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Large cutaneous ulcers are, in severe cases, life threatening 1 , 2 . As the global population ages, non-healing ulcers are becoming increasingly common 1 , 2 . Treatment currently requires the transplantation of pre-existing epithelial components, such as skin grafts, or therapy using cultured cells 2 . Here we develop alternative supplies of epidermal coverage for the treatment of these kinds of wounds. We generated expandable epithelial tissues using in vivo reprogramming of wound-resident mesenchymal cells. Transduction of four transcription factors that specify the skin-cell lineage enabled efficient and rapid de novo epithelialization from the surface of cutaneous ulcers in mice. Our findings may provide a new therapeutic avenue for treating skin wounds and could be extended to other disease situations in which tissue homeostasis and repair are impaired. Four transcription factors that specify keratinocyte cell fate, facilitate in vivo reprogramming of wound-resident mesenchymal cells, epithealization and regeneration of skin epithelial tissues in mice.

Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unifocal mucosal or cutaneous ulcer that is histologically characterized by proliferating EBV-positive atypical B cells. While EBVMCU demonstrates a histology similar to that of EBV-positive diffuse large B-cell lymphoma (DLBCL), their clinical behavior differs. Thus, characterizing distinguishing features of EBVMCU and EBV-positive DLBCL is critical. To identify unique characteristics between EBVMCU and lymphoma, we analyzed the clinicopathological and genetic features of 34 Japanese patients with EBVMCU and compared them to those of 24 EBV-positive DLBCL patients and 25 EBV-negative DLBCL patients. All patients with EBVMCU had localized ulcerative lesions, and 31 patients (91%) were using immunosuppressants, such as methotrexate (MTX) or hydroxycarbamide. All patients that were followed up with exhibited good prognosis following immunosuppressant reduction or chemotherapy. In addition, 17 EBV-positive DLBCL patients, and 15 EBV-negative DLBCL patients, received chemotherapy (P < 0.001, P < 0.001, respectively). Our data showed that EBVMCU did not increase indicators associated with lymphoma prognosis, such as soluble interleukin 2 receptor (sIL-2R) and lactate dehydrogenase (LDH) compared to those in the EBV-positive DLBCL or EBV-negative DLBCL groups (sIL-2R, P < 0.001, P = 0.025; LDH, P = 0.018, P = 0.038, respectively). However, histologically, EBVMCU exhibited EBV-positive, variable-sized, atypical B-cell proliferation. Thus, EBVMCU was histologically classified as: (1) polymorphous; (2) large cell-rich; (3) classic Hodgkin lymphoma-like; and (4) mucosa-associated lymphoid tissue lymphoma-like. Moreover, genetic analysis showed that immunoglobin heavy chain (IGH) gene rearrangement did not differ significantly between EBVMCU and EBV-positive DLBCL (44% vs. 32%; P = 0.377), or between EBVMCU and EBV-negative DLBCL (44% vs. 58%; P = 0.280). Therefore, it is difficult to distinguish EBVMCU from EBV-positive DLBCL using only pathological and genetic findings, suggesting that clinical information is important in accurately distinguishing between EBVMCU and EBV-positive DLBCL.

A 19-year-old man with leukocyte adhesion deficiency type 1 had severe periodontitis and a chronic open sacral wound that were corrected by periodic administration of ustekinumab, an antibody to interleukin-12 and interleukin-23 signaling. LAD1 is a primary immunodeficiency resulting from mutations in ITGB2, which encodes the common CD18 subunit of the β2 integrins; the β2 integrins are required for the adhesion of neutrophils to endothelium and the transmigration of neutrophils into tissues. Patients with LAD1 typically have recurrent skin infections that can be chronic and refractory. Recurrent oral ulcers cause severe pain and difficulty eating, and severe periodontitis leads to complete loss of adult teeth in almost all patients. 1 The mucocutaneous lesions in LAD1 were widely assumed to be due to infections that were a result of the relative tissue neutropenia caused by . . .

Abstract Background Cutaneous squamous cell carcinoma (cSCC) is characterized by a high tumor mutational burden due to solar damage and a favorable response to anti-PD-1 immunotherapy. Yet, we encounter tumors arising in areas with minimal sun exposure, such as cSCC that develops in chronically inflamed skin, also known as Marjolin’s Ulcer (MU). The response of MU-SCC to immunotherapy remains unknown. Methods We performed a retrospective analysis of patients diagnosed with cSCC and treated with cemiplimab or pembrolizumab in a single tertiary medical center. Patients lost to follow up were excluded. Results Of the 84 eligible patients, 9 (11%) had MU-SCC. Of these, 2 (22%) reached partial response (PR), and none reached complete response (CR). In contrast, of the 75 patients with solar damage-related cSCC, 40 had PR (53%), and 20 had CR (26%). The difference between the two subtypes was significant (P < .001). Interestingly, 3 patients with MU-SCC received a second-line chemo-immunotherapy and experienced a partial response that continued for 5 to 21 months. Patients with MU-SCC had a significantly shorter median time to progression (TTP) (1.6 vs 51.6 months, P < .001) and progression-free survival (PFS) (1.6 vs 15.4 months, P < .001). Overall survival (OS) was not significantly shorter (17.4 vs 36.7 months, P = .096). Multivariate analysis confirmed that MU-SCC is an independent risk factor for shorter TTP (HR 5.5, 95% CI 2.2-14.0, P < .001) and PFS (HR 3.5, 95% CI 1.5-8.1, P = .003). Conclusions This study suggests that immunotherapy is less beneficial in SCC-MU. More work is needed to verify our findings and explore other treatment options.

The purpose of this study was to permit bone marrow mesenchymal stem cells (BMSCs) to reach their full potential in the treatment of chronic wounds. A biocompatible multifunctional crosslinker based temperature sensitive hydrogel was developed to deliver BMSCs, which improve the chronic inflammation microenvironments of wounds. A detailed in vitro investigation found that the hydrogel is suitable for BMSC encapsulation and can promote BMSC secretion of TGF-β1 and bFGF. In vivo , full-thickness skin defects were made on the backs of db/db mice to mimic diabetic ulcers. It was revealed that the hydrogel can inhibit pro-inflammatory M1 macrophage expression. After hydrogel association with BMSCs treated the wound, significantly greater wound contraction was observed in the hydrogel + BMSCs group. Histology and immunohistochemistry results confirmed that this treatment contributed to the rapid healing of diabetic skin wounds by promoting granulation tissue formation, angiogenesis, extracellular matrix secretion, wound contraction and re-epithelialization. These results show that a hydrogel laden with BMSCs may be a promising therapeutic strategy for the management of diabetic ulcers.

Lymphomatoid papulosis (LyP) is a rare, chronic, recurrent, self-healing, indolent cutaneous lymphoproliferative disorder. Histologically, it resembles malignant lymphoma; however, its clinical manifestations are predominantly characterized by benign behaviors, including recurrent papules, nodules, and necrotic lesions. We report a case of a middle-aged female who initially presented with a giant ulcer on the right foot and was surgically treated at another hospital as a keratoacanthoma (KA). Over subsequent months, she developed scattered papules and nodules on the trunk and limbs. A comprehensive clinical and histopathological reassessment confirmed a diagnosis of LyP Type A. Notably, the initial ulcerative lesion represented an atypical feature of LyP rather than a conventional KA. Finally, the patient was successfully treated with methotrexate and interferon, resulting in complete resolution of the skin lesions without recurrence. In summary, this case highlights that a giant ulcer exhibiting pseudoepitheliomatous hyperplasia (PEH) in histopathology may indicate LyP. Careful assessment for atypical lymphocytic infiltration and further immunohistochemical evaluation are essential for accurate diagnosis. When single clinical or histopathological findings are insufficient to provide a comprehensive understanding of the disease, thorough evaluation and dynamic monitoring are critical for diagnosing and managing complex cases.

Background We postulated that the worse prognosis of melanoma with advancing age reflected more aggressive tumor biology and that in younger patients the prognosis would be more favorable. Materials and Methods The expanded AJCC melanoma staging database contained 11,088 patients with complete data for analysis, including mitotic rate. Results With increasing age by decade, primary melanomas were thicker, exhibited higher mitotic rates, and were more likely to be ulcerated. In a multivariate analysis of patients with localized melanoma, thickness and ulceration were highly significant predictors of outcome at all decades of life (except for patients younger than 20 years). Mitotic rate was significantly predictive in all age groups except patients <20 and >80 years. For patients with stage III melanoma, there were four independent variables associated with patient survival: number of nodal metastases, patient age, ulceration, and mitotic rate. Patients younger than 20 years of age had primary tumors with slightly more aggressive features, a higher incidence of sentinel lymph node metastasis, but, paradoxically, more favorable survival than all other age groups. In contrast, patients >70 years old had primary melanomas with the most aggressive prognostic features, were more likely to be head and neck primaries, and were associated with a higher mortality rate than the other age groups. Surprisingly, however, these patients had a lower rate of sentinel lymph node metastasis per T stage. Among patients between the two age extremes, clinicopathologic features and survival tended to be more homogeneous. Conclusions Melanomas in patients at the extremes of age have a distinct natural history.

Chronic nonhealing wounds are complex complications of diabetes and are characterized by impaired vascular networks and persistent inflammation, making them challenging to treat. Studies have demonstrated that hair follicles possess tissue regenerative potential; however, their role in diabetic wounds remains unclear. This study aimed to investigate the impact of blood glucose levels on hair follicle activity and compare the effects of hair follicle transplantation under hyperglycemic and normoglycemic conditions on full-thickness skin wound healing in both normal and diabetic mice. The results revealed that hyperglycemia inhibited hair follicle activity. Nevertheless, hair follicle transplantation under both hyperglycemic and normoglycemic conditions promoted granulation tissue formation, collagen remodeling, and angiogenesis while reducing chronic inflammation, thereby enhancing the healing quality of diabetic wounds. Notably, hair follicles derived from normoglycemic conditions were more effective at promoting diabetic wound healing. This study provides an innovative strategy for skin regeneration in the treatment of diabetic wounds.

Due to the dramatic reduction of sea cucumber Isostichopus badionotus populations in the Yucatan Peninsula by overfishing and poaching, aquaculture has been encouraged as an alternative to commercial catching and restoring wild populations. However, the scarcity of broodstock, the emergence of a new disease in the auricularia larvae stage, and the development of skin ulceration syndrome (SUS) in the culture have limited aquaculture development. This study presents the changes in the intestine and skin microbiota observed in early and advanced stages of SUS disease in cultured juvenile I . badionotus obtained during an outbreak in experimental culture through 16S rRNA gene sequencing and histological evidence. Our results showed inflammation in the intestines of juveniles at both stages of SUS. However, more severe tissue damage and the presence of bacterial clusters were detected only in the advanced stages of SUS. Differences in the composition and structure of the intestinal and skin bacterial community from early and advanced stages of SUS were detected, with more evident changes in the intestinal microbial communities. These findings suggest that SUS was not induced by a single pathogenic bacterium. Nevertheless, a decrease in the abundance of Vibrio and an increase in Halarcobacter (syn. Arcobacter ) was observed, suggesting that these two bacterial groups could be keystone genera involved in SUS disease.

This article reports the diagnosis and treatment of a 50-year-old female patient with systemic sclerosis complicated by a nonhealing wound on her left hand. Following comprehensive treatments including debridement, vacuum sealing drainage, ozone therapy, skin grafting, and phalangeal fusion, the wound healed successfully. This article highlights the potentially contradictory role of interleukin-6 inhibitors in the treatment of patients with systemic sclerosis and ulcers as well as emphasizes the application value of ozone therapy in improving tissue hypoxia and promoting healing.