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BACKGROUND: Dystrophic epidermolysis bullosa (DEB) describes a rare genetic blistering disorder characterized by fragile skin. This study aimed to classify the frequency, demographics, cost, and comorbidities associated with emergency department (ED) visits due to DEB.
METHODS: The Nationwide Emergency Department Sample (NEDS) was analyzed for pediatric (age <18) ED visits from 2015 to 2019. DEB was identified with ICD-10-CM code Q81.2. Weighted frequency, prevalence, and 95% confidence intervals (CIs) of comorbidities were determined among ED visits with and without a DEB diagnosis.
RESULTS: From 2015 to 2019, 53 (weighted 242) cases of DEB among 27,223,220 pediatric ED visits were captured. Patients with DEB were more likely to visit the ED in summer compared with those without a diagnosis of DEB (35.7% vs. 21.4%, P < .05). More than half of patients with DEB were admitted to the hospital (56.2%, 95% CI: 39.3-72.5, P < .001) versus only 3.4% (95% CI: 3.1-3.7) of other patients. For ED visits with a secondary DEB diagnosis, the top three primary diagnoses were fever, constipation, and bone marrow transplant aftercare. Patients with DEB had higher rates of hypertension, cellulitis, sepsis, acute and chronic kidney injury, esophageal obstruction, gastroesophageal reflux disease, cardiomyopathy, and anxiety, compared to patients without DEB (all P < .001).
CONCLUSIONS: DEB is a complex blistering disorder with multisystemic manifestations. Patients with DEB have significantly higher admission rates and commonly present with infectious or gastrointestinal complications. Understanding the features of ED visits due to DEB can better prepare healthcare teams and improve patient outcomes.

OBJECTIVE: The aim of this study is to systematically review randomized controlled clinical trials (RCTs) studying various types of regenerative medicine methods (such as platelet-rich plasma, stromal vascular fraction, cell therapy, conditioned media, etc.) in treating specific dermatologic diseases. Rejuvenation, scarring, wound healing, and other secondary conditions of skin damage were not investigated in this study.
METHODS: Major databases, including PubMed, Scopus, and Web of Science, were meticulously searched for RCTs up to January 2024, focusing on regenerative medicine interventions for specific dermatologic disorders (such as androgenetic alopecia, vitiligo, alopecia areata, etc.). Key data extracted encompassed participant characteristics and sample sizes, types of regenerative therapy, treatment efficacy, and adverse events.
RESULTS: In this systematic review, 64 studies involving a total of 2888 patients were examined. Women constituted 44.8% of the study population, while men made up 55.2% of the participants, with an average age of 27.64 years. The most frequently studied skin diseases were androgenetic alopecia (AGA) (45.3%) and vitiligo (31.2%). The most common regenerative methods investigated for these diseases were PRP and the transplantation of autologous epidermal melanocyte/keratinocyte cells, respectively. Studies reported up to 68.4% improvement in AGA and up to 71% improvement in vitiligo. Other diseases included in the review were alopecia areata, melasma, lichen sclerosus et atrophicus (LSA), inflammatory acne vulgaris, chronic telogen effluvium, erosive oral lichen planus, and dystrophic epidermolysis bullosa. Regenerative medicine was found to be an effective treatment option in all of these studies, along with other methods. The regenerative medicine techniques investigated in this study comprised the transplantation of autologous epidermal melanocyte/keratinocyte cells, isolated melanocyte transplantation, cell transplantation from hair follicle origins, melanocyte-keratinocyte suspension in PRP, conditioned media injection, a combination of PRP and basic fibroblast growth factor, intravenous injection of mesenchymal stem cells, concentrated growth factor, stromal vascular fraction (SVF), a combination of PRP and SVF, and preserving hair grafts in PRP.
CONCLUSIONS: Regenerative medicine holds promise as a treatment for specific dermatologic disorders. To validate our findings, it is recommended to conduct numerous clinical trials focusing on various skin conditions. In our study, we did not explore secondary skin lesions like scars or ulcers. Therefore, assessing the effectiveness of this treatment method for addressing these conditions would necessitate a separate study.

BACKGROUND: During the last 10 years, in Romania, progress has been made for the welfare of patients suffering from epidermolysis bullosa (EB). In five university hospitals, affiliated with the National Program for the Treatment of Rare Diseases, highly trained specialists diagnose and treat patients with this rare condition. Regarding diagnosis, limitations still exist as immunofluorescence mapping and molecular genetic analysis are not accessible, and generally not reimbursed. Our objective is to present the experience in diagnosing EB patients at Colentina Clinical Hospital, highlighting genotype-phenotype correlations observed in our cohort of patients.
METHODS: The records of the patients enrolled between 2012 and 2024 were analyzed considering clinical aspects, and, when available, immunofluorescence mapping, transmission electron microscopy, and genetic molecular analysis.
RESULTS: Fifty-six patients were identified, of whom 31 cases were of dystrophic EB, three were of junctional EB, and 11 were of simplex EB. For 11 cases, the EB type could not be determined. Regarding EB simplex, two patients with KRT5 mutations and three patients with KRT14 mutations with various clinical expressions, from mild phenotype to severe forms, were identified. Three severe junctional EB patients were registered in our database and for one of the patients, two previously unreported mutations in the LAMA3 gene were identified. Regarding dystrophic EB, 31 cases were identified, of which 25 were recessive dystrophic cases and six were dominant dystrophic cases. Molecular genetic testing was performed for 15 patients, and the most common variant was c.425A>G, identified in six cases.
CONCLUSIONS: Two previously unreported mutations were identified, namely, COL7A1 c.5416G>C, a heterozygous missense variant in a patient with a mild phenotype, mainly with nail involvement, and COL7A1 c.5960del, a variant that generates a frameshift in exon 72 resulting in a premature stop codon; this variant was identified in two siblings with a severe recessive dystrophic.
CONCLUSIONS: Important steps have been made in identifying the correct and complete diagnosis, as well as the characterization of EB patients addressing our reference center. The findings underscore the pivotal role of molecular genetic testing in confirming diagnoses and elucidating inheritance patterns, especially in cases with atypical presentations or de novo mutations.

Epidermolysis Bullosa (EB) is an extremely rare and disabling inherited genetic skin disease with a predisposition to develop bullous lesions on the skin and inner mucous membranes, occurring after mild friction or trauma, or even spontaneously. Within the spectrum of EB forms, dystrophic EB (DEB) represents the most intriguing and challenging in terms of clinical management, especially with regard to pregnancy, due to the highly disabling and life-threatening phenotype. Disappointingly, in the literature little focus has been directed towards pregnancy and childbirth in DEB patients, resulting in a lack of sound evidence and guidance for patients themselves and clinicians. The current study aims to contribute to the DEB literature with an updated summary of the existing evidence regarding the obstetrical and anesthesiological management of this rare disease. Furthermore, this literature review sought to answer the question of whether, and if so, in which way, the pregnancy condition may alter the course of the underlying dermatologic skin disease. Having all this information is indispensable when counseling a patient with DEB who desires a child or is expecting one. Finally, we reported own experience with a pregnant woman with a recessive DEB whom we recently managed, with a favorable outcome.

Gene editing nucleases, base editors, and prime editors are potential locus-specific genetic treatment strategies for recessive dystrophic epidermolysis bullosa; however, many recessive dystrophic epidermolysis bullosa COL7A1 pathogenic nucleotide variations (PNVs) are unique, making the development of personalized editing reagents challenging. A total of 270 of the ∼320 COL7A1 epidermolysis bullosa PNVs reside in exons that can be skipped, and antisense oligonucleotides and gene editing nucleases have been used to create in-frame deletions. Antisense oligonucleotides are transient, and nucleases generate deleterious double-stranded DNA breaks and uncontrolled mixtures of allele products. We developed a twin prime editing strategy using the PEmax and recently evolved PE6 prime editors and dual prime editing guide RNAs flanking COL7A1 exon 5. Prime editing-mediated deletion of exon 5 with a homozygous premature stop codon was achieved in recessive dystrophic epidermolysis bullosa fibroblasts, keratinocytes, and induced pluripotent stem cells with minimal double-stranded DNA breaks, and collagen type VII protein was restored. Twin prime editing can replace the target exon with recombinase attachment sequences, and we exploited this to reinsert a normal copy of exon 5 using the Bxb1 recombinase. These findings demonstrate that twin prime editing can facilitate locus-specific, predictable, in-frame deletions and sequence replacement with few double-stranded DNA breaks as a strategy that may enable a single therapeutic agent to treat multiple recessive dystrophic epidermolysis bullosa patient cohorts.

UNASSIGNED: Dystrophic epidermolysis bullosa (DEB), a rare genetic skin disease caused by loss-of-function mutations in COL7A1, the gene encoding type VII collagen (COL7), is characterized by skin blistering, scarring, and extracutaneous manifestations that markedly reduce patient quality-of-life. Beremagene geperpavec-svdt (\'B-VEC\') is a gene therapy employing a non-integrating, replication-defective herpes simplex virus type 1 (HSV-1)-based vector encoding two copies of full-length human COL7A1 to restore COL7 protein after topical administration to DEB wounds. B-VEC was approved in the United States in 2023 as the first topical gene therapy and the first approved treatment for DEB. However, few providers have experience with use of this gene therapy.
UNASSIGNED: Data was obtained through literature review and the experience of providers who participated in the B-VEC clinical study or initiated treatment after B-VEC approval.
UNASSIGNED: This review discusses the burden of disease, describes the clinical trial outcomes of B-VEC, and provides physician and patient/caregiver recommendations as a practical guide for the real-world use of B-VEC, which can be administered in-office or at the patient\'s home.
UNASSIGNED: By continuing to optimize the practical aspects of B-VEC administration, the focus will continue to shift to patient-centric considerations and improved patient outcomes.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of skin fragility disorders characterized by blister formation following minor trauma. Four major types are distinguished based on the level of cleavage within the skin. Most EB forms present severely disabling cutaneous and systemic signs and symptoms. Management relies on daily time-consuming and distressing topical medications, and symptomatic treatment of systemic findings. Disease manifestations, symptoms, and daily care strongly affect patient and caregiver quality of life (QoL). To date, there are two validated EB-specific questionnaires, the \"Quality of Life in Epidermolysis Bullosa\" (QOLEB) and the \"Epidermolysis Bullosa Burden of Disease\" (EB-BoD) for the evaluation of patient and family disease burden, respectively. The aim of our study was to develop an Italian translation of the two questionnaires and to pilot-test them.
METHODS: The guidelines for translation and cross-cultural adaptation of health-related QoL measures were followed. Initially, two separate translations were generated for each questionnaire, and subsequently reconciled by an expert committee. This was followed by a back-translation process. The original texts and all translations underwent revision by the expert committee, resulting in definitive versions. The final versions were then tested in a pilot study involving cognitive debriefing in a group of 17 families, representative of all EB major types.
RESULTS: The translation and reconciliation process led to minor changes to obtain semantic/idiomatic/cultural equivalence of the Italian versions with the original ones and to reconcile the questions with the answer options. The cognitive debriefing process showed a good understanding and did not require text modifications.
CONCLUSIONS: The Italian versions of the QOLEB and EB-BoD provide valuable tools in everyday clinical practice of reference centers, and they allow the participation in multicenter international real-life observational studies as well as in controlled clinical trials. They enable the identification of disease-specific psychological and socioeconomic challenges for EB patients and their families, guiding targeted interventions to ensure appropriate and timely care.

The heritable condition epidermolysis bullosa (EB) is a rare but potentially devastating and life-threatening condition that is characterized primarily by cutaneous fragility, manifested when the dermis and epidermis fail to adhere properly. EB has no cure, and because of its rarity, few healthcare professionals have experience in treating it. Most families with an EB child are forced to rely on family caregiving which can be disruptive to family routines but, more importantly, place enormous time and emotional and financial burdens on the family. EB can be extremely painful, and families are often caught in the bind of trying to manage overwhelming financial burdens in an effort to help their children cope with excruciating pain. For many years, the nonprofit organization NoBabyBlisters.org has worked on five continents with families caring for EB children. Many of these families reside in under-developed nations with hot climates and limited healthcare resources. Over time, the healthcare professionals with NoBabyBlisters.org have worked with EB families both internationally and in the United States to develop a series of simple tips or \"hacks\" that may provide relief or great benefit to these children. The objective of this article is to share these field-tested tips with a wider audience. This is not a scientific study or a systematic review and is offered as a companion article to an earlier article on the same subject.

Fibronectin serves as a platform to guide and facilitate deposition of collagen and fibrillin microfibrils. During development of fibrotic diseases, altered fibronectin deposition in the extracellular matrix (ECM) is generally an early event. After this, dysregulated organization of fibrillins and fibrillar collagens occurs. Because fibronectin is an essential orchestrator of healthy ECM, perturbation of its ECM-organizational capacity may be involved in development of fibrosis. To investigate this, we employed recessive dystrophic epidermolysis bullosa as a disease model with progressive, severe dermal fibrosis. Fibroblasts from donors with recessive dystrophic epidermolysis bullosa in 2-dimensional and 3-dimensional cultures displayed dysregulated fibronectin deposition. Our analyses revealed that increase of profibrotic dipeptidyl peptidase-4-positive fibroblasts coincides with altered fibronectin deposition. Dipeptidyl peptidase-4 inhibitors normalized deposition of fibronectin and subsequently of fibrillin microfibrils and collagen I. Intriguingly, proteomics and inhibitor and mutagenesis studies disclosed that dipeptidyl peptidase-4 modulates ECM deposition through the proteolysis of the fibronectin N-terminus. Our study provides mechanistic insights into the observed profibrotic activities of dipeptidyl peptidase-4 and extends the understanding of fibronectin-guided ECM assembly in health and disease.