ENDOSCOPIC EVALUATION OF POST-FUNDOPLICATION ANATOMY AND CORRELATION WITH SYMPTOMATOLOGY

​ Open in a separate windowEndoscopic aspect of fundoplication anatomy: Normal aspect of Nissen fundoplication     

Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial

BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)     

Effect of correcting for gestational age at birth on population prevalence of early childhood undernutrition

Background

Postmenstrual and/or gestational age-corrected age (CA) is required to apply child growth standards to children born preterm (< 37 weeks gestational age). Yet, CA is rarely used in epidemiologic studies in low- and middle-income countries (LMICs), which may bias population estimates of childhood undernutrition. To evaluate the effect of accounting for GA in the application of growth standards, we used GA-specific standards at birth (INTERGROWTH-21st newborn size standards) in conjunction with CA for preterm-born children in the application of World Health Organization Child Growth Standards postnatally (referred to as ‘CA’ strategy) versus postnatal age for all children, to estimate mean length-for-age (LAZ) and weight-for-age (WAZ) z scores at 0, 3, 12, 24, and 48-months of age in the 2004 Pelotas (Brazil) Birth Cohort.

Results

At birth (n = 4066), mean LAZ was higher and the prevalence of stunting (LAZ < ?2) was lower using CA versus postnatal age (mean ± SD): ? 0.36 ± 1.19 versus ? 0.67 ± 1.32; and 8.3 versus 11.6%, respectively. Odds ratio (OR) and population attributable risk (PAR) of stunting due to preterm birth were attenuated and changed inferences using CA versus postnatal age at birth [OR, 95% confidence interval (CI): 1.32 (95% CI 0.95, 1.82) vs 14.7 (95% CI 11.7, 18.4); PAR 3.1 vs 42.9%]; differences in inferences persisted at 3-months. At 12, 24, and 48-months, preterm birth was associated with stunting, but ORs/PARs remained attenuated using CA compared to postnatal age. Findings were similar for weight-for-age z scores.

Conclusions

Population-based epidemiologic studies in LMICs in which GA is unused or unavailable may overestimate the prevalence of early childhood undernutrition and inflate the fraction of undernutrition attributable to preterm birth.

     

Bauhinia forficata in the treatment of diabetes mellitus: a patent review

Introduction: Diabetes Mellitus has been considered an epidemic by the World Health Organization, with a high risk of morbidity and mortality. The treatment of this pathology consists in glycemic control, which can be done by oral hypoglycemic agents, insulin therapy, dietary guidance, regular physical activity, and psychosocial support. In addition, other adjuvant treatments are employed, such as phytotherapic, and one of the most used plants is Bauhinia forficata.

Areas covered: In the current review, patents using Bauhinia forficata for the Diabetes Mellitus treatment have been analyzed. There were 03 patents in WIPO, 01 in Espacenet, 01 in USPTO, and 02 in INPI.

Expert opinion: Patents on the adjuvant treatment of Diabetes Mellitus by Bauhinia forficata are discussed. Although there are some phytotherapy products containing this medicinal plant which has hypoglycemic effect here is still a need for the development of more products based on natural resources, for the treatment of this pathology, without side effects and with other benefits, to assist in the glycemia control in diabetic patients, and to improve their quality of life.     

Macromolecule nanotherapeutics: approaches and challenges

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Schematic illustration of the systemic delivery of macromolecules in the clinic using nanotherapeutics. After systemic administration of formulations, interaction can be with target cell surface (gold and iron oxide nanoparticles (NP)) or delivery system can be internalized. Endonuclease sensitive actives (siRNA, mRNA) are protected by encapsulation in delivery system. Target cell entry can be by interactions between targeting ligand on the surface of delivery system (surface functionalized cyclodextrin based NP) or by endocytosis (liposomes and nucleic acid coated gold NP). After endocytosis, delivery system can facilitate endosomal escape via endosome disruption. Protein expression occurs by translation of free mRNA in cytoplasm. For delivery systems with extracellular site of action, efficacy is achieved by initiating downstream signaling cascade. Cell surface ligands can be proteins or genetic material for extracellularly acting delivery systems.     

Drug therapies for polymyalgia rheumatica: a pharmacotherapeutic update

Introduction: Polymyalgia rheumatica (PMR), a common disease in individuals older than 50 in the western world, is characterized by bilateral inflammatory pain involving the shoulder girdle and less commonly the neck and pelvic girdle. The main goals of the currently available treatment are to induce remission and prevent relapse.

Areas covered: This review briefly presents the main epidemiological and clinical features of PMR and discusses in depth both its classical management as well as new therapies used in PMR.

Expert opinion: In general, patients with isolated PMR experience a rapid response (in less than seven days) to 12.5–25 mg/prednisone/day. Methotrexate is the conventional disease-modifying antirheumatic drug most commonly used for disease management, especially for relapses of the disease. However, this agent often yields a modest effect. Randomized controlled trials do not support the use of antitumor necrosis factor agents in PMR. Several case series and retrospective studies have highlighted the efficacy of the anti-interleukin-6 receptor antibody tocilizumab in PMR. However, controlled trials are needed to fully establish the efficacy of this biologic agent in PMR. The potential beneficial effect of the Janus-kinase inhibitors remains to be determined.     

A biomarker for tegumentary and visceral leishmaniasis based on a recombinant Leishmania hypothetical protein

The measures for leishmaniasis control include the precise diagnosis of disease. However, although several recombinant antigens have been tested with this biotechnological purpose, no effective product exists, which could detects patients with the active disease, as well as differentiates them from cured and treated patients. In this study, a conserved Leishmania hypothetical protein, which was identified in Leishmania infantum parasites, but evaluated to presents high homology in the amino acid sequences between distinct parasite species, was evaluated for the diagnosis of tegumentary and visceral leishmaniasis. In addition, PBMCs collected from treated and untreated mucosal leishmaniasis (ML) and visceral leishmaniasis (VL) patients, as well as in healthy subjects living in endemic region of disease, were in vitro stimulated, when IFN-γ, IL-4 and IL-10 levels were evaluated in the cell supernatant. Regarding the serological analyses, ELISA experiments using the recombinant protein (rLiHyL) and a human serological panel revealed high sensitivity and specificity values to detect both diseases, while control antigens showed worst results. Regarding the cellular response, results showed that rLiHyL-stimulated cells produced higher IFN-γ and lower IL-4 and IL-10 levels in the supernatants. Also, the anti-protein antibody production was evaluated in these patients, and data showed higher IgG2 and lower IgG1 levels found in the treated patients and healthy controls, demonstrating the stimulation of a Th1-type response induced by the rLiHyL protein. In conclusion, this hypothetical protein can be considered as antigenic in TL and VL, as well as a vaccine candidate to be tested in future studies to protect against disease.     

Detection of regulatory T cell phenotypic markers and cytokines in patients with human papillomavirus infection

Infection with human papillomavirus (HPV) is the main cause of cervical cancer. Viral persistence is considered the main risk factor for neoplastic progression and evidence suggests that regulatory T cells (Treg) play an important role in the failure of viral elimination. The aim of this study was to detect phenotypic markers of Treg and cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β, in the cervical microenvironment of HPV-infected patients. One hundred and one samples of uterine cervix embedded in paraffin were analyzed. We used immunohistochemistry to examine the coexpression of the CD25/FOXP3 and CD4/TGF-β markers, and the expression of GITR and IL-10 in cells present in the cervical stroma. We detected a microenvironment composed of high proportions of CD25⁺FOXP3⁺, CD4⁺TGFβ⁺, IL-10⁺, and GITR⁺ cells in samples with high viral loads and severe lesions of HPV-infected patients. The abundance of these markers, indicative of the presence of Treg cells and immunosuppressive cytokines, was significantly associated with severe lesions and elevated viral loads in the examined samples. These results suggest that Treg cells may be involved in maintaining a microenvironment favorable for viral persistence and neoplastic progression. Our findings support those of previous studies that suggested that these markers could be used to predict HPV persistence and neoplastic progression, and as potential targets for immune response modulation.     

Eryptosis of non-parasitized erythrocytes is related to anemia in Plasmodium berghei low parasitema malaria of Wistar rats

Parasitology Research - It is known that premature elimination of non-parasitized RBCs (nRBCs) plays an important role in the pathogenesis of malarial anemia, in which suicidal death process...