scholarly journals Recent advances in understanding and managing Paget’s disease

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1485
Author(s):  
Ian R Reid
Keyword(s):  
Disease Progression ◽  
Paget’S Disease ◽  
Cost Effective ◽  
Paget's Disease ◽  
Symptomatic Disease ◽  
Joint Replacement Surgery ◽  
Replacement Surgery ◽  
Primary Endpoints ◽  
History Of ◽  
Biochemical Indices

Paget’s disease is a condition which continues to challenge and surprise. The dramatic fall in its incidence over the last three decades has been an enormous surprise, as is the capacity of a single infusion of the potent bisphosphonate, zoledronate, to produce biochemical remission in 90% of patients, remissions which usually persist for many years and raise the possibility of a cure in some patients. However, challenges in its management remain. The trials carried out in Paget’s disease have almost always had biochemical indices as their primary endpoints. From these studies, we also know that bone pain is relieved, quality of life improved, bone histology normalised, and radiological lesions healed. Thus, disease progression is halted. Studies have not been powered to assess whether clinically important endpoints such as fracture and the need for joint replacement surgery are diminished, although these complications are well established as part of the natural history of the condition. Since disease progression is prevented by potent bisphosphonates, it is likely that disease complications will also be prevented. Zoledronate also reduces the frequency of follow-up needed and therefore provides a very cost-effective intervention in those who have symptomatic disease or are at risk of complications.

scholarly journals A rare case of Paget’s disease affecting the cervical spine

2019 ◽  
Vol 101 (2) ◽  
pp. e38-e42
Author(s):  
J Holton ◽  
M Jones ◽  
Z Klezl ◽  
M Czyz ◽  
M Grainger ◽  
...  
Keyword(s):  
Cervical Spine ◽  
Independent Living ◽  
Paget’S Disease ◽  
Posterior Part ◽  
Cord Compression ◽  
Bone Cell ◽  
Paget's Disease ◽  
History Of ◽  
Posterior Instrumented Fusion ◽  
Degenerative Cervical Spine

We present the case of a 75-year-old man with a rapidly progressive cervical myelopathy on a background of a 3-year history of neck pain and a severely degenerative cervical spine. The patient developed progressive myelopathy over a six-month period and suffered from worsening kyphosis. Suspicion of an underlying oncological process prompted transfer to our tertiary referral unit. Biopsy was consistent for Paget’s disease, an extremely rare diagnosis of the cervical spine. Magnetic resonance imaging revealed cord compression between C4 and C6 with associated cord signal change indicative of myelopathy. A three-level corpectomy and posterior instrumented fusion was performed. There was significant blood loss (3.5l) intraoperatively, consistent with a diagnosis of Paget’s disease of the bone. Cell salvage was used, as was neuromonitoring for both the anterior and posterior part of the procedure. Postoperatively, neurological function improved slightly and the patient required community neurorehabilitation to allow independent living.

scholarly journals Cerebrovascular fibromuscular dysplasia

2017 ◽  
Vol 7 (3) ◽  
pp. 225-236 ◽  
Author(s):  
Andrea M. Harriott ◽  
Eli Zimmerman ◽  
Aneesh B. Singhal ◽  
Michael R. Jaff ◽  
Mark E. Lindsay ◽  
...  
Keyword(s):  
Disease Progression ◽  
Fibromuscular Dysplasia ◽  
Massachusetts General Hospital ◽  
Case Series ◽  
Antiplatelet Agents ◽  
Cerebrovascular Event ◽  
Symptomatic Disease ◽  
Surveillance Imaging ◽  
History Of

AbstractBackground:Fibromuscular dysplasia (FMD) is a rare noninflammatory, nonatherosclerotic arteriopathy of medium-sized arteries affecting up to 7% of the population. The disease can affect any artery but commonly affects renal, extracranial carotid, and vertebral arteries. The epidemiology and natural course of cerebrovascular FMD is unknown and requires further investigation.Methods:We present demographic and outcomes data on a case series of 81 patients with cerebrovascular FMD from Massachusetts General Hospital presenting between 2011 and 2015 followed by a review of the peer-reviewed literature.Results:Patients were a median age of 53 years (±12 SD) and the majority were women. Approximately 50% had a history of tobacco use and more than two-thirds had hypertension. Most patients were on monoplatelet therapy with aspirin; during follow-up, 7 of 67 had progressive disease or additional symptoms. One of 67 patients had a cerebrovascular event: TIA. There were 5 of 67 who had noncerebrovascular events or disease progression and 1 death of unclear cause.Conclusions:Cerebrovascular FMD may present with myriad symptoms. Our data support that patients with FMD with symptomatic disease have a low rate of recurrent symptoms or disease progression and can be managed conservatively with stroke risk modification, antiplatelet agents, surveillance imaging, and counseling.

scholarly journals Extramammary Paget's Disease: A Case Report

2020 ◽  
Vol 8 (1) ◽  
pp. 83-85
Author(s):  
Anita Shah ◽  
Yogesh Poudel ◽  
Anuj Poudel
Keyword(s):  
Paget’S Disease ◽  
Paget's Disease ◽  
Extramammary Paget’S Disease ◽  
Erythematous Plaque ◽  
Eosinophilic Cytoplasm ◽  
Topical Glucocorticoids ◽  
Atypical Cells ◽  
History Of ◽  
White Scale ◽  
Extramammary Paget's Disease

A 60- year-old man presented with four year history of a non- healing rash. The rash was pruritic and painless. He had previously been treated empirically with oral and topical antibiotics, topical antifungal agents, and topical glucocorticoids without improvement. The physical examination revealed an erythematous plaque with superficial white scale affecting the skin of the groin and scrotum. Skin biopsy and histopathology revealed epidermal infiltration by large atypical cells that had eosinophilic cytoplasm and prominent nucleoli, findings were consistent with Pagets disease. Extramammary Paget's disease (EMPD) is an intraepithelial adenocarcinoma that is sometimes misdiagnosed as dermatitis clinically. It most commonly involves the vulva and in perianal skin, scrotum, penis and axilla. The patient was kept on regular surveillance. The patient has increased intensity of itching and increase in size of lesion after six months of diagnosis.

scholarly journals Molecular insights into an ancient form of Paget’s disease of bone

2019 ◽  
Vol 116 (21) ◽  
pp. 10463-10472 ◽  
Author(s):  
Barry Shaw ◽  
Carla L. Burrell ◽  
Darrell Green ◽  
Ana Navarro-Martinez ◽  
Daniel Scott ◽  
...  
Keyword(s):  
Direct Sequencing ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Paget’S Disease Of Bone ◽  
Paget's Disease Of Bone ◽  
North West ◽  
Sequestosome 1 ◽  
The North ◽  
History Of ◽  
Skeletal Samples

Paget’s disease of bone (PDB) is a chronic skeletal disorder that can affect one or several bones in individuals older than 55 y of age. PDB-like changes have been reported in archaeological remains as old as Roman, although accurate diagnosis and natural history of the disease is lacking. Six skeletons from a collection of 130 excavated at Norton Priory in the North West of England, which dates to medieval times, show atypical and extensive pathological changes resembling contemporary PDB affecting as many as 75% of individual skeletons. Disease prevalence in the remaining collection is high, at least 16% of adults, with age at death estimations as low as 35 y. Despite these atypical features, paleoproteomic analysis identified sequestosome 1 (SQSTM1) or p62, a protein central to the pathological milieu of PDB, as one of the few noncollagenous human sequences preserved in skeletal samples. Targeted proteomic analysis detected >60% of the ancient p62 primary sequence, with Western blotting indicating p62 abnormalities, including in dentition. Direct sequencing of ancient DNA excluded contemporary PDB-associated SQSTM1 mutations. Our observations indicate that the ancient p62 protein is likely modified within its C-terminal ubiquitin-associated domain. Ancient miRNAs were remarkably preserved in an osteosarcoma from a skeleton with extensive disease, with miR-16 expression consistent with that reported in contemporary PDB-associated bone tumors. Our work displays the use of proteomics to inform diagnosis of ancient diseases such as atypical PDB, which has unusual features presumably potentiated by yet-unidentified environmental or genetic factors.

scholarly journals Reduced E-cadherin expression correlates with disease progression in Paget's disease of the vulva but not Paget's disease of the breast

2008 ◽  
Vol 21 (10) ◽  
pp. 1192-1199 ◽  
Author(s):  
Patricia E Ellis ◽  
Salvador Diaz Cano ◽  
Mark Fear ◽  
David P Kelsell ◽  
Lucy Ghali ◽  
...  
Keyword(s):  
Disease Progression ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
E Cadherin

scholarly journals Early Experiences with Indigenous Medicated Spacers in the Management of Infected Hip Prosthesis.

2013 ◽  
Vol 11 (1) ◽  
pp. 32-36
Author(s):  
Pankaj Chand ◽  
Suchil Rana Magar ◽  
Bishnu Babu Thapa ◽  
Bachhu Ram KC ◽  
Amit Joshi ◽  
...  
Keyword(s):  
Hip Prosthesis ◽  
Revision Arthroplasty ◽  
Recurrent Infection ◽  
Cost Effective ◽  
Deep Infection ◽  
Two Stage ◽  
Joint Replacement Surgery ◽  
Replacement Surgery ◽  
Walking Capacity ◽  
Postoperative Dislocation

Introduction: Joint replacement surgery, has become one of the most frequent prosthetic surgeries over the past decades due to its success in restoring function to disabled arthritic individual. A two-stage revision arthroplasty is a well-accepted method for the treatment of a deep infection of a hip with a joint implant. In the present study, the results of three infected hips with the interim use of an indigenous cemented prosthesis along with gentamycin impregnated cement beads were assessed with a two stage revision. Methods: Three consecutive patients who were managed with a two-stage revision hip arthroplasty for the treatment of a previous infection, with retained implants, were followed clinically and radiographically for an average of 15 months. Following removal of implants and debridement (first stage), an indigenous medicated prosthesis along with antibiotic coated cement beads were implanted, for an interim phase of six - eight weeks aft er which a new prosthesis was placed ( second stage ).In this period antibiotics ( both intravenous and oral) were administered to the patients. Results: In a mean follow up period of 15 months, there is no evidence of recurrent infection in all three patients, as of now. The use of antibiotic coated cement prosthesis along with gentamycin mixed cement beads was associated with a satisfactory hip score, and better walking capacity in the interim period, a lower transfusion requirement at the time of reimplantation, and no postoperative dislocation. Conclusions: Locally prepared medicated spacer and gentamycin coated beads help in eradicating hip infection, besides being more cost effective. Medical Journal of Shree Birendra Hospital; Jan-June 2012/vol.11/Issue1/32-36 DOI: http://dx.doi.org/10.3126/mjsbh.v11i1.7765

scholarly journals Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis

2016 ◽  
Author(s):  
Julia Steinberg ◽  
Graham R. S. Ritchie ◽  
Theodoros I. Roumeliotis ◽  
Raveen L. Jayasuriya ◽  
Roger A. Brooks ◽  
...  
Keyword(s):  
Disease Progression ◽  
Cartilage Degeneration ◽  
Common Disease ◽  
Primary Chondrocytes ◽  
Joint Replacement Surgery ◽  
Model Studies ◽  
Replacement Surgery ◽  
Integrated Pathway ◽  
Independent Replication ◽  
Molecular Landscape

ABSTRACTBackgroundOsteoarthritis (OA) is a common disease characterized by cartilage degeneration and joint remodeling. The underlying molecular changes underpinning disease progression are incompletely understood, but can be characterized using recent advances in genomics technologies, as the relevant tissue is readily accessible at joint replacement surgery. Here we investigate genes and pathways that mark OA progression, combining genome-wide DNA methylation, RNA sequencing and quantitative proteomics in isolated primary chondrocytes from matched intact and degraded articular cartilage samples across twelve patients with OA undergoing knee replacement surgery.ResultsWe identify 49 genes differentially regulated between intact and degraded cartilage at multiple omics levels, 16 of which have not previously been implicated in OA progression. Using independent replication datasets, we replicate statistically significant signals and show that the direction of change is consistent for over 90% of differentially expressed genes and differentially methylated CpG probes. Three genes are differentially regulated across all 3 omics levels: AQP1, COL1A1 and CLEC3B, and all three have evidence implicating them in OA through animal or cellular model studies. Integrated pathway analysis implicates the involvement of extracellular matrix degradation, collagen catabolism and angiogenesis in disease progression. All data from these experiments are freely available as a resource for the scientific community.ConclusionsThis work provides a first integrated view of the molecular landscape of human primary chondrocytes and identifies key molecular players in OA progression that replicate across independent datasets, with evidence for translational potential.

scholarly journals Statin Use and Its Effects on Skeletal Related Events in Patients with Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5774-5774 ◽  
Author(s):  
Fernando M Vargas Madueno ◽  
Amin Benyounes ◽  
Gentry King ◽  
Kuan-Hsiang Gary Huang ◽  
Gabor Varadi
Keyword(s):  
Multiple Myeloma ◽  
Vitamin D ◽  
Alcohol Abuse ◽  
Statin Therapy ◽  
Paget’S Disease ◽  
Paget's Disease ◽  
Exact Test ◽  
History Of ◽  
Skeletal Related Events ◽  
Statin Use

Abstract Introduction: Skeletal related events (SRE) in multiple myeloma (MM) patients are associated with significant morbidity and mortality. Studies assessing the anti myeloma effect of statins in conjunction with chemotherapy have shown conflicting results with regards to overall survival or disease response. To our knowledge there have been no studies evaluating the effect of statins on SRE. Here we sought to assess the relationship between statin use and the presence of SRE. Methods: We retrospectively reviewed 101 patients seen at our institution between the years 2007-2012 who had a diagnosis of MM separating them in 2 groups, patients on statin therapy (n=50) and those without statin therapy (n=51). Statin use was considered if present prior to the occurrence of a SRE. SRE were defined as pathologic fractures, necessity for orthopedic intervention, radiation therapy or spinal cord compression. MM stage as per the International Staging System (ISS), as well as history of osteoporosis, malignancy, hypothyroidism, Paget's disease of the bone, alcohol abuse, smoking status, calcium-vitamin D, and bisphosphonate use were also recorded. Results: In our cohorts the prevalence of SRE was significantly lower in patients on statin medication when compared to statin naive patients, (36% vs. 58.8% respectively, p = 0.029, Fisher's exact test, Figure 1). No significant differences were noted between statin treated group and statin naive group in the following variable subgroups (Fisher's exact test): the history of smoking or alcohol abuse, the documented diagnosis of osteoporosis, coexistent malignancy, hypothyroidism, or Paget's disease of the bone, and the use of other medications including bisphosphonates or calcium - vitamin D supplementation. There were no significant differences in distribution of cancer staging (according to ISS) when we compared between statin use status (chi-square test for trend). Conclusion: The use of statins was associated with a decrease in the prevalence of SRE in patients with MM. This was found independent of disease stage, history of osteoporosis or second malignancy, and bisphosphonate use. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Hydrocephalus and Headaches in Paget’s Disease of the Skull: Complete Relief by Ventriculo-Atrial Shunt

1984 ◽  
Vol 11 (1) ◽  
pp. 69-72 ◽  
Author(s):  
Chantal Hausser ◽  
Georges Elie Ouaknine ◽  
Jacques Sylvestre
Keyword(s):  
Paget’S Disease ◽  
Paget's Disease ◽  
Neurological Dysfunction ◽  
Complete Relief ◽  
Communicating Hydrocephalus ◽  
Intellectual Function ◽  
History Of ◽  
Atrial Shunt ◽  
First Time ◽  
Shunting Procedure

SUMMARYA 76 year old patient with a long history of headaches was found to have Paget’s disease and communicating hydrocephalus. There were (otherwise) no neurological or musculo-skeletal manifestations of Paget’s disease, but moderate impairment of intellectual function was present. Treatment with disphosphonates did not bring any significant improvement, but three days following a ventriculo-atrial shunting procedure, the patient became headache-free for the first time in several years.In the literature, patients with hydrocephalus have been shown to respond quite unevenly to atrio-ventricular shunting, but in most instances the descriptions concerned advanced cases with well-established symptoms of dementia, ataxia and incontinence. Our case is reported to stress the importance of early diagnosis and management of hydrocephalus in Paget’s disease for the prevention of widespread neurological dysfunction.

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