RESUMO
Introduction: Patients with colonic obstruction are at risk for emergency resection, which is a risk factor for increased mortality and morbidity. In left-sided obstructive colon cancer, the principle of bridge-to-surgery is already recommended to reduce complications. From this treatment strategy, the obstruction treatment is derived. In this treatment strategy, bowel wall distention is reduced by minimizing stool production through laxatives and dietary measures. Short-term outcomes have already shown promising results. This study aims to evaluate long-term outcomes in patients treated with this obstruction treatment. Methods: This is a multicenter prospective study that included patients who presented with symptomatic colonic obstruction and radiologic confirmation of obstruction between May 2019 and August 2020 in the contributing hospitals. Patients with malignant and benign colonic obstruction were included. Follow-up in this study consisted of at least 36 months. Endpoints of the study included 1- and 3-year stoma and mortality rates. Results: Ninety-eight patients were included in this study. For the overall cohort complication, reoperation, and readmission rates after one year were 37%, 14%, and 10% respectively. Overall, 3-year mortality was 21%. The presence of a stoma after 1 year was 18%, and after 3 years 17% in this cohort. Conclusion: Long-term results of this study indicate that obstruction treatment has acceptable long-term outcomes in terms of mortality and stoma rates, compared to literature on emergency surgery and bridge-to-surgery alternatives. Permanent stoma rates are lower, compared to the literature on other treatment strategies in bowel obstruction. (AU)
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Obstrução Intestinal/mortalidade , Obstrução Intestinal/terapia , Seguimentos , Resultado do Tratamento , Estomas CirúrgicosRESUMO
Human leukocyte antigen (HLA)-G is an immune checkpoint molecule that is highly expressed in papillary thyroid carcinoma (PTC). The HLA-G gene presents several functional polymorphisms distributed across the coding and regulatory regions (5'URR: 5' upstream regulatory region and 3'UTR: 3' untranslated region) and some of them may impact HLA-G expression and human malignancy. To understand the contribution of the HLA-G genetic background in PTC, we studied the HLA-G gene variability in PTC patients in association with tumor morbidity, HLA-G tissue expression, and plasma soluble (sHLA-G) levels. We evaluated 185 PTC patients and 154 healthy controls. Polymorphic sites defining coding, regulatory and extended haplotypes were characterized by sequencing analyses. HLA-G tissue expression and plasma soluble HLA-G levels were evaluated by immunohistochemistry and ELISA, respectively. Compared to the controls, the G0104a(5'URR)G*01:04:04(coding)UTR-03(3'UTR) extended haplotype was underrepresented in the PTC patients, while G0104a(5'URR)G*01:04:01(coding)UTR-03(3'UTR) was less frequent in patients with metastatic and multifocal tumors. Decreased HLA-G tissue expression and undetectable plasma sHLA-G were associated with the G010102a(5'URR)G*01:01:02:01(coding)UTR-02(3'UTR) extended haplotype. We concluded that the HLA-G variability was associated with PTC development and morbidity, as well as the magnitude of the encoded protein expression at local and systemic levels.
Assuntos
Antígenos HLA-G , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/genética , Antígenos HLA-G/genética , Regiões 3' não Traduzidas , Morbidade , Neoplasias da Glândula Tireoide/genética , Proteínas de Ligação ao GTPRESUMO
As BRAF, TERT, HLA-G, and microRNAs have been individually associated with papillary thyroid carcinoma (PTC), we aimed to evaluate the individual and collaborative role of these markers in PTC in the same patient cohort. HLA-G and BRAF tumor expression was evaluated by immunohistochemistry. Using molecular methods, BRAFV600E and TERT promoter mutations were evaluated in thyroid fine needle aspirates. MicroRNA tumor profiling was investigated using massively parallel sequencing. We observed strong HLA-G (67.96%) while BRAF (62.43%) staining was observed in PTC specimens. BRAF overexpression was associated with poor response to therapy. The BRAFV600E (52.9%) and TERTC228T (13%) mutations were associated with extrathyroidal extension, advanced-age, and advanced-stage cancer. The TERT rs2853669 CC+TC genotypes (38%) were overrepresented in metastatic tumors. Nine modulated microRNAs targeting the BRAF, TERT, and/or HLA-G genes were observed in PTC and involved with cancer-related signaling pathways. The markers were individually associated with PTC features, emphasizing the synergistic effect of BRAFV600E and TERTC228T; however, their collaborative role on PTC outcome was not fully demonstrated. The differentially expressed miRNAs targeting the BRAF and/or HLA-G genes may explain their increased expression in the tumor milieu.
Assuntos
Carcinoma Papilar , MicroRNAs , Telomerase , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Antígenos HLA-G/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Regiões Promotoras Genéticas , Telomerase/genética , Telomerase/metabolismo , Mutação , MicroRNAs/genéticaRESUMO
Despite advances in clinical genetic testing, including the introduction of exome sequencing (ES), more than 50% of individuals with a suspected Mendelian condition lack a precise molecular diagnosis. Clinical evaluation is increasingly undertaken by specialists outside of clinical genetics, often occurring in a tiered fashion and typically ending after ES. The current diagnostic rate reflects multiple factors, including technical limitations, incomplete understanding of variant pathogenicity, missing genotype-phenotype associations, complex gene-environment interactions, and reporting differences between clinical labs. Maintaining a clear understanding of the rapidly evolving landscape of diagnostic tests beyond ES, and their limitations, presents a challenge for non-genetics professionals. Newer tests, such as short-read genome or RNA sequencing, can be challenging to order, and emerging technologies, such as optical genome mapping and long-read DNA sequencing, are not available clinically. Furthermore, there is no clear guidance on the next best steps after inconclusive evaluation. Here, we review why a clinical genetic evaluation may be negative, discuss questions to be asked in this setting, and provide a framework for further investigation, including the advantages and disadvantages of new approaches that are nascent in the clinical sphere. We present a guide for the next best steps after inconclusive molecular testing based upon phenotype and prior evaluation, including when to consider referral to research consortia focused on elucidating the underlying cause of rare unsolved genetic disorders.
Assuntos
Exoma , Testes Genéticos , Humanos , Exoma/genética , Análise de Sequência de DNA , Fenótipo , Sequenciamento do Exoma , Doenças RarasRESUMO
Introduction: The introduction of Enhanced Recovery After Surgery led to increasing twenty-four hours discharge pathways, for example in laparoscopic cholecystectomy and bariatric surgery. However, implementation in colorectal surgery still must set off. This systematic review assesses safety and feasibility of twenty-four hours discharge in colorectal surgery in terms of readmission and complications in current literature. Secondary outcome was identification of factors associated with success of twenty-four hours discharge. Methods: Pubmed and EMBASE databases were searched to identify studies investigating twenty-four hours discharge in colorectal surgery, without restriction of study type. Search strategy included keywords relating to ambulatory management and colorectal surgery. Studies were scored according to MINORS score. Results: Thirteen studies were included in this systematic review, consisting of six prospective and seven retrospective studies. Number of participants of the included prospective studies ranged from 5 to 157. Median success of discharge was 96% in the twenty-four hours discharge group. All prospective studies showed similar readmission and complication rates between twenty-four hours discharge and conventional postoperative management. Factors associated with success of twenty-four hours discharge were low ASA classification, younger age, minimally invasive approach, and relatively shorter operation time. Conclusions: Twenty-four hours discharge in colorectal surgery seems feasible and safe, based on retro- and prospective studies. Careful selection of patients and establishment of a clear and adequate protocol are key items to assure safety and feasibility. Results should be interpreted with caution, due to heterogeneity. To confirm results, an adequately powered prospective randomized study is needed. (AU)
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Alta do Paciente , Neoplasias Colorretais/cirurgia , Tempo de Internação , Complicações Pós-Operatórias , Período Pós-OperatórioRESUMO
Traditional studies on the evolution of antibiotic resistance development use approaches that can range from laboratory-based experimental studies, to epidemiological surveillance, to sequencing of clinical isolates. However, evolutionary trajectories also depend on the environment in which selection takes place, compelling the need to more deeply investigate the impact of environmental complexities and their dynamics over time. Herein, we explored the within-patient adaptive long-term evolution of a Pseudomonas aeruginosa hypermutator lineage in the airways of a cystic fibrosis (CF) patient by performing a chronological tracking of mutations that occurred in different subpopulations; our results demonstrated parallel evolution events in the chromosomally encoded class C ß-lactamase (blaPDC). These multiple mutations within blaPDC shaped diverse coexisting alleles, whose frequency dynamics responded to the changing antibiotic selective pressures for more than 26 years of chronic infection. Importantly, the combination of the cumulative mutations in blaPDC provided structural and functional protein changes that resulted in a continuous enhancement of its catalytic efficiency and high level of cephalosporin resistance. This evolution was linked to the persistent treatment with ceftazidime, which we demonstrated selected for variants with robust catalytic activity against this expanded-spectrum cephalosporin. A "gain of function" of collateral resistance toward ceftolozane, a more recently introduced cephalosporin that was not prescribed to this patient, was also observed, and the biochemical basis of this cross-resistance phenomenon was elucidated. This work unveils the evolutionary trajectories paved by bacteria toward a multidrug-resistant phenotype, driven by decades of antibiotic treatment in the natural CF environmental setting. IMPORTANCE Antibiotics are becoming increasingly ineffective to treat bacterial infections. It has been consequently predicted that infectious diseases will become the biggest challenge to human health in the near future. Pseudomonas aeruginosa is considered a paradigm in antimicrobial resistance as it exploits intrinsic and acquired resistance mechanisms to resist virtually all antibiotics known. AmpC ß-lactamase is the main mechanism driving resistance in this notorious pathogen to ß-lactams, one of the most widely used classes of antibiotics for cystic fibrosis infections. Here, we focus on the ß-lactamase gene as a model resistance determinant and unveil the trajectory P. aeruginosa undertakes on the path toward a multidrug-resistant phenotype during the course of two and a half decades of chronic infection in the airways of a cystic fibrosis patient. Integrating genetic and biochemical studies in the natural environment where evolution occurs, we provide a unique perspective on this challenging landscape, addressing fundamental molecular mechanisms of resistance.
Assuntos
Fibrose Cística , Infecções por Pseudomonas , Humanos , Cefalosporinase/genética , Fibrose Cística/microbiologia , Ceftazidima/farmacologia , Infecções por Pseudomonas/microbiologia , Pseudomonas/metabolismo , Testes de Sensibilidade Microbiana , beta-Lactamases/metabolismo , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Celiac disease (CD) is an immune-mediated systemic disorder triggered by gluten and related prolamins in genetically predisposed individuals. Here, we described a case of a 31-year-old Caucasian woman who exhibited cerebellar and psychiatric dysfunctions. The patient underwent single-photon emission computed tomography (SPECT-CT) before and after a gluten-free diet (GFD). There was an improvement in cerebellar perfusion accompanied by a remission of cerebellar manifestations. The maintenance of the psychiatric manifestations was related to the persistence of the hypoperfusion in the frontal lobes. The patient's psychiatric symptoms did not change after 4 months under a GFD in the hospital. To our knowledge, this is the first case that shows the relationship between improvement in cerebellar perfusion and remission of cerebellar clinical manifestations in a CD patient under a GFD.
Assuntos
Doença Celíaca , Ataxia Cerebelar , Adulto , Doença Celíaca/complicações , Doença Celíaca/diagnóstico por imagem , Ataxia Cerebelar/complicações , Ataxia Cerebelar/diagnóstico por imagem , Dieta Livre de Glúten , Feminino , Humanos , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Increasing evidence shows that chronic inflammation plays an important role in thyroid tumorigenesis. Cytokines as central mediators in inflammatory microenvironment can present both pro-tumour and anti-tumour effects and cytokine release may be influenced by soluble HLA-G (sHLA-G), an immune checkpoint molecule whose expression can also be induced by certain cytokines. AIM: To understand the role of these soluble factors in papillary thyroid cancer (PTC). METHODS: We evaluated plasma levels of sHLA-G and of 13 cytokines using ELISA and flow cytometry, respectively, in PTC patients at two time points: pre- and post-thyroidectomy; and control subjects. RESULTS: Compared with controls, IL-6 levels were increased, while IL-1ß, IFN-α and TGF-ß1 levels were decreased in pre-thyroidectomy PTC patients. IFN-α and TGF-ß1 efficiently discriminated patients from controls and were associated with extrathyroidal extension and lymph node metastasis, respectively. In addition, TNF and IL-13 were associated with male gender, lymph node metastasis and Hashimoto thyroiditis, and sHLA-G with tumour invasion. Compared with pre-thyroidectomy, IL-4, IL-10, TNF, IFN-α and TGF-ß1 levels were increased in post-thyroidectomy. CONCLUSION: There are significant changes in the cytokine profile after surgical removal of the thyroid tumour, and IFN-α e TGF-ß1 showed to be promising cytokines for discriminating PTC patients from controls. We also found that different cytokines are associated with clinicohistopathological characteristics of PTC related to poor prognosis, suggesting that cytokines seem to play an important role in PTC development and management.
Assuntos
Carcinoma Papilar/metabolismo , Citocinas/sangue , Antígenos HLA-G/sangue , Câncer Papilífero da Tireoide/metabolismo , Adulto , Biomarcadores/metabolismo , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , TireoidectomiaRESUMO
Streptococcus pyogenes infection continues to be a worldwide public health problem causing various diseases in humans and plays an important role in the pathogenesis of rheumatic fever and rheumatic heart disease. We developed a vaccine candidate to prevent S. pyogenes infections, identified as StreptInCor, that presented promising results in mouse models. A certified and independent laboratory conducted two repeated intramuscular dose toxicity tests (28 days, four weekly injections). The first test, composed of four experimental groups treated with 0 (vehicle), 50, 100 or 200 µg/500 µL StreptInCor, did not show significant alterations in clinical, hematological, biochemical or anatomopathological parameters related to the administration of StreptInCor. In addition to the parameters mentioned above, we evaluated the cardiac function and valves of animals by echocardiography before and after administration of 200 µg/500 µL StreptInCor versus placebo. We did not observe any changes related to StreptInCor administration, including changes in cardiac function and valves in animals, after receiving the highest dose of this vaccine candidate. The results obtained in the two repeated intramuscular dose toxicity tests showed that this vaccine formulation did not induce harmful effects to the tissues and organs studied, indicating that the candidate vaccine is well tolerated in minipigs.
Assuntos
Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/administração & dosagem , Streptococcus pyogenes/imunologia , Adsorção , Animais , Feminino , Injeções Intramusculares , Masculino , Modelos Animais , Vacinas Estreptocócicas/efeitos adversos , Suínos , Porco Miniatura , Testes de ToxicidadeRESUMO
Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome.
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Abstract:The Neotropical bee Centris (Hemisiella) dichrootricha is a solitary bee that nests in pre-existing cavities that occur in the rain forest. This study describes the nesting biology of C. dichrootricha and its preference for nesting in Cerrado and gallery forest habitats. The study was conducted from January 2012 and December 2013, in Mirador State Park in the municipality of Formosa da Serra Negra, Maranhão State, Brazil. For this, wooden trap-nests of 6, 8, 10, 12, 14 and 16 mm in diameter were used; a total of 300 trap-nests were placed in the gallery forest and Cerrado areas, respectively. Traps were monitored monthly and all completed nests were collected and replaced with empty ones. The nests were then taken to the laboratory to analyze bee development and emergence, nests characteristics and parasites presence. The species used 29 of the trap-nests, which had diameters of 8, 10, 12 and 14 mm. A total of 87 C. dichrootricha specimens emerged. The nests were parasitized by two bee species, Mesocheira bicolor (Apinae) and Coelioxys sp. (Megachilinae), and one fly species, Antrax sp. (Diptera). The highest nesting incidence of 72.4 % was observed in the gallery forest, whereas only 27.6 % in the Cerrado; this difference in habitat use was significant (χ² = 5.56; p < 0.05; DF = 1). For the nests that were built in the gallery forest, 80.9% of the soil originated from the Cerrado. The females were significantly larger than the males (F1, 76 = 595.19; p < 0.001). There were 11 pollen types that belonged to six families. Pollen of the family Malpighiaceae was most frequently used, with four species represented (Byrsonima crassifolia, B. rotunda, B. spicata and Heteropterys sp.). C. dichrootricha showed a preference for nesting in cavities of various diameters in gallery forest sites. The present study provides a novel description of the nesting habits and biology of C. dichrootricha in habitats of Central/Southern Maranhão. C. dichrootricha primarily used resources from the Cerrado, including soil to build their nests, pollen and floral oils; we concluded that gallery forest and Cerrado areas are intrinsically related to the maintenance of local populations of this species. Rev. Biol. Trop. 64 (3): 1041-1056. Epub 2016 September 01.
ResumenCentris (Hemisiella) dichrootricha es una especie de abeja solitaria neotropical, que anida en cavidades preexistentes y vive en la selva tropical. El presente estudio describe la biología de anidación de C. dichrootricha y su preferencia de nidificación por áreas en Cerrado y Bosque de Galería. El área de estudio se localiza en el Parque Estadual de Mirador, municipio de Formosa da Serra Negra, Maranhão. El método empleado fue el de nidos trampa de madera de diferentes diámetros, 6, 8, 10, 12, 14 y 16 mm, colocándose 300 nidos trampa por área. Las trampas fueron monitoreadas mensualmente y todos los nidos terminados fueron recogidos y sustituidos por otros vacíos. Los nidos completos fueron llevados al laboratorio para analizar el desarrollo de la abeja, la emergencia, las características de los nidos y la presencia de parásitos. La especie ocupó 29 nidos de los diámetros de 8, 10, 12 y 14 mm. Emergieron 87 individuos de C. dichrootricha. Los nidos fueron parasitados por tres especies: Mesocheira bicolor (Apinae), Coelioxys sp. (Megachilinae) y Antrax sp. (Diptera). En el Bosque de Galería se presentó la mayor nidificación (72.4 %) y en el Cerrado solamente 27.6 %, de esta forma, hubo diferencias significativas entre los hábitats (χ² = 5.56; p < 0.05; G. L.= 1). Los nidos fundados en el bosque de galería presentaron 80.9 % de sedimento originario del Cerrado. Las hembras fueron significativamente más grandes que los machos (F1, 76 = 595.19; p < 0.001). Hubo 11 tipos de polen pertenecientes a seis familias. Los tipos de polinización de la familia Malpighiaceae fueron los más representativos, con cuatro especies: Byrsonima crassifolia, B. rotunda, B. spicata y Heteropterys sp. C. dichrootricha mostró preferencia por nidificar en cavidades con diámetros variados y en el bosque de galería. El presente estudio contribuye con la descripción de los hábitos de nidificación y la biología de la especie para las áreas de Cerrado en la región centrosur de Maranhão. C. dichrootricha utilizó en su mayoría recursos provenientes del Cerrado, tanto sedimento para construir el nido, como material polínico y aceite floral. Estós datos indican que el bosque de galería y el Cerrado están intrínsecamente relacionados con el mantenimiento y conservación de C. dichrootricha.
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Animais , Masculino , Feminino , Abelhas/fisiologia , Florestas , Comportamento de Nidação/fisiologia , Pólen/classificação , Estações do Ano , Especificidade da Espécie , Fatores de Tempo , Brasil , Fatores Sexuais , Distribuição por Sexo , Distribuição AnimalRESUMO
The Neotropical bee Centris (Hemisiella) dichrootricha is a solitary bee that nests in pre-existing cavities that occur in the rain forest. This study describes the nesting biology of C. dichrootricha and its preference for nesting in Cerrado and gallery forest habitats. The study was conducted from January 2012 and December 2013, in Mirador State Park in the municipality of Formosa da Serra Negra, Maranhão State, Brazil. For this, wooden trap-nests of 6, 8, 10, 12, 14 and 16 mm in diameter were used; a total of 300 trap-nests were placed in the gallery forest and Cerrado areas, respectively. Traps were monitored monthly and all completed nests were collected and replaced with empty ones. The nests were then taken to the laboratory to analyze bee development and emergence, nests characteristics and parasites presence. The species used 29 of the trap-nests, which had diameters of 8, 10, 12 and 14 mm. A total of 87 C. dichrootricha specimens emerged. The nests were parasitized by two bee species, Mesocheira bicolor (Apinae) and Coelioxys sp. (Megachilinae), and one fly species, Antrax sp. (Diptera). The highest nesting incidence of 72.4 % was observed in the gallery forest, whereas only 27.6 % in the Cerrado; this difference in habitat use was significant (χ² = 5.56; p < 0.05; DF = 1). For the nests that were built in the gallery forest, 80.9% of the soil originated from the Cerrado. The females were significantly larger than the males (F1, 76 = 595.19; p < 0.001). There were 11 pollen types that belonged to six families. Pollen of the family Malpighiaceae was most frequently used, with four species represented (Byrsonima crassifolia, B. rotunda, B. spicata and Heteropterys sp.). C. dichrootricha showed a preference for nesting in cavities of various diameters in gallery forest sites. The present study provides a novel description of the nesting habits and biology of C. dichrootricha in habitats of Central/Southern Maranhão. C. dichrootricha primarily used resources from the Cerrado, including soil to build their nests, pollen and floral oils; we concluded that gallery forest and Cerrado areas are intrinsically related to the maintenance of local populations of this species.
Assuntos
Abelhas/fisiologia , Florestas , Comportamento de Nidação/fisiologia , Distribuição Animal , Animais , Brasil , Feminino , Masculino , Pólen/classificação , Estações do Ano , Distribuição por Sexo , Fatores Sexuais , Especificidade da Espécie , Fatores de TempoRESUMO
Hydrolysis of xyloglucan from Tamarindus indica and Hymenaea courbaril seeds with endoglucanase (EGII), which randomly breaks the (1â4)-linked ß-glycosidic bonds of the polymer chain, was monitored in real time using time-dependent viscometry analysis (TDV). For both samples there was a decrease in the intrinsic viscosity ([η]), viscosity average molar mass (Mv), radius de gyration (Rg) and persistence length (Lp) immediately after the addition of the enzyme. It was observed the formation of oligosaccharides and oligomers composed of â¼2 units, up to 140min. Galactose-containing side chains two positions away from the non-substituted glucose, modulated the action of EGII, and the complete hydrolysis of the XG oligomers occurred after 24h. The results demonstrate for the first time the real-time degradation of xyloglucan as well the macromolecular and oligosaccharide composition during the EGII hydrolysis process.
Assuntos
Celulase/química , Glucanos/química , Xilanos/química , Cromatografia , Hidrólise , Fatores de Tempo , ViscosidadeRESUMO
BACKGROUND: Silicosis is an occupational disease for which no effective treatment is currently known. Systemic administration of bone marrow-derived mononuclear cells (BMDMCs) has shown to be safe in lung diseases. However, so far, no studies have analyzed whether bronchoscopic instillation of autologous BMDMCs is a safe route of administration in patients with silicosis. METHODS: We conducted a prospective, non-randomized, single-center longitudinal study in five patients. Inclusion criteria were age 18-50 years, chronic and accelerated silicosis, forced expiratory volume in 1 s <60 % and >40 %, forced vital capacity ≥60 % and arterial oxygen saturation >90 %. The exclusion criteria were smoking, active tuberculosis, neoplasms, autoimmune disorders, heart, liver or renal diseases, or inability to undergo bronchoscopy. BMDMCs were administered through bronchoscopy (2 × 10(7) cells) into both lungs. Physical examination, laboratory evaluations, quality of life questionnaires, computed tomography of the chest, lung function tests, and perfusion scans were performed before the start of treatment and up to 360 days after BMDMC therapy. Additionally, whole-body and planar scans were evaluated 2 and 24 h after instillation. RESULTS: No adverse events were observed during and after BMDMC administration. Lung function, quality of life and radiologic features remained stable throughout follow-up. Furthermore, an early increase of perfusion in the base of both lungs was observed and sustained after BMDMC administration. CONCLUSION: Administration of BMDMCs through bronchoscopy appears to be feasible and safe in accelerated and chronic silicosis. This pilot study provides a basis for prospective randomized trials to assess the efficacy of this treatment approach. CLINICAL TRIALS. GOV IDENTIFIER: NCT01239862 Date of Registration: November 10, 2010.
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Transplante de Medula Óssea/métodos , Broncoscopia/métodos , Leucócitos Mononucleares/transplante , Pulmão/diagnóstico por imagem , Silicose/terapia , Adulto , Transplante de Medula Óssea/efeitos adversos , Estudos de Viabilidade , Citometria de Fluxo , Volume Expiratório Forçado , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão , Projetos Piloto , Estudos Prospectivos , Capacidade de Difusão Pulmonar , Tomografia Computadorizada de Emissão de Fóton Único , Capacidade Pulmonar Total , Transplante Autólogo , Capacidade VitalRESUMO
INTRODUCTION: Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and represents 3-4% of the malignant neoplasms that affect this gland. Approximately 25% of these cases are hereditary due to activating mutations in the REarranged during Transfection (RET) proto-oncogene. The course of MTC is indolent, and survival rates depend on the tumor stage at diagnosis. The present article describes clinical evidence-based guidelines for the diagnosis, treatment, and follow-up of MTC. OBJECTIVE: The aim of the consensus described herein, which was elaborated by Brazilian experts and sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism, was to discuss the diagnosis, treatment, and follow-up of individuals with MTC in accordance with the latest evidence reported in the literature. MATERIALS AND METHODS: After clinical questions were elaborated, the available literature was initially surveyed for evidence in the MedLine-PubMed database, followed by the Embase and Scientific Electronic Library Online/Latin American and Caribbean Health Science Literature (SciELO/Lilacs) databases. The strength of evidence was assessed according to the Oxford classification of evidence levels, which is based on study design, and the best evidence available for each question was selected. RESULTS: Eleven questions corresponded to MTC diagnosis, 8 corresponded to its surgical treatment, and 13 corresponded to follow-up, for a total of 32 recommendations. The present article discusses the clinical and molecular diagnosis, initial surgical treatment, and postoperative management of MTC, as well as the therapeutic options for metastatic disease. CONCLUSIONS: MTC should be suspected in individuals who present with thyroid nodules and family histories of MTC, associations with pheochromocytoma and hyperparathyroidism, and/or typical phenotypic characteristics such as ganglioneuromatosis and Marfanoid habitus. Fine-needle nodule aspiration, serum calcitonin measurements, and anatomical-pathological examinations are useful for diagnostic confirmation. Surgery represents the only curative therapeutic strategy. The therapeutic options for metastatic disease remain limited and are restricted to disease control. Judicious postoperative assessments that focus on the identification of residual or recurrent disease are of paramount importance when defining the follow-up and later therapeutic management strategies.
Assuntos
Biomarcadores Tumorais/sangue , Calcitonina/sangue , Carcinoma Medular/diagnóstico , Carcinoma Medular/terapia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/terapia , Biomarcadores/análise , Biópsia por Agulha Fina , Brasil , Calcitonina/metabolismo , Carcinoma Medular/secundário , Carcinoma Neuroendócrino , Diagnóstico Diferencial , Medicina Baseada em Evidências/métodos , Saúde da Família , Seguimentos , Humanos , Mutação , Feocromocitoma/diagnóstico , Feocromocitoma/metabolismo , Feocromocitoma/terapia , Prognóstico , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/secundário , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia/métodosRESUMO
Introdução O carcinoma medular de tireoide (CMT) origina-se das células parafoliculares da tireoide e corresponde a 3-4% das neoplasias malignas da glândula. Aproximadamente 25% dos casos de CMT são hereditários e decorrentes de mutações ativadoras no proto-oncogene RET (REarranged during Transfection). O CMT é uma neoplasia de curso indolente, com taxas de sobrevida dependentes do estádio tumoral ao diagnóstico. Este artigo descreve diretrizes baseadas em evidências clínicas para o diagnóstico, tratamento e seguimento do CMT. Objetivo O presente consenso, elaborado por especialistas brasileiros e patrocinado pelo Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia, visa abordar o diagnóstico, tratamento e seguimento dos pacientes com CMT, de acordo com as evidências mais recentes da literatura. Materiais e métodos: Após estruturação das questões clínicas, foi realizada busca das evidências disponíveis na literatura, inicialmente na base de dados do MedLine-PubMed e posteriormente nas bases Embase e SciELO – Lilacs. A força das evidências, avaliada pelo sistema de classificação de Oxford, foi estabelecida a partir do desenho de estudo utilizado, considerando-se a melhor evidência disponível para cada questão. Resultados Foram definidas 11 questões sobre o diagnóstico, 8 sobre o tratamento cirúrgico e 13 questões abordando o seguimento do CMT, totalizando 32 recomendações. Como um todo, o artigo aborda o diagnóstico clínico e molecular, o tratamento cirúrgico inicial, o manejo pós-operatório e as opções terapêuticas para a doença metastática. Conclusões O diagnóstico de CMT deve ser suspeitado na presença de nódulo tireoidiano e história ...
Introduction Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and represents 3-4% of the malignant neoplasms that affect this gland. Approximately 25% of these cases are hereditary due to activating mutations in the REarranged during Transfection (RET) proto-oncogene. The course of MTC is indolent, and survival rates depend on the tumor stage at diagnosis. The present article describes clinical evidence-based guidelines for the diagnosis, treatment, and follow-up of MTC. Objective The aim of the consensus described herein, which was elaborated by Brazilian experts and sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism, was to discuss the diagnosis, treatment, and follow-up of individuals with MTC in accordance with the latest evidence reported in the literature. Materials and methods: After clinical questions were elaborated, the available literature was initially surveyed for evidence in the MedLine-PubMed database, followed by the Embase and Scientific Electronic Library Online/Latin American and Caribbean Health Science Literature (SciELO/Lilacs) databases. The strength of evidence was assessed according to the Oxford classification of evidence levels, which is based on study design, and the best evidence available for each question was selected. Results Eleven questions corresponded to MTC diagnosis, 8 corresponded to its surgical treatment, and 13 corresponded to follow-up, for a total of 32 recommendations. The present article discusses the clinical and molecular diagnosis, initial surgical treatment, and postoperative management of MTC, as well as the therapeutic options for metastatic disease. Conclusions 7 .
Assuntos
Humanos , Calcitonina/sangue , Carcinoma Medular/diagnóstico , Carcinoma Medular/terapia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Biomarcadores Tumorais/sangue , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/terapia , Biópsia por Agulha Fina , Brasil , Biomarcadores/análise , Calcitonina/metabolismo , Carcinoma Medular/secundário , Diagnóstico Diferencial , Medicina Baseada em Evidências/métodos , Saúde da Família , Seguimentos , Mutação , Prognóstico , Feocromocitoma/diagnóstico , Feocromocitoma/metabolismo , Feocromocitoma/terapia , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/secundário , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia/métodosRESUMO
Differently from most hormones, which commonly are specialized molecules able to influence other cells, tissues and systems, thyroid hormones (TH) are pleiotropic peptides, whose primordial function is difficult to identify. The complex action of TH on human economy can be easily witnessed by examining the diverse consequences of TH excess and deficiency during development and after maturity. In particular, different manifestations in bone modeling and remodeling reflect the circumstantial consequences of thyroid disturbances, which are age dependent. While hyperthyroidism during childhood enhances bone mineralization and accelerates epiphyseal maturation, in adults it induces bone loss by predominant activation of osteoclast activity. Furthermore, the syndrome of TH resistance is a multifaceted condition in which different sites exhibit signs of hormone excess or deficiency depending on the configuration of the TH receptor isoform. The investigation of the impact of TH resistance on the skeleton still remains to be elucidated. We present here a thorough review of the action of TH on bone and of the impact of thyroid disorders, including hyper- and hypothyroidism and the syndrome of TH resistance, on the skeleton.
Assuntos
Osso e Ossos/metabolismo , Hipotireoidismo/metabolismo , Minerais/metabolismo , Síndrome da Resistência aos Hormônios Tireóideos/metabolismo , Tireotoxicose/metabolismo , Animais , Calcificação Fisiológica/fisiologia , Cálcio/metabolismo , Bases de Dados Bibliográficas , Epífises/crescimento & desenvolvimento , Humanos , Osteoclastos/metabolismo , Osteoporose/etiologia , Fósforo/metabolismo , Doenças da Glândula Tireoide/metabolismo , Tireotoxicose/complicações , Tiroxina/metabolismo , Tri-Iodotironina/metabolismoRESUMO
Differently from most hormones, which commonly are specialized molecules able to influence other cells, tissues and systems, thyroid hormones (TH) are pleiotropic peptides, whose primordial function is difficult to identify. The complex action of TH on human economy can be easily witnessed by examining the diverse consequences of TH excess and deficiency during development and after maturity. In particular, different manifestations in bone modeling and remodeling reflect the circumstantial consequences of thyroid disturbances, which are age dependent. While hyperthyroidism during childhood enhances bone mineralization and accelerates epiphyseal maturation, in adults it induces bone loss by predominant activation of osteoclast activity. Furthermore, the syndrome of TH resistance is a multifaceted condition in which different sites exhibit signs of hormone excess or deficiency depending on the configuration of the TH receptor isoform. The investigation of the impact of TH resistance on the skeleton still remains to be elucidated. We present here a thorough review of the action of TH on bone and of the impact of thyroid disorders, including hyper- and hypothyroidism and the syndrome of TH resistance, on the skeleton.
Diferentemente da maioria dos hormônios, que usualmente são moléculas especializadas capazes de influenciar outras células, tecidos e sistemas, os hormônios da tireoide (HT) são peptídeos pleiotrópicos, cuja função primordial é difícil de identificar. A ação complexa dos HT na fisiologia humana pode ser facilmente reconhecida ao observar as diversas consequências do excesso e da deficiência de HT durante e após o pleno desenvolvimento. Em particular as diferentes manifestações na modelação e remodelação óssea refletem que as consequências esqueléticas das disfunções tireoidianas dependem das circunstâncias e variam com a idade. Enquanto o hipertireoidismo durante a infância aumenta a mineralização óssea e acelera a maturação epifisária, em adultos induz a perda óssea pela ativação predominante da ação osteoclástica. Além disso, a síndrome de resistência ao HT é uma condição multifacetada na qual diferentes tecidos apresentam sinais de excesso ou deficiência hormonal, dependendo da predominância da expressão das diversas isoformas do receptor de HT. O impacto da resistência ao HT sobre o esqueleto ainda é motivo de investigação. Apresentamos aqui uma revisão abrangente sobre as ações ósseas dos HT e o impacto no esqueleto dos distúrbios da tireoide, incluindo hipo e hipertireoidismo e síndrome de resistência ao HT.
Assuntos
Animais , Humanos , Osso e Ossos/metabolismo , Hipotireoidismo/metabolismo , Minerais/metabolismo , Síndrome da Resistência aos Hormônios Tireóideos/metabolismo , Tireotoxicose/metabolismo , Calcificação Fisiológica/fisiologia , Cálcio/metabolismo , Bases de Dados Bibliográficas , Epífises/crescimento & desenvolvimento , Osteoclastos/metabolismo , Osteoporose/etiologia , Fósforo/metabolismo , Doenças da Glândula Tireoide/metabolismo , Tireotoxicose/complicações , Tiroxina/metabolismo , Tri-Iodotironina/metabolismoRESUMO
We evaluated the outcome of the retrograde endovascular hypogastric artery preservation (REHAP) technique for the treatment of complex aortoiliac aneurysms (AIAs). Perioperative and long-term outcomes were assessed for 12 patients (mean age 77 years, range 64-86 years) who underwent elective endovascular AIA repair via aortouniiliac endografting and REHAP between January 2004 and January 2011. Preoperative images obtained by computed tomography were used for planning. Postoperative images were obtained one and six months after surgery, and once a year thereafter. Technical success was achieved in all cases. No patients exhibited endoleak related to the endoprosthesis, occlusion of implanted components, hip and/or buttock claudication, or colon or spinal cord ischemia during follow-up. This hybrid procedure illustrates the potential of REHAP in the treatment of AIA cases.