Oral and Craniofacial Anomalies of Bardet-Biedl Syndrome: Dental Management in the Context of a Rare Disease.

J Dent Res. 2017 Nov;96(12):1361-1369

Authors: Panny A, Glurich I, Haws RM, Acharya A

Abstract
Standardized guidelines for the oral health management of patients with rare diseases exhibiting morphologic anomalies are currently lacking. This review considers Bardet-Biedl syndrome (BBS), a monogenic autosomal recessive nonmotile ciliopathy, as an archetypal condition. Dental anomalies are present in a majority of individuals affected by BBS due to abnormal embryonic orofacial and tooth development. Genetically encoded intrinsic oral structural anomalies and heterogeneous BBS clinical phenotypes and consequent oral comorbidities confound oral health management. Since the comorbid spectrum of BBS phenotypes spans diabetes, renal disease, obesity, sleep apnea, cardiovascular disease, and cognitive disorders, a broad spectrum of collateral oral disease may be encountered. The genetic impact of BBS on the anatomic development of oral components and oral pathology encountered in the context of various BBS phenotypes and their associated comorbidities are reviewed herein. Challenges encountered in managing patients with BBS are highlighted, emphasizing the spectrum of oral pathology associated with heterogeneous clinical phenotypic expression. Guidelines for provision of care across the spectrum of BBS clinical phenotypes are considered. Establishment of integrated medical-dental delivery models of oral care in the context of rare diseases is emphasized, including involvement of caregivers in the context of managing these patients with special needs.

PMID: 28662344 [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 2017/11/01

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.

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 2017/11/01

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.

Economic Evaluation in Duchenne Muscular Dystrophy: Model Frameworks for Cost-Effectiveness Analysis.

Pharmacoeconomics. 2017 Feb;35(2):249-258

Authors: Landfeldt E, Alfredsson L, Straub V, Lochmüller H, Bushby K, Lindgren P

Abstract
BACKGROUND: Several treatments are on the horizon for Duchenne muscular dystrophy (DMD), a terminal orphan disease. In many jurisdictions, decisions regarding pricing and reimbursement of these health technologies comprise evidence of value for money.
OBJECTIVE: The objective of this study was to develop a cost-effectiveness model based on the Duchenne muscular dystrophy Functional Ability Self-Assessment Tool (DMDSAT), a new rating scale created specifically to measure disease progression in clinical practice and trials and model DMD in economic evaluations, and compare it with two alternative model structures.
METHODS: We constructed three Markov cohort state-transition models to evaluate the cost-effectiveness of a hypothetical intervention for DMD versus standard of care in a UK setting. Model I was based on the DMDSAT, model II on stages of disease as defined in the DMD clinical care guidelines and model III on patients' ventilation status. The conceptual model structures were formulated in collaboration with three DMD experts.
RESULTS: All three models were judged to have good validity with regards to the appropriateness of the choice of modelling technique, conceptual representation of the disease, model input data and model outcomes. Across frameworks, lifetime direct medical costs with standard of care ranged between £217,510 and £284,640, total costs between £624,240 and £713,840, and total number of quality-adjusted life-years between 5.96 and 7.17.
CONCLUSIONS: We present a first version of a model for the economic evaluation of treatments for DMD based on the DMDSAT, as well as two alternative frameworks encompassing conventional staging of disease progression. Our findings should be helpful to inform health technology assessments and health economic programmes of future treatments for DMD.

PMID: 27798808 [PubMed - indexed for MEDLINE]

[Surgical treatment of a complex adolescent carpal fracture : A rare injury to the growing skeleton].

Unfallchirurg. 2017 Mar;120(3):252-256

Authors: Saul D, Ammon JC, August F

Abstract
We report the case of a 15-year-old boy with combined fractures of the scaphoid, capitate, and hamate that represents a rare variation of the well-known Fenton's syndrome. Fixation was performed for the unstable fractures of the scaphoid and capitate with the use of cannulated Herbert screws and K‑wires respectively. K‑wires were removed after 6 months, with subsequent physiotherapy. After 6 months, CT confirmed complete consolidation of the two surgically treated carpal fractures and the conservatively treated fracture of the hamate. Regarding function, the patient is able to incorporate the hand into his school-related activities and has a good range of motion, with strong closure of the fist.

PMID: 27770167 [PubMed - indexed for MEDLINE]

A first description of the Colombian national registry for rare diseases.

BMC Res Notes. 2017 Oct 26;10(1):514

Authors: Mateus HE, Pérez AM, Mesa ML, Escobar G, Gálvez JM, Montaño JI, Ospina ML, Laissue P

Abstract
OBJECTIVE: Orphan diseases must be considered a public health concern, underlying country-specific challenges for their accurate and opportune diagnosis, classification and management. Orphan disease registries have not yet been created in South America, a continent having a population of ~ 415 million inhabitants. In Colombia ~ 3 million of patients are affected by rare diseases. The aim of the present study was to establish the first Colombian national registry for rare diseases. The registry was created after the establishment of laws promoting the development of clinical guidelines for diagnosis, management, census and registry of patients suffering rare diseases.
RESULTS: In total, 13,215 patients were recorded in the Colombian registry. The survey reported 653 rare diseases. The most common diseases were congenital factor VIII deficiency (hemophilia A) (8.5%), myasthenia gravis (6.4%), von Willebrand disease (5.9%), short stature due to growth hormone qualitative anomaly (4.2%), bronchopulmonary dysplasia (3.9%) and cystic fibrosis (3.2%). Although, a marked under-reporting of cases was observed, some pathologies displayed similar behavior to that reported by other initiatives and databases. The data currently available in the registry provides a baseline for improvement regarding local and regional surveys and the start for better understanding rare diseases in Colombia.

PMID: 29073918 [PubMed - in process]

11 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 2017/10/27

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.

Analysis of First-Year Twitter Metrics of a Rare Disease Community for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) on Social Media: #BPDCN.

Curr Hematol Malig Rep. 2017 Oct 24;:

Authors: Pemmaraju N, Utengen A, Gupta V, Thompson MA, Lane AA

Abstract
PURPOSE OF REVIEW: The use of Twitter, one of the most commonly engaged social media platforms in the world, is increasing among the general public. Notably, this trend has also been observed among those involved in the healthcare field. With its ability to readily connect diverse groups of stakeholders in a given area of interest, Twitter has become a focal point for those involved in increasing awareness and information exchange in orphan disease fields. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic malignancy with generally poor long-term outcomes for adult patients and no standard therapeutic guidelines. Coupled with its low incidence rate, the disease has experienced a number of name changes over the past three decades (e.g., blastic NK cell lymphoma, CD4+CD56+ hematodermic tumor), thereby historically resulting in difficulties in its clinico-pathologic diagnosis and treatment approaches. All of these factors have led to a striking gap in terms of accurate information available to patients and the general public. Therefore, there is an urgent need for the development of more venues for the dissemination of information, particularly online, for this rare cancer.
RECENT FINDINGS: In this context, we began the Twitter medical community, #BPDCN, over a year ago, to help fill this information void. Now, completing its first year of existence, we aimed to analyze the metrics of Twitter use in order to better understand and to describe the characteristics and reach in of #BPDCN, and to determine the feasibility of starting and maintaining a disease-specific hashtag community in a particularly rare cancer.

PMID: 29064025 [PubMed - as supplied by publisher]

Drug Synergism of Proteasome Inhibitors and Mitotane by Complementary Activation of ER Stress in Adrenocortical Carcinoma Cells.

Horm Cancer. 2016 Dec;7(5-6):345-355

Authors: Kroiss M, Sbiera S, Kendl S, Kurlbaum M, Fassnacht M

Abstract
Mitotane is the only drug approved for treatment of the orphan disease adrenocortical carcinoma (ACC) and was recently shown to be the first clinically used drug acting through endoplasmic reticulum (ER)-stress induced by toxic lipids. Since mitotane has limited clinical activity as monotherapy, we here study the potential of activating ER-stress through alternative pathways. The single reliable NCI-H295 cell culture model for ACC was used to study the impact MG132, bortezomib (BTZ) and carfilzomib (CFZ) on mRNA and protein expression of ER-stress markers, cell viability and steroid hormone secretion. We found all proteasome inhibitors alone to trigger expression of mRNA (spliced X-box protein 1, XBP1) and protein markers indicative of the inositol-requiring enzyme 1 (IRE1) dependent pathway of ER-stress but not phosphorylation of eukaryotic initiation factor 2α (eIF2α), a marker of the PRKR-like endoplasmic reticulum kinase (PERK)-dependent pathway. Whereas mitotane alone activated both pathways, combination of BTZ and CFZ with low-dose mitotane blocked mitotane-induced eIF2α phosphorylation but increased XBP1-mRNA splicing indicating that proteasome inhibitors can commit signalling towards a single ER-stress pathway in ACC cells. By applying the median effect model of drug combinations using cell viability as a read out, we determined significant drug synergism between mitotane and both BTZ and CFZ. In conclusion, combination of mitotane with activators of ER-stress through the unfolded protein response is synergistic in an ACC cell culture model. Since proteasome inhibitors are readily available clinically, they are attractive candidates to study for ACC treatment in clinical trials in combination with mitotane.

PMID: 27631436 [PubMed - indexed for MEDLINE]

Hidradenitis Suppurativa: A Novel Model of Care and an Integrative Strategy to Adopt an Orphan Disease.

J Cutan Med Surg. 2017 Oct 01;:1203475417736290

Authors: Gulliver W, Landells IDR, Morgan D, Pirzada S

Abstract
Unnecessary investigations, inappropriate treatment, worsening disease, and frustration for both patients and health care professionals are the hallmarks of hidradenitis suppurativa (HS) management. In light of a new treatment algorithm and biologic therapies made available to patients, an HS model of care is outlined in this article. The recommendations and management strategy presented here have been developed to help address the currently unmet needs of this patient population. The patient-centred model of care and disease management strategies were developed through the guidance and recommendations of HS medical experts in Newfoundland and Labrador. This article lays the foundation for the resources and steps required to change the status of this orphan disease and firmly embed patients with HS within a coordinated and integrative system of care.

PMID: 29056071 [PubMed - as supplied by publisher]

Imaging features of rare mesenychmal liver tumours: beyond haemangiomas.

Br J Radiol. 2017 Nov;90(1079):20170373

Authors: Thampy R, Elsayes KM, Menias CO, Pickhardt PJ, Kang HC, Deshmukh SP, Ahmed K, Korivi BR

Abstract
Tumours arising from mesenchymal tissue components such as vascular, fibrous and adipose tissue can manifest in the liver. Although histopathology is often necessary for definitive diagnosis, many of these lesions exhibit characteristic imaging features. The radiologist plays an important role in suggesting the diagnosis, which can direct appropriate immunohistochemical staining at histology. The aim of this review is to present clinical and imaging findings of a spectrum of mesenchymal liver tumours such as haemangioma, epithelioid haemangioendothelioma, lipoma, PEComa, angiosarcoma, inflammatory myofibroblastic tumour, solitary fibrous tumour, leiomyoma, leiomyosarcoma, Kaposi sarcoma, mesenchymal hamartoma, undifferentiated embryonal sarcoma, rhabdomyosarcoma and hepatic metastases. Knowledge of the characteristic features of these tumours will aid in guiding the radiologic diagnosis and appropriate patient management.

PMID: 28766950 [PubMed - indexed for MEDLINE]

A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory.

Elife. 2016 Dec 21;5:

Authors: Mathew RS, Tatarakis A, Rudenko A, Johnson-Venkatesh EM, Yang YJ, Murphy EA, Todd TP, Schepers ST, Siuti N, Martorell AJ, Falls WA, Hammack SE, Walsh CA, Tsai LH, Umemori H, Bouton ME, Moazed D

Abstract
The SNARE-mediated vesicular transport pathway plays major roles in synaptic remodeling associated with formation of long-term memories, but the mechanisms that regulate this pathway during memory acquisition are not fully understood. Here we identify miRNAs that are up-regulated in the rodent hippocampus upon contextual fear-conditioning and identify the vesicular transport and synaptogenesis pathways as the major targets of the fear-induced miRNAs. We demonstrate that miR-153, a member of this group, inhibits the expression of key components of the vesicular transport machinery, and down-regulates Glutamate receptor A1 trafficking and neurotransmitter release. MiR-153 expression is specifically induced during LTP induction in hippocampal slices and its knockdown in the hippocampus of adult mice results in enhanced fear memory. Our results suggest that miR-153, and possibly other fear-induced miRNAs, act as components of a negative feedback loop that blocks neuronal hyperactivity at least partly through the inhibition of the vesicular transport pathway.

PMID: 28001126 [PubMed - indexed for MEDLINE]

Anaesthesia and orphan disease: airway and anaesthetic management in Huntington's disease.

BMJ Case Rep. 2017 Oct 19;2017:

Authors: Nguyen PT, Meeks D, Liotiri D

Abstract
We present a case that highlights the issues surrounding the delivery of a safe general anaesthetic to a patient with Huntington's disease (HD) and bulbar dysfunction. In the case of a 46-year-old patient undergoing laparoscopic percutaneous endoscopic gastrostomy tube insertion, we discuss the rationale behind our chosen method and anaesthetic agents as well as airway issues specific to HD. In a patient whose condition would not allow for an awake fibreoptic intubation, we opted for a modified rapid sequence induction. Special considerations were made with regard to muscle relaxation given the complications associated with inadequate paralysis and reversal in patients with HD. The technique we describe may also apply to other patient categories, such as patients with movement disorders, bulbar dysfunction and dementia.

PMID: 29054944 [PubMed - in process]

Will the RACE for Children Act lead to new treatments for pediatric cancer?

Cancer. 2017 01 01;123(2):189

Authors: Fink JL

PMID: 28067946 [PubMed - indexed for MEDLINE]

Long-term effects of systemic gene therapy in a canine model of myotubular myopathy.

Muscle Nerve. 2017 Nov;56(5):943-953

Authors: Elverman M, Goddard MA, Mack D, Snyder JM, Lawlor MW, Meng H, Beggs AH, Buj-Bello A, Poulard K, Marsh AP, Grange RW, Kelly VE, Childers MK

Abstract
INTRODUCTION: X-linked myotubular myopathy (XLMTM), a devastating pediatric disease caused by the absence of the protein myotubularin, results from mutations in the MTM1 gene. While there is no cure for XLMTM, we previously reported effects of MTM1 gene therapy using adeno-associated virus (AAV) vector on muscle weakness and pathology in MTM1-mutant dogs. Here, we followed 2 AAV-infused dogs over 4 years.
METHODS: We evaluated gait, strength, respiration, neurological function, muscle pathology, AAV vector copy number (VCN), and transgene expression.
RESULTS: Four years following AAV-mediated gene therapy, gait, respiratory performance, neurological function and pathology in AAV-infused XLMTM dogs remained comparable to their healthy littermate controls despite a decline in VCN and muscle strength.
CONCLUSIONS: AAV-mediated gene transfer of MTM1 in young XLMTM dogs results in long-term expression of myotubularin transgene with normal muscular performance and neurological function in the absence of muscle pathology. These findings support a clinical trial in patients. Muscle Nerve 56: 943-953, 2017.

PMID: 28370029 [PubMed - indexed for MEDLINE]

Nance-Horan syndrome-The oral perspective on a rare disease.

Am J Med Genet A. 2017 Jan;173(1):88-98

Authors: Gjørup H, Haubek D, Jacobsen P, Ostergaard JR

Abstract
The present study describes seven patients with Nance-Horan syndrome, all referred to a specialized oral care unit in the Central Denmark Region. A literature search on "Nance Horan Syndrome" resulted in 53 publications among which 29 reported on dental findings. Findings reported in these papers have been systematized to obtain an overview of the reported findings and the terminology on dental morphology. All seven patients included in the present study showed deviations of crown morphology on incisors and/or molars. The only consistent and very clear dental aberration was alterations in the tooth morphology that is screwdriver-shaped incisors and bud molars being most pronounced in the permanent dentition, but were also present in the primary dentition. In addition, three patients had supernumerary teeth, and three had dental agenesis. In conclusion, a dental examination as a part of the diagnostic process may reveal distinct characteristics of the dental morphology, which could be of diagnostic value and facilitate an early diagnosis. In the description of molar morphology in NHS patients, it is recommended to use the term "bud molar." The combination of congenital cataract, screwdriwer-shaped incisors and bud-shaped molars is a strong clinical indication of Nance-Horan syndrome. © 2016 Wiley Periodicals, Inc.

PMID: 27616609 [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 2017/10/19

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.

DIGNiFI: Discovering causative genes for orphan diseases using protein-protein interaction networks.

BMC Syst Biol. 2017 Mar 14;11(Suppl 3):23

Authors: Liu X, Yang Z, Lin H, Simmons M, Lu Z

Abstract
BACKGROUND: An orphan disease is any disease that affects a small percentage of the population. Orphan diseases are a great burden to patients and society, and most of them are genetic in origin. Unfortunately, our current understanding of the genes responsible for inherited orphan diseases is still quite limited. Developing effective computational algorithms to discover disease-causing genes would help unveil disease mechanisms and may enable better diagnosis and treatment.
RESULTS: We have developed a novel method, named as DIGNiFI (Disease causIng GeNe FInder), which uses Protein-Protein Interaction (PPI) network-based features to discover and rank candidate disease-causing genes. Specifically, our approach computes topologically similar genes by taking into account both local and global connected paths in PPI networks via Direct Neighbors and Local Random Walks, respectively. Furthermore, since genes with similar phenotypes tend to be functionally related, we have integrated PPI data with gene ontology (GO) annotations and protein complex data to further improve the performance of this approach. Results of 128 orphan diseases with 1184 known disease genes collected from the Orphanet show that our proposed methods outperform existing state-of-the-art methods for discovering candidate disease-causing genes. We also show that further performance improvement can be achieved when enriching the human-curated PPI network data with text-mined interactions from the biomedical literature. Finally, we demonstrate the utility of our approach by applying our method to identifying novel candidate genes for a set of four inherited retinal dystrophies. In this study, we found the top predictions for these retinal dystrophies consistent with literature reports and online databases of other retinal dystrophies.
CONCLUSIONS: Our method successfully prioritizes orphan-disease-causative genes. This method has great potential to benefit the field of orphan disease research, where resources are scarce and greatly needed.

PMID: 28361678 [PubMed - indexed for MEDLINE]

Nursing Management of Advanced Merkel Cell Carcinoma.

Oncol Nurs Forum. 2016 Nov 01;43(6):680-683

Authors: Lowry PA, Freeman ML, Russell JS

Abstract
Merkel cell carcinoma (MCC) is a rare and lethal skin cancer with few known treatment options. Management of this disease is challenging, and oncology nurses must understand the medical, physical, and psychosocial burden that MCC places on the patient and family caregivers. Patients must navigate a complex medical and insurance network that often fails to support patients with rare cancers. Nurses must advocate for these patients to ensure quality comprehensive cancer care.

PMID: 27768129 [PubMed - indexed for MEDLINE]

Liver transplantation for children with acute liver failure associated with secondary hemophagocytic lymphohistiocytosis.

Liver Transpl. 2016 Sep;22(9):1245-53

Authors: Amir AZ, Ling SC, Naqvi A, Weitzman S, Fecteau A, Grant D, Ghanekar A, Cattral M, Nalli N, Cutz E, Kamath B, Jones N, De Angelis M, Ng V, Avitzur Y

Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening systemic disease, characterized by overwhelming stimulation of the immune system and categorized as primary or secondary types. Occasionally, acute liver failure (ALF) may dominate the clinical presentation. Given the systemic nature of HLH and risk of recurrence, HLH is considered by many a contraindication to liver transplantation (LT). The aim of this study is to review our single-center experience with LT in children with secondary HLH and ALF (HLH-ALF). This is a cross-sectional, retrospective study of children with secondary HLH-ALF that underwent LT in 2005-2014. Of 246 LTs, 9 patients (3 males; median age, 5 years; range, 0.7-15.4 years) underwent LT for secondary HLH-ALF. Disease progression was rapid with median 14 days (range, 6-27 days) between first symptoms and LT. Low fibrinogen/high triglycerides, elevated ferritin, hemophagocytosis on liver biopsy, and soluble interleukin 2 receptor levels were the most commonly fulfilled diagnostic criteria; HLH genetic studies were negative in all patients. Immunosuppressive therapy after LT included corticosteroids adjusted to HLH treatment protocol and tacrolimus. Thymoglobulin (n = 5), etoposide (n = 4), and alemtuzumab (n = 2) were used in cases of recurrence. Five (56%) patients experienced HLH recurrence, 1 requiring repeat LT, and 3 died. Overall graft and patient survival were 60% and 67%, respectively. Six patients are alive and well at a median of 24 months (range, 15-72 months) after transplantation. In conclusion, LT can be beneficial in selected patients with secondary HLH-ALF and can restore good health in an otherwise lethal condition. Liver Transplantation 22 1245-1253 2016 AASLD.

PMID: 27216884 [PubMed - indexed for MEDLINE]