The Potential Role of Probiotics, Especially Butyrate Producers, in the Management of Gastrointestinal Mucositis Induced by Oncologic Chemo-Radiotherapy.

Many clinical studies have now highlighted how the composition of the intestinal microbiota can regulate the effects of many oncological therapies. In particular, the modulation of microbial composition has been shown to enhance their efficacy and reduce potential side effects. Numerous adverse events induced by chemotherapy and radiotherapy appear to be strongly associated with an alteration in the intestinal microbiota caused by these treatments. This supports the hypothesis that the modulation or correction of the microbiota may decrease the toxic impact of therapies, improving patient compliance and quality of life. Among the most debilitating disorders related to oncological treatments is certainly mucositis, and recent clinical data highlight how the deficiency of short-chain fatty acids, especially butyrate, and specifically the lack of certain bacterial groups responsible for its production (butyrate producers), is strongly associated with this disorder. It is hypothesized that restoring these elements may influence the onset and severity of adverse events. Therefore, the intake of probiotics, especially butyrate producers, and specifically Clostridium butyricum (CBM588), currently the only cultivable and usable strain with a history of data proving its safety, could be a valuable ally in oncological therapies, reducing the associated discomfort and improving compliance, efficacy, and quality of life for patients.

Regulatory T Cells in the Pathogenesis of Graves' Disease.

Maintaining a delicate balance between the prompt immune response to pathogens and tolerance towards self-antigens and commensals is crucial for health. T regulatory (Treg) cells are pivotal in preserving self-tolerance, serving as negative regulators of inflammation through the secretion of anti-inflammatory cytokines, interleukin-2 neutralization, and direct suppression of effector T cells. Graves' disease (GD) is a thyroid-specific autoimmune disorder primarily attributed to the breakdown of tolerance to the thyroid-stimulating hormone receptor. Given the limitations of currently available GD treatments, identifying potential pathogenetic factors for pharmacological targeting is of paramount importance. Both functional impairment and frequency reduction of Tregs seem likely in GD pathogenesis. Genome-wide association studies in GD have identified polymorphisms of genes involved in Tregs' functions, such as CD25 (interleukin 2 receptor), and Forkhead box protein P3 (FOXP3). Clinical studies have reported both functional impairment and a reduction in Treg frequency or suppressive actions in GD, although their precise involvement remains a subject of debate. This review begins with an overview of Treg phenotype and functions, subsequently delves into the pathophysiology of GD and into the existing literature concerning the role of Tregs and the balance between Tregs and T helper 17 cells in GD, and finally explores the ongoing studies on target therapies for GD.

Laser Treatment Monitoring with Reflectance Confocal Microscopy.

Laser treatments have become popular in Dermatology. In parallel to technologic development enabling the availability of different laser wavelengths, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to explore morphologic and qualitative skin characteristics. Specifically, RCM can be applied to cosmetically sensitive skin areas such as the face, without the need for skin biopsies. For these reasons, apart from its current use in skin cancer diagnosis, our systematic review reveals how RCM can be employed in the field of laser treatment monitoring, being particularly suitable for the evaluation of variations in epidermis and dermis, and pigmentary and vascular characteristics of the skin. This systematic review article aims to provide an overview on current applications of RCM laser treatment monitoring, while describing RCM features identified for different applications. Studies on human subjects treated with laser treatments, monitored with RCM, were included in the current systematic review. Five groups of treatments were identified and described: skin rejuvenation, scar tissue, pigmentary disorders, vascular disorders and other. Interestingly, RCM can assist treatments with lasers targeting all chromophores in the skin and exploiting laser induced optical breakdown. Treatment monitoring encompasses assessment at baseline and examination of changes after treatment, therefore revealing details in morphologic alterations underlying different skin conditions and mechanisms of actions of laser therapy, as well as objectify results after treatment.

Dermoscopy, confocal microscopy and optical coherence tomography features of main inflammatory and autoimmune skin diseases: A systematic review.

BACKGROUND/OBJECTIVES: Non-invasive skin imaging features of main skin inflammatory and autoimmune diseases have been reported, although a comprehensive review of their correlation with histopathologic features is currently lacking. Therefore, the aim of this paper was to review the correlation of dermoscopic, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) criteria of main inflammatory and autoimmune skin diseases with their corresponding histopathologic criteria correlation. METHODS: Studies on human subjects affected by main inflammatory and autoimmune diseases, defining the correlation of dermoscopic, RCM or OCT with histopathologic criteria, were included in the review. Five groups of diseases were identified and described: psoriasiform, spongiotic and interface dermatitis, bullous diseases and scleroderma. RESULTS: Psoriasiform dermatitis was typified by white scales, corresponding to hyperkeratosis, and vessels, observed with RCM and OCT. Spongiosis, corresponding to dark areas within the epidermis with RCM and OCT, was the main feature of spongiotic dermatitis. Interface dermatitis was characterised by dermoepidermal junction obscuration. Blisters, typical of bullous diseases, were visualised as dark areas with RCM and OCT while scleroderma lesions were characterised by dermoscopic fibrotic beams, related to dermal thickness variations, with specific OCT and histopathologic correlations. CONCLUSIONS: Although the role of RCM and OCT has yet to be defined in clinical practice, non-invasive skin imaging shows promising results on inflammatory and autoimmune skin diseases, due to the correlation with histopathologic features.

Surgical Lip Remodeling Following Permanent Filler Injection: A Scoping Review.

ABSTRACT: Over the years, several techniques have been introduced to obtain permanent lip enhancement, such as the use of silicone lip implants or the off-label use of permanent fillers. Although some reports indicate that permanent lip filler is safe, many others describe early- and late-onset complications. The main issue with permanent lip fillers is the lack of a standard technique to correct undesirable results. The aim of this scoping review was to list and evaluate the surgical pathways described in literature to correct lip deformity resulted from the injection of permanent fillers. The methods and the inclusion criteria of this work were specified in advance and documented in a protocol, according to the PRISMA 2009 checklist. The research was carried out on electronic databases PubMed, Cochrane Library, and Scopus databases identifying articles from March 1991 to December 2020 and conducted up to December 23rd, 2020. Articles language was limited to English. The selection process identified 3 retrospective studies eligible for inclusion. 73 patients and a total of 111 lips (72 upper and 39 lower) were considered. Two early complications were identified, 1 suture dehiscence and 1 total lip mucosa necrosis. Surgical lip remodeling following permanent filler injection seems to be an effective approach although the surgical pathway needs to be customized per each patient. Complication rate seems to be coherent to lip surgery performed with reconstructive purposes. To confirm these data case-control studies with much wider cohorts are needed to reach statistical significance.

Biophysical and Biological Tools to Better Characterize the Stability, Safety and Efficacy of a Cosmeceutical for Acne-Prone Skin.

(1) Background: Acne is a widespread skin disease, especially among adolescents. Following the COVID-19 pandemic and the use of masks, the problem has been affecting a greater number of people, and the attention of the skin care beauty routine cosmetics has been focused on the "Maskne", caused by the sebum excretion rate (SER) that stimulates microbial proliferation. (2) Methods: the present study was focused on the rheological characterization and quality assurance of the preservative system of an anti-acne serum. The biological effectiveness (cytotoxicity-skin and eye irritation-antimicrobial, biofilm eradication and anti-inflammatory activity) was evaluated in a monolayer cell line of keratinocytes (HaCaT) and on 3D models (reconstructed human epidermis, RHE and human reconstructed corneal epithelium, HCE). The Cutibacterium acnes, as the most relevant acne-inducing bacterium, is chosen as a pro-inflammatory stimulus and to evaluate the antimicrobial activity of the serum. (3) Results and Conclusions: Rheology allows to simulate serum behavior at rest, extrusion and application, so the serum could be defined as having a solid-like behavior and being pseudoplastic. The preservative system is in compliance with the criteria of the reference standard. Biological effectiveness evaluation shows non-cytotoxic and irritant behavior with a good antimicrobial and anti-inflammatory activity of the formulation, supporting the effectiveness of the serum for acne-prone skin treatment.

Hyperdiluted calcium hydroxylapatite for the treatment of skin laxity of the neck.

Despite being a common concern, there are very few minimally invasive treatments targeting neck skin laxity (NSL) reported in the literature. To assess the efficacy of hyperdiluted calcium hydroxyapatite (hy-CaHA) for the treatment of NSL, according to the NSL scale, and to estimate safety. Twenty patients showing NSL were treated with hy-CaHA 1:2. To evaluate the efficacy of hy-CaHA treatment for NSL, pictures of treated subjects were collected before and 3 months after treatment and graded according to the NSL scale, and T-student's test was applied to estimate differences. Hy-CaHA for the neck was effective according to the previously unreported NSL scale (p < 0.001) and safe. There were no major adverse events reported. This study supports the efficacy (according to the NSL scale) and safety of hy-CaHA (1:2) for NSL. Our results also highlight the utility of the newly developed NSL scale, being a useful tool to evaluate the level of NSL before treatment and to measure the outcome.

Combined laser assisted treatment for permanent hair removal for skin types I-V with Alexandrite 755 nm and ND:YAG 1064 nm lasers.

This retrospective cohort study regarding hair removal procedures considers all the data collected in three different clinical centers from 2017 to 2019. The device used to perform the treatments was composed of an Alexandrite 755 nm and an Nd:YAG 1064 nm laser, that delivered both wavelengths in a blended simultaneous emission (Thunder MT, Quanta System, Samarate, Italy). The improvement evaluated after five sessions of treatment by an external referee was: 83.0% for armpits, 82.1% for the bikini line, 82.2% for legs, 79.6% for thorax, and 81.6% for the back. The collected temporary skin reaction data reported in this study were all acceptable and transitory resolving in less than 1 week. The level of erythema and perifollicular edema were all signs of the reached treatment endpoint. First degree burns, hyper, and hypopigmentation were also reported in a few cases but these, all resolved before the follow-up visit without any permanent skin effects. No adverse effects were thus reported to have happened. This retrospective study demonstrates the efficacy of combining Alexandrite and Nd:YAG lasers in a mixed modality with simultaneous emission. This technology permitted to treat patients with skin types I-V without any reported permanent side effects and with a high pain tolerability compared to the use of Nd:YAG in single mode.

Skin vascular lesions: A new therapeutic option with sequential laser-assisted technique.

Treatment of skin unaesthetic vascular lesions is still suboptimal. In this article, we present a multicenter study evaluating the efficacy and safety of the sequential 755 nm Alexandrite and 1064 nm ND:YAG lasers for the treatment of acquired and congenital vascular lesions of the skin. A total of 171 patients were included in the study (141 female and 30 male), median age 38, skin type from I to IV. Numbers of patients categorized for treated disease: 22 spider angiomas, 67 facial telangiectasia/spider veins, 58 leg telangiectasia/reticular leg veins, 24 port wine stains (PWS). Of those lesions 30.7% was on legs, 63.7% on face (6.7% on forehead, 10.1% on temples, 21.7% on cheeks, 25.2% on nose, 1.7% on chin) and 5.6% on chest. Spider angiomas required from 1 to 3 treatments. Facial telangiectasias had been treated from 1 to 4 times. Leg telangiectasias needed from 2 to 6 treatment sessions. Regarding PWS, it takes from 6 to 9 laser treatment to reach the clearance of the lesion. All the vascular disorders treated showed marked improvement while side effects were limited to low pain sensation and transitory fenomena. This sequential treatment is an effective, safe, and new approach for unaesthetic skin vascular lesions.

Ultrapulsed CO2 Resurfacing of Photodamaged Facial Skin in Vegan and Omnivore Patients: A Multicentric Study.

BACKGROUND AND OBJECTIVES: Skin photoaging is related to extrinsic environmental exposures, mainly represented by ultraviolet radiation. One of the treatment options is laser resurfacing. As nutritional status is involved in cutaneous photodamage, we evaluated whether dietary patterns can also influence the response to facial resurfacing. Our prospective multicentric study involves three dermatologic centers specialized in laser therapy in northern Italy. The study aims to compare the outcome of a CO2 ablative laser therapy between omnivore and vegan patients. STUDY DESIGN/MATERIALS AND METHODS: Fifty-three omnivore and fifty-three vegan women undergoing ultrapulsed CO2 resurfacing for photodamaged facial skin were enrolled in this study. Clinical improvement was evaluated 3 and 6 months after the treatment using the modified Dover score. RESULTS: After laser treatment, vegans showed slower complete re-epithelialization (P < 0.001*) and disappearance of the erythema (P < 0.001*). After 3 and 6 months, vegans showed worse outcomes in terms of fine lines (P < 0.001* and P < 0.001*, respectively) and tactile roughness (P = 0.003* and ​​​​P = 0.002*, respectively) compared with omnivores, while they did not differ in mottled pigmentation. CONCLUSIONS: The present study suggests that diet influences the clinical outcome of fractioned CO2 laser treatment. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Transvascular Hydrolysis of Hyaluronic Acid Filler With Hyaluronidase: An Ex Vivo Study.

BACKGROUND: Despite the favorable safety profile of hyaluronic acid (HA) dermal fillers, side effects can occur. Skin necrosis is one of the most severe early-occurring complications resulting from accidental vascular impairment. Hyaluronidase (HYAL) is commonly used to degrade HA chains, allowing the degraded product to pass through vessels, and thus relieving the vascular obstruction. OBJECTIVE: The purpose of this study is to evaluate, in an ex vivo setting, the capability of HYAL to degrade crosslinked HA that was injected into human vessels. MATERIALS AND METHODS: During a neck dissection, a portion of the anterior jugular vein and facial artery was harvested. The vein and artery specimens were filled with 25 mg/mL of crosslinked HA filler. Each specimen was soaked in 0.5 mL of HYAL (300 IU/mL), in its own test tube, for 4 hours, after which the remaining HA was quantified. RESULTS: The remaining HA volume was found to be 0.02 mL in the vein segment and 0.002 mL in the artery segment. CONCLUSION: A single administration of HYAL may not be adequate to restore blood flow in the event of embolism, and relatively high doses of this enzyme must be injected hourly into the affected tissue until resolution is complete.

A Practical Approach for the In Vitro Safety and Efficacy Assessment of an Anti-Ageing Cosmetic Cream Enriched with Functional Compounds.

(1) Background: Cosmeceuticals are topical products applied to human skin to prevent skin ageing and maintain a healthy skin appearance. Their effectiveness is closely linked to the compounds present in a final formulation. In this article, we propose a panel of in vitro tests to support the efficacy assessment of an anti-ageing cream enriched with functional compounds. (2) Methods: biocompatibility and the irritant effect were evaluated on reconstructed human epidermis (RHE) and corneal epithelium (HCE) 3D models. After a preliminary MTT assay, normal human dermal fibroblasts (NHDF) and keratinocytes (HaCaT) were used to evaluate the extracellular matrix (ECM) protein synthesis, and interleukin-6 (IL-6) and metalloproteinase-1 (MMP-1) production. (3) Results: data collected showed good biocompatibility and demonstrated the absence of the irritant effect in both 3D models. Therefore, we demonstrated a statistical increase in collagen and elastin productions in NHDF cells. In HaCaT cells, we highlighted an anti-inflammatory effect through a reduction in IL-6 levels in inflammatory stimulated conditions. Moreover, the reduction of MMP-1 production after UV-B radiation was demonstrated, showing significant photo-protection. (4) Conclusion: a multiple in vitro assays approach is proposed for the valid and practical assessment of the anti-ageing protection, anti-inflammatory and biocompatible claims that can be assigned to a cosmetic product containing functional compounds.

Emerging drugs for the treatment of vitiligo.

Introduction: Vitiligo is a relatively common autoimmune depigmenting disorder of the skin. There has been a great advance in understanding the pathological basis, which has led to the development and utilization of various new molecules in treating vitiligo. This review aims at a comprehensively describing the treatments available and the emerging treatment aspects and the scope for future developments.Areas covered: This study comprehensively summarizes the current concepts in the pathogenesis of vitiligo with special focus on the cytokine and signaling pathways, which are the targets for newer drugs. JAK kinase signaling pathways and the cytokines involved are the focus of vitiligo treatment in current research, followed by antioxidant mechanisms and repigmenting mechanisms. Topical immunosuppressants may be an alternative to steroids in localized vitiligo. Newer repigmenting agents like basic fibroblast growth factors, afamelanotide have been included and a special emphasis is laid on the upcoming targeted immunotherapy.Expert opinion: The treatment of vitiligo needs to be multimodal with emphasis on targeting different limbs of the pathogenesis. Topical and oral JAK inhibitors are the most promising new class of drugs currently available for treating vitiligo and acts best in conjunction with NB-UVB.

Immune profile of hyaluronic acid hydrogel polyethylene glycol crosslinked: An in vitro evaluation in human polymorphonuclear leukocytes.

Neauvia hydrogel (N-Gel) is a hyaluronic acid-based dermal filler, cross-linked with polyethylene glycol. This filler contains sodium hyaluronate at different concentrations, poly(ethylene glycol) diglycidyl ether cross-linked, glycine, and l-prolyne. Assessing any effects of N-Gel on immunity and inflammation is of crucial importance. The aim of the study was to characterize the ability of N-Gel to modulate human polymorphonuclear leukocyte (PMN) functions, including migration, oxidative metabolism, and production of proinflammatory mediators. N-Gel was tested on isolated human PMN. Spontaneous and N-formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated migration were examined using the Boyden Chamber technique, whereas the oxidative metabolism was assessed through spectrofluorometric measurement of reactive oxygen species (ROS) production under resting conditions and after stimulation with fMLP. Tumor necrosis factor (TNF)-α and interleukin (IL)-8 mRNA levels were measured by real-time PCR after stimulation with fMLP or Escherichia coli lipopolysaccharide. This study showed that N-Gel reduced fMLP-induced migration and ROS production without affecting these functions in resting cells. In addition, incubation of PMN with N-Gel effectively reduced both TNF-α and IL-8 mRNA levels. N-Gel modulates critical functions of human PMN such as migration and oxidative metabolism, indicating its potential as an anti-inflammatory agent.

Cross-linked hyaluronic acid filler hydrolysis with hyaluronidase: Different settings to reproduce different clinical scenarios.

Skin necrosis is the most severe complication arising from hyaluronic acid (HA) injection. To avoid skin necrosis, hyaluronidase should be injected along the course of the involved artery, to allow blood flow restoration. We evaluated the ability of hyaluronidase to degrade a HA filler in two simulated clinical situations-a compression case and an embolization case-to identify differences in the hyaluronidase injection. In the compression case, a bolus of HA filler was directly soaked in hyaluronidase solution; in the embolization case, a vein harvested from a living patient was filled with the same HA filler and then soaked in hyaluronidase. We then evaluated the quantity of HA remaining after 2 hr. While we found hydrolysis of HA in both cases, in the compression case, we detected almost complete hydrolysis, whereas in the embolization case we observed a reduction of the 60%. Our results support the hypothesis that vessel compression can be resolved with only one injection of hyaluronidase, while in the case of vascular embolization, repeated perivascular injections should be performed owing to the reduction of hyaluronidase activity.

An Italian experience of a new personalized injective protocol (Botutouch) for botulinum toxin application in aesthetic medicine.

Botulinum toxin typeA (BoNTA) is widely used in aesthetic medicine as primary treatment to reduce facial wrinkles. Major unmet needs in the field of the injection techniques include dilution factor, injected volume and site. Since 2013, an innovative protocol has been developed in our clinic that works on a double dilution volume, identifies the injection site according to the specific anatomical-functional characteristics of each patient's musculature and applies a gentle massage to the injected area to optimize the toxin spread in the muscle. We retrospectively retrieved medical records of subjects that underwent aesthetic treatments in our outpatient Italian clinics from 2013. In cobotulinum toxin A was used in double dilution (100 AU in 5 mL of physiologic solution) and followed by a gentle massage after the injection to increase the distribution into the muscle. 197 subjects, most of them drug-naïve (81.7%), underwent 869 BoNTA treatments. On average, higher total units and volumes were applied in first visits or older subjects whereas the lower ones were preferred in following visits or younger subjects. As perceived by the patients, the effects of BoNTA lasted more than 6 months in about 38% of the cases. 95.9% of subjects declared to be satisfied,whereas 5.2% of adverse events were observed (4.8% hematoma, 0.2% ptosis, and 0.2% tenderness). To date, we offer a BoNTA treatment with the aim to maximize the results and consequent patient's satisfaction, with low incidence of complications.

Remodeling of collagen constituting interlobular septa of subcutaneous adipose tissue following microwaves application.

In this study, the application of a recently introduced device based on electromagnetic energy transfer by microwaves for fat reduction, permitted to study specifically the modifications of thick fibrous collagen interlobular septa in the subcutaneous adipose tissue, related to the formation of large clusters of adipocytes. The use of Picrosirius red staining associated with circularly polarized microscopy gave evidence of appreciable modifications of the fibrous connective tissue forming septa. Compact fibrotic bundles of collagen I forming interlobular septa appeared reduced or dissolved, in part substituted by the increase of more diffuse and finely reticular collagen III. Remodeling of fibrous collagen, which formed bridles involved in the appearance at the surface of the skin of dimpling/orange peer pattern typical of cellulite, was observed.

Chemical and mechanical characterization of hyaluronic acid hydrogel cross-linked with polyethylen glycol and its use in dermatology.

Hydrogels based on hyaluronic acid are used to restore volume, hydration, and skin tone, as well as to correct scars, asymmetries or defects of the soft tissue. Hyaluronic acid is often chemically crosslinked with different crosslinking agents in order to improve its mechanical and biological properties. Here we focused on defining the chemical and mechanical characterization of a new hydrogel with specific characteristics: hyaluronic acid polyethylene glycol (PEG)-crosslinked with a high concentration of hyaluronic acid (28 mg/mL), manufactured by MatexLab Spa, via Carlo Urbani 2, ang Via Enrico Fermi, Brindisi, Italy. We made a quantitative and qualitative analysis of the content of sodium hyaluronate in the hydrogel after polymerization and sterilization processes and also evaluated histologically the bio integration of these hydrogels in the cutaneous soft tissues. The results suggest that hyaluronic acid hydrogel PEG-crosslinked have great bio integration, great chemical and mechanical properties, compared with other products available on the market, that are cross-linked with different cross-linking agents. The nontoxicity and nonimmunogenicity of PEG guarantee the lack of allergic and immunological reactions. The PEG-crosslinking technology guarantees a high duration time of the implanted hydrogel because of more resistant physiological degradation.

Hyaluronic Acid Injections to Correct Lips Deformity Following Surgical Removal of Permanent Implant.

One of the most attractive areas of the face are the lips, they are crucial for emotion and communication, both during animation and at rest. Throughout the years, several techniques to obtain permanent lip enhancement have been introduced, such as the use of nonresorbable fillers. The main problem related to permanent fillers is that undesirable results could not always be repaired; although lip sequelae can be addressed surgically, some surgeons will not perform this type of procedure due to its complexity and the lack of guidelines.In this paper, the authors present a case of a labial incompetence developed after lips implant removal performed elsewhere; after clinical examination the patient was planned for surgery, although during preoperative instrumental examination (chest X-ray) a solitary pulmonary nodule was noted; further investigation performed with needle biopsy revealed a lung cancer. For this reason, the surgical procedure planned for lip restoration was not performed; however, the patient asked for a minimally invasive procedure, thus to improve, although temporarily, her lips appearance.For the aforementioned reasons, the patient was treated just with hyaluronic acid injections achieving a pleasant result, solving also the labial incompetence at rest.To the best of the author's knowledge, this paper represents the first one describing the use of hyaluronic acid injections to restore lip competence following surgical removal of permanent implant.

Skin Necrosis and Vision Loss or Impairment After Facial Filler Injection.

Purpose of the present study is to objectively evaluate the number of severe vascular complications, represented by skin necrosis and vision loss or impairment, following facial filler injection. The investigators implemented a review of the literature including articles published on PubMed database without limitation about year of publication, including all reports concerning skin necrosis and vision loss or impairment related to the injection of fillers for cosmetic uses. The search highlighted 45 articles and a total of 164 cases of skin necrosis and vision loss or impairment after injection of different substances. The injection site most frequently associated with complications was the nose (44.5%), followed by glabella (21%), nasolabial fold (15%), and forehead (10%). Results of the present study suggest that injectable filler can cause severe complications even in expertized hands. Treatments in the new defined "Dangerous triangle" must be carefully carried out. Despite our expectations, the highest rates of sever adverse events have been associated with autologous fat transfer practice.