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Annals of Oncology : Official Journal... Dec 2019Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) has been tested in advanced melanoma patients at various centers. We conducted a... (Meta-Analysis)
Meta-Analysis
Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) has been tested in advanced melanoma patients at various centers. We conducted a systematic review and meta-analysis to assess its efficacy on previously treated advanced metastatic cutaneous melanoma. The PubMed electronic database was searched from inception to 17 December 2018 to identify studies administering TIL-ACT and recombinant interleukin-2 (IL-2) following non-myeloablative chemotherapy in previously treated metastatic melanoma patients. Objective response rate (ORR) was the primary end point. Secondary end points were complete response rate (CRR), overall survival (OS), duration of response (DOR) and toxicity. Pooled estimates were derived from fixed or random effect models, depending on the amount of heterogeneity detected. Analysis was carried out separately for high dose (HD) and low dose (LD) IL-2. Sensitivity analyses were carried out. Among 1211 records screened, 13 studies (published 1988 - 2016) were eligible for meta-analysis. Among 410 heavily pretreated patients (some with brain metastasis), 332 received HD-IL-2 and 78 LD-IL-2. The pooled overall ORR estimate was 41% [95% confidence interval (CI) 35% to 48%], and the overall CRR was 12% (95% CI 7% to 16%). For the HD-IL-2 group, the ORR was 43% (95% CI 36% to 50%), while for the LD-IL-2 it was 35% (95% CI 25% to 45%). Corresponding pooled estimates for CRR were 14% (95% CI 7% to 20%) and 7% (95% CI 1% to 12%). The majority of HD-IL-2 complete responders (27/28) remained in remission during the extent of follow-up after CR (median 40 months). Sensitivity analyses yielded similar results. Higher number of infused cells was associated with a favorable response. The ORR for HD-IL-2 compared favorably with the nivolumab/ipilimumab combination following anti-PD-1 failure. TIL-ACT therapy, especially when combined with HD-IL-2, achieves durable clinical benefit and warrants further investigation. We discuss the current position of TIL-ACT in the therapy of advanced melanoma, particularly in the era of immune checkpoint blockade therapy, and review future opportunities for improvement of this approach.
Topics: Combined Modality Therapy; Disease-Free Survival; Dose-Response Relationship, Drug; Humans; Interleukin-2; Lymphocytes, Tumor-Infiltrating; Melanoma; Recombinant Proteins; Remission Induction; Skin Neoplasms; Transplantation, Autologous; Melanoma, Cutaneous Malignant
PubMed: 31566658
DOI: 10.1093/annonc/mdz398 -
Orbit (Amsterdam, Netherlands) Oct 2017This is a systematic review of eyebrow reconstruction options, using the PubMed database, as well as dermatology and plastic surgery texts. Eyebrow reconstruction... (Review)
Review
This is a systematic review of eyebrow reconstruction options, using the PubMed database, as well as dermatology and plastic surgery texts. Eyebrow reconstruction options in various clinical scenarios (small, large, medial, lateral, and total defects) are presented. The goals of eyebrow reconstruction are to provide structural, functional, and aesthetic restoration. A good understanding of various eyebrow reconstruction techniques is essential for plastic, dermatologic, and oculoplastic surgeons.
Topics: Eyebrows; Hair; Humans; Ophthalmologic Surgical Procedures; Plastic Surgery Procedures; Skin Transplantation; Surgical Flaps
PubMed: 28700281
DOI: 10.1080/01676830.2017.1337171 -
The Cochrane Database of Systematic... Mar 2019Indications for the use of negative pressure wound therapy (NPWT) are broad and include prophylaxis for surgical site infections (SSIs). While existing evidence for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Indications for the use of negative pressure wound therapy (NPWT) are broad and include prophylaxis for surgical site infections (SSIs). While existing evidence for the effectiveness of NPWT remains uncertain, new trials necessitated an updated review of the evidence for the effects of NPWT on postoperative wounds healing by primary closure.
OBJECTIVES
To assess the effects of negative pressure wound therapy for preventing surgical site infection in wounds healing through primary closure.
SEARCH METHODS
We searched the Cochrane Wounds Specialised Register, CENTRAL, Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus in February 2018. We also searched clinical trials registries for ongoing and unpublished studies, and checked reference lists of relevant included studies as well as reviews, meta-analyses, and health technology reports to identify additional studies. There were no restrictions on language, publication date, or setting.
SELECTION CRITERIA
We included trials if they allocated participants to treatment randomly and compared NPWT with any other type of wound dressing, or compared one type of NPWT with another type of NPWT.
DATA COLLECTION AND ANALYSIS
Four review authors independently assessed trials using predetermined inclusion criteria. We carried out data extraction, 'Risk of bias' assessment using the Cochrane 'Risk of bias' tool, and quality assessment according to GRADE methodology.
MAIN RESULTS
In this second update we added 25 intervention trials, resulting in a total of 30 intervention trials (2957 participants), and two economic studies nested in trials. Surgeries included abdominal and colorectal (n = 5); caesarean section (n = 5); knee or hip arthroplasties (n = 5); groin surgery (n = 5); fractures (n = 5); laparotomy (n = 1); vascular surgery (n = 1); sternotomy (n = 1); breast reduction mammoplasty (n = 1); and mixed (n = 1). In three key domains four studies were at low risk of bias; six studies were at high risk of bias; and 20 studies were at unclear risk of bias. We judged the evidence to be of low or very low certainty for all outcomes, downgrading the level of the evidence on the basis of risk of bias and imprecision.Primary outcomesThree studies reported mortality (416 participants; follow-up 30 to 90 days or unspecified). It is uncertain whether NPWT has an impact on risk of death compared with standard dressings (risk ratio (RR) 0.63, 95% confidence interval (CI) 0.25 to 1.56; very low-certainty evidence, downgraded once for serious risk of bias and twice for very serious imprecision).Twenty-five studies reported on SSI. The evidence from 23 studies (2533 participants; 2547 wounds; follow-up 30 days to 12 months or unspecified) showed that NPWT may reduce the rate of SSIs (RR 0.67, 95% CI 0.53 to 0.85; low-certainty evidence, downgraded twice for very serious risk of bias).Fourteen studies reported dehiscence. We combined results from 12 studies (1507 wounds; 1475 participants; follow-up 30 days to an average of 113 days or unspecified) that compared NPWT with standard dressings. It is uncertain whether NPWT reduces the risk of wound dehiscence compared with standard dressings (RR 0.80, 95% CI 0.55 to 1.18; very low-certainty evidence, downgraded twice for very serious risk of bias and once for serious imprecision).Secondary outcomesWe are uncertain whether NPWT increases or decreases reoperation rates when compared with a standard dressing (RR 1.09, 95% CI 0.73 to 1.63; 6 trials; 1021 participants; very low-certainty evidence, downgraded for very serious risk of bias and serious imprecision) or if there is any clinical benefit associated with NPWT for reducing wound-related readmission to hospital within 30 days (RR 0.86, 95% CI 0.47 to 1.57; 7 studies; 1271 participants; very low-certainty evidence, downgraded for very serious risk of bias and serious imprecision). It is also uncertain whether NPWT reduces incidence of seroma compared with standard dressings (RR 0.67, 95% CI 0.45 to 1.00; 6 studies; 568 participants; very low-certainty evidence, downgraded twice for very serious risk of bias and once for serious imprecision). It is uncertain if NPWT reduces or increases the risk of haematoma when compared with a standard dressing (RR 1.05, 95% CI 0.32 to 3.42; 6 trials; 831 participants; very low-certainty evidence, downgraded twice for very serious risk of bias and twice for very serious imprecision. It is uncertain if there is a higher risk of developing blisters when NPWT is compared with a standard dressing (RR 6.64, 95% CI 3.16 to 13.95; 6 studies; 597 participants; very low-certainty evidence, downgraded twice for very serious risk of bias and twice for very serious imprecision).Quality of life was not reported separately by group but was used in two economic evaluations to calculate quality-adjusted life years (QALYs). There was no clear difference in incremental QALYs for NPWT relative to standard dressing when results from the two trials were combined (mean difference 0.00, 95% CI -0.00 to 0.00; moderate-certainty evidence).One trial concluded that NPWT may be more cost-effective than standard care, estimating an incremental cost-effectiveness ratio (ICER) value of GBP 20.65 per QALY gained. A second cost-effectiveness study estimated that when compared with standard dressings NPWT was cost saving and improved QALYs. We rated the overall quality of the reports as very good; we did not grade the evidence beyond this as it was based on modelling assumptions.
AUTHORS' CONCLUSIONS
Despite the addition of 25 trials, results are consistent with our earlier review, with the evidence judged to be of low or very low certainty for all outcomes. Consequently, uncertainty remains about whether NPWT compared with a standard dressing reduces or increases the incidence of important outcomes such as mortality, dehiscence, seroma, or if it increases costs. Given the cost and widespread use of NPWT for SSI prophylaxis, there is an urgent need for larger, well-designed and well-conducted trials to evaluate the effects of newer NPWT products designed for use on clean, closed surgical incisions. Such trials should initially focus on wounds that may be difficult to heal, such as sternal wounds or incisions on obese patients.
Topics: Bandages; Blister; Hematoma; Humans; Negative-Pressure Wound Therapy; Orthopedic Procedures; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Reoperation; Seroma; Skin Transplantation; Surgical Procedures, Operative; Surgical Wound Dehiscence; Surgical Wound Infection; Wound Healing; Wounds and Injuries
PubMed: 30912582
DOI: 10.1002/14651858.CD009261.pub4 -
Acta Neurologica Scandinavica Feb 2019Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early- and late-onset, rare, progressive disorder,...
Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early- and late-onset, rare, progressive disorder, predominantly manifesting as length-dependent, small fiber dominant, axonal polyneuropathy and frequently associated with cardiac disorders and other multisystem diseases. ATTRm amyloidosis is due to variants in the TTR gene, with the substitution Val30Met as the most frequent mutation. TTR mutations lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, and formation of amyloid fibrils, which are consecutively deposited extracellularly in various tissues, such as nerves, heart, brain, eyes, intestines, kidneys, or the skin. Neuropathy may not only include large nerve fibers but also small fibers, and not only sensory and motor fibers but also autonomic fibers. Types of TTR variants, age at onset, penetrance, and clinical presentation vary between geographical areas. Suggestive of a ATTRm amyloidosis are a sensorimotor polyneuropathy, positive family history, autonomic dysfunction, cardiomyopathy, carpal tunnel syndrome, unexplained weight loss, and resistance to immunotherapy. If only sensory A-delta or C fibers are affected, small fiber neuropathy ensues. Diagnostic tests for small fiber neuropathy include determination of intraepidermal nerve fiber density, laser-evoked potentials, heat- and cold-detection thresholds, and measurement of the electrochemical skin conductance. Therapy currently relies on liver transplantation and TTR-stabilizers (tafamidis, diflunisal).
Topics: Amyloid Neuropathies, Familial; Humans; Mutation; Prealbumin
PubMed: 30295933
DOI: 10.1111/ane.13035 -
The Journal of Clinical and Aesthetic... Jun 2018The objective of this systematic review was to investigate the etiologies of hair loss of the eyebrow and eyelash that required hair transplantation, the optimal... (Review)
Review
The objective of this systematic review was to investigate the etiologies of hair loss of the eyebrow and eyelash that required hair transplantation, the optimal surgical technique, patient outcomes, and common complications. A total of 67 articles including 354 patients from 18 countries were included in this study. Most patients were women with an average age of 29 years. The most common etiology requiring hair transplantation was burns, occurring in 57.6 percent of cases. Both eyebrow and eyelash transplantation use follicular unit transplantation techniques most commonly; however, other techniques involving composite grafts and skin flaps continue to be utilized effectively with minimal complication rates. In summary, many techniques have been developed for use in eyebrow/eyelash transplantation and the selection of technique depends upon the dermatologic surgeon's preferences and the unique presentations of their patients.
PubMed: 29942421
DOI: No ID Found -
Current Oncology (Toronto, Ont.) Jun 2023The purpose of this systematic review and meta-analysis was to compare the risk of non-melanoma skin cancer (NMSC) and melanoma development in renal transplant... (Meta-Analysis)
Meta-Analysis Review
The purpose of this systematic review and meta-analysis was to compare the risk of non-melanoma skin cancer (NMSC) and melanoma development in renal transplant recipients who receive calcineurin inhibitors to that of patients treated with other immunosuppressive agents, and investigate the possible association between the type of maintenance immunosuppression and the incidence of NSMC and melanoma in this group of patients. The authors searched databases such as PubMed, Scopus, and Web of Science for articles that would help establish the influence of calcineurin inhibitors on skin cancer development. The inclusion criteria for the study consisted of randomized clinical trials, cohort studies, and case-control studies that compared patients who received kidney transplants and were treated with a calcineurin inhibitor (CNI), such as cyclosporine A (CsA) or tacrolimus (Tac), to those who received alternative immunosuppressants and did not receive a CNI. Seven articles were analyzed overall. The results revealed a correlation between CNI treatment in renal transplant recipients and increased total skin cancer risk (OR 1.28; 95% CI: 0.10-16.28; < 0.01), melanoma risk (OR 1.09; 95% CI: 0.25-4.74; < 0.01), and NMSC risk (OR 1.16; 95% CI: 0.41-3.26; < 0.01). In conclusion, the calcineurin inhibitors used after kidney transplantation are associated with a higher risk of skin cancer-both non-melanoma and melanoma-when compared with other immunosuppressive therapies. This finding suggests that careful monitoring for skin lesions in post-transplant patients must be conducted. However, the decision on the kind of immunotherapy used should always be considered on an individual basis for each renal transplant recipient.
Topics: Humans; Adult; Calcineurin Inhibitors; Kidney Transplantation; Incidence; Immunosuppressive Agents; Skin Neoplasms; Randomized Controlled Trials as Topic
PubMed: 37366913
DOI: 10.3390/curroncol30060430 -
International Journal of Dermatology Nov 2022Brunsting-Perry pemphigoid (BPP) is a rare, autoimmune bullous skin disorder classified within the spectrum of mucous membrane pemphigoid (MMP). (Review)
Review
BACKGROUND
Brunsting-Perry pemphigoid (BPP) is a rare, autoimmune bullous skin disorder classified within the spectrum of mucous membrane pemphigoid (MMP).
MATERIALS AND METHODS
An a priori protocol was designed based on PRISMA guidelines. PubMed and Scopus databases were searched for English-language articles concerning BPP published between 1950 and July 2021.
RESULTS
Thirty-six articles including 63 BPP patients were analyzed. The mean age at diagnosis was 62.9 years (range: 27-86). BPP was shown to be characterized by vesiculobullous lesions (46/63, 73.0%) on an erythematous base, erosions or ulcerations (27/63, 42.9%), atrophic scars (49/63, 77.8%), and milia (4/63, 6.3%). Exclusive oral mucosal involvement was documented in 22.2% of cases, usually manifesting after the cutaneous onset of the disease. Subepidermal blistering was a constant finding, often with an eosinophil-rich inflammatory infiltrate (21/58, 36.2%). Positive direct immunofluorescence was found in 92.0% of patients, almost always with linear IgG ± C3 deposits along the basement membrane (43/46, 93.5%). BP180 (12/15, 80.0%), BP230 (5/15, 33.3%), and laminin 332 (3/15, 20.0%) were the most frequently identified target antigens.
CONCLUSIONS
BPP nosologic position remains uncertain, given the overlap with other autoimmune bullous diseases, such as MMP, bullous pemphigoid, and epidermolysis bullosa acquisita, particularly in its BPP-like variant. Nonpredominant oral mucosal lesions may appear during the course of the disease, generally after cutaneous manifestations. Positivity of DIF and anti-BP180/230 autoantibodies detected on ELISA/immunoblotting in the absence of anticollagen VII antibodies may provide guidance in diagnosing BPP.
Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases; Epidermolysis Bullosa Acquisita; Humans; Immunoglobulin G; Middle Aged; Pemphigoid, Bullous; Skin Diseases, Vesiculobullous
PubMed: 35049061
DOI: 10.1111/ijd.16045 -
Cells, Tissues, Organs 2021Immunodeficient mouse models with human skin xenografts have been developed in the past decades to study different conditions of the skin. Features such as follow-up...
Immunodeficient mouse models with human skin xenografts have been developed in the past decades to study different conditions of the skin. Features such as follow-up period and size of the graft are of different relevance depending on the purpose of an investigation. The aim of this study is to analyze the different mouse models grafted with human skin. A systematic review of the literature was performed in line with the PRISMA statement using MEDLINE/PubMed databases from January 1970 to June 2020. Articles describing human skin grafted onto mice were included. Animal models other than mice, skin substitutes, bioengineered skin, postmortem or fetal skin, and duplicated studies were excluded. The mouse strain, origin of human skin, graft dimensions, follow-up of the skin graft, and goals of the study were analyzed. Ninety-one models were included in the final review. Five different applications were found: physiology of the skin (25 models, mean human skin graft size 1.43 cm2 and follow-up 72.92 days), immunology and graft rejection (17 models, mean human skin graft size 1.34 cm2 and follow-up 86 days), carcinogenesis (9 models, mean human skin graft size 1.98 cm2 and follow-up 253 days), skin diseases (25 models, mean human skin graft size 1.55 cm2 and follow-up 86.48 days), and would healing/scars (15 models, mean human skin graft size 2.54 cm2 and follow-up 129 days). The follow-up period was longer in carcinogenesis models (253 ± 233.73 days), and the skin graft size was bigger in wound healing applications (2.54 ± 3.08 cm2). Depending on the research application, different models are suggested. Careful consideration regarding graft size, follow-up, immunosuppression, and costs should be analyzed and compared before choosing any of these mouse models. To our knowledge, this is the first systematic review of mouse models with human skin transplantation.
Topics: Animals; Humans; Mice; Skin; Skin Transplantation; Skin, Artificial; Transplantation, Heterologous; Wound Healing
PubMed: 34521089
DOI: 10.1159/000516154 -
Frontiers in Medicine 2023The Ehlers-Danlos syndromes (EDS) comprise a group of inherited connective tissue disorders presenting with variable fragility to skin, soft tissue, and certain internal...
INTRODUCTION
The Ehlers-Danlos syndromes (EDS) comprise a group of inherited connective tissue disorders presenting with variable fragility to skin, soft tissue, and certain internal organs, which can cause significant complications, particularly arterial rupture, bowel perforation and joint difficulties. Currently, there are 14 proposed subtypes of EDS, with all except one subtype (hypermobile EDS) having an identified genetic etiology. An understanding of the extracutaneous features and complications within each subtype is key to maximizing clinical care and reducing the risk of further complications.
METHODS
A systematic review of EDS-related extracutaneous features and complications was undertaken.
RESULTS
We identified 839 EDS cases that met the inclusion criteria. We noted a high prevalence of joint hypermobility amongst kyphoscoliotic (39/39, 100%), spondylodysplastic (24/25, 96.0%), and hypermobile (153/160, 95.6%) EDS subtypes. The most common musculoskeletal complications were decreased bone density (39/43, 90.7%), joint pain (217/270, 80.4%), and hypotonia/weakness (79/140, 56.4%). Vascular EDS presented with cerebrovascular events (25/153, 16.3%), aneurysm (77/245, 31.4%), arterial dissection/rupture (89/250, 35.5%), and pneumothorax/hemothorax. Chronic pain was the most common miscellaneous complication, disproportionately affecting hypermobile EDS patients (139/157, 88.5%). Hypermobile EDS cases also presented with chronic fatigue (61/63, 96.8%) and gastrointestinal complications (57/63, 90.5%). Neuropsychiatric complications were noted in almost all subtypes.
DISCUSSION
Understanding the extracutaneous features and complications of each EDS subtype may help diagnose and treat EDS prior to the development of substantial comorbidities and/or additional complications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308151, identifier CRD42022308151.
PubMed: 36756177
DOI: 10.3389/fmed.2023.1053466 -
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