Materiały źródłowe

• #1 Dupuytren Contracture – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK526074/

  Dupuytren contracture is a myofibroblastic disease that affects the hands. It usually results in painless cords that eventually lead to flexion contracture of the fingers. […] Dupuytren disease is predominantly a myofibroblastic disease that affects the palmar and digital fascia of the hand and results in contracture deformities. The disease begins in the palm as painless nodules that form along longitudinal lines of tension. The nodules form cords that produce contracture deformities within fascial bands and tissues of the hand. […] The pathophysiology of Dupuytren disease involves abnormal myofibroblastic growth in the hand, predominantly composed of type III collagen. Numerous cytokines include interleukin-1, transforming growth factor beta-1, transforming growth factor beta-2, epidermal growth factor, platelet-derived growth factor, and connective tissue growth factor. Dupuytren contracture progresses through 3 phases: proliferative, involution, and residual. The proliferative phase has a characteristically high concentration of immature myofibroblasts and fibroblasts arranged in a whorled pattern. In the involution phase, fibroblasts become aligned in the longitudinal axis of the hand, following lines of tension. In the residual phase, relatively acellular collagen-rich chords remain, causing contracture deformity. The disorder is not always progressive, and in at least 50-70% of patients, it may stabilize or even regress.

• #2 Dupuytren’s Contracture

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3552604/

  Dupuytren’s disease is a fibroproliferative disorder of the palmar fascia. It is characterized by hyperproliferation of type 3 collagen scar tissue in the palms and digits. […] While Dupuytren’s disease has no single etiology, a genetic predisposition has been identified. It is thought to be autosomal dominant with variable penetrance. […] Histologically, the disease has 3 stages: proliferative, involution, and residual phases. During the proliferative stage, mediators such as transforming growth factor 1 induce cell transformation to myofibroblasts. During the involution stage, myofibroblasts produce collagen and alpha-smooth muscle actin, which are thought to play a role in contraction. These 2 elements create the nodules and contraction of the disease. […] Other mediators of the disease process that have been looked at include fibroblast growth factor, platelet-derived growth factor, myoglobin, tyrosine kinase, and metalloproteinase. […] The treatment of Dupuytren’s disease is fraught with concern. The patient’s symptoms and complaints are often mild compared to the risks of intervention tendon rupture and neurovascular injury. In addition, there is a high recurrence rate whether treated surgically or nonoperatively.

• #3 Dupuytren Contracture: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/329414-overview

  Although the underlying etiology for the development of Dupuytren disease is uncertain, the basic pathophysiology involves fibroblast proliferation, and collagen deposition leading to contractures of the palmar fascia. Investigators have proposed several hypotheses for the pathogenesis of Dupuytren disease. Al-Qattan hypothesizes that an individual with a genetic predisposition to develop Dupuytren disease experiences a second inciting event (ie, smoking, diabetes, trauma, alcoholism), resulting in microvascular ischemia. […] The localized ischemia causes two events to take place in the palmar fascia: (1) the conversion of adenosine triphosphate to hypoxanthine and (2) the conversion of xanthine dehydrogenase to xanthine oxidase. […] Xanthine oxidase acts as a catalyst for the oxidation of hypoxanthine to xanthine and uric acid; this conversion results in the production of free radicals. Free radicals result in fibroblast proliferation and the production of numerous cytokines. Interleukin 1 (IL-1) is the most abundant cytokine in Dupuytren disease and, via its receptor, upregulates the production of transforming growth factor beta (TGF-beta), fibroblast growth factor, epidermal-derived growth factor, and platelet-derived growth factor. […] This milieu of cytokines and growth factors results in the proliferation of fibroblasts and their differentiation into myofibroblasts (the primary cell type in Dupuytren disease).

• #4

  https://www.orthobullets.com/hand/6058/dupuytrens-disease

  Dupuytren’s Disease is a benign proliferative disorder characterized by decreased hand function that begins as a painless nodule and can progress to form diseased cords and contractures of the palm and fingers […] Pathophysiology: cytokine-mediated transformation of normal fibroblasts into abnormal myofibroblasts, turning normal fascial bands into pathological cords […] contractile properties are abnormal and exaggerated […] adjacent myofibroblasts connect via extracellular fibronectin to act together to create contracted tissue […] increase in ratio of type III to type I collagen […] increase in free radical formation […] cytokines released by macrophages and lymphocytes have been implicated […] TGFbeta1, TGFbeta2, epidermal growth factor, PDGF, connective tissue growth factor.

• #5 Dupuytren Contracture: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/329414-overview

  Increased levels of nerve growth factor are present, which induce fibroblast transformation to myofibroblasts, especially during stages II-III. The splicing of fibronectin affects collagen binding. Platelet activation produces lysophosphatidic acid (LPA). LPA is a signaling molecule for cell proliferation and myofibroblast contraction. After binding to its receptor on myofibroblasts, LPA leads to a decrease in cyclic adenosine monophosphate and an increase in intracellular calcium levels. These events mediate smooth muscle contraction of the myofibrils within the myofibroblast. Normal palmar fascia is primarily composed of type I collagen; Dupuytren disease is associated with an increase in type III collagen. […] The ratio of type III collagen to type I collagen increases, the reverse of the normal pattern, in the palmar fascia. […] Excess type III collagen production occurs from an increased density of fibroblasts secondary to enhanced stimulation and diminished apoptosis, as well as an imbalance between the collagenases and their endogenous inhibitors. Dupuytren fascia exhibits an increased ratio of tissue inhibitors of metalloproteinases (TIMP) to matrix metalloproteinases (MMP).

• #6 Dupuytren Contracture | Musculoskeletal Key

  https://musculoskeletalkey.com/dupuytren-contracture/

  An increase in glycosaminoglycans, matrix metalloproteinase activity, the presence of fibrofatty tissue between the skin and fascia, trauma, and microtrauma caused by free radicals also have been theorized as playing a role in the development of Dupuytren contracture. […] Dupuytren disease progresses through several stages: proliferative, involutional, and residual. […] In the proliferative stage, nodules, composed of type III collagen and fibroblasts, develop and expand to displace the subcutaneous tissue and fuse to the skin. […] Myofibroblasts then replace the fibroblasts as the predominant cell type, producing type III collagen and causing contraction. […] The lateral digital cord may extend distally and contribute to a flexion contracture of the distal interphalangeal joint. […] Metacarpophalangeal and distal interphalangeal joint contractures seem to result from pretendinous and lateral cord development.

• #7 Dupuytren Contracture Workup: Approach Considerations, Histologic Findings

  https://emedicine.medscape.com/article/329414-workup

  Histologic analyses of lesions resulting from Dupuytren contractures indicate physiologic characteristics of hypertrophic scar formation, including the following: myofibroblastic proliferation with increased water levels, an increase in type III collagen, chondroitin sulfate, and reducible cross-linkages. In addition, surrounding tissue without clinical manifestations reveal newly formed type III collagen, reducible cross-links, and fibroblasts with myofibroblastic characteristics, such as intracellular microfilaments, as well as basement lamina-like condensation. This suggests that Dupuytren disease spreads by migrating along the altered collagen bundles and clinically silent areas are affected on a microscopic level. […] A histologic staging system was proposed by Luck in 1959. He described three progressive stages, as follows: Proliferative stage: This is characterized by intense cellularity with collagen fibrils randomly arranged and surrounded by proliferating fibroblasts. Involution stage: The collagen fibrils are organized along lines of tension; the myofibroblast is the predominant cell and aggregates near the collagen fibrils. Residual stage: Collagen is uniformly oriented, with few to no cells and fibrosis; this stage is analogous to that of wound healing. […] In all stages, a core of type I collagen is surrounded by type III collagen. Studies suggest that the percentage of type III collagen changes with the stage of the disease.

• #8 Dupuytren’s contracture – Wikipedia

  https://en.wikipedia.org/wiki/Dupuytren%27s_contracture

  Dupuytren’s contracture (also called Dupuytren’s disease, Morbus Dupuytren, Palmar fibromatosis and historically as Viking disease or Celtic hand) is a condition in which one or more fingers become permanently bent in a flexed position. […] The cause is unknown but might have a genetic component. […] The underlying mechanism involves the formation of abnormal connective tissue within the palmar fascia. […] In Dupuytren’s contracture, the palmar fascia within the hand becomes abnormally thick, which can cause the fingers to curl and can impair finger function. […] Normally, the palmar fascia consists of collagen type I, but in Dupuytren patients, the collagen changes to collagen type III, which is significantly thicker than collagen type I.

• #9 Dupuytren Contracture: Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/329414-overview

  The myofibroblasts are indirectly connected to collagen, and the contractile force is transmitted from the intracellular actin microfilaments to the collagen bundles. Ultimately, the end result is contracture from excess deposition of type III collagen and the formation of cross-links between myofibroblasts and collagen. Another hypothesis by Vi et al suggests an up regulation of the gene transcript POSTN mRNA that encodes the protein periostin. […] Periostin is secreted by diseased cord myofibroblasts into the extracellular matrix. It promotes the transition of palmar fascia fibroblasts into a myofibroblast phenotype, thereby enhancing disease progression. […] Additionally, periostin is prevalent during the early stages of bone fracture repair and vascular injury. Hueston advanced the extrinsic theory, suggesting that Dupuytren nodules arise de novo and progress to cords. […] Vasomotor disturbance and neurovascular mediation by the skin are possible contributors to the development of Dupuytren disease. […] In contrast, McFarlane postulated the intrinsic theory, that the cords of more advanced Dupuytren disease are derived from normal fascia. A combination of these ideas forms the synthesis theory, which states that the nodules and pretendinous cords represent different forms of the disease.

• #10 Dupuytren’s Contracture – Team Bone

  https://teambone.com/education/education-clinical/basic-anatomy-pathology-of-the-hand/dupuytrens-contracture/

  In the residual phase, the nodules decrease in size and may become acellular fibrous cords. Gosset believes that the nodules and cords do not represent two stages of the disease but rather two forms originating in two different tissues, the subcutaneous fat and palmar fascia. Hueston believes that the nodules develop subcutaneously and only later may involve the palmar fascia and overlying skin. Nevertheless, contractures of the metacarpophalangeal and PIP joints, as well as displacement of digital neurovascular bundles, result from predictable patterns of fascial cord involvement.

• #11 Dupuytren Contracture – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK526074/

  Transformation of the normal fascial bands into pathological cords causes unique hand deformities. Central cords originate from the pretendinous bands and cause skin pitting and metacarpal phalangeal (MCP) joint contracture. Natatory cords are responsible for webspace contractures. Spiral cords are the most important part of the disease process and can cause proximal interphalangeal (PIP) contracture. A spiral cord originates from 4 main structures: pretendinous band, spiral band, lateral digital sheath, and Grayson ligament. Surgeons should be aware that the spiral cord causes displacement of the neurovascular bundle centrally, superficially, and proximally in the digit. […] Risk factors for increased severity and recurrence of disease after treatment include male gender, onset before age 50, bilateral disease, sibling/parent involvement, or the presence of Garrod pads, Ledderhose, or Peyronies diseases. There are also genetic factors involved in Dupuytren disease. In a genome-wide association study (GWAS) of Dupuytren disease by Dolmans et al. in 2011 identified 9 susceptibility genetic loci. Six loci contained genes encoding proteins involved in Wnt signaling, including RSPO2, WNT4, and SRFP4. Research has progressed, and now, 26 known loci have been described. Additionally, Wnt7b is expressed in Dupuytren nodules. Much remains to be discovered in our understanding of the molecular signaling pathways involved in the progression of Dupuytren disease. Future work focused on how changes in Wnt signaling influence stromal cell phenotypes may eventually help identify new targets for treating disease.

• #12 Dupuytren Contracture: Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/16941-dupuytrens-contracture

  Dupuytren contracture (sometimes also called Dupuytren disease) is a genetic disorder that makes the tissue under the skin of your palms and fingers thicken and tighten. […] Experts arent sure what causes Dupuytren contracture. Its considered a genetic disorder because its been proven that youre much more likely to develop Dupuytren contracture if one of your family members has had it. […] Dupuytren contracture is the most common inherited disorder that affects connective tissue.

• #13 Dupuytren’s risk factors | The British Dupuytren’s Society

  https://dupuytrens-society.org.uk/information/risk-factors/

  No one really knows what causes Dupuytren’s contracture. […] The gene (a unit of genetic material that determines your body’s characteristics) that causes Dupuytren’s contracture is passed to you from your parents. Dupuytren’s condition is an autosomal dominant disorder. This means that you only need to inherit the gene that causes it from one of your parents, rather than both of them, for you to get the condition. […] To date nine different genes have been identified that are associated with developing Dupuytren’s, and the way they are inherited and cause the disease is not clearly understood. […] The causal relationship is unknown, but one could speculate that poor circulation in the extremities (often seen in diabetic patients) may lead to hypoxia, ischaemia and thus to increased levels of TGF and PDGF, setting the whole Dupuytren’s reaction off. Another hypothesis is that increased glucose levels can stimulate the glycolyzation of collagen, thus stimulating cords and nodules to form.

• #14 Unique microRNA profile in Dupuytren’s contracture supports deregulation of β-catenin pathway | Modern Pathology

  https://www.nature.com/articles/modpathol2010146

  Dupuytren’s contracture, a proliferative disease of unknown origin, is characterized by an abnormal fibroblast proliferation process. […] The miRNAs identified may have a function in the pathogenesis of Dupuytren’s contracture by targeting and regulating important pathways. […] Several studies have investigated the molecular pathogenesis of Dupuytren’s contracture. […] Differentially expressed miRNAs could potentially have a function in the underlying mechanisms of its pathogenesis by dysregulating Dupuytren’s contracture-associated genes. […] An altered miRNA pattern could suggest involvement of miRNAs in the pathogenesis of Dupuytren’s contracture. […] It is now clear that aberrant -catenin signaling and its cellular accumulation can lead to various diseases including cancer and fibroproliferative diseases such as Dupuytren’s contracture.

• #15 Unique microRNA profile in Dupuytren’s contracture supports deregulation of β-catenin pathway | Modern Pathology

  https://www.nature.com/articles/modpathol2010146

  Possible mechanisms explaining -catenin accumulation include alterations in the Wnt/-catenin signaling pathway, which makes it potentially the most important pathway involved in Dupuytren’s contracture pathogenesis. […] The Dupuytren’s contracture-associated miRNAs identified here contribute to regulation of some of the genes related to this pathway, namely WNT5A, ZIC1, and TGFB1. […] Our findings suggest that miRNAs have a function in the pathogenesis of Dupuytren’s contracture by regulating important genes of the -catenin pathway.

• #16 Thieme E-Journals – Handchirurgie · Mikrochirurgie · Plastische Chirurgie / Abstract

  https://doi.org/10.1055/a-1794-5668

  Background The biological mechanism of Dupuytrens contracture needs to be further studied in order to minimize postoperative recurrence and provide a pathological basis for the development of new therapeutic targets. […] Conclusion TNF-, DKK-1 and TGF-1 may play a role in the pathogenesis of palmar aponeurosis contracture, and there is a relationship between them. The study of the relationship between the three and their related signaling pathways provides a therapeutic target and a basis for the prevention and early treatment of palmar aponeurotic contracture.

• #17 The prevalence of Dupuytren’s disease in patients with diabetes mellitus | Communications Medicine

  https://www.nature.com/articles/s43856-023-00332-7

  Dupuytrens disease (DD) is a fibroproliferative hand disorder associated with various medical conditions, including diabetes mellitus (DM). […] The association between these two diseases has been theorized to be related to the pathogenesis of each disease. DM leads to the formation of advanced glycation end products (AGEs), which are also associated with other systemic fibroses. It has been shown that patients with diabetes and DD have higher levels of AGEs than controls. […] The increased AGEs in DD increase fascial stiffness, which through mechanotransduction, accentuates Dupuytrens contractures. […] Additionally, the hyperglycemia associated with chronic diabetes can further contribute to systematic increases in fibrosis. […] This hyperglycemia and fibrosis have been further associated with TGF activation, increased WNT signaling, and matrix metalloproteinase (MMP) dysregulation. This increased WNT and TGF activity, along with MMP dysregulation, has also been strongly implicated in the pathogenesis of DD.

• #18 Dupuytren’s Disease – Dupuytren’s Contracture – OrthoInfo – AAOS

  https://orthoinfo.aaos.org/en/diseases–conditions/dupuytrens-disease/

  Dupuytren’s disease is a condition that affects the palmar fascia the fibrous layer of tissue that lies underneath the skin and above the tendons, nerves, blood vessels, and bones in the palm and fingers. […] In patients with Dupuytren’s, the fascia thickens and contracts (shortens) over time. The fascia may pull on the fingers during this process, causing them to be forced inward, toward the palm. This may make it difficult or impossible to fully straighten the fingers, resulting in what is known as a „Dupuytren’s contracture.” […] The cause of Dupuytren’s disease is not completely known, but most evidence points toward genetics as having the most important role. […] There are anecdotal reports (based on personal accounts) of Dupuytren’s developing or worsening after a person experiences an injury or an open wound (including surgery) to their hand; however, there is no good evidence to support this.

• #19 Dupuytren’s Contracture: What is it? Symptoms, Causes & Treatment | The Hand Society

  https://www.assh.org/handcare/condition/dupuytrens-contracture

  The exact cause of Dupuytrens contracture is unknown and very complex. It is a hereditary disease. This means family history and ancestry play a role. […] The problem is more common in men, people over age 40, and people of Northern European descent. It is less common in African and Middle Eastern descent. Smoking, diabetes, alcohol, lower body mass index, and aging are also all related to Dupuytrens. […] There is no evidence that hand injuries or specific jobs lead to a higher risk of developing Dupuytrens contracture. There may be a mild relationship to trauma in someone who is at risk. […] It is difficult to predict how the disease will progress. Some people have only small lumps or cords while others will develop severely bent fingers. There are a variety of risk factors. The disease tends to be more severe if it occurs at an earlier age.

• #20 Dupuytren’s contracture | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/dupuytrens-contracture

  Dupuytren’s contracture is a thickening and shortening of tissue in the palm, resulting in clawed fingers as they are pulled towards the hand. […] The exact trigger that causes the palmar fascia to thicken and contract is unknown. Potential risk factors include manual labour with vibration exposure, prior hand trauma, smoking, hyperlipidemia, Peyronie disease and complex regional pain syndrome (CRPS). A family history of the condition is often present. […] Treatment depends on the severity of the condition. In its earlier stages, treatment may include injections of corticosteroids into the fascia. These medications reduce any localised tenderness and may help to delay subsequent thickening of the tissue. More recent treatments showing promise include therapy with calcium channel blockers, treatment with gamma-interferon and percutaneous needle fasciotomy.

• #21 Dupuytren’s disease is a work-related disorder: results of a population-based cohort study | Occupational & Environmental Medicine

  https://oem.bmj.com/content/80/3/137

  Dupuytrens disease (DD) is a fibroproliferative disorder of the hands, characterised by the development of fibrous nodules and cords that may cause disabling contractures of the fingers. […] The role of manual work exposure in the aetiology of DD is controversial. […] Manual work exposure is a risk factor for DD, with a clear doseresponse relationship. […] We found that manual work was associated with the Dupuytrens disease, and that an increasing level of manual work exposure is associated with an increasing risk of having Dupuytrens disease. […] Our findings are consistent with previous results derived from different methodological approaches. […] The role of manual activities in the pathophysiology of Dupuytrens disease is not yet fully understood. There is consensus that Dupuytrens disease is a result of a localised inflammatory process, in which highly contractile myofibroblasts are induced to proliferate and differentiate by cytokines produced by local immune cells.

• #22 Dupuytren’s disease is a work-related disorder: results of a population-based cohort study | Occupational & Environmental Medicine

  https://oem.bmj.com/content/80/3/137

  It has been proposed that mechanical stress in the palmar fascia could lead to local changes in the microvascular endothelium and subsequent microvascular ischaemia, leading to the production of oxygen-free radicals, which in turn promote the differentiation from fibroblasts to myofibroblasts. […] Nonetheless, the exact causal relationship between mechanical stress and Dupuytrens disease remains incompletely understood and requires further research.

• #23 Dupuytren’s risk factors | The British Dupuytren’s Society

  https://dupuytrens-society.org.uk/information/risk-factors/

  Phenobarbitone the association between Dupuytren’s disease and antiepileptic therapy is mediated through the peripheral stimulation of tissue growth factors and not through the central release of growth hormone or through alterations in liver metabolism. […] Smoking affects the circulation, narrowing blood vessels away from the heart, and thus causing hypoxia (low oxygen) in the tissues. […] There is more evidence of a link between liver cirrhosis and Dupuytren’s, where the cause of the cirrhosis was not significant. […] A possible (though speculative) reason for the connection is that liver cirrhosis is another fibrosing disease. […] Increased glucose levels in the tissues increase the substrate for producing collagen, hence the higher incidence in people with (poorly regulated) diabetes.

• #24 Dupuytren’s: a systems biology disease | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar3438

  The presence of immune cells and related phenomena in DD tissue suggests DD may be immune-related. […] The specialised mesenchymal cells expressing smooth muscle -actin may explain the contractility observed in DD; they resemble the myofibroblasts of granulation tissue thought to be responsible for contraction during wound healing. […] Among the cytokines, transforming growth factor- is thought to be a significant inducer of myofibroblast transdifferentiation because of its ability to up-regulate -smooth muscle actin and collagen in fibroblasts, both in vivo and in vitro. […] The complex biology of DD may constitute an invitation to a systems level approach. […] The experimental data appear to be more consistent with DD being a systems biology disease. […] The pathways are expected to be integrals of gene expression, signalling and metabolic networks, as should be the approach and data analysis. […] Recognition of DD as a systems biology disease should also affect therapy.

• #25 Dupuytren’s Disease – Dupuytren’s Contracture – OrthoInfo – AAOS

  https://orthoinfo.aaos.org/en/diseases–conditions/dupuytrens-disease/

  Collagenases are enzymes that break down collagen, and a targeted collagenase was created to specifically break down the collagen in Dupuytren’s cords without damaging the collagen of the other important structures of the hand. […] While this is a good non-operative alternative to surgery, it should be noted that recurrence (return) of the disease is higher with this treatment than with surgery. […] The goal of surgery is to reduce the contracture and improve motion in the affected fingers. […] There is no known cure for Dupuytren’s contracture; however, surgery is intended to „set back the clock” by reducing the restricting (limiting) effect of the cords by either disrupting or removing them. […] Unfortunately, the healing tissues will form with the same potential to develop cords in the future but the gains in hand function can still be significant.

• #26 Update on Dupuytren’s Contracture – John Erickson, MD

  https://www.johnericksonmd.com/news/update-on-dupuytrens-contracture/

  Dupuytrens disease is a benign, fibroproliferative disorder affecting the hands of many adults. The condition is characterized by abnormal deposition of collagen within the palmar fascia of the hand leading to development of nodules and cords in the palm. […] Myofibroblast cells and alterations in collagen remodeling have been implicated in the pathogenesis of Dupuytrens contracture. […] There is no known cure for Dupuytrens disease. However, current treatment is aimed at reducing flexion contractures, improving joint range of motion, and restoring hand function. […] Collagenase injections dissolve Dupuytrens tissue, allowing the surgeon to disrupt the pathologic cords as an office-based procedure.

• #27 About XIAFLEX® for Dupuytren’s Contracture

  https://dupuytrens-contracture.xiaflex.com/patient/about-xiaflex/

  XIAFLEX is an FDA-approved nonsurgical injectable treatment for adults with Dupuytrens contracture when a cord can be felt. […] The mechanism of action of XIAFLEX in Dupuytrens contracture is not fully understood. […] XIAFLEX is injected into the collagen cord that is causing the contracture. After injection, the XIAFLEX enzymes are thought to attach to the collagen that makes up the rope-like cord in the palm, unwinding the collagen and eventually breaking it down.

• #28 Connext Successfully Completes Dose Escalation Part of CNT201 Phase 1/2 Clinical Trial for Dupuytren’s Contracture

  https://www.prnewswire.com/news-releases/connext-successfully-completes-dose-escalation-part-of-cnt201-phase-12-clinical-trial-for-dupuytrens-contracture-302445006.html

  Currently, Endo’s Xiaflex is the only commercially available collagenase injection for Dupuytren’s contracture. CNT201 is being developed as an alternative to Xiaflex and is expected to significantly improve patient access to non-surgical treatment. […] Collagenase is originally produced by fermentation of the pathogenic microorganism Clostridium histolyticum, which carries inherent risks of contamination with various toxins. In contrast, CNT201 is the world’s first recombinant collagenase therapeutic developed using genetic engineering technology, eliminating the risk of contamination from toxins or animal-derived substances. This ensures superior quality, consistent efficacy, and differentiated safety profiles. […] „By confirming both safety and efficacy in the dose escalation part of Phase 1/2 study, CNT201 offers a new non-surgical treatment option for patients with Dupuytren’s contracture.

• #29 Connext Successfully Completes Dose Escalation Part of CNT201 Phase 1/2 Clinical Trial for Dupuytren’s Contracture

  https://www.prnewswire.co.uk/news-releases/connext-successfully-completes-dose-escalation-part-of-cnt201-phase-12-clinical-trial-for-dupuytrens-contracture-302445024.html

  The trial was conducted in an open-label format and confirmed both the safety and efficacy of CNT201: no dose-limiting toxicities were observed, and clear therapeutic benefits were demonstrated. […] CNT201 is the world’s first recombinant collagenase therapeutic developed using genetic engineering technology, eliminating the risk of contamination from toxins or animal-derived substances. This ensures superior quality, consistent efficacy, and differentiated safety profiles. […] „By confirming both safety and efficacy in the dose escalation part of Phase 1/2 study, CNT201 offers a new non-surgical treatment option for patients with Dupuytren’s contracture.”

• #30 Dupuytren’s contracture | Better Health Channel

  https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/dupuytrens-contracture

  Depending on the severity of the condition, surgery options may include cutting the fascia bands through small incisions in the palm, removing the thickened fascia, removing the fascia and associated skin, and using a skin graft to seal the palm, or amputation of an affected finger, if the contracture has returned so many times that corrective surgery is no longer possible.

• #31 The prevalence of Dupuytren’s disease in patients with diabetes mellitus | Communications Medicine

  https://www.nature.com/articles/s43856-023-00332-7

  Overall, the reported findings may be explained by the increased accumulation of AGEs associated with diabetes and at a higher level in type 2 diabetes. Future studies investigating the relationship between AGE accumulation and the development and progression of DD may elucidate the connection between DD and DM.

• #32 Inflammatory Markers Involved in the Pathogenesis of Dupuytren’s Contracture – Critical Reviews™ in Eukaryotic Gene Expression – Begell House Digital Library

  https://www.dl.begellhouse.com/references/6dbf508d3b17c437,5e26170318c965c3,7c10b22965af4029.html

  Dupuytren’s disease is a common fibroproliferative disease that can result in debilitating hand deformities. […] the pathophysiology of this connective tissue disorder is associated with both local and systemic processes (e.g., fibrosis, inflammation). […] a better understanding of the systemic circulation of Dupuytren related cytokines and growth factors may provide important insights into disease progression. […] Progress in the development of any disease modifying biologic treatment for Dupuytren has been hampered by the lack of clinically useful biomarkers. […] Identification of such markers may transcend their use in Dupuytren treatment, because fibrotic biological processes fundamental to Dupuytren are relevant to fibrosis in many other connective tissues and organs with collagen-based tissue compartments. […] This narrative review provides a broad overview of previous studies and emphasizes the importance of inflammatory mediators as candidate circulating biomarkers for monitoring Dupuytren’s disease.

• #33 Dupuytren’s: a systems biology disease | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar3438

  Dupuytren’s disease (DD) is an ill-defined fibroproliferative disorder of the palm of the hands leading to digital contracture. […] Cellular components and processes associated with DD pathogenesis include altered gene and protein expression of cytokines, growth factors, adhesion molecules, and extracellular matrix components. […] Free radicals and localised ischaemia have been suggested to trigger the proliferation of DD tissue. […] The three stages of DD growth (proliferative, involutional, and residual) appear to involve dysdifferentiation into myofibroblasts. […] DD is associated with abundance of collagen, fibronectin, integrins, cytokines and many other growth factors, as well as altered expression of several genes, but unlike the involvement of known oncogenes and suppressor genes in cancer development, our knowledge of the exact aetiopathogenesis of DD remains poor despite significant understanding of its biology.

• #34 Dupuytren’s Disease: Pathobiochemistry and Clinical Management | SpringerLink

  https://link.springer.com/book/10.1007/978-3-642-78517-7

  In this volume a distinguished group of internationally renowned clinicians and basic researchers discuss the present state of knowledge of the etiology and pathogenesis of Dupuytren’s contracture, a disease responsible for a considerable portion of disabilities within the working population all over the world. […] Although the riddle of how the contracture of the palmar fascia develops is still unsolved, the data on the pathobiochemistry and clinic of Dupuytren’s Disease achieved in recent years has led to a better understanding of the biochemical and morphological processes underlying the deformation and malfunction of the afflicted tissues. […] Research in Dupuytren’s Disease now enters the era of molecular medicine, which opens up new experimental means of studying the pathological changes which occur during the formation of the contracture on a molecular level.

• #35 Dupuytren’s Disease: Pathobiochemistry and Clinical Management | SpringerLink

  https://link.springer.com/book/10.1007/978-3-642-78517-7

  In particular, data are presented as to the role of specific biological macromolecules influencing the phenotype expression of the palmar fascia cells which are involved in autoimmune reactions and present both at the cell surface as well as in the extracellular matrix to regulate cell-to-cell and cell-to-matrix interactions. […] Complementary evaluations of morphological, epidemiological, and clinical data contribute essentially to the present understanding of the etiology and pathogenesis of Dupuytren’s Disease.

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