Current use of fluid biomarkers as outcome measures in Multiple Sclerosis (MS): a review of ongoing pharmacological clinical trials.

The present study aims to describe the state of the art of fluid biomarkers use in ongoing multiple sclerosis (MS) clinical trials.A review of 608 ongoing protocols in the clinicaltrials.gov and EudraCT databases was performed. The trials enrolled patients with a diagnosis of relapsing remitting MS, secondary progressive MS, and/or primary progressive MS according to Revised McDonald criteria or relapsing MS according to Lublin et al. (2014). The presence of fluid biomarkers among the primary and/or secondary study outcomes was assessed.Overall, 5% of ongoing interventional studies on MS adopted fluid biomarkers. They were mostly used as secondary outcomes in phase 3-4 clinical trials to support the potential disease-modifying properties of the intervention. Most studies evaluated neurofilament light chains (NfLs). A small number considered other novel fluid biomarkers of neuroinflammation and neurodegeneration such as glial fibrillary acid protein (GFAP).Considering the numerous ongoing clinical trials in MS, still a small number adopted fluid biomarkers as outcome measures, thus testifying the distance from clinical practice. In most protocols, fluid biomarkers were used to evaluate the effectiveness of approved second-line therapies, but also, new drugs (particularly Bruton kinase inhibitors). NfLs were also adopted to monitor disease progression after natalizumab suspension in stable patients, cladribine efficacy after anti-CD20 discontinuation, and the efficacy of autologous hematopoietic stem cell transplant (AHSCT) compared to medical treatment. Nevertheless, further validation studies are needed for all considered fluid biomarkers to access clinical practice, and cost-effectiveness in the "real word" remains to be clarified.

Time interval between pulse dye laser treatments of port-wine stains: 30 years of experience.

Port-wine stains (PWS) are frequently refractory to laser treatments. The aim of this study is to evaluate the role of treatment interval time. From 1990, 216 patients underwent Pulsed Dye Laser sessions. The laser sessions were scheduled at a minimum interval of 4 weeks to a maximum of 48 weeks. Clinical outcomes were assessed 8 weeks after the last laser session. Better results were obtained with 8 weeks interval time between therapy session, and high efficacies were also found for intervals of 4, 6 and 10 weeks. For greater interval instead, the effectiveness is significantly lower.

The influence of social media on patients' perception of aesthetic treatment outcome. Satisfaction with tattoo removal: A model.

The level of patient satisfaction following tattoo removal often varies and frequently diverge from clinical objectivity. This study assesses how much social media can influence patient satisfaction after picosecond laser (PSL) tattoo removal, in light of the growing influence they have on consumers. Twenty-seven patients were treated with PSL for removal of professional black tattoo. Two groups of patients were identified: those who were already being treated at our institute or had been referred by other physicians (group 1) and those who found us through social media (group 2). Clinical improvement was evaluated 8 weeks after the final laser session and patients' satisfaction was assessed. In both groups, clinical results were homogeneous; however, Group 2 patients' subjective Global Aesthetic Improvement Scale scores were lower than those reported by clinicians (p=0.035), while Group 1 was globally more satisfied (p<0.001). We can affirm that the influence of social media on the perceptions and expectations of patients can affect their level of satisfaction. Particularly for people who are influenced by social media, it is essential to provide explanations prior to laser treatments, in order to clarify what may actually be expected from laser sources.

Hybrid fractional laser treatment for photodamaged facial skin rejuvenation 6 years following fractional CO2 : Comparison of clinical outcome and patients' satisfaction.

OBJECTIVES: Fractional carbon dioxide (CO2 ) laser resurfacing is considered an effective treatment for skin rejuvenation. The request for clinical effectiveness with shorter downtime has led to the development of new hybrid technologies, including a traditional Er:YAG (erbium-doped yttrium aluminium garnet) fractional laser 2940 nm combined with a simultaneous nonablative 1470 nm wavelength. The aim of this study is to compare clinical outcomes and patients' satisfaction with face resurfacing performed with both the CO2  laser and the hybrid laser. METHODS: Nineteen women underwent ultrapulsed CO2 fractional resurfacing for photodamaged facial skin; the same patients underwent the hybrid laser after almost 6 years. Clinical outcomes and patients' satisfaction were evaluated 6 months after the treatment and compared between the two technologies. RESULTS: After both CO2 and hybrid treatment a significant improvement was found in terms of fine lines (p < 0.001 and p = 0.004, respectively), tactile roughness (p < 0.001 and p = 0.002, respectively), and mottled pigmentation (both p < 0.001). Healing times and complications were greater with the CO2 laser. Comparing the two technologies, patients showed better results with the CO2 laser for each score's item, but greater satisfaction with the hybrid laser (p = 0.012). CONCLUSIONS: The present study confirms CO2 laser as the most effective treatment; however, the new hybrid technology revealed good results associated with faster healing and less discomfort.

Laser removal of tattoos in vegan and omnivore patients.

BACKGROUND: Clinical outcomes of tattoo removal vary widely among different patients; it is known that tattoo-related features (such as pigments' type or quality, the use of multicolored inks, tattoo location size, location, layering, and duration) and personal habits (as smoking or skin phototype) could influence the clinical response to treatment, the possible role of nutrition in affecting the laser treatment of tattoos has never been investigated. AIMS: This study aims to compare the clinical response of tattoos removal between omnivore and vegan patients treated with Q-switched laser (QSL). PATIENTS/METHODS: Twenty omnivore and twenty vegan patients treated for professional black tattoo removal with Nd:YAG QSL were enrolled in this study. The number of laser sessions and the median days required for complete healing were recorded; clinical improvement was evaluated 4 weeks after the last laser session. RESULTS: The two groups were not different at the baseline in terms of sex, age, skin phototype, tattoos' age, location, and density. Vegans needed more laser sessions (p < 0.001) to achieve the best outcome, showed worst clinical responses (p = 0.001) and needed more days for complete healing (p = 0.006) compared to omnivores. CONCLUSION: The results of this study point out the influence of vegan diet on QLS removal of tattoos.

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.

Picosecond Laser treatment of Striae Distensae: In vivo Evaluation of Results by 3D Analysis, Reflectance Confocal Microscopy, and Patient's Satisfaction.

BACKGROUND AND OBJECTIVES: The efficacy of picosecond laser (PSL) in the treatment of striae distensae (SD) has been recently reported; otherwise, the base for this improvement has not been clarified yet. The aim of this study is to treat long-lasting SD with PLS and to describe their in vivo morphological variations after treatment using three-dimensional (3D) imaging and reflectance confocal microscopy (RCM). STUDY DESIGN/MATERIALS AND METHODS: A total of 27 patients asking for treatment for SD were treated with four monthly sessions of PLS. Clinical improvement was estimated through a blinded evaluation performed by two independent dermatologists, Global Assessment Improvement Scale (GAIS), patients' satisfaction, 3D imaging, and RCM assessments at baseline and 6 months after the last laser session. RESULTS: Although a clinical improvement of SD was observed in 81.4% of patients according to physicians' GAIS, only 66.6% of patients reported subjective improvement and satisfaction after treatment (P = 0.04). 3D imaging revealed a significant improvement in terms of skin texture (P < 0.001) and mean SD depth (P < 0.001). Otherwise, RCM highlighted collagen remodeling and the appearance of new dermal papillae in all the treated SD compared with baseline. CONCLUSIONS: The present study confirms that PLS represents a safe treatment option for SD; herein, we report morphological documentation of skin variations after PLS treatment. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Comparison of microfocused ultrasound with visualization for skin laxity among vegan and omnivore patients.

BACKGROUND: The aging of facial structures depends on genetic, anatomic, chronologic, and environmental factors that affect the skin and underlying tissues. Microfocused ultrasound with visualization (MFU-V) has emerged as a safe and effective treatment for skin laxity. As the nutritional status may contribute to skin aging, it would be interesting to evaluate whether different dietary patterns can also influence the response to MFU-V treatment for skin laxity. AIMS: The aim of this study is to compare the outcome of MFU-V therapy between omnivore and vegan patients. METHODS: Twenty-seven vegan and twenty-seven omnivorous women who underwent MFU-V treatment for laxity of lower face and neck were enrolled. The clinical outcome was evaluated using the FLR (Facial Laxity Rating) scale after 3 and 6 months from treatment. RESULTS: At baseline, no significant differences were found in terms of FLR scale in both treated sites. After 3 months, reduction in FLR scale was significantly lower for vegans both on face (P = .04) and neck (P = .004). At 6 months, vegan patients had a worse clinical outcome on lower face (P = .001) and neck (P < .001). CONCLUSION: The present study suggests that a vegan diet may negatively influence the outcome of a MFU-V treatment.

Comparison of Postsurgical Scars Between Vegan and Omnivore Patients.

BACKGROUND: Postsurgical skin healing can result in different scars types, ranging from a fine line to pathologic scars, in relation to patients' intrinsic and extrinsic factors. Although the role of nutrition in influencing skin healing is known, no previous studies investigated if the vegan diet may affect postsurgical wounds. OBJECTIVE: The aim of this study was to compare surgical scars between omnivore and vegan patients. METHODS AND MATERIALS: This is a prospective observational study. Twenty-one omnivore and 21 vegan patients who underwent surgical excision of a nonmelanoma skin cancer were enrolled. Postsurgical complications and scar quality were evaluated using the modified Scar Cosmesis Assessment and Rating (SCAR) scale. RESULTS: Vegans showed a significantly lower mean serum iron level (p < .001) and vitamin B12 (p < .001). Wound diastasis was more frequent in vegans (p = .008). After 6 months, vegan patients had a higher modified SCAR score than omnivores (p < .001), showing the worst scar spread (p < .001), more frequent atrophic scars (p < .001), and worse overall impression (p < .001). CONCLUSION: This study suggests that a vegan diet may negatively influence the outcome of surgical scars.

Calcium redistribution contributes to the hard-to-cook phenotype and increases PHA-L lectin thermal stability in common bean low phytic acid 1 mutant seeds.

Seed phytic acid reduces mineral bioavailability by chelating minerals. Consumption of common bean seeds with the low phytic acid 1 (lpa1) mutation improved iron status in human trials but caused adverse gastrointestinal effects, presumably due to increased stability of lectin phytohemagglutinin L (PHA-L) compared to the wild type (wt). A hard-to-cook (HTC) defect observed in lpa1 seeds intensified this problem. We quantified the HTC phenotype of lpa1 common beans with three genetic backgrounds. The HTC phenotype in the lpa1 black bean line correlated with the redistribution of calcium particularly in the cell walls, providing support for the "phytase-phytate-pectin" theory of the HTC mechanism. Furthermore, the excess of free cations in the lpa1 mutation in combination with different PHA alleles affected the stability of PHA-L lectin.

Multicenter study of vacuum-assisted precise tissue release for the treatment of cellulite in a cohort of 112 Italian women assessed with cellulite dimples scale at rest.

Objectives and background: Tissue stabilized-guided subcision (TS-GS) treatment has emerged as a single session treatment for cellulite dimples. To date, studies on a few patients were reported. We present data concerning efficacy and safety of TS-GS for cellulite in a cohort of Italian patients.Patients and Methods: This is a retrospective study involving 122 patients requiring cellulite treatment, classified according to validate cellulite dimples scale at rest, at T0. TS-GS technique is assessed in terms of efficacy (masked evaluations of pre- and post-treatment pictures, satisfaction of patients and variations in cellulite dimples scale at rest), safety of results at 12 months follow-up (T1). U nivariate and multivariate analyses were carried out to evaluate variables associated with the size effect.Results: Masked evaluations of 112 patients completing the study resulted in the correct selection of pre- and post-treatment images in all cases and all patients were satisfied. The mean cellulite dimples scale at rest score improved ≥1 point at T1. We found a significant association between size effect, higher satisfaction (p < .01), cellulite grading at T0 (p < .01), higher BMI (p = .037); a higher BMI was correlated to an increased cellulite grading at T0 (p = .02). Only minor and temporary adverse events were reported.Conclusions: We confirm herein the clinical efficacy and safety of TS-GS for cellulite dimples treatment in a cohort of Italian patients assessed with the validated cellulite dimples scale at rest.

Double phase treatment with flashlamp-pumped pulsed-dye laser and long pulsed Nd:YAG laser for resistant port wine stains in adults. Preliminary reports.

BACKGROUND: Flashlamp-pumped pulsed (FLPP) dye laser still represents the standard treatment for the majority of port wine stains (PWSs), but the results on thick PWSs remain unpredictable, and many of these lesions fail to completely respond. Our aim was to report on the results obtained on unresponsive PWSs to standard laser treatments, by using a double phase laser treatment strategy using two laser passes in the same session. METHODS: Eleven adult patients with facial PWS resistant to dye laser were enrolled. Laser sessions were scheduled every 8 weeks, and each of them consisting of two laser passes. In phase one, two different laser wavelengths (595 nm and 1064 nm) were delivered consecutively to each affected area. In the second phase, the PWS was treated using a pulse stacking technique with the 1064 nm Nd:YAG. RESULTS: One patient was lost to follow-up. Among the remaining ten, 5 (50%) patients showed an excellent improvement (>75%), 3 (30%) patients showed a good improvement (51-75%), and 2 (20%) patients had no or minimal improvement (0-25%). CONCLUSIONS: Our results suggest that the combination of different wavelengths in the same session can be helpful for PWSs resistant to standard laser treatments. However, in most patients two treatment phases were necessary.

Non-ablative fractionated laser skin resurfacing for the treatment of aged neck skin.

BACKGROUND: Aging of the neck skin includes poikiloderma of Civatte, skin laxity and wrinkles. While the vascular alterations of poikiloderma of Civatte can be effectively treated with lasers or intense pulsed light, a successful treatment of dyschromia, skin laxity and wrinkles is still difficult to achieve. OBJECTIVE: To evaluate the safety and efficacy of non-ablative fractional 1540 erbium glass laser for the treatment of aged neck skin, also by means of in vivo reflectance confocal microscopy (RCM). METHODS: A prospective study for neck resurfacing in 18 women with aged neck skin. Six laser treatments were performed in 4-week intervals with a 1540-nm erbium-glass fiber laser. RESULTS: By using a 6-point grading scale, the mean score (±SD; range) at baseline was 3.6 (±1.5; 1-6) for skin dyschromia, 2.9 (±1.4; 1-6) for laxity and 3.3 (±1.3; 1-5) for wrinkles. Three months after the last laser session, we found a significant clinical improvement of dyschromia (p = 0.0002; Wilcoxon test), and wrinkles (p = 0.0004; Wilcoxon test), with a mean (±SD) reduction of 2.5 (±1.0) and 1.9 (±1.1) points in the 6-point grading scale, respectively. No change was observed in laxity. These results were also supported by structural changes documented by RCM. CONCLUSION: Non-ablative fractional 1540 erbium glass laser was both safe and effective for the treatment of dyschromia and wrinkles, but not effective for the laxity of the neck skin.

Variables affecting clinical response to treatment of facial port-wine stains by flash lamp-pumped pulsed dye laser: the importance of looking beyond the skin.

The response of port-wine stains (PWS) to conventional laser treatment in adults is difficult to predict. To assess the influence of local or systemic hemodynamic variables on the clearance of PWS by using flash lamp-pumped pulsed (FLPP) dye laser. All consecutive patients ages 18 years or older undergoing laser treatment for a facial PWS were eligible. Laser sessions were scheduled every 8 weeks. All patients were evaluated based on a standard scale with four evaluation categories, from no or minimal improvement to total or almost total clearance. Clearance was achieved by 50.1 % (95 % confidence interval 35.6-64.7) of patients after a maximum of 15 treatment sessions. In multivariate analysis, increased age, a newly described Type III capillaroscopic pattern, and presence of lesions in dermatome V2 were all associated with a reduced clinical response to treatment. In a model restricted to demographic pattern and patient characteristics, arterial hypertension was also associated with a lower clinical response. A strong association was found between arterial hypertension and the Type III capillaroscopic pattern. Age, arterial hypertension, capillaroscopic pattern, and body location should be considered when planning laser treatment of PWS.

Combination of fractional erbium-glass laser and topical therapy in melasma resistant to triple-combination cream.

BACKGROUND: Melasma is a common melanosis often difficult to treat. OBJECTIVE: The aim of this paper was to report on the safety and efficacy of non-ablative fractional photothermolysis combined with the use of triple-combination cream (TCC) on a large population with melasma resistant (i.e., with no complete/near-complete clearing) to TCC alone. METHODS: Seventy-six patients with resistant melasma underwent a combined treatment protocol. The protocol consisted of a TCC (hydroquinone 4%, retinoic acid 0.03%, hydrocortisone butyrate 0.1%) applied daily for 10 days followed by four laser treatments performed in 3-week intervals with a fractional 1540-nm erbium-glass laser. During these intervals, and for 3 months after the last laser session, TCC was also applied daily following a "pulse-therapy" scheme. Improvement was assessed by the melasma-area-and-severity-index (MASI) score. RESULTS: At 1 month, marked (>75%) and moderate (51-75%) clearing of melasma were observed in 46 of 76 (67.1%) and 12 of 76 (21%) cases, respectively. At 6 months, we noticed a marked improvement in 16 of 76 (21.1%) and no improvement in 33 of 76 (43.4%) patients. CONCLUSION: Our study proposes the combination of NFP/TCC as a useful therapy for patients with melasma resistant to TCC alone, but it shows that its long-term efficacy is limited.

Melasma and low-energy Q-switched laser: treatment assessment by means of in vivo confocal microscopy.

Melasma is an acquired disorder of pigmentation for which several therapeutical options are currently available. Among them, low-energy Q-switched Nd:YAG laser (1,064 nm) has been successfully applied in case series although its long-term efficacy has yet to be proven. In vivo confocal microscopy is a novel imaging technique that permits to explore the skin tissue at a nearly histologic resolution. The aim of our study was to evaluate the laser treatment efficacy by means of confocal microscopy at different time points to elucidate the mechanism of action of the laser and its possible drawbacks. Eight women who presented with melasma on the face were subjected to low-energy Q-switched Nd:YAG laser treatment and then analyzed by means of confocal microscopy. An overall improvement of melasma was noticed clinically and microscopically by means of confocal microscopy. Four cases revealed the presence of dendritic-shaped cells upon confocal microscopy and those patients were the ones presenting with a relapse of the disease. The interpretation of these cells is that they could represent reasonably activated melanocytes. This opens the question whether laser treatment should be modulated to avoid side-effects associated with its use. Confocal microscopy has emerged as an excellent tool for a better understanding of the changes occurring during laser treatment.

Random fractional ultrapulsed CO2 resurfacing of photodamaged facial skin: long-term evaluation.

Although numerous papers have recently been published on ablative fractional resurfacing, there is a lack of information in literature on very long-term results. The aim of this retrospective study is to evaluate the efficacy, adverse side effects, and long-term results of a random fractional ultrapulsed CO2 laser on a large population with photodamaged facial skin. Three hundred twelve patients with facial photodamaged skin were enrolled and underwent a single full-face treatment. Six aspects of photodamaged skin were recorded using a 5 point scale at 3, 6, and 24 months after the treatment. The results were compared with a non-parametric statistical test, the Wilcoxon's exact test. Three hundred one patients completed the study. All analyzed features showed a significant statistical improvement 3 months after the procedure. Three months later all features, except for pigmentations, once again showed a significant statistical improvement. Results after 24 months were similar to those assessed 18 months before. No long-term or other serious complications were observed. From the significant number of patients analyzed, long-term results demonstrate not only how fractional ultrapulsed CO2 resurfacing can achieve good results on photodamaged facial skin but also how these results can be considered stable 2 years after the procedure.

Laser skin rejuvenation: epidermal changes and collagen remodeling evaluated by in vivo confocal microscopy.

Fractionated carbon dioxide (CO2) laser resurfacing is an effective treatment of skin aging. Several studies investigated the morphologic changes due to this laser treatment by using skin biopsies or animal model. Recently, reflectance confocal microscopy (RCM) has emerged as a new tool that can "optically" scan the skin in vivo with a nearly histologic resolution and in a totally noninvasive modality. Our study aims to analyze the skin changes following the ablative fractional CO2 laser sessions by using RCM. Ten patients were subjected to ablative fractional CO2 laser sessions for skin aging. Confocal microscopic images were acquired at baseline (w0), 3 weeks (w3), 6 weeks (w6), and 12 weeks (w12) after laser session. Previously identified confocal parameters were used to assess the skin aging at baseline and after treatment. At w3, the epidermis showed a complete disappearance of the mottled pigmentation upon RCM along with the presence of few Langherans' cells. The collagen type as seen upon RCM observed at baseline was replaced by a newly formed collagen type of long, bright and straight fibers (collagen remodeling). These fibers were parallel arranged and observed throughout the entire RCM mosaic. At w6 and w12 the confocal aspects of the skin was unchanged compared to w3. RCM confirmed the presence of an intense collagen remodeling following laser resurfacing. In line with previous studies, this collagen showed a peculiar arrangement and distribution. The collagen remodeling was still present after 3 months and confirms the long-term effect of the treatment. This is the first time that the skin can be analyzed in vivo at patient's bedside. In the near future, RCM can be an essential adjunct for Clinicians to measure the effects of laser treatment and possibly to gain new insights into the development of side effects.

Nonablative fractional photothermolysis for acne scars: clinical and in vivo microscopic documentation of treatment efficacy.

Fractional photothermolysis has been shown to improve various types of scarring, including atrophic acne scars. The aim of the present authors was to assess the efficacy and safety of the nonablative fractional photothermolysis in the treatment of moderate and severe acne scars. Eighty-seven patients with moderate or severe acne scarring were treated with six sessions with a 1540-nm Erbium glass fiber laser at 3-week intervals. Six months after the final session, 7/87 (8%) patients showed a moderate improvement, whereas 80/87 (92%) patients had a marked improvement. In a subset of patients, the present authors also applied in vivo reflectance confocal microscopy to highlight the relevant microscopic changes. Hence, early and late posttreatment findings, most importantly the replacement of a coarser collagen with a new one, similar to the collagen seen in healthy skin, were observed. In accordance to previous studies, the present authors conclude that nonablative fractional photothermolysis is a safe and effective treatment for moderate or severe acne scarring.