Single-cell chromatin accessibility and transposable element landscapes reveal shared features of tissue-residing immune cells.

Tissue adaptation is required for regulatory T (Treg) cell function within organs. Whether this program shares aspects with other tissue-localized immune populations is unclear. Here, we analyzed single-cell chromatin accessibility data, including the transposable element (TE) landscape of CD45+ immune cells from colon, skin, adipose tissue, and spleen. We identified features of organ-specific tissue adaptation across different immune cells. Focusing on tissue Treg cells, we found conservation of the Treg tissue adaptation program in other tissue-localized immune cells, such as amphiregulin-producing T helper (Th)17 cells. Accessible TEs can act as regulatory elements, but their contribution to tissue adaptation is not understood. TE landscape analysis revealed an enrichment of specific transcription factor binding motifs in TE regions within accessible chromatin peaks. TEs, specifically from the LTR family, were located in enhancer regions and associated with tissue adaptation. These findings broaden our understanding of immune tissue residency and provide an important step toward organ-specific immune interventions.

Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells.

Murine regulatory T (Treg) cells in tissues promote tissue homeostasis and regeneration. We sought to identify features that characterize human Treg cells with these functions in healthy tissues. Single-cell chromatin accessibility profiles of murine and human tissue Treg cells defined a conserved, microbiota-independent tissue-repair Treg signature with a prevailing footprint of the transcription factor BATF. This signature, combined with gene expression profiling and TCR fate mapping, identified a population of tissue-like Treg cells in human peripheral blood that expressed BATF, chemokine receptor CCR8 and HLA-DR. Human BATF+CCR8+ Treg cells from normal skin and adipose tissue shared features with nonlymphoid T follicular helper-like (Tfh-like) cells, and induction of a Tfh-like differentiation program in naive human Treg cells partially recapitulated tissue Treg regenerative characteristics, including wound healing potential. Human BATF+CCR8+ Treg cells from healthy tissue share features with tumor-resident Treg cells, highlighting the importance of understanding the context-specific functions of these cells.

Allogeneic amnion transplantation for the management of cutaneous graft-versus-host disease with associated ulcers: A promising therapeutic strategy.

Allogeneic hematopoietic stem cell transplantation (alloSCT) is the cornerstone treatment for various hematopoietic disorders, but its utility is often compromised by chronic graft-versus-host disease (cGvHD), affecting skin integrity and leading to ulcer formations. Traditional treatments, including systemic and topical therapies, frequently fail in severe cases. This study retrospectively examines three patients with therapy-resistant ulcers due to cGvHD post-alloSCT treated at the University Hospital of Regensburg in 2023. We evaluated the therapeutic impact of human amniotic membrane (hAM) transplantation-a novel approach utilizing hAM's anti-inflammatory, anti-microbial, and anti-fibrotic properties for wound healing. Surgical debridement was followed by hAM application and routine follow-up. HAM transplantation led to complete wound closure in two out of three patients and a significant reduction in local pain and infection rates. The treatment alleviated the need for regular dressing changes within three months in two patients, demonstrating the hAM's efficacy in fostering rapid and sustained healing. The utilization of hAM represents a promising alternative for the management of refractory skin ulcers in cGvHD patients, particularly when conventional methods are inadequate.

Digital Volumetric Measurements Based on 3D Scans of the Lower Limb: A Valid and Reproducible Method for Evaluation in Lymphedema Therapy.

BACKGROUND: Exact quantification of volumetric changes of the extremities is difficult and often error-prone. The aim of this study was to establish a standardized method based on 3-dimensional (3D) scans. Furthermore, this study tests the method in terms of reproducibility and evaluates volume changes after surgical therapy in patients suffering from lymphedema on the lower extremity. METHODS: 3D scans of the lower limb were performed with a mobile 3D scanner; "repeatability" and "interobserver reliability" of digital volumetry were tested. Furthermore, the method was applied on 31 patients suffering from chronic lymphedema. RESULTS: Calculations of repeatability of the volume based on 20 3D scans of the same lower leg showed a mean volume of 2.488 ± 0.011 liters (range: 2.470-2.510). The mean volume of the different examiners did not differ significantly (F(2,18) = 1.579, P = 0.233). The paired t-test showed a significant mean volume decrease of 375 mL (95% confidence interval = 245/505 mL) between pretreatment and post-treatment (t (30) = 5.892, P < 0.001). CONCLUSIONS: 3D volumetry is a noninvasive, easy, and quick method to assess volume changes of the lower leg. Other than the low costs, it is reproducible and precise and therefore ideal for evolution of therapy in lymphedema.

An ACS-NSQIP Data Analysis of 30-Day Outcomes Following Surgery for Bell's Palsy.

BACKGROUND: There exists a paucity of large-scale, multi-institutional studies that investigate the outcomes of surgery for Bell's palsy (BP). Here, we utilize a large, multi-institutional database to study the risk factors and early-stage outcomes following surgical procedures in BP. METHODS: We reviewed the American College of Surgeons National Surgical Quality Improvement Program database (2008-2019) to identify patients who underwent surgery for the diagnosis of BP. We extracted data on comorbidities and preoperative blood values, and 30-day postoperative outcomes. RESULTS: Two hundred fifty-seven patients who underwent surgery for BP symptoms over the 12-year review period were identified. Muscle grafts (n=50; 19%) and fascial grafts (n=48; 19%) accounted for the majority of procedures. The most common comorbidities were hypertension (n=89; 35%) and obesity (n=79; 31%). Complications occurred in 26 (10.1%) cases. Additionally, length of hospital stay was significantly associated with both surgical and medical complications (3.9±4.7 versus 1.5±2.0; P <0.01) and (3.2±3.8 versus 1.4±2.0; P <0.01), respectively. Preoperative creatinine, blood urea nitrogen, and alkaline phosphatase were identified as potential predictors of poor postoperative outcomes. CONCLUSION: Based on multi-institutional analysis, complication rates following surgery for BP were found to be overall low and seen to correlate with length of hospital stay. Reoperations and readmissions were the most frequent complications after surgery for BP. The preoperative evaluation of routine laboratory values may help refine patient eligibility and risk stratification. In addition, our findings call for future large-scale prospective studies in the field of facial palsy surgery to further improve the quality of care and optimize perioperative protocols.

The Influence of Scar Patterns After Reduction Mammoplasty on Eye Movement and Gaze Pattern: An Eye-Tracking Investigation.

BACKGROUND: Given that scars are acknowledged as the primary cause of postoperative dissatisfaction following reduction mammoplasty, it is imperative to comprehend the patient's visual perception of different scar patterns in order to enhance patient satisfaction. To achieve this, eye-tracking technology provides an unbiased method of evaluating how observers assess breast scars. METHODS: 58 participants (32 females and 26 males) between the ages of 19 and 82 years (mean age of 29.47 ± 10.98 years) were shown 18 color photographs, taken at 3 viewing angles (right 45° oblique, frontal and frontal view with arms raised), from 6 patients undergone reduction mammoplasty with the inverted T-scar technique (3 patients) or no-vertical-scar technique (3 patients). The images were presented to every participant for a fixed duration of 5 s each. Eye-tracking device was used to collect and analyze the gaze data of viewers. RESULTS: The nipple-areola complex (NAC) and the periareolar scar captured observers' gaze faster, had longer duration and more count of eye fixation than all other parts of breast scars, regardless of the viewing angle and scar pattern. Moreover, the scar region in the inverted T-scar pattern received greater and faster visual attraction of observer's gaze than the no-vertical-scar pattern. CONCLUSION: The NAC and the periareolar scar seem to be perceived as the most important regions for breast aesthetics. The findings can be helpful to assist plastic surgeons in determining the most appropriate technique for reduction mammoplasty, meanwhile underlining the importance of a fine periareolar scar and symmetric NAC for excellent aesthetic outcomes. This is to our best knowledge the first study using eye-tracking technology in evaluating reduction mammoplasty outcomes. This study explored the influence of different scar patterns after reduction mammoplasty on eye movements and gaze patterns among observers. The study have validated the significance of the NAC and the periareolar scar for breast aesthetics and revealed that the scar region in the inverted T-scar pattern may be judged less visually attractive than the no-vertical-scar pattern. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors  www.springer.com/00266 .

Breast Lipofilling: Is the Bra Really Full? Clinical Bra Pressure Measurement and In Vitro Testing of Processed and Unprocessed Fat Cells.

BACKGROUND: Breast lipofilling, a popular cosmetic and reconstructive procedure, involves the transplantation of autologous fat to enhance breast volume and contour. Despite its widespread use, cell processing and the aftertreatment remain controversial. This study investigates the pressure applied by a compression bra and reports in vitro stress tests of processed and unprocessed fat cells. METHODS: Clinical bra pressure measurements were conducted on a cohort of 45 patients following lipofilling, reduction mammoplasties and DIEP flaps. Laboratory analysis included cell vitality testing using Resazurin assays of processed and unprocessed fat cells after exposure to mechanical or hyperbaric pressure. RESULTS: Our findings show a mean overall pressure value of the compression bra for all patients of 6.7 ± 5.7 mmHg (range 0-35). Cell processing is superior to sedimentation only regarding fat cell vitality. However, neither mechanical pressure within the specified range nor hyperbaric oxygen exposure significantly affected fat graft survival as measured by Resazurin assays. CONCLUSION: The in vitro measurements showed that it was impossible to harm fat cells with external pressure during lipofilling procedures, regardless of their processing. In the clinical context, the compression bra applied pressure values deceeding the perfusion pressure and may therefore not diminish oxygen supply nor harm the transplanted cells. Therefore, we recommend the use of a compression bra for all lipofilling procedures around the breast. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.

Exosomes from Adipose-Tissue-Derived Stem Cells Induce Proapoptotic Gene Expression in Breast Tumor Cell Line.

Lipofilling is an option for breast reconstruction after tumor resection to avoid the complications of an implant-based reconstruction. Although some concerns exist regarding the oncological safety of tissue rich in mesenchymal stem cells with their proangiogenic and proliferation-supportive properties, there are also reports that adipose-tissue-derived stem cells can exhibit antitumoral properties. We isolated primary adipose-tissue-derived stem cells. Both conditioned medium and exosomes were harvested from the cell culture and used to treat the breast cancer cell line MCF-7. Cell viability, cytotoxicity, and gene expression of MCF-7 cells in response to the indirect co-culture were evaluated. MCF-7 cells incubated with exosomes from adipose-tissue-derived stem cells show reduced cell viability in comparison to MCF-7 cells incubated with adipose-tissue-derived stem-cell-conditioned medium. Expression of proapoptotic genes was upregulated, and expression of antiapoptotic genes was downregulated. The debate about the oncological safety of autologous fat grafting after tumor resection continues. Here, we show that exosomes from adipose-tissue-derived stem cells exhibit some antitumoral properties on breast cancer cell line MCF-7.

The effect of radiotherapy on fat engraftment for complete breast reconstruction using lipofilling only.

PURPOSE: Lipofilling has been established as a standard technique for contour enhancement following breast reconstruction. However, there is a paucity in current literature regarding the use of this technique for complete reconstruction of the female breast as an alternative to conventional techniques, such as expander or flap-based procedures. In particular, the influence of pre-operative irradiation for successful reconstruction has rarely been examined in published studies. Here, the authors describe their experience with successful fat injection in pre-radiated breasts in comparison with non-pre-radiated patients. METHODS: In this retrospective study, we examined a total of 95 lipofilling treatments on 26 patients (28 breasts). All of them experienced mastectomy following breast cancer; local breast defects after partial resection of the gland were not included in this study. In total, 47 lipofilling procedures in 12 non-irradiated patients (14 breasts) and 48 procedures in 14 irradiated women (also 14 breasts) were performed. Per session, approximately 297 ± 112 cc of adipose tissue was grafted in group A (no radiotherapy) and approximately 259 ± 93 cc was grafted in group B (radiotherapy). RESULTS: Among the group of women without pre-operative radiation, 71% of breast reconstructions limited to lipofilling only showed constant engraftment of fat tissue with a successful reconstructive result, whereas only 21% of the patients with pre-radiated breasts showed complete reconstruction of the breast with a permanent fat in-growth. CONCLUSION: Preoperative radiotherapy significantly impedes successful completion of breast reconstructions planned only by autologous fat transfer. Patients should be selected individually and carefully for complete breast reconstruction using lipofilling only.

Incidence and Risk Factors of Postoperative Complications After Rhinoplasty: A Multi-Institutional ACS-NSQIP Analysis.

OBJECTIVE: Despite the popularity of rhinoplasty, outcome research has been mainly limited to single-surgeon or single-institution reports. Therefore, we performed a multi-institutional analysis to present a broader portrait of the postoperative outcomes and risk factors for adverse events after rhinoplasty surgery. METHODS: We reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2009-2019) to identify patients who underwent rhinoplasty. The postoperative outcomes of interest included 30-day mortality, reoperation, readmission, and surgical and medical complications. We also analyzed risk factors for complication occurrence, including patient comorbidities and preoperative laboratory values. RESULTS: We identified 835 patients, 72% (n=602) of whom underwent a primary, 21% (n=175) a secondary, and 6.7% (n=58) a cleft nasal deformity procedure. The average patient age was 41±17 years, with most patients being female (n=472; 57%) and white (n=643; 77%). Complications rates were generally low, with reoperation (n=19; 2.3%) and superficial incisional infection (n=9; 1.1%) account for the most common general and surgical adverse event, respectively. Multivariable analysis revealed male sex ( P =0.04) and higher ASA scores ( P <0.0001) as risk factors for complications. Low serum albumin ( P =0.04) and hematocrit ( P =0.003) levels were associated with the occurrence of any complication, whereas low serum albumin ( P =0.02) also correlated with the incidence of surgical adverse events. CONCLUSION: Complication rates after rhinoplasty were overall low and seemed to correlate with male sex and ASA scores. We identified preoperative albumin and hematocrit as predictive biomarkers of adverse events. Preoperative nutritional optimization and management of low hematocrit may improve postoperative outcomes.