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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 -
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 -
Archives of Dermatological Research Aug 2022Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is... (Review)
Review
Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is available about the feasibility and efficacy of therapies alternative to systemic treatment and surgical excision, both of which often lead to unsatisfactory results or complications. We conducted a systematic review to evaluate the efficacy and safety of topical and intralesional sodium thiosulfate, extracorporeal shock-wave lithotripsy (ESWL), and laser for calcinosis cutis. PubMed, Embase, and Web of Science were searched. Reports of calciphylaxis and treatment combined with systemic medications were excluded. A total of 40 studies including 136 patients were analysed. Partial or complete remission after monotherapy was observed in 64% to 81% of cases. Self-applied topical sodium thiosulfate required patient's adherence (mean treatment duration, 4.9 months; range 2-24). Laser therapy enabled complete remission of microcalcifications after a single procedure (57%; 12/21). ESWL and intralesional sodium thiosulfate injections decreased calcinosis-associated pain (median reduction in VAS score, 3; range 0-9 and 1; range 0-5, respectively). The most common adverse event was scarring and hyperkeratosis, observed after CO laser (56%; 10/18). Intralesional sodium thiosulfate injections caused transient pain in over 11% of patients. Recurrences within the follow-up were rare (2%; 3/136). This study provides an overview of minimally invasive and local therapies that in selected cases might transcend conventional treatment. The limitation of this study is the poor level of evidence, which emerges mainly from non-randomized studies at high risk of bias.
Topics: Administration, Cutaneous; Calcinosis; Humans; Immunotherapy; Pain; Remission Induction
PubMed: 34165603
DOI: 10.1007/s00403-021-02264-5 -
Clinical Transplantation Jun 2021The incidence of melanoma is steadily rising around the world. There is uncertainty about the safety of solid organ transplantation in patients with a prior history of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The incidence of melanoma is steadily rising around the world. There is uncertainty about the safety of solid organ transplantation in patients with a prior history of melanoma.
AIM
To review studies reporting patients with a history of melanoma before solid organ transplantation.
METHODS
Electronic searches of Medline, Embase, and the Cochrane library up to March 2020. All study designs, in any language and without sample size restriction, were eligible for inclusion. Risk of bias was assessed using established tools, and meta-analysis was performed using a random-effects model.
RESULTS
We identified 41 studies reporting 703 100 transplant recipients and 1692 had pre-transplantation melanomas. Risk of death, expressed as a hazard ratio, in patients with pre-transplantation melanoma relative to those without prior melanoma, was 1.32 (95% CI: 1.09-1.59). After transplantation, 13.1% of patients with pre-transplantation melanoma developed new or recurrent melanoma (IQR: 4.8%-18.2%).
CONCLUSIONS
Around 1-in-400 transplant recipients had a prior history of melanoma. This was associated with a greater than 1-in-10 risk of new or recurrent melanoma after transplantation and an increased risk of death. A 5-year waiting time between a melanoma diagnosis and transplantation has been recommended based on historic registry data, but very little additional information is available to justify or revise this.
Topics: Humans; Melanoma; Organ Transplantation; Proportional Hazards Models; Skin Neoplasms; Transplant Recipients
PubMed: 33720403
DOI: 10.1111/ctr.14287 -
Antioxidants (Basel, Switzerland) Jan 2022Psoriasis is a chronic, immune-mediated inflammatory dermatosis characterized by the appearance of erythematous plaques, covered by white scales, occasionally... (Review)
Review
Psoriasis is a chronic, immune-mediated inflammatory dermatosis characterized by the appearance of erythematous plaques, covered by white scales, occasionally pruritogenic, and distributed mainly on the extensor areas. Oxidative stress is defined as an imbalance or a transient or chronic increase in the levels of free oxygen/nitrogen radicals, either as a result of the exaggerated elevation in their production or the decrease in their ability to be eliminated by antioxidant systems. Although the pathogenesis of psoriasis remains far from elucidated, there are studies that delineate an involvement of oxidative stress in this skin disorder. Thus, a systematic search was computed in PubMed/Medline, Web of Science and SCOPUS and, in total, 1293 potentially eligible articles exploring this research question were detected. Following the removal of duplicates and the exclusion of irrelevant manuscripts based on the screening of their titles and abstracts (n = 995), 298 original articles were selected for full-text review. Finally, after we applied the exclusion and inclusion criteria, 79 original articles were included in this systematic review. Overall, the data analyzed in this systematic review point out that oxidative stress markers are elevated in psoriasis and share an association with the duration and severity of the disease. The concentrations of these biomarkers are impacted on by anti-psoriasis therapy. In addition, the crosstalk between psoriasis and oxidative stress is influenced by several polymorphisms that arise in genes encoding markers or enzymes related to the redox balance. Although the involvement of oxidative stress in psoriasis remains undisputable, future research is needed to explore the utility of assessing circulating serum, plasma, urinary and/or skin biomarkers of oxidative stress and of studying polymorphisms in genes regulating the redox balance, as well as how can these findings be translated into the management of psoriasis, as well in understanding its pathogenesis and evolution.
PubMed: 35204165
DOI: 10.3390/antiox11020282 -
Annals of Medicine and Surgery (2012) Aug 2020The objective of this study is to assess the current literature on the effectiveness of fibrin glue on survival of skin grafts. Fibrin glue is a possible alternative to... (Review)
Review
BACKGROUND
The objective of this study is to assess the current literature on the effectiveness of fibrin glue on survival of skin grafts. Fibrin glue is a possible alternative to secure skin grafts instead of traditional methods (i.e. sutures or staples).
METHODS
Data Sources: MEDLINE, Scopus, Embase, Informit, CINAHL and the Cochrane Central Register of Controlled Trials, no limit on the earliest date of publication.
STUDY ELIGIBILITY CRITERIA
Randomised, non-randomised controlled trials and cohort studies.
PARTICIPANTS
and Interventions: Participants were patients with skin grafting/skin transplantation. The intervention was fibrin glue in any form (bovine, human pooled plasma or autologous) and comparator any form of affixing skin grafts (e.g. sutures or staples).Study Appraisal and Synthesis Methods: Studies were appraised using the Cochrane risk of bias tool and assessed for clinical heterogeneity. Effect sizes were calculated and illustrated with forest plots.
RESULTS
190 publications were narrowed to 15 relevant publications, of which eight were pooled in meta-analysis. The outcomes examined were: graft survival by percentage; graft survival reported as events; post-operative incidence of haematoma or seroma; pain reported after dressing changes via a visual analogue scale; length of stay in days (Glass's delta 2 was 0.48 95% CI 0.09, 0.97); and surgical time in minutes. Only length of stay showed a difference between groups and it favoured fibrin glue.
CONCLUSIONS
While there may be benefits to the use of fibrin glue in skin graft patients, it is difficult to conclude this from the current evidence. Limitations were significant heterogeneity in outcomes measured and exclusion off non-English papers.
PubMed: 32577231
DOI: 10.1016/j.amsu.2020.06.006