The importance of effective registries in pulmonary diseases and how to optimize their output.

Chron Respir Dis. 2019 Jan-Dec;16:1479973119881777

Authors: Chorostowska-Wynimko J, Wencker M, Horváth I

Abstract
Randomized controlled trials (RCTs) are essential for the approval of new therapies; however, because of their design, they provide little insight concerning disease epidemiology/etiology and current clinical practice. Particularly, in lung disease, rigid inclusion/exclusion criteria can limit the generalizability of pivotal trial data. Noninterventional studies (NIS), conducted through the well-established mechanism of patient registries, are undervalued as a means to close data gaps left by RCTs by providing essential data that can guide patient care at different levels from clinical decision-making to health-care policy. While NIS contribute valuable data in all disease areas, their importance in rare diseases cannot be underestimated. In respiratory disease, registries have been essential in understanding the natural history and different phenotypes of rare conditions, such as alpha 1 antitrypsin deficiency, cystic fibrosis, and idiopathic pulmonary fibrosis. Importantly, additional therapeutic outcome data were generated. While measures for enhancing data quality in RCTs have evolved significantly, the approach and effectiveness of registries is variable. Within this article, we review the contribution of registries to pulmonary disease and make recommendations for their effective management. Additionally, we assess limitations of registry data as well as challenges to registry operation, including the impact of the European Union General Data Protection Regulation.

PMID: 31645111 [PubMed - indexed for MEDLINE]

50 Years Ago in The Journal of Pediatrics: Intestinal Obstruction Complicating Familial Mediterranean Fever.

J Pediatr. 2019 Jun;209:22

Authors: Hashkes PJ

PMID: 31128728 [PubMed - indexed for MEDLINE]

Primary Adrenal Hodgkin Lymphoma: A Rare Disease Manifestation.

Am Surg. 2020 Mar 01;86(3):e147-e149

Authors: Jenkins FG, Grova M, Maygarden SJ, Kim LT

PMID: 32223825 [PubMed - indexed for MEDLINE]

Gene Therapy Approaches to a Rare Retinal Disease: Choroideremia.

Dtsch Arztebl Int. 2020 01 17;117(3):30

Authors: Birtel J, Holz FG, Herrmann P

PMID: 32031510 [PubMed - indexed for MEDLINE]

Treatment and long-term outcome in primary distal renal tubular acidosis.

Nephrol Dial Transplant. 2019 06 01;34(6):981-991

Authors: Lopez-Garcia SC, Emma F, Walsh SB, Fila M, Hooman N, Zaniew M, Bertholet-Thomas A, Colussi G, Burgmaier K, Levtchenko E, Sharma J, Singhal J, Soliman NA, Ariceta G, Basu B, Murer L, Tasic V, Tsygin A, Decramer S, Gil-Peña H, Koster-Kamphuis L, La Scola C, Gellermann J, Konrad M, Lilien M, Francisco T, Tramma D, Trnka P, Yüksel S, Caruso MR, Chromek M, Ekinci Z, Gambaro G, Kari JA, König J, Taroni F, Thumfart J, Trepiccione F, Winding L, Wühl E, Ağbaş A, Belkevich A, Vargas-Poussou R, Blanchard A, Conti G, Boyer O, Dursun I, Pınarbaşı AS, Melek E, Miglinas M, Novo R, Mallett A, Milosevic D, Szczepanska M, Wente S, Cheong HI, Sinha R, Gucev Z, Dufek S, Iancu D, European dRTA Consortium, Kleta R, Schaefer F, Bockenhauer D

Abstract
BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome.
METHODS: We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form.
RESULTS: Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%). The median (range) presentation age was 0.5 (0-54) years and age at last follow-up was 11.0 (0-70.0) years. Adult height was slightly below average with a mean (SD score) of -0.57 (±1.16). There was an increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (35%) and adults (82%). Nephrocalcinosis was reported in 88%. Nephrolithiasis was more common with SLC4A1 mutations (42% versus 21%). Thirty-six percent had hearing loss, particularly in ATP6V1B1 (88%). The median (interquartile range) prescribed dose of alkali (mEq/kg/day) was 1.9 (1.2-3.3). Adequate metabolic control (normal plasma bicarbonate and normocalciuria) was achieved in 158 patients (51%), more commonly in countries with higher gross domestic product (67% versus 23%), and was associated with higher height and estimated glomerular filtration rate.
CONCLUSION: Long-term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD Stage 5. However, 82% of adult patients have CKD Stages 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.

PMID: 30773598 [PubMed - indexed for MEDLINE]

Spectrum of neurodevelopmental disease associated with the GNAO1 guanosine triphosphate-binding region.

Epilepsia. 2019 03;60(3):406-418

Authors: Kelly M, Park M, Mihalek I, Rochtus A, Gramm M, Pérez-Palma E, Axeen ET, Hung CY, Olson H, Swanson L, Anselm I, Briere LC, High FA, Sweetser DA, Undiagnosed Diseases Network, Kayani S, Snyder M, Calvert S, Scheffer IE, Yang E, Waugh JL, Lal D, Bodamer O, Poduri A

Abstract
OBJECTIVE: To characterize the phenotypic spectrum associated with GNAO1 variants and establish genotype-protein structure-phenotype relationships.
METHODS: We evaluated the phenotypes of 14 patients with GNAO1 variants, analyzed their variants for potential pathogenicity, and mapped them, along with those in the literature, on a three-dimensional structural protein model.
RESULTS: The 14 patients in our cohort, including one sibling pair, had 13 distinct, heterozygous GNAO1 variants classified as pathogenic or likely pathogenic. We attributed the same variant in two siblings to parental mosaicism. Patients initially presented with seizures beginning in the first 3 months of life (8/14), developmental delay (4/14), hypotonia (1/14), or movement disorder (1/14). All patients had hypotonia and developmental delay ranging from mild to severe. Nine had epilepsy, and nine had movement disorders, including dystonia, ataxia, chorea, and dyskinesia. The 13 GNAO1 variants in our patients are predicted to result in amino acid substitutions or deletions in the GNAO1 guanosine triphosphate (GTP)-binding region, analogous to those in previous publications. Patients with variants affecting amino acids 207-221 had only movement disorder and hypotonia. Patients with variants affecting the C-terminal region had the mildest phenotypes.
SIGNIFICANCE: GNAO1 encephalopathy most frequently presents with seizures beginning in the first 3 months of life. Concurrent movement disorders are also a prominent feature in the spectrum of GNAO1 encephalopathy. All variants affected the GTP-binding domain of GNAO1, highlighting the importance of this region for G-protein signaling and neurodevelopment.

PMID: 30682224 [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 2020/04/14

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.

Hermansky-Pudlak Syndrome.

Semin Respir Crit Care Med. 2020 Apr;41(2):238-246

Authors: De Jesus Rojas W, Young LR

Abstract
Hermansky-Pudlak syndrome (HPS) is a multisystemic autosomal recessive disorder characterized by oculocutaneous albinism, bleeding diathesis, and lethal pulmonary fibrosis (PF) in some HPS subtypes. During middle adulthood, ground-glass opacities, reticulation, and traction bronchiectasis develop with progression of PF. HPS is an orphan disease occurring in 1 in 500,000 to 1,000,000 individuals worldwide, though the prevalence is 1 in 1,800 in individuals with Puerto Rican heritage. Recessive mutations or disruptions in HPS genes alter the function of HPS proteins which are components of biogenesis of lysosome-related organelle complexes and are critical for intracellular protein trafficking. Diagnosis and management of HPS-related comorbidities represent a challenge to physicians, and a multidisciplinary clinical approach is necessary for early detection, health management, and surveillance of PF in patients with HPS types 1, 2, and 4. Treatment options for individuals with HPS-PF include pirfenidone and lung transplantation. In this article, we describe the epidemiology, genetics, clinical manifestations, and management of HPS.

PMID: 32279294 [PubMed - as supplied by publisher]

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 2020/04/11

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 2020/04/11

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.

State of knowledge about information sources and health care centres for rare diseases among affected people in Germany.

Cent Eur J Public Health. 2020 Mar;28(1):82-84

Authors: Hanisch M, Wiemann S, Bohner L, Jung S, Kleinheinz J

Abstract
OBJECTIVES: About four million people are affected by rare diseases in Germany and 30 million in the EU. In 2013, a national action plan for people with rare diseases was adopted in Germany which is also aimed at improving the information situation and better gathering of information for affected patients and their families. Since then, various sources of information and medical care structures have been made available. The aim of this study was to evaluate the state of knowledge about information sources and health care centres for rare diseases among those affected.
METHODS: The study was carried out as anonymous survey among the member associations of the German Alliance for Chronic Rare Diseases (German acronym ACHSE e. V.). For this, a questionnaire was developed which in addition to questions on gender, age and disease comprised free text input referring to knowledge of health care centres or expert centres and source of information on rare diseases in Germany.
RESULTS: A total of 484 individuals suffering from 96 different rare diseases participated in the survey. Of these, 74.47% are aware of medical or dental care centres for treatment of their types of rare disease; 69.31% use self-help groups as a source of information, only a few respondents know government-sponsored "se-atlas" and "Orphanet".
CONCLUSION: The majority of the respondents know medical care centres, most participants use self-help groups as information source, however, government-supported portals are largely unknown so that there is a need for further information in this regard.

PMID: 32228824 [PubMed - indexed for MEDLINE]

Neuropsychiatric symptoms, skin disease, and weight loss: necrolytic migratory erythema and a glucagonoma.

Lancet. 2020 03 21;395(10228):985

Authors: Boujan N, Géraud C

PMID: 32199485 [PubMed - indexed for MEDLINE]

Same results, 20% of the cost: Short-course total neoadjuvant therapy.

Int J Radiat Oncol Biol Phys. 2020 03 15;106(4):672-673

Authors: Parikh PJ, Chapman W

PMID: 31924409 [PubMed - indexed for MEDLINE]

17 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 2020/04/09

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.

High-specific-activity iodine 131 metaiodobenzylguanidine for the treatment of metastatic pheochromocytoma or paraganglioma: a novel therapy for an orphan disease.

Curr Opin Endocrinol Diabetes Obes. 2020 Apr 03;:

Authors: Jimenez C, Núñez R, Wendt R

Abstract
PURPOSE OF REVIEW: Pheochromocytomas and paragangliomas represent less than 1% of all endocrine tumors. Approximately 15-20% of these tumors are malignant. The definition of malignancy relies on the presence of metastasis. Metastatic pheochromocytomas and paragangliomas are usually advanced, incurable tumors with limited therapeutic options. About 50-60% of these tumors express the noradrenaline transporter in their cell membranes. Recently, the United States Food and Drug Administration approved high-specific-activity iodine 131 metaiodobenzylguanidine (HSA-I-131-MIBG) for the treatment of metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter. This review reports the benefits and toxicity of HSA-I-131-MIBG, its physical and dosimetric aspects, and radiation safety precautions, as well as its potential therapeutic value for other malignancies (neuroblastoma, gastroenteropancreatic neuroendocrine tumors, and medullary thyroid carcinoma).
RECENT FINDINGS: A phase 2 clinical trial with HSA-I-131-MIBG reported an impressive clinical benefit rate, acceptable toxicity and long-term benefits.
SUMMARY: HSA-I-131-MIBG is an effective medication for metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter.

PMID: 32250976 [PubMed - as supplied by publisher]

Non-CF bronchiectasis: Orphan disease no longer.

Respir Med. 2020 Mar 27;166:105940

Authors: Imam JS, Duarte AG

Abstract
Bronchiectasis is a complex, chronic respiratory condition, characterized by frequent cough and exertional dyspnea due to a range of conditions that include inherited mucociliary defects, inhalational airway injury, immunodeficiency states and prior respiratory infections. For years, bronchiectasis was classified as either being caused by cystic fibrosis or non-cystic fibrosis. Non-cystic fibrosis bronchiectasis, once considered an orphan disease, is more prevalent worldwide in part due to greater availability of chest computed tomographic imaging. Identification of the cause of non-cystic fibrosis bronchiectasis with the use of chest imaging, laboratory testing, and microbiologic assessment of airway secretions can lead to initiation of specific therapies aimed at slowing disease progression. Nonpharmacologic therapies such as airway clearance techniques and pulmonary rehabilitation improve patient symptoms. Inhaled corticosteroids should not be routinely prescribed unless concomitant asthma or COPD is present. Inhaled antibiotics prescribed to individuals with >3 exacerbations per year are well tolerated, reduce airway bacteria load and may reduce the frequency of exacerbations. Likewise, chronic macrolide therapy reduces the frequency of exacerbations. Medical therapies for cystic fibrosis bronchiectasis may not be effective in treatment of non-cystic fibrosis bronchiectasis.

PMID: 32250872 [PubMed - as supplied by publisher]

Sex Differences in Clinical Presentation and Outcomes among Patients with Complement-Gene-Variant-Mediated Thrombotic Microangiopathy.

J Clin Med. 2020 Mar 31;9(4):

Authors: Aigner C, Gaggl M, Kain R, Prohászka Z, Garam N, Csuka D, Sunder-Plassmann R, Piggott LC, Haninger-Vacariu N, Schmidt A, Sunder-Plassmann G

Abstract
Sex differences among patients with complement-gene-variant-mediated thrombotic microangiopathy (cTMA) are not well established. We examined demographic and clinical data from female and male patients with a history of cTMA enrolled in the Vienna thrombotic microangiopathy (TMA) cohort. Follow-up was three years after first presentation with cTMA. In this single-center study, we identified 51 patients with a first manifestation of cTMA between 1981 and 2019; 63% were female (p = 0.09). The median age at diagnosis did not differ between females and males. There was also no disparity between the sexes with regard to renal function or the need for renal replacement therapy at presentation. Furthermore, we observed similar use of plasma or eculizumab therapy and a comparable evolution of renal function of female and male patients. More females showed risk haplotypes of complement factor H (CFH) and CD46 (97% vs. 68%, p = 0.01), but there was no difference in the prevalence of rare pathogenic variants in complement-associated genes with regard to sex. In conclusion, the majority of cTMA patients enrolled in the Vienna TMA cohort were female. Clinical presentation and renal function did not differ between the sexes, but females more frequently presented with cTMA risk haplotypes.

PMID: 32244370 [PubMed - as supplied by publisher]

Synkinesis Between Orbicularis Oculi and Procerus Muscles: Video Presentation of an Unusual Type of Aberrant Innervation after Cosmetic Rhinoplasty.

Aesthetic Plast Surg. 2019 02;43(1):98-101

Authors: Eshraghi B, Ghadimi H, Nikdel M, Hajizadeh F

Abstract
BACKGROUND: Synkinesis is a recognized complication following peripheral facial nerve paralysis. Different types of synkinesis have been described, with oral-ocular and ocular-oral synkinesis being the most common. Ocular-nasal synkinesis has been reported in two patients following cosmetic rhinoplasty. However, synkinesis between the orbicularis oculi and procerus muscles has not been reported by now.
METHODS: This is an interventional case report.
RESULTS: Two women, aged 42 and 37 years, presented with unilateral contraction of the medial eyebrow muscles (procerus) with spontaneous or voluntary blinking, 4 and 5 months after cosmetic rhinoplasty, respectively. Both were successfully treated with injection of botulinum toxin A.
CONCLUSIONS: Surgical trauma is inevitable during every procedure, including rhinoplasty, and may damage the fine structures including branches of the facial nerve innervating the muscles. Gentle tissue handling may minimize iatrogenic injury to the fine motor branches of the facial nerve and prevent subsequent aberrant innervation and synkinesis. Botulinum toxin A injection can effectively, yet temporarily, resolve the unintentional contractions and provide significant patient comfort.
LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266 .

PMID: 30327854 [PubMed - indexed for MEDLINE]

8 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 2020/04/03

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.

Fulminant Myocarditis: Epidemiology, Pathogenesis, Diagnosis, and Management.

Am J Cardiol. 2019 12 15;124(12):1954-1960

Authors: Sharma AN, Stultz JR, Bellamkonda N, Amsterdam EA

Abstract
Fulminant myocarditis (FM) is a rare, distinct form of myocarditis that has been difficult to classify. Since 1991, the definition of FM has evolved, and it is currently considered an acute illness with hemodynamic derangement and arrhythmias due to a severe inflammatory process requiring support of cardiac pump function and/or urgent management of serious arrhythmias. Diagnosis is aided through use of biomarkers and cardiac imaging, but endocardial biopsy remains the gold standard. Recent evidence has revealed that patients with FM are significantly more likely to die or require heart transplantation than those with the nonfulminant form, refuting previous studies proposing a paradoxically low mortality in patients with FM. Acute hemodynamic derangement is managed by intensive contemporary pharmacologic and interventional approaches, whereas the role of immunosuppressive therapy has not been clarified. Early recognition and aggressive management are essential for favorable outcomes. In conclusion, FM is an inflammatory process requiring intensive support, and it causes a higher morbidity and mortality than acute nonfulminant myocarditis.

PMID: 31679645 [PubMed - indexed for MEDLINE]