Chilaiditi Syndrome Is a Rare Disease With Features That Resemble Pneumoperitoneum.

Clin Gastroenterol Hepatol. 2019 02;17(3):A30

Authors: Kathawa J, George K, Piper M

PMID: 29574238 [PubMed - indexed for MEDLINE]

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 2020/03/31

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 2020/03/31

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.

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 2020/03/28

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.

Detailed overview on rare malignant ovarian tumors.

Bull Cancer. 2020 Mar;107(3):385-390

Authors: Aust S, Eberst L, Tredan O, Rousset-Jablonski C, Treilleux I, Méeus P, Chopin N, Beurrier F, Charreton A, Véronique D, Hallouz A, Coulon A, Ricoeur A, Mastier C, Bouhamama A, Racadot S, Devouassoux-Shisheboran M, Haddad V, Ray-Coquard I

Abstract
The group of rare malignant ovarian tumors includes the group of germ cell tumors, sex cords stromal ovarian tumors, small cell carcinoma, malignant Brenner tumors, rare epithelial tumors such as mucinous carcinoma, clear cell carcinoma, or low-grade serous carcinoma, as well as ovarian carcinosarcoma. Together they comprise about 10% of all ovarian tumors. Due to their low prevalence and their heterogeneity, data and treatment recommendations are limited. Even though all ovarian tumors are staged according to the FIGO staging of epithelial ovarian tumors, treatment differs especially in germ cell tumors and sex cords stromal ovarian tumors. Non-epithelial ovarian tumors can arise from a variety of ovarian precursor cells such as germ cells, granulosa cells, theca cells, or stromal fibroblasts. As can be expected already due to their divergent precursor lesions, these malignancies are substantially different but united by their rarity. This overview article gives a comprehensive summary on the pathology and clinical presentation, as well as therapy recommendations of a selection of those rare ovarian tumors, based on the latest national guidelines and related important publications.

PMID: 32115180 [PubMed - indexed for MEDLINE]

The role of patients' associations.

Bull Cancer. 2020 Mar;107(3):381-384

Authors: Hélaine A, Podevin M

Abstract
The role of patient groups has grown steadily stronger since the first General Meeting of cancer patients in 1999 and the emergence of the rare diseases issue in the mid-eighties. This article demonstrates the role of a patient group (SOS DESMOIDE) gathering people suffering from a rare disease (the desmoid tumor) in the stimulation of scientific and medical research as well as the improvement of patient care, information and support provided to patients. It substantiates these elements with numerous socio-medico-psychological surveys, scientific publications and medical research implemented by medical teams and supported, even sometimes initiated, by SOS DESMOIDE. This research effort illustrates the significant impact of a partnership between patients and physicians-researchers on medical and scientific breakthroughs in a specific pathological field.

PMID: 31812285 [PubMed - indexed for MEDLINE]

Rare Presentation of Postsurgical Pyoderma Gangrenosum Presenting as Necrotizing Soft Tissue Infection.

Adv Skin Wound Care. 2019 Nov;32(11):507-511

Authors: Flynn RL, Chowdhury MH, Rudolph J, Einstein S

Abstract
Pyoderma gangrenosum (PG) is a rare inflammatory neutrophilic dermatosis believed to be mediated by an autoimmune reaction. Typical treatment includes autolytic debridement, management of exudate, protection from trauma, and steroid therapy. A diagnosis of exclusion, PG is frequently mistaken for a wound infection, but antibiotics do not alleviate the condition. Incision and debridement has been observed to cause further spread of the lesions because of pathergy resulting from the additional trauma. This case report describes a patient who was misdiagnosed with necrotic soft tissue infection that was actually postsurgical PG.

PMID: 31498172 [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 2020/03/26

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.

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 2020/03/26

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.

Immunotherapy for mesothelioma: a critical review of current clinical trials and future perspectives.

Transl Lung Cancer Res. 2020 Feb;9(Suppl 1):S100-S119

Authors: Gray SG, Mutti L

Abstract
At the clinical level the role of immunotherapy in cancer is currently at a pivotal point. Therapies such as checkpoint inhibitors are being approved at many levels in cancers such as non-small cell lung cancer (NSCLC). Mesothelioma is a rare orphan disease associated with prior exposure to asbestos, with a dismal prognosis. Various clinical trials for checkpoint inhibitors have been conducted in this rare disease, and suggest that such therapies may play a role as a treatment option for a proportion of patients with this cancer. Most recently approved as a salvage therapy in mesothelioma was granted in Japan, regulatory approval for their use in the clinic elsewhere lags. In this article we review the current pertinent clinical trials of immunotherapies in malignant mesothelioma, discuss the current issues that may affect the clinical outcomes of such therapies and further evaluate potential candidate new avenues that may become future targets for immunotherapy in this cancer.

PMID: 32206576 [PubMed]

Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome.

J Exp Med. 2020 Jun 01;217(6):

Authors: Béziat V, Tavernier SJ, Chen YH, Ma CS, Materna M, Laurence A, Staal J, Aschenbrenner D, Roels L, Worley L, Claes K, Gartner L, Kohn LA, De Bruyne M, Schmitz-Abe K, Charbonnier LM, Keles S, Nammour J, Vladikine N, Maglorius Renkilaraj MRL, Seeleuthner Y, Migaud M, Rosain J, Jeljeli M, Boisson B, Van Braeckel E, Rosenfeld JA, Dai H, Burrage LC, Murdock DR, Lambrecht BN, Avettand-Fenoel V, Vogel TP, Undiagnosed Diseases Network, Esther CR, Haskologlu S, Dogu F, Ciznar P, Boutboul D, Ouachée-Chardin M, Amourette J, Lebras MN, Gauvain C, Tcherakian C, Ikinciogullari A, Beyaert R, Abel L, Milner JD, Grimbacher B, Couderc LJ, Butte MJ, Freeman AF, Catherinot É, Fieschi C, Chatila TA, Tangye SG, Uhlig HH, Haerynck F, Casanova JL, Puel A

Abstract
Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven different truncating mutations, one of which was recurrent. The mutant alleles encode GP130 receptors bearing the transmembrane domain but lacking both the recycling motif and all four STAT3-recruiting tyrosine residues. Upon overexpression, the mutant proteins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6, IL-11, LIF, and OSM. Moreover, the patients' heterozygous leukocytes and fibroblasts respond poorly to IL-6 and IL-11. Consistently, patients with STAT3 and IL6ST mutations display infectious and allergic manifestations of IL-6R deficiency, and some of the skeletal abnormalities of IL-11R deficiency. DN STAT3 and IL6ST mutations thus appear to underlie clinical phenocopies through impairment of the IL-6 and IL-11 response pathways.

PMID: 32207811 [PubMed - as supplied by publisher]

Rare synovium pseudotumor of the knee.

Tunis Med. 2019 Feb;97(2):304-306

Authors: Aichouni N, Benmoussa Y, Nasri S, Kane M, Skiker I, Kamaoui I

Abstract
It is a rare synovium pseudotumor that mainly concerns the male adult, of unknown etiology, espe-cially observed in the knee, especially in the suprapatellar recess. The arboreal lipoma consists of hypertrophic synovial villi and contains fat in very large quantities, so that the mass has a lipoma-tous appearance. The diagnosis is based on an MRI that shows hypertrophy of synovial villi appear-ing as a fatty signal on all sequences. However the diagnosis is established after synovial biopsy.

PMID: 31539087 [PubMed - indexed for MEDLINE]

Eculizumab for Severe Thrombotic Microangiopathy Secondary to Surgical Invasive Stress and Bleeding.

Intern Med. 2020;59(1):93-99

Authors: Fujita Y, Terashita M, Yazawa M, Yamasaki Y, Imamura T, Kibayashi J, Sawai T, Hidaka Y, Ohtani K, Inoue N, Shibagaki Y

Abstract
Atypical hemolytic uremic syndrome (aHUS) is an extremely rare condition caused by an excessive activation of the complement pathway based on genetic or acquired dysfunctions in complement regulation, leading to thrombotic microangiopathy (TMA). A complement-amplifying condition (CAC) can trigger aHUS occurrence along with complement abnormality. We herein report a case of severe TMA after laparoscopic myomectomy in a healthy woman. This case was eventually diagnosed as complement-mediated TMA secondary to surgical invasive stress as a CAC, with no definitive diagnosis of aHUS despite a genetic test. The patient fully recovered after several eculizumab administrations.

PMID: 31902910 [PubMed - indexed for MEDLINE]

Platypnoea-orthodeoxia syndrome after pulmonary lobectomy: a rare entity with a difficult diagnosis.

Interact Cardiovasc Thorac Surg. 2019 11 01;29(5):811-812

Authors: Krasas A, Tzifa A, Mallios D, Iliadis K

Abstract
Platypnoea-orthodeoxia syndrome (POS) is a rare clinical entity. It is characterized by position-dependent dyspnoea and oxygen desaturation in the upright position with orthodeoxia resolving in the supine position, and is mainly associated with cardiac defects. Only 9 cases of post-lobectomy POS have been reported in the literature. We describe a case of POS in a woman who underwent a lobectomy and in whom POS was diagnosed and treated.

PMID: 31280322 [PubMed - indexed for MEDLINE]

Catastrophic cerebral infarction during extracorporeal life support due to a rare anomaly in the circle of Willis.

Interact Cardiovasc Thorac Surg. 2019 11 01;29(5):816-817

Authors: Sonobe A, Kato H, Mathis BJ, Hiramatsu Y

Abstract
During extracorporeal life support (ECLS) in infants, cannulation of the right common carotid artery may result in a devastating ischaemic neurological injury. Herein, we present a case of an infant who encountered bilateral cerebral infarction during ECLS via the right carotid artery due to a rare and tragic anomaly of the circle of Willis. The magnetic resonance angiography complemented computed tomography in diagnosing the infarction and identifying this unique anatomy.

PMID: 31280292 [PubMed - indexed for MEDLINE]

Towards a national genomics medicine service: the challenges facing clinical-research hybrid practices and the case of the 100 000 genomes project.

J Med Ethics. 2018 06;44(6):397-403

Authors: Dheensa S, Samuel G, Lucassen AM, Farsides B

Abstract
Clinical practice and research are governed by distinct rules and regulations and have different approaches to, for example, consent and providing results. However, genomics is an example of where research and clinical practice have become codependent. The 100 000 genomes project (100kGP) is a hybrid venture where a person can obtain a clinical investigation only if he or she agrees to also participate in ongoing research-including research by industry and commercial companies. In this paper, which draws on 20 interviews with professional stakeholders involved in 100kGP, we investigate the ethical issues raised by this project's hybrid nature. While some interviewees thought the hybrid nature of 100kGP was its vanguard, interviewees identified several tensions around hybrid practice: how to decide who should be able to participate; how to determine whether offering results might unduly influence participation into wide-ranging but often as yet unknown research and how to ensure that patients/families do not develop false expectations about receiving results. These areas require further debate as 100kGP moves into routine healthcare in the form of the national genomic medicine service. To address the tensions identified, we explore the appropriateness of Faden et al.'s framework of ethical obligations for when research and clinical care are completely integrated. We also argue that enabling ongoing transparent and trustworthy communication between patients/families and professionals around the kinds of research that should be permitted in 100kGP will help to understand and ensure that expectations remain realistic. Our paper aims to encourage a focused discussion about these issues and to inform a new 'social contract' for research and clinical care in the health service.

PMID: 29496751 [PubMed - indexed for MEDLINE]

De novo EIF2AK1 and EIF2AK2 Variants Are Associated with Developmental Delay, Leukoencephalopathy, and Neurologic Decompensation.

Am J Hum Genet. 2020 Mar 16;:

Authors: Mao D, Reuter CM, Ruzhnikov MRZ, Beck AE, Farrow EG, Emrick LT, Rosenfeld JA, Mackenzie KM, Robak L, Wheeler MT, Burrage LC, Jain M, Liu P, Calame D, Küry S, Sillesen M, Schmitz-Abe K, Tonduti D, Spaccini L, Iascone M, Genetti CA, Koenig MK, Graf M, Tran A, Alejandro M, Undiagnosed Diseases Network, Lee BH, Thiffault I, Agrawal PB, Bernstein JA, Bellen HJ, Chao HT

Abstract
EIF2AK1 and EIF2AK2 encode members of the eukaryotic translation initiation factor 2 alpha kinase (EIF2AK) family that inhibits protein synthesis in response to physiologic stress conditions. EIF2AK2 is also involved in innate immune response and the regulation of signal transduction, apoptosis, cell proliferation, and differentiation. Despite these findings, human disorders associated with deleterious variants in EIF2AK1 and EIF2AK2 have not been reported. Here, we describe the identification of nine unrelated individuals with heterozygous de novo missense variants in EIF2AK1 (1/9) or EIF2AK2 (8/9). Features seen in these nine individuals include white matter alterations (9/9), developmental delay (9/9), impaired language (9/9), cognitive impairment (8/9), ataxia (6/9), dysarthria in probands with verbal ability (6/9), hypotonia (7/9), hypertonia (6/9), and involuntary movements (3/9). Individuals with EIF2AK2 variants also exhibit neurological regression in the setting of febrile illness or infection. We use mammalian cell lines and proband-derived fibroblasts to further confirm the pathogenicity of variants in these genes and found reduced kinase activity. EIF2AKs phosphorylate eukaryotic translation initiation factor 2 subunit 1 (EIF2S1, also known as EIF2α), which then inhibits EIF2B activity. Deleterious variants in genes encoding EIF2B proteins cause childhood ataxia with central nervous system hypomyelination/vanishing white matter (CACH/VWM), a leukodystrophy characterized by neurologic regression in the setting of febrile illness and other stressors. Our findings indicate that EIF2AK2 missense variants cause a neurodevelopmental syndrome that may share phenotypic and pathogenic mechanisms with CACH/VWM.

PMID: 32197074 [PubMed - as supplied by publisher]

A Rapidly Enlarging Neck Mass: A Case Report.

Am J Med. 2019 12;132(12):e858-e859

Authors: Moale A, Zimmerman J

PMID: 31326410 [PubMed - indexed for MEDLINE]

Development of Autoimmune Interstitial Lung Disease in a Patient with Inclusion Body Myositis.

Am J Med. 2019 12;132(12):e854-e855

Authors: He C, Lee JS, Cool CD, Wicklund MP, Fischer A

PMID: 31310746 [PubMed - indexed for MEDLINE]

Predicting disease-causing variant combinations.

Proc Natl Acad Sci U S A. 2019 06 11;116(24):11878-11887

Authors: Papadimitriou S, Gazzo A, Versbraegen N, Nachtegael C, Aerts J, Moreau Y, Van Dooren S, Nowé A, Smits G, Lenaerts T

Abstract
Notwithstanding important advances in the context of single-variant pathogenicity identification, novel breakthroughs in discerning the origins of many rare diseases require methods able to identify more complex genetic models. We present here the Variant Combinations Pathogenicity Predictor (VarCoPP), a machine-learning approach that identifies pathogenic variant combinations in gene pairs (called digenic or bilocus variant combinations). We show that the results produced by this method are highly accurate and precise, an efficacy that is endorsed when validating the method on recently published independent disease-causing data. Confidence labels of 95% and 99% are identified, representing the probability of a bilocus combination being a true pathogenic result, providing geneticists with rational markers to evaluate the most relevant pathogenic combinations and limit the search space and time. Finally, the VarCoPP has been designed to act as an interpretable method that can provide explanations on why a bilocus combination is predicted as pathogenic and which biological information is important for that prediction. This work provides an important step toward the genetic understanding of rare diseases, paving the way to clinical knowledge and improved patient care.

PMID: 31127050 [PubMed - indexed for MEDLINE]