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Gut Microbes Jul 2018The gut microbiota has been recognized as an important factor in the development of metabolic diseases such as obesity and is considered an endocrine organ involved in... (Review)
Review
The gut microbiota has been recognized as an important factor in the development of metabolic diseases such as obesity and is considered an endocrine organ involved in the maintenance of energy homeostasis and host immunity. Dysbiosis can change the functioning of the intestinal barrier and the gut-associated lymphoid tissues (GALT) by allowing the passage of structural components of bacteria, such as lipopolysaccharides (LPS), which activate inflammatory pathways that may contribute to the development of insulin resistance. Furthermore, intestinal dysbiosis can alter the production of gastrointestinal peptides related to satiety, resulting in an increased food intake. In obese people, this dysbiosis seems be related to increases of the phylum Firmicutes, the genus Clostridium, and the species Eubacterium rectale, Clostridium coccoides, Lactobacillus reuteri, Akkermansia muciniphila, Clostridium histolyticum, and Staphylococcus aureus.
Topics: Dysbiosis; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Obesity
PubMed: 29667480
DOI: 10.1080/19490976.2018.1465157 -
Health Psychology Research 2022Male sexual dysfunction is a series of conditions, most notably including erectile dysfunction (ED), Peyronie's disease (PD), and premature ejaculation (PE), defined by...
Male sexual dysfunction is a series of conditions, most notably including erectile dysfunction (ED), Peyronie's disease (PD), and premature ejaculation (PE), defined by impaired sexual functioning. The prevalence of male sexual dysfunction increases with age and is relatively high with greater than 50% of men aged 40 to 70 describing some degree of erectile dysfunction. Risk factors for male sexual dysfunction include age, diabetes mellitus (DM), cancer, stroke, hypertension, penile trauma, depression, anxiety, and disturbance in central serotonin neurotransmission and 5-HT postsynaptic receptor functioning. Sexual questionnaires including the International Index of Erectile Dysfunction, Sexual Health Inventory for Men, and the Premature Ejaculation Diagnostic Tool are useful in screening for these disorders. Focused history and physical can establish diagnoses. For a condition to be diagnosed as male sexual dysfunction, the patient or their partner must view their sexual functioning as impaired. Treatment of male sexual dysfunction is etiology dependent. For ED, first-line therapy is a phosphodiesterase-5 inhibitor or mental health care for psychogenic ED. More complicated cases may be treated with injections, surgery, or shockwave therapy. PD is either treated with medications for pain management, collagenase clostridium histolyticum injection, corpoplasty, plication, or shockwave therapy. PE may be treated behaviorally or with SSRIs as first line medication.
PubMed: 35999971
DOI: 10.52965/001c.37533 -
Cureus Apr 2023Peyronie's disease is an acquired connective tissue disease of the tunica albuginea of the penis which usually presents with penile curvature/deformity and a palpable... (Review)
Review
Peyronie's disease is an acquired connective tissue disease of the tunica albuginea of the penis which usually presents with penile curvature/deformity and a palpable penile plaque. It is more common in Caucasian men over the fifth decade of life, but it is an under-reported disease. Conservative and non-surgical options are supported by limited evidence except for intralesional injection of collagenase clostridium histolyticum and have limited success. The improved outcome of surgical treatment is accompanied by the risk of erectile dysfunction. This is a brief overview of Peyronie's disease, its impact on the patient, and the available treatment options.
PubMed: 37143639
DOI: 10.7759/cureus.37037 -
Journal of Plastic Surgery and Hand... Oct 2016This study aims to provide a comprehensive review of the role of Collagenase Clostridium histolyticum (CCH). (Review)
Review
OBJECTIVE
This study aims to provide a comprehensive review of the role of Collagenase Clostridium histolyticum (CCH).
METHODS
This review is based on a literature review and practical experience.
RESULTS
This review provides practical management strategies for using collagenase by sharing clinical experiences over the past few years; logistical aspects of in-clinic treatment, lessons learned, and novel approaches to correct traditionally hard-to-treat contractures are discussed. In addition a brief, yet comprehensive overview is provided on the pathophysiology of the disease, the mechanism of collagenase action and results of clinical studies.
CONCLUSION
CCH has an evolving role as one of the tools available for treating Dupuytren's disease.
Topics: Clinical Trials as Topic; Comorbidity; Dose-Response Relationship, Drug; Dupuytren Contracture; Exercise Therapy; Humans; Injections, Intralesional; Microbial Collagenase; Recurrence; Splints
PubMed: 27050718
DOI: 10.3109/2000656X.2016.1159568 -
BMC Cancer Jun 2022Gastric cancer is one of the deadliest cancers, currently available therapies have limited success. Cancer-associated fibroblasts (CAFs) are pivotal cells in the stroma...
BACKGROUND
Gastric cancer is one of the deadliest cancers, currently available therapies have limited success. Cancer-associated fibroblasts (CAFs) are pivotal cells in the stroma of gastric tumors posing a great risk for progression and chemoresistance. The poor prognostic signature for CAFs is not clear in gastric cancer, and drugs that target CAFs are lacking in the clinic. In this study, we aim to identify a poor prognostic gene signature for CAFs, targeting which may increase the therapeutic success in gastric cancer.
METHODS
We analyzed four GEO datasets with a network-based approach and validated key CAF markers in The Cancer Genome Atlas (TCGA) and The Asian Cancer Research Group (ACRG) cohorts. We implemented stepwise multivariate Cox regression guided by a pan-cancer analysis in TCGA to identify a poor prognostic gene signature for CAF infiltration in gastric cancer. Lastly, we conducted a database search for drugs targeting the signature genes.
RESULTS
Our study revealed the COL1A1, COL1A2, COL3A1, COL5A1, FN1, and SPARC as the key CAF markers in gastric cancer. Analysis of the TCGA and ACRG cohorts validated their upregulation and poor prognostic significance. The stepwise multivariate Cox regression elucidated COL1A1 and COL5A1, together with ITGA4, Emilin1, and TSPAN9 as poor prognostic signature genes for CAF infiltration. The search on drug databases revealed collagenase clostridium histolyticum, ocriplasmin, halofuginone, natalizumab, firategrast, and BIO-1211 as the potential drugs for further investigation.
CONCLUSIONS
Our study demonstrated the central role of extracellular matrix components secreted and remodeled by CAFs in gastric cancer. The gene signature we identified in this study carries high potential as a predictive tool for poor prognosis in gastric cancer patients. Elucidating the mechanisms by which the signature genes contribute to poor patient outcomes can lead to the discovery of more potent molecular-targeted agents and increase the therapeutic success in gastric cancer.
Topics: Cancer-Associated Fibroblasts; Computational Biology; Humans; Prognosis; Stomach Neoplasms
PubMed: 35739492
DOI: 10.1186/s12885-022-09736-5 -
The Journal of Hand Surgery, European... Feb 2015Safety was evaluated for collagenase Clostridium histolyticum (CCH) based on 11 clinical trials (N = 1082) and compared with fasciectomy data in a structured literature... (Review)
Review
Safety was evaluated for collagenase Clostridium histolyticum (CCH) based on 11 clinical trials (N = 1082) and compared with fasciectomy data in a structured literature review of 48 European studies (N = 7727) for treatment of Dupuytren's contracture. Incidence of adverse events was numerically lower with CCH vs. equivalent complications from fasciectomy (median [range] incidence), including nerve injury (0% vs. 3.8% [0%-50+%]), neurapraxia (4.4% vs. 9.4% [0%-51.3%]), complex regional pain syndrome (0.1% vs. 4.5% [1.3%-18.5%]) and arterial injury (0% vs. 5.5% [0.8%-16.5%]). Tendon injury (0.3% vs. 0.1% [0%-0.2%]), skin injury (16.2% vs. 2.8% [0%-25.9%]) and haematoma (77.7% vs. 2.0% [0%-25%]) occurred at a numerically higher incidence with CCH than surgery. Adverse events in CCH trials not reported after fasciectomy included peripheral oedema; extremity pain; injection site pain, haemorrhage and swelling; tenderness; pruritus and lymphadenopathy. CCH-related adverse events were reported as predominantly injection-related and transient. These results may support clinical decision-making for treatment of Dupuytren's contracture.
Topics: Dupuytren Contracture; Fasciotomy; Humans; Injections, Intralesional; Microbial Collagenase; Treatment Outcome
PubMed: 24698851
DOI: 10.1177/1753193414528843 -
Journal of Orthopaedic Surgery (Hong... 2020We intend to assess the efficacies and limitations of collagenase clostridium histolyticum (CCH) and fasciectomy in treating Dupuytren's contracture, and the associated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We intend to assess the efficacies and limitations of collagenase clostridium histolyticum (CCH) and fasciectomy in treating Dupuytren's contracture, and the associated complications and rate of recurrences aiming to present a treatment algorithm.
METHODS
A literature search within the PubMed, Web of Sciences, Cochrane Library, and EMBASE databases was performed using the combined key words 'Dupuytren, palmar aponeurosis contracture, collagenase clostridium histolyticum and fasciectomy', including all possible studies with a set of predefined inclusion and exclusion criteria.
RESULTS
Thirty studies were assessed for eligibility from 215 identified records. Seventeen publications satisfied the inclusion criteria including 2142 joints in 1784 patients. The mean follow-up time was 18.0 months (3-60).
CONCLUSION
Acceptable contractures release was obtained in both techniques. Severe complications associated with fasciectomy outrank those of CCH, whereas the low rate of recurrence favors the fasciectomy technique.
Topics: Clostridium; Dupuytren Contracture; Fasciotomy; Humans; Microbial Collagenase; Treatment Outcome
PubMed: 32484064
DOI: 10.1177/2309499020921747 -
Patient Preference and Adherence 2017The safety and efficacy of the use of collagenase (CCH) for the treatment of Peyronie's disease has been confirmed over the past several years. However, identification... (Review)
Review
The safety and efficacy of the use of collagenase (CCH) for the treatment of Peyronie's disease has been confirmed over the past several years. However, identification of the ideal patient population for use of this treatment is not well established. Multiple studies have attempted to delineate various patient-specific factors that may predict response to treatment with CCH, with the intent of enhancing patient selection. To date, these include baseline curvature severity, duration of disease, disease phase at presentation, plaque calcification, baseline erectile function, plaque size, age, comorbid diabetes, previous penile trauma, responsiveness to first treatment cycle, baseline penile shortening or pain, prior treatment with intralesional injection, compliance with plaque modeling, and atypical curvature. In addition, other studies have sought to explore various aspects of treatment with CCH that may affect patient perspective of treatment. They have focused on patient-reported outcomes, female partner considerations, cost of treatment, and potential confounders of patient satisfaction. This review provides a summary and analysis of currently available literature on topics of patient selection and perspectives in regard to treatment of Peyronie's disease with CCH.
PubMed: 28280315
DOI: 10.2147/PPA.S113507 -
Therapeutic Advances in Urology Jun 2016Peyronie's disease (PD) is a connective tissue disorder resulting in the abnormal accumulation of scar or plaques in the tunica albuginea of the penis. The condition is... (Review)
Review
OBJECTIVES
Peyronie's disease (PD) is a connective tissue disorder resulting in the abnormal accumulation of scar or plaques in the tunica albuginea of the penis. The condition is characterized by two phases: an active, inflammatory phase, and a stable, chronic phase. Collagenase Clostridium histolyticum (CCH) was isolated in the mid-1900s and postulated as a potential pharmacologic strategy for breaking down the abnormal connective tissue plaques of PD. Prior to the introduction of CCH, a wide variety of treatment modalities for PD were used in clinical practice, including oral and topical medications, intralesional injections, electromotive drug administration, extracorporeal shockwave therapy, traction, and invasive surgery, all with variable results. This review aims to examine the known data surrounding the use of intralesional CCH injections in the treatment of PD.
METHODS
CCH is a recently US Food and Drug Administration approved pharmacologic treatment for PD. Clinical trials using intralesional CCH injection therapy for the treatment of PD were reviewed for clinical safety and efficacy of treatment.
RESULTS
Studies demonstrated that CCH treatment administered in multiple cycles led to significant benefit in both the psychological and physical aspects of PD. The strongest evidence for CCH's effectiveness was revealed in large, multicenter randomized controlled trials (Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies I and II) in which intralesional CCH was combined with manual modeling of the penis. Although adverse events from treatment are relatively common, the majority are mild to moderate in degree, including penile pain, swelling, and bruising, which all resolve spontaneously.
CONCLUSION
Overall, evidence indicates that CCH is a valuable, effective, and safe minimally invasive treatment option for men with PD.
PubMed: 27247629
DOI: 10.1177/1756287216637569 -
British Medical Bulletin Jun 2016In the last few years, the use of collagenase clostridium histolyticum for management of Dupuytren's contracture has increased. The procedure of enzymatic fasciectomy... (Review)
Review
INTRODUCTION
In the last few years, the use of collagenase clostridium histolyticum for management of Dupuytren's contracture has increased. The procedure of enzymatic fasciectomy has become popular because it is non-invasive, safe and fast to perform.
SOURCES OF DATA
A systematic search was performed on Medline (PubMed), Web of Science and Scopus databases using the combined keywords 'Dupuytren collagenase' and 'Dupuytren clostridium histolyticum'. Forty-three studies were identified. The quality of the studies was assessed using the Coleman Methodological Score.
AREAS OF AGREEMENT
The use of collagenase clostridium histolyticum provides better outcomes in patients with mild-moderate joint contracture, with lower complications and side effects than open fasciectomy. Manipulation can be performed 2-7 days after the injection. The use of collagenase is cost-effective.
AREAS OF CONTROVERSY
Most of the studies did not report patient-related outcomes. The role of dynamic splint has to be investigated with randomized clinical trials.
GROWING POINTS
The shorter recovery time and the low incidence of serious or major adverse effects are the main advantages of this new technology.
AREAS TIMELY FOR DEVELOPING RESEARCH
There is a need to perform studies with longer follow-up because the recurrence rate seems to increase with time. Further investigations are necessary to assess whether it is safe and effective to inject two or more cords at the same time.
Topics: Clostridium histolyticum; Cost-Benefit Analysis; Dupuytren Contracture; Fasciotomy; Humans; Injections, Intralesional; Microbial Collagenase; Range of Motion, Articular; Treatment Outcome
PubMed: 27151958
DOI: 10.1093/bmb/ldw020