Melasma and reflectance confocal microscopy: from baseline to treatment monitoring.

Melasma is a frequent condition worldwide, and it represents one of the most challenging disorders to treat in cosmetic dermatology. One of the critical factors for treatment prognosis is the assessment of the depth and distribution of pigment within the hyperpigmented area. Nowadays, non-invasive skin imaging techniques, such as reflectance confocal microscopy (RCM), have been used to estimate pigment distribution and depth within different skin layers. This article aims to provide a systematic review of RCM applications in melasma, providing terminology and investigating characteristics of melasma at baseline and after medical and laser treatment. Our results support the recognition of two main types of melasma, epidermal and mixed type, thanks to the role of RCM in highlighting the precise pigment depth location in the skin non-invasively. RCM treatment monitoring enables the objectification of pigment variations after treatment and the identification of prognostic factors for different treatment modalities. After the era of the application of RCM as a technique applied strictly to skin cancers, additional cosmetic applications are emerging, such as the application of melasma treatment monitoring.

Safety and efficacy of a class II medical device based on highly purified and standardized plant extracts in the management of post-menopausal patients with vulvar and vaginal atrophy: a single-center prospective observational study.

BACKGROUND: Despite the gold standard treatment for genitourinary syndrome of menopause (GSM) is based on the use of local or systemic estrogen-containing products, the typical long-term side effects of hormonal treatments and, most importantly, the contraindications in patients with history of breast and endometrial neoplasms do limit in some extent its use. As hyaluronic acid and some highly purified botanicals have clearly demonstrated their anti-inflammatory and mucosa-protecting properties, we have tested, in women with GSM, a class II vaginal medical device containing hyaluronate gel and a mucoadhesive active enriched with purified alkylamides from Zanthoxylum bungeanum, triterpenes from Centella asiatica and high molecular weight polysaccharides from Tamarindus indica. METHODS: Our single-center, open-label, prospective and observational study was conducted on 50 menopausal women enrolled at the Department of Maternal-Fetal Medicine at Umberto I Polyclinic Hospital in Rome, Italy. Gel administration lasted 150 days and was performed daily for the first 12 days and every 48 hours for the remaining 138 days. Clinical evaluations were performed at baseline and after 12, 57 and 150 days. Besides product safety, main outcomes of our study were: 1) vaginal health (by Vaginal Health Index score [VHI]); 2) sexual quality of life (by Female Sexual Distress Scale [FSDS]); and 3) percentage of women declaring regular sexual activity. RESULTS: The product was safe with no specific adverse events reported. It significantly improved VHI (about 5% after 57 days and 8% after 150 days), FSDS (about 7% after 57 days and 10% after 150 days), and sexual activity (about 20% after 150 days). It also reduced dryness, dyspareunia, burning, itching, and dysuria incidence, respectively by about 18%, 14%, 14%, 27% and 11% after 150 days. CONCLUSIONS: In women with GSM, the intravaginal administration of a hyaluronate-based gel enriched with purified botanical actives endowed with anti-inflammatory and mucosal-protecting properties, reduced painful sensation during sexual acts and increased regular sexual activity.

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.

Bifidobacterium breve PRL2020: Antibiotic-Resistant Profile and Genomic Detection of Antibiotic Resistance Determinants.

Antibiotics are one of the greatest scientific achievements of modern medicine, but excessive use is creating challenges for the future of medicine. Antibiotic resistance (AR) is thought to cause changes in bowel habits and an increased risk of gastroenteritis, but it may also increase the risk of overweight, obesity, autoimmune and atopic diseases, and a low response to vaccines and cancer, likely mediated by antibiotic-induced gut dysbiosis. Probiotic add-on therapy could partially prevent antibiotic-induced gut dysbiosis, but their antibiotic sensitivity features likely limits this potential. The EFSA (European Food Safety Authority) guidelines consider the use of probiotics whose antibiotic-resistant profile could be transferable an important hazard. Recently, a strain of B. breve (PRL2020) has shown to be resistant to amoxicillin and amoxicillin-clavulanate (AC) by applying the microdilution protocol according EFSA guidelines. After verifying that horizontal gene transfer is unlikely to take place, this feature suggests its concomitant use with these specific antibiotics. The results of our tests demonstrated that the strain PRL2020 is indeed endowed with amoxicillin- and AC-resistant properties and that it is also insensitive to ampicillin. In-depth analysis of the annotated genome sequence of B. breve PRL2020 was employed to query the Comprehensive Antibiotic Resistance Database (CARD) using Resistance Gene Identifier (RGI) software (version 5.2.1). The similarity among the AR determinants found was studied through nucleotide sequence alignment, and it was possible to verify not only the absence of genes explaining these features in the flanking regions but also the presence of genetic sequences (rpoB and erm(X)) putatively responsible for rifampicin and erythromycin resistance. Both features are not phenotypically expressed, and for these antibiotics, the strain is within the EFSA limits. Analysis of the flanking regions of these genes revealed possible mobile elements upstream and downstream only in the case of the erm(X) gene, but the features of the Insertion Sequences (IS) are described as not to cause horizontal transfer. Our findings on strain PRL2020 demonstrate that its AR profile is compatible with antibiotics when taken with the aim of reducing the risk of dysbiosis.

Efficacy of Pegylated Hyaluronic Acid Filler Enriched with Calcium Hydroxyapatite: A 24-Week Post-Market, Observational, Prospective, Open-Label, Single-Center Study.

Recently, thanks to the greater discovery of the mechanisms of facial aging, an alternative to invasive plastic surgery has found space with less invasive aesthetic procedures, also based on an increasingly pressing request. We are specifically referring to dermal filler injection into or under the skin which leads to immediate rejuvenation and aesthetic improvements. In this study, we wanted to analyze the results obtained through the use of NEAUVIA Organic Stimulate, particularly with regard to its effectiveness, which is a cross-linked polymeric hydrogel, containing stabilized sodium hyaluronate 26 mg/mL and calcium hydroxyapatite (1%), glycine and L-proline in buffer pyrogen-free water, in its main indication, namely, the temporary correction of congenital and acquired deficiencies of the soft tissues of the face by intradermal injection. Initially, 70 patients were enrolled, but 10 did not complete the study due to non-observance of the investigation rules, so they were excluded from the protocol. The collected data demonstrate an efficient mechanical effect of the pegylated polymeric acid matrix enriched with low concertation of calcium hydroxyapatite and in accordance with other evidence in vitro and in vivo, and the mechanical support of the interstitial connective space improves the homestays of the anatomical layer rebalancing the physiological activity of the dermis cells.

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.

Syphilitic balanitis of Follmann in a patient with a history of previous infection.

We report a case of syphilitic balanitis of Follmann arising in a man with a history of prior infection with syphilis. Few cases have been described in the literature. In our case, a man with history of multiple unprotected sexual contacts presented with erosive balanitis and painless inguinal bilateral lymphadenopathy. All tests for sexually transmitted infections (STIs) performed were negative with the exception of serology for syphilis. We made the diagnosis of syphilitic balanitis of Follmann that was confirmed by prompt resolution after treatment.

Nonsurgical Reshaping of the Lower Jaw With Hyaluronic Acid Fillers: A Retrospective Case Series.

Introduction: Nonsurgical aesthetic treatments of the lower face are increasing in demand. In particular, they aim to restore facial youth following the changes due to progressive resorption of facial skeleton and atrophy of facial fat compartments which give the perception of a descent face. Objectives: The aim of this research is to describe the nonsurgical reshaping of the aged lower jaw by means of hyaluronic acid fillers. Methods: A retrospective analysis of data from adult female patients undergoing treatment with hyaluronic acid injections in the lower third of the face was performed. Injection techniques, relevant anatomy of the anatomical area and rheological properties of the fillers to be used are highlighted. Results: Thirty-six consecutive patients were enrolled (100% female; mean age: 45.7 years). A minimum of 4 up to 7 vials of hyaluronic acid filler was injected to achieve the desired results. The visual analogue scale was used to assess patient satisfaction. Thirty-two patients (88.8%) rated their appearance post-treatment with a satisfaction score ranging between 85% and 100%. A total absence of ecchymosis and/or swelling in the early postoperative days has been highlighted. There were no cases of infection, paresthesia, hematoma or necrosis. Conclusions: For those patients not willing to undergo surgery, the jawline remodelling with hyaluronic acid fillers seems to be a viable option for ameliorating the definition of the lower third of the face. Nonetheless, it is mandatory to perform multilayer injections using fillers with different rheological properties.

An Italian Online Survey Regarding the Use of Hyaluronidase in Previously Hyaluronic Acid-Injected Noses Looking for Surgical Rhinoplasty.

Background: Nonsurgical nasal reshaping (nSNR) with hyaluronic acid (HA) filler is a well-established procedure performed to ameliorate nasal appearance and is considered a valid alternative to surgical rhinoplasty in selected patients. Objectives: The aim of our study is to evaluate the decision-making process and management of patients undergoing rhinoplasty, with previous HA filler injection, and evaluate if consensus could be achieved to recommend guidelines. Methods: Between April and May 2021, an online survey was sent to 402 Italian surgeons of different specialties. The survey collected information regarding the types of treatment of patients who have previously undergone nSNR, who should undergo surgical rhinoplasty. For those surgeons using hyaluronidase, an additional information was collected. Results: In a range of time of 2 months (April and May 2021), a total of 72 surgeons replied and completed the survey: out of the 402 questionnaires sent, the response rate was approximately 18%. The majority of respondents (61.5%) replied to inject hyaluronidase (HYAL) in patients who had to undergo a rhinoplasty but reported previous nSNR. Of the surgeons who use HYAL, 70% performed rhinoplasty after a waiting time of 3 to 4 weeks. Conclusions: Either direct surgical approach or hyaluronidase injection first seems to be a viable options. The use of HYAL before surgery is the choice with the broadest consensus in our survey. However, a larger case-control study with long follow-ups is necessary to understand if in patient seeking surgical rhinoplasty who already received nSNR, the injection of hyaluronidase before surgery is mandatory, recommended, or not.

Rheological Investigation as Tool to Assess Physicochemical Stability of a Hyaluronic Acid Dermal Filler Cross-Linked with Polyethylene Glycol Diglycidyl Ether and Containing Calcium Hydroxyapatite, Glycine and L-Proline.

(1) Background: Dermal fillers are commonly used in aesthetic practice and their rheological characterization is of much interest today, as well as the stability study of the finished formula against external stimuli of a different nature (biological and physicochemical). Rheological tools have been exploited to characterize the physiochemical behaviour of a hyaluronic acid (HA) based dermal filler subjected to different thermal conditions over time. The collected results provide an index of its rheological stability. (2) Methods: After a preliminary Amplitude sweep test, the Frequency sweep test was performed in order to study the stability of a HA dermal filler cross-linked with Polyethylene Glycol Diglycidyl Ether (PEGDE) and containing Calcium Hydroxyapatite (CaHA), Glycine and L-Proline subjected to different conditions. Also, a shear rate ramp test was performed in order to investigate the filler's flow behavior. (3) Results and Conclusions: G' (elastic modulus), G'' (viscous modulus) and consequentially tan δ (tangent of the phase angle) show a similar trend at different thermal conditions, underlining that the product is not affected by the storage conditions. The viscosity of the dermal filler decreases with an increasing shear rate, so a non-Newtonian shear thinning pseudoplastic behavior was demonstrated in all tested conditions.

Botulinum toxin type A injections for masticatory muscles hypertrophy: A systematic review.

The aim of this study is to compare the efficacy of single-point injection of botulinum toxin A versus multi-point operative protocols found in the literature in reducing hypertrophy in patients with masticatory muscle hypertrophy. A systematic review was performed in accordance with the Park et al., 2018 guidelines, selecting articles from PubMed, Google Scholar, Web of Science and Ovid databases up to July 8, 2020.28 studies met the eligibility criteria. 748 patients were treated for masseter hypertrophy (MH) and 4 patients for temporal muscle hypertrophy. As for MH: in 45.2% of cases 3 injection sites (IS) were used, in 18.8% 1 IS, in 16.2% 2 IS, in 13% 5 IS, in 4.1% 6 IS, 2.7% 4 IS. At three months, the mean reduction in masseter muscle thickness is 26-31% when 1 IS was used, 28% in 2 IS, 12-27% in 3 IS and 22-30% in 6 IS. Heterogeneity of results, high bias level and selective reports led to a difficult efficacy comparison of the injection techniques described. Data suggest that the lowest number of IS possible should be used until stronger evidences are presented. Homogeneity in pre- and post-operative protocols is needed to establish a reliable setting for the condition under study.

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.

Quercetin as a possible complementary agent for early-stage COVID-19: Concluding results of a randomized clinical trial.

Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection. Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19. Methods: This was an open-label randomized controlled clinical trial conducted at the department of medicine, King Edward Medical University, Lahore, PK. Patients were randomized to receive either standard of care (SC) plus an oral quercetin supplement (500 mg Quercetin Phytosome®, 1st week, TDS: 2nd week, BDS) (n = 50, quercetin group) or SC alone (n = 50, control group). Results: After one week of treatment, patients in the quercetin group showed a speedy recovery from COVID-19 as compared to the control group, i.e., 34 patients (vs. 12 in the control group) tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (p = 0.0004), and 26 patients (vs. 12 in the control group) had their COVID-19-associated acute symptoms resolved (p = 0.0051). Patients in the quercetin group also showed a significant fall in the serum lactate dehydrogenase (LDH) mean values i.e., from 406.56 ± 183.92 to 257.74 ± 110.73 U/L, p = 0.0001. Quercetin was well-tolerated by all the 50 patients, and no side effects were reported. Conclusion: Our results, suggest the possible therapeutic role of quercetin in early-stage COVID-19, including speedy clearance of SARS-CoV-2, early resolution of the acute symptoms and modulation of the host's hyperinflammatory response. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04861298.

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.

In Vitro Hair Growth Promoting Effect of a Noncrosslinked Hyaluronic Acid in Human Dermal Papilla Cells.

Dermal papilla cells (DPCs) are a source of nutrients and growth factors, which support the proliferation and growth of keratinocytes as well as promoting the induction of new hair follicles and maintenance of hair growth. The protection from reactive oxygen species (ROS) and the promotion of angiogenesis are considered two of the basal mechanisms to preserve the growth of the hair follicle. In this study, a noncrosslinked hyaluronic acid (HA) filler (HYDRO DELUXE BIO, Matex Lab S.p.A.) containing several amino acids was tested with in vitro assays on human follicle dermal papilla cells (HFDPCs). The experiments were carried out to investigate the possible protection against oxidative stress and the ability to increase the vascular endothelial growth factor (VEGF) release. The results demonstrated the restoration of cell viability against UVB-induced cytotoxicity and an increase in the VEGF secretion. These data demonstrate the capability of the product to modulate human dermal papilla cells, suggesting a future use in mesotherapy, a minimally invasive local intradermal therapy (LIT), after further clinical investigations.

Comparative Physicochemical Analysis among 1,4-Butanediol Diglycidyl Ether Cross-Linked Hyaluronic Acid Dermal Fillers.

(1) Background: Injectable hyaluronic acid (HA) dermal fillers are used in several chirurgical practices and in aesthetic medicine. HA filler stability can be enhanced through different cross-linking technologies; one of the most frequently cross-linker used is 1,4-butanediol diglycidyl ether (BDDE), also present in the HA-BDDE dermal filler family of the company Matex Lab S.p.A. (Brindisi, Italy). Our overview is focused on their characterization, drawing a correlation between matrix structure, rheological and physicochemical properties related to their cross-linking technologies. (2) Methods: Four different injectable HA hydrogels were characterized through optical microscopic examination and rheological behavior investigation. (3) Results: The cross-linked HA dermal fillers showed a fibrous "spiderweb-like" matrix structure and an elastic and solid-like profile. (4) Conclusions: The comparative analysis represents a preliminary characterization of these injectable medical devices in order to identify their best field of application.

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.

Toward Physicochemical and Rheological Characterization of Different Injectable Hyaluronic Acid Dermal Fillers Cross-Linked with Polyethylene Glycol Diglycidyl Ether.

(1) Background: Injectable hyaluronic acid (HA) dermal fillers are used to restore volume, hydration and skin tone in aesthetic medicine. HA fillers differ from each other due to their cross-linking technologies, with the aim to increase mechanical and biological activities. One of the most recent and promising cross-linkers is polyethylene glycol diglycidyl ether (PEGDE), used by the company Matex Lab S.p.A., (Brindisi, Italy) to create the HA dermal filler PEGDE family. Over the last few years, several studies have been performed to investigate the biocompatibility and biodegradability of these formulations, but little information is available regarding their matrix structure, rheological and physicochemical properties related to their cross-linking technologies, the HA content or the degree of cross-linking. (2) Methods: Seven different injectable HA hydrogels were subjected to optical microscopic examination, cohesivity evaluation and rheological characterization in order to investigate their behavior. (3) Results: The analyzed cross-linked dermal fillers showed a fibrous "spiderweb-like" matrix structure, with each medical device presenting different and peculiar rheological features. Except for HA non cross-linked hydrogel 18 mg/mL, all showed an elastic and cohesive profile. (4) Conclusions: The comparative analysis with other literature works makes a preliminary characterization of these injectable medical devices possible.