Efficacy and safety of intermittent hemodialysis in infants and young children with inborn errors of metabolism.

Background: Intermittent hemodialysis (IHD) is the most efficient form of renal replacement therapy (RRT) for removing toxic substances from patients' bodies. However, the efficacy and safety of IHD in infants and young children with inborn errors of metabolism are still not clear.

Methods: This retrospective study included patients with urea cycle disorders, maple syrup urine disease, and methylmalonic acidemia who received IHD or non-IHD RRT at our hospital between 2001 and 2012 to remove ammonia, leucine, or methylmalonic acid.

Myostatin and insulin-like growth factor I: potential therapeutic biomarkers for pompe disease.

Objective: Myostatin and insulin-like growth factor 1 (IGF-1) are serum markers for muscle growth and regeneration. However, their value in the clinical monitoring of Pompe disease - a muscle glycogen storage disease - is not known. In order to evaluate their possible utility for disease monitoring, we assessed the levels of these serum markers in Pompe disease patients receiving enzyme replacement therapy (ERT).

Real-time computed optical interferometric tomography.

High-resolution real-time tomography of scattering tissues is important for many areas of medicine and biology. However, the compromise between transverse resolution and depth-of-field in addition to low sensitivity deep in tissue continue to impede progress towards cellular-level volumetric tomography. Computed imaging has the potential to solve these long-standing limitations.

Analysis of lyso-globotriaosylsphingosine in dried blood spots.

Recently, lyso-globotriaosylsphingosine (lyso-Gb3) was found to be elevated in plasma of treatment naive male patients and some female patients with Fabry Disease (FD). This study tested whether lyso-Gb3 could be analyzed in dried blood spots (DBS) from filter cards and whether concentrations are elevated in newborn infants with FD. Lyso-Gb3 concentrations were analyzed in DBS following extraction using a novel HPLC-mass spectrometry (MS)/MS method.

Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma.

Background: The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti-PD-1 antibody lambrolizumab (previously known as MK-3475) in patients with advanced melanoma.

Methods: We administered lambrolizumab intravenously at a dose of 10 mg per kilogram of body weight every 2 or 3 weeks or 2 mg per kilogram every 3 weeks in patients with advanced melanoma, both those who had received prior treatment with the immune checkpoint inhibitor ipilimumab and those who had not.

Web-based newborn screening system for metabolic diseases: machine learning versus clinicians.

Background: A hospital information system (HIS) that integrates screening data and interpretation of the data is routinely requested by hospitals and parents. However, the accuracy of disease classification may be low because of the disease characteristics and the analytes used for classification.

Objective: The objective of this study is to describe a system that enhanced the neonatal screening system of the Newborn Screening Center at the National Taiwan University Hospital.

Fatty Acid oxidation disorders in a chinese population in taiwan.

Background: Fatty acid oxidation (FAO) disorders are a heterogeneous group of inborn errors in the transportation and oxidation of fatty acids. FAO disorders were thought to be very rare in the Chinese population. Newborn screening for FAO disorders beginning in 2002 in Taiwan may have increased the diagnosis of this group of diseases.

More IMPATIENT: A Gridding-Accelerated Toeplitz-based Strategy for Non-Cartesian High-Resolution 3D MRI on GPUs.

Several recent methods have been proposed to obtain significant speed-ups in MRI image reconstruction by leveraging the computational power of GPUs. Previously, we implemented a GPU-based image reconstruction technique called the Illinois Massively Parallel Acquisition Toolkit for Image reconstruction with ENhanced Throughput in MRI (IMPATIENT MRI) for reconstructing data collected along arbitrary 3D trajectories. In this paper, we improve IMPATIENT by removing computational bottlenecks by using a gridding approach to accelerate the computation of various data structures needed by the previous routine.

Pompe disease: early diagnosis and early treatment make a difference.

Pompe disease (glycogen storage disease type II or acid maltase deficiency) is a lysosomal disorder in which acid α-glucosidase (GAA) deficiencies lead to intralysosomal accumulation of glycogen in all tissues; most notably in skeletal muscles. Both the patient's age at the onset of Pompe disease symptoms and the rate of deterioration caused by the disease can vary considerably. In classical infant-onset Pompe disease (IOPD), symptoms start very early in life, and death occurs soon afterward if the disease remains untreated.

Chemical castration of melanoma patients does not increase the frequency of tumor-specific CD4 and CD8 T cells after peptide vaccination.

Peptide vaccination against tumor-associated antigens remains one of the most common methods of immunization in cancer vaccine clinical trials. Although peptide vaccination has been reported to increase circulating antigen-specific T-cells, they have had limited clinical efficacy and there is a necessity to increase their capacity to generate strong antitumor responses. We sought to improve the clinical efficacy of peptide-based vaccines in cancer immunotherapy of metastatic melanoma using a LHRH agonist (leuprolide) as adjuvant.

Newborn screening for citrin deficiency and carnitine uptake defect using second-tier molecular tests.

Background: Tandem mass spectrometry (MS/MS) analysis is a powerful tool for newborn screening, and many rare inborn errors of metabolism are currently screened using MS/MS. However, the sensitivity of MS/MS screening for several inborn errors, including citrin deficiency (screened by citrulline level) and carnitine uptake defect (CUD, screened by free carnitine level), is not satisfactory. This study was conducted to determine whether a second-tier molecular test could improve the sensitivity of citrin deficiency and CUD detection without increasing the false-positive rate.

Diagnosing mucopolysaccharidosis IVA.

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of biochemical genetics laboratory directors and clinicians involved in the diagnosis of MPS IVA, convened by BioMarin Pharmaceutical Inc.

TIGER: tiled iterative genome assembler.

Background: With the cost reduction of the next-generation sequencing (NGS) technologies, genomics has provided us with an unprecedented opportunity to understand fundamental questions in biology and elucidate human diseases. De novo genome assembly is one of the most important steps to reconstruct the sequenced genome. However, most de novo assemblers require enormous amount of computational resource, which is not accessible for most research groups and medical personnel.

Lyso-globotriaosylsphingosine (lyso-Gb3) levels in neonates and adults with the Fabry disease later-onset GLA IVS4+919G>A mutation.

Lyso-globotriaosylsphingosine (lyso-Gb3) is a useful biomarker in the diagnosis and monitoring of treatment for Fabry disease. However, it is unclear whether lyso-Gb3 is elevated in patients with later-onset Fabry disease. Thus, we measured lyso-Gb3 levels from dried blood spots (DBS) from male newborns with the Fabry disease later-onset phenotype, IVS4+919G>A mutation, and their family members.

Promising outcomes in glutaric aciduria type I patients detected by newborn screening.

Glutaric aciduria type I (GA-I) is an inborn error of lysine and tryptophan metabolism. Clinical manifestations of GA-I include dystonic or dyskinetic cerebral palsy, but when the symptoms occur, treatment is not effective. In Taiwan, newborn screening for GA-I started in 2001; we wish to evaluate the outcomes of patients detected through newborn screening.

Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients.

Purpose: Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing phase II clinical trial testing the efficacy of ACT using TIL in patients with metastatic melanoma and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response.

Experimental Design: Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL, followed by two cycles of high-dose interleukin (IL)-2 therapy.

The role of alpha-synuclein in melanin synthesis in melanoma and dopaminergic neuronal cells.

The relatively high co-occurrence of Parkinson's disease (PD) and melanoma has been established by a large number of epidemiological studies. However, a clear biological explanation for this finding is still lacking. Ultra-violet radiation (UVR)-induced skin melanin synthesis is a defense mechanism against UVR-induced damage relevant to the initiation of melanoma, whereas, increased neuromelanin (NM), the melanin synthesized in dopaminergic neurons, may enhance the susceptibility to oxidative stress-induced neuronal injury relevant to PD.

A novel 3670-base pair mitochondrial DNA deletion resulting in multi-systemic manifestations in a child.

Mitochondrial DNA (mtDNA) deletion is a rare occurrence that results in defects to oxidative phosphorylation. The common clinical presentations of mtDNA deletion vary but include mitochondrial myopathy, Pearson syndrome, Kearns-Sayre syndrome, and progressive external ophthalmoplegia. Here, we report the case of a 10-year-old boy who presented with progressive deterioration of his clinical status (which included hypoglycemia, short stature, sensorineural hearing loss, retinitis pigmentosa, and chronic gastrointestinal dysmotility) that progressed to acute deterioration with pancreatitis, Fanconi syndrome, lactic acidosis, and acute encephalopathy.

Combining targeted therapy with immunotherapy (interferon-α): Rational, efficacy in gastrointestinal stromal tumor model and implications in other malignancies.

Imatinib revolutionized gastrointestinal stromal tumor (GIST) treatment but median-progression-free-survival of unresectable/metastatic disease is < 2 y. B-RAF(V600)-mutated-melanoma responds to vemurafenib dramatically but median-progression-free-survival is < 9 mo. Combining imatinib with immunotherapy (peginterferon α-2b) in GIST showed significant induction of antitumor immunity and highly promising clinical outcomes.

Application of mass spectrometry in newborn screening: about both small molecular diseases and lysosomal storage diseases.

Many genetic diseases, especially the inborn errors of metabolism, have very low incidences, so developing a newborn screening test for each disease is not practical. This obstacle was overcome by employing the tandem mass spectrometry (MS/MS) technology. In the analysis, the samples can be injected directly into the flowing system without passing through a column, and both acylcarnitine and amino acid profiles can be obtained at the same time.

Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin.

Purpose: Glycogen storage diseases are a group of inborn errors of glycogen synthesis or catabolism. The outcome for untreated patients can be devastating. Given the genetic heterogeneity and the limited availability of enzyme study data, the definitive diagnosis of glycogen storage diseases is made on the basis of sequence analysis of selected potentially causative genes.

Changes in tumor morphology and cyclin-dependent kinase inhibitor expression in metastatic melanoma treated with selective second-generation BRAF inhibitor.

Dermatologic toxicities associated with anticancer-targeted therapy include hand-foot skin reactions, vasculitis, cutaneous epithelial proliferations, such as keratosis, keratoacanthoma, and invasive squamous cell carcinoma. In this case report, we describe alterations of tumor morphology and patterns of cyclin-dependent kinase inhibitor (CDKI) expression in a patient who received GSK2118436, a second-generation RAF inhibitor, for stage IV (M1c) metastatic melanoma. To explore the effects of GSK2118436 on the expression patterns of CDKI (p16, p21, p27, p57), we immunohistochemically evaluated in vivo melanoma cells pre- and posttreated with GSK2118436.