Langerhans Cell Histiocytosis in an Adult: A Discussion of Epidemiology and Treatment Options.

J Craniofac Surg. 2020 Jan/Feb;31(1):e70-e73

Authors: El-Arab KK, Luedke AI, Julian BT, Ferrauiola J, Miller FR, Wang HT

Abstract
Langerhans cell histiocytosis (LCH) is a rare disorder defined by the abnormal proliferation of Langerhans cells. While LCH can present at any age, it is classically described as a pediatric condition, and is therefore overlooked in the adult patient. Additionally, depending on tumor burden and location, LCH can manifest with a host of oral and systemic symptoms which further confuses the clinical presentation and ultimate diagnosis.The authors present a unique report of an elderly Hispanic male diagnosed with mandibular LCH who sought primary tumor excision after neoadjuvant chemotherapy. In this study, a fibula-free flap was used for subsequent reconstruction.The purpose of the study is 2-fold: to highlight the variability of LCH in both patient symptomatology and demographics, as well as the role of plastic reconstructive surgery in definitive LCH management, particularly in the setting of single system unifocal disease.

PMID: 31634312 [PubMed - indexed for MEDLINE]

Australian Genomics: A Federated Model for Integrating Genomics into Healthcare.

Am J Hum Genet. 2019 07 03;105(1):7-14

Authors: Stark Z, Boughtwood T, Phillips P, Christodoulou J, Hansen DP, Braithwaite J, Newson AJ, Gaff CL, Sinclair AH, North KN

Abstract
Australian Genomics is a national collaborative research partnership of more than 80 organizations piloting a whole-of-system approach to integrating genomics into healthcare that is based on federation principles. The aim of Australian Genomics is to assess the application of genomic testing in healthcare at the translational interface between research and clinical delivery, with an emphasis on robust evaluation of outcomes. It encompasses two bodies of work: a research program prospectively providing genomic testing through exemplar clinical projects in rare diseases, cancers, and reproductive carrier screening and interdependent programs for advancing the diagnostic, health informatics, regulatory, ethical, policy, and workforce infrastructure necessary for the integration of genomics into the Australian health system.

PMID: 31271757 [PubMed - indexed for MEDLINE]

Cystic Fibrosis: Proteostatic correctors of CFTR trafficking and alternative therapeutic targets.

Expert Opin Ther Targets. 2019 08;23(8):711-724

Authors: Hanrahan JW, Sato Y, Carlile GW, Jansen G, Young JC, Thomas DY

Abstract
Introduction: Cystic fibrosis (CF) is the most frequent lethal orphan disease and is caused by mutations in the CFTR gene. The most frequent mutation F508del-CFTR affects multiple organs; infections and subsequent infections and complications in the lung lead to death. Areas covered: This review focuses on new targets and mechanisms that are attracting interest for the development of CF therapies. The F508del-CFTR protein is retained in the endoplasmic reticulum (ER) but has some function if it can traffic to the plasma membrane. Cell-based assays have been used to screen chemical libraries for small molecule correctors that restore its trafficking. Pharmacological chaperones are correctors that bind directly to the F508del-CFTR mutant and promote its folding and trafficking. Other correctors fall into a heterogeneous class of proteostasis modulators that act indirectly by altering cellular homeostasis. Expert opinion: Pharmacological chaperones have so far been the most successful correctors of F508del-CFTR trafficking, but their level of correction means that more than one corrector is required. Proteostasis modulators have low levels of correction but hold promise because some can correct several different CFTR mutations. Identification of their cellular targets and the potential for development may lead to new therapies for CF.

PMID: 31169041 [PubMed - indexed for MEDLINE]

The Genomic Medicine Integrative Research Framework: A Conceptual Framework for Conducting Genomic Medicine Research.

Am J Hum Genet. 2019 06 06;104(6):1088-1096

Authors: Horowitz CR, Orlando LA, Slavotinek AM, Peterson J, Angelo F, Biesecker B, Bonham VL, Cameron LD, Fullerton SM, Gelb BD, Goddard KAB, Hailu B, Hart R, Hindorff LA, Jarvik GP, Kaufman D, Kenny EE, Knight SJ, Koenig BA, Korf BR, Madden E, McGuire AL, Ou J, Wasserstein MP, Robinson M, Leventhal H, Sanderson SC

Abstract
Conceptual frameworks are useful in research because they can highlight priority research domains, inform decisions about interventions, identify outcomes and factors to measure, and display how factors might relate to each other to generate and test hypotheses. Discovery, translational, and implementation research are all critical to the overall mission of genomic medicine and prevention, but they have yet to be organized into a unified conceptual framework. To fill this gap, our diverse team collaborated to develop the Genomic Medicine Integrative Research (GMIR) Framework, a simple but comprehensive tool to aid the genomics community in developing research questions, strategies, and measures and in integrating genomic medicine and prevention into clinical practice. Here we present the GMIR Framework and its development, along with examples of its use for research development, demonstrating how we applied it to select and harmonize measures for use across diverse genomic medicine implementation projects. Researchers can utilize the GMIR Framework for their own research, collaborative investigations, and clinical implementation efforts; clinicians can use it to establish and evaluate programs; and all stakeholders can use it to help allocate resources and make sure that the full complexity of etiology is included in research and program design, development, and evaluation.

PMID: 31104772 [PubMed - indexed for MEDLINE]

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 2020/03/11

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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 2020/03/10

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.

Coronary Involvement in Behçet's Disease: what are its Risks and Prognosis? (Rare Cases and Literature Review).

Braz J Cardiovasc Surg. 2020 01 01;34(6):749-758

Authors: Vural U, Kizilay M, Aglar AA

Abstract
OBJECTIVE: In our clinic, we aimed to investigate the effect of preoperative risk factors and postoperative complications on reoperation and mortality in cases with Behçet's disease which presents very rare coronary artery involvement.
METHODS: Thirteen patients with Behçet's Disease who had undergone coronary artery bypass grafting in our center between 2003 and 2015 were analyzed. We evaluated the clinical and laboratory findings, complications and mortality rates of our patients in light of the literature.
RESULTS: The mean age was 38.5 (30-55; 3 women). The mean time from onset of Behçet's disease to coronary artery disease was 4,7 (3-11) years. Fifty-four percent of the patients were asymptomatic. Coronary artery disease of these was exposed while peripheral vascular surgery was planned due to complications of Behçet's disease. Symptomatic patients presented angina pectoris (31%), acute coronary syndrome (8%) and arrhythmia (8%). In coronary pathology of patients, distal type obstruction (31%), aneurysm and pseudoaneurysm (31%), proximal segment thrombus (15%), chronic type stenosis and occlusions (31%) were present. Early mortality (15%) was due to acute myocardial infarction while the late mortality (15%) was due to cerebral and gastrointestinal bleeding. Reoperation was due to bleeding in one case on the 1st postoperative day and due to acute pulmonary embolism in another case in the 3rdpostoperative year.
CONCLUSION: In Behçet's disease, coronary artery bypass grafting is a procedure with high mortality, especially in the acute period. The on-pump surgery technique in these cases can be safely performed for multiple bypasses and in patients above 40 years old.

PMID: 31241876 [PubMed - indexed for MEDLINE]

Rare occurrence of Hirayama disease in Brazil.

Arq Neuropsiquiatr. 2019 05 01;77(5):370-371

Authors: Bogoni M, Teixeira BCA, Cioni M

PMID: 31189004 [PubMed - indexed for MEDLINE]

Refined Disease Risk Index for Hematological Malignancies, Including Rare Disorders, After Allogeneic Stem Cell Transplantation.

Transplant Proc. 2019 Dec;51(10):3437-3443

Authors: Fujiwara S, Hattori N, Matsui T, Nakata A, Sasaki Y, Shimada S, Murai S, Abe M, Baba Y, Watanuki M, Kawaguchi Y, Arai N, Kabasawa N, Tsukamoto H, Uto Y, Yanagisawa K, Harada H, Nakamaki T

Abstract
OBJECTIVE: The refined disease risk index (R-DRI) is a well-designed prognostic parameter that is based on only the disease type and status and is used for stratifying patients undergoing allogeneic hematopoietic stem cell transplantation (allo HSCT) into 4 risk groups. However, the application of the R-DRI for rare diseases has remained unclear.
METHODS: We evaluated 135 patients who underwent allo HSCT for hematological malignancies including rare diseases, such as acute leukemia of ambiguous lineage, acute T-cell leukemia/lymphoma, extranodal natural killer T-cell lymphoma, and lymphoblastic lymphoma, at our institute.
RESULTS: According to the R-DRI, overall survival (OS) and progression-free survival at 2 years for patients with the low, intermediate, high, and very high groups were 66.7% and 66.7%, 60.8% and 56.0%, 27.1% and 23.7%, and 5.9% and 5.1%, respectively (P < .0001 and P < .0001, respectively). OS showed no significant difference between B-cell non-Hodgkin lymphoma (B-NHL) and T-cell non-Hodgkin lymphoma (T-NHL) (P = .71). Moreover, OS at 1 year was 80%, 14.3%, 60%, and 0% for the intermediate risk group, the very high-risk group of B-NHL, the intermediate risk group, and the high-risk group of T-NHL, respectively (P = .035).
CONCLUSION: We showed the applicability of the R-DRI for hematological malignancies, including rare disorders. However, we suggest that T-NHL patients may be better to be assigned between the nodal group and the extranodal group in the R-DRI.

PMID: 31733801 [PubMed - indexed for MEDLINE]

Neonatal oesophageal perforation: The role for non-operative management.

J Paediatr Child Health. 2018 08;54(8):872-874

Authors: Hodgson K, Togo A, Moore AM, Moody A, King SK, Zani A

Abstract
AIM: Isolated oesophageal perforation in neonates is a rare but potentially life-threatening condition. Although management has historically been operative, conservative management (antibiotics, bowel rest, parenteral nutrition) is now more routinely used. The aim of this study was to evaluate the management of this condition in two large neonatal surgical centres.
METHODS: A retrospective cohort study was conducted for neonates admitted to The Hospital for Sick Children (Toronto, Canada) or The Royal Children's Hospital (Melbourne, Australia) with a diagnosis of oesophageal perforation, from 2006 to 2016. Patients with oesophageal atresia or tracheo-oesophageal fistula were excluded. Data were collected from chart review regarding demographics, clinical course, management and outcomes.
RESULTS: Eleven neonates with oesophageal perforation were identified over a 10-year period at the two centres. Median gestational age at birth was 25.3 weeks (interquartile range 24.2-28.8) and the majority (7/11, 64%) of neonates were extremely low birthweight. Diagnosis was made on day 1 of life for 9 of 11 (81%) neonates and was secondary to nasogastric tube insertion in 10 of 11 (91%) neonates. Only four (36%) neonates had symptomatic complications. All neonates were managed with bowel rest and intravenous antibiotics for a median of 7 days (interquartile range 7-10); two patients required operative intervention. Three neonates (27%) developed chronic lung disease and two (19%) died prior to discharge.
CONCLUSIONS: Oesophageal perforation is severe complication secondary to instrumentation of the upper gastrointestinal tract in neonates. Prompt and accurate diagnosis is crucial. Non-operative management is effective for the majority, though morbidity is common.

PMID: 29602257 [PubMed - indexed for MEDLINE]

Pilomatrix Carcinoma: A Rare Hair Cell Tumor.

Am Surg. 2020 Jan 01;86(1):e38-e39

Authors: Briley T, Sobiesk JL, Chu Q

PMID: 32077434 [PubMed - indexed for MEDLINE]

A RARE CASE OF ISCHEMIC COLITIS: CEFUROXIME-RELATED ANAPHYLACTIC SHOCK.

Gastroenterol Nurs. 2019 Sep/Oct;42(5):448-450

Authors: Gül Utku Ö, Ergül B, Balci M, Oğuz D

PMID: 31574074 [PubMed - indexed for MEDLINE]

Cognitive Abilities of Dogs with Mucopolysaccharidosis I: Learning and Memory.

Animals (Basel). 2020 Feb 28;10(3):

Authors: Provoost L, Siracusa C, Stefanovski D, Che Y, Li M, Casal M

Abstract
Mucopolysaccharidosis I (MPS I) results from a deficiency of a lysosomal enzyme, alpha-L-iduronidase (IDUA). IDUA deficiency leads to glycosaminoglycan (GAG) accumulation resulting in cellular degeneration and multi-organ dysfunction. The primary aims of this pilot study were to determine the feasibility of cognitive testing MPS I affected dogs and to determine their non-social cognitive abilities with and without gene therapy. Fourteen dogs were tested: 5 MPS I untreated, 5 MPS I treated, and 4 clinically normal. The treated group received intrathecal gene therapy as neonates to replace the IDUA gene. Cognitive tests included delayed non-match to position (DNMP), two-object visual discrimination (VD), reversal learning (RL), attention oddity (AO), and two-scent discrimination (SD). Responses were recorded as correct, incorrect, or no response, and analyzed using mixed effect logistic regression analysis. Significant differences were not observed among the three groups for DNMP, VD, RL, or AO. The MPS I untreated dogs were excluded from AO testing due to failing to pass acquisition of the task, potentially representing a learning or executive function deficit. The MPS I affected group (treated and untreated) was significantly more likely to discriminate between scents than the normal group, which may be due to an age effect. The normal group was comprised of the oldest dogs, and a mixed effect logistic model indicated that older dogs were more likely to respond incorrectly on scent discrimination. Overall, this study found that cognition testing of MPS I affected dogs to be feasible. This work provides a framework to refine future cognition studies of dogs affected with diseases, including MPS I, in order to assess therapies in a more comprehensive manner.

PMID: 32121123 [PubMed]

A case report of Proteus syndrome (PS).

BMC Med Genet. 2020 01 21;21(1):15

Authors: Zeng X, Wen X, Liang X, Wang L, Xu L

Abstract
BACKGROUND: Proteus syndrome (PS) is an extremely rare disease characterized by excessive chimeric growth of cells, and progressive and irregular asymmetrical hyperplasia.
CASE PRESENTATION: Herein, a PS case with atypical clinical features and syndromes was reported, to improve the understanding of the diagnosis and treatment of the disease. The case was a 3-year-and-11-month-old male child. He was admitted due to a primary diagnosis of McCune-Albright syndrome. After admission, the lesion samples from the milk coffee spots, and nodular thickening skin at hands and feet were subjected to genetic screening. Genetic testing results confirmed the diagnosis of PS.
CONCLUSIONS: Based on the clinical manifestations, laboratory tests, imaging data, and literature reviewing, the etiology, diagnosis, treatment and prognosis of PS have been analyzed and discussed.

PMID: 31964351 [PubMed - indexed for MEDLINE]

Hypertrophic Cardiomyopathy in Noonan Syndrome Treated by MEK-Inhibition.

J Am Coll Cardiol. 2019 05 07;73(17):2237-2239

Authors: Andelfinger G, Marquis C, Raboisson MJ, Théoret Y, Waldmüller S, Wiegand G, Gelb BD, Zenker M, Delrue MA, Hofbeck M

PMID: 31047013 [PubMed - indexed for MEDLINE]

Rare Mesenteric Arterial Diseases: Fibromuscular Dysplasia and Segmental Arterial Mediolysis and Literature Review.

Intern Med. 2019 Dec 01;58(23):3393-3400

Authors: Ko M, Kamimura K, Sakamaki A, Niwa Y, Tominaga K, Mizuno K, Terai S

Abstract
Fibromuscular dysplasia (FMD) and segmental arterial mediolysis (SAM) are noninflammatory, nonatherosclerotic arterial diseases that cause aneurysm, occlusion, and thromboses. These diseases are rarely seen in mesenteric arterial lesions; however, as they can be lethal if appropriate management is not provided, the accumulation of clinical information from cases is essential. We herein report the cases of a 57-year-old man diagnosed with FMD and a 63-year-old man diagnosed with SAM. We conclude that an early diagnosis with imaging modalities and clinical information followed by the appropriate treatment improves the prognosis of these arterial diseases.

PMID: 31327836 [PubMed - indexed for MEDLINE]

Simulating the Impact of Elevated Levels of Interleukin-6 on the Pharmacokinetics of Various CYP450 Substrates in Patients with Neuromyelitis Optica or Neuromyelitis Optica Spectrum Disorders in Different Ethnic Populations.

AAPS J. 2019 03 18;21(3):42

Authors: Machavaram KK, Endo-Tsukude C, Terao K, Gill KL, Hatley OJ, Gardner I, Parrott N, Ducray PS

Abstract
A physiologically based pharmacokinetic (PBPK) model was used to simulate the impact of elevated levels of interleukin (IL)-6 on the exposure of several orally administered cytochrome P450 (CYP) probe substrates (caffeine, S-warfarin, omeprazole, dextromethorphan, midazolam, and simvastatin). The changes in exposure of these substrates in subjects with rheumatoid arthritis (and hence elevated IL-6 levels) compared with healthy subjects were predicted with a reasonable degree of accuracy. The PBPK model was then used to simulate the change in oral exposure of the probe substrates in North European Caucasian, Chinese, and Japanese population of patients with neuromyelitis optica (NMO) or NMO spectrum disorder with elevated plasma IL-6 levels (up to 100 pg/mL). Moderate interactions [mean AUC fold change, ≤ 2.08 (midazolam) or 2.36 (simvastatin)] was predicted for CYP3A4 probe substrates and weak interactions (mean AUC fold change, ≤ 1.29-1.97) were predicted for CYP2C19, CYP2C9, and CYP2D6 substrates. No notable interaction was predicted with CYP1A2. Although ethnic differences led to differences in simulated exposure for some of the probe substrates, there were no marked differences in the predicted magnitude of the change in exposure following IL-6-mediated suppression of CYPs. Decreased levels of serum albumin (as reported in NMO patients) had little impact on the magnitude of the simulated IL-6-mediated drug interactions. This PBPK modeling approach allowed us to leverage knowledge from different disease and ethnic populations to make predictions of cytokine-related DDIs in a rare disease population where actual clinical studies would otherwise be difficult to conduct.

PMID: 30887238 [PubMed - indexed for MEDLINE]

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 2020/02/29

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.

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 2020/02/28

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.

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 2020/02/27

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.