Literature Watch
Metachronous gallbladder metastasis from renal cell carcinoma-a rare clinical manifestation.
Metachronous gallbladder metastasis from renal cell carcinoma-a rare clinical manifestation.
Wien Klin Wochenschr. 2016 Sep;128(17-18):669-71
Authors: Mrak K, Lackner C, Mischinger HJ, Kornprat P
Abstract
Renal cell carcinoma (RCC) represents a rare tumor entity accounting for approximately 3 % of all malignancies in the adult population. Approximately 30 % of all patients suffering from RCC develop metastases after nephrectomy and another 30 % of patients suffer from synchronous metastases at the date of diagnosis. Gallbladder metastases represent an extremely rare clinical condition and up to date there are only 35 published cases of gallbladder metastasis from RCC. Surgical resection should be the treatment of choice in any case based on the reported data in literature. In spite of the small series of cases, survival can be improved even in patients suffering from additional sites of metastases.
PMID: 27624324 [PubMed - indexed for MEDLINE]
First report of otitis externa caused by Schizophyllum commune and review of the literature.
First report of otitis externa caused by Schizophyllum commune and review of the literature.
Wien Klin Wochenschr. 2016 May;128(9-10):387-90
Authors: Matos T, Tomazin R, Battelino S
Abstract
Basidiomycete Schizophyllum commune is a widely distributed cellulolytic fungus that is a well-known pathogen. It can cause a wide range of different infections, and here we describe the first case of otitis externa and a molecularly based identification process.
PMID: 26802032 [PubMed - indexed for MEDLINE]
Systematic Computational Identification of Variants That Activate Exonic and Intronic Cryptic Splice Sites.
Systematic Computational Identification of Variants That Activate Exonic and Intronic Cryptic Splice Sites.
Am J Hum Genet. 2017 May 04;100(5):751-765
Authors: Lee M, Roos P, Sharma N, Atalar M, Evans TA, Pellicore MJ, Davis E, Lam AN, Stanley SE, Khalil SE, Solomon GM, Walker D, Raraigh KS, Vecchio-Pagan B, Armanios M, Cutting GR
Abstract
We developed a variant-annotation method that combines sequence-based machine-learning classification with a context-dependent algorithm for selecting splice variants. Our approach is distinctive in that it compares the splice potential of a sequence bearing a variant with the splice potential of the reference sequence. After training, classification accurately identified 168 of 180 (93.3%) canonical splice sites of five genes. The combined method, CryptSplice, identified and correctly predicted the effect of 18 of 21 (86%) known splice-altering variants in CFTR, a well-studied gene whose loss-of-function variants cause cystic fibrosis (CF). Among 1,423 unannotated CFTR disease-associated variants, the method identified 32 potential exonic cryptic splice variants, two of which were experimentally evaluated and confirmed. After complete CFTR sequencing, the method found three cryptic intronic splice variants (one known and two experimentally verified) that completed the molecular diagnosis of CF in 6 of 14 individuals. CryptSplice interrogation of sequence data from six individuals with X-linked dyskeratosis congenita caused by an unknown disease-causing variant in DKC1 identified two splice-altering variants that were experimentally verified. To assess the extent to which disease-associated variants might activate cryptic splicing, we selected 458 pathogenic variants and 348 variants of uncertain significance (VUSs) classified as high confidence from ClinVar. Splice-site activation was predicted for 129 (28%) of the pathogenic variants and 75 (22%) of the VUSs. Our findings suggest that cryptic splice-site activation is more common than previously thought and should be routinely considered for all variants within the transcribed regions of genes.
PMID: 28475858 [PubMed - in process]
Thymosin α1: a single drug with multiple targets in cystic fibrosis.
Thymosin α1: a single drug with multiple targets in cystic fibrosis.
Nat Med. 2017 May 05;23(5):536-538
Authors: Cantin AM, Hanrahan JW
PMID: 28475572 [PubMed - in process]
Malnutrition among Hospitalized Children in the United States: Changing Prevalence, Clinical Correlates, and Practice Patterns between 2002 and 2011.
Malnutrition among Hospitalized Children in the United States: Changing Prevalence, Clinical Correlates, and Practice Patterns between 2002 and 2011.
J Acad Nutr Diet. 2017 Apr 28;:
Authors: Carvalho-Salemi J, Salemi JL, Wong-Vega MR, Spooner KK, Juarez MD, Beer SS, Canada NL
Abstract
BACKGROUND: Pediatric malnutrition has been associated with adverse clinical outcomes, longer lengths of stay, and higher health care costs.
OBJECTIVE: To characterize prevalence, temporal trends, and short-term clinical outcomes of coded diagnoses of pediatric malnutrition (CDM) across sociodemographic, clinical, and hospital characteristics from 2002 to 2011.
DESIGN: This study is a retrospective cross-sectional analysis of nationally representative data from the Nationwide Inpatient Sample and the Kids' Inpatient Database.
PARTICIPANTS/SETTING: The study sample included pediatric inpatient hospitalizations in the United States.
MAIN OUTCOME MEASURES: International Classification of Diseases-9th Revision-Clinical Modification diagnosis codes were used to identify CDM and coded malnutrition subtypes based on an etiology-related definition of pediatric malnutrition.
STATISTICAL ANALYSES: The national frequency and prevalence of CDM overall and across patient- and hospital-level characteristics were estimated for children aged 1 month to 17 years. Logistic regression was used to assess the association between CDM and each characteristic. Analyses evaluated conditions associated with the highest burden and risk of CDM, and compared clinical outcomes across malnutrition subtypes. Joinpoint regression was used to describe temporal trends in CDM.
RESULTS: Of the 2.1 million pediatric patients hospitalized annually, more than 54,600 had CDM, a national prevalence of 2.6%. Considerable variation was observed based on primary diagnosis, with fluid and electrolyte disorders contributing the most malnutrition cases. Highest CDM rates were among patients with stomach cancer, cystic fibrosis, and human immunodeficiency virus. Patients with CDM experienced worse clinical outcomes, longer lengths of stay, and increased costs of inpatient care. The overall prevalence of CDM increased from 1.9% in 2002 to 3.7% in 2011, an 8% annual increase, and temporal increases were observed in nearly all population subgroups.
CONCLUSIONS: Despite improvements, pediatric malnutrition remains underdiagnosed in inpatient settings when relying exclusively on International Classification of Diseases-based codes, which underscores the need for a national benchmarking program to estimate the true prevalence, clinical significance, and cost of pediatric malnutrition.
PMID: 28473256 [PubMed - as supplied by publisher]
GZF1 Mutations Expand the Genetic Heterogeneity of Larsen Syndrome.
GZF1 Mutations Expand the Genetic Heterogeneity of Larsen Syndrome.
Am J Hum Genet. 2017 May 04;100(5):831-836
Authors: Patel N, Shamseldin HE, Sakati N, Khan AO, Softa A, Al-Fadhli FM, Hashem M, Abdulwahab FM, Alshidi T, Alomar R, Alobeid E, Wakil SM, Colak D, Alkuraya FS
Abstract
Larsen syndrome is characterized by the dislocation of large joints and other less consistent clinical findings. Heterozygous FLNB mutations account for the majority of Larsen syndrome cases, but biallelic mutations in CHST3 and B4GALT7 have been more recently described, thus confirming the existence of recessive forms of the disease. In a multiplex consanguineous Saudi family affected by severe and recurrent large joint dislocation and severe myopia, we identified a homozygous truncating variant in GZF1 through a combined autozygome and exome approach. Independently, the same approach identified a second homozygous truncating GZF1 variant in another multiplex consanguineous family affected by severe myopia, retinal detachment, and milder skeletal involvement. GZF1 encodes GDNF-inducible zinc finger protein 1, a transcription factor of unknown developmental function, which we found to be expressed in the eyes and limbs of developing mice. Global transcriptional profiling of cells from affected individuals revealed a shared pattern of gene dysregulation and significant enrichment of genes encoding matrix proteins, including P3H2, which hints at a potential disease mechanism. Our results suggest that GZF1 mutations cause a phenotype of severe myopia and significant articular involvement not previously described in Larsen syndrome.
PMID: 28475863 [PubMed - in process]
A cumulative effect involving malfunction of the PTH1R and ATP4A genes explains a familial gastric neuroendocrine tumor with hypothyroidism and arthritis.
A cumulative effect involving malfunction of the PTH1R and ATP4A genes explains a familial gastric neuroendocrine tumor with hypothyroidism and arthritis.
Gastric Cancer. 2017 May 04;:
Authors: Calvete O, Herraiz M, Reyes J, Patiño A, Benitez J
Abstract
BACKGROUND: Type I gastric neuroendocrine tumors (gNETs) classically arise because of hypergastrinemia and involve destruction of parietal cells, which are responsible for gastric acid secretion through the ATP4A proton pump and for intrinsic factor production.
METHODS: By whole exome sequencing, we studied a family with three members with gNETs plus hypothyroidism and rheumatoid arthritis to uncover their genetic origin.
RESULTS: A heterozygous missense mutation in the ATP4A gene was identified. Carriers of this variant had low ferritin and vitamin B12 levels but did not develop gNETs. A second heterozygous mutation was also uncovered (PTH1R p.E546K). Carriers exhibited hypothyroidism and one of them had rheumatoid arthritis. Gastrin activates parathyroid hormone like hormone/parathyroid hormone 1 receptor (PTH1R) signaling, which is involved in gastric cell homeostasis. Activation of parathyroid hormone/PTH1R, which is upregulated by thyrotropin in the thyroid, is also involved in RANKL expression, which regulates bone homeostasis. Thyrotropin and RANKL expression were deregulated in PTH1R mutation carriers, suggesting a link between the PTH1R gene, hypothyroidism, rheumatoid arthritis, and gastric disease. Only patients with both mutations developed gNETs plus hypothyroidism and rheumatoid arthritis.
CONCLUSION: Both mutations suggest that a collaborative mechanism is operative in this family, in which mutations in these genes affect the function and viability of parietal cells and lead to the achlorhydria that drives hypergastrinemia and the formation of gNETs.
PMID: 28474257 [PubMed - as supplied by publisher]
Use of Clinical Exome Sequencing in Isolated Congenital Heart Disease.
Use of Clinical Exome Sequencing in Isolated Congenital Heart Disease.
Circ Cardiovasc Genet. 2017 Jun;10(3):
Authors: Zahavich L, Bowdin S, Mital S
PMID: 28473349 [PubMed - in process]
Notice of Correction to PAR-17-176 "From Genomic Association to Causation: A Convergent Neuroscience Approach for Integrating Levels of Analysis to Delineate Brain Function in Neuropsychiatry (Collaborative U01)"
Notice of Correction to PAR-17-179 " From Genomic Association to Causation: A Convergent Neuroscience Approach for Integrating Levels of Analysis to Delineate Brain Function in Neuropsychiatry (U01)"
Notice of Information Regarding the "Announcement of Antimicrobial Resistance Rapid, Point-of-Need Diagnostic Test Challenge Competition"
Notice of Reissuance of the "Modeling of Infectious Disease Agent Study Research Projects (R01)" Funding Opportunity Announcement
Modeling of Infectious Disease Agent Study Research Projects (R01)
pharmacogenomics; +16 new citations
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"systems biology"; +44 new citations
44 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/05/05
PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The Undiagnosed Diseases Network: Accelerating Discovery about Health and Disease.
The Undiagnosed Diseases Network: Accelerating Discovery about Health and Disease.
Am J Hum Genet. 2017 Feb 02;100(2):185-192
Authors: Ramoni RB, Mulvihill JJ, Adams DR, Allard P, Ashley EA, Bernstein JA, Gahl WA, Hamid R, Loscalzo J, McCray AT, Shashi V, Tifft CJ, Undiagnosed Diseases Network, Wise AL
Abstract
Diagnosis at the edges of our knowledge calls upon clinicians to be data driven, cross-disciplinary, and collaborative in unprecedented ways. Exact disease recognition, an element of the concept of precision in medicine, requires new infrastructure that spans geography, institutional boundaries, and the divide between clinical care and research. The National Institutes of Health (NIH) Common Fund supports the Undiagnosed Diseases Network (UDN) as an exemplar of this model of precise diagnosis. Its goals are to forge a strategy to accelerate the diagnosis of rare or previously unrecognized diseases, to improve recommendations for clinical management, and to advance research, especially into disease mechanisms. The network will achieve these objectives by evaluating patients with undiagnosed diseases, fostering a breadth of expert collaborations, determining best practices for translating the strategy into medical centers nationwide, and sharing findings, data, specimens, and approaches with the scientific and medical communities. Building the UDN has already brought insights to human and medical geneticists. The initial focus has been on data sharing, establishing common protocols for institutional review boards and data sharing, creating protocols for referring and evaluating patients, and providing DNA sequencing, metabolomic analysis, and functional studies in model organisms. By extending this precision diagnostic model nationally, we strive to meld clinical and research objectives, improve patient outcomes, and contribute to medical science.
PMID: 28157539 [PubMed - indexed for MEDLINE]
Ovarian cancer in children and adolescents: A rare disease that needs more attention.
Ovarian cancer in children and adolescents: A rare disease that needs more attention.
Maturitas. 2016 Jun;88:3-8
Authors: Baert T, Storme N, Van Nieuwenhuysen E, Uyttebroeck A, Van Damme N, Vergote I, Coosemans A
Abstract
Ovarian cancer is rare in childhood. This explains why there are only scattered reports on it in the literature and why there is a lack of specific pediatric treatment. This paper gives an overview of the Belgian data from 2004 to 2013 and reviews the literature. To index ovarian masses and malignancies in children better in the future, worldwide data collection should be improved and reproducible definitions of 'childhood', 'malignancy' and 'ovarian mass' need to be adopted.
PMID: 27105689 [PubMed - indexed for MEDLINE]
Abdominal symptoms in cystic fibrosis and their relation to genotype, history, clinical and laboratory findings.
Abdominal symptoms in cystic fibrosis and their relation to genotype, history, clinical and laboratory findings.
PLoS One. 2017;12(5):e0174463
Authors: Tabori H, Arnold C, Jaudszus A, Mentzel HJ, Renz DM, Reinsch S, Lorenz M, Michl R, Gerber A, Lehmann T, Mainz JG
Abstract
BACKGROUND & AIMS: Abdominal symptoms (AS) are a hallmark of the multiorgan-disease cystic fibrosis (CF). However, the abdominal involvement in CF is insufficiently understood and, compared to the pulmonary manifestation, still receives little scientific attention. Aims were to assess and quantify AS and to relate them to laboratory parameters, clinical findings, and medical history.
METHODS: A total of 131 patients with CF of all ages were assessed with a new CF-specific questionnaire (JenAbdomen-CF score 1.0) on abdominal pain and non-pain symptoms, disorders of appetite, eating, and bowel movements as well as symptom-related quality of life. Results were metrically dimensioned and related to abdominal manifestations, history of surgery, P. aeruginosa and S. aureus colonization, genotype, liver enzymes, antibiotic therapy, lung function, and nutritional status.
RESULTS: AS during the preceding 3 months were reported by all of our patients. Most common were lack of appetite (130/131) and loss of taste (119/131) followed by abdominal pain (104/131), flatulence (102/131), and distention (83/131). Significantly increased AS were found in patients with history of rectal prolapse (p = 0.013), distal intestinal obstruction syndrome (p = 0.013), laparotomy (p = 0.022), meconium ileus (p = 0.037), pancreas insufficiency (p = 0.042), or small bowel resection (p = 0.048) as well as in patients who have been intermittently colonized with P. aeruginosa (p = 0.006) compared to patients without history of these events. In contrast, no statistically significant associations were found to CF-associated liver disease, chronic pathogen colonization, lung function, CF-related diabetes, and nutritional status.
CONCLUSION: As the complex abdominal involvement in CF is still not fully understood, the assessment of the common AS is of major interest. In this regard, symptom questionnaires like the herein presented are meaningful and practical tools facilitating a wider understanding of the abdominal symptoms in CF. Furthermore, they render to evaluate possible abdominal effects of novel modulators of the underlying cystic fibrosis transmembrane (conductance) regulator (CFTR) defect.
PMID: 28472055 [PubMed - in process]
Increased Fat Absorption from Enteral Formula Through an In-Line Digestive Cartridge in Patients with Cystic Fibrosis.
Increased Fat Absorption from Enteral Formula Through an In-Line Digestive Cartridge in Patients with Cystic Fibrosis.
J Pediatr Gastroenterol Nutr. 2017 May 03;:
Authors: Freedman S, Orenstein D, Black P, Brown P, McCoy K, Stevens J, Grujic D, Clayton R
Abstract
OBJECTIVES: Supplemental enteral nutrition (EN) is used by approximately 12% of people with cystic fibrosis (CF). The objective of this study was to evaluate the safety, tolerability, and fat absorption of a new in-line digestive cartridge (Relizorb) that hydrolyzes fat in enteral formula provided to patients with CF.
METHODS: Patients with CF receiving EN participated in a multicenter, randomized, double-blind, crossover trial with an open-label safety evaluation period. Plasma omega-3 fatty acid (FA) concentrations were measured and used as markers of fat absorption. Gastrointestinal (GI) symptoms were recorded to evaluate safety and tolerability. Information regarding the effect of EN on appetite and breakfast consumption was also collected.
RESULTS: Prior to study entry, participants had received EN for a mean of 6.6 years at a mean volume of approximately 800 mL, yet had a mean body mass index of only 17.5 kg/m and omega-3 FA plasma concentrations were only 60% of levels found in normal healthy subjects. Compared with placebo, cartridge use resulted in a statistically significant 2.8-fold increase in plasma omega-3 FA concentrations. There were no adverse experiences associated with cartridge use, and a decrease in the frequency and severity of most symptoms of malabsorption was observed with cartridge use. Participants reported increased preservation of appetite and breakfast consumption with cartridge use compared with their pre-study regimen.
CONCLUSIONS: Use of this in-line digestive cartridge was safe and well tolerated, and resulted in significantly increased levels of plasma omega-3 FA used with enteral formula, suggesting an overall increased fat absorption.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
PMID: 28471913 [PubMed - as supplied by publisher]
Comprehensive Review on Colorectal Cancer and Transplant.
Comprehensive Review on Colorectal Cancer and Transplant.
Am J Transplant. 2017 May 04;:
Authors: Prenner S, Levitsky J
Abstract
Colon cancer (CRC) is a common malignancy worldwide. Some studies suggest that organ recipients are at a higher risk for CRC than the general population. The underlying transplant indications and their inherent risk factors for CRC may drive the variation in incidence rates that are seen in patients receiving different allografts. Recipients with cystic fibrosis are now recognized as a population at high risk for CRC at a young age. Transplant recipients have high mortality following a CRC diagnosis, even if it is detected at an early stage. Certain types of immunosuppression have been shown to accelerate cancer transformation and may contribute to the more aggressive phenotype seen in organ recipients. Given the high incidence and progressive nature of post-transplant CRC, shorter screening intervals with a modality that can detect early stage polyps may be essential to prevent mortality. Future research is needed to better elucidate the role of immunosuppression in carcinogenesis. This comprehensive review examines CRC risk, screening, and management specific to organ transplant candidates and recipients. This article is protected by copyright. All rights reserved.
PMID: 28471512 [PubMed - as supplied by publisher]
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