Schneidermccarty7489
BGFF MDI is the second FDC triple therapy approved for COPD treatment. BGFF MDI improves important patient outcomes in COPD, including exacerbation risk. The unique co-suspension technology allows delivery of 3 active ingredients in 1 inhaler, a potential benefit to overcome adherence and technique-related barriers. These benefits must be gently weighed against the increased risk of pneumonia.
The findings from phase 3 trials support the efficacy and safety of triple therapy in COPD. Future studies are needed to confirm potential mortality benefit and the role of triple therapy in patients without an exacerbation history.
The findings from phase 3 trials support the efficacy and safety of triple therapy in COPD. Future studies are needed to confirm potential mortality benefit and the role of triple therapy in patients without an exacerbation history.Acute corneal hydrops usually resolves alone or with medical therapy along the first 4-6 weeks. However, depending on the severity of the corneal edema or the size of the Descemet break, self-healing might be difficult. Years ago, those patients had no more options than corneal transplantation, but surgical alternatives are on the rise in this century. These surgeries are becoming more popular with a variety of techniques relegating penetrating keratoplasty to a residual role. These techniques aim to accelerate corneal healing, reduce the edema, improve visual acuity and prevent from severe complications that may appear if corneal hydrops is not treated rapidly. Feasibility and safety are the favorable aspects of these techniques since the complications rates described remain low. In this review, we emphasize the recently published studies that describe both the techniques and their results.
To analyse the morpho-functional outcomes of dexamethasone intravitreal implant (Ozurdex) injected after lens surgery in diabetic patients with coexisting cataract and macular oedema.
This is a non-randomized, perspective, single-group study on 17 eyes with a diagnosis of cataract and early and advanced diabetic macular oedema. All eyes underwent combined phacoemulsification and Ozurdex injection at the end of surgery and morpho-functional outcomes were analysed in 3 months follow-up.
Foveal thickness decreased significantly from 349.6 ± 19.8 (95% CI) at baseline to 310.7 ± 17.5 (95% CI) 90 days after surgery (
< 0.01).Mean BCVA (LogMAR) improved significantly from 0.38 ± 0.08 (95% CI) at baseline to 0.15 ± 0.06 (95% CI) after 90 days (
< 0.01). Any ocular or systemic complications were observed during follow-up.
Dexamethasone intravitreal implant combined with phacoemulsification may be safe and effective to improve morpho-functional outcomes in diabetic patients with coexisting cataract and macular oedema.
Dexamethasone intravitreal implant combined with phacoemulsification may be safe and effective to improve morpho-functional outcomes in diabetic patients with coexisting cataract and macular oedema.
Pituitary resistance to thyroid hormone (PRTH) is often seen in congenital hypothyroidism (CH), presenting as elevated TSH values despite (high-)normal TH values achieved by levothyroxine treatment. Here we describe a girl with CH who was referred because of difficulties interpreting thyroid function tests. She was thought to have PRTH associated with CH, but genetic studies discovered a pathogenic variant in THRB, causing resistance to TH (RTH-β).
Clinical, genetic and biochemical data of the proband's family were collected.
The three-year-old girl was diagnosed with CH due to a homozygous pathogenic c.470del p.(Asn157Thrfs*3) SLC5A5 variant in the neonatal period. She needed a notably high levothyroxine dose to normalize TSH, leading to high FT4 levels. There were no signs of hyperthyroidism. Sequencing identified a heterozygous pathogenic c.947G>A p.(Arg316His) THRB variant.
To our knowledge, this is the first report of concomitant SLC5A5 and THRB variants causing CH and RTH-β.
To our knowledge, this is the first report of concomitant SLC5A5 and THRB variants causing CH and RTH-β.
Acute myocardial infarction (MI), caused by acute coronary artery obstruction, is a common cardiovascular event leading to mortality. Nuclear dot protein 52 (NDP52) is an essential selective autophagy adaptor, although its function in MI is still obscure. This study was designed to examine the function of NDP52 in MI and the associated mechanisms.
Our results revealed that MI challenge overtly impaired myocardial geometry and systolic function, along with cardiomyocyte apoptosis, myocardial interstitial fibrosis, and mitochondrial damage, and NDP52 nullified such devastating responses. Further studies showed the blockade of mitochondrial clearance is related to MI-induced buildup of damaged mitochondria. Mechanistic approaches depicted that 7-day MI induced abnormal mitophagy flux, resulting in poor lysosomal clearance of injured mitochondria. NDP52 promoted mitophagy flux through recruitment of RAB7 and TBK1. Upon protein colocalization, TBK1 phosphorylated RAB7, in line with the finding that chloroquine or a TBK1 inhibitor reversed NDP52-dependent beneficial responses.
This study denoted a novel mechanism that NDP52 promotes cardioprotection against ischemic heart diseases through interaction with TBK1 and RAB7, leading to RAB7 phosphorylation, induction of mitophagy to clear ischemia-induced impaired mitochondria, thus preventing cardiomyocyte apoptosis in MI.
Our results indicate that NDP52 promotes autophagic flux and clears damaged mitochondria to diminish ROS and cell death in a TBK1/RAB7-dependent manner and thus limits MI induced injury.
Our results indicate that NDP52 promotes autophagic flux and clears damaged mitochondria to diminish ROS and cell death in a TBK1/RAB7-dependent manner and thus limits MI induced injury.Common methods for evaluating history of traumatic brain injury (TBI) include self-report, electronic medical record review (EMR), and structured interviews such as the Head Trauma Events Characteristics (HTEC). Each has strengths and weaknesses, but little is known regarding how TBI diagnostic rates or the associated symptom profile differ among them. This study examined 200 Veterans recruited within the VA Portland Health Care System, each evaluated for TBI using self-report, EMR, and HTEC. Participants also completed validated questionnaires assessing chronic symptom severity in broad health-related domains (pain, sleep, quality of life, post-concussive symptoms). The HTEC was more sensitive (80% of participants in our cohort) than either self-report or EMR alone (40%). As expected from the high sensitivity, participants screening positive for TBI through the HTEC included many people with mild or no post-concussive symptoms. Participants were grouped according to degree of concordance across these diagnostic methods no TBI, n = 43; or TBI-positive in any one method (TBI-1dx, n = 53), positive in any two (TBI-2dx, n = 45), or positive in all three (TBI-3dx, n = 59). The symptom profile of the TBI-1dx group was indistinguishable from the no TBI group. The TBI-3dx group had the most severe symptom profile. Our results show that understanding the exact methods used to ascertain TBI is essential when interpreting results from other studies, given that results and conclusions may differ dramatically depending on the method. This issue will become even more critical when interpreting data merged from multiple sources within newer, centralized repositories (e.g., Federal Interagency Traumatic Brain Injury Research [FITBIR]).Aim To estimate the cost-savings from conversion to biosimilar pegfilgrastim-cbqv that can be reallocated to provide budget-neutral expanded access to FOLFIRINOX in patients with metastatic pancreatic cancer. Methods Simulation modeling in a panel of 2500 FOLFIRINOX-treated patients, using varying treatment duration (1-12 cycles) and conversion rates (10-100%), to estimate cost-savings and additional FOLFIRINOX treatment that could be budget neutral. Results In a 2500-patient panel at 100% conversion, savings of US$6,907.41 per converted patient over 12 cycles of prophylaxis translate to US$17.3 million and could provide 72,273 additional FOLFIRINOX doses or 6023 full 6-month regimens. Conclusion Conversion to biosimilar CIN/FN prophylaxis can generate significant cost-savings and provide budget-neutral expanded access to FOLFIRINOX treatment for patients with metastatic pancreatic cancer.The aim of the current research was to investigate the prognostic significance of pretreatment hemoglobin-to-red cell distribution width ratio (HRR) in patients with renal cell carcinoma (RCC). The neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio (LMR) and HRR were analyzed retrospectively to assess their prognostic value using Kaplan-Meier curves and Cox regression analysis in 198 patients with RCC. High HRR (0.72) and high LMR (2.43) were found to be associated with longer progression-free survival and overall survival. A multivariate analysis identified International Metastatic Renal Cell Carcinoma Database Consortium prognostic score, tumor stage, node stage, LMR and HRR as independent prognostic factors for progression-free survival, as well as International Metastatic Renal Cell Carcinoma Database Consortium score, neutrophil-to-lymphocyte ratio and HRR for overall survival. HRR is a an independent prognostic parameter predicting the progression and survival of patients with RCC.Backgroud Epigenetic disorders play an important role in the pathogenesis of autoimmune thyroiditis (AIT). Therefore, to explore the possible role of DNA methylation in AIT is of great significance to explore the pathogenesis of AIT.
From May 2019 to June 2019, whole blood samples were collected from 176 AIT patients and 176 controls from different water iodine levels in Shandong Province, China. click here According to the Illumina Methylation of 850K BeadChip results of this research group in the early stage, HLA-DPB1 and PDCD1LG2 genes related to cell adhesion molecule pathway with significant differences were selected, and MethylTargetTM assay was used to verify the methylation level in 176 cases and 176 controls. The relative mRNA levels of HLA-DPB1 and PDCD1LG2 genes were detected by QRT-PCR.
There were multiple differential methylation sites (DMS) of HLA-DPB1 and PDCD1LG2 genes in the total case and control population and the case and health control population with different water iodine levels. Some target regions of HLA-DPB1 and PDCD1LG2 genes were negatively correlated with relative mRNA expression in the total case and control populations and in the case and control population with different water iodine levels.
There was indeed a change in genomic DNA methylation status in patients with AIT. The methylation patterns of HLA-DPB1 and PDCD1LG2 genes related to cell adhesion molecule pathway may be different under different areas with different water iodine levels. HLA-DPB1 and PDCD1LG2 genes related to the cell adhesion molecules pathway may play a role in the occurrence and development of AIT.
There was indeed a change in genomic DNA methylation status in patients with AIT. The methylation patterns of HLA-DPB1 and PDCD1LG2 genes related to cell adhesion molecule pathway may be different under different areas with different water iodine levels. HLA-DPB1 and PDCD1LG2 genes related to the cell adhesion molecules pathway may play a role in the occurrence and development of AIT.
