our institution and 256 (19.6%) had plasmacytomas (Ps) (paraskeletal -PPs- 17.6%, extramedullary -EMPs-1.9%). Patients with Ps had lower serum M-protein and less advanced ISS stage than those without. At first relapse, 192 out of 967 patients (19.8%) developed Ps (PPs 14.6%, EMPs 5.1%). The only factor associated with Ps at relapse was the presence of Ps at diagnosis (46% vs 13%, p < 0.00001) with no impact with exposure to novel drugs or previous autologous stem-cell transplantation (ASCT). The median overall survival (OS) was 45, 44 and 20 months for patients without Ps, PPs and EMPs, respectively (p = 0.013). Patients with PPs who underwent ASCT had similar OS than those without Ps (98 vs. 113 months) and significantly longer than those with EMPs (98 vs 47 months, p = 0.006). In patients non-eligible for ASCT the presence of PPs or EMPs was associated with shorter OS compared with patients without Ps (32 vs. 24 vs. 6 months, p = 0.009). In the relapsed setting, a significant survival benefit was observed beyond the year 2000, but still with significant differences among patients without Ps, PPs and EMPs (37 vs 22 vs 16 months, p = 0.003). Importantly, rescue therapy with combinations of proteasome-inhibitors plus immunomodulatory drugs was associated with prolonged OS from first relapse (over 6 years), even in patients with EMPs.


Assuntos
Mieloma Múltiplo , Plasmocitoma , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia , Plasmocitoma/diagnóstico , Plasmocitoma/terapia , Complexo de Endopeptidases do Proteassoma , Transplante Autólogo
15.
Clin Adv Hematol Oncol ; 20(8): 506-515, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36125957

RESUMO

The development of high-throughput technologies has allowed us to characterize the molecular landscape of hematologic neoplasms and identify somatic mutations. As a result, we can now use these technologies to screen for and diagnose neoplastic disease, model risk factors for progression, make treatment decisions, track response to treatment, and design clinical trials. Waldenström macroglobulinemia (WM), which is a lymphoplasmacytic lymphoma, serves as a good example of how genomic data collected at the bench can be applied at the bedside. MYD88 L265P and CXCR4 nonsense and frameshift mutations are the most common recurrent variants observed in patients who have WM, with detection rates of 90% and 40%, respectively. Knowing about these mutations has made it possible to develop agents that target the underlying signaling pathways. In this review, we describe the various treatment strategies for WM and detail the genotype of the malignant WM cell.


Assuntos
Linfoma de Células B , Macroglobulinemia de Waldenstrom , Humanos , Linfoma de Células B/genética , Mutação , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/uso terapêutico , Transdução de Sinais , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Macroglobulinemia de Waldenstrom/genética
16.
Rev. colomb. cardiol ; 29(4): 495-501, jul.-ago. 2022. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1408011

RESUMO

Resumen La derivada aVR es frecuentemente olvidada al interpretar un electrocardiograma. Esto se explica en gran medida debido a que no aporta información específica sobre el ventrículo izquierdo. Sin embargo, tiene gran utilidad en términos tanto de diagnóstico como de pronóstico en múltiples condiciones clínicas, como el síndrome coronario agudo, la pericarditis, la disección aórtica, la intoxicación por antidepresivos tricíclicos, las arritmias y múltiples trastornos de la conducción cardiaca. El objetivo de este artículo es resaltar la importancia clínica de esta derivada y así incentivar su evaluación sistemática en la práctica clínica.


Abstract aVR lead is a frequently forgotten derivative when interpreting an electrocardiogram. This may be largely explained by the fact that it does not provide specific information on the left ventricle. However, it is very useful in terms of both, diagnosis and prognosis, of different clinical entities such as acute coronary syndrome, pericarditis, aortic dissection, tricyclic antidepressants intoxication, arrhythmias and multiple cardiac conduction disorders. The main purpose of this article is to highlight the clinical importance of aVR lead and thus encourage its use in clinical practice.

17.
Front Oncol ; 12: 936993, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35865461

RESUMO

Introduction: Multiple myeloma (MM) is considered an incurable hematological neoplasm. For transplant-eligible patients, initial treatment includes an induction phase followed by an autologous stem cell transplantation (ASCT). Despite the introduction of several drugs in the past years, relapses still occur. Nevertheless, some patients achieve sustained responses after successful induction treatment and ASCT. Methods: We retrospectively evaluated all patients diagnosed with MM in our institution who underwent induction treatment and ASCT between 1990 and 2015. The subset of patients who achieved a sustained response (any degree) for 5 or more years after ASCT without further treatment or signs of progression were distinguished as "long-term responders" (LTRs). In the non-LTR group, a cohort referred to as "prolonged responders" (PLRs) showed sustained response of at least 5 years after ASCT but eventually relapsed. We collected and analyzed clinical and laboratory data. Results: Two hundred and fifty patients were diagnosed with MM and received induction treatment and ASCT at our institution in the study period. Among them, 54 (21.6%) patients met the criteria for LTR. Some diagnostic features such as a younger age, female gender, ECOG performance status of 0, lower International Staging System (ISS) stage, lower bone marrow plasma cell infiltration, and lower serum levels of calcium, C-reactive protein, and lactate dehydrogenase (LDH) were found to be more prevalent in LTR. Female gender, an ECOG performance status of 0, a localized Durie-Salmon stage, an ISS of I-II, the absence of bone disease, and an LDH within normal range were also predictive of longer progression-free survival (PFS) and overall survival (OS) in the whole cohort. The depth of the response achieved after induction and ASCT as well as the administration of an IMID-based maintenance regimen may play a role in the differences observed on PFS between cohorts. A detectable M-protein with a monoclonal gammopathy of undetermined significance (MGUS)-like behavior was detected in one-third of LTR after ASCT. Although relapses continue to occur in patients who achieve a 5-year treatment-free period after ASCT, a plateau is observed in the survival curves at approximately 21 years of follow-up.

18.
Mol Ther Methods Clin Dev ; 26: 207-223, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-35859694

RESUMO

Autologous cell immunotherapy using B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cells is an effective novel treatment for multiple myeloma (MM). This therapy has only been used for relapsed and refractory patients, at which stage the endogenous T cells used to produce the CAR-T cells are affected by the immunosuppressive nature of advanced MM and/or side effects of previous therapies. An alternative pool of "fitter" T cells is found in leukocytoapheresis products that are routinely collected to obtain hematopoietic progenitor cells for autologous stem cell transplantation (ASCT) early in the treatment of MM. However, to mobilize the progenitor cells, patients are dosed with granulocyte colony-stimulating factor (G-CSF), which is reported to adversely affect T cell proliferation, function, and differentiation. Here, we aimed to first establish whether G-CSF treatment negatively influences T cell phenotype and to ascertain whether previous exposure of T cells to G-CSF is deleterious for anti-BCMA CAR-T cells. We observed that G-CSF had a minimal impact on T cell phenotype when added in vitro or administered to patients. Moreover, we found that CAR-T cell fitness and anti-tumor activity were unaffected when generated from G-CSF-exposed T cells. Overall, we showed that ASCT apheresis products are a suitable source of T cells for anti-BCMA CAR-T cell manufacture.

19.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1431292

RESUMO

Introducción: El Perú posee un gran número revistas de áreas biomédicas, pero solo algunas han logrado visibilizar e indizar sus publicaciones en diferentes medios de indización de alcance global. Objetivo: Analizar las características de publicación de la Revista del Cuerpo Médico Hospital Nacional Almanzor Aguinaga Asenjo (Chiclayo) a partir de indicadores bibliométricos. Material y métodos: Estudio descriptivo que analiza 587 registros bibliográficos de los artículos publicados en la revista durante 2011-2020, a partir de indicadores de impacto científico y análisis de términos. Resultados: La mayor producción de artículos corresponde a originales (60%; X̅=66). Los artículos publicados sobre medicina general obtuvieron más impacto en años anteriores. Los temas más frecuentes fueron estudios sobre pacientes de hospitales de Chiclayo, Lambayeque con casos de covid-19. Conclusiones: La Revista del Cuerpo Médico HNAAA se perfila como una publicación seriada de importancia para visibilizar la producción nacional y local por la cobertura temática en especialidades médicas de relevancia regional que publica.


Background: There are several journals about biomedical areas in Peru, however only a few have managed to make their publications avisible and indexed in different global indexing media. Objective: To analyze the main publication characteristics from Revista del Cuerpo Médico Hospital Nacional Almanzor Aguinaga Asenjo (Chiclayo) based on bibliometric methods. Material and methods: Descriptive study that analyzes 587 articles published by the journal from 2011 to 2020, based on bibliometric methods and indicators: citations, scientific impact and co-word analysis. Results: Original articles were the highest types of document published (60%; X̅=66). Published research articles on general medicine received more impact in previous years than the recents. Most frequent topic analyzed were studies about patients from hospitals in Chiclayo city (Lambayeque) with covid-19 clinical cases. Conclusion: Revista del Cuerpo Médico HNAAA is emerging as an important serial publication to make local, national, and international production visible due to thematic coverage in relevant medical specialties.

20.
Rev. chil. infectol ; 39(3): 273-286, jun. 2022. ilus, tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1407794

RESUMO

INTRODUCCIÓN: A pesar de la probada eficacia y seguridad de las vacunas contra la COVID-19, la cobertura de vacunación pediátrica sigue siendo baja en muchos países. Aún existen dudas y temores en los padres sobre la vacunación en sus hijos bajo 12 años de edad. OBJETIVO: Evaluar las percepciones e intención de los padres de vacunar a sus hijos bajo 12 años en Perú. METODOLOGÍA: Estudio transversal analítico, a partir de una encuesta que recopiló la percepción de los padres sobre el riesgo de contagio por COVID-19, necesidad de vacunación y desarrollo de eventos adversos por la vacuna en niños bajo 12 años. Evaluamos los factores asociados a la intención de vacunación mediante razones de prevalencia crudas (RPc) y ajustadas (RPa) con intervalos de confianza al 95% (IC 95%). RESULTADOS: El 83,5% de los padres tenían la intención de vacunar a sus hijos bajo 12 años. En el análisis multivariado, los factores asociados a una disminución de la intención de vacunación fueron pensar que la vacuna no es necesaria (RPa: 0,65; IC 95% 0,44 - 0,94), que no protegería (RPa: 0,14; IC 95% 0,03 - 0,63), que no sería segura (RPa: 0,80; IC 95% 0,70 - 0,92) y que ocasionaría efectos negativos a largo plazo (RPa: 0,92; IC 95% 0,85 - 1,00). Por otro lado, residir en la Selva (RPa: 1,09; IC 95%: 1,03-1,15) o en la Sierra (RPa: 1,06; IC 95%: 1,00-1,11) se asoció a una mayor prevalencia de intención. CONCLUSIONES: En Perú, un 16,5% de padres no vacunaría a sus hijos bajo 12 años, ya que perciben que la vacuna no es necesaria y no protegería contra la COVID-19, además de tener la preocupación de posibles eventos adversos.


BACKGROUND: Despite the proven efficacy and safety of COVID-19 vaccines, pediatric vaccination coverage remains low in many countries. There are still doubts and fears in parents about vaccination in their children under 12 years of age. AIM: To evaluate the perceptions and intention of parents to vaccinate their children under 12 years of age. METHODS: Analytical cross-sectional study based on an online survey that evaluated the parents' perceptions regarding the risk of COVID-19 infection, the need for a vaccine, and the vaccine adverse events in their children under 12 years. We assessed the factors associated with the intention to vaccinate through crude (cPR) and adjusted prevalence rates (aPR), with confidence interval of 95% (CI 95%). RESULTS: 83.5% of respondents had the intention to vaccinate their children under 12 years of age. In the multivariate analysis, the factors associated with a decrease in the intention to vaccinate were to believe that the vaccine was not necessary (aPR 0.65; 95% CI 0.44 - 0.94), that it would not protect (aPR: 0.14; 95% CI 0.03 - 0.63), it would not be safe (aPR: 0.80; 95% CI 0.70 - 0.92) and it would cause long-term side effects (aPR: 0.92; 95% CI 0.85 - 1.00). On the other hand, living on the highlands or jungle was associated with an increase in the intention. CONCLUSION: In Peru, 16.5% of parents would not vaccinate their children under 12 years of age, because they perceived that the vaccine was not necessary and would not protect against COVID-19. In addition, they expressed concerns about the development of possible adverse events.


Assuntos
Humanos , Criança , Adolescente , Adulto , Intenção , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Pais , Percepção , Peru/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Estudos Transversais , Análise Multivariada , Inquéritos e Questionários
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