Chronic invasive fungal sinusitis: characterization and shift in management of a rare disease.

Int Forum Allergy Rhinol. 2016 Dec;6(12):1294-1300

Authors: D'Anza B, Stokken J, Greene JS, Kennedy T, Woodard TD, Sindwani R

Abstract
BACKGROUND: Chronic invasive fungal sinusitis (CIFS) is a rare subtype of mycotic diseases involving the paranasal sinuses. It is characterized by a slow onset and invasive organisms with non-granulomatous inflammation seen on histopathology. Historically, treatment has involved radical surgical resection. The purpose of this study was to describe the presentation, comorbidities, and role of more conservative treatment options.
METHODS: This is a multi-institutional retrospective case series of 6 patients with CIFS over 15 years. Patients' medical comorbidities, imaging results, operative procedures, pathological findings including organisms identified, antimicrobial medications used, and outcomes were reviewed.
RESULTS: The mean time from onset of symptoms to diagnosis was 6 months. Cultures and fungal PCR identified Aspergillus species in every case. All 6 patients were found to have systemic comorbidities, with many being diabetic. Imaging findings ranged from thickening of sinus mucosa to invasion of the orbit and skull base. Treatment included long-term antifungal therapy and conservative endoscopic surgery in all but 1 patient, who had an open approach. Every patient was free of invasive fungal disease at last follow-up, with a range of 1 to 27 months.
CONCLUSION: CIFS is an insidious disease often with months between symptom onset and diagnosis. It is differentiated from chronic granulomatous invasive fungal sinusitis (CGIFS) by a lack of granulomas on histopathology and an association with diabetes mellitus. Endoscopic debridement combined with long-term oral voriconazole was an effective treatment strategy in this series.

PMID: 27463614 [PubMed - indexed for MEDLINE]

26 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 2017/11/08

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.

26 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 2017/11/08

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.

[Complement factor B mutation in atypical hemolytic uremic syndrome. Rare cause of rare disease].

G Ital Nefrol. 2017 Apr;34(2):74-81

Authors: Visconti L, Cernaro V, Ardissino G, Sgarbanti M, Ferrara D, Visconti G, Santoro D, Buemi M

Abstract
Hemolytic uremic syndrome (HUS) is a rare disease characterized by microangiopathic hemolysis, platelet consumption and multiple organ failure with predominant renal involvement. In the most of cases (85-90%), it is associated with enteric infection due to Shiga-toxin or verocytotoxin (STEC-VTEC)-producer Escherichia coli. Rarely, in about 10-15% of cases, HUS develops in the presence of a disorder of alternative complement pathway regulation and it is defined atypical (aHUS). We describe the case of a 65-year-old man who came to our attention with a clinical presentation of aHUS and a clinical course characterized by rapidly progressive acute renal failure (ARF), which required renal replacement treatments, and by a stable clinical picture of hematological impairment as a marker of a non-severe and self-limiting form. The clinical and laboratory course allowed us not to perform specific therapies such as plasma exchange and/or block of the complement with eculizumab. Less than two weeks after hospital admission, there was a gradual recovery of renal function with spontaneous diuresis and hematological remission. Genetic screening has revealed a heterozygous mutation in the complement factor B (CFB) that is not described in the literature and therefore not yet characterized in the genotype/phenotype correlation, also for the extreme rarity of the forms associated with CFB alteration. In conclusion, the presence of a new mutation in the CFB, such as the one described in our case, is probably associated with the development of aHUS but has not led to a poor prognosis, as generally reported in the literature for known variants of the CFB.

PMID: 28682564 [PubMed - indexed for MEDLINE]

De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability.

Am J Hum Genet. 2017 Nov 02;101(5):768-788

Authors: Küry S, van Woerden GM, Besnard T, Proietti Onori M, Latypova X, Towne MC, Cho MT, Prescott TE, Ploeg MA, Sanders S, Stessman HAF, Pujol A, Distel B, Robak LA, Bernstein JA, Denommé-Pichon AS, Lesca G, Sellars EA, Berg J, Carré W, Busk ØL, van Bon BWM, Waugh JL, Deardorff M, Hoganson GE, Bosanko KB, Johnson DS, Dabir T, Holla ØL, Sarkar A, Tveten K, de Bellescize J, Braathen GJ, Terhal PA, Grange DK, van Haeringen A, Lam C, Mirzaa G, Burton J, Bhoj EJ, Douglas J, Santani AB, Nesbitt AI, Helbig KL, Andrews MV, Begtrup A, Tang S, van Gassen KLI, Juusola J, Foss K, Enns GM, Moog U, Hinderhofer K, Paramasivam N, Lincoln S, Kusako BH, Lindenbaum P, Charpentier E, Nowak CB, Cherot E, Simonet T, Ruivenkamp CAL, Hahn S, Brownstein CA, Xia F, Schmitt S, Deb W, Bonneau D, Nizon M, Quinquis D, Chelly J, Rudolf G, Sanlaville D, Parent P, Gilbert-Dussardier B, Toutain A, Sutton VR, Thies J, Peart-Vissers LELM, Boisseau P, Vincent M, Grabrucker AM, Dubourg C, Undiagnosed Diseases Network, Tan WH, Verbeek NE, Granzow M, Santen GWE, Shendure J, Isidor B, Pasquier L, Redon R, Yang Y, State MW, Kleefstra T, Cogné B, GEM HUGO, Deciphering Developmental Disorders Study, Petrovski S, Retterer K, Eichler EE, Rosenfeld JA, Agrawal PB, Bézieau S, Odent S, Elgersma Y, Mercier S

Abstract
Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a whole-exome sequencing approach, we identified 19 exceedingly rare de novo CAMK2A or CAMK2B variants in 24 unrelated individuals with intellectual disability. Variants were assessed for their effect on CAMK2 function and on neuronal migration. For both CAMK2A and CAMK2B, we identified mutations that decreased or increased CAMK2 auto-phosphorylation at Thr286/Thr287. We further found that all mutations affecting auto-phosphorylation also affected neuronal migration, highlighting the importance of tightly regulated CAMK2 auto-phosphorylation in neuronal function and neurodevelopment. Our data establish the importance of CAMK2A and CAMK2B and their auto-phosphorylation in human brain function and expand the phenotypic spectrum of the disorders caused by variants in key players of the glutamatergic signaling pathway.

PMID: 29100089 [PubMed - in process]

Practical videoconference training: Experience from a Norwegian resource centre for rare disorders.

Commun Med. 2015;12(2-3):199-209

Authors: Hagen K, Hummelvoll G

Abstract
A pilot programme was developed for training professionals to communicate in counselling situations via videoconferencing, with participants from Norwegian resource centres for rare disorders. The programme was conducted at three videoconferencing studios, and entailed three sessions involving role play, feedback, reflection, and discussion. After each session, participants received a short web-based questionnaire. The programme was generally perceived as realistic, with 95% of participants considering it to be a suitable training method and 94% reporting greater awareness of how to engage successfully in dialogue during videoconferencing. Those who experienced technical difficulties reported significantly lower satisfaction with the role play, feedback, and discussion segments. Experiences conveyed in the feedback and reflection segments are described, demonstrating the importance of an appropriate technical infrastructure and giving useful insights into how videoconferences should be performed. The programme could be replicated and developed further and offered to professionals who give counselling services via videoconferences.

PMID: 29048147 [PubMed - indexed for MEDLINE]

32 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 2017/11/03

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.

Nothing But NET: A Review of Neuroendocrine Tumors and Carcinomas.

Neoplasia. 2017 Oct 29;19(12):991-1002

Authors: Oronsky B, Ma PC, Morgensztern D, Carter CA

Abstract
This review covers the diverse topic of neuroendocrine neoplasms (NENs), a relatively rare and heterogeneous tumor type, comprising ~2% of all malignancies, with a prevalence of <200,000 in the United States, which makes it an orphan disease (Basu et al., 2010).(1) For functional purposes, NENs are divided into two groups on the basis of clinical behavior, histology, and proliferation rate: well differentiated (low grade to intermediate grade) neuroendocrine tumors and poorly differentiated (high grade) neuroendocrine carcinoma (Bosman et al., 2010)(2); this histological categorization/dichotomization is highly clinically relevant with respect to impact on treatment and prognosis even though it is not absolute since a subset of tumors with a low-grade appearance behaves similarly to high-grade lesions. Given the relative dearth of evidenced-based literature about this orphan disease as a whole (Modlin et al., 2008),(3) since the focus of most articles is on particular anatomic subtypes of NENs (i.e., gastroenteropancreatic or pulmonary), the purpose of this review is to summarize the presentation, pathophysiology, staging, current standard of care treatments, and active areas of current research.

PMID: 29091800 [PubMed - as supplied by publisher]

Case-finding for alpha1-antitrypsin deficiency in Kazakh patients with COPD.

Multidiscip Respir Med. 2017;12:23

Authors: Zhumagaliyeva A, Ottaviani S, Greulich T, Gorrini M, Vogelmeier C, Karazhanova L, Nurgazina G, DeSilvestri A, Kotke V, Barzon V, Zorzetto M, Corsico A, Ferrarotti I

Abstract
BACKGROUND: Alpha-1-antitrypsin deficiency (AATD) is an under-diagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to screen for AATD in Kazakh patients with COPD using dried blood spot specimens.
METHODS: The alpha1-antitrypsin (AAT) concentration was determined by nephelometry, PCR was used to detect PiS and PiZ alleles; and isoelectric focusing was used to confirm questionable genotype results and detect rare AAT variants.
RESULTS: To this aim, 187 Kazakh subjects with COPD were recruited. Blood samples were collected as dried blood spot. Genotyping of 187 samples revealed 3 (1.6%) PI*MZ and 1 (0.53%) PI*MS, Phenotyping identified also two sample (1.1%) with phenotype PiMI. Allelic frequencies of pathological mutations Z, S and I resulted 0.8%, 0.3%, 0.5%, respectively, in COPD Kazakh population.
CONCLUSION: This study proved that AATD is present in the Kazakh population. These results support the general concept of targeted screening for AAT deficiency in countries like Kazakhstan, with a large population of COPD patients and low awareness among care-givers about this genetic condition.

PMID: 29090095 [PubMed]

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]