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Histopathology Feb 2021Owing to a sharp increase in the frequency of diagnosis of colorectal adenomas in the current era of population screening, distinctive morphological features are... (Review)
Review
Owing to a sharp increase in the frequency of diagnosis of colorectal adenomas in the current era of population screening, distinctive morphological features are increasingly being observed. These may present diagnostic challenges and cause clinical management issues. Paneth cell metaplasia is a more common occurrence, but the incidence rates of squamous metaplasia, clear cell metaplasia, osseous metaplasia, neuroendocrine differentiation and signet-ring cell-like lesion are low, and they can be seen in <1% of colorectal adenomas. Their histomorphological characteristics are quite unique; ancillary studies are not very helpful and often not needed. In this review, we give an overview and describe the potential clinical consequences of such incidental and special morphological findings in colorectal adenomas.
Topics: Adenoma; Colorectal Neoplasms; Humans; Incidence; Metaplasia; Neuroendocrine Cells; Ossification, Heterotopic; Paneth Cells
PubMed: 32981102
DOI: 10.1111/his.14263 -
Bone Apr 2018Heterotopic ossification (HO), a serious disorder of extra-skeletal bone formation, occurs as a common complication of trauma or in rare genetic disorders. Many... (Review)
Review
Heterotopic ossification (HO), a serious disorder of extra-skeletal bone formation, occurs as a common complication of trauma or in rare genetic disorders. Many conserved signaling pathways have been implicated in HO; however, the exact underlying molecular mechanisms for many forms of HO are still unclear. The emerging picture is that dysregulation of bone morphogenetic protein (BMP) signaling plays a central role in the process, but that other conserved signaling pathways, such as Hedgehog (HH), Wnt/β-catenin and Fibroblast growth factors (FGF), are also involved, either through cross-talk with BMP signaling or through other independent mechanisms. Deep understanding of the conserved signaling pathways is necessary for the effective prevention and treatment of HO. In this review, we update and integrate recent progress in this area. Hopefully, our discussion will point to novel promising, druggable loci for further translational research and successful clinical applications.
Topics: Animals; Bone Morphogenetic Proteins; Fibroblast Growth Factors; Humans; Myositis Ossificans; Ossification, Heterotopic; Signal Transduction; Transforming Growth Factor beta
PubMed: 28455214
DOI: 10.1016/j.bone.2017.04.014 -
Developmental Dynamics : An Official... Feb 2018Fibrodysplasia Ossificans Progressiva is a rare human disease of heterotopic ossification. FOP patients experience progressive development of ectopic bone within fibrous... (Review)
Review
Fibrodysplasia Ossificans Progressiva is a rare human disease of heterotopic ossification. FOP patients experience progressive development of ectopic bone within fibrous tissues that contributes to a gradual loss of mobility and can lead to early mortality. Due to lack of understanding of the etiology and progression of human FOP, and the fact that surgical interventions often exacerbate FOP disease progression, alternative therapeutic methods are needed, including modeling in animals, to study and improve understanding of human FOP. In this review we provide an overview of the existing animal models of FOP and the key mechanistic findings from each. In addition, we highlight the specific advantages of a new adult zebrafish model, generated by our lab, to study human FOP. Developmental Dynamics 247:279-288, 2018. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Disease Models, Animal; Disease Progression; Humans; Ossification, Heterotopic; Zebrafish
PubMed: 29139166
DOI: 10.1002/dvdy.24606 -
Translational Research : the Journal of... Aug 2017Heterotopic ossification (HO) is a common occurrence after multiple forms of extensive trauma. These include arthroplasties, traumatic brain and spinal cord injuries,... (Review)
Review
Heterotopic ossification (HO) is a common occurrence after multiple forms of extensive trauma. These include arthroplasties, traumatic brain and spinal cord injuries, extensive burns in the civilian setting, and combat-related extremity injuries in the battlefield. Irrespective of the form of trauma, heterotopic bone is typically endochondral in structure and is laid down via a cartilaginous matrix. Once formed, the heterotopic bone typically needs to be excised surgically, which may result in wound healing complications, in addition to a risk of recurrence. Refinements of existing diagnostic modalities, like micro- and nano-CT are being adapted toward early intervention. Trauma-induced HO is a consequence of aberrant wound healing, systemic and local immune system activation, infections, extensive vascularization, and innervation. This intricate molecular crosstalk culminates in activation of stem cells that initiate heterotopic endochondral ossification. Development of animal models recapitulating the unique traumatic injuries has greatly facilitated the mechanistic understanding of trauma-induced HO. These same models also serve as powerful tools to test the efficacy of small molecules which specifically target the molecular pathways underlying ectopic ossification. This review summarizes the recent advances in the molecular understanding, diagnostic and treatment modalities in the field of trauma-induced HO.
Topics: Humans; Ossification, Heterotopic; Wound Healing; Wounds and Injuries
PubMed: 28668522
DOI: 10.1016/j.trsl.2017.06.004 -
Advanced Science (Weinheim,... Oct 2023Traumatic heterotopic ossification (THO) represents one of the most prominent contributors to post-traumatic joint dysfunction, which currently lacks an effective and...
Traumatic heterotopic ossification (THO) represents one of the most prominent contributors to post-traumatic joint dysfunction, which currently lacks an effective and definitive preventative approach. Inflammatory activation due to immune dyshomeostasis during the early stages of trauma is believed to be critical in initiating the THO disease process. This study proposes a dual-homeostatic modulation (DHM) strategy to synergistically prevent THO without compromising normal trauma repair by maintaining immune homeostasis and inducing stem cell homeostasis. A methacrylate-hyaluronic acid-based hydrogel spray device encapsulating a curcumin-loaded zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, CZC) nanoparticles (CZCH) is designed. Photo-crosslinked CZCH is used to form hydrogel films fleetly in periosteal soft tissues to achieve sustained curcumin and CeO2 nanoparticles release in response to acidity and reactive oxygen species (ROS) in the inflammatory microenvironment. In vitro experiments and RNA-seq results demonstrated that CZCH achieved dual-homeostatic regulation of inflammatory macrophages and stem cells through immune repolarization and enhanced efferocytosis, maintaining immune cell homeostasis and normal differentiation. These findings of the DHM strategy are also validated by establishing THO mice and rat models. In conclusion, the CZCH hydrogel spray developed based on the DHM strategy enables synergistic THO prevention, providing a reference for a standard procedure of clinical operations.
Topics: Rats; Mice; Animals; Hydrogels; Curcumin; Ossification, Heterotopic; Wound Healing; Inflammation
PubMed: 37635177
DOI: 10.1002/advs.202302905 -
The New England Journal of Medicine Sep 2017
Topics: Adult; Foreign Bodies; Humans; Male; Neck Pain; Ossification, Heterotopic; Temporal Bone
PubMed: 28953433
DOI: 10.1056/NEJMicm1703542 -
Nature Communications Oct 2022Heterotopic ossification is the most disabling feature of fibrodysplasia ossificans progressiva, an ultra-rare genetic disorder for which there is currently no...
Heterotopic ossification is the most disabling feature of fibrodysplasia ossificans progressiva, an ultra-rare genetic disorder for which there is currently no prevention or treatment. Most patients with this disease harbor a heterozygous activating mutation (c.617 G > A;p.R206H) in ACVR1. Here, we identify recombinant AAV9 as the most effective serotype for transduction of the major cells-of-origin of heterotopic ossification. We use AAV9 delivery for gene replacement by expression of codon-optimized human ACVR1, ACVR1R206H allele-specific silencing by AAV-compatible artificial miRNA and a combination of gene replacement and silencing. In mouse skeletal cells harboring a conditional knock-in allele of human mutant ACVR1 and in patient-derived induced pluripotent stem cells, AAV gene therapy ablated aberrant Activin A signaling and chondrogenic and osteogenic differentiation. In Acvr1(R206H) knock-in mice treated locally in early adulthood or systemically at birth, trauma-induced endochondral bone formation was markedly reduced, while inflammation and fibroproliferative responses remained largely intact in the injured muscle. Remarkably, spontaneous heterotopic ossification also substantially decreased in in Acvr1(R206H) knock-in mice treated systemically at birth or in early adulthood. Collectively, we develop promising gene therapeutics that can prevent disabling heterotopic ossification in mice, supporting clinical translation to patients with fibrodysplasia ossificans progressiva.
Topics: Adult; Animals; Humans; Mice; Activin Receptors, Type I; Genetic Therapy; Mice, Transgenic; MicroRNAs; Mutation; Myositis Ossificans; Ossification, Heterotopic; Osteogenesis; Adenoviridae
PubMed: 36258013
DOI: 10.1038/s41467-022-33956-9 -
Respiratory Care Apr 2015Dendriform pulmonary ossification is a rare condition often diagnosed by either surgery or postmortem examination. We report a 43-y-old man with a history of... (Review)
Review
Dendriform pulmonary ossification is a rare condition often diagnosed by either surgery or postmortem examination. We report a 43-y-old man with a history of nonproductive cough for 1 y. His physical examination was unremarkable. Chest computed tomography showed multiple bilateral micronodules in both lower lobes; however, the patient's pulmonary function was normal. Flexible bronchoscopy with transbronchial biopsies revealed branching ossification. Pulmonary ossification is a chronic process characterized by progressive metaplastic ossification. We reviewed a total of 42 cases of dendriform pulmonary ossification reported in the medical literature: most of these cases were diagnosed by autopsy. Despite its rarity, dendriform pulmonary ossification should be considered in the differential diagnosis of diffuse lung disease. Bronchoscopy with transbronchial biopsies must be considered as a potential diagnostic procedure.
Topics: Adult; Biopsy; Bronchoscopy; Chile; Cough; Diagnosis, Differential; Humans; Lung; Lung Diseases; Male; Ossification, Heterotopic; Rare Diseases
PubMed: 25316886
DOI: 10.4187/respcare.03531 -
International Orthopaedics Jul 2022This scoping review aims to map and summarise the available literature on heterotopic ossification (HO) following hip arthroscopy, with particular focus on incidence,... (Review)
Review
PURPOSE
This scoping review aims to map and summarise the available literature on heterotopic ossification (HO) following hip arthroscopy, with particular focus on incidence, distribution as per Brooker classification, efficacy of prophylactic measures and factors that may influence the likelihood of production of HO.
METHODS
A computer-based search was performed on PubMed, Embase, Emcare, Cinahl, ISI web of science and Scopus using the terms 'heterotopic ossification' and 'hip arthroscopy'. Articles reporting heterotopic ossification following hip arthroscopy for any condition were included after two-stage title/abstract and full-text screening.
RESULTS
Of the 663 articles retrieved, 45 studies were included. The proportion of patients with HO ranged from 0 to 44%. The majority of the cases were either Brooker grade I or II. Of the six studies investigating the effect of NSAID prophylaxis, five reported a significantly lower incidence of heterotopic ossification associated with its use. Weak evidence suggests that an outside-in arthroscopic approach, no capsular closure, male sex and mixed cam and pincer resection may be associated with an increased risk of HO.
CONCLUSION
Although there is a large variation in rates of HO following hip arthroscopy in the current literature, the majority of studies report a low incidence. Evidence exists advocating the administration of post-operative NSAIDs to reduce the incidence of HO following hip arthroscopy. This, combined with the low risk of complications, means there is a favourable risk-benefit ratio for prophylactic NSAID used in HA. Future research should work to identify patient clinical and demographic factors which may increase the risk of development of HO, allowing clinicians to risk stratify and select only specific patients who would benefit from receiving NSAID prophylaxis.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Hip; Arthroscopy; Humans; Incidence; Male; Odds Ratio; Ossification, Heterotopic; Postoperative Complications
PubMed: 35482060
DOI: 10.1007/s00264-022-05402-4 -
International Journal of Molecular... Jun 2022The term heterotopic ossification (HO) describes bone formation in tissues where bone is normally not present. Musculoskeletal trauma induces signalling events that in... (Review)
Review
The term heterotopic ossification (HO) describes bone formation in tissues where bone is normally not present. Musculoskeletal trauma induces signalling events that in turn trigger cells, probably of mesenchymal origin, to differentiate into bone. The aetiology of HO includes extremely rare but severe, generalised and fatal monogenic forms of the disease; and as a common complex disorder in response to musculoskeletal, neurological or burn trauma. The resulting bone forms through a combination of endochondral and intramembranous ossification, depending on the aetiology, initiating stimulus and affected tissue. Given the heterogeneity of the disease, many cell types and biological pathways have been studied in efforts to find effective therapeutic strategies for the disorder. Cells of mesenchymal, haematopoietic and neuroectodermal lineages have all been implicated in the pathogenesis of HO, and the emerging dominant signalling pathways are thought to occur through the bone morphogenetic proteins (BMP), mammalian target of rapamycin (mTOR), and retinoic acid receptor pathways. Increased understanding of these disease mechanisms has resulted in the emergence of several novel investigational therapeutic avenues, including palovarotene and other retinoic acid receptor agonists and activin A inhibitors that target both canonical and non-canonical signalling downstream of the BMP type 1 receptor. In this article we aim to illustrate the key cellular and molecular mechanisms involved in the pathogenesis of HO and outline recent advances in emerging molecular therapies to treat and prevent HO that have had early success in the monogenic disease and are currently being explored in the common complex forms of HO.
Topics: Bone Morphogenetic Proteins; Humans; Ossification, Heterotopic; Osteogenesis; Receptors, Retinoic Acid; Signal Transduction
PubMed: 35805978
DOI: 10.3390/ijms23136983