Ultrasound and Helium Plasma-Assisted Liposuction for Body Contouring: A Single-Retrospective Cohort Study of 639 Patients.

BACKGROUND: Over the past two decades, liposuction techniques have significantly evolved, moving from basic fat removal to sophisticated methods aimed at improving safety, efficiency, and cosmetic outcomes. This study evaluates the efficacy and safety of a combined approach using ultrasound-assisted liposuction (UAL) and helium plasma radiofrequency (HPRF) technology to enhance skin tightening without the need for extensive surgical interventions. METHODS: We conducted a retrospective analysis of 639 patients who underwent the combined UAL and HPRF liposuction technique. The patient cohort had an average age of 31.5 years and a mean BMI of 27.9 kg/m2. The procedure predominantly targeted the abdomen, with an average of 2.4 body areas treated per patient. Surgical duration averaged 118 minutes, with a mean aspirate volume of 1698 mL. RESULTS: Minimal residual skin laxity was observed in 87% of patients, and 91% achieved excellent improvement in body contouring. The complication rates were low, with minor occurrences of seroma (5.6%) and a very low incidence of infection (0.3%). This combined technique demonstrated safety and efficacy, providing significant skin tightening and reducing recovery time compared to more invasive procedures. CONCLUSIONS: The combined use of UAL and HPRF technology offers a safe and effective method for enhancing skin tightening and improving body contouring outcomes. Despite the promising results, this study acknowledges the limitations of its retrospective design. Future prospective, multicenter studies are recommended to further validate these findings. This technique represents a significant advancement in the field of cosmetic surgery, emphasizing minimally invasive solutions with substantial esthetic benefits. LEVEL OF EVIDENCE IV: 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 .

Defining the Inframammary Fold by Liposuction: An Essential Tool in Aesthetic Shaping of the Reconstructed Breast. Technique and Long-term Results in a Series of Patients.

BACKGROUND: A good inframammary fold (IMF) definition and position is essential to achieve a satisfactory and natural result in breast surgery. This structure can be damaged, especially during mastectomies. Multiple methods are reported in the literature to restore IMF or improve its definition. In this study, we present the results achieved in a series of patients treated with subdermal liposuction. METHODS: We report on all our patients who underwent IMF liposuction between January 2016 and June 2020. Subdermal liposuction was performed with a blunt 3 mm cannula along the new IMF to promote skin retraction and adherence between skin and fascia. Results were evaluated subjectively by the patients and objectively by 8 individuals not involved with the treatment. RESULTS: We performed IMF liposuction in 88 breasts (69 patients), aged 21-74 (mean 52) years for 82 implant-based reconstructions, 2 tuberous breasts, and 4 contralateral breast augmentations. Mean follow-up was 28 months (6-64). Subjective results: the overall result evaluated with the VAS scale reached 86.6/100. All the 22 patients interviewed judged as well defined the new inframammary fold. Objective results: in 83% of cases the definition of the inframammary fold was judged as good or excellent, while symmetry with contralateral IMF, natural appearance, and overall aesthetic outcome were judged as good. CONCLUSION: Based on our long-term satisfactory results, we recommend the technique of subdermal liposuction to improve the definition of IMF in breast reconstruction after mastectomy and other breast procedures. It is effective, easy to perform, minimally invasive, and durable. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Meta-analysis of the effects of venous super-drainage in deep inferior epigastric artery perforator flaps for breast reconstruction.

INTRODUCTION: Venous congestion is the most common vascular complication of the deep inferior epigastric artery perforator (DIEP) flaps. Adding a second venous drainage by anastomosing a flap vein and a recipient vein (super-drainage) is considered the solution of choice. Evidence to support this procedure, had not yet been confirmed by an analysis of the literature. We aimed to provide this evidence. MATERIALS AND METHODS: We searched the literature (MedLine, Scopus, EMBASE, Cochrane Library, and Google Scholar), for studies discussing venous congestion and venous super-drainage in DIEP flap for breast reconstruction. Thirteen of the 35 articles compared results between one or two venous anastomoses. Meta-analysis was performed following PRISMA guidelines. Pooled risk ratio (RRs) for congestion, fat necrosis, partial necrosis, and total necrosis with corresponding 95% confidence intervals (CI) were calculated using a fixed-effect model with the Mantel-Haenszel method. The need to return to surgery (95% CI) was estimated with a random effect model using the DerSimonian and Liard method. RESULTS: We showed a statistically significant advantage of super-drainage to reduce the venous congestion of the flap (RR: 0.12, 95% CI: 0.04-0.34, p-value <.001), partial flap necrosis (RR: 0.50, 95% CI: 0.30-0.84, p-value .008), total flap necrosis (RR: 0.31, 95% CI: 0.11-0.85, p-value .023), and the need to take the patient back to surgery for perfusion-related complications (RR: 0.45, 95% CI: 0.21-0.99, p value .048). CONCLUSIONS: Performing a second venous anastomosis between the SIEV and a recipient vein (venous superdrainage) reduces venous congestion and related complications in DIEP flaps for breast reconstruction.

Autologous platelet-rich fibrin: a novel method for tracheoesophageal puncture site closure: a case report.

Closure of a tracheoesophageal puncture site performed during voice prosthesis implantation may sometimes be required. Besides local techniques, more elaborate procedures, such as closure by means of free microvascular flaps, have been advocated. In this report, we describe a case of local treatment of a hard-to-heal fistula with local application of autologous platelet-rich fibrin matrix in a 77-year-old male patient. At one-week follow-up, the size of the fistula had decreased dramatically but some leakage remained when drinking. After one month, the patient was able to drink and eat normally without any leakage. There was no recurrence of the leakage at two years' follow-up. In summary, local application of platelet-rich fibrin seems to be a simple, safe and effective procedure for tracheoesophageal fistula closure.

Microsurgical Reconstruction of the Nose: The Aesthetic Approach to Total Defects.

BACKGROUND: Reconstruction of complex defects involving nose and close facial units represents an aesthetic and functional challenge. Restoring satisfactory nasal shape, combining aesthetic, nasal function and patent airways is mandatory. In this paper, we describe our approach to total nose defects and we report our 20-year experience in microvascular nose reconstruction.Clinical cases are shown to illustrate different surgical techniques and the evolution of our approach. METHODS: Nasal reconstruction procedures were performed on 21 patients between 2000 and 2020 using the radial forearm flap (RFF) or anterolateral thigh (ALT) flap. Reported reconstructions included total/subtotal nasal defects, caused by cancer resections. The key point of our approach is the expanded forehead flap for skin coverage. Reconstruction is completed by cartilage grafts to restore nasal framework and to shape nasal tip. Ancillary procedures were needed in some cases to optimize aesthetic outcomes. RESULTS: Twenty-one patients completed the multistage nasal reconstruction. The RFF flap was used in 56% of the cases (n = 11), while the ALT flap was used in 44% (n = 10) of our case series. No difference has been detected in the number of reconstructive stages required to achieve the final result comparing RFF and ALT reconstruction (3.3 vs. 3.1 reconstructive steps). Ancillary procedures were performed in 7 patients. CONCLUSION: Microvascular tissue transfer plays a key role in full-thickness nasal defects restoration. Comparing the two groups, both the RFF and ALT are effective and reliable options in lining reconstruction, although with different indications. Expanded forehead flap, combined to free cartilage graft, is our gold standard to provide external skin coverage to rebuild the nasal framework. According to our current approach, accurate preoperative planning, supported by modern technologic tools, multistage reconstruction, and ancillary procedures are useful to accomplish satisfactory functional and aesthetic outcomes.

Different Hydraulic Constructs to Optimize the Venous Drainage of DIEP Flaps in Breast Reconstruction: Decisional Algorithm and Review of the Literature.

BACKGROUND: Venous congestion is the most common perfusion-related complication of deep inferior epigastric artery perforator (DIEP) flap. Several hydraulic constructs can be created for venous superdrainage in case of flap venous engorgement or as a preventive measure. These can be classified based on the choice of the draining vein of the flap, either a second deep inferior epigastric vein (DIEV) or a superficial inferior epigastric vein (SIEV), and of the recipient vein, either a vein of the chest or the DIEV. METHODS: We conducted a comprehensive systematic literature review in Medline, Scopus, EMBASE, Cochrane Library, and Google Scholar to find publications that reported on venous congestion in DIEP flap. The keywords used were DIEP Flap, breast reconstruction, venous congestion, supercharging, superdrainage, SIEV, and DIEV. RESULTS: Based on the studies found in the literature, we developed an algorithm to guide the surgeon's decision when choosing the veins for the superdrainage anastomosis. CONCLUSION: Several alternatives for venous anastomosis in superdrainage are available. We propose an algorithm to simplify the choice. The use of the ipsilateral SIEV to be connected to a vein of the chest appears to be advantageous. The anatomical position that allows the easiest anastomosis dictates which chest vein to favor.

Chest Wall Masculinization in Female-to-Male Transsexuals: Our Treatment Algorithm and Life Satisfaction Questionnaire.

Esthetic masculinization of the chest wall is one of the first surgical steps in female-to-male transsexual (FTMTS) reassignment.This surgical procedure is not a simple mastectomy: it is required for removal of breast tissue with glandular resection and skin excess revision, to reduce and replace the nipple-areola complex in the right location, minimizing chest wall scars. The creation of an esthetically pleasing male chest allows the patient to live at ease in the male gender role.In this article, we present our series of 68 FTMTSs who underwent bilateral mastectomies for surgical sexual reassignment (a total of 136 mastectomies) according to our algorithm, in the period between January 2010 and December 2017. We selected 4 different operative procedures, classified as subcutaneous ("pull-through" and "concentric circular" techniques) and skin extended ("ultrathin vertical bipedicle" and free nipple graft).We achieved a total complication rate of 6.6%, less than that reported in the literature; additional procedures for esthetic improvements were performed in 14.7% of cases. The mean patient satisfaction was approximately 4.57% of a maximal value of 5 (excellent).To help surgeons in choosing the most appropriate FTMTS surgical technique and to reduce unfavorable results, we propose the use of our treatment algorithm in preoperative evaluation of the chest wall according to the breast volume, degree of glandular ptosis, and skin elasticity.

A field screening test for the assessment of concentrations and mobility of potentially toxic elements in soils: a case study on urban soils from Rome and Novi Sad.

The increasing demand for environmental pollution control results in the development and use of new procedures for the determination of dangerous chemicals. Simple screening methods, which can be used directly in the field for a preliminary assessment of soil contamination, seem to be extremely advantageous. In our laboratory, we developed and optimized a rapid test for a preliminary evaluation of both the concentration and the mobility of some potentially toxic metals in soils. This screening test consists of a single extraction of the soil sample with a buffer solution, followed by the titration of the extracted solution with dithizone to determine the contents of bi-valent heavy metals (such as Pb, Cu, Zn, and Cd). This screening method was then directly applied in the field during the sampling campaign in the framework of an Italian-Serbian collaborative project, finalized in the study of metal availability in soils. The results obtained in the field with the rapid test were compared with those obtained in the laboratory following the conventional procedure commonly used to evaluate metal bioavailability (diethylenetriaminepentaacetic extraction). Moreover, selected samples were analyzed sequentially in the laboratory using the standardized BCR three-step sequential extraction procedure. The screening test gave results conceptually in good agreement with those obtained via the BCR procedure. These preliminary data show that the proposed screening test is a reliable method for the preliminary rapid evaluation of metal total concentrations and of potential metal mobility in soils, supporting sampling activities directly in the field.

Reconstruction of a complex pelvic perineal defect with pedicled anterolateral thigh flap combined with bilateral lotus petal flap: a case report.

Reconstructing extensive perineal defects represents a challenge, and reconstructive choice requires a careful physical assessment of previous radiotherapy, pre-existing scars, the presence of stomas, and the availability of donor sites. We report a case of a patient affected by an anal carcinoma who underwent a pelvic exenteration and bilateral inguinal iliac obturator lymph node dissection. We performed a pedicled anterolateral thigh flap (ALT) combined with bilateral lotus petal flaps (LPF) to reconstruct the pelvic-perineal area. The result was good, and no major post-operative complications were reported. Bilateral LPF, combined with a pedicled ALT, may represent a valid option in pelvic-perineal reconstruction following a wide oncological resection.

Modified bilobed flap for one-stage earlobe reconstruction: a case report.

Many techniques have been described in the literature for the reconstruction of congenital or acquired defects of the earlobe. Most techniques for earlobe reconstruction use adjacent tissue to compose a pedicled or bilobed flap, but usually require a two-stage procedure, or need a skin graft; more rarely reconstructive methods that led to a satisfactory result and a pleasant appearance in one-stage procedure have been described. We describe a personal and geometrical modification of the double-lobed flap according to Gavello's original technique, which allows to shape the anatomical curvature of the earlobe and to reduce the skin retraction without adding any scars or skin graft. In our opinion, the revisited reconstructive technique provides lots of advantages, improves aesthetical results and provides more natural appearance.

Microsurgical Reconstruction with and without Microvascular Anastomosis of Oncological Defects of the Upper Limb.

INTRODUCTION: The choice of the most adequate surgical technique for upper limb defects remains challenging. The aim of this article is to discuss the main microsurgical (pedicled or free) reconstructive options for the post-oncological reconstruction of different anatomical areas of the upper extremity. MATERIALS AND METHODS: We reviewed different reconstructive methods reported in the literature needing microsurgical expertise and compared them to our clinical experience, in order to provide further guidance in the choice of different flaps for upper limb soft tissue reconstruction. Six clinical cases, one for each anatomical district, are presented as examples of possible solutions. RESULTS: We report the options available in the literature for post-oncologic upper limb reconstruction, dividing them by anatomical area and type of flap: local flaps, regional flaps, free flaps, and distant pedicled flaps. Our examples of the reconstruction of each anatomical area of the upper limb include one reverse ulnar pedicled perforator flap, one free Antero-Lateral Thigh (ALT) flow-through flap, one perforator-based lateral arm flap, two myocutaneous latissimus dorsi pedicled flaps, and one parascapular perforator-plus flap. CONCLUSIONS: In oncological cases, it is important to consider reconstructive options that provide stable tissue and allow for the early healing of the donor and recipient site if the patient needs to undergo adjuvant radiotherapy or chemotherapy. A wider range of flap options is essential when choosing the proper technique according to the patient's needs, surgeon's preference, and logistical possibilities. Perforator flaps combine the advantages of other flaps, but they require microsurgical expertise. Free flap reconstruction remains the gold standard to obtain a better overall and cosmetic outcome in complex and wide defects, where no suitable local pedicled flap option exists. The pedicled latissimus dorsi flap should still be included among the reconstructive options for its strong vascularization, size, and arc of transposition.

Comparison between stem cells harvested from wet and dry lipoaspirates.

Adipose-derived stem cells (ASC) are usually isolated from lipoaspirates, but it is not known if the anesthetic solution injected into adipose tissue affects cell yield and functions. Two different samples were drawn from the abdominal region of female subjects. In the first, a physiological solution containing lidocaine/adrenaline was injected (wet liposuction, WL), while in the contralateral area, the sample was collected without injecting any solution (dry liposuction, DL). The aspirates were processed to investigate the yield of the stromal-vascular fraction (SVF) cells and ASC frequency, growth rate, apoptosis, and differentiation potential. The solid dried mass of fresh WL isolates was lower than that of DL isolates (p < 0.01) due to the presence, in the former, of a liquid solution. As a consequence, the amount of WL-SVF cells was 18.7% lower than those obtained from DL (p < 0.01); this difference was also observed under culture conditions. In addition, the number of colony-forming unit-fibroblasts (CFU-Fs) obtained from 1 × 10(3) SVF cells was 25.5% lower in WL-aspirates than DL-aspirates (p < 0.05) owing, at least in part, to the observed presence of ASC [corrected] in the liquid solution of the WL isolates. After WL and DL, no differences were observed in ASC growth rate, apoptosis, or differentiation potential toward adipogenic, osteogenic, and endothelial cell lineages. In conclusion, WL yields about 40% fewer ASC than DL due to the combined effect of tissue dilution and the reduced frequency of ASC in the SVF. The main biological features of ASC are suitable for cell-based therapies.

Tensor fascia latae perforator flap: An alternative reconstructive choice for anterolateral thigh flap when no sizable skin perforator is available.

INTRODUCTION: The anterolateral thigh flap (ALT) is a versatile flap and very useful for the reconstruction of different anatomical districts. The main disadvantage of this flap is the anatomical variability in number and location of perforators. In general, absence of perforators is extremely rare. In literature, it is reported to be from 0.89% to 5.4%. If no sizable perforators are found, an alternative reconstructive strategy must be considered. Tensor fascia lata (TFL) perforator flap can be a good alternative in these cases: Perforator vessels are always present, the anatomy is more constant and it is possible to harvest it through the same surgical access. The skin island of the flap can be very large and can be thinned removing a large part of the muscle allowing its use for almost the same indications of the ALT flap. MATERIALS AND METHODS: We report 11 cases of reconstruction firstly planned with the ALT flap, then converted into TFL perforator flap. RESULTS AND CONCLUSION: The result was always satisfactory in terms of the donor site morbidity and reconstructive outcome.

Nanodiamond Influence on the Nucleation and Growth of YBCO Superconducting Film Deposited by Metal-Organic Decomposition.

It was recently shown that the introduction of nanodiamond (ND) into a superconducting metal-organic deposited YBa2Cu3O7-δ (YBCO) film produces an increase in critical current density in self-field conditions (B = 0 T). Such improvement appears to be due to the formation of denser and smoother films than the samples deposited without ND. This paper presents the work done to understand the role of ND during YBCO nucleation and growth. A detailed study on YBCO+ND films quenched at different temperatures of the crystallization process was carried out. Results showed that the reaction responsible for YBCO production appeared effectively affected by ND. In particular, ND stabilizes one of the YBCO precursors, BaF2(1-x)Ox, whose conversion into YBCO requires a prolonged time. Therefore, the YBCO nucleation is slowed down by ND and begins when the experimental conditions favor both thermodynamically and kinetically the formation of YBCO along the c-axis. This effect has important implications because the growth of a highly epitaxial c-axis YBCO film enables excellent superconducting performance.

Radial forearm flap versus antero-lateral thigh flap in oral soft tissue reconstruction: update and statistical analysis on our 77 consecutive cases for an objective selection criteria.

BACKGROUND AND AIM: The radial forearm free flap (RFFf) and the antero-lateral thigh flap (ALTf) are considered the "key flaps" for oral cavity reconstruction. Nowadays, the literature lacks of an objective and standardized decision-making algorithm for the flap choice. The aim of this study is to describe a decision-making algorithm concerning the more appropriate flap, RFFf or ALTf, in the reconstruction of intra-oral soft tissues based on the volumetric analysis of the defect with a pre-operative Magnetic Resonance Imaging (MRI), updating our previous surgical experience. METHODS: We conducted a retrospective observational study including 77 patients who underwent microsurgical reconstruction with RFFf or ALTf after tumor resection of the soft tissues in the oral cavity. During follow-up, patients were evaluated using the UW-QOL questionnaire. RESULTS: Analyzing the scores of the UW-QOL questionnaire based on the size of the tumor on preoperative MRI we found that for tumor volume <50cc and between 50-70cc, the patients reconstructed with RFFfobtained statistically significant better scores compared to the ALTf group, while for tumor volume >70cc, the patients reconstructed with ALTf reported statistically significant better scores. CONCLUSIONS: Pre-operative RMI-guided volumetric assessment of oral cancer plays a key role in the planning of adequate soft tissue reconstruction and can objectively help surgeons in the correct choice of the flap (RFFf vs. ALTf) for each case based on preoperative tumor size, suggesting for defects <50cc and between 50 and 70 cc a reconstruction with RFFf, while for defects >70cc a reconstruction with ALTf.

Adipose-derived stromal vascular fraction (SVF) for the treatment of androgenic alopecia (AGA): a systematic review.

BACKGROUND AND AIM: Androgenetic alopecia (AGA) is a common chronic, hereditary, cutaneous and androgen-dependent condition. Low self-esteem and negatively impact quality of life are often consequences of AGA. Clinical treatment of AGA using SVF (Stromal vascular fraction) has been effective. In fact, hair follicle is affected by various environment factors and one of the most important factors is the vascularity of the scalp which is itself affected bySVF. METHODS: During October 2022 we carried out a systematic review to identify all scientific publications discussing about hair loss treatment with stromal vascular fraction or adipose stem cell. We selected 140 articles. After screening process, we kept 9 articles complying with inclusion criteria.  Results: No serious adverse events were reported in all studies. Despite standardized protocol was not found, all studies reported a statistically significant increase in the number (density) of hair after SVF treatment. Two studies found a significant improvement at pull test. An increase of hair diameter was noticed after treatment. The combination between medical therapy and SVF proved to be advantageous. CONCLUSIONS: SVF is nowadays at the center of studies in the field of regenerative medicine due to its potential applications in many branches of medicine and surgery. The initial results are very promising but furthermore studies are necessary to establish a methodical and systematic research capable of demonstrating its real benefits and the creation of homogenous treatment protocols.

Role of Autologous Fat Grafting in the Conservative Treatment of Fecal Incontinence in Children.

Treatment of organic fecal incontinence in children, typical of anorectal malformations, is most often conservative; however, when necessary, it can be surgical. Autologous fat grafting, or lipofilling, can be used to improve fecal incontinence. We present our experience with the echo-assisted anal-lipofilling and its effects on fecal incontinence in children and on the quality of life of the entire family. Under general anesthesia, fat tissue was harvested according to the traditional technique, and processed in a closed system Lipogems® set. Injection of the processed adipose tissue was guided by trans-anal ultrasound assistance. Ultrasound and manometry were also used for follow-up. From November 2018, we performed 12 anal-lipofilling procedures in six male patients (mean age 10.7 years). Five children had a stable improvement in bowel function with Krickenbeck's scale scores going from soiling grade 3 pre-treatment in 100% of children to grade 1 post-treatment in 75% of them. No major post-operative complications developed. An increase in thickness of the sphincteric apparatus was shown at ultrasound during follow-up. The quality of life of the entire family, evaluated with a questionnaire, improved after the surgical treatment of the children. Anal-lipofilling is a safe and effective procedure to reduce organic fecal incontinence thereby benefiting both the patients and their families.

Folded Radial Forearm Free Flap for the Reconstruction of Total Soft Palate Defects: Operative Technique.

The surgical plan to reconstruct the palate must be carefully prepared given the morphological peculiarity of the soft palate forming both the roof of the mouth and the floor of the nasal cavity. This article focuses on the use of folded radial forearm free flaps to manage isolated defects of the soft palate in the absence of tonsillar pillar involvement. Methods: Three patients affected by squamous cell carcinoma of the palate underwent resection of the soft palate and immediate reconstruction with a folded radial forearm free flap. Results: All three patients showed good short-term morphological-functional outcomes as far as swallowing, breathing, and phonation were concerned. Conclusions: The folded radial forearm free flap seems to be an efficacious way to manage localized defects of the soft palate, given the positive outcomes of the three patients treated, and in accordance with other authors. In general, the radial forearm free flap was confirmed to be a versatile solution for those intraoral defects of the soft tissue requiring a limited quantity of volume as in the case of the soft palate.

Altered pathways of keratinization, extracellular matrix generation, angiogenesis, and stromal stem cells proliferation in patients with systemic sclerosis.

Objective: Systemic sclerosis is characterized by endothelial dysfunction, autoimmunity abnormalities, and fibrosis of the skin and internal organs. The pathogenetic mechanisms underlying systemic sclerosis vasculopathy are still not clarified. A complex cellular and extracellular network of interactions has been studied, but it is currently unclear what drives the activation of fibroblasts/myofibroblasts and the extracellular matrix deposition. Methods: Using RNA sequencing, the aim of the work was to identify potential functional pathways implied in systemic sclerosis pathogenesis and markers of endothelial dysfunction and fibrosis in systemic sclerosis patients. RNA-sequencing analysis was performed on RNA obtained from biopsies from three systemic sclerosis patients and three healthy controls enrolled in our University Hospital. RNA was used to generate sequencing libraries that were sequenced according to proper transcriptomic analyses. Subsequently, we performed gene set enrichment analysis of differentially expressed genes on the entire list of genes that compose the RNA-sequencing expression matrix. Results: Gene set enrichment analysis revealed that healthy controls were characterized by gene signatures related to stromal stem cells proliferation, cytokine-cytokine receptor interaction, macrophage-enriched metabolic network, whereas systemic sclerosis tissues were enriched in signatures associated with keratinization, cornification, retinoblastoma 1 and tumor suppressor 53 signaling. Conclusion: According to our data, RNA-sequencing and pathway analysis revealed that systemic sclerosis subjects display a discrete pattern of gene expression associated with keratinization, extracellular matrix generation, and negative regulation of angiogenesis and stromal stem cells proliferation. Further analysis on larger numbers of patients is needed; however, our findings provide an interesting framework for the development of biomarkers useful to explore potential future therapeutic approaches.