Global Health Perspective in Sarcomas and Other Rare Cancers.

Am Soc Clin Oncol Educ Book. 2018 May 23;(38):916-924

Authors: Florou V, Nascimento AG, Gulia A, de Lima Lopes G

Abstract
Sarcomas, rare and heterogenous malignancies that comprise less than 1% of all cancers, have poor outcomes in the metastatic and refractory setting. Their management requires a multidisciplinary approach that consists of medical and surgical oncologists, radiation oncologists, and pathologists as well as ancillary support. In addition to systemic treatments, most patients will require surgical resection and radiation therapy, which mandates the use of the latest technologies and specialized expertise. Management guidelines have been developed in high-income countries, but their applicability in low-income countries, where resources may be limited, remains a challenge. In this article, we propose the best possible evidence-based practices specifically for income-constrained settings to overcome this challenge. In addition, we review the different methods that can be used in low-income countries to access new and expensive treatments, which often times carry prohibitive costs for these areas.

PMID: 30231406 [PubMed - indexed for MEDLINE]

13 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 2018/11/27

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.

13 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 2018/11/27

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.

Perspective From the 5th International Pemphigus and Pemphigoid Foundation Scientific Conference.

Front Med (Lausanne). 2018;5:306

Authors: Lee J, Werth VP, Hall RP, Eming R, Fairley JA, Fajgenbaum DC, Harman KE, Jonkman MF, Korman NJ, Ludwig RJ, Murrell DF, Musette P, Naik HB, Sadik CD, Yamagami J, Yale ML, Payne AS

Abstract
The 5th Scientific Conference of the International Pemphigus and Pemphigoid Foundation (IPPF), "Pemphigus and Pemphigoid: A New Era of Clinical and Translational Science" was held in Orlando, Florida, on May 15-16, 2018. Scientific sessions covered recent, ongoing, and future clinical trials in pemphigus and bullous pemphigoid, disease activity and quality of life instruments, and the IPPF Natural History Study. Furthermore, the meeting provided an opportunity to hear firsthand from patients, investigators, and industry about their experience enrolling for clinical trials.

PMID: 30467542 [PubMed]

Advanced Adrenocortical Carcinoma - What to do when First-Line Therapy Fails?

Exp Clin Endocrinol Diabetes. 2018 Nov 23;:

Authors: Megerle F, Kroiss M, Hahner S, Fassnacht M

Abstract
Adrenocortical carcinoma is a rare endocrine malignant disease with a generally unfavorable but heterogeneous prognosis. Although even in advanced stages a subset of patients experiences long-term disease stabilisation, effective systemic treatment options are limited. Mitotane is the only approved drug and the combination of etoposide, doxorubicin and cisplatin (plus mitotane) is currently considered as treatment standard for advanced adrenocortical carcinoma based on the results of a large randomized phase III trial. However, progression-free survival is often limited and further treatment options are frequently needed. Here we summarize the current knowledge about second and third-line therapeutic modalities (local and systemic) in advanced disease. Following the recent ESE-ENSAT guidelines local therapies play an important role for these patients. Regarding systemic therapies the best data are available for gemcitabine+capecitabine or streptozotocin (both with or without mitotane). Furthermore, we introduce our own approach to patients with advanced adrenocortical carcinoma based on our experience as a large multidisciplinary clinic dedicated to the care of patients with this orphan disease.

PMID: 30469158 [PubMed - as supplied by publisher]

[Fabry disease - the profile of an orphan disease].

Ther Umsch. 2018 Nov;75(4):217-224

Authors: Tamò R, Zweifel SA, Beuschlein F, Nowak A

Abstract
Fabry disease - the profile of an orphan disease Abstract. Fabry disease is a lysosomal storage disease, characterized by a deficient lysosomal function. The main pathophysiological mechanism is the deficiency of the enzyme α-galactosidase A. As a result, an accumulation of the substrate globotriaosylceramide occurs in tissues of affected patients. Fabry disease is a X chromosome-linked disease, hence women with one allele often show only mild symptoms. Frequent and unspecific initial symptoms in childhood include acroparesthesias, hypo- and anhidrosis, and angiokeratoma. Life-threatening complications such as progressive kidney insufficiency, cardiomyopathy, and cerebrovascular insult manifest only in later adulthood. The diagnosis requires the measurement of the α-galactosidase A activity in blood plasma or white blood cells. Approved therapeutic methods are the enzyme-replacement therapy and pharmacologic chaperone.

PMID: 30468120 [PubMed - in process]

Genetic variation in CRHR1 is associated with short-term respiratory response to corticosteroids in preterm infants at risk for bronchopulmonary dysplasia.

Pediatr Res. 2018 Nov 22;:

Authors: Lewis T, Truog W, Norberg M, Ballard PL, Torgerson D, TOLSURF Study Group

Abstract
BACKGROUND: Bronchopulmonary dysplasia (BPD) is an orphan disease and advances in prevention and treatment are lacking. The clinical efficacy of systemic corticosteroid therapy to reduce the severity of lung disease and BPD is highly variable. Our objective was to assess whether candidate SNPs in corticosteroid metabolism and response genes are associated with short-term phenotypic response to systemic corticosteroids in infants at high risk for BPD.
METHODS: Pharmacogenetic analysis of data from a large randomized controlled trial (TOLSURF) in infants treated with dexamethasone or hydrocortisone using multivariate linear regression. The primary outcome was a change in respiratory severity score (RSS, mean airway pressure x FiO2) at day 7 of corticosteroid treatment.
RESULTS: rs7225082 in the intron of CRHR1 is significantly associated with the magnitude of decrease in RSS 7 days after starting treatment with systemic corticosteroid (meta-analysis P = 2.8 × 10-4). Each T allele at rs7225082 is associated with a smaller absolute change in RSS at day 7, i.e., less response to systemic corticosteroids.
CONCLUSION: Genetic variability is associated with corticosteroid responsiveness with regard to respiratory status in preterm infants. Identification of genetic markers of corticosteroid responsiveness may allow for therapeutic individualization, with the goal of optimizing the risk-to-benefit ratio for an individual child.

PMID: 30467342 [PubMed - as supplied by publisher]

Dose adjustment in orphan disease populations: the quest to fulfill the requirements of physiologically based pharmacokinetics.

Expert Opin Drug Metab Toxicol. 2018 Nov 22;:1-16

Authors: Howard M, Barber J, Alizai N, Rostami-Hodjegan A

Abstract
INTRODUCTION: While the media is engaged and fascinated by the idea of 'Precision Medicine', the nuances related to 'Precision Dosing' seem to be largely ignored. Assuming the 'right drug' is selected, clinicians still need to decide on the 'right dose' for individuals. Ideally, optimal dosing should be studied in clinical trials; however, many drugs on the market lack evidence-based dosing recommendations, and small groups of patients (orphan disease populations) are dependent on local guidance and clinician experience to determine drug dosage adjustments. Areas Covered: This report explores the current understanding of dosing adjustment in special populations and examines the requirements for developing 'in silico' models for pediatric, elderly and pregnant patients. The report also highlights current use of modeling to provide evidence-based recommendations for drug labeling in the absence of complete clinical trials in orphan disease populations. Expert Opinion: Physiologically based pharmacokinetics (PBPK) is an attractive prospect for determining the best drug dosage adjustments in special populations. However, it is not sufficient for individualized, or even stratified dosing, unless the systems (drug-independent) data required to build robust PBPK models are obtained. Such models are not a substitute for clinical trials, but they are an alternative to undocumented and inconsistent guesswork.

PMID: 30465453 [PubMed - as supplied by publisher]

Rare anemias due to genetic iron metabolism defects.

Mutat Res. 2018 Jul - Sep;777:52-63

Authors: Brissot P, Bernard DG, Brissot E, Loréal O, Troadec MB

Abstract
Anemia is defined by a deficiency of hemoglobin, an iron-rich protein that binds oxygen in the blood. It can be due to multiple causes, either acquired or genetic. Alterations of genes involved in iron metabolism may be responsible, usually at a young age, for rare forms of chronic and often severe congenital anemia. These diseases encompass a variety of sideroblastic anemias, characterized by the presence of ring sideroblasts in the bone marrow. Clinical expression of congenital sideroblastic anemia is either monosyndromic (restricted to hematological lineages) or polysyndromic (with systemic expression), depending on whether iron metabolism, and especially heme synthesis, is directly or indirectly affected. Beside sideroblastic anemias, a number of other anemias can develop due to mutations of key proteins acting either on cellular iron transport (such as the DMT1 transporter), plasma iron transport (transferrin), and iron recycling (ceruloplasmin). Contrasting with the aforementioned entities which involve compartmental, and sometimes, systemic iron excess, the iron refractory iron deficiency anemia (IRIDA) corresponds to a usually severe anemia with whole body iron deficiency related to chronic increase of plasma hepcidin, the systemic negative regulator of plasma iron. Once clinically suggested, these diseases are confirmed by genetic testing in specialized laboratories.

PMID: 30115430 [PubMed - indexed for MEDLINE]

Successful Treatment of Type 1 Cryoglobulinemic Vasculitis With Cardiac Involvement.

Can J Cardiol. 2018 03;34(3):343.e1-343.e3

Authors: Cao XX, Tian Z, Lin L, Sun J, Su W, Zhou DB, Li J

Abstract
Cryoglobulinemic vasculitis is a rare and frequently fatal type of myocarditis. Cardiac manifestations in type 1 cryoglobulinemic vasculitis have never been reported to our knowledge. We report a rare case of type 1 cryoglobulinemic vasculitis with cardiac involvement in a patient who experienced progressive heart failure during the diagnosis. The diagnosis was made by the presence of cryoglobulins and endomyocardial biopsy results. After bortezomib-containing treatments, plasma cryoglobulin levels returned to normal, and the patient's clinical condition gradually improved.

PMID: 29395708 [PubMed - indexed for MEDLINE]

Left pericardial congenital defect: the heart shows its moves at CMR.

Eur Heart J Cardiovasc Imaging. 2017 11 01;18(11):1270

Authors: Moura-Ferreira S, Budts W, Bogaert J

PMID: 28679167 [PubMed - indexed for MEDLINE]

[Dermatofibrosarcoma: Management].

Bull Cancer. 2018 Nov;105(11):1094-1101

Authors: Penel N, El Bedoui S, Robin YM, Decanter G

Abstract
Dematofibrosarcoma protuberans (DFSP) are very rare (1 to 4 incident cases per million of inhabitants). The local spreading of DFSP is underestimated. The histological diagnosis is challenging but we now know a specific marker (translocation t(17;22)(q22;q13) (COL1A1;PDGFB)). The risk of metastatic relapse is low (and related to fibrosarcoma component); the risk of local relapse depends on the quality of surgery. Management of localized DFSP is based on large resection with meticulous analysis of margins (with or without Mohs microsurgery). Advanced stages not amenable to surgery or metastatic DFSP (with presence of COL1A1;PDGFB) are best treated with imatinib. Locally advanced DFSP potentially amenable to curative intent surgery could be treated with imatinib as neo-adjuvant treatment. The management of these tumours requires multidisciplinary expertise.

PMID: 30297237 [PubMed - indexed for MEDLINE]

Dark Colored Urine in a 2-Year-Old Child.

Clin Chem. 2017 03;63(3):786-788

Authors: Peake RW, Bodamer OA

PMID: 28242834 [PubMed - indexed for MEDLINE]

[Sjældent syndrom som differentialdiagnose ved markant fregnedannelse].

Ugeskr Laeger. 2016 11 21;178(47):

Authors: Lings K, Lauridsen MF, Hansen LK

PMID: 27908317 [PubMed - indexed for MEDLINE]

[Erdheim-Chester disease : An important differential diagnosis and its main symptoms].

Z Rheumatol. 2018 Nov 14;:

Authors: Knitza J, Kampylafka E, Wacker J, Schett G, Manger B

Abstract
BACKGROUND: During the last 3 years 4 patients were admitted to this hospital with a wide variety of different symptoms, in whom Erdheim-Chester disease (ECD) was diagnosed via different diagnostic pathways.
OBJECTIVE: Based on four clinical cases of ECD and using additional information from the literature, this article presents the symptoms of ECD. Furthermore, similarities and differences in comparison to important rheumatological differential diagnoses are presented.
RESULTS: The ECD is a multi-organ orphan disease. Typical for the disease are long bone involvement, periarterial inflammation especially of the aorta, retroperitoneal and perirenal fibrosis with so-called hairy kidneys in abdominal computed tomography (CT) scans. Treatment is increasingly directed towards the presence of a BRAF mutation, which enables targeted and effective treatment with BRAF inhibitors.
CONCLUSION: The ECD is a rare differential diagnosis to rheumatic diseases that causes various and often nonspecific symptoms. Due to modern diagnostic methods with imaging procedures and biopsies it is possible to establish a precise diagnosis and provide a targeted and effective treatment.

PMID: 30430236 [PubMed - as supplied by publisher]

Increasing access to specialty care for rare diseases: a case study using a foundation sponsored clinic network for patients with neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis.

BMC Health Serv Res. 2018 Aug 29;18(1):668

Authors: Merker VL, Dai A, Radtke HB, Knight P, Jordan JT, Plotkin SR

Abstract
BACKGROUND: Our primary aim was to assess the ability of a non-profit foundation-sponsored clinic network to facilitate access to specialized care for patients with neurofibromatoses (NF), a group of neurogenetic disorders including NF1, NF2, and schwannomatosis (SWN). Our secondary aim was to identify how our findings in NF could be applied more broadly to other rare diseases.
METHODS: We retrospectively reviewed aggregate data on patient volume reported by specialty NF clinics in a nonprofit network from 2008 to 2015. We classified clinics as high or low volume for disease type (NF1 and NF2/schwannomatosis) and pediatric/adult care. We compared clinic-level data to self-reported patient-level data from a large online patient registry.
RESULTS: Between 2008 and 2015, the number of certified NF clinics grew from 32 to 50, and annual patient volume rose from 6776 to 10,245 patients (13% of the total estimated U.S. NF patient population). For patient registry participants (n = 4476), the median driving distance to the nearest network clinic was 51.3 miles. Driving distances to reach high-volume centers were elevated for adults compared to children (295.8 vs. 67.9 miles), and schwannomatosis and NF2 patients compared to NF1 patients (310.9 vs. 368.1 vs. 161.7 miles). Of registry participants reporting their location of care (n = 2271), only 43.2% received care in a network specialty clinic, with especially low rates of attendance in the Southwest and Far West.
CONCLUSIONS: While the number of certified NF clinics and volume of patients seen in these clinics has increased, many NF patients still do not attend specialty clinics and/or travel a significant distance for care. Geographic access to care is more limited for adults, patients with rarer conditions, and patients in the Western U.S. Potential measures to improve access to specialty care for people living with NF and other rare diseases are discussed.

PMID: 30157837 [PubMed - indexed for MEDLINE]

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

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

These pubmed results were generated on 2018/11/15

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.

PSMD12 haploinsufficiency in a neurodevelopmental disorder with autistic features.

Am J Med Genet B Neuropsychiatr Genet. 2018 Nov 13;:

Authors: Khalil R, Kenny C, Hill RS, Mochida GH, Nasir R, Partlow JN, Barry BJ, Al-Saffar M, Egan C, Stevens CR, Gabriel SB, Barkovich AJ, Ellison JW, Al-Gazali L, Walsh CA, Chahrour MH

Abstract
Protein homeostasis is tightly regulated by the ubiquitin proteasome pathway. Disruption of this pathway gives rise to a host of neurological disorders. Through whole exome sequencing (WES) in families with neurodevelopmental disorders, we identified mutations in PSMD12, a core component of the proteasome, underlying a neurodevelopmental disorder with intellectual disability (ID) and features of autism spectrum disorder (ASD). We performed WES on six affected siblings from a multiplex family with ID and autistic features, the affected father, and two unaffected mothers, and a trio from a simplex family with one affected child with ID and periventricular nodular heterotopia. We identified an inherited heterozygous nonsense mutation in PSMD12 (NM_002816: c.367C>T: p.R123X) in the multiplex family and a de novo nonsense mutation in the same gene (NM_002816: c.601C>T: p.R201X) in the simplex family. PSMD12 encodes a non-ATPase regulatory subunit of the 26S proteasome. We confirm the association of PSMD12 with ID, present the first cases of inherited PSMD12 mutation, and demonstrate the heterogeneity of phenotypes associated with PSMD12 mutations.

PMID: 30421579 [PubMed - as supplied by publisher]

Hemizygous Fabry disease associated with membranous nephropathy: A rare case report
.

Clin Nephrol. 2018 Sep;90(3):227-231

Authors: Zhou W, Ni Z, Zhang M

Abstract
BACKGROUND: Fabry disease may coexist with various glomerular diseases, including IgA nephropathy, focal segmental glomerulosclerosis, etc. In this study, we report a rare case of Fabry disease associated with membranous nephropathy (MN).
CASE PRESENTATION: A 30-year-old man with nephrotic proteinuria, normal renal function, and no other extrarenal manifestations underwent a renal biopsy in February 2017. Light microscopy and immunofluorescence indicated MN (stage 1). Under an electron microscope, there were subepithelial electron-dense deposits and abundant zebra bodies in podocytes. Both the findings of low-activity α-galactosidase A (α-Gal A, GLA) and base deletion in exon 7 of the GLA gene (GLA-E07.1286_*7 del, a newly reported mutation) confirmed that this patient was simultaneously afflicted with Fabry disease.
CONCLUSION: This case report is an important reminder of the role of kidney biopsy, especially electron microscopy, as an indicator of Fabry disease and its rare coexistence with MN.
.

PMID: 29792392 [PubMed - indexed for MEDLINE]

Identification and molecular typing of Naegleria fowleri from a patient with primary amebic meningoencephalitis in China.

Int J Infect Dis. 2018 Jul;72:28-33

Authors: Zhang LL, Wu M, Hu BC, Chen HL, Pan JR, Ruan W, Yao LN

Abstract
Naegleria fowleri is the only Naegleria spp. known to cause an acute, fulminant, and rapidly fatal central nervous system infection in humans called primary amebic meningoencephalitis (PAM). In 2016, a patient with suspected PAM was found in Zhejiang Province of China. The pathogen was identified by microscopic examination and PCR. The positive PCR products were sequenced and the sequences were aligned using the NCBI BLAST program. The homologous and phylogenetic analysis was conducted using MEGA 6 program. On microscopy of direct smears, motile cells with pseudopodia were observed, and the motion characteristics of the pseudopodia as well as the cell morphology suggested that the pathogens were amoeba trophozoites. Wright-Giemsa-stained smears showed amoeba trophozoites of various shapes, which measured 10-25μm in size; these were characterized by a prominent, centrally placed nucleolus and a vacuolated cytoplasm. PCR was negative for Entamoeba histolytica and Entamoeba dispar, but positive for Naegleria spp. and N. fowleri. The nucleotide sequences acquired in this study have been submitted to GenBank with accession numbers KX909928 and KX909927, respectively. The BLAST analysis revealed that the sequences of KX909928 and KX909927 had 100% similarity with the sequence of the N. fowleri gene (KT375442.1). Sequence alignment and the phylogenetic tree revealed that the N. fowleri collected in this study was classified as genotype 2 and was most closely related to Naegleria lovaniensis. This study confirmed N. fowleri as the agent responsible for the infection in this patient. PAM normally progresses rapidly and is generally universally fatal within a week. Unfortunately this patient died at 2 weeks after the onset of symptoms.

PMID: 29751112 [PubMed - indexed for MEDLINE]