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 2020/08/22

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.

Evolution of genomic and T cell repertoire heterogeneity of malignant pleural mesothelioma under dasatinib treatment.

Clin Cancer Res. 2020 Aug 14;:

Authors: Chen R, Lee WC, Fujimoto J, Li J, Hu X, Mehran R, Rice D, Swisher SG, Sepesi B, Tran HT, Chow CW, Little LD, Gumbs C, Haymaker C, Heymach JV, Wistuba II, Lee JJ, Futreal PA, Zhang J, Reuben A, Tsao AS, Zhang J

Abstract
PURPOSE: Malignant pleural mesothelioma (MPM) is considered an orphan disease with few treatment options. Despite multimodality therapy, the majority of MPM recur and eventually become refractory to any systemic treatment. One potential mechanism underlying therapeutic resistance may be intratumor heterogeneity (ITH), making MPM challenging to eradicate. However, the ITH architecture of MPM and its clinical impact have not been well studied.
EXPERIMENTAL DESIGN: We delineated the immunogenomic ITH by multi-region whole exome sequencing (WES) and T cell receptor (TCR) sequencing of 69 longitudinal MPM specimens from 9 patients with resectable MPM, who were treated with dasatinib.
RESULTS: The median total mutation burden (TMB) before dasatinib treatment was 0.65/Mb, similar with that of post-dasatinib treatment (0.62/Mb). The median proportion of mutations shared by any given pair of two tumor regions within the same tumors was 80% prior to and 83% post-dasatinib treatment indicating a relatively homogenous genomic landscape. T cell clonality, a parameter indicating T cell expansion and reactivity was significantly increased in tumors after dasatinib treatment. Furthermore, on average, 82% of T cell clones were restricted to individual tumor regions, with merely 6% of T cell clones shared by all regions from the same tumors indicating profound TCR heterogeneity. Interestingly, patients with higher T cell clonality and higher portion of T cells present across all tumor regions in post-dasatinib treated tumors had significantly longer survival.
CONCLUSIONS: Despite the homogeneous genomic landscape, the TCR repertoire is extremely heterogeneous in MPM. Dasatinib may potentially induce T cell response leading to improved survival.

PMID: 32816946 [PubMed - as supplied by publisher]

APP gene copy number changes reflect exogenous contamination.

Nature. 2020 Aug;584(7821):E20-E28

Authors: Kim J, Zhao B, Huang AY, Miller MB, Lodato MA, Walsh CA, Lee EA

PMID: 32814883 [PubMed - in process]

Myxofibrosarcoma that Developed Rapidly in the Breast of an Elderly Man and Recurred Early after Surgery: A Case Report.

Tokai J Exp Clin Med. 2020 Jul 20;45(2):53-57

Authors: Tsuda B, Ogura G, Kumaki N, Sakaeda S, Ishida R, Mizuno M, Yokoyama K, Terao M, Morioka T, Okamura T, Imagawa K, Kohno M, Watanabe T, Niikura N

Abstract
BACKGROUND: Myxofibrosarcoma is a rare disease occurring subcutaneously in the limbs. We report a case of a rapidly growing myxofibrosarcoma in the breast of an elderly man that recurred early after surgery.
CASE PRESENTATION: A 73-year-old man presented with a breast mass. Physical findings showed a large tumor in the right breast, and malignancy was suspected on ultrasonography. Computed tomography (CT) revealed tumor invasion into the pectoralis major and pectoralis minor muscles. Positron emission tomography/CT showed no abnormality in other organs. Needle biopsy results excluded breast cancer but did not provide a definitive diagnosis. However, the tumor grew rapidly before further results were available, so emergency mastectomy was performed. The final pathological diagnosis was high-grade myxofibrosarcoma. Postoperative radiotherapy was started because of remnant tumor. The wound became worsened and swollen, and needle biopsy 10 days after the start of therapy indicated recurrence. Radical resection and thoracoplasty were performed. Postoperative pathological specimens showed no residual tumor. Radical radiation therapy was resumed. The patient has shown no recurrence after an year.
CONCLUSIONS: It is important to consult a soft tissue oncologist for tumors in the breast and perform appropriate examination and treatment if soft tissue tumors cannot be ruled out.

PMID: 32602101 [PubMed - indexed for MEDLINE]

Computed Tomographic 3-Dimensional Virtual Dissection Aiding Surgical Planning in a Rare Pediatric Case of Bicuspid Aortic Valve With Ascending Aorta Pseudoaneurysm.

Circ Cardiovasc Imaging. 2020 03;13(3):e010089

Authors: Steele J, Alsaied T, Crotty EJ, Tretter JT

PMID: 32114826 [PubMed - indexed for MEDLINE]

Galactokinase deficiency: lessons from the GalNet registry.

Genet Med. 2020 Aug 18;:

Authors: Rubio-Gozalbo ME, Derks B, Das AM, Meyer U, Möslinger D, Couce ML, Empain A, Ficicioglu C, Juliá Palacios N, De Los Santos De Pelegrin MM, Rivera IA, Scholl-Bürgi S, Bosch AM, Cassiman D, Demirbas D, Gautschi M, Knerr I, Labrune P, Skouma A, Verloo P, Wortmann SB, Treacy EP, Timson DJ, Berry GT

Abstract
PURPOSE: Galactokinase (GALK1) deficiency is a rare hereditary galactose metabolism disorder. Beyond cataract, the phenotypic spectrum is questionable. Data from affected patients included in the Galactosemias Network registry were collected to better characterize the phenotype.
METHODS: Observational study collecting medical data of 53 not previously reported GALK1 deficient patients from 17 centers in 11 countries from December 2014 to April 2020.
RESULTS: Neonatal or childhood cataract was reported in 15 and 4 patients respectively. The occurrence of neonatal hypoglycemia and infection were comparable with the general population, whereas bleeding diathesis (8.1% versus 2.17-5.9%) and encephalopathy (3.9% versus 0.3%) were reported more often. Elevated transaminases were seen in 25.5%. Cognitive delay was reported in 5 patients. Urinary galactitol was elevated in all patients at diagnosis; five showed unexpected Gal-1-P increase. Most patients showed enzyme activities ≤1%. Eleven different genotypes were described, including six unpublished variants. The majority was homozygous for NM_000154.1:c.82C>A (p.Pro28Thr). Thirty-five patients were diagnosed following newborn screening, which was clearly beneficial.
CONCLUSION: The phenotype of GALK1 deficiency may include neonatal elevation of transaminases, bleeding diathesis, and encephalopathy in addition to cataract. Potential complications beyond the neonatal period are not systematically surveyed and a better delineation is needed.

PMID: 32807972 [PubMed - as supplied by publisher]

The Perlman syndrome DIS3L2 exoribonuclease safeguards endoplasmic reticulum-targeted mRNA translation and calcium ion homeostasis.

Nat Commun. 2020 05 26;11(1):2619

Authors: Pirouz M, Wang CH, Liu Q, Ebrahimi AG, Shamsi F, Tseng YH, Gregory RI

Abstract
DIS3L2-mediated decay (DMD) is a surveillance pathway for certain non-coding RNAs (ncRNAs) including ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), and RMRP. While mutations in DIS3L2 are associated with Perlman syndrome, the biological significance of impaired DMD is obscure and pathological RNAs have not been identified. Here, by ribosome profiling (Ribo-seq) we find specific dysregulation of endoplasmic reticulum (ER)-targeted mRNA translation in DIS3L2-deficient cells. Mechanistically, DMD functions in the quality control of the 7SL ncRNA component of the signal recognition particle (SRP) required for ER-targeted translation. Upon DIS3L2 loss, sustained 3'-end uridylation of aberrant 7SL RNA impacts ER-targeted translation and causes ER calcium leakage. Consequently, elevated intracellular calcium in DIS3L2-deficient cells activates calcium signaling response genes and perturbs ESC differentiation. Thus, DMD is required to safeguard ER-targeted mRNA translation, intracellular calcium homeostasis, and stem cell differentiation.

PMID: 32457326 [PubMed - indexed for MEDLINE]

Homozygous GRN mutations: new phenotypes and new insights into pathological and molecular mechanisms.

Brain. 2020 01 01;143(1):303-319

Authors: Huin V, Barbier M, Bottani A, Lobrinus JA, Clot F, Lamari F, Chat L, Rucheton B, Fluchère F, Auvin S, Myers P, Gelot A, Camuzat A, Caillaud C, Jornéa L, Forlani S, Saracino D, Duyckaerts C, Brice A, Durr A, Le Ber I

Abstract
Homozygous mutations in the progranulin gene (GRN) are associated with neuronal ceroid lipofuscinosis 11 (CLN11), a rare lysosomal-storage disorder characterized by cerebellar ataxia, seizures, retinitis pigmentosa, and cognitive disorders, usually beginning between 13 and 25 years of age. This is a rare condition, previously reported in only four families. In contrast, heterozygous GRN mutations are a major cause of frontotemporal dementia associated with neuronal cytoplasmic TDP-43 inclusions. We identified homozygous GRN mutations in six new patients. The phenotypic spectrum is much broader than previously reported, with two remarkably distinct presentations, depending on the age of onset. A childhood/juvenile form is characterized by classical CLN11 symptoms at an early age at onset. Unexpectedly, other homozygous patients presented a distinct delayed phenotype of frontotemporal dementia and parkinsonism after 50 years; none had epilepsy or cerebellar ataxia. Another major finding of this study is that all GRN mutations may not have the same impact on progranulin protein synthesis. A hypomorphic effect of some mutations is supported by the presence of residual levels of plasma progranulin and low levels of normal transcript detected in one case with a homozygous splice-site mutation and late onset frontotemporal dementia. This is a new critical finding that must be considered in therapeutic trials based on replacement strategies. The first neuropathological study in a homozygous carrier provides new insights into the pathological mechanisms of the disease. Hallmarks of neuronal ceroid lipofuscinosis were present. The absence of TDP-43 cytoplasmic inclusions markedly differs from observations of heterozygous mutations, suggesting a pathological shift between lysosomal and TDP-43 pathologies depending on the mono or bi-allelic status. An intriguing observation was the loss of normal TDP-43 staining in the nucleus of some neurons, which could be the first stage of the TDP-43 pathological process preceding the formation of typical cytoplasmic inclusions. Finally, this study has important implications for genetic counselling and molecular diagnosis. Semi-dominant inheritance of GRN mutations implies that specific genetic counselling should be delivered to children and parents of CLN11 patients, as they are heterozygous carriers with a high risk of developing dementia. More broadly, this study illustrates the fact that genetic variants can lead to different phenotypes according to their mono- or bi-allelic state, which is a challenge for genetic diagnosis.

PMID: 31855245 [PubMed - indexed for MEDLINE]

Conservative management of a rare case of atrial septal hematoma after pediatric cardiac surgery.

J Card Surg. 2020 Jan;35(1):207-210

Authors: Alshamdin FD, Dawary MA, Khouqeer FA

Abstract
Atrial septal hematoma is uncommon complication that may happen after any cardiac intervention. Although it is rare, it can pose a challenging situation in the postoperative care. Multiple management approaches has been described with different outcomes. Here we are reporting a boy, aged 13 years, with dilated aortic root who underwent aortic root replacement with valve preservation. Postoperative course was complicated by atrial septal hematoma. A nonsurgical management approach was chosen based on the patient clinical condition. Regression in size with complete resolution of the hematoma was observed during the follow up.

PMID: 31614023 [PubMed - indexed for MEDLINE]

Rare case of iatrogenic aortic valve leaflet tear following a diagnostic coronary angiogram.

J Card Surg. 2020 Jan;35(1):204-206

Authors: Madigan M, McIsaac S, Garg A, Alqahtani A, Kumar A, Atoui R

Abstract
We report a rare case of a 44-year-old male who underwent a diagnostic coronary angiogram following a non-ST elevation myocardial infarction complicated by an aortic valve leaflet tear requiring surgical intervention. Routine transthoracic echocardiogram demonstrated a mobile echogenic structure prolapsing into the left ventricular outflow tract. An intraoperative transesophageal echocardiogram confirmed that the structure originated from the ventricular side of left coronary cusp, causing malcoaptation between left and right coronary cusps, and subsequent moderate to severe aortic regurgitation.

PMID: 31573092 [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 2020/08/18

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.

Abernethy malformation and hepatocellular carcinoma: a serious consequence of a rare disease.

BMJ Case Rep. 2020 Jan 06;13(1):

Authors: Jaklitsch M, Sobral M, Carvalho AM, Marques HP

Abstract
Congenital portosystemic shunts (CPSS) are a rare vascular consequence of embryogenetic vascular alterations or the persistence of the fetal circulation elements, first described by John Abernethy in 1793 and classified by Morgan and Superina, into complete and partial portosystemic shunts. Its prevalence to this day has not been defined. We present a patient series of a 44-year-old and 47-year-old man and woman, with this rare congenital malformation and underlining hepatocellular carcinoma (HCC) treatment strategies. Over half of the individuals with CPSS have benign or malignant liver tumours, ranging from nodular regenerative hyperplasia, focal nodular hyperplasia, adenomas, HCC and hepatoblastomas. Additionally, it is known that half of individuals with Abernethy malformation type Ib will develop one or multiple types of tumours. There seems to be a direct association with tumorigenesis and CPSS, which is the primary consequence of absent portal flow. Surgery is the treatment of choice, either as a curative resection or orthotopic liver transplantation if recommended as per the criteria, in which replacing the hepatic parenchyma in the setting of an Abernathy malformation will correct the underlining hyper-arterialisation.

PMID: 31911408 [PubMed - indexed for MEDLINE]

Tetralogy of Fallot With Interatrial Communication of the Inferior Sinus Venosus Type: A Rare Association Causing Post-Operative Desaturation.

World J Pediatr Congenit Heart Surg. 2019 11;10(6):801-802

Authors: Agrawal G, Das A

Abstract
This case report describes a rare association of tetralogy of Fallot with interatrial communication of the inferior sinus venosus type (inferior sinus venosus defect). The patient underwent intracardiac repair for tetralogy of Fallot at 8 months of age. His postoperative course was complicated by desaturation. On reexploration, interatrial communication of the inferior sinus venosus type was revealed which went unnoticed on transthoracic echocardiogram as well as on computerized tomogram.

PMID: 31701832 [PubMed - indexed for MEDLINE]

Alternative access schemes for pharmaceuticals in Europe: Towards an emerging typology.

Health Policy. 2019 07;123(7):630-634

Authors: Löblová O, Csanádi M, Ozierański P, Kaló Z, King L, McKee M

Abstract
European governments employ sophisticated health technology assessment and regulatory procedures to identify which pharmaceuticals to fund publicly. However, there are persisting demands from patients for those drugs excluded from positive reimbursement lists, leading to the emergence of what are here termed "alternative access schemes". This paper presents a purposive review of these schemes based on available scholarly and grey literature, illustrated with real-world examples from recent practice. It puts forward an original typology of alternative access schemes based on their marketing authorization (regulation) and reimbursement (redistribution) status. We describe the complex, multidimensional policy trade-offs between the principles of patient freedom of choice, clinical autonomy, encouragement of innovation, evidence-informed decisions on safety and quality, access to treatment, and financial sustainability, involved in marketing authorization and reimbursement decisions. We discuss the ways in which alternative access schemes differ and conclude that our typology can illuminate salient policy dilemmas raised by alternative access schemes in national drug reimbursement systems.

PMID: 31130319 [PubMed - indexed for MEDLINE]

Tuberous sclerosis complex: new insights into clinical and therapeutic approach.

J Nephrol. 2019 Jun;32(3):355-363

Authors: Volpi A, Sala G, Lesma E, Labriola F, Righetti M, Alfano RM, Cozzolino M

Abstract
Tuberous sclerosis complex (TSC) is a complex disease with many different clinical manifestations. Despite the common opinion that TSC is a rare condition, with a mean incidence of 1/6000 live births and a prevalence of 1/20,000, it is increasingly evident that in reality this is not true. Its clinical sequelae span a range of multiple organ systems, in particular the central nervous system, kidneys, skin and lungs. The management of TSC patients is heavily burdensome in terms of time and healthcare costs both for the families and for the healthcare system. Management options include conservative approaches, surgery, pharmacotherapy with mammalian target of rapamycin inhibitors and recently proposed options such as therapy with anti-EGFR antibody and ultrasound-guided percutaneous microwaves. So far, however, no systematically accepted strategy has been found that is both clinically and economically efficient. Thus, decisions are tailored to patients' characteristics, resource availability and clinical and technical expertise of each single center. This paper reviews the pathophysiology and the clinical (diagnostic-therapeutic) management of TSC.

PMID: 30406604 [PubMed - indexed for MEDLINE]

Necrotising fasciitis caused by aeromonas sobria: Not just a simple catfish sting.

Med J Malaysia. 2019 12;74(6):543-544

Authors: Ng BW, Ong KC, Ahmad-Azraf A, Abdul-Muttalib AW

Abstract
Necrotising fasciitis is a life-threatening infection of the soft tissue which can be caused by different microorganisms, but infection caused by Aeromonas spp. or Vibrio spp. is frequently associated with higher mortality rate. Necrotising fasciitis progresses rapidly and often need aggressive surgical intervention. We present a rare case of necrotising fasciitis cause by Aeromonas sobria which mortality was successfully prevented by swift diagnosis and aggressive surgery.

PMID: 31929484 [PubMed - indexed for MEDLINE]

Japanese Encephalitis presenting with cerebral venous sinus thrombosis: a case report.

Med J Malaysia. 2019 12;74(6):537-539

Authors: Neo RJ

Abstract
A 17-year-old man from Sarawak presented with acute encephalitis syndrome. Serologic testing revealed raised Japanese Encephalitis (JE) IgM antibody titre in which first serum JE was negative followed by positive second serum JE IgM one week later. Magnetic resonance imaging (MRI) and Magnetic resonance venogram (MRV) showed cerebral venous sinus thrombosis (CVST) which is a rare presentation of JE. Early identification of CVST is important as anticoagulation needs to be started to reduce adverse neurological sequelae and improve prognosis.

PMID: 31929482 [PubMed - indexed for MEDLINE]

'It would be much easier if we were just quiet and disappeared': Parents silenced in the experience of caring for children with rare diseases.

Health Expect. 2019 12;22(6):1251-1259

Authors: Currie G, Szabo J

Abstract
BACKGROUND: Parent experiences of caring for children with neurodevelopmental disease have been silenced and constrained by social, political and health influences. There is a need to co-construct new meanings and interpretations of parenting a child with complex disabilities by having an increased understanding of the struggles and barriers for parents.
METHODS: A hermeneutic phenomenology approach was applied in this inquiry. Fifteen parents of children with rare neurodevelopmental diseases participated in semi-structured interviews.
RESULTS: Parents experienced silencing or being silenced within interactions with health-care and social care systems and providers. Interpretive thematic analysis revealed three insights: (a) parents experience a sense of disconnect and silencing as little is known or understood by health-care providers about the experience of caring for children at home; (b) parents make strong efforts to be heard and acquire services within health and social systems as fighters, saviours and navigators; and (c) parents sacrifice themselves to the caregiving role and become therapists and caregivers to their medically fragile children at the cost of losing themselves as parents.
CONCLUSION: An understanding of parents' experiences in caring for a child with a rare neurodevelopmental disease may provide insight to systemic health and social support challenges faced by families and mitigate appropriate and supportive policies and services.

PMID: 31466132 [PubMed - indexed for MEDLINE]

Further clinical interpretation and implications of KEYNOTE-048 findings - Authors' reply.

Lancet. 2020 08 08;396(10248):379-380

Authors: Burtness B, Zhang Y, Harrington KJ, Rischin D

PMID: 32771104 [PubMed - indexed for MEDLINE]

Recurrence of breast cancer after anaesthesia - Author's reply.

Lancet. 2020 08 08;396(10248):377-378

Authors: Sessler DI

PMID: 32771100 [PubMed - indexed for MEDLINE]