[Urothelial tumors in children].

Bull Cancer. 2017 Feb;104(2):195-201

Authors: Grapin-Dagorno C, Peycelon M, Philippe-Chomette P, Berrebi D, El Ghoneimi A, Orbach D

Abstract
Urothelial tumors are very rare in children (to date, only about 150 cases have been reported worlwide). Only 20% occur before the age of ten. The aim of this study is to specify the clinicopathologic features of urothelial tumor in young patients, which require a slightly different approach to treatment. On the basis of the WHO/ISUP (World Health Organisation/International Society of Urological Pathology) consensus classification report, these lesions are usually low-grade lesions, non invasive, and rarely recurrent. The sex ratio is three boys to one girl. These tumors are located preferentially in the low urinary tract, especially in the bladder. The main symptom is the macroscopic hematuria, which requires ultrasound examination in all cases. Cystoscopy is indicated in case of lesion of the bladder wall, or in case of persistent or recurrent hematuria, to obtain definitive diagnosis and biopsies. The tumors are mainly located on the posterior or lateral bladder wall above the trigone or near the ureteral orifices. Treatment is based on the transurethral resection of the lesion. The subsequent monitoring is sparsely codified, due to the exceptional occurrence of these tumors in the paediatric age group. These patients are likely to have better outcome than older patients, but it is due to the predominance of noninvasive papillary urothelial tumors. Tumor recurrences are not uncommon. In case of invasive, high-grade urothelial carcinomas, metastases or even lethal outcome may occur in rare cases.

PMID: 28034440 [PubMed - indexed for MEDLINE]

[Nasopharyngeal adenoid cystic carcinoma, a rare but highly challenging disease with unmet therapeutic needs: A case-report and review of the literature].

Cancer Radiother. 2016 Jul;20(5):400-4

Authors: Afani L, Errihani H, Benchafai I, Lalami Y

Abstract
Nasopharyngeal adenoid cystic carcinoma is a rare tumour. Compared with others nasopharyngeal tumours, it is characterised by slow evolution but it is locally aggressive and has a high tendency to recurrences. Due to the rarity of cases, no consensus exists about treatment approaches. We report the case of 45-year-old-man with a locally advanced adenoid cystic carcinoma. The patient received concurrent chemoradiation and had a good objective response. After one year, he developed a paucisymptomatic lung metastasis. The follow-up showed local recurrence after 3 years. One cycle of chemotherapy was given but poorly supported. Carbon ion radiotherapy was proposed. The aim of this work is to review the literature concerning this rare malignancy and discusses treatment approaches in initial situations and during recurrences.

PMID: 27131394 [PubMed - indexed for MEDLINE]

Encapsulating Peritoneal Sclerosis - Rare Cause Of Bowel Obstruction.

Pol Przegl Chir. 2015 Jul 01;87(7):371-4

Authors: Dec P, Józefowicz M, Lesińska A, Kubisa B

PMID: 26351794 [PubMed - indexed for MEDLINE]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/02/12

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.

Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors.

Sci Transl Med. 2017 Feb 08;9(376):

Authors: Doulatov S, Vo LT, Macari ER, Wahlster L, Kinney MA, Taylor AM, Barragan J, Gupta M, McGrath K, Lee HY, Humphries JM, DeVine A, Narla A, Alter BP, Beggs AH, Agarwal S, Ebert BL, Gazda HT, Lodish HF, Sieff CA, Schlaeger TM, Zon LI, Daley GQ

Abstract
Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small-molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and up-regulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA.

PMID: 28179501 [PubMed - in process]

Turning the Unknown into Known: Data Mining Is Increasingly Used to Prospect for Rare-Disease Biology and Treatments.

IEEE Pulse. 2017 Jan-Feb;8(1):28-32

Authors: Mertz L

Abstract
Taken as a whole, rare diseases are not very rare. Even though a rare disease by definition is one that affects fewer than 200,000 Americans or fewer than one in 2,000 Europeans at any time, when rare diseases are considered together, they affect some 350 million people worldwide, or about 5% of the population (Figure 1). What is even more alarming is that 7,800 of the approximately 8,000 known rare diseases have no treatments available. It's not that rare diseases are harder to treat than more widespread illnesses. Rather, compared to more common disorders, rare diseases simply do not draw the same level of attention from granting agencies, pharmaceutical companies, medical professionals, and researchers, so they languish in the shadows.

PMID: 28129139 [PubMed - indexed for MEDLINE]

Case report of a Li-Fraumeni syndrome-like phenotype with a de novo mutation in CHEK2.

Medicine (Baltimore). 2016 Jul;95(29):e4251

Authors: Zhuang X, Li Y, Cao H, Wang T, Chen J, Liu J, Lin L, Ye R, Li X, Liu S, Li W, Lv Y, Zhang J, He C, Xu X, Wang Z, Huang C, Liu X, Wang L

Abstract
BACKGROUND: Cases of multiple tumors are rarely reported in China. In our study, a 57-year-old female patient had concurrent squamous cell carcinoma, mucoepidermoid carcinoma, brain cancer, bone cancer, and thyroid cancer, which has rarely been reported to date.
METHODS: To determine the relationship among these multiple cancers, available DNA samples from the thyroid, lung, and skin tumors and from normal thyroid tissue were sequenced using whole exome sequencing.
RESULTS: The notable discrepancies of somatic mutations among the 3 tumor tissues indicated that they arose independently, rather than metastasizing from 1 tumor. A novel deleterious germline mutation (chr22:29091846, G->A, p.H371Y) was identified in CHEK2, a Li-Fraumeni syndrome causal gene. Examining the status of this novel mutation in the patient's healthy siblings revealed its de novo origin.
CONCLUSION: Our study reports the first case of Li-Fraumeni syndrome-like in Chinese patients and demonstrates the important contribution of de novo mutations in this type of rare disease.

PMID: 27442652 [PubMed - indexed for MEDLINE]

Rare cardiovascular diseases: from European legislations to classification and clinical practice.

Kardiol Pol. 2015;73(3):135-41

Authors: Podolec P, Stępniewski J, Podolec J, Kopeć G

PMID: 25371302 [PubMed - indexed for MEDLINE]

Data quality in rare cancers registration: the report of the RARECARE data quality study.

Tumori. 2017 Jan 21;103(1):22-32

Authors: Trama A, Marcos-Gragera R, Sánchez Pérez MJ, van der Zwan JM, Ardanaz E, Bouchardy C, Melchor JM, Martinez C, Capocaccia R, Vicentini M, Siesling S, Gatta G, RARECARE working group contributing to the data quality study

Abstract
PURPOSE: Rare cancers represent 22% of all tumors in Europe; however, the quality of the data of rare cancers may not be as good as the quality of data for common cancer. The project surveillance of rare cancers in Europe (RARECARE) had, among others, the objective of assessing rare cancer data quality in population-based cancer registries (CRs). Eight rare cancers were considered: mesothelioma, liver angiosarcoma, sarcomas, tumors of oral cavity, CNS tumors, germ cell tumors, leukemia, and malignant digestive endocrine tumors.
METHODS: We selected data on 18,000 diagnoses and revised, on the basis of the pathologic and clinical reports (but not on pathologic specimens), unspecified morphology and topography codes originally attributed by CR officers and checked the quality of follow-up of long-term survivors of poor prognosis cancers.
RESULTS: A total of 38 CRs contributed from 13 European countries. The majority of unspecified morphology and topography cases were confirmed as unspecified. The few unspecified cases that, after the review, changed to a more specific diagnosis increased the incidence of the common cancer histotypes. For example, 11% of the oral cavity epithelial cancers were reclassified from unspecified to more specific diagnoses: 8% were reclassified as squamous cell carcinoma (commoner) and only 1% as adenocarcinoma (rarer). The revision confirmed the majority of long-term survivors revealing a relative high proportion of mesothelioma long-term survivors. The majority of appendix carcinoids changed behavior from malignant to borderline lesions.
CONCLUSIONS: Our study suggests that the problem of poorly specified morphology and topography cases is mainly one of difficulty in reaching a precise diagnosis. The awareness of the importance of data quality for rare cancers should increase among registrars, pathologists, and clinicians.

PMID: 27716878 [PubMed - indexed for MEDLINE]

Abnormal increase of intraocular pressure in fellow eye after severe ocular trauma: A case report.

Medicine (Baltimore). 2016 Aug;95(31):e4411

Authors: Vaajanen A, Tuulonen A

Abstract
BACKGROUND: An ocular injury can lead to secondary glaucoma in the traumatized eye in 3% to 20% of cases. Literature on the risk of developing elevated intraocular pressure in the nontraumatized fellow eye is scant. Clinicians treating ocular traumas should also bear in mind sympathetic ophthalmia, a rare bilateral granulomatous panuveitis following accidental or surgical trauma to 1 eye.
CASE REPORT: We report a case of high-pressure glaucoma of the fellow eye without any signs of uveitis. The left eye of a 24-year-old man was injured in an inadvertent movement during a free-time table-tennis match. The eye was severely crushed, leading to blindness. His right eye developed medically uncontrolled high-pressure glaucoma only 1 month after the injury.
CONCLUSION: To the best of our knowledge, there are no previous reports of post-traumatic glaucoma in the nontraumatized eye after open-globe injury.

PMID: 27495058 [PubMed - indexed for MEDLINE]

Case Report: Traumatic Carotid-Cavernous Fistula.

J Trauma Nurs. 2016 Jan-Feb;23(1):42-4

Authors: Pülhorn H, Chandran A, Nahser H, McMahon C

Abstract
Carotid-cavernous fistulae (CCFs) are a rare complication of head trauma, with potentially serious consequences. We report the case of a 45-year-old male patient who presented with posttraumatic CCF 2 months after sustaining a head injury. Appropriate imaging in the form of computed tomography of the head, magnetic resonance imaging of the head, and digital subtraction angiography of the intracranial vessels was performed, and the CCF was successfully coil embolized. This resulted in good resolution of the patient's symptoms. We discuss the cause, presentation, diagnosis, and treatment of CCFs. Carotid-cavernous fistulae are a rare sequela of craniofacial trauma; therefore, a high index of suspicion must be maintained to establish a diagnosis and prevent serious consequences.

PMID: 26745539 [PubMed - indexed for MEDLINE]

Gene-targeting pharmaceuticals for single-gene disorders.

Hum Mol Genet. 2016 Apr 15;25(R1):R18-26

Authors: Beaudet AL, Meng L

Abstract
The concept of orphan drugs for treatment of orphan genetic diseases is perceived enthusiastically at present, and this is leading to research investment on the part of governments, disease-specific foundations and industry. This review attempts to survey the potential to use traditional pharmaceuticals as opposed to biopharmaceuticals to treat single-gene disorders. The available strategies include the use of antisense oligonucleotides (ASOs) to alter splicing or knock-down expression of a transcript, siRNAs to knock-down gene expression and drugs for nonsense mutation read-through. There is an approved drug for biallelic knock-down of the APOB gene as treatment for familial hypercholesterolemia. Both ASOs and siRNAs are being explored to knock-down the transthyretin gene to prevent the related form of amyloidosis. The use of ASOs to alter gene-splicing to treat spinal muscular atrophy is in phase 3 clinical trials. Work is progressing on the use of ASOs to activate the normally silent paternal copy of the imprinted UBE3A gene in neurons as a treatment for Angelman syndrome. A gene-activation or gene-specific ramp-up strategy would be generally helpful if such could be developed. There is exciting theoretical potential for converting biopharmaceutical strategies such gene correction and CRISPR-Cas9 editing to a synthetic pharmaceutical approach.

PMID: 26628634 [PubMed - indexed for MEDLINE]

LORD: a phenotype-genotype semantically integrated biomedical data tool to support rare disease diagnosis coding in health information systems.

AMIA Annu Symp Proc. 2015;2015:434-40

Authors: Choquet R, Maaroufi M, Fonjallaz Y, de Carrara A, Vandenbussche PY, Dhombres F, Landais P

Abstract
Characterizing a rare disease diagnosis for a given patient is often made through expert's networks. It is a complex task that could evolve over time depending on the natural history of the disease and the evolution of the scientific knowledge. Most rare diseases have genetic causes and recent improvements of sequencing techniques contribute to the discovery of many new diseases every year. Diagnosis coding in the rare disease field requires data from multiple knowledge bases to be aggregated in order to offer the clinician a global information space from possible diagnosis to clinical signs (phenotypes) and known genetic mutations (genotype). Nowadays, the major barrier to the coding activity is the lack of consolidation of such information scattered in different thesaurus such as Orphanet, OMIM or HPO. The Linking Open data for Rare Diseases (LORD) web portal we developed stands as the first attempt to fill this gap by offering an integrated view of 8,400 rare diseases linked to more than 14,500 signs and 3,270 genes. The application provides a browsing feature to navigate through the relationships between diseases, signs and genes, and some Application Programming Interfaces to help its integration in health information systems in routine.

PMID: 26958175 [PubMed - indexed for MEDLINE]

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/02/07

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.

Risk Evaluation and Mitigation Strategies (REMSs): Are They Improving Drug Safety? A Critical Review of REMSs Requiring Elements to Assure Safe Use (ETASU).

Drugs R D. 2017 Feb 03;:

Authors: Boudes PF

Abstract
Risk Evaluation and Mitigation Strategies (REMSs) with Elements to Assure Safe Use (ETASU) are requested for drugs with significant safety risks. We reviewed REMS programs issued since 2011 to evaluate their rationales, characteristics, and consistencies, and evaluated their impact on improving drug safety. We conducted a literature search and a survey of relevant websites (FDA, manufacturers, and REMSs). ETASU characteristics were summarized. REMS risks were compared with labeled risks, including black box warnings. Forty-two programs were analyzed. Seven incorporated drugs of the same class. Most drugs (57%) were indicated for an orphan disease. A single risk was mentioned in 24 REMSs, and multiple risks in 18. Embryo-fetal toxicity and abuse or misuse were the most frequent risks. All risks were identified during clinical development but some were hypothetical. Thirty-six drugs had a black box warning. REMS risks and black box risks differed for 11 drugs. A drug with multiple indications could have a REMS for one of them but not for another. Most REMSs required prescriber training and certification, half required dispenser certification and patient enrolment. REMSs were revised multiple times and only three (7%) were discontinued. No data were available to establish whether REMSs were effective in improving drug safety. Some REMSs were deemed inefficient. REMSs with ETASU continue to be implemented but their impact on improving drug safety is still not documented. Hence, one of the main requirements of the FDA Amendments Act of 2007 is not being addressed. In addition, REMSs are complex and their logic is inconsistent; we recommend a thorough re-evaluation of the REMS program.

PMID: 28160230 [PubMed - as supplied by publisher]

Pediatric pulmonology year in review 2015: Part 3.

Pediatr Pulmonol. 2016 Jul;51(7):747-53

Authors: Birnkrant DJ, Yilmaz O, Nicolai T, Black JB, Mhanna MJ, Noah TL

Abstract
Our journal covers a broad range of research and scholarly topics related to children's respiratory disorders. For updated perspectives on the rapidly expanding knowledge in our field, we will summarize the past year's publications in our major topic areas, as well as selected publications in these areas from the core clinical journal literature outside our own pages. The current review (Part 3) covers articles on asthma, diagnostic testing/endoscopy, respiratory complications of neuromuscular disorders, and rare lung diseases. Pediatr Pulmonol. 2016;51:747-753. © 2016 Wiley Periodicals, Inc.

PMID: 27105321 [PubMed - indexed for MEDLINE]

Exploring the usability of EUCERD core indicators for rare diseases.

Ann Ist Super Sanita. 2015;51(4):342-5

Authors: Ferrelli RM, De Santis M, Gentile AE, Taruscio D

Abstract
In the context of the Community Programme in the field of Health, the European Commission financed a series of initiatives to support the development and use of indicators for planning health services for Rare Diseases (RDs). The European Project for Rare Disease National Plans Development (EUROPLAN) elaborated a set of 59 process and outcome indicators, for monitoring the implementation and for evaluating the impact of the National Plans on RDs. Due to the high number and difficulty in handling the indicators, the subsequent Joint Action "Working for RDs" planned to derive a selection of 21 core indicators that were adopted by the European Union Committee of Experts on RDs in June 2013. The descriptive study carried out in the framework of the Joint Action to select the key indicators to orient policies for RDs shows that core indicators represent an excellent opportunity to share knowledge and comparability among Member States.

PMID: 26783222 [PubMed - indexed for MEDLINE]

7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/02/01

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.

10 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/01/31

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.

9 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2017/01/28

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.