-
Erickson Malmberg posted an update 2 weeks ago
Detecting inflammation is among the most important aims of medical imaging. Inflammatory process involves immune system activity and local tissue response. The role of PET with fludeoxyglucose F 18 has been expanded. Systemic vasculitides and cardiopulmonary inflammatory disorders constitute a wide range of diseases with multisystemic manifestations. PET with fludeoxyglucose F 18 is useful in their diagnosis, assessment, and follow-up. selleck chemicals This article provides an overview of the current status and potentials of hybrid molecular imaging in evaluating cardiopulmonary and vascular inflammatory diseases focusing on the potential for PET with fludeoxyglucose F 18/MR imaging and PET/CT scans.Primary Hyperoxaluria type I (PH1) is a rare disease caused by mutations in the AGXT gene encoding alanineglyoxylate aminotransferase (AGT), a liver enzyme involved in the detoxification of glyoxylate, the failure of which results in accumulation of oxalate and kidney stones formation. The role of protein misfolding in the AGT deficit caused by most PH1-causing mutations is increasingly being recognized. In addition, the genetic background in which a mutation occurs is emerging as a critical risk factor for disease onset and/or severity. Based on these premises, in this study we have analyzed the clinical, biochemical and cellular effects of the p.Ile56Asn mutation, recently described in a PH1 patient, as a function of the residue at position 11, a hot-spot for both polymorphic (p.Pro11Leu) and pathogenic (p.Pro11Arg) mutations. We have found that the p.Ile56Asn mutation induces a structural defect mostly related to the apo-form of AGT. The effects are more pronounced when the substitution of Ile56 is combined with the p.Pro11Leu and, at higher degree, the p.Pro11Arg mutation. As compared with the non-pathogenic forms, AGT variants display reduced expression and activity in mammalian cells. Vitamin B6, a currently approved treatment for PH1, can overcome the effects of the p.Ile56Asn mutation only when it is associated with Pro at position 11. Our results provide a first proof that the genetic background influences the effects of PH1-causing mutations and the responsiveness to treatment and suggest that molecular and cellular studies can integrate clinical data to identify the best therapeutic strategy for PH1 patients.
Metachromatic leukodystrophy (MLD) is an autosomal recessive disorder caused by deficient arylsulfatase A (ASA) activity and characterized by neurological involvement that results in severe disability and premature death. We examined the safety and tolerability of intrathecally delivered recombinant human ASA (rhASA; SHP611, now TAK-611) in children with MLD (NCT01510028). Secondary endpoints included change in cerebrospinal fluid (CSF) sulfatide and lysosulfatide levels, and motor function (assessed by Gross Motor Function Measure-88 total score).
Twenty-four children with MLD who experienced symptom onset aged ≤ 30months were enrolled. Patients received rhASA every other week (EOW) for 38weeks at 10, 30, or 100mg (cohorts 1-3; n=6 per cohort), or 100mg manufactured using a revised process (cohort 4; n=6).
No rhASA-related serious adverse events (SAEs) were observed; 25% of patients experienced an SAE related to the intrathecal device or drug delivery method. Mean CSF sulfatide and lysosulfatide levels fell to within normal ranges in both 100mg cohorts following treatment. Although there was a general decline in motor function over time, there was a tendency towards a less pronounced decline in patients receiving 100mg.
Intrathecal rhASA was generally well tolerated at doses up to 100mg EOW. These preliminary data support further development of rhASA as a therapy for patients with MLD.
Intrathecal rhASA was generally well tolerated at doses up to 100 mg EOW. These preliminary data support further development of rhASA as a therapy for patients with MLD.Breast malignancies are the leading type of cancer among women. Its prevention and early detection, particularly in young women, remains challenging. To this end, cell-free DNA (cfDNA) detected in body fluids demonstrates great potential for early detection of tissue transformation and altered molecular setup, such as epigenetic profiles. Aberrantly methylated cfDNA in body fluids could therefore serve as a potential diagnostic and prognostic tool in breast cancer management. Abnormal methylation may lead to both an activation of oncogenes via hypomethylation and an inactivation of tumor suppressor genes by hypermethylation. We update the state of the art in the area of aberrant cfDNA methylation analyses as a diagnostic and prognostic tool in breast cancer, report on the main technological challenges, and provide an outlook for advancing the overall management of breast malignancies based on cfDNA as a target for diagnosis and tailored therapies.
Hypofractionated radiotherapy (Hypo-RT) is now considered the standard of care for the majority of patients receiving whole-breast irradiation (WBI). However, there are few data on the use of Hypo-RT in human epidermal growth factor receptor 2 (HER2)-positive patients receiving concurrent anti-HER2 therapy. In this study, we sought to examine patterns of WBI in HER2-positive patients.
Using the National Cancer Data Base, we identified women with nonmetastatic HER2-positive breast cancer diagnosed between 2010 and 2015 who received WBI. The Hypo-RT group was defined as those receiving 21 or fewer fractions. All other patients were in the conventional radiotherapy (RT) group. Multivariate logistic regression was used to identify predictors of Hypo-RT utilization. Five-year overall survival was estimated by the Kaplan-Meier method.
The study included 15,776 patients, of whom 17.7% received Hypo-RT. The rate of Hypo-RT utilization increased from 7.4% in 2010 to 29.3% in 2015 (P= .004). Predictors of Hypo-RTt significantly associated with overall survival.
There has been an ongoing debate concerning the predictors of contralateral paratracheal lymph nodes metastasis (LNM) in unilateral papillary thyroid cancer (PTC). This study aimed to explore the value of pretracheal-laryngeal lymph nodes (LNs) in frozen section in predicting contralateral paratracheal LNM.
A total of 242 patients with unilateral PTC were enrolled in this prospective study. Patients who underwent total thyroidectomy and bilateral central lymph nodes dissection (LND) were divided into two groups according to positive or negative contralateral paratracheal LNs. Patients’ demographics and clinicopathological features were compared between the two groups. Validity indexes and consistency of pretracheal-laryngeal LNs in frozen sections were calculated.
LNM rates in central, ipsilateral paratracheal, pretracheal-laryngeal, and contralateral paratracheal regions were 55.37%, 47.03%, 23.55% and 14.05%, respectively. Only pretracheal-laryngeal LNM, regardless of whether detected in frozen or paraffin sections, were independent risk factors for contralateral paratracheal LNM (OR=2.