-
BMJ Clinical Evidence Mar 2015Vitiligo is an acquired skin disorder characterised by white (depigmented) patches in the skin, due to the loss of functioning melanocytes. The extent and distribution... (Review)
Review
INTRODUCTION
Vitiligo is an acquired skin disorder characterised by white (depigmented) patches in the skin, due to the loss of functioning melanocytes. The extent and distribution of vitiligo often changes during the course of a person's lifetime and its progression is unpredictable.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of surgical interventions for vitiligo in adults and in children? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found four studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: blister grafts, cultured cellular transplantation, non-cultured cellular transplantation, punch/mini grafts, and split thickness skin grafts.
Topics: Humans; Melanocytes; Skin Transplantation; Vitiligo
PubMed: 25800413
DOI: No ID Found -
Dermatologic Therapy Jun 2022Cyclosporine-A (Cyc-A) was initially prescribed as systemic therapy for patients receiving solid organ transplants or in patients with graft versus host disease (GVHD).... (Review)
Review
Cyclosporine-A (Cyc-A) was initially prescribed as systemic therapy for patients receiving solid organ transplants or in patients with graft versus host disease (GVHD). Topical Cyc-A is an ideal form of cyclosporine in the treatment of mucocutaneous disorders as it causes fewer systemic side effects and has more stable results than steroids; however, poor absorption through the skin makes the development of new formulations necessary to improve skin permeability. The aim of this study was to evaluate the efficacy and safety of topical Cyc-A in different dermatological conditions. A thorough systematic review was performed on PubMed/Medline, Embase, Scopus, and Web of Science databases as well as Google Scholar, and relevant studies from 2000 until January 3, 2022, were selected. The study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). Topical Cyc-A was observed to be an effective medication in the treatment of oral lichen planus, psoriasis, burning mouth syndrome, Pyoderma Gangrenosum, and Zoon's balanitis. Adverse side effects such as dysphagia, burning sensation, lips swelling, and gastrointestinal upset were reported following Cyc-A mouthwash use, whereas mild erythema, dryness, and fissuring of the skin were observed following the Cyc-A lipogel application. Topical Cyc-A was found to be a good alternative to traditional treatment regimens for immune-mediated mucocutaneous conditions. Cyc-A can be considered as a safe and efficient option in cases of long-term treatment as it does not have the same adverse effects of long-term steroids.
Topics: Cyclosporine; Dermatology; Humans; Lichen Planus, Oral; Male; Psoriasis; Steroids
PubMed: 35384191
DOI: 10.1111/dth.15490 -
Journal of Autoimmunity Dec 2023Autoimmune diseases (AIDs) are a series of immune-mediated lethal diseases featured by over-activated immune cells attacking healthy self-tissues and organs due to the... (Review)
Review
Autoimmune diseases (AIDs) are a series of immune-mediated lethal diseases featured by over-activated immune cells attacking healthy self-tissues and organs due to the loss of immune tolerance, which always causes severe irreversible systematical organ damage and threatens human health heavily. To date, there are still no definitive cures for the treatment of AIDs due to their pathogenesis has not been clearly understood. Besides, the current clinical treatments of AIDs majorly rely on glucocorticoids and immune suppressors, which can lead to serious side effects. In the past years, there are increasing studies demonstrating that an imbalance of gut microbiota is intimately related to the pathogenesis of various AIDs, shedding light on the development of therapeutics by targeting the gut microbiota for the management of AIDs. Among all the approaches targeting the gut microbiota, fecal microbiota transplantation (FMT) has attracted increasing interest, and it has been proposed as a possible strategy to intervene in the homeostasis of gut microbiota for the treatment of various diseases. However, despite the reported good curative effects and clinical studies conducted on FMT, the detailed mechanisms of FMT for the effective treatment of those diseases have not been figured out. To fully understand the mechanisms of the therapeutic effects of FMT on AIDs and improve the therapeutic efficacy of FMT treatment, a systematic review of this topic is necessary. Hence, in this review paper, the potential mechanisms of FMT for the treatment of various AIDs were summarized, including promotion, shaping, activation, or inhibition of the host immune system via the interactions between the microorganisms and the gut immune system, gut-brain, gut-liver, gut-kidney axis, and so on. Then, applications of FMT for the treatment of various AIDs were detailed presented. Finally, the current challenges and potential solutions for the development of FMT formulations and FMT therapeutics were comprehensively discussed.
Topics: Humans; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Treatment Outcome; Autoimmune Diseases; Feces
PubMed: 37690971
DOI: 10.1016/j.jaut.2023.103109 -
American Journal of Transplantation :... Dec 2016Azathioprine, a purine antimetabolite immunosuppressant, photosensitizes the skin and causes the production of mutagenic reactive oxygen species. It is postulated to... (Meta-Analysis)
Meta-Analysis Review
Azathioprine, a purine antimetabolite immunosuppressant, photosensitizes the skin and causes the production of mutagenic reactive oxygen species. It is postulated to increase the risk of squamous cell carcinoma (SCC) and other skin cancers in organ transplant recipients (OTRs), but evidence from multiple, largely single-center studies to date has been inconsistent. We aimed to resolve the issue of azathioprine's carcinogenicity by conducting a systematic review of the relevant literature and pooling published risk estimates to evaluate the risks of SCC, basal cell carcinoma (BCC), keratinocyte cancers (KCs) overall and other skin cancers in relation to azathioprine treatment. Twenty-seven studies were included in total, with risk estimates from 13 of these studies able to be pooled for quantitative analysis. The overall summary estimate showed a significantly increased risk of SCC in relation to azathioprine exposure (1.56, 95% confidence interval [CI] 1.11-2.18). No significant associations between azathioprine treatment and BCC (0.96, 95% CI 0.66-1.40) or KC (0.84, 95% CI 0.59-1.21) risk were observed. There was significant heterogeneity between studies for azathioprine risk estimates and the outcomes of SCC, BCC and KC. The pooled findings of available evidence support the contention that treatment with azathioprine increases the risk of SCC in OTRs.
Topics: Azathioprine; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Graft Rejection; Humans; Immunosuppressive Agents; Organ Transplantation; Postoperative Complications; Prognosis; Risk Factors; Skin Neoplasms
PubMed: 27163483
DOI: 10.1111/ajt.13863 -
The Cochrane Database of Systematic... Jul 2022Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited... (Review)
Review
BACKGROUND
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has emerged as a potential intervention for severe SSc refractory to conventional treatment.
OBJECTIVES
To assess the benefits and harms of autologous hematopoietic stem cell transplantation for the treatment of systemic sclerosis (specifically, non-selective myeloablative HSCT versus cyclophosphamide; selective myeloablative HSCT versus cyclophosphamide; non-selective non-myeloablative HSCT versus cyclophosphamide).
SEARCH METHODS
We searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and trial registries from database insertion to 4 February 2022.
SELECTION CRITERIA
We included RCTs that compared HSCT to immunomodulators in the treatment of SSc.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, extracted study data, and performed risk of bias and GRADE assessments to assess the certainty of evidence using standard Cochrane methods.
MAIN RESULTS
We included three RCTs evaluating: non-myeloablative non-selective HSCT (10 participants), non-myeloablative selective HSCT (79 participants), and myeloablative selective HSCT (36 participants). The comparator in all studies was cyclophosphamide (123 participants). The study examining non-myeloablative non-selective HSCT had a high risk of bias given the differences in baseline characteristics between the two arms. The other studies had a high risk of detection bias for participant-reported outcomes. The studies had follow-up periods of one to 4.5 years. Most participants had severe disease, mean age 40 years, and the duration of disease was less than three years. Efficacy No study demonstrated an overall mortality benefit of HSCT when compared to cyclophosphamide. However, non-myeloablative selective HSCT showed overall survival benefits using Kaplan-Meier curves at 10 years and myeloablative selective HSCT at six years. We graded our certainty of evidence as moderate for non-myeloablative selective HSCT and myeloablative selective HSCT. Certainty of evidence was low for non-myeloablative non-selective HSCT. Event-free survival was improved compared to cyclophosphamide with non-myeloablative selective HSCT at 48 months (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.16 to 0.74; moderate-certainty evidence). There was no improvement with myeloablative selective HSCT at 54 months (HR 0.54 95% CI 0.23 to 1.27; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not report event-free survival. There was improvement in functional ability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI, scale from 0 to 3 with 3 being very severe functional impairment) with non-myeloablative selective HSCT after two years with a mean difference (MD) of -0.39 (95% CI -0.72 to -0.06; absolute treatment benefit (ATB) -13%, 95% CI -24% to -2%; relative percent change (RPC) -27%, 95% CI -50% to -4%; low-certainty evidence). Myeloablative selective HSCT demonstrated a risk ratio (RR) for improvement of 3.4 at 54 months (95% CI 1.5 to 7.6; ATB -37%, 95% CI -18% to -57%; RPC -243%, 95% CI -54% to -662%; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; low-certainty evidence). The non-myeloablative non-selective HSCT trial did not report HAQ-DI results. All transplant modalities showed improvement of modified Rodnan skin score (mRSS) (scale from 0 to 51 with the higher number being more severe skin thickness) favoring HSCT over cyclophosphamide. At two years, non-myeloablative selective HSCT showed an MD in mRSS of -11.1 (95% CI -14.9 to -7.3; ATB -22%, 95% CI -29% to -14%; RPC -43%, 95% CI -58% to -28%; moderate-certainty evidence). At 54 months, myeloablative selective HSCT at showed a greater improvement in skin scores than the cyclophosphamide group (RR 1.51, 95% CI 1.06 to 2.13; ATB -27%, 95% CI -6% to -47%; RPC -51%, 95% CI -6% to -113%; moderate-certainty evidence). The NNTB was 4 (95% CI 3 to 18). At one year, for non-myeloablative non-selective HSCT the MD was -16.00 (95% CI -26.5 to -5.5; ATB -31%, 95% CI -52% to -11%; RPC -84%, 95% CI -139% to -29%; low-certainty evidence). No studies reported data on pulmonary arterial hypertension. Adverse events In the non-myeloablative selective HSCT study, there were 51/79 serious adverse events with HSCT and 30/77 with cyclophosphamide (RR 1.7, 95% CI 1.2 to 2.3), with an absolute risk increase of 26% (95% CI 10% to 41%), and a relative percent increase of 66% (95% CI 20% to 129%). The number needed to treat for an additional harmful outcome was 4 (95% CI 3 to 11) (moderate-certainty evidence). In the myeloablative selective HSCT study, there were similar rates of serious adverse events between groups (25/34 with HSCT and 19/37 with cyclophosphamide; RR 1.43, 95% CI 0.99 to 2.08; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not clearly report serious adverse events.
AUTHORS' CONCLUSIONS
Non-myeloablative selective and myeloablative selective HSCT had moderate-certainty evidence for improvement in event-free survival, and skin thicknesscompared to cyclophosphamide. There is also low-certainty evidence that these modalities of HSCT improve physical function. However, non-myeloablative selective HSCT and myeloablative selective HSCT resulted in more serious adverse events than cyclophosphamide; highlighting the need for careful risk-benefit considerations for people considering these HSCTs. Evidence for the efficacy and adverse effects of non-myeloablative non-selective HSCT is limited at this time. Due to evidence provided from one study with high risk of bias, we have low-certainty evidence that non-myeloablative non-selective HSCT improves outcomes in skin scores, forced vital capacity, and safety. Two modalities of HSCT appeared to be a promising treatment option for SSc though there is a high risk of early treatment-related mortality and other adverse events. Additional research is needed to determine the effectiveness and adverse effects of non-myeloablative non-selective HSCT in the treatment of SSc. Also, more studies will be needed to determine how HSCT compares to other treatment options such as mycophenolate mofetil, as cyclophosphamide is no longer the first-line treatment for SSc. Finally, there is a need for a greater understanding of the role of HSCT for people with SSc with significant comorbidities or complications from SSc that were excluded from the trial criteria.
Topics: Adult; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Humans; Randomized Controlled Trials as Topic; Scleroderma, Systemic
PubMed: 35904231
DOI: 10.1002/14651858.CD011819.pub2 -
Transplant Infectious Disease : An... Apr 2022Dematiaceous fungi cause a number of infectious syndromes referred to as phaeohyphomycosis among both immunocompetent and immunocompromised hosts. We performed a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dematiaceous fungi cause a number of infectious syndromes referred to as phaeohyphomycosis among both immunocompetent and immunocompromised hosts. We performed a systematic review to characterize these infections in solid organ transplant recipients (SOTR).
METHODS
We searched PubMed database (last searched 1/6/2022) for English-language reports on dematiaceous fungal infections in SOTR. Included reports needed individualized demographic, treatment, and outcome data; pediatric reports were excluded. A universally applicable bias assessment was performed on reports. Models for infection type and outcome were created using the Bayesian paradigm.
RESULTS
We included 149 reports on 201 cases of dematiaceous fungal infections in SOTR. The mean age was 54 years, 72% were men, and kidney recipients accounted for 61% of cases. Skin and soft tissue infection (SSTI) was the most common infectious syndrome (73%). Death from infection occurred in 7% of cases (14/201), with disseminated (32%) cases having the highest mortality. Our model for infection type predicted the relative probability of central nervous system infection to be highest in liver recipients. Across all transplant types, higher relative probabilities of disseminated and pulmonary infections occur in the early post-transplant period, and the predicted probabilities for these infection types decreased after 100 months post-transplantation.
DISCUSSION
We identified SSTI as the most common dematiaceous fungal infections in SOTR. Disseminated infections carried the worst prognosis. The evidence in this review is limited by the heterogeneity of included cases. No funding source was used, and this review's protocol was not registered.
Topics: Antifungal Agents; Bayes Theorem; Child; Humans; Male; Middle Aged; Mycoses; Organ Transplantation; Transplant Recipients
PubMed: 35253959
DOI: 10.1111/tid.13819 -
Wound Repair and Regeneration :... Mar 2021Chronic painful ulcers caused by pyoderma gangrenosum (PG) and cutaneous vasculitis remain to be a therapeutic challenge. Skin grafts have been used with success in... (Review)
Review
Chronic painful ulcers caused by pyoderma gangrenosum (PG) and cutaneous vasculitis remain to be a therapeutic challenge. Skin grafts have been used with success in selected cases but are generally avoided due to the fear of pathergy. The aim of this study was to investigate the safety and efficacy of skin grafting in the treatment of primary vasculitic ulcer (PVU) and PG. MEDLINE, Embase, the Cochrane Library, Clinicaltrial.gov, and WHO International Clinical Trials Registry Platform (ICTRP) were searched from inception to March 2020. A search for grey literature was conducted in May 2020. We included studies assessing the efficacy and safety of skin grafting in the treatment of PG and PVU. Studies were only included if skin grafting was performed after establishment of PG or PVU diagnosis. A total of 721 articles was identified through the database search of which 92 were included in this study. Ten articles were identified by handsearching the reference list of included studies. Finally, 102 articles describing 212 wounds in 153 patients were included. Complete healing was found in 75.5% of the wounds. The average time to complete was 10.8 weeks (95% CI 6.1-15.6). The mean donor site healing time was 1.9 weeks (95% CI 0.52-3.20). Pathergy was reported in 8 (5.2%) patients. One patient had severe infection related to skin grafting. A statistically significant difference in the number of patients receiving preoperative (P = .0079) and postoperative (P = .002) immunosuppressive therapy was found between the groups with complete healing/reduction and no improvement/aggravation. This systematic review finds the current evidence on efficacy and safety of skin grafting in treatment of PG and PVU to be promising but limited to the size and lack of studies superior to case reports and case series. Future placebo-controlled trials are required to draw a stronger conclusion.
Topics: Humans; Pyoderma Gangrenosum; Skin Transplantation; Ulcer; Vasculitis; Wound Healing
PubMed: 33377584
DOI: 10.1111/wrr.12882 -
Journal of Reconstructive Microsurgery Mar 2023Functional muscle transfer (FMT) can provide wound closure and restore adequate muscle function for patients with oncologic extremity defects. Herein we describe our... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Functional muscle transfer (FMT) can provide wound closure and restore adequate muscle function for patients with oncologic extremity defects. Herein we describe our institutional experience with FMT after oncological resection and provide a systematic review and meta-analysis of the available literature on this uncommon procedure.
METHODS
A single-institution retrospective review was performed, including all patients who received FMT after oncological resection from 2005 to 2021. For the systematic review and meta-analysis, PubMed, Cochrane, Medline, and Embase libraries were queried according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines; results were pooled, weighted by study size, and analyzed.
RESULTS
The meta-analysis consisted of seven studies with 70 patients overall, demonstrating a mean Medical Research Council (MRC) score of 3.78 (95% confidence interval: 2.97-4.56; < 0.01). The systematic review included 28 studies with 103 patients. Receipt of adjuvant chemotherapy was associated with significantly lower mean MRC score (3.00 ± 1.35 vs. 3.90 ± 1.36; = 0.019). Seventy-four percent of the patients underwent free FMT, with the most common donor muscle being the latissimus dorsi (55%). The flap loss rate was 0.8%. Neoadjuvant chemotherapy ( = 0.03), radiotherapy ( = 0.05), pedicled FMTs ( = 0.01), and a recipient femoral nerve ( = 0.02) were associated with significantly higher complication rates. The institutional retrospective review identified 13 patients who underwent FMT after oncological resection with a median follow-up time of 21 months (range: 6-74 months). The most common tumor necessitating FMT was undifferentiated pleomorphic sarcoma (77%), and the most common donor muscle was the latissimus dorsi (62%). A high body mass index was associated with prolonged neuromuscular recovery ( = 0.87, = 0.002).
CONCLUSION
FMT after oncological resection may contribute to improved extremity function. Careful consideration of risk factors and preoperative planning is imperative for successful FMT outcomes.
Topics: Humans; Plastic Surgery Procedures; Skin Transplantation; Neoplasms; Extremities; Muscles; Retrospective Studies; Treatment Outcome
PubMed: 35768008
DOI: 10.1055/a-1887-7530 -
The Journal of Heart and Lung... Dec 2014Lung transplant candidates and recipients have significant impairments in skeletal muscle mass, strength and function--individual measures of sarcopenia. Skeletal muscle... (Review)
Review
Lung transplant candidates and recipients have significant impairments in skeletal muscle mass, strength and function--individual measures of sarcopenia. Skeletal muscle dysfunction has been observed in the pre-transplant and post-transplant period and could have an important effect on transplant outcomes. A systematic review was performed to characterize the techniques used to study sarcopenia and assess the level of impairment throughout the transplant process. Electronic databases were searched (inception to July 2013) for prospective studies measuring at least 1 element of sarcopenia (muscle mass, strength, or function) in lung transplant patients. Eighteen studies were included, and study quality was assessed using the Downs and Black scale. A variety of measurements were used to evaluate sarcopenia in 694 lung transplant patients. Muscle mass in 7 studies was assessed using bioelectrical impedance (n = 4), computed tomography or magnetic resonance imaging (n = 2), or skin folds (n = 1), and was significantly reduced. Quadriceps strength was examined in 14 studies with computerized dynamometer (n = 10) and hand-held dynamometer (n = 4). Quadriceps strength was reduced in the pre-transplant period (mean range, 49%-86% predicted; n = 455 patients), further reduced immediately after transplant (51%-72%, n = 126), and improved beyond 3 months after transplant (58%-101%, n = 164). Only 2 studies measured lower extremity function (sit-to-stand test). A multitude of measurement techniques have been used to assess individual measures of sarcopenia, with reduced muscle mass and quadriceps strength observed in the pre-transplant and post-transplant period. Further standardization of measurement techniques is needed to assess the clinical effect of sarcopenia in lung transplantation.
Topics: Adult; Humans; Lung Transplantation; Magnetic Resonance Imaging; Middle Aged; Muscle Strength; Muscle, Skeletal; Prevalence; Sarcopenia; Tomography, X-Ray Computed
PubMed: 25044057
DOI: 10.1016/j.healun.2014.06.003 -
The British Journal of Surgery Jul 2016Radiation-induced fibrosis (RIF) is a late complication of radiotherapy that results in progressive functional and cosmetic impairment. Autologous fat has emerged as an... (Review)
Review
BACKGROUND
Radiation-induced fibrosis (RIF) is a late complication of radiotherapy that results in progressive functional and cosmetic impairment. Autologous fat has emerged as an option for soft tissue reconstruction. There are also sporadic reports suggesting regression of fibrosis following regional lipotransfer. This systematic review aimed to identify cellular mechanisms driving RIF, and the potential role of lipotransfer in attenuating these processes.
METHODS
PubMed, OVID and Google Scholar databases were searched to identify all original articles regarding lipotransfer for RIF. All articles describing irradiated fibroblast or myofibroblast behaviour were included. Data elucidating the mechanisms of RIF, role of lipotransfer in RIF and methods to quantify fibrosis were extracted.
RESULTS
Ninety-eight studies met the inclusion criteria. A single, definitive model of RIF is yet to be established, but four cellular mechanisms were identified through in vitro studies. Twenty-one studies identified connective tissue growth factor and transforming growth factor β1 cytokines as drivers of fibrotic cascades. Hypoxia was demonstrated to propagate fibrogenesis in three studies. Oxidative stress from the release of reactive oxygen species and free radicals was also linked to RIF in 11 studies. Purified autologous fat grafts contain cellular and non-cellular properties that potentially interact with these processes. Six methods for quantifying fibrotic changes were evaluated including durometry, ultrasound shear wave elastography, thermography, dark field imaging, and laser Doppler and laser speckle flowmetry.
CONCLUSION
Understanding how lipotransfer causes regression of RIF remains unclear; there are a number of new hypotheses for future research.
Topics: Adipose Tissue; Biomechanical Phenomena; Fibrosis; Humans; Hypoxia; Oxidative Stress; Platelet-Derived Growth Factor; Radiotherapy; Skin; Transforming Growth Factor beta1; Transplantation, Autologous; Tumor Necrosis Factor-alpha
PubMed: 27169866
DOI: 10.1002/bjs.10180