A Novel Skin Splint for Accurately Mapping Dermal Remodeling and Epithelialization During Wound Healing.

The mouse excisional dorsal full-thickness wound model with a silicon splint fixed on the skin has been widely used to mimic human wound healing. However, the method cannot accurately quantify dermal remodeling, since the initial point of epithelialization on the wound surface is unclear. To overcome this limitation, we have developed a novel mouse excisional wound model to assess the degree of epithelial extension and regeneration, using a plastic ring-shaped splint fixed beneath the surrounding epidermal tissue. At the end of the experiment, tissue samples were fixed in formalin, the splint was excised, and paraffin sections were prepared. Splint holes, corresponding to the prior location of the splint, were evident on the tissue cross-sections, and the epidermis above the holes was considered the initial excision site. The epidermal contraction and epithelial regeneration, as independent essential tissue alterations in wound healing, could be distinguishable and quantified. Compared with previous splint models, this method provides an accurate evaluation of epidermal processes in wound healing, and can be a platform to assess the effects of various wound healing factors. J. Cell. Physiol. 232: 1225-1232, 2017. © 2016 Wiley Periodicals, Inc.

The Selective Centrifugation Ensures a Better In Vitro Isolation of ASCs and Restores a Soft Tissue Regeneration In Vivo.

Autologous fat grafting procedures in plastic surgery have been extensively used to reinforce soft tissue in congenital or acquired tissue impairments. With this background, the aim of this study is firstly to examine the impact of a selective centrifugation on existing adipose stem cells (ASCs) in terms of stemness profile maintenance and, secondly, to investigate the effect of restoring volume in reconstruction on patients affected by soft tissue damage. After centrifugation, the fat graft products were separated into two layers and subsequently examined in vitro for the expression of CD34, CD90, CD117, CD105, CD29, CD31, CD44, CD73, CD133, CD14 and CD45 markers by flow cytometry and gene expression analyses were performed for Sox2, WNT3A, END, CD44, FUT4, COLL1, CTNNB1, hbEGF, KRTLG, MMP2 and VIM genes. The results showed that in the middle-high density (MHD) layer there was a peak concentration of ASCs, compared to another layer obtained after centrifugation. Research carried out on patients under treatment for soft tissue regeneration using cells obtained from MHD layer selection will be fundamental in comparative analysis. These studies will lead to an adequate standardization of outcomes, provided that treatment is performed through cell selection. Therefore, a unique procedure in tissue reconstruction and regeneration through fat grafting is presented here.

Tumor Microenvironment Versus Cancer Stem Cells in Cholangiocarcinoma: Synergistic Effects?

Cholangiocarcinoma (CCAs) may be defined as tumors that derived from the biliary tree with the differentiation in the biliary epithelial cells. This tumor is malignant, extremely aggressive with a poor prognosis. It can be treated surgically and its pathogenesis is poorly understood. The tumor microenvironment (TME) is a very important factor in the regulation of tumor angiogenesis, invasion, and metastasis. Besides cancer stem cells (CSCs) can modulate tumor growth, stroma formation, and migratory capability. The initial stage of tumorigenesis is characterized by genetic mutations and epigenetic alterations due to intrinsic factors which lead to the generation of oncogenes thus inducing tumorigenesis. CSCs may result from precancerous stem cells, cell de-differentiation, normal stem cells, or an epithelial-mesenchymal transition (EMT). CSCs have been found in the cancer niche, and EMT may occur early within the tumor microenvironment. Previous studies have demonstrated evidence of cholangiocarcinoma stem cells (CD133, CD24, EpCAM, CD44, and others) and the presence of these markers has been associated with malignant potential. The interaction between TME and cholangiocarcinoma stem cells via signaling mediators may create an environment that accommodates tumor growth, yielding resistance to cytotoxic insults (chemotherarapeutic). While progress has been made in the understanding of the mechanisms, the interactions in the tumorigenic process still remain a major challenge. Our review, addresses recent concepts of TME-CSCs interaction and will emphasize the importance of early detection with the use of novel diagnostic mechanisms such as CCA-CSC biomarkers and the importance of tumor stroma to define new treatments. J. Cell. Physiol. 231: 768-776, 2016. © 2015 Wiley Periodicals, Inc.

Modified fish-incision technique in brachioplasty: a surgical approach to correct excess skin and fat of the upper arm (restoring the armpit contour).

UNLABELLED: Brachial ptosis is one of the consequences of massive weight loss. At an early stage, brachial ptosis can be corrected by liposuction, dermolipectomy and liposuction, or minibrachioplasty while the most advanced stage requires extended brachioplasty. Since brachioplasty was first described, various techniques have been proposed in the management of upper extremity contour deformities. Modifications to the original technique were mainly made to shape arm contour, to obtain good morphological reconstruction with attention directed toward improving and refining the resulting scar. We describe a modified approach to the "fish incision" technique defining a preoperative marking procedure that permits the reduction of overcorrection problems to reshape and improve the contour of the armpit with camouflage of scar sequelae. Our modifications to the original technique focus on incision placement along the medial bicipital groove and armpit, based on the the drawings of the tails following dynamic lines of the armpit contour established by the underlying muscles. We drew the tails slightly with a 60° angle between the tails and the width depending on patient's arm contour and on the excess of the skin in the armpit to be removed. The modified technique has obtained satisfactory results for patients and may be considered as a new surgical approach in the management of brachial ptosis. 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.

Study of a Subcutaneous Lesion of the Shoulder: The Saint Paolino Tumor.

In certain small counties in southern Italy, traditional Catholic festivals are observed by erecting tall, large, and weighty wagons referred to as "lilies." These wagons are borne on the shoulders of several individuals known as "cradles." This practice has given rise to the emergence of a distinct subcutaneous neoformation on the shoulder. This study investigates the unique clinical and anatomopathological attributes of "Saint Paolino tumor" (named in honor of the Catholic patron of the widely celebrated lilies festival). This tumor presents as a posttraumatic intermittent chronic lesion occurring on the shoulder, necessitating differential diagnosis from other cutaneous and soft tissue lesions such as spontaneous lipomas, elastofibroma, Madelung disease, and liposarcoma.

Human adipose CD34+ CD90+ stem cells and collagen scaffold constructs grafted in vivo fabricate loose connective and adipose tissues.

Stem cell based therapies for the repair and regeneration of various tissues are of great interest for a high number of diseases. Adult stem cells, instead, are more available, abundant and harvested with minimally invasive procedures. In particular, mesenchymal stem cells (MSCs) are multi-potent progenitors, able to differentiate into bone, cartilage, and adipose tissues. Human adult adipose tissue seems to be the most abundant source of MSCs and, due to its easy accessibility; it is able to give a considerable amount of stem cells. In this study, we selected MSCs co-expressing CD34 and CD90 from adipose tissue. This stem cell population displayed higher proliferative capacity than CD34(-) CD90(-) cells and was able to differentiate in vitro into adipocytes (PPARγ(+) and adiponectin(+)) and endothelial cells (CD31(+) VEGF(+) Flk1(+)). In addition, in methylcellulose without VEGF, it formed a vascular network. The aim of this study was to investigate differentiation potential of human adipose CD34(+) /CD90(+) stem cells loaded onto commercial collagen sponges already used in clinical practice (Gingistat) both in vitro and in vivo. The results of this study clearly demonstrate that human adult adipose and loose connective tissues can be obtained in vivo, highlighting that CD34(+) /CD90 ASCs are extremely useful for regenerative medicine.

Antibiotics in Dentistry: A Narrative Review of the Evidence beyond the Myth.

Antibiotics have undoubtedly revolutionized medicine and the health and survival of patients with life-threatening infections, being nonetheless free from potential adverse effects, and the risk of intestinal dysbiosis, antimicrobial resistance, and the resulting consequences for the patient's health and the public purse. The present study narratively reviewed the epidemiological data on worldwide antibiotic consumption and administration in dental practice, patients' adherence to prescriptions, the antimicrobial resistance phenomenon in dentistry, and the evidence supporting and recommending appropriate antibiotic use in dental care. Eligible systematic reviews and original studies in humans published in the English language from January 2000 to 26 January 2023 were considered. A total of 78 studies, 47 on the epidemiology of antibiotic use and prescription in dentistry, 6 on antibiotic therapy in dentistry, 12 on antibiotic prophylaxis in dentistry, 0 on adherence of dental patients to antibiotic prescription, and 13 on antimicrobial resistance in dentistry, were presently considered. Retrieved evidence revealed that antibiotics are frequently overused and misused in dental practice, dental patients frequently do not adhere to prescriptions, and antimicrobial resistance in dentistry is a still rising phenomenon also secondary to improper oral antiseptics use. The present findings highlighted the need to establish more evidence-based and accurate antibiotic prescriptions to sensitize dentists and dental patients to minimize and rationalize the use of antibiotics only when it is indicated and necessary, improve patients' adherence, and enhance knowledge and awareness of the antimicrobial resistance in dentistry.

An Unconventional Oral Candidiasis in an Immunocompetent Patient.

Oral candidiasis (OC) is an opportunistic fungal infection of the oral mucosae, sustained by Candida albicans or other non-albican Candida species (NAC), usually eradicated by conventional antifungals of the classes of azoles, polyenes, or derivative from echinocandins. OC usually occurs under predisposing local or systemic factors. C. lusitaniae is an opportunistic strain that is rarely responsible for human infection and occurs mainly in severe immunocompromised states. The present work reported an unconventional case of OC in an otherwise healthy immunocompetent woman sustained by C. lusitaniae and a multi-resistant strain of C. albicans.

Nuck Cyst Presenting as a Recidive Inguinal Hernia: A Rare Case Treated in Plastic Surgery.

The canal of Nuck is the female equivalent to the male processus vaginalis. Due to its rarity and the lack of awareness among physicians, a cyst in the canal of Nuck is a seldom-encountered entity in clinical practice and is commonly misdiagnosed. We report on a case of 42-year-old woman who presented with a painful swelling at her right groin and skin hypertrophy of the abdomen. The patient underwent successful open herniorrhaphy with excision of the cyst and mesh repair of the inguinal canal. The results were excellent both in the aesthetic and functional terms. In 1 month, there was a complete recovery with a return to social life. The 3-month healing score was 3 of 13 on the Vancouver Scar Scale. The technique is effective and reproducible. The patient's aesthetic and functional outcomes were excellent. In the following 6 months of follow-up, there were no recurrences or late complications.

Successful Treatment of Wound Dehiscence by Innovative Type 1 Collagen Flowable Gel: A Case Report.

The growing demand for postbariatric body-contouring surgery after massive weight loss goes hand-in-hand with an increase in wound complications. Consequently, surgical reoperation or conservative management is necessary and represents a difficult challenge to healthcare professionals. Moreover, it is well known that postbariatric patients present aberrant wound healing due to multifactorial causes, such as preoperative illness, nutritional deficiencies, and vascular disease. To treat such complex wounds, several methods have been recommended, such as the use of negative pressure wound therapy, tissue-engineered skin substitutes, and collagen-based wound dressings. The case presented here is of a patient with deep wound dehiscence of the inner left thigh, 1 week after a medial thigh lift procedure, successfully managed with Vergenix Flowable Gel, a human recombinant type I collagen produced in plants. After 2 weeks of treatment, wound dehiscence was replaced with granulation tissue, and after 4 weeks, the patient was completely healed, with an acceptable aesthetic outcome of the surgical scar.

COVID-19 Related Information on Pediatric Dental Care including the Use of Teledentistry: A Narrative Review.

In addition to the direct impact of the SARS-CoV-2 infection, the COVID-19 pandemic reports multiple effects on people's health and psycho-physical well-being. In the dental field, oral hygiene sessions, regular dental check-ups, and aerosol-generating procedures were commonly postponed, thus resulting in repercussions on oral health also favored by the changing eating and oral hygiene habits during the multiple lockdowns. Furthermore, dental settings and practices were generally perceived as at high risk for SARS-CoV-2 transmission, thus unsafe, and by general and pediatric dentists themselves. Last, the consequences of stress related to deprivation of social life and playful activities should not be underestimated in children, exposing them to the deleterious effects of bad oral habits, with repercussions on the balanced growth and development of the stomatognathic system. The present work intends to analyze the medium-term and long-term impact of COVID-19 on pediatric oral and dental care provision, reviewing pediatric dentistry practice and oral and dental needs of pedodontics patients during the first peak and the various waves of the COVID-19 pandemic, and lessons learned.

Effects of a new centrifugation method on adipose cell viability for autologous fat grafting.

The use of adipose tissue transfer in plastic and reconstructive surgery is not new and has been studied extensively. Due to different results with regard to adipose cell damage and the level of survival of the transferred tissue in clinical practice, the authors aimed to investigate the effects of centrifugation on fat aspirates to optimize the centrifugal force for fat transplantation and to obtain an increased number of intact adipose progenitor cells. The following different centrifugation forces were evaluated in vitro in terms of fat decantation: 3,000 rpm (1,500×g), 1,300 rpm (250×g), and 500 rpm (50×g). Moreover, the density level, morphology of fat cells, cell viability, and progenitor cell number also were evaluated. Centrifugation leads to a good fat tissue density, with a significant number of progenitor cells, and efficiently removes the liquid portion. High centrifugal forces (at 3,000 rpm) caused significant damage to fat cells with low cell viability, whereas very low centrifugal forces (at 500 rpm) showed little effect on adipose tissue density, resembling fat decantation. Fat aspirates, withdrawn from 30 healthy donors in vivo, were centrifuged at different rotations per minute (rpm), as follows. For the 10 patients in group A, Coleman's technique was used with a centrifugation of the aspirated fat at 3,000 rpm (1,500×g) for 3 min. For the 10 patients in group B, the authors' technique was used, with centrifugation of the aspirated fat at 1,300 rpm (250×g) for 5 min. For the 10 patients in group C, simple decantation of fat was used. In conclusion, a centrifugal force of 1,300 rpm resulted in better density of adipose tissue, with good cell viability and increased ability to preserve a significant number of progenitor cells.

Large single cutaneous metastasis of colon adenocarcinoma mimicking a squamous cell carcinoma of the skin: A case report.

INTRODUCTION: Metastases represent one of the most outstanding characteristics of malignant neoplasms and are relatively rare in the skin, in spite of the great extension of the cutaneous organs. Development of cutaneous metastases from colon cancer is a rare event, usually occurring in widely disseminated disease and commonly leading to a poor prognosis. As to location, cutaneous metastases often favor areas close to the primary malignancy, such as lung cancer and skin metastases on the trunk. However, remote sites as the scalp may be also involved. CASE PRESENTATION: We present the case of a 92-year-old female patient with a massive single nodular skin lesion on her left supraclavicular area, that came back positive for cutaneous metastasis of colon adenocarcinoma. DISCUSSION: Cutaneous metastasis of colorectal cancer a rare event (2.3%-6%) that usually occur two years after the detection or resection of the primary tumor. It seldom occurs before the identification of the primary tumor and involvement of secondary organs, such as the liver. There are few cases reported with only cutaneous metastases. CONCLUSION: In conclusion, dermatological evaluation of patients who are undergoing screening or who have already been diagnosed with cancer is extremely important.

Limberg fasciocutaneous transposition flap for the coverage of an exposed hip implant in a patient affected by ewing sarcoma.

INTRODUCTION: Hemipelvectomy with immediate reconstruction with prosthetic devices for the surgical treatment of malignant tumors is an invasive procedure with many possible complications such as wound breakdown, seroma, hematoma and infection.The treatment of an exposed hip implant in these cluster of patient is extremely challenging and the literature shows how negative pressure wound therapy and myocutaneous, both pedicled and free, flaps are workhorses in these situations. CASE REPORT: In this paper we report a successful coverage of exposed prosthetic hip implant with a local fasciocutaneous flap in a patient in which any other kind of reconstruction was not feasible. DISCUSSION: Fasciocutaneous flaps can be considered as an easily performed and minimally invasive surgical procedure, particularly reliable even in patients in poor general conditions, with preservation of future flap options.

Aggressiveness pattern and second primary tumor risk associated with basaloid squamous cell carcinoma of the larynx.

Basaloid squamous cell carcinoma (BSCC) is a rare, aggressive and distinct variant of squamous cell carcinoma (SCC) of the upper respiratory and digestive tract. We have evaluated disease specific survival (DSS) and overall survival (OS) through Kaplan-Meier method and mortality risk through univariate statistical analysis of Cox in 42 cases of BSCC and other 42 of laryngeal SCC (LSCC) matched for both age and sex. We demonstrated that laryngeal BSCC is a more aggressive tumor than LSCC as is associated to higher nodal recurrence of pathology (5 vs 2 patients, overall risk, OR 2.7), a reduced survival (median survival 34 vs 40 months, OR 3.2 for mortality); in addition, basaloid patients have a higher risk to be affected by second primary tumors (13 vs 3 patients, OR 5.8) and a higher probability to die for this second tumor (Hazard Risk, HR 4.4). The analysis of survival shows an increased mortality risk concurrent with the parameters assessed by univariate analyses that assume a predictive and statistical significance in second tumor and grading in basaloid LSSC.

An innovative regenerative treatment of scars with dermal micrografts.

BACKGROUND: Pathological scars occur following injuries and are often considered esthetically unattractive. Several strategies have been attempted to improve these types of scars using both surgical and nonsurgical methods. The most common treatments include cryotherapy, intralesional corticosteroid injections, 5-fluorouracil, bleomycin, interferon, and verapamil. AIMS: In this study, we aim to investigate the effectiveness of dermal autologous micrografts in the treatment of pathological scars resulting from burns, trauma, or any iatrogenic source. METHODS: We used a new clinical practice called Rigenera Protocol to obtain autologous micrografts which were in turn injectable in the patients. RESULTS: A significant improvement was observed in appearance and texture of the exaggerated scars in all cases following already 4 months of autologous micrograft treatment We have also shown that these micrografts are composed of mesenchymal stem cells and in addition, histological evaluation verified restoration of the structural layers immediately below the epidermis and a horizontal realignment of collagen fibers in the papillary dermis. CONCLUSION: Our results clearly demonstrate the optimal outcomes obtained following treatment with dermal micrografts on exaggerated scars with different etiologies. However, further studies are required to confirm the efficacy of this new technique.

The role of adipose stem cells in inflammatory bowel disease: From biology to novel therapeutic strategies.

Inflammatory bowel diseases are an increasing phenomenon in western countries and in growing populations. The physiopathology of these conditions is linked to intestinal stem cells homeostasis and regenerative potential in a chronic inflammatory microenvironment. Patients with IBD present an increased risk of developing colorectal cancer (CRC), or colitis associated cancer (CAC). Conventional treatment for IBD target the inflammatory process (and include anti-inflammatory and immunosuppressive drugs) with biological agents emerging as a therapeutic approach for non-responders to traditional therapy. Conventional treatment provides scarce results and present severe complications. The intestinal environment may host incoming stem cells, able to engraft in the epithelial damaged sites and differentiate. Therefore, stem cell therapies represent an emerging alternative in inflammatory bowel diseases, with current investigations on the use of haematopoietic and mesenchymal stem cells, in particular adipose stem cells, apparently fundamental as regenerators and as immune-modulators. Here, we discuss stem cells in intestinal homeostasis and as therapeutic agents for the treatment of inflammatory bowel diseases.

From Inflammation to Cancer in Inflammatory Bowel Disease: Molecular Perspectives.

Inflammatory bowel diseases (IBD) are associated with an increased risk of colitis-associated colorectal carcinoma (CAC). CAC is one of the most important causes of morbidity and mortality in patients with Crohn's disease and ulcerative colitis. The aim of the present review was to discuss the most important signaling pathways and genetic alterations involved in carcinogenesis related to IBD, focusing on the molecular aspects of cancer stem cell physiology and the impact of the inflammatory microenvironment. Molecular mechanisms involved in CAC development differ from those in sporadic colorectal cancer, reflecting the prominent role of inflammation-induced carcinogenesis in the development of CAC. The alteration of the physiological microenvironment is thought to be responsible for the initiation of carcinogenesis in IBD. Furthermore, cancer stem cells seem to have a fundamental role in the generation and growth of CAC. We also address prevention and treatment modalities of CAC and its involvement in IBD.

Persistence of CD34 Stem Marker in Human Lipoma: Searching for Cancer Stem Cells.

BACKGROUND: Lipomas are benign solid tumours that develop in soft tissues with origin in mesenchymal progenitors. Macroscopically, they appear as soft-elastic nodules, varying in volume from a few millimiters to several centimetres and can enlarge progressively. Although they are usually asymptomatic, they can cause symptoms due to nerve or vessel compression. Microscopically they appear as fibrous connective tissue stroma with embedded adipocytes, and absence of inflammation. Up to now no characterisation of stem cell population present in this tissue has been performed. METHODS: Cytofluorimetric, biological and molecular biology analyses have been performed in order to test superficial cell markers and gene expression profile related to stemness and apoptotic activity of cells present in lipoma tissues compared to those of adipose tissue's cells. RESULTS: Our results confirmed that CD34(+) cells in lipoma were present around small adipocytes, showing several altered biological activity such as proliferation, apoptotis and stemness. CONCLUSIONS: The data emerging from the comparison of the lipoma cells and normal adipose tissue, suggests the presence of cell precursors involved in the development of the lipoma. This hypothesis requires further investigation and may indicate new thresholds in the study of benign tumour pathogenesis.

Expression of cancer stem cell biomarkers as a tool for a correct therapeutic approach to hepatocellular carcinoma.

Liver cancer is the fifth most commonly diagnosed malignancy and the second most frequent cause of cancer death in men worldwide. Amongst liver cancers, hepatocellular carcinoma (HCC) represents the major histological subtype and it is one of the most common malignant human tumors worldwide. Research into the molecular biology of hepatocarcinogenesis has identified several biomarkers, which could provide additional informations in order to better understand the biology of HCC. A large number of biomarkers have been shown to have potential predictive significance and a wide variety of molecular markers have been proven to be excellent diagnostic tools for HCC but it is difficult to characterize HCC with a single biomarker. Thus, signatures of a combination of biomarkers may be more valuable for the diagnosis, staging and prognosis of HCC. Specifically, a correlation of HCC-CSCs phenotype to specific hepatic cancer subtypes and to specific clinical and pathological features has not yet been reported in human liver tumors. In this view we will first discuss the possible sources of liver stem cells and their relation with liver cancer development and we will secondly focus on the prognostic significance of clinical and pathological features of HCC.