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Dermatology and Therapy Jun 2024Actinic keratosis (AK) is an intraepithelial condition characterized by the development of scaly, erythematous lesions after repeated exposure to ultraviolet radiation.... (Review)
Review
Actinic keratosis (AK) is an intraepithelial condition characterized by the development of scaly, erythematous lesions after repeated exposure to ultraviolet radiation. Significant immunosuppression is a risk factor for the development of AK and subsequent lesion progression to squamous cell carcinoma. Immunocompromised patients (ICPs), particularly organ transplant recipients, often have more advanced or complex AK presentations and an increased risk of skin carcinomas versus non-ICPs with AK, making lesions more difficult to treat and resulting in worse treatment outcomes. The recent "Personalising Actinic Keratosis Treatment" (PAKT) consensus reported that delivering patient-centric care may play a role in supporting better clinical outcomes and patient satisfaction with treatments for chronic dermatologic conditions such as AK, which require repeated cycles of treatment. Additionally, currently published guidance and recommendations were considered by the PAKT panel to be overly broad for managing ICPs with their unique and complex needs. Therefore, the "Personalising Actinic Keratosis Treatment for Immunocompromised Patients" (IM-PAKT) panel was established to build upon general recommendations from the PAKT consensus. The panel identified current gaps in guidance for AK care in ICPs, offered practical care approaches based on typical ICP scenarios, and highlighted the need to adapt AK management to optimize care and improve treatment outcomes in ICPs. In particular, dermatologists should establish collaborative and transparent relationships with patients' multidisciplinary teams to enhance overall care for patients' comorbidities: given their increased risk of progression to malignancy, earlier assessments/interventions and frequent follow-ups are vital.The panel also developed a novel "triage" tool outlining effective treatment follow-up and disease surveillance plans tailored to patients' risk profiles, guided by current clinical presentation and relevant medical history. Additionally, we present the panel's expert opinion on three fictional ICP scenarios to explain their decision-making process for assessing and managing typical ICPs that they may encounter in clinical practice.
PubMed: 38902589
DOI: 10.1007/s13555-024-01215-y -
British Journal of Cancer Jun 2024Despite ongoing research and recent advances in therapy, metastatic melanoma remains one of the cancers with the worst prognosis. Here we studied the postsynaptic cell...
BACKGROUND
Despite ongoing research and recent advances in therapy, metastatic melanoma remains one of the cancers with the worst prognosis. Here we studied the postsynaptic cell adhesion molecule Neuroligin 4X (NLGN4X) and investigated its role in melanoma progression.
METHODS
We analysed histologic samples to assess the expression and predictive value of NLGN4X in human melanoma. The oncogenic role of NLGN4X was determined by loss or gain-of-function experiments in vitro as well as by analysis of tumorspheres, which were grafted to human skin organoids derived from pluripotent stem cells. Whole genome expression analysis and validation experiments were performed to clarify the molecular mechanism.
RESULTS
We identified that suppression of NLGN4X down regulated the prefoldin member Von Hippel-Lindau binding protein 1 (VBP1). Moreover, loss of VBP1 was sufficient for accumulation of HIF1A and HIF1A signalling was further shown to be essential for the acquisition of migratory properties in melanoma. We re-established NLGN4X expression in late stage melanoma lines and observed decreased tumour growth after transplantation to human skin organoids generated from pluripotent stem cells. In line, we showed that high amounts of NLGN4X and its target VBP1 in human patient samples had a beneficial prognostic effect on patient survival.
CONCLUSION
In view of these findings, we propose that decreased amounts of NLGN4X are indicative of a metastatic melanoma phenotype and that loss of NLGN4X provides a novel mechanism for HIF induction.
PubMed: 38902533
DOI: 10.1038/s41416-024-02758-9 -
The Journal of Investigative Dermatology Jun 2024Methods for describing and reporting the clinical and histological characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not...
Methods for describing and reporting the clinical and histological characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians' and scientists' ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. Here we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from HS patients. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help consistently classify specimens in biobanks based on histological features and more accurately report and select samples used in translational research projects.
PubMed: 38901775
DOI: 10.1016/j.jid.2024.02.041 -
Advances in Skin & Wound Care Jul 2024Conventional flap repair surgery has several drawbacks, including operational complexity, donor site damage, and high risk. In this case series, the authors explored an...
Conventional flap repair surgery has several drawbacks, including operational complexity, donor site damage, and high risk. In this case series, the authors explored an alternative approach for repairing exposed tendon wounds caused by trauma using absorbable gelatin sponges (AGSs) and autologous thigh skin grafts. This report presents two cases of lower-extremity skin necrosis with tendon exposure following wound debridement. The treatment approach involved early debridement, negative-pressure wound therapy, and wound irrigation with 0.9% sodium chloride. Upon achieving controlled wound infection, AGSs were applied to the exposed tendon to prevent degeneration and promote wound healing. Subsequently, areas where granulation tissue failed to cover the tendon were repaired using AGSs and 0.25-mm-thick autologous mesh skin grafts harvested from the thigh. Complete wound healing was achieved in both cases, on the 20th and 12th day after skin grafting, respectively. The proposed method proved successful in repairing exposed tendon wounds, effectively preventing infection and necrosis.
Topics: Humans; Skin Transplantation; Male; Wound Healing; Gelatin Sponge, Absorbable; Transplantation, Autologous; Middle Aged; Tendon Injuries; Debridement; Adult; Female; Treatment Outcome
PubMed: 38899825
DOI: 10.1097/ASW.0000000000000166 -
Skin Research and Technology : Official... Jun 2024To evaluate the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated dark... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
The investigation and comparison of the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated infraorbital dark circles and wrinkles: A controlled blinded randomized clinical trial.
BACKGROUND
To evaluate the efficacy and safety of stromal vascular fraction (SVF), platelet rich plasma (PRP), and 1064-nm Q-switched Nd:YAG laser in reducing nanofat treated dark circles and wrinkles under the eyes.
METHOD
This study was a single-blinded randomized clinical trial conducted on patients with suborbital darkening under the eyes that randomly divided into control and case groups. In the control group, 15 patients were treated with one session of nanofat injection only, and five patients of each intervention groups received one session of nanofat+SVF injection, nanofat+PRP injection, and nanofat injection+Nd:YAG laser, respectively. Assessments methods were (1) evaluation of the degree of darkness and repair under the eyes by a blinded dermatologist based on clinical photographs, (2) investigating patient satisfaction, (3) using biometric variables for color, thickness, and density of the skin (only 3 months after the treatment), and (4) recording the possible adverse effects.
CONCLUSION
In terms of the extent of reduction in the intensity of darkness under the eyes, the combined treatment of nanofat injection together with SVF, PRP, and Nd:YAG laser had a much greater therapeutic effect than nanofat injection alone. In all three groups of combined treatments, patients were 100% satisfied. In terms of biometric variables, amount of changes in colorimeter, complete and dermal thickness, complete and dermal density, between the different groups was statistically significant. The use of combined treatments including nanofat with SVF injection, PRP, and 1064 Q-switched Nd:YAG laser may be more effective than nanofat alone, in reducing infraorbital dark circles and wrinkles.
Topics: Humans; Skin Aging; Female; Lasers, Solid-State; Platelet-Rich Plasma; Middle Aged; Single-Blind Method; Adult; Cosmetic Techniques; Treatment Outcome; Male; Patient Satisfaction
PubMed: 38899793
DOI: 10.1111/srt.13793 -
International Wound Journal Jun 2024Vasculitic and pyoderma gangrenosum ulcers are traditionally treated with immunosuppressants, and the role of surgery in the treatment of these atypical ulcers remains...
Vasculitic and pyoderma gangrenosum ulcers are traditionally treated with immunosuppressants, and the role of surgery in the treatment of these atypical ulcers remains unclear. This study aimed to investigate the need for surgical intervention as well as the outcome and safety of skin grafting in the treatment of 46 patients with vasculitic ulcers and 34 with pyoderma gangrenosum ulcers using data recorded in the validated Wound Registry. Of the 80 patients with atypical ulcers, 14% (n = 11) were treated surgically; these patients were older (p = 0.039), had lower mobility status (p = 0.002), and more often pulmonary diseases, rheumatoid arthritis, and previous arterial procedures (p = 0.007; p = 0.031; p = 0.031, respectively) than those treated conservatively. Of 181 ulcers, 15% (n = 27) were surgically treated, 78% once and 22% multiple times. During follow-up, 92.3% of both surgically and conservatively treated ulcers with available data healed. Of the surgically treated ulcers, median healing time after first surgical procedure was 96 days, and post-surgical complications were considered mild or unrelated to surgery. Our results suggest that if surgery is indicated, skin grafting is a safe and efficient treatment method provided that multidisciplinary approach is applied.
Topics: Humans; Pyoderma Gangrenosum; Male; Female; Skin Transplantation; Middle Aged; Aged; Wound Healing; Adult; Treatment Outcome; Aged, 80 and over; Retrospective Studies; Skin Ulcer; Vasculitis
PubMed: 38899689
DOI: 10.1111/iwj.14943 -
Skin Research and Technology : Official... Jun 2024Successful usage of autologous skin cell suspension (ASCS) has been demonstrated in some clinical trials. However, its efficacy and safety have not been verified. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Successful usage of autologous skin cell suspension (ASCS) has been demonstrated in some clinical trials. However, its efficacy and safety have not been verified. This latest systematic review and meta-analysis aim to examine the effects of autologous epidermal cell suspensions in re-epithelialization of skin lesions.
METHODS
Relevant articles were retrieved from PubMed, Embase, Cochrane Database, Web of Science, International Clinical Trials Registry Platform, China National Knowledge Infrastructureris, VIP Database for Chinese Technical Periodicals and Wanfang database. The primary output measure was the healing time, and the secondary outputs were effective rate, size of donor site for treatment, size of study treatment area, operation time, pain scores, repigmentation, complications, scar scale scores and satisfaction scores. Data were pooled and expressed as relative risk (RR), mean difference (MD) and standardized mean difference (SMD) with a 95% confidence interval (CI).
RESULTS
Thirty-one studies were included in this systematic review and meta-analysis, with 914 patients who received autologous epidermal cell suspensions (treatment group) and 883 patients who received standard care or placebo (control group). The pooled data from all included studies demonstrated that the treatment group has significantly reduced healing time (SMD = -0.86; 95% CI: -1.59-0.14; p = 0.02, I= 95%), size of donar site for treatment (MD = -115.41; 95% CI: -128.74-102.09; p<0.001, I= 89%), operation time (MD = 25.35; 95% CI: 23.42-27.29; p<0.001, I= 100%), pain scores (SMD = -1.88; 95% CI: -2.86-0.90; p = 0.0002, I= 89%) and complications (RR = 0.59; 95% CI: 0.36-0.96; p = 0.03, I= 66%), as well as significantly increased effective rate (RR = 1.20; 95% CI: 1.01-1.42; p = 0.04, I= 77%). There were no significant differences in the size of study treatment area, repigmentation, scar scale scores and satisfaction scores between the two groups.
CONCLUSION
Our meta-analysis showed that autologous epidermal cell suspensions is beneficial for re-epithelialization of skin lesions as they significantly reduce the healing time, size of donar site for treatment, operation time, pain scores and complications, as well as increased effective rate. However, this intervention has minimal impact on size of treatment area, repigmentation, scar scale scores and satisfaction scores.
Topics: Humans; Randomized Controlled Trials as Topic; Epidermal Cells; Transplantation, Autologous; Re-Epithelialization; Treatment Outcome; Wound Healing; Skin Diseases
PubMed: 38898373
DOI: 10.1111/srt.13820 -
Microsurgery Jul 2024Epidermolysis bullosa (EB) encompasses a range of rare genetic dermatological conditions characterized by mucocutaneous fragility and a predisposition to blister...
Epidermolysis bullosa (EB) encompasses a range of rare genetic dermatological conditions characterized by mucocutaneous fragility and a predisposition to blister formation, often triggered by minimal trauma. Blisters in the pharynx and esophagus are well-documented, particularly in dystrophic EB (DEB). However, there have been few reports of mucocutaneous squamous cell carcinoma (SCC) in the head and neck region, for which surgery is usually avoided. This report presents the first case of free jejunal flap reconstruction after total pharyngolaryngoesophagectomy for hypopharyngeal cancer in a 57-year-old patient with DEB. The patient with a known diagnosis of DEB had a history of SCC of the left hand and esophageal dilatation for esophageal stricture. PET-CT imaging during examination of systemic metastases associated with the left-hand SCC revealed abnormal accumulation in the hypopharynx, which was confirmed as SCC by biopsy. Total pharyngolaryngoesophagectomy was performed, followed by reconstruction of the defect using a free jejunal flap. A segment of the jejunum, approximately 15 cm in length, was transplanted with multiple vascular pedicles. The patient made an uneventful recovery postoperatively and was able to continue oral intake 15 months later with no complications and no recurrence of SCC in the head and neck region. While cutaneous SCC is common in DEB, extracutaneous SCC is relatively rare. In most previous cases, non-surgical approaches with radiotherapy and chemotherapy were chosen due to skin fragility and multimorbidity. In the present case, vascular fragility and mucosal damage of the intestinal tract were not observed, and routine vascular and enteric anastomoses could be performed, with an uneventful postoperative course. Our findings suggest that highly invasive surgery, including free tissue transplantation such as with a free jejunal flap, can be performed in patients with DEB.
Topics: Humans; Hypopharyngeal Neoplasms; Middle Aged; Free Tissue Flaps; Epidermolysis Bullosa Dystrophica; Jejunum; Plastic Surgery Procedures; Male; Carcinoma, Squamous Cell; Pharyngectomy; Esophagectomy; Laryngectomy
PubMed: 38895936
DOI: 10.1002/micr.31207 -
International Journal of Molecular... May 2024Pathogenic variants in the gene lead to a systemic disease with karyomegalic interstitial nephritis (KIN) at the forefront clinically. The phenotypic-genotypic features...
Pathogenic variants in the gene lead to a systemic disease with karyomegalic interstitial nephritis (KIN) at the forefront clinically. The phenotypic-genotypic features of a mutation-related disease involving five members of a Hungarian Caucasian family are presented. Each had adult-onset chronic kidney disease of unknown cause treated with renal replacement therapy and elevated liver enzymes. Short stature, emaciation, latte-colored skin, freckles, and a hawk-like nose in four patients, a limited intellect in two patients, and chronic restrictive lung disease in one patient completed the phenotype. Severe infections occurred in four patients. All five patients had ceased. Four patients underwent autopsy. KIN and extrarenal karyomegaly were observed histologically; the livers showed no specific abnormality. The genotyping using formalin-fixed tissue samples detected a hitherto undescribed homozygous mutation (c.1673_1674insT/p.Met558lfs*4; exon 5) in three of these patients and a heterozygous mutation in one patient. The reason for the heterozygosity is discussed. In addition, 56 family members consented to the screening for mutation from which 17 individuals proved to be heterozygous carriers; a blood chemistry evaluation of their kidney and liver function did not find any abnormality. The clinical presentation of FAN1-related disease was multifaceted, and not yet described manifestations were observed besides kidney and liver disease. Mutation in this gene should be suspected in adults with small kidneys of unknown cause, elevated liver enzymes, and recurrent infections, even without a family history.
Topics: Humans; Male; Female; Hungary; Mutation; Adult; Phenotype; Pedigree; Middle Aged; Exodeoxyribonucleases; Multifunctional Enzymes; Endodeoxyribonucleases; Genotype; Renal Insufficiency, Chronic
PubMed: 38892095
DOI: 10.3390/ijms25115907 -
Lasers in Surgery and Medicine Jun 2024Under optimal conditions, afferent and efferent human skin graft microcirculation can be restored 8-12 days postgrafting. Still, the evidence about the reperfusion...
OBJECTIVES
Under optimal conditions, afferent and efferent human skin graft microcirculation can be restored 8-12 days postgrafting. Still, the evidence about the reperfusion dynamics beyond this period in a dermato-oncologic setting is scant. We aimed to characterise the reperfusion of human skin grafts over 4 weeks according to the necrosis extension (less than 20%, or 20%-50%) and anatomic location using laser speckle contrast imaging (LSCI).
METHODS
Over 16 months, all eligible adults undergoing skin grafts following skin cancer removal on the scalp, face and lower limb were enroled. Perfusion was assessed with LSCI on the wound margin (control skin) on day 0 and on the graft surface on days 7, 14, 21 and 28. Graft necrosis extension was determined on day 28.
RESULTS
Forty-seven grafts of 47 participants were analysed. Regardless of necrosis extension, graft perfusion equalled the control skin by day 7, surpassed it by day 21, and stabilised onwards. Grafts with less than 20% necrosis on the scalp and lower limb shared this reperfusion pattern and had a consistently better-perfused centre than the periphery for the first 21 days. On the face, the graft perfusion did not differ from the control skin from day 7 onwards, and there were no differences in reperfusion within the graft during the study.
CONCLUSION
Skin graft reperfusion is a protracted process that evolves differently in the graft centre and periphery, influenced by postoperative time and anatomic location. A better knowledge of this process can potentially enhance the development of strategies to induce vessel ingrowth into tissue-engineered skin substitutes.
PubMed: 38890796
DOI: 10.1002/lsm.23815