Clinical characteristics of 248 patients with Krabbe disease: quantitative natural history modeling based on published cases.

Genet Med. 2019 Mar 22;:

Authors: Komatsuzaki S, Zielonka M, Mountford WK, Kölker S, Hoffmann GF, Garbade SF, Ries M

Abstract
PURPOSE: Krabbe disease (OMIM 245200) is an orphan neurometabolic disorder caused by a deficiency of the lysosomal enzyme galactocerebrosidase (GALC). Hard clinical endpoints and biomarker-phenotype correlations are useful for future clinical trials.
METHODS: We performed a quantitative analysis of published cases (N = 248) with Krabbe disease, stratified by age at disease onset: early infantile (age 0-6 months), late infantile (age 7-36 months), juvenile/adolescent (age 37-180 months), and adult onset (>180 months). Main outcome measures were age of disease onset and survival. Cerebrospinal fluid (CSF) protein concentrations were explored as a potential predictor of survival. STROBE criteria were respected.
RESULTS: Median age of onset was 4 months (early infantile), 14 months (late infantile), 48 months (juvenile), and 384 months (adult). Age of disease onset and therefore disease subtype determined survival rates. CSF protein concentrations predicted age at onset and survival rates in Krabbe disease. Patients with a CSF protein content ≤61.5 mg/dl survived significantly longer than patients with CSF protein values above this threshold.
CONCLUSION: We define the estimated survival in published Krabbe disease cases and demonstrate an association of CSF protein concentration with disease severity. These data inform patient care and clinical trials.

PMID: 30899093 [PubMed - as supplied by publisher]

A case study of an adaptive design for a clinical trial with 2 doses and 2 endpoints in a rare disease area.

Pharm Stat. 2018 11;17(6):797-810

Authors: Quan H, Xu Y, Chen Y, Gao L, Chen X

Abstract
Patient recruitment is challenging in rare disease clinical trials. To save time and resources, an inferential seamless phase II/III clinical trial design is considered for a clinical trial in a rare disease area. In particular, 2 doses compared to a placebo control are evaluated at phase II (ie, stage I). Based on the results of a phase II intermediate endpoint, additional patients may be enrolled into the 2 doses and control, 1 selected dose and control, or none of the 3 treatment arms at stage II. All patients including those of unselected dose (s) will be followed for the measurements of the phase III (ie, stage II) primary and secondary endpoints and incorporated in the final analysis. Under a reasonable condition, the type I error rate will be controlled at the nominal level if the same nominal level is applied for testing a dose effect based on either only the data of patients of stage I (in case the dose is not selected for stage II) or data of patients of stages I and II combined. A graphical testing procedure is also introduced for multiplicity adjustments to account for the 2 doses and 2 endpoints for the overall type I error rate control. Moreover, an imputation approach is proposed for conditional power calculation at stage I for a sample size adaptive design. Simulations are carried out under different parameter configurations to compare the performances of various approaches. The trial example is further used to illustrate the applications of the methods.

PMID: 30221446 [PubMed - indexed for MEDLINE]

Mammary Hibernoma: A Case Report of a Rare Disease.

Rev Bras Ginecol Obstet. 2018 Apr;40(4):232-234

Authors: Neves Filho EHC, Lima GAF, Alves ÂRM, Sousa VM, Cunha MDPSSD

Abstract
Mammary hibernomas are extremely rare benign tumors composed of brown fat cells, with only five cases previously reported in the literature. We report the case of a 42-year-old female patient with a painless growing mass in her right breast. A partial mastectomy was performed, and the diagnosis of hibernoma was confirmed by the histological features and the immunohistochemical profile. Although hibernoma is a benign tumor, its main differential diagnoses include aggressive lesions, making the accurate diagnosis essential to provide adequate care to the patient.

PMID: 29597239 [PubMed - indexed for MEDLINE]

Neural Stem Cells and Human Induced Pluripotent Stem Cells to Model Rare CNS Diseases.

CNS Neurol Disord Drug Targets. 2017;16(8):915-926

Authors: De Filippis L, Zalfa C, Ferrari D

Abstract
BACKGROUND & OBJECTIVE: Despite the great effort spent over recent decades to unravel the pathological mechanisms underpinning the development of central nervous system disorders, most of them still remain unclear. In particular, the study of rare CNS diseases is hampered by the lack of postmortem samples and of reliable epidemiological studies, thus the setting of in vitro modeling systems appears essential to dissect the puzzle of genetic and environmental alterations affecting neural cells viability and functionality. The isolation and expansion in vitro of embryonic (ESC) and fetal neural stem cells (NSC) from human tissue have allowed the modeling of several neurological diseases "in a dish" and have also provided a novel platform to test potential therapeutic strategies in a pre-clinical setting. In recent years, the development of induced pluripotent stem cell (iPS) technology has added enormous value to the aforementioned approach, thanks to their capability for generating diseaserelevant cell phenotypes in vitro and to their perspective use in autologous transplantation. However, while the potentiality of ESC, NSC and iPS has been widely sponsored, the pitfalls related to the available protocols for differentiation and the heterogeneity of lines deriving from different individuals have been poorly discussed. Here we present pro and contra of using ESC, NSC or iPS for modeling rare diseases like Lysosomal Storage disorders and Motor Neuron Diseases.
CONCLUSION: In this view, the advent of gene editing technologies is a unique opportunity to standardize the data analysis in preclinical studies and to tailor clinical protocols for stem cell-mediated therapy.

PMID: 28641519 [PubMed - indexed for MEDLINE]

Treatment options for pyoderma gangrenosum.

J Dtsch Dermatol Ges. 2017 Jan;15(1):34-40

Authors: Quist SR, Kraas L

Abstract
Pyoderma gangrenosum (PG) is an orphan disease. While research on such disorders is based on only few randomized multicenter as well as retrospective studies, most of the data comes from case series of small patient groups. Apart from topical and intralesional therapeutic options for early stages and mild disease courses, treatment predominantly involves systemic therapeutic agents. Besides systemic corticosteroids and cyclosporine A (CsA), options also include intravenous immunoglobulins (IVIG) and biologics such as the TNFα inhibitors infliximab, adalimumab, and etanercept; the interleukin (IL) 12/23 antibody ustekinumab; the IL-1 receptor antagonist anakinra; and the IL-1β antibody canakinumab. The best evidence-based study data is available for CsA, prednisolone, and infliximab; the latter especially in patients with concomitant ulcerative colitis or Crohn's disease. A response to IVIG and canakinumab has been reported in smaller case series. First described by Brocq almost 100 years ago, it was soon recognized that PG did in fact require treatment. To this day, however, such treatment remains a clinical challenge. Despite the severe - albeit rare -clinical picture, improvement in therapeutic options may be expected in the future, primarily due to further clinical studies - especially with a greater number of patients, a better understanding of the etiopathogenesis, as well as the use of modern targeted therapies with higher efficacy and a lower rate of side effects than conventional immunosuppressants such as prednisolone and CsA.

PMID: 28140549 [PubMed - indexed for MEDLINE]

Nasopharyngeal metastasis of breast carcinoma with HER 2 discordance: a case report.

ANZ J Surg. 2018 May;88(5):508-509

Authors: Copson B, Pratap U, McLean C, Hayes T

PMID: 26909745 [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 2019/03/21

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 2019/03/20

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.

27 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 2019/03/19

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.

27 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 2019/03/19

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.

ALS/FTD mutant CHCHD10 mice reveal a tissue-specific toxic gain-of-function and mitochondrial stress response.

Acta Neuropathol. 2019 Mar 14;:

Authors: Anderson CJ, Bredvik K, Burstein SR, Davis C, Meadows SM, Dash J, Case L, Milner TA, Kawamata H, Zuberi A, Piersigilli A, Lutz C, Manfredi G

Abstract
Mutations in coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10), a mitochondrial protein of unknown function, cause a disease spectrum with clinical features of motor neuron disease, dementia, myopathy and cardiomyopathy. To investigate the pathogenic mechanisms of CHCHD10, we generated mutant knock-in mice harboring the mouse-equivalent of a disease-associated human S59L mutation, S55L in the endogenous mouse gene. CHCHD10S55L mice develop progressive motor deficits, myopathy, cardiomyopathy and accelerated mortality. Critically, CHCHD10 accumulates in aggregates with its paralog CHCHD2 specifically in affected tissues of CHCHD10S55L mice, leading to aberrant organelle morphology and function. Aggregates induce a potent mitochondrial integrated stress response (mtISR) through mTORC1 activation, with elevation of stress-induced transcription factors, secretion of myokines, upregulated serine and one-carbon metabolism, and downregulation of respiratory chain enzymes. Conversely, CHCHD10 ablation does not induce disease pathology or activate the mtISR, indicating that CHCHD10S55L-dependent disease pathology is not caused by loss-of-function. Overall, CHCHD10S55L mice recapitulate crucial aspects of human disease and reveal a novel toxic gain-of-function mechanism through maladaptive mtISR and metabolic dysregulation.

PMID: 30877432 [PubMed - as supplied by publisher]

Swept-Source Optical Coherence Tomography Angiography of an Amalric Choroidal Infarction in a Rare Presentation of Giant Cell Arteritis With Bilateral Corneal Edema.

Ophthalmic Surg Lasers Imaging Retina. 2018 10 01;49(10):e157-e160

Authors: Tran AQ, Yannuzzi NA, Motulsky EH, Zhou XY, Galor A, Dubovy SR, Rosenfeld PJ, Lam BL

Abstract
A 73-year-old woman with 2 weeks of progressive painless vision loss was found to have bilateral corneal edema, jaw claudication, and temporal headache. Multimodal imaging revealed an Amalric choroidal infarct in the left eye visualized by widefield indocyanine green angiography and swept-source optical coherence tomography angiography (SS-OCTA). Prompt intravenous corticosteroid treatment resulted in 20/20 vision, and giant cell arteritis (GCA) was confirmed by a temporal artery biopsy. The case underscores the use of widefield SS-OCTA as a non-invasive test to aid in the diagnosis of GCA, as well as bilateral cornea edema as a rare presentation of GCA. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e157-e160.].

PMID: 30395679 [PubMed - indexed for MEDLINE]

Hope and foresight for your patients with ALS.

Lancet Neurol. 2018 05;17(5):383

Authors: The Lancet Neurology

PMID: 29656733 [PubMed - indexed for MEDLINE]

Giant periosteal aggressive epithelioid osteoblastoma: 21-year-old male presents case in the midshaft of his femur.

Skeletal Radiol. 2018 Oct;47(10):1443-1448

Authors: Sonnylal L, Peterson JR, Decilveo AP, O'Connor IT, Wittig JC

Abstract
We report a rare case of giant periosteal osteoblastoma in the femur of a 21-year-old male. The patient presented with a painful, firm, non-tender mass in his left thigh. The pain was worse at night and was temporarily relieved with NSAIDS. He had no fevers, night sweats, or weight loss. The patient underwent preoperative radiological studies including plain radiographs, MRI, bone scan, and CT scan. An open biopsy was subsequently performed that was consistent with an aggressive, epithelioid osteoblastoma. Pathology demonstrated a neoplasm characterized by cohesive sheets of epithelioid osteoblasts, mixed with areas of conventional osteoblastoma displaying prominent osteoblastic rimming of woven bone trabeculae in a fibrovascular stroma. The patient subsequently underwent resection, cryosurgery, fixation, and bone grafting with cortical strut allografts. At final follow-up, 32 months postoperatively, there was no evidence of local recurrence. The patient had resumed all his normal activities. He could run without pain and had no restrictions with activities. The goal of this case report is to aid professionals in the diagnosis and treatment of highly uncommon aggressive osteoblastomas.

PMID: 29525944 [PubMed - indexed for MEDLINE]

Synchronous bilateral lipoma arborescens of bicipitoradial bursa-a rare entity.

Skeletal Radiol. 2018 Oct;47(10):1425-1429

Authors: Kalia V, Daher O, Garvin G, Chhibber S, Shepherd J

Abstract
Lipoma arborescens is a rare non-neoplastic condition that affects the synovial lining of joints and bursae accounting for less than 1% of all lipomatous lesions. Characterized by villous proliferation of the synovium, it is an uncommon cause of intra/periarticular mass presenting as a painless, slowly progressive longstanding swelling, and is sometimes accompanied by intermittent monoarticular effusions. We describe a rare case of bilateral lipoma arborescens in the bicipitoradial bursae in a young male referred for MRI evaluation of spontaneous bilateral elbow swelling. We chose to bring this case to light because of the rare simultaneous involvement of the bicipitoradial bursae bilaterally and the role of MR in providing a definite diagnosis, hence obviating the need for biopsy and avoiding consideration of other complex intra/periarticular masses.

PMID: 29500484 [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 2019/03/15

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.

Lemierre's syndrome: One rare disease-Two case studies.

J Clin Pharm Ther. 2019 Feb;44(1):122-124

Authors: Le C, Gennaro D, Marshall D, Alaev O, Bryan A, Gelfman A, Wang Z

Abstract
WHAT IS KNOWN AND OBJECTIVE: Lemierre's syndrome is often misdiagnosed as a common cold or viral infection. Fusobacterium necrophorum is the most common causative organism. The recommended treatment regimen is 6 weeks of a beta-lactam antibiotic along with metronidazole.
CASE DESCRIPTION: We present two cases of Lemierre's syndrome with internal jugular vein thrombophlebitis and positive blood cultures for F. necrophorum. The first case was successfully treated with 6 weeks of a beta-lactam antibiotic and 4 weeks of metronidazole, while the second case was successfully treated with 4 weeks of a beta-lactam antibiotic and 2 weeks of metronidazole.
WHAT IS NEW AND CONCLUSION: Two cases of Lemierre's syndrome were treated successfully with only 2-4 weeks of metronidazole therapy. Shorter duration of metronidazole therapy should be explored in future studies.

PMID: 30484880 [PubMed - indexed for MEDLINE]

Imaging of coronary artery fistulas by multidetector CT angiography using third generation dual source CT scanner.

Clin Imaging. 2019 Jan - Feb;53:89-96

Authors: Sharma A, Pandey NN, Kumar S

Abstract
Coronary artery fistulas are rare cardiac conditions which constitute a subgroup of anomalies of the coronary arteries. Though majority are asymptomatic, they may be associated with high prevalence of late symptoms and complications. Accurate identification of the fistulas, their hemodynamic significance and associated conditions generally influence management strategies. Dual source computed tomographic evaluation is valuable in delineating its precise morphology with identification and characterization of associated anomalies, thereby assisting in mapping the ideal treatment option.

PMID: 30317136 [PubMed - indexed for MEDLINE]

Pott Puffy Tumor.

J Am Osteopath Assoc. 2018 Jan 01;118(1):55

Authors: Morris MS, Wilkins SE

PMID: 29309099 [PubMed - indexed for MEDLINE]

Nephroblastoma Arising in a Primary Testicular Teratoma in a Nonatrophic Testis of a 50-Year-Old Man.

J Am Osteopath Assoc. 2018 Jan 01;118(1):45-49

Authors: Kromka JJ, Turner K, Elisco A, Hale N

Abstract
Extrarenal nephroblastoma is an extremely rare tumor thought to be related to teratoid tumors of germ cell origin. Because few cases have been reported, no standard method for categorizing and managing these tumors exists. To our knowledge, there have only been 3 adult cases of nephroblastoma arising in a germ cell tumor of testicular origin in a nonatrophic testis, all in men aged 19 to 22 years and with aggressive clinical courses. We report a case of nephroblastoma in a nonatrophic testis, with nephroblastoma being the only non-germ cell component, in an older patient and with a more indolent clinical course that was responsive to localized treatment.

PMID: 29309092 [PubMed - indexed for MEDLINE]