Long-term clinical and histological safety and efficacy of the CO2 laser for treatment of genitourinary syndrome of menopause: an original study.

OBJECTIVE: This study aimed to evaluate histological modifications of the vaginal mucosa after repeated microablative fractional CO2 laser treatments. As secondary objectives we evaluated the clinical effects associated with repeated microablative fractional CO2 laser treatments using validated questionnaires. METHODS: A prospective intervention study was performed in the Division of Gynecology and Obstetrics, Urogynecology Unit, IRCCS San Raffaele Scientific Institute with 15 postmenopausal women complaining of genitourinary syndrome of menopause symptoms. The cohort of patients was submitted to at least two previous laser treatment cycles in the past years. The Vaginal Health Index (VHI), visual analog scale (VAS), Female Sexual Function Index (FSFI), Urinary Distress Inventory-6 (UDI-6), International Consultation on Incontinence Questionnaire - Urinary Incontinence (ICIQ-UI) and 5-point Likert scale were used. Moreover, histological examinations were carried out on all samples. RESULTS: At 4 weeks after the last treatment, the VHI score and all FSFI items were significantly increased compared with baseline. We observed a statistically significant decrease in both frequency and severity for all urinary symptoms after the follow-up. We observed a statistically significant increase in the number of epithelial cell layers with a consequent increase in epithelial thickness, in the number of glycogen-filled cells and in the number of papillae after the laser treatment. No signs of fibrosis were observed as neovascularization was observed in each woman. CONCLUSIONS: This is the first study demonstrating the histological persistency of efficacy in repeated annually laser treatment cycles, with tissue changes always leading to regenerative results without any sign of fibrosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04868812 (release date: 27 April 2021).

In Vitro Evaluation of the Biological Availability of Hyaluronic Acid Polyethylene Glycols-Cross-Linked Hydrogels to Bovine Testes Hyaluronidase.

During last years, hyaluronic acid- (HA-) based dermal fillers have grown rapidly and continuously, as reported by the American Society of Aesthetic Plastic Surgery (ASAPS). In fact, HA fillers are considered the gold standard technique for soft tissue augmentation, deep skin hydration, and facial recontouring, playing a key role as an alternative to plastic surgery. HA fillers are less invasive, more biocompatible, and safer and with a more natural and immediate result if compared to plastic surgery. Hence, the safety of HA-based dermal fillers plays a crucial role, mostly in terms of biocompatibility and adjustability in case of unpleasant results and side effects such as, tyndall effect, edema, or granulomas. Hyaluronidase is a naturally occurring enzyme, present in the human body, and can degrade HA fillers avoiding more severe complications. In this article, we analyzed the bioavailability of hyaluronidase degradation of five fillers of Neauvia® hydrogels line (MatexLab SA, Lugano, CH), composed of pure hyaluronic acid and based on PEGDE cross-linking (polyethylene glycol) technology that guarantees a higher biocompatibility and an optimal biointegration and rheological characteristics. The performed in vitro testing is based on the colorimetric determination of the N-acetyl-D-glucosamine (NAG) present in solution after incubation with hyaluronidase, determined at different time points in order to assess the kinetic of each product degradation (1h, 3h, 6h, 24h, 48h, 72h, 120h, and 168h). The aim of this study was to assess, in vitro, how the difference in HA content and PEGDE concentration of the analyzed fillers can influence the product biocompatibility, intended as product enzymatic clearance and duration in time. The results demonstrated that the method was reproducible and easy to perform and that all the analyzed fillers are naturally immediately available for hyaluronidase-mediated degradation.

Remodeling the neck and the lower jaw with dehoxycholate injections.

Nonsurgical cosmetic facial procedures have gained popularity in recent decades. These procedures are commonly referred to as facial rejuvenation, and only a few are performed in the neck region. Herein, the authors describe their experience with off-label use of deoxycholic acid (DC) injections on 18 patients for remodeling of the neck and lower jaw. The injection protocol was personalized for each patient, and lidocaine was always premixed with the DC. After the initial injection visit, at least 3 months passed before further injections were considered. All documented side effects, including swelling and dysesthesia, resolved spontaneously. All patients received follow-up for at least 3 months, and only 2 patients required a second session of injections. By personalizing the injection protocol for each patient, good outcomes were achieved, including aesthetic enhancement of the shape and contour of the jaw and neck. Although the study is limited by the relatively small sample size, the results are promising and warrant additional investigations.

Morphological evidences following pegylated filler treatment in human skin.

In this study, microscopic, histochemical and ultrastructural observations in human skin are presented, 8 months after an injection of a novel PEGylated filler. Morphological features demonstrated an excellent integration of the filler with the connective tissue components and an effective interpenetration with the ground substance. The filler appears uniformly distributed inside the hypodermis. No segregation or encapsulation of cells and other structures was observed nor evidence of immunological adverse reaction. Furthermore, observed ultrastructural modifications of fibroblasts supports a stimulatory effect of molecular components production of the extracellular matrix, contributing to the cutaneous connective tissue renewal.

In vitro evaluation of collagen production on human fibroblasts treated with hyaluronic acid peg cross-linked with micromolecules of calcium hydroxyapatite in low concentration.

Neauvia Stimulate® is a biocompatible, injectable hyaluronic acid (HA) filler (26 mg/ml) PEG cross-linked with 1% of calcium hydroxyapatite (CaHA) for facial soft-tissue augmentation that provides volume to tissues, followed by a process of neocollagenesis for improving skin quality. The aim of the present study is to evaluate the possible modulation of collagen synthesis after treating human fibroblasts cultured in vitro with the product (Lot. 160517-26-1/2 PEG). The experimental model proposed, despite being an in vitro system, allows the derivation of useful information to predict the possible activity of the product in further in vivo application. Human fibroblasts (PEU cells) were treated with the product for 24 h at increasing concentrations of compared to control (untreated cells). The modulation of collagen synthesis was evaluated using a specific colorimetric kit (Sircol, Soluble Collagen Assay Kit). Increment of collagen production, 37.62% and 97.39% at concentrations of 1.25 mg/ml and 2.5 mg/ml of product, respectively, was considered to be statistically significant (*p values≤0.05 and **p values≤0.01) when compared with control (untreated cells). In conclusion, Hyaluronic Acid Hydrogel 26 mg/ml PEG cross-linked with calcium hydroxyapatite in low concentrations (1%) determines a statistical increment in neocollagenesis.

Clinical and histological changes in Hidradenitis suppurativa following 1064 nm nd:YAG intralesional laser treatment.

Hidradenitis Suppurativa (HS) is recently attracting much attention and awareness, often because it is misdiagnosed for years, restricting the therapeutic options. Moreover, this pathology arises in areas such as the inguinal region, that may cause embarrassment in young patients. Wrong diagnosis and delay in appropriate treatments lead to an exacerbation of the symptoms and a progression of the disease, which at the last stage can only be managed through extensive surgical excisions, ablation and vaporization of nodules with CO2 laser systems or aggressive chemotherapies such as anti-TNF-alpha like adalimumab (Humira®-AbbVie Inc. North Chicago, Illinois USA). In our study, we present an alternative low-invasive treatment that presents a successful outcome, supported by clinical and histological evaluation, limited however only for early stages of HS, highlighting the importance of raising awareness among physicians and patients by stressing the importance of an early diagnosis.

A new hyaluronic acid polymer in the augmentation and restoration of labia majora.

Aesthetic surgery of female external genitalia has gained increasing popularity over the past decade, with reduction of the labia minora (labiaplasty) being the procedure most commonly requested and performed. Female external genitalia lose elasticity and volume with age, but few studies describe the techniques for labia majora augmentation. Currently, very few studies have investigated the effectiveness and safety of labia majora augmentation with hyaluronic acid (HA) injection. This study aims to evaluate the effectiveness and safety of labia majora augmentation with hyaluronic acid filler injection. We retrospectively analyzed 37 patients affected by hypotrophy of the labia majora, treated with HA dermal filler 28mg/ml PEG crosslinked (Neauvia® Intense Rose, Matex Lab, Switzerland) between May 2015 and July 2016. Global evaluation of the aesthetics of the intimate area and clinical data were investigated with VAS (Visual Analogic Scale) ad hoc. Adverse events and complications were recorded. A total of 37 women affected by labia majora hypotrophy were treated with 28mg/ml HA dermal filler. A significant clinical improvement was observed in the score provided by both patients and doctor. Only mild adverse events and complications were recorded. HA hydrogel with a novel crosslinking agent is able to provide a considerable rejuvenation with a simple outpatient procedure and to bring a significant clinical improvement. HA-based filler infiltration treatment in labia majora is repeatable, has virtually no complications, and is reversible.

Laser treatment of leg ulcers: selected concepts.

An overview on different laser devices, available for the treatment of the different phases of wound healing: debridement, wound repair and scars correction.

Between history and gossip: the state of women relative to syphilis, a traditionally male disease.

Despite the new World Health Organization data remind us how syphilis is a disease which affects both sexes equally, this pathology has always been mainly considered a male disease. While several famous men are known to be affected by syphilis, there are very few women affected by this pathology of which we have historical records. Through the lives of Mary Todd Lincoln, Catherine of Aragon, Karen Blixen and Florence Foster Jenkins, this article would like to grant dignity to all the women who contracted syphilis in the wrong historical era where, for a woman, admitting to contracting it was shameful. Through the important women who lived their lives fighting against this disease and its complications, we would like to pay tribute to all those women who still today, in an era of antibiotics and where syphilis is a treatable pathology, they cannot be cured because they are both geographically and socially disadvantaged.

A short novel about the spread of two important diseases in history: syphilis and SARS.

Throughout the centuries, the undefended nature of man has very often manifested in cases of epidemics, which have determined scenarios of suffering and death. Through "historical" observation lens, it is possible to understand the relationship between the spread of viruses, bacteria and parasites responsible for these epidemics and the displacement of ancient or contemporary travellers. We have analysed two infective diseases, syphilis and SARS, and their role in history and in medicine.

Sexual function after fractional microablative CO2 laser in women with vulvovaginal atrophy.

OBJECTIVE: To investigate the effects of fractional microablative CO2 laser on sexual function and overall satisfaction with sexual life in postmenopausal women with vulvovaginal atrophy (VVA). METHOD: This prospective study included 77 postmenopausal women (mean age 60.6 ± 6.2 years) treated for VVA symptoms with the fractional microablative CO2 laser system (SmartXide(2) V(2)LR, Monalisa Touch, DEKA, Florence, Italy). Sexual function and quality of life were evaluated with the Female Sexual Function Index (FSFI) and the Short Form 12 (SF-12), respectively, both at baseline and at 12-week follow-up. A 10-mm visual analog scale was used to measure the overall satisfaction with sexual life and the intensity of VVA symptoms (vaginal burning, vaginal itching, vaginal dryness, dyspareunia and dysuria) before and after the study period. RESULTS: We observed a significant improvement in the total score and the scores in each specific domain of the FSFI at 12-week follow-up compared to baseline (p < 0.001). After concluding the laser treatment, the overall satisfaction with sexual life significantly improved (p < 0.001). Seventeen (85%) out of 20 (26%) women, not sexually active because of VVA severity at baseline, regained a normal sexual life at the 12-week follow-up. Finally, we also found a significant improvement in each VVA symptom (p < 0.001) and in quality-of-life evaluation, both for the scores in the physical (p = 0.013) and mental (p = 0.002) domains. CONCLUSIONS: Fractional microablative CO2 laser treatment is associated with a significant improvement of sexual function and satisfaction with sexual life in postmenopausal women with VVA symptoms.

Iron supplementation in young iron-deficient females causes gastrointestinal redox imbalance: protective effect of a fermented nutraceutical.

The aim of this study was to assess whether the concomitant supplementation of certified fermented papaya preparation (FPP, ORI, Gifu, Japan) together with iron supplementation could beneficially affect lipid peroxidation either systemically and at a intraluminal gut level in women with low iron stores. Treatment compliance and iron absorption was assessed as well. Fifty-two non-pregnant, fertile, non-smokers, healthy women with iron deficiency were recruited. The women were given iron supplements (100 mg Fe/d as ferrous sulfate) to be taken daily for 12 weeks (group A). Group B patients were also supplemented with 6g/day of a FPP. A detailed life style questionnaire was administered to all subjects. Iron, ferritin, transferrin receptors (Tf R) and malondialdehyde (MDA) in plasma were measured. The RBCs lysate was used for the estimation of superoxide dismutase (SOD) and glutathione peroxidase (GPx). The total and free iron concentration as well as analysis of oxidative stress in the feces was measured. FPP-supplemented subjects showed a significantly lower degree of gastrointestinal discomfort (p less than 0.05) and abolished the iron supplementation-induced increase of MDA (p less than 0.001) and the depletion of SOD and GPx (p less than 0.01). Moreover, the nutraceutical co-administration brought about a significant reduction of gut oxidative damage and lower fecal content of either total and free iron (p less than 0.05 vs group A). Overall, group B showed a better TfR/ferritin ratio response (p less than 0.05 vs group A). While iron supplementation maintains its clinical relevance considering the prevalence of iron deficiency among females, a careful clinical evaluation and a protective nutraceutical co-administration, as our data suggest with FPP, should be considered.

A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study.

OBJECTIVE: This pilot study aimed to assess the efficacy and feasibility of fractional CO2 laser in the treatment of vulvovaginal atrophy (VVA) in postmenopausal women. METHODS: VVA symptoms were assessed before and after three applications of laser over 12 weeks in 50 women (age 59.6 ± 5.8 years) dissatisfied with previous local estrogen therapies. Subjective (visual analog scale) and objective (Vaginal Health Index Score, VHIS) measures were used during the study period to assess VVA. Quality of life was measured by using the SF-12. A subjective scale to evaluate the degree of pain related to the laser application and the degree of difficulty to perform the laser procedure was used. RESULTS: Fractional CO2 laser treatment was effective to improve VVA symptoms (vaginal dryness, vaginal burning, vaginal itching, dyspareunia, dysuria; p < 0.001) at 12-week follow-up, as well as the VHIS (13.1 ± 2.5 at baseline vs. 23.1 ± 1.9; p < 0.001). Both physical and mental scores of quality of life were significantly improved in comparison with baseline (p < 0.001). Satisfaction with the laser procedure was reported by 42 women (84%) and a minimal discomfort was experienced at the first laser application, mainly because of the insertion and the movements of the probe. Finally, the technique was very easy to perform in all women starting from the second application at week 4 and no adverse events were recorded during the study period. CONCLUSIONS: A 12-week treatment with the fractional CO2 laser was feasible and induced a significant improvement of VVA symptoms by ameliorating vaginal health in postmenopausal women. Further controlled studies should be performed to confirm the present data and to assess the long-term effects of the laser procedure on vaginal tissues.

A double-blind, rct testing beneficial modulation of BDNF in middle-aged, life style-stressed subjects: a clue to brain protection?

INTRODUCTION: The aim of this prospective study was to see whether LD-1227, a quality-controlled marine nutraceuticals shown to protect experimental stress-induced hyppocampal degeneration, could beneficially modulate BDNF, as measured in the serum, in otherwise healthy but work-stressed individuals. MATERIALS AND METHODS: Forty-eight men and women between the ages of 38 and 62 reporting high-demanding work activity but with an overall positive attitude towards their personal life were recruited. Subjects were divided in two group (24 patients each) and blindly supplemented for 2 month with: a) LD-1227 400mg or b) placebo. A third group of healthy non-stressed subjects was used as well. Blood samples were taken before and after the supplementation period. Unstimulated saliva was collected and tested for amylase while serum levels were used to measure BDNF. State Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI) and psychological well-being assessment (PSWB) were measured too. Patients with Val66Met functional polymorphism of BDNF excluded those given their reported association with an impaired release of BDNF. RESULTS: RESULTS showed that, as compared to healthy, non-stressed individuals, stressed ones has a trend decrease of BDNF and this was significantly increased by LD 12-1227 supplementation and the same inverse phenomenon occurred to salivary amylase (p<0.05). No change was noted in the PSQI score but, either STAI or PSWB tests scored better in LD-1227 supplemented subjects. CONCLUSION: The present data suggest that LD-1227 is beneficially affecting neuromodulation and related symptoms during common stressful life conditions and may have the potential as tools in a neuroprotective clinical strategy.

Effect of Celergen, a marine derivative, on in vitro hepatocarcinogenesis.

The aim of this study was to test for a potential anticarcinogenic effect of Celergen, a marine derivative devoid of traceable amounts of inorganic arsenic, on cell proliferation, cell cycle progression and apoptosis in the HepG2 human liver cancer cell line. Celergen significantly inhibited the proliferation of cancer cells in a dose-dependent manner while limiting the cell cycle progression at the G1 phase and significantly inducing apoptosis. Further examination showed that Celergen enhanced expression of the p21(CIPl1WAF1), GADD153 genes and downregulated the c-myc gene. These results suggest that Celergen exerts promising chemopreventive properties to be further investigated.

Prophylactic strategies in recurrent vulvovaginal candidiasis: a 2-year study testing a phytonutrient vs itraconazole.

The aim of the present study was to assess the clinical efficacy of a one week/month treatment with a phytocompound with antimycotic properties (K-712, with following 100 mg composition: 10 mg of oleoresin from Pseudowintera colorata at 30 percent concentration in Polygodial together with trace amounts of Olea europea) in recurrent vulvo-vaginal candidiasis (RVVC), as compared to once a week treatment with an azole drug for 24 months follow up. This prospective randomized study involving 122 women (19 to 63 years old) with a history of proven episodes of RVVC in the prior 12 months. Patients were allocated in two treatment groups of 61 patients each and given A) Itraconazole 200 mg orally once a week or B) 1 tab twice a day of K-712 for one week/month. Each treatment schedule was well tolerated with 19 patients in the azole group complaining of transient mild symptoms (nausea, abdominal discomfort, unpleasant taste), while only 3 patients on K-712 reported slight dyspepsia. The number of relapses was significantly lower in the K-712-treated group as compared to the itraconazole-group (22 vs 39, p less than 0.05). Moreover, the former group showed a significantly decreased number of cases resistant or dose-dependent susceptible as compared to group A (p less than 0.05 vs itraconazole) and the same occurred for the occurrence of non-albicans species (group A 64.1 percent vs group B 31.8 percent, p less than 0.05). The overall mycological cure at the end of the 2-year study showed a comparable benefit between the two groups. From these data it appears that the present antifungal phytonutrient is equally effective as itraconazole in the overall treatment of RVVC over a 2-year follow-up, but yielding a significantly better prophylactic effect and also maintenance benefit with lower relapse rate, antifungal susceptibility and growth of azole-resistant species.