ABSTRACT
PURPOSE: Multiple myeloma (MM) is a highly heterogeneous, incurable disease most frequently diagnosed in the elderly. Therefore, data on clinical characteristics and outcomes in the very young population are scarce. PATIENTS AND METHODS: We analyzed clinical characteristics, response to treatment, and survival in 103 patients with newly diagnosed MM age 40 years or younger compared with 256 patients age 41-50 years and 957 patients age 51 years or older. RESULTS: There were no statistical differences in sex, isotype, International Scoring System, renal involvement, hypercalcemia, anemia, dialysis, bony lesions, extramedullary disease, and lactate dehydrogenase (LDH). The most used regimen in young patients was cyclophosphamide, bortezomib, dexamethasone, followed by cyclophosphamide, thalidomide, dexamethasone and bortezomib, thalidomide, dexamethasone. Of the patients age 40 years or younger, only 53% received autologous stem-cell transplant (ASCT) and 71.1% received maintenance. There were no differences in overall survival (OS) in the three patient cohorts. In the multivariate analysis, only high LDH, high cytogenetic risk, and ASCT were statistically associated with survival. CONCLUSION: In conclusion, younger patients with MM in Latin America have similar clinical characteristics, responses, and OS compared with the elderly.
Subject(s)
Multiple Myeloma , Humans , Aged , Adult , Middle Aged , Multiple Myeloma/therapy , Multiple Myeloma/drug therapy , Bortezomib/therapeutic use , Thalidomide/therapeutic use , Latin America/epidemiology , Treatment Outcome , Dexamethasone/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prognosis , Cyclophosphamide/therapeutic useABSTRACT
INTRODUCTION/BACKGROUND: Multiple Myeloma (MM) is a plasma cell derived clonal disorder that represents around 1% of all newly diagnosed neoplasms. Limited data regarding MM treatment in Latin America is available, and access to novel agents for a substantial portion of the population is limited by their high costs. MATERIALS (OR PATIENTS) AND METHODS: RENEHOC is a bidirectional (retrospective and prospective) multicenter observational registry of hematological malignancies in Colombia. MM patients included up to July 2020 were analyzed on this report. RESULTS: 890 are reported with a median follow-up of 18 months (IQR: 7-42 months). Patients were classified by age group (≤ or > 65 years). Median age at diagnosis was 67 years (IQR: 59-75 years) and 47.1% of patients were women. 709 patients (79.6%) received Bortezomib-based schemes as part of the first line. Two hundred and fifty-two patients (28.3%) were consolidated with Autologous Stem Cell Transplantation (ASCT) in first-line. ASCT consolidation and age were the main independent factors influencing outcomes; in the non-ASCT cohort, 5-year overall survival was 48.7% (CI 41.8-55.2) compared to 80.7% (CI 73-86.4) in ASCT patients. CONCLUSION: This data depicts the reality of MM in Colombia, which likely reflects other Latin American countries, where access barriers to diagnosis and treatment are echoed in advanced stage diagnosis and a low rate of transplants. These seem to negatively impact survival despite the availability of most novel drugs approved for this disease. Thus, emphasizing the paradox that prevails in most of the region: availability without equitable access.
Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Aged , Bortezomib/therapeutic use , Colombia/epidemiology , Female , Humans , Male , Multiple Myeloma/diagnosis , Multiple Myeloma/epidemiology , Multiple Myeloma/therapy , Prospective Studies , Registries , Retrospective Studies , Transplantation, AutologousABSTRACT
Abstract Chagas disease (CD) is a protozoan zoonosis caused by Trypanosoma cruzi. Reactivation of CD occurs via drug-induced immunosuppression before and during transplantation. Here, we report the case of a 62-year-old man diagnosed with classic Hodgkin lymphoma who received highly aggressive conditioning chemotherapy before undergoing stem cell transplantation (SCT). The patient tested positive for CD in pre-transplantation evaluation. The patient exhibited persistent fever and elevated C-reactive protein levels before and after SCT, and was treated with antibiotics. Micro-Strout test showed evidence of trypomastigotes and he was treated with benznidazole until tested negative. Post-transplantation seropositive patients should be screened for possible reactivation.
Subject(s)
Humans , Animals , Male , Trypanosoma cruzi , Chagas Disease , Hematopoietic Stem Cell Transplantation/adverse effects , Zoonoses , Immunosuppression Therapy , Middle AgedABSTRACT
Chagas disease (CD) is a protozoan zoonosis caused by Trypanosoma cruzi. Reactivation of CD occurs via drug-induced immunosuppression before and during transplantation. Here, we report the case of a 62-year-old man diagnosed with classic Hodgkin lymphoma who received highly aggressive conditioning chemotherapy before undergoing stem cell transplantation (SCT). The patient tested positive for CD in pre-transplantation evaluation. The patient exhibited persistent fever and elevated C-reactive protein levels before and after SCT, and was treated with antibiotics. Micro-Strout test showed evidence of trypomastigotes and he was treated with benznidazole until tested negative. Post-transplantation seropositive patients should be screened for possible reactivation.
Subject(s)
Chagas Disease , Hematopoietic Stem Cell Transplantation , Trypanosoma cruzi , Animals , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunosuppression Therapy , Male , Middle Aged , ZoonosesABSTRACT
Myasthenia gravis is a neuromuscular autoimmune disease characterized by fatigable weakness of skeletal muscles that results from an antibody-mediated immunological attack directed at acetylcholine postsynaptic receptors. Autologous hematopoietic stem cell transplantation is considered as a treatment option in refractory cases of myasthenia gravis. A 56-year-old Colombian male presented with six months of progressive hoarseness and dysphagia, with a positive repetitive stimulation test suggestive of end plate neuromuscular disease. Myasthenia gravis was confirmed with serology testing that reported presence of circulating acetylcholine postsynaptic receptors antibodies. The patient received several lines of pharmacological treatment and thymectomy without control of symptoms, requiring admission to the intensive care unit and mechanical ventilation in two occasions. Patient underwent autologous hematopoietic stem cell transplantation and has been in complete clinical remission for 65 months. Hematopoietic stem cell transplantation is a well-tolerated treatment that should be considered over conventional therapy in selected patients with refractory myasthenia gravis.
Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Myasthenia Gravis/therapy , Autoantibodies , Humans , Male , Middle Aged , Myasthenia Gravis/immunology , Myasthenia Gravis/surgery , Receptors, Cholinergic/immunology , Thymectomy , Transplantation, Autologous , Treatment OutcomeABSTRACT
PURPOSE: The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity. METHODS: This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review. RESULTS: The studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure. CONCLUSIONS: We observed that there is an important relationship between CYP450 and cisplatin, involving increased toxicity. However, the possible mechanisms described for the involvement of CYP450 enzymes in nephrotoxicity and hepatotoxicity induced by cisplatin need to be confirmed by further studies. Therefore, there is a need for a deeper investigation focusing on cisplatin toxicity mediated by CYP450 enzymes, which would undoubtedly contribute to a better understanding of the mechanisms that have been implicated so far.
Subject(s)
Antineoplastic Agents/adverse effects , Cisplatin/adverse effects , Cytochrome P-450 Enzyme System/metabolism , Animals , Apoptosis/drug effects , Chemical and Drug Induced Liver Injury/enzymology , Chemical and Drug Induced Liver Injury/etiology , Cytochrome P-450 CYP2E1/metabolism , Cytochrome P-450 CYP4A/metabolism , Humans , Kidney Diseases/chemically induced , Kidney Diseases/enzymology , Reactive Oxygen Species/metabolismABSTRACT
Propolis is a polyphenol-rich resinous substance extensively used to improve health and prevent diseases. The effects of polyphenols from different sources of propolis on atherosclerotic lesions and inflammatory and angiogenic factors were investigated in LDL receptor gene (LDLr-/-) knockout mice. The animals received a cholesterol-enriched diet to induce the initial atherosclerotic lesions (IALs) or advanced atherosclerotic lesions (AALs). The IAL or AAL animals were divided into three groups, each receiving polyphenols from either the green, red or brown propolis (250 mg/kg per day) by gavage. After 4 weeks of polyphenol treatment, the animals were sacrificed and their blood was collected for lipid profile analysis. The atheromatous lesions at the aortic root were also analyzed for gene expression of inflammatory and angiogenic factors by quantitative real-time polymerase chain reaction and immunohistochemistry. All three polyphenol extracts improved the lipid profile and decreased the atherosclerotic lesion area in IAL animals. However, only polyphenols from the red propolis induced favorable changes in the lipid profiles and reduced the lesion areas in AAL mice. In IAL groups, VCAM, MCP-1, FGF, PDGF, VEGF, PECAM and MMP-9 gene expression was down-regulated, while the metalloproteinase inhibitor TIMP-1 gene was up-regulated by all polyphenol extracts. In contrast, for advanced lesions, only the polyphenols from red propolis induced the down-regulation of CD36 and the up-regulation of HO-1 and TIMP-1 when compared to polyphenols from the other two types of propolis. In conclusion, polyphenols from propolis, particularly red propolis, are able to reduce atherosclerotic lesions through mechanisms including the modulation of inflammatory and angiogenic factors.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Atherosclerosis/drug therapy , Plant Extracts/pharmacology , Polyphenols/pharmacology , Propolis/chemistry , Animals , Aorta/drug effects , Aorta/metabolism , Atherosclerosis/pathology , Atherosclerosis/prevention & control , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Cholesterol/blood , Down-Regulation , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Inflammation/drug therapy , Inflammation/pathology , Inflammation/prevention & control , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Platelet-Derived Growth Factor/genetics , Platelet-Derived Growth Factor/metabolism , Real-Time Polymerase Chain Reaction , Receptors, LDL/genetics , Receptors, LDL/metabolism , Tissue Inhibitor of Metalloproteinase-1/genetics , Tissue Inhibitor of Metalloproteinase-1/metabolism , Up-Regulation , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/metabolism , Vascular Endothelial Growth Factors/genetics , Vascular Endothelial Growth Factors/metabolismABSTRACT
Taurine concentrations were determined in gliomas from 16 patients and in meningiomas from 15 patients. After imaging analysis and clinical evaluation to consider the level of functional deterioration by the scale of Karnosky, tissue was obtained by surgery. Tumoral, peritumoral and extratumoral samples were taken and analyzed by HPLC with fluorescence detector. The concentration of taurine (nmol/mg protein) was higher in tumoral and peritumoral tissues than in the extratumoral samples for gliomas. In the case of meningiomas, the taurine concentration was higher in tumoral than in peritumoral and extratumoral samples. These modifications might be due to specific functions of this amino acid, being either protective or involved in the proliferation of cells. The differential distribution in the two types of tumors could be related to the malignancy of them, which is higher in gliomas than in meningiomas.
Subject(s)
Brain Neoplasms/chemistry , Glioma/chemistry , Meningeal Neoplasms/chemistry , Meningioma/chemistry , Taurine/analysis , Adolescent , Adult , Aged , Brain Neoplasms/pathology , Glioma/pathology , Humans , Image Processing, Computer-Assisted , Male , Meningeal Neoplasms/pathology , Meningioma/pathology , Middle AgedABSTRACT
El sustrato 1 del receptor de la insulina (IRS-1) es una de las moléculas más importantes en la transducción de señales, que permiten la incorporación de glucosa a la célula. Variaciones genéticas del IRS-1 han sido relacionadas con alteraciones de su función y diversas anormalidades metabólicas. Considerando la escasa información sobre las bases genéticas de las enfermedades cardiovasculares en nuestro país, el objetivo del presente estudio fue determinar la asociación entre la mutación G972R del gen IRS-1 y enfermedad coronaria en individuos de la población de la IX Región (Chile). Estudios de casos y controles, que evaluó 111 individuos (33 a 74 años), con enfermedad coronaria comprobada por angiografía y 116 controles (20 a 68 años). La genotipificación de la mutación G972R fue realizada mediante la técnica de PCR-RFLP. La mutación G972R fue más frecuente en individuos con enfermedad coronaria que en controles (17 por ciento vs. 6 por ciento, p=0,016). La OR asociada a esta mutación fue 3,21 (I.C. 95 por ciento, 1,28 - 8,06, p<0.05). Adicionalmente, el genotipo heterocigoto GR para la mutación G972R fue asociado a niveles más bajos de HDL-C (p=0,048) y a mayores niveles de glucosa (p=0,006) en los individuos controles. La mutación G972R del gen IRS-1 fue asociada a enfermedad coronaria en la población analizada, lo que sugiere un importante rol de IRS-1 en la patogénesis de desordenes metabólicos asociados a EC.
Subject(s)
Male , Adult , Humans , Female , Middle Aged , Coronary Disease/genetics , Coronary Disease/metabolism , Receptor, Insulin/genetics , Insulin Resistance/genetics , Uric Acid/blood , Case-Control Studies , Phosphoproteins/genetics , Genotype , Lipids/blood , Mutation , Risk Factors , Signal Transduction/geneticsABSTRACT
The effect of estradiol benzoate, progesterone and a sequential treatment with both on the activity of the enzyme monoamine-oxidase (MAO) was assessed in mitochondria from hypothalami of ovariectomized rats. A differential effect on the subtypes A and B MAO was found according to the type of treatment. Estradiol benzoate administration decreases MAO activity, mainly that of MAO-A. Progesterone alone had no effect, and sequential treatment with estradiol benzoate plus progesterone restored sexual behavior and produced a significant increase of MAO-A activity, whitout changes in total MAO activity. Since MAO-A is an isoform of MAO that preferentially uses norepinephrine and serotonin as substrates and MAO-B acts on phenylethylamine and benzylamine as substrates, our findings suggest that the restoration of sexual behabior after the treatment with estradiol benzoate followed by progesterone may be associated with the differential effect exerted by the hormones on MAO subtypes, rather than to the simple decrease in hypothalamic monoamine concentrations as reported in the literature
