Mitral Valve Endocarditis: A Rare Manifestation of Lyme Disease.

Ann Thorac Surg. 2019 08;108(2):e85-e86

Authors: Haddad O, Gillinov M, Fraser T, Shrestha N, Pettersson GB

Abstract
Valvular involvement in Lyme disease is rare. Confirmation of Borrelia species as the causative agent with polymerase chain reaction was done in a few cases in Europe and the United States. We describe a case of mitral regurgitation with a preoperative diagnosis of myxomatous mitral valve degeneration. During surgery, the surgeon suspected infective rather than degenerative etiology; the results of tissue cultures were negative. However, universal bacterial polymerase chain reaction on explanted valve tissue detected Borrelia burgdorferi DNA. If a surgeon suspects infective endocarditis at the time surgery, appropriate specimens should be sent for histopathologic analysis, culture, and polymerase chain reaction assay.

PMID: 30690018 [PubMed - indexed for MEDLINE]

Inflammatory response and its relation to sphingolipid metabolism proteins: Chaperones as potential indirect anti-inflammatory agents.

Adv Protein Chem Struct Biol. 2019;114:153-219

Authors: Yagci ZB, Esvap E, Ozkara HA, Ulgen KO, Olmez EO

Abstract
Lysosome is the organelle responsible for breaking down macromolecules to maintain homeostasis and to fight infection. The disruption of normal lysosomal function due to mutations in the sphingolipid metabolism proteins leads to a class of lysosomal storage diseases (LSDs). Defective autophagy and activation of inflammation are observed in most LSDs. The crosstalk between these key metabolic pathways suggests that therapeutic approaches used in the treatment of LSDs may provide anti-inflammatory therapies against chronic inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease. Here, we review the role of sphingolipids in the inflammatory response and build a protein-protein interaction network for proteins related with sphingolipid metabolism and inflammation to identify key interaction partners for the crosstalk between sphingolipids and inflammation. In addition, we present an overview of LSDs in relation with sphingolipids and inflammation, and review the pharmacological chaperones identified for these diseases.

PMID: 30635081 [PubMed - indexed for MEDLINE]

Response to Immunotherapy in Combination With Mitotane in Patients With Metastatic Adrenocortical Cancer.

J Endocr Soc. 2019 Dec 01;3(12):2295-2304

Authors: Head L, Kiseljak-Vassiliades K, Clark TJ, Somerset H, King J, Raeburn C, Albuja-Cruz M, Weyant M, Cleveland J, Wierman ME, Leong S

Abstract
Adrenocortical carcinoma (ACC) is a rare orphan disease with a dismal prognosis. Surgery remains the first-line treatment, but most patients eventually develop metastatic disease. Mitotane is often used with chemotherapy with modest success. Little information is available concerning the efficacy of immunotherapy in combination with mitotane. We conducted a retrospective review of our initial six patients with metastatic ACC, for whom mitotane alone or with chemotherapy failed, and who were subsequently treated with a combination of pembrolizumab and mitotane, between July 2016 and March 2019. Imaging was analyzed per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Two patients had a partial response and four patients had stable disease (8 to 19 months). One patient had grade 3 hepatitis and pembrolizumab was discontinued after 8 months. She died with disease progression 16 months after initiating pembrolizumab. One patient developed brain metastasis after 19 months of treatment and was transitioned to hospice. One patient had focal pneumonitis after 18 months of treatment, and pembrolizumab was discontinued. Three remaining patients continue pembrolizumab plus mitotane at the time of this writing. The current standard of care for ACC is a combination of etoposide, doxorubicin, cisplatin, and mitotane with an overall survival of 14.8 months. All six patients lived for at least 16 months after starting pembrolizumab added to mitotane therapy. The therapy appeared to be effective in both microsatellite instability-high and microsatellite stable tumors, suggesting some synergistic effect with mitotane. Combined immunotherapy and mitotane should be considered in future clinical trials in patients with ACC.

PMID: 31745526 [PubMed]

Paroxysmal Hypertension Associated With Urination.

Hypertension. 2019 11;74(5):1068-1074

Authors: Lou Y, Fan L, Hou X, Dominiczak AF, Wang JG, Staessen JA, Almustafa B, Ching S, Persu A, Bursztyn M, Cai J, Zhang H

PMID: 31564165 [PubMed - indexed for MEDLINE]

Establishing an online physical exercise program for people with hemophilia.

Wien Klin Wochenschr. 2019 Nov;131(21-22):558-566

Authors: Wagner B, Seuser A, Krüger S, Herzig ML, Hilberg T, Ay C, Hasenöhrl T, Crevenna R

Abstract
BACKGROUND: Hemophilia is a congenital bleeding disorder with an estimated frequency of 1:10,000 births. Repeated joint bleeding is a hallmark of the disorder and leads to painful hemophilic arthropathy. Regular exercise can help improve joint stability and function, reduce the risk of injury and bleeding and improve physical fitness and quality of life. This method paper describes an online training concept aiming to offer access to appropriate exercise instructions for people with hemophilia who are not able to attend regular training at a hemophilia center.
METHODS: The online exercise program is accessible through the homepage of the Department of Physical Medicine, Rehabilitation and Occupational Medicine of the Medical University Vienna as well as through scanning a QR code printed on information material using a smart phone or tablet.
RESULTS: The program contains exercises to improve mobility, coordination, muscular strength and flexibility. A brief introduction is given by a hematologist, a pediatrician and a physiatrist. An introductory video informs about contraindications and essential precautions, such as medical attendance and sufficient factor therapy to consider before starting the training. Another video gives advice on the exercise composition. The demonstrated exercises are explained by a physician and are available for adults and children. To individualize training recommendations and offer further diagnostic tools and physical treatment options as necessary, the Department of Physical Medicine, Rehabilitation and Occupational Medicine of the Medical University of Vienna will establish consultation hours for people with hemophilia.
CONCLUSION: As hemophilia is an orphan disease, patients are mainly treated in specialized centers. For patients who live far from these centers or have limited access to a training there for other reasons, the physical medicine consultation hour and the implementation of online exercise instructions offer individually adapted exercise information for a regular home-based training to benefit from increased physical fitness and joint stability.

PMID: 31535221 [PubMed - indexed for MEDLINE]

An unique case of congenital varices of the four pulmonary veins.

Eur Heart J. 2018 09 07;39(34):3262

Authors: Gentille Lorente DI

PMID: 29617767 [PubMed - indexed for MEDLINE]

Mutations in ANKLE2, a ZIKA Virus Target, Disrupt an Asymmetric Cell Division Pathway in Drosophila Neuroblasts to Cause Microcephaly.

Dev Cell. 2019 Nov 14;:

Authors: Link N, Chung H, Jolly A, Withers M, Tepe B, Arenkiel BR, Shah PS, Krogan NJ, Aydin H, Geckinli BB, Tos T, Isikay S, Tuysuz B, Mochida GH, Thomas AX, Clark RD, Mirzaa GM, Lupski JR, Bellen HJ

Abstract
The apical Par complex, which contains atypical protein kinase C (aPKC), Bazooka (Par-3), and Par-6, is required for establishing polarity during asymmetric division of neuroblasts in Drosophila, and its activity depends on L(2)gl. We show that loss of Ankle2, a protein associated with microcephaly in humans and known to interact with Zika protein NS4A, reduces brain volume in flies and impacts the function of the Par complex. Reducing Ankle2 levels disrupts endoplasmic reticulum (ER) and nuclear envelope morphology, releasing the kinase Ballchen-VRK1 into the cytosol. These defects are associated with reduced phosphorylation of aPKC, disruption of Par-complex localization, and spindle alignment defects. Importantly, removal of one copy of ballchen or l(2)gl suppresses Ankle2 mutant phenotypes and restores viability and brain size. Human mutational studies implicate the above-mentioned genes in microcephaly and motor neuron disease. We suggest that NS4A, ANKLE2, VRK1, and LLGL1 define a pathway impinging on asymmetric determinants of neural stem cell division.

PMID: 31735666 [PubMed - as supplied by publisher]

[Chondrocalcinosis: idiopathic or manifestation of rare metabolic diseases?]

Orthopade. 2019 Nov;48(11):949-956

Authors: Knitza J, Kleyer A, Schett G, Manger B

Abstract
Calcification in hyaline and fibrocartilage is caused by the deposition of calcium pyrophosphate dehydrate, commonly referred to as chondrocalcinosis. Clinically, this can lead to arthritis symptoms similar to a gout attack -"pseudogout". Nonetheless, also chronic or asymptomatic disease courses are possible. The prevalence of chondrocalcinosis increases with age. The diagnostic workup of degenerative joint disease, therefore, often reveals calcifications of articular cartilage as harmless incidental findings. However, particularly in patients younger than 60 years of age, chondrocalcinosis can be the symptom of an underlying metabolic disease. This review article highlights these rare diseases and presents unusual manifestations of chondrocalcinosis.

PMID: 31515589 [PubMed - indexed for MEDLINE]

Determination of Varying Group Sizes for Pooling Procedure.

Comput Math Methods Med. 2019;2019:4381084

Authors: Xiong W, Lu H, Ding J

Abstract
Pooling is an attractive strategy in screening infected specimens, especially for rare diseases. An essential step of performing the pooled test is to determine the group size. Sometimes, equal group size is not appropriate due to population heterogeneity. In this case, varying group sizes are preferred and could be determined while individual information is available. In this study, we propose a sequential procedure to determine varying group sizes through fully utilizing available information. This procedure is data driven. Simulations show that it has good performance in estimating parameters.

PMID: 31065292 [PubMed - indexed for MEDLINE]

Cancer cachexia: an orphan with a future.

J Cachexia Sarcopenia Muscle. 2019 02;10(1):3-5

Authors: Lainscak M, Rosano GMC

PMID: 30920780 [PubMed - indexed for MEDLINE]

Efficient design and analysis of randomized controlled trials in rare neurological diseases: An example in Guillain-Barré syndrome.

PLoS One. 2019;14(2):e0211404

Authors: van Leeuwen N, Walgaard C, van Doorn PA, Jacobs BC, Steyerberg EW, Lingsma HF

Abstract
BACKGROUND: Randomized controlled trials (RCTs) pose specific challenges in rare and heterogeneous neurological diseases due to the small numbers of patients and heterogeneity in disease course. Two analytical approaches have been proposed to optimally handle these issues in RCTs: covariate adjustment and ordinal analysis. We investigated the potential gain in efficiency of these approaches in rare and heterogeneous neurological diseases, using Guillain-Barré syndrome (GBS) as an example.
METHODS: We analyzed two published GBS trials with primary outcome 'at least one grade improvement' on the GBS disability scale. We estimated the treatment effect using logistic regression models with and without adjustment for prognostic factors. The difference between the unadjusted and adjusted estimates was disentangled in imbalance (random differences in baseline covariates between treatment arms) and stratification (change of the estimate due to covariate adjustment). Second, we applied proportional odds regression, which exploits the ordinal nature of the GBS disability score. The standard error of the estimated treatment effect indicated the statistical efficiency.
RESULTS: Both trials were slightly imbalanced with respect to baseline characteristics, which was corrected in the adjusted analysis. Covariate adjustment increased the estimated treatment effect in the two trials by 8% and 18% respectively. Proportional odds analysis resulted in lower standard errors indicating more statistical power.
CONCLUSION: Covariate adjustment and proportional odds analysis most efficiently use the available data and ensure balance between the treatment arms to obtain reliable and valid treatment effect estimates. These approaches merit application in future trials in rare and heterogeneous neurological diseases like GBS.

PMID: 30785890 [PubMed - indexed for MEDLINE]

Incidence of acquired thrombotic thrombocytopenic purpura in Germany: a hospital level study.

Orphanet J Rare Dis. 2019 Nov 15;14(1):260

Authors: Miesbach W, Menne J, Bommer M, Schönermarck U, Feldkamp T, Nitschke M, Westhoff TH, Seibert FS, Woitas R, Sousa R, Wolf M, Walzer S, Schwander B

Abstract
BACKGROUND: Acquired thrombotic thrombocytopenic Purpura (aTTP) is a life-threatening ultra-orphan disease with a reported annual incidence between 1.5 and 6.0 cases per million in Europe and mainly affecting otherwise young and healthy adults aged 40 years on average. The goal of this study was to assess the incidence of aTTP in Germany.
METHODS: A systematic review was performed to determine the published evidence on the aTTP epidemiology in Germany. To obtain additional evidence on the proportion of aTTP cases within the national Thrombotic Microangiopathy (TMA) population a hospital-level study was performed, using a retrospective data collection approach. Diagnosis of aTTP was confirmed if ADAMTS13 level were < 10% and/or the medical records explicitly mentioned aTTP diagnosis. The aggregated hospital data were then projected to the national level using logistic regression techniques.
RESULTS: The systematic literature search did not provide incidence estimates of aTTP in Germany. Eight centers (≈27% of the top 30 TMA hospitals) delivered data according to a predefined data collection form. On average (year 2014-2016) a total number of 172 aTTP episodes per year was projected (95% confidence interval [95%CI]: 132-212). The majority were newly diagnosed aTTP cases (n = 121; 95%CI: 105-129), and 51 were recurrent aTTP cases (95%CI: 27-84). The average annual projected incidence (year 2014-2016) of aTTP episodes was 2.10 per million inhabitants in Germany (95%CI: 1.60-2.58).
CONCLUSIONS: The determined annual incidence of newly diagnosed aTTP cases and the overall annual incidence of aTTP episodes in Germany confirm the ultra-orphan character of aTTP. An external validation against international registries (France, UK and USA) shows that our findings are quite comparable with those international incidence rates.

PMID: 31730475 [PubMed - in process]

[Tularemia: A case report].

Ann Dermatol Venereol. 2019 Feb;146(2):131-134

Authors: Kervyn A, Le Guern A, Gillard M, Bataille M, Modiano P

Abstract
BACKGROUND: Tularaemia is a zoonotic disease caused by inoculation with the Gram-negative coccobacillus Francisella tularensis. It was first described in the United States in 1911 and is a rare disease with an annual reported incidence in France between 2002 and 2012 of 0.07 cases per 100,000 habitants. Reporting of the disease in humans has been mandatory in France since 2003.
PATIENTS AND METHODS: Herein we report a case of tularaemia following a tick bite in a patient in the north of France.
DISCUSSION: Tularaemia is a rare form of zoonosis that should be sought in the event of unexplained adenitis. Clinical presentations vary, and in certain cases only dermatological signs are manifest. Diagnosis is confirmed by bacterial serology. Rapid initiation of suitable antibiotics produces a favourable and benign outcome in most cases. However, the offending organism, which is potentially lethal, is classed as a potential bioterrorism agent.

PMID: 30638683 [PubMed - indexed for MEDLINE]

Platypnea-Orthodeoxia Syndrome Masked by Delirium in an 85-Year-Old Woman.

J Am Med Dir Assoc. 2018 01;19(1):92-93

Authors: Brito LAR, Fukushima FB, Bazan R, Fusco DR, Vidal EIO

PMID: 29191765 [PubMed - indexed for MEDLINE]

Dental-craniofacial manifestation and treatment of rare diseases.

Int J Oral Sci. 2019 02 20;11(1):9

Authors: Luo E, Liu H, Zhao Q, Shi B, Chen Q

Abstract
Rare diseases are usually genetic, chronic and incurable disorders with a relatively low incidence. Developments in the diagnosis and management of rare diseases have been relatively slow due to a lack of sufficient profit motivation and market to attract research by companies. However, due to the attention of government and society as well as economic development, rare diseases have been gradually become an increasing concern. As several dental-craniofacial manifestations are associated with rare diseases, we summarize them in this study to help dentists and oral maxillofacial surgeons provide an early diagnosis and subsequent management for patients with these rare diseases.

PMID: 30783081 [PubMed - indexed for MEDLINE]

Cytopathologic characteristics of HPV-related small cell carcinoma of the oropharynx.

Cancer Cytopathol. 2019 02;127(1):35-43

Authors: Allison DB, Rooper LM, Mustafa S, Maleki Z, Wakely PE, Ali SZ

Abstract
BACKGROUND: Human papillomavirus (HPV)-related squamous cell carcinoma (SqCC) of the oropharynx is an epidemiologically and clinically distinct form of SqCC that is associated with an improved prognosis. However, HPV-related small cell carcinoma of the oropharynx is a rare and newly described variant that is associated with aggressive clinical behavior and poor outcomes. To date, fewer than 2 dozen reports of this entity exist in the literature, and there is no discussion of cytopathologic features. This article reports 6 cases and discusses the salient cytomorphologic findings, ancillary studies, and challenges when this entity is encountered.
METHODS: Anatomic pathology archives were searched to identify patients with a diagnosis of HPV-related small cell carcinoma of the oropharynx. Medical records were reviewed to document the following: age, sex, smoking status, other relevant clinical history, primary location, treatment, and clinical outcome. Both p16 and high-risk HPV in situ hybridization (ISH) studies were positive in at least 1 specimen from each patient. The pathologic diagnoses, cytomorphologic characteristics, immunocytochemical stains, and HPV ISH studies were reviewed and recorded for all available cases.
RESULTS: Six patients with 11 cytopathology specimens of HPV-related small cell carcinoma of the oropharynx were identified. The mean age was 61.3 years, and all patients died with widely metastatic disease (mean, 23 months; range, 12-48 months). Mixed small cell carcinoma and SqCC components were present in half of the cases.
CONCLUSIONS: The identification of a small cell component can be reliably performed with cytology preparations and is crucial because this (and not the HPV status) determines the prognosis.

PMID: 30468701 [PubMed - indexed for MEDLINE]

Rapid Paediatric Sequencing (RaPS): comprehensive real-life workflow for rapid diagnosis of critically ill children.

J Med Genet. 2018 11;55(11):721-728

Authors: Mestek-Boukhibar L, Clement E, Jones WD, Drury S, Ocaka L, Gagunashvili A, Le Quesne Stabej P, Bacchelli C, Jani N, Rahman S, Jenkins L, Hurst JA, Bitner-Glindzicz M, Peters M, Beales PL, Williams HJ

Abstract
BACKGROUND: Rare genetic conditions are frequent risk factors for, or direct causes of, paediatric intensive care unit (PICU) admission. Such conditions are frequently suspected but unidentified at PICU admission. Compassionate and effective care is greatly assisted by definitive diagnostic information. There is therefore a need to provide a rapid genetic diagnosis to inform clinical management.To date, whole genome sequencing (WGS) approaches have proved successful in diagnosing a proportion of children with rare diseases, but results may take months to report. Our aim was to develop an end-to-end workflow for the use of rapid WGS for diagnosis in critically ill children in a UK National Health Service (NHS) diagnostic setting.
METHODS: We sought to establish a multidisciplinary Rapid Paediatric Sequencing team for case selection, trio WGS, rapid bioinformatics sequence analysis and a phased analysis and reporting system to prioritise genes with a high likelihood of being causal.
RESULTS: Trio WGS in 24 critically ill children led to a molecular diagnosis in 10 (42%) through the identification of causative genetic variants. In 3 of these 10 individuals (30%), the diagnostic result had an immediate impact on the individual's clinical management. For the last 14 trios, the shortest time taken to reach a provisional diagnosis was 4 days (median 8.5 days).
CONCLUSION: Rapid WGS can be used to diagnose and inform management of critically ill children within the constraints of an NHS clinical diagnostic setting. We provide a robust workflow that will inform and facilitate the rollout of rapid genome sequencing in the NHS and other healthcare systems globally.

PMID: 30049826 [PubMed - indexed for MEDLINE]

Nodular Regenerative Hyperplasia of the Liver: A Rare Vascular Complication in Systemic Sclerosis.

J Rheumatol. 2018 01;45(1):103-106

Authors: Graf L, Dobrota R, Jordan S, Wildi LM, Distler O, Maurer B

Abstract
OBJECTIVE: To investigate nodular regenerative hyperplasia (NRH) as a vascular complication of systemic sclerosis (SSc) with microvasculopathy as a common denominator.
METHODS: Cases of SSc-NRH were identified by systematic literature review and by screening the Zurich cohort. NRH had to be diagnosed by liver biopsy.
RESULTS: Literature review retrieved 22 cases. In our cohort, 1.4% of patients with SSc were diagnosed with NRH. Most had vasculopathy, were positive for anticentromere antibodies, had elevated alkaline phosphatase and gamma-glutamyl transferase levels, normal liver morphology on ultrasound yet increased stiffness on ultrasound elastography, and had portal hypertension.
CONCLUSION: NRH might represent a rare yet potentially life-threatening vascular complication in SSc.

PMID: 29093156 [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 2019/11/13

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.

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 2019/11/12

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.