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BACKGROUND: Diffuse invasion remains a primary cause of treatment failure in pediatric high-grade glioma (pHGG). Identifying cellular driver(s) of pHGG invasion is needed for anti-invasion therapies. METHODS: Ten highly invasive patient-derived orthotopic xenograft (PDOX) models of pHGG were subjected to isolation of matching pairs of invasive (HGGINV) and tumor core (HGGTC) cells. RESULTS: pHGGINV cells were intrinsically more invasive than their matching pHGGTC cells. CSC profiling revealed co-positivity of CD133 and CD57 and identified CD57+CD133- cells as the most abundant CSCs in the invasive front. In addition to discovering a new order of self-renewal capacities, i.e., CD57+CD133- > CD57+CD133+ > CD57-CD133+ > CD57-CD133- cells, we showed that CSC hierarchy was impacted by their spatial locations, and the highest self-renewal capacities were found in CD57+CD133- cells in the HGGINV front (HGGINV/CD57+CD133- cells) mediated by NANOG and SHH over-expression. Direct implantation of CD57+ (CD57+/CD133- and CD57+/CD133+) cells into mouse brains reconstituted diffusely invasion, while depleting CD57+ cells (i.e., CD57-CD133+) abrogated pHGG invasion. CONCLUSION: We revealed significantly increased invasive capacities in HGGINV cells, confirmed CD57 as a novel glioma stem cell marker, identified CD57+CD133- and CD57+CD133+ cells as a new cellular driver of pHGG invasion and suggested a new dual-mode hierarchy of HGG stem cells.
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Antígeno AC133 , Neoplasias Encefálicas , Antígenos CD57 , Glioma , Invasividade Neoplásica , Células-Tronco Neoplásicas , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo , Humanos , Animais , Glioma/patologia , Glioma/imunologia , Glioma/metabolismo , Camundongos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Antígenos CD57/metabolismo , Criança , Antígeno AC133/metabolismoRESUMO
BACKGROUND: Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It's capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM. MATERIALS AND METHODS: 23 patient tumor samples were implanted into the brains of NOD/SCID mice (1 × 105 cells/mouse). Tumor histology, gene expression (RNAseq), and growth rate of the developed patient-derived orthotopic xenograft (PDOX) models were compared with the originating patient tumors during serial subtransplantations. Anti-tumor activities of SVV-001 were examined in vivo; and therapeutic efficacy validated in vivo via single i.v. injection (1 × 1011 viral particle) with or without fractionated (2 Gy/day x 5 days) radiation followed by analysis of animal survival times, viral infection, and DNA damage. RESULTS: PDOX formation was confirmed in 17/23 (73.9%) GBMs while maintaining key histopathological features and diffuse invasion of the patient tumors. Using differentially expressed genes, we subclassified PDOX models into proneural, classic and mesenchymal groups. Animal survival times were inversely correlated with the implanted tumor cells. SVV-001 was active in vitro by killing primary monolayer culture (4/13 models), 3D neurospheres (7/13 models) and glioma stem cells. In 2/2 models, SVV-001 infected PDOX cells in vivo without harming normal brain cells and significantly prolonged survival times in 2/2 models. When combined with radiation, SVV-001 enhanced DNA damages and further prolonged animal survival times. CONCLUSION: A panel of 17 clinically relevant and molecularly annotated PDOX modes of GBM is developed, and SVV-001 exhibited strong anti-tumor activities in vitro and in vivo.
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Neoplasias Encefálicas , Glioblastoma , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Animais , Camundongos , Glioblastoma/radioterapia , Glioblastoma/metabolismo , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos NOD , Camundongos SCID , Modelos Animais de Doenças , Linhagem Celular TumoralRESUMO
Glioblastoma multiforme (GBM) is a highly aggressive malignancy and represents the most common brain tumor in adults. To better understand its biology for new and effective therapies, we examined the role of GDP-mannose pyrophosphorylase B (GMPPB), a key unit of the GDP-mannose pyrophosphorylase (GDP-MP) that catalyzes the formation of GDP-mannose. Impaired GMPPB function will reduce the amount of GDP-mannose available for O-mannosylation. Abnormal O-mannosylation of alpha dystroglycan (α-DG) has been reported to be involved in cancer metastasis and arenavirus entry. Here, we found that GMPPB is highly expressed in a panel of GBM cell lines and clinical samples and that expression of GMPPB is positively correlated with the WHO grade of gliomas. Additionally, expression of GMPPB was negatively correlated with the prognosis of GBM patients. We demonstrate that silencing GMPPB inhibits the proliferation, migration, and invasion of GBM cells both in vitro and in vivo and that overexpression of GMPPB exhibits the opposite effects. Consequently, targeting GMPPB in GBM cells results in impaired GBM tumor growth and invasion. Finally, we identify that the Hippo/MMP3 axis is essential for GMPPB-promoted GBM aggressiveness. These findings indicate that GMPPB represents a potential novel target for GBM treatment.
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Neoplasias Encefálicas , Inativação Gênica , Glioblastoma , Adulto , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/metabolismo , Manose , Metaloproteinase 3 da Matriz/metabolismoRESUMO
Bacteremia due to gram-negative bacilli (GNB) is one of the most frequent causes of admission and prolongation of hospital stay. Nevertheless, optimal duration of antibiotic treatment is not clearly established. We designed an observational, prospective study of a cohort of adult patients with uncomplicated GNB bacteremia. They were classified according to the duration of treatment in short (7-10 days) or long (> 10 days) course. Mortality and bacteremia recurrence rate were evaluated, and propensity score for receiving short-course treatment was calculated. A total of 395 patients met eligibility criteria including 232 and 163 who received long- and short-course therapy, respectively. Median age was 71 years, 215 (54.4% male) and 51% had a urinary source. Thirty-day mortality was 12%. In multivariate analysis by logistic regression stratified according to propensity score quartile for receiving short-course therapy showed no association of duration of treatment with 30-day mortality or 90-day recurrence rate. Based on the results observed in our cohort, short-course therapy could be as safe and effective as longer courses.
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Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Estudos de Coortes , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Due to its long half-life, dalbavancin offers benefits for long-duration treatments, especially osteoarticular and infective endocarditis (IE). We evaluated the efficacy and costs of IE treatment, comparing dalbavancin with standard of care (SOC). METHODS: Retrospective multicenter cohort study of adult patients with Gram-positive cocci definite IE. Dalbavancin was used as a sequential therapy before discharge. Efficacy was a combined variable of clinical cure and absence of recurrence in 12-month follow-up. Length of hospital stay and the associated costs were analyzed in both groups of treatment. RESULTS: Twenty-two patients received dalbavancin and 47 SOC. The efficacy was similar between the groups (dalbavancin 18 [72%] vs SOC 44 [94%], P = 0.198). Hospital stay was shorter in the dalbavancin group (dalbavancin 22 days [16-34] vs SOC 37 days [23-49], P = 0.001), especially in those with E. faecalis IE (dalbavancin 30 days [20-36] vs SOC 65 days [46-74], P <0.001). A reduction of cost was observed between both groups (dalbavancin, 12,206 [8998-17,283] vs SOC 16,249 [11,496-22,367], P = 0.032). CONCLUSION: Dalbavancin could be a safe and effective option in the sequential treatment of patients with IE. Also, a cost reduction was detected, due to a significant shortness of hospital stay.
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Endocardite Bacteriana , Endocardite , Adulto , Humanos , Antibacterianos/efeitos adversos , Estudos de Coortes , Padrão de Cuidado , Estudos Retrospectivos , Teicoplanina/efeitos adversos , Endocardite Bacteriana/tratamento farmacológico , Endocardite/tratamento farmacológico , Custos e Análise de CustoRESUMO
Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models. Methods: We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice. Results: Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% in high-grade glioma, 64.2% in medulloblastoma, 50% in ATRT, 33.8% in ependymoma, and 11.6% in low-grade gliomas. Detailed characterization confirmed their replication of the histopathological and genetic abnormalities of the original patient tumors. Conclusions: The protocol is easy to follow, without a sterotactic frame, in order to generate large cohorts of tumor-bearing mice to meet the needs of biological studies and preclinical drug testing.
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For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of preclinical cancer models and are even finding their way into clinical practice as part of functional precision medicine programs. The PDMC Consortium, supported by the Division of Cancer Biology in the National Cancer Institute of the National Institutes of Health, seeks to understand the biological principles that govern the various PDMC behaviors, particularly in response to perturbagens, such as cancer therapeutics. Based on collective experience from the consortium groups, we provide insight regarding PDMCs established both in vitro and in vivo, with a focus on practical matters related to developing and maintaining key cancer models through a series of vignettes. Although every model has the potential to offer valuable insights, the choice of the right model should be guided by the research question. However, recognizing the inherent constraints in each model is crucial. Our objective here is to delineate the strengths and limitations of each model as established by individual vignettes. Further advances in PDMCs and the development of novel model systems will enable us to better understand human biology and improve the study of human pathology in the lab.
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Positron emission tomography (18FDG PET-CT) is a widely used method to help in the diagnosis of infective endocarditis (IE). Lipomatous hypertrophy of the interatrial septum (LHIS) is an uncommon fat deposition in the region of the interatrial septum. PET-CT images of LHIS may be indistinguishable from changes associated with IE.
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Introduction: Recurrent Aphthous Stomatitis, also known as aphthous ulcers or simply aphthous, is considered the most common of oral mucosal lesions. Objective: To describe the prevalence of recurrent aphthous stomatitis. Methods: Descriptive, cross-sectional and prospective study. 847 patients who attended the Family Medical Office No. 28, San Francisco comunity, Manzanillo, from July 1, 2021 to June 30, 2022, Cuba, were evaluated. A calibrated and trained assistant investigator evaluated the following variables: Clinical classification of recurrent aphthous stomatitis (minor aphthosis, major aphthosis, or aphthosis herpetiformis), lesion pain intensity, lesion location, and risk factors (viral infection), bacterial infection, immunological alterations, psychosomatic alterations, oral trauma, gastrointestinal alterations, endocrine factors, allergic conditions, heredity, blood and nutritional deficiencies, smoking), age group, sex, race, and duration of the lesion. Results: Aphthous stomatitis occurred in 30.46%, with greater frequency in the age group 30 - 39 years (24.42%). Minor aphthosis was the most frequent with 91.09%. The duration of the lesion of 10 to 12 days predominated with 37.60%, the most frequent location corresponded to the edge and tip of the tongue with 32.94% and the most representative pain intensity was mild with a total of 63.18%. The highest frequency among the risk factors corresponded to psychosomatic alterations with 100%. Conclusions: Recurrent Aphthous Stomatitis had a prevalence greater than 30% with a predominance of the female sex and young adults. Minor Aphtosis and a stay time of more than 10 days were the most frequent. The most common location is the tongue and bottom of the vestibular sulcus with the possible existence of a relationship between the mobile parts of the mouth. Stress, the main risk factor, exacerbated by Covid-19.
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The MAPK-interacting kinases 1 and 2 (MNK1/2) have generated increasing interest as therapeutic targets for acute myeloid leukemia (AML). We evaluated the therapeutic potential of the highly-selective MNK1/2 inhibitor Tomivosertib on AML cells. Tomivosertib was highly effective at blocking eIF4E phosphorylation on serine 209 in AML cells. Such inhibitory effects correlated with dose-dependent suppression of cellular viability and leukemic progenitor colony formation. Moreover, combination of Tomivosertib and Venetoclax resulted in synergistic anti-leukemic responses in AML cell lines. Mass spectrometry studies identified novel putative MNK1/2 interactors, while in parallel studies we demonstrated that MNK2 - RAPTOR - mTOR complexes are not disrupted by Tomivosertib. Overall, these findings demonstrate that Tomivosertib exhibits potent anti-leukemic properties on AML cells and support the development of clinical translational efforts involving the use of this drug, alone or in combination with other therapies for the treatment of AML.
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OBJECTIVES: Acute cholangitis is one of the most frequent complications in patients carrying biliary stents. The aim of our study is to analyze the demographic and clinical characteristics, as well as the microbiological profile and evolution of patients with acute bacteremic cholangitis, comparing them based upon they were or not biliary stent carriers. METHODS: We performed a retrospective analysis of all consecutive patients over 18 years-old with a stent placement in our center between 2008 and 2017 were included. We compared them with our prospective cohort of patients with a diagnosis of acute bacteremic cholangitis. Primary outcome was 30-day mortality. Secondary outcome was clinical cure at day 7, 14-day mortality and 90-day recurrence. RESULTS: Two hundred and seventy-three patients were analyzed, including 156 in the stent-related (SR) and 117 in the stent not-related (SNR) group, respectively. Stent-related colangitis patients were younger, with more comorbidities and with a greater severity of infection. Escherichia coli and Klebsiella pneumonia were the most frequent isolation. Enterococcus spp. was the third most frequent isolation in SR group but were uncommon in SNR patients; where E. coli was the most prevalent microorganism. Septic shock (HR 3.44, 95% [CI 1.18-8.77]), inadequate empirical treatment (HR 2.65, 95% CI [1.38-.7.98]) and advanced neoplasia (HR 2.41, 95% CI [1.55-6.44]) were independent 30-day mortality risk factors. The 90-day recurrence rate significantly higher in those patients with stent-related cholangitis (29% vs. 13%, p=0.016) and stent replacement was associated with lower recurrence rate (HR 0.38, 95% CI [0.11-0.77]). CONCLUSIONS: Clinical and microbiological profile, as well as outcome of patients with SR and SNR cholangitis were different. In SR group, recurrence rate was high and stent replacement was associated with a lower risk.
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Colangite , Escherichia coli , Adolescente , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , StentsRESUMO
BACKGROUND: Treatment optimization for serious infections, such as Staphylococcus aureus bacteremia (SAB), is a challenge for antimicrobial stewardship teams. Currently, SAB guidelines recommend a completely intravenous therapy (CIT). OBJECTIVES: The objective of the study was to analyze the usefulness and safety of oral sequential therapy (OST) in SAB. PATIENTS AND METHODS: We conducted a retrospective, observational study in a tertiary teaching hospital in Spain. The inclusion criteria were complicated and non-complicated monomicrobial SAB and an adequate duration of therapy, with patients classified into OST or CIT. The primary endpoint was the 90-day recurrence of S. aureus infection. We also analyzed the mortality, the length of the hospital stay, and the duration of the intravenous antibiotic administration. RESULTS: Of a total of 201 patients with SAB, 125 (62%) underwent OST. The most commonly administered oral antibiotic was trimethoprim-sulfamethoxazole (66% of patients). Of those administered OST, 43% had complicated bacteremia (most with an osteoarticular source of infection), and 6% had an intravascular device. The 90-day recurrence rate was 4%, with no differences between the two groups. The duration of the therapy (22 [16-28] vs. 13 days [8-17] for CIT and OST, respectively; p < 0.001) and the hospital stay (36 [27-71] vs. 18 days [13-29] for CIT and OST, respectively; p < 0.001) were shorter for OST. MRSA was related with mortality (OR 4.4, 95% CI [1.67-11.37]; p = 0.003). CONCLUSIONS: OST for properly selected patients with SAB could be a safe therapeutic option and can reduce their use of CIT and their hospital stay.
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Antibacterianos/administração & dosagem , Gestão de Antimicrobianos , Bacteriemia/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Administração Intravenosa , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Centros de Atenção TerciáriaRESUMO
OBJECTIVES: Acute cholangitis is one of the most frequent complications in patients carrying biliary stents. The aim of our study is to analyze the demographic and clinical characteristics, as well as the microbiological profile and evolution of patients with acute bacteremic cholangitis, comparing them based upon they were or not biliary stent carriers. METHODS: We performed a retrospective analysis of all consecutive patients over 18 years-old with a stent placement in our center between 2008 and 2017 were included. We compared them with our prospective cohort of patients with a diagnosis of acute bacteremic cholangitis. Primary outcome was 30-day mortality. Secondary outcome was clinical cure at day 7, 14-day mortality and 90-day recurrence. RESULTS: Two hundred and seventy-three patients were analyzed, including 156 in the stent-related (SR) and 117 in the stent not-related (SNR) group, respectively. Stent-related colangitis patients were younger, with more comorbidities and with a greater severity of infection. Escherichia coli and Klebsiella pneumonia were the most frequent isolation. Enterococcus spp. was the third most frequent isolation in SR group but were uncommon in SNR patients; where E. coli was the most prevalent microorganism. Septic shock (HR 3.44, 95% [CI 1.18-8.77]), inadequate empirical treatment (HR 2.65, 95% CI [1.38-.7.98]) and advanced neoplasia (HR 2.41, 95% CI [1.55-6.44]) were independent 30-day mortality risk factors. The 90-day recurrence rate significantly higher in those patients with stent-related cholangitis (29% vs. 13%, p=0.016) and stent replacement was associated with lower recurrence rate (HR 0.38, 95% CI [0.11-0.77]). CONCLUSIONS: Clinical and microbiological profile, as well as outcome of patients with SR and SNR cholangitis were different. In SR group, recurrence rate was high and stent replacement was associated with a lower risk.
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BACKGROUND: In recent years, several scores and algorithms have been developed in order to guide empirical antibiotic treatment in patients with gram-negative bacilli (GNB) bacteraemia according to the risk of extended-spectrum ß-lactamase (BL) producing. Some of these algorithms do not have easy applicability or present some limitations in their validation. The aim of our study was to validate a recently designed decision tree in our prospective cohort of bacteraemia due to gram-negative bacilli. METHODS: We prospectively identified and analyzed all bacteraemia due to gram-negative bacilli in adult patients in our centre between January 2015 and December 2016. Previously developed clinical decision tree was used to classify patients in each of the terminal nodes. Patients were classified as BL group according to whether they were producers of any type of BL. The statistical power of the tree was analyzed by receiver operating characteristics (ROC) curve and by calculation of C-statistics. RESULTS: A total of 448 episodes of bacteraemia were included; 132 (29.5%) were BL group; 68 (15.1%) ESBL producing, 43 (9.6%) due to AmpC and 21 (4.7%) isolates of Pseudomonas aeruginosa. The original clinical decision tree was modified according to the results of our multivariate analysis. The modified tree has a sensitivity of 71%, specificity of 92%, predictive positive value (PPV) of 79% and predictive negative value (NPV) of 88% generating an ROC curve with a C-statistic of 0.76. CONCLUSIONS: An easy-to-apply clinical decision tree could be used at the exact moment of diagnosis and adjust the empirical antibiotic treatment in patients with gram-negative bacilli bacteraemia.
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Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Técnicas de Apoio para a Decisão , Árvores de Decisões , Bactérias Gram-Negativas/enzimologia , Infecções por Bactérias Gram-Negativas/diagnóstico , beta-Lactamases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Adulto Jovem , Resistência beta-LactâmicaRESUMO
Introducción: La hemorragia obstétrica es considerada una causa mayor de mortalidad materna. El reconocimiento de las mujeres con riesgo de desarrollar complicaciones durante la hemorragia obstétrica, es la primera acción para promover un tratamiento optimizado y evitar la muerte. Objetivo: Identificar los factores de riesgo de complicaciones en pacientes con hemorragia obstétrica. Métodos: Estudio observacional, analítico de casos y controles, con 12 casos (con complicaciones) y 24 controles (sin complicaciones). Se aplicó las medidas resúmenes para cada tipo de variables y la determinación de los factores de riesgos mediante la aplicación del odds ratio (OR), se utilizó el paquete estadístico SPSS versión 26.0, con un intervalo de confianza (IC) del 95 por ciento. Resultados: La combinación del choque hipovolémico, más la insuficiencia renal aguda, fue la complicación más frecuente para un 13,8 por ciento. Predominó la atonía uterina para un 50,0 por ciento como causa de hemorragia.Las variables predictivas de complicaciones fueron: el valor de creatinina ≥ 113 µmol/L (OR= 19,08; IC: 2,75-138,36), índice internacional normalizado ≥ 2 (OR= 4,66; IC: 1,46-14,90), hematocrito < 0,23 (OR= 4,00; IC: 1,76-9,08) y hemoglobina < 70 g/L (OR= 2,22; IC: 1,25-3,95). Conclusiones: La creatinina ≥ 113 µmol/L, índice internacional normalizado ≥ 2, hematocrito < 0,23 y hemoglobina < 70 g/L son los principales factores de riesgo identificados para el desarrollo de complicaciones durante la hemorragia obstétrica(AU)
Introduction: Obstetric hemorrhage is considered a major cause of maternal mortality. Recognition of women at risk of developing complications during obstetric hemorrhage is the first action to promote optimized treatment and avoid death. Objective: Identify risk factors for complications in patients with obstetric hemorrhage. Methods: Observational, analytical case-control study, with 12 cases (with complications) and 24 controls (without complications). The summary measures were applied for each type of variables and the determination of the risk factors by applying the odds ratio (OR), the SPSS statistical package version 26.0 was used, with a confidence interval (CI) of 95 percent. Results: The combination of hypovolemic shock, plus acute renal failure, was the most frequent complication for 13.8 percent. Uterine atony predominated for 50.0 percent as the cause of hemorrhage. The predictive variables of complications were: creatinine value ≥ 113 µmol/L (OR= 19.08; CI: 2.75-138.36), international normalized ratio ≥ 2 (OR= 4.66; CI: 1. 46-14.90), hematocrit < 0.23 (OR= 4.00; CI: 1.76-9.08) and hemoglobin < 70 g/L (OR= 2.22; CI: 1.25-3.95). Conclusions: Creatinine ≥ 113 µmol/L, international normalized ratio ≥ 2, hematocrit < 0.23 and hemoglobin < 70 g/L are the main risk factors identified for the development of complications during obstetric hemorrhage(AU)
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Humanos , Fatores de Risco , Hemorragia Pós-Parto/diagnóstico , Complicações do Trabalho de Parto/etiologia , Estudos de Casos e Controles , Estudo Observacional , Unidades de Terapia IntensivaRESUMO
BACKGROUND: Cutaneous leishmaniasis (CL) is a skin disease caused by the protozoan parasite Leishmania. Few studies have assessed the influence of the sample collection site within the ulcer and the sampling method on the sensitivity of parasitological and molecular diagnostic techniques for CL. Sensitivity of the technique can be dependent upon the load and distribution of Leishmania amastigotes in the lesion. METHODOLOGY/PRINCIPAL FINDINGS: We applied a quantitative real-time PCR (qPCR) assay for Leishmania (Viannia) minicircle kinetoplast DNA (kDNA) detection and parasite load quantification in biopsy and scraping samples obtained from 3 sites within each ulcer (border, base, and center) as well as in cytology brush specimens taken from the ulcer base and center. A total of 248 lesion samples from 31 patients with laboratory confirmed CL of recent onset (≤3 months) were evaluated. The kDNA-qPCR detected Leishmania DNA in 97.6% (242/248) of the examined samples. Median parasite loads were significantly higher in the ulcer base and center than in the border in biopsies (P<0.0001) and scrapings (P = 0.0002). There was no significant difference in parasite load between the ulcer base and center (P = 0.80, 0.43, and 0.07 for biopsy, scraping, and cytology brush specimens, respectively). The parasite load varied significantly by sampling method: in the ulcer base and center, the descending order for the parasite load levels in samples was: cytology brushes, scrapings, and biopsies (P<0.0001); in the ulcer border, scrapings had higher parasite load than biopsies (P<0.0001). There was no difference in parasite load according to L. braziliensis and L. peruviana infections (P = 0.4). CONCLUSION/SIGNIFICANCE: Our results suggest an uneven distribution of Leishmania amastigotes in acute CL ulcers, with higher parasite loads in the ulcer base and center, which has implications for bedside collection of diagnostic specimens. The use of scrapings and cytology brushes is recommended instead of the more invasive biopsy.
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DNA de Cinetoplasto/genética , Leishmania/genética , Leishmaniose Cutânea/parasitologia , Carga Parasitária , Úlcera Cutânea/parasitologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Leishmania/classificação , Leishmaniose Cutânea/patologia , Masculino , Pessoa de Meia-Idade , Úlcera Cutânea/patologia , Especificidade da Espécie , Adulto JovemRESUMO
RESUMEN La estomatitis aftosa recurrente es una enfermedad inflamatoria crónica. Se caracteriza por lesiones aftosas en la mucosa bucal. Para su tratamiento, se han introducido variadas terapéuticas como la terapia láser; un método sencillo, indoloro, no invasivo y cada vez más aceptado por los pacientes. Se presenta una paciente de 37 años de edad, atendida en la consulta estomatológica del Hospital Clínico-Quirúrgico Docente "Celia Sánchez Manduley", de Manzanillo, Granma; con aftas bucales de pequeño tamaño, de forma redondeada y bien delimitadas en la mucosa interna del labio inferior y en el surco vestibular a nivel de incisivos inferiores. Se comprueba la eficacia del láser en el tratamiento de la estomatitis aftosa recurrente; para brindar al paciente un estado general satisfactorio, contribuir a su mejoría definitiva en un período de 5 días en aftas menores y mejorar la calidad de vida de los pacientes durante su curación.
ABSTRACT Recurrent aphthous stomatitis is a chronic inflammatory disease characterized by aphthous lesions in the buccal mucosa. Various therapeutic methods like laser therapy have been recently introduced. This is a simple, painless, non-invasive method very much accepted by patients. We present a 37-year-old woman with small mouth sores, rounded and well-defined on the internal mucosa of the lower lip and in vestibular groove at the level of lower incisors, attended at the Stomatological Clinic of "Celia Sánchez Manduley" Clinical Surgical Teaching Hospital of Manzanillo, Granma. The effectiveness of laser in the recurrent aphthous stomatitis treatment was verified, to obtain a satisfactory general patient´s state and a 5 days effective improvement in minor aphthae, considering patients´ life quality during healing period.