Lung Cancer Clinical Trials in Latin America in the Era of Cooperative Groups: A 20-Year Analysis.

PURPOSE: The aim of this study is to characterize lung cancer treatment clinical trials in Latin America before (January 2001-December 2011) and after (January 2012-December 2021) the organization of major Latin American oncology cooperative groups. MATERIALS AND METHODS: Interventional clinical trials were identified in ClinicalTrials.gov using the search terms "lung cancer," country filters for 20 Latin American countries, and study start dates January 1, 2001-December 31, 2011, and January 1, 2012-December 31, 2021. Clinical trials were categorized as either originating in Latin America (LA) or outside Latin America (non-LA) with participation of Latin American countries. Descriptive statistics, two-sided Z-scores, and chi-square analyses with 95% CIs were calculated. RESULTS: Overall, 273 clinical trials involving Latin American countries between 2001 and 2021 were identified. Comparing 2001-2011 with 2012-2021, there was an increase in total clinical trials (100 v 173; P < .001). Only 9% (26 of 273) of all trials were LA trials. There was a marked decrease in the proportion of LA trials (14% v 7%, P = .058) and estimated enrollment to LA trials (3,245 v 1,190 patients; P < .001). Recruiting of patients with EGFR (29% v 7%; P < .01) and KRAS (18% v 2%; P < .01) driver mutations also decreased. Trial participation was highest in Brazil, Mexico, Argentina, Chile, and Peru and increased over time: Brazil (61 v 108; 77% increase), Mexico (40 v 88; 120% increase), Argentina (50 v 78; 56% increase), Chile (25 v 57; 128% increase), and Peru (14 v 37; 164% increase). CONCLUSION: There was a significant increase in clinical trial participation by Latin American countries, from 2001-2011 to 2012-2021. However, there were few clinical trials which originated in Latin America or focused on patients with driver mutations.

Treating Glabellar Lines With Botulinum Toxin: Does Your Patient Need to Frown Steadily?

BACKGROUND: The variable relationship between the orbicularis supercilii and frontalis muscles may cause side effects with botulin toxin; steadily frowning is the usual recommendation. Eliminating the need to frown until all injections are over might enhance efficacy and lessen the neurotoxicity risks related to muscle exhaustion. OBJECTIVES: The goal of this study was to investigate whether the digital caliper-assessed distances between the medial and lateral corrugator injection sites and the midline differed significantly in patients persistently frowning from patients resting. METHODS: Seventy-six individuals with glabellar wrinkles treated with botulinum toxin in the authors' private practices for glabellar lines voluntarily contributed their retrospective data about the positions of injection sites. The investigators had freely chosen to inject the medial and lateral sections of the corrugator supercilii during persistent maximum frown or at rest. RESULTS: The mean differences in distances between the medial and lateral injection points and the estimated midline were clinically trivial (1.0 ± 1.28 and 1.5 ± 2.53 mm, respectively), although the distances between the relaxed and contracted medial and lateral injection sites exceeded 1.8 and 2.5 mm in 33.9% and 46.4% of patients, respectively. Distance differences, not significant before 40 years old, were statistically significant only for the lateral injections in older patients (on average, 1.9 ± 3.01 mm). CONCLUSIONS: The average distances from the medial and lateral injection points and the midline appear minimally different in patients who frown until all injections are over and, conversely, patients who rest. Persistently frowning might be advisable only in patients older than 40. Facial asymmetries may be a confounding factor.

Development and Validation of a Photonumeric Scale to Assess Marionette Lines.

BACKGROUND: A validated scale is needed for objective and reproducible comparisons of marionette lines before and after treatment in clinical studies. OBJECTIVE: To describe the development and validation of a 5-point photonumeric marionette lines scale. METHODS: The scale was developed to include an assessment guide, verbal descriptors, and real and morphed subject images for each scale grade. Intrarater and interrater reliability was evaluated in initial scale validation (web-based review) ( N = 51 ) and live-subject validation ( N = 75 ) studies, each completed during 2 sessions. RESULTS: In the initial scale validation study, intrarater agreement for 2 physician raters was near perfect (weighted kappa = 0.92 and 0.94). Interrater agreement was excellent during sessions 1 and 2 (intraclass correlation coefficients of 0.94 and 0.95, respectively). In the live-subject validation study, intrarater agreement for 3 physician raters showed a strong correlation (mean weighted kappa = 0.77). Interrater agreement was high during live-subject validation sessions 1 and 2 (intraclass correlation coefficients = 0.89 for both sessions). CONCLUSION: This new marionette lines scale is a validated and reliable scale for physician rating of marionette line severity.

Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer.

BACKGROUND: Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in the United States. METHODS: We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer. Participants who had previously received one to three lines of therapy and had high FRα tumor expression (≥75% of cells with ≥2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes. RESULTS: A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%). CONCLUSIONS: Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.).

The Scarface Score: Deciphering Response to DNA Damage Agents in High-Grade Serous Ovarian Cancer-A GEICO Study.

Genomic Instability (GI) is a transversal phenomenon shared by several tumor types that provide both prognostic and predictive information. In the context of high-grade serous ovarian cancer (HGSOC), response to DNA-damaging agents such as platinum-based and poly(ADP-ribose) polymerase inhibitors (PARPi) has been closely linked to deficiencies in the DNA repair machinery by homologous recombination repair (HRR) and GI. In this study, we have developed the Scarface score, an integrative algorithm based on genomic and transcriptomic data obtained from the NGS analysis of a prospective GEICO cohort of 190 formalin-fixed paraffin-embedded (FFPE) tumor samples from patients diagnosed with HGSOC with a median follow up of 31.03 months (5.87-159.27 months). In the first step, three single-source models, including the SNP-based model (accuracy = 0.8077), analyzing 8 SNPs distributed along the genome; the GI-based model (accuracy = 0.9038) interrogating 28 parameters of GI; and the HTG-based model (accuracy = 0.8077), evaluating the expression of 7 genes related with tumor biology; were proved to predict response. Then, an ensemble model called the Scarface score was found to predict response to DNA-damaging agents with an accuracy of 0.9615 and a kappa index of 0.9128 (p < 0.0001). The Scarface Score approaches the routine establishment of GI in the clinical setting, enabling its incorporation as a predictive and prognostic tool in the management of HGSOC.

Effectiveness and safety of a narrow band spectrum intense pulsed-light dye with long pulse Nd:YAG laser for treating facial vascular lesions.

OBJECTIVE: Different devices are currently used for treating facial vascular lesions (FVL). This paper presents the aesthetic outcomes using different light-based and laser devices, including narrow band spectrum intense pulsed-light dye (NB-Dye-VL), Pulsed dye laser (PDL)-neodymium-doped yttrium-aluminum-garnet (Nd:YAG) dual-therapy, and either PDL or LP Nd:YAG for treating FVL in a clinical setting. METHODS: A retrospective and single-center study conducted on subjects ≥18 years with FVL. Patients underwent treatment with either PDL + LP Nd:YAG dual-therapy, NB-Dye-VL, PDL, or LP Nd:YAG, according to the patient and lesion characteristics. The primary outcome was the weighted degree of satisfaction. RESULTS: The cohort consisted of fourteen patients, nine women (64.3%) and five men (35.7%). The most prevalent FVL types treated were rosacea (28.6%; 4/14) and spider hemangioma (21.4%; 3/14). Seven patients underwent PDL + Nd:YAG (50.0%), three were treated with NB-Dye-VL (21.4%), and PDL or LP Nd:YAG was performed in two patients each (14.3%). Eleven patients rated their treatment outcome as excellent (78.6%), and three as very good (21.4%). Practitioners 1 and 2 classified treatment results as excellent in eight cases (57.1%) each. No serious or permanent adverse events were reported. Two (14.3%) patients, one treated with PDL and the other with PDL + LP Nd:YAG dual-therapy, had post-treatment purpura, which was successfully resolved with topical treatment after 5 and 7 days, respectively. CONCLUSIONS: NB-Dye-VL and the PDL + LP Nd:YAG dual-therapy devices achieve excellent aesthetic outcomes for treating a wide range of FVL.

Infraorbital Hollow Rejuvenation: Considerations, Complications, and the Contributions of Midface Volumization.

Infraorbital hollows are one of the most common target areas for facial aesthetic treatment; however, they are often perceived to be challenging to treat due to the complex anatomy of the periorbital area, concurrent deformities, and risk of complications. Treatment options include surgical (eg, lower eyelid blepharoplasty with fat transposition or injections) and nonsurgical approaches (eg, fillers). Among these approaches, filler injections have become common practice because they are minimally invasive and provide long-term patient satisfaction. In particular, hyaluronic acid (HA) fillers have been shown to be safe and effective for infraorbital hollow rejuvenation. This review provides an overview of infraorbital hollows, including periorbital anatomy, etiology, clinical assessment, and overlapping deformities, such as malar mounds, festoons, and dark circles under the eyes. Patient and HA filler product selection, injection techniques, as well as potential adverse events, such as bruising/swelling, lower eyelid and malar edema, and vascular occlusions, are discussed. This review also highlights the importance of midfacial volumization to improve outcomes in the infraorbital region and in the overall aesthetic appearance. By selecting appropriate patients and attaining proficiency in periorbital anatomy and infraorbital hollow rejuvenation techniques, clinicians can safely and successfully perform HA filler injections that result in high patient satisfaction.

Effect of virtual reality and music therapy on anxiety and perioperative pain in surgical extraction of impacted third molars.

BACKGROUND: The objective of this study was to evaluate the effect of virtual reality (VR) and music therapy on anxiety and perioperative pain in patients undergoing extraction of impacted third molars. METHODS: A total of 275 patients who had to undergo surgery for third-molar extraction participated in a randomized controlled trial and were divided into 3 parallel groups: music therapy intervention (n = 91), VR intervention (n = 93), and control (n = 91). The Spielberger State-Trait Anxiety Inventory and the visual analog scale of pain intensity were used as measurements in this study. RESULTS: Patients in the music therapy and VR groups showed a greater reduction in anxiety level scores after third-molar extraction surgery (reduction in total anxiety in music group: 15.12; 95% CI, 13.16 to 17.08; Rosenthal r, 1.61; P < .001; reduction in total anxiety in VR group: 9.80; 95% CI, 7.66 to 11.95; Rosenthal r, 0.97; P < .001; reduction in total anxiety in control group: 9.80; 95% CI, 7.66 to 11.95; Rosenthal r, 0.97; P < .001). The intensity of pain after the intervention was lower in patients in the music therapy group than patients in the control group (P = .04). After the intervention, the music therapy and VR groups presented a significant decrease in systolic blood pressure (P < .05), diastolic blood pressure (P < .05), and heart rate (P < .05) compared with the control group. CONCLUSIONS: These findings suggest that the use of music therapy and VR during third-molar extraction surgery reduces anxiety and improves the patient's physiological parameters. PRACTICAL IMPLICATIONS: Implementation of these interventions (noninvasive, nonpharmacologic, economic) in the field of oral and maxillofacial surgery and dentistry could improve procedures performed under local anesthesia, improving the clinical experience of patients. This clinical trial was registered with the Australian New Zealand Clinical Trials Registry. The registration number is ACTRN12622000384752.

Body Contouring Using a Combination of Pulsed Ultrasound and Unipolar Radio Frequency: A Prospective Pilot Study.

OBJECTIVE: To assess the efficacy and safety of a new non-invasive body contouring device in patients with localized fat in abdomen or in abdomen and hips. Additionally, we also evaluated the patient satisfaction with the procedure. METHODS: Prospective and non-randomized open label study. The patients underwent four sessions, separated by 1 week each, with the Alma PrimeX, a non-invasive body contouring device that combines pulsed non-focus ultrasound and a Unipolar radiofrequency. The primary end point was the mean change in fat tissue thickness, assessed by diagnostic ultrasound, from baseline to 3-months after the last treatment-session. RESULTS: Fifteen subjects were evaluated. As compared to pre-treatment thickness, Hodges-Lehmann median difference (95% CI) was - 85.3 (- 107.5 to - 62.0) mm, p = 0.0001; - 70.3 (- 95.0 to - 48.5) mm, p = 0.0001; - 100.0 (- 140.5 to - 49.5) mm, p = 0.0039; and - 71.8 (- 132.5 to - 23.0) mm, p = 0.0078 in infraumbilical, supraumbilical, right hip, and left hip, respectively. Pretreatment fat volume was significantly reduced from 32.9% to 31.2%, p = 0.0006. The median (interquartile range) degree of patient satisfaction was 4.0 (1.0-5.0), with 13 (86.7%) patients being "Highly satisfied" or "Satisfied" with the treatment results. The most common adverse event was discomfort, followed by erythema. All the adverse events were mild and were successfully resolved without treatment. CONCLUSIONS: Combine therapy of a Pulsed non-focus ultrasound and Unipolar radiofrequency using the non-invasive device Alma PrimeX was an effective and safe treatment for reducing fat tissue thickness in abdomen and hips in patients with localized fat. Patients' satisfaction with the procedure was high. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Transgenerational effects of parental crude oil exposure on the morphology of adult Fundulus grandis.

The current study involved exposing adult F0 Gulf killifish (Fundulus grandis) to Macondo-252 oil for 36 to 44 days and assessing the effects of this oiling on the swimming performance and morphology in two generations of progeny reared in clean water. Following exposure to oil, the F0 fish were used as broodstock to generate four lineages of F1 fish using a full-matrix mating design derived from the gametes of clean and oil-exposed parents. Later, the four lineages of F1 fish were used as broodstock to create an F2 generation of the same four lineages. We found few differences in embryonic outcome (% dead,% hatched, and% unhatched) in any of the four lineages of F1 and F2 fish. However, as adults, F1 and F2 fish derived from oil-exposed males from the F0 generation had significantly lower critical swimming speeds (Ucrit) than both the control and maternally oil-exposed lineages. Additionally, progeny of oil-exposed fish had altered body shape based on the statistical analysis of two-dimensional landmark-based geometric morphometrics. Fish from oil-exposed lineages showed increased body depth, altered spinal curvature, and changes in the upward angle of projection of the head. Both generations had a significant main effect of maternal and paternal oil exposure on shape; however, F0 paternal oil exposure explained more of the variance in shape across both generations relative to F0 maternal exposure. Our findings demonstrate that parental exposure to oil can impact the shape and aerobic swimming capacity of offspring for at least two generations after the original paternal oiling.

Comparative Study between the Combination of Dexamethasone and Bupivacaine for Third Molar Surgery Postoperative Pain: A Triple-Blind, Randomized Clinical Trial.

Objectives: To compare the possible benefits of the combination of dexamethasone-bupivacaine with articaine-epinephrine as an anaesthetic block after third molar surgery. Materials and Methods: Triple-blind, randomized, controlled, parallel, phase 3 clinical trial. Two groups: experimental (93 patients) with standard anaesthetic block: 40/0.005 mg/mL articaine-epinephrine and submucosal reinforcement with 0.8 mg dexamethasone-5% bupivacaine; and control group (91 patients) with standard block: 40/0.005 mg/mL articaine-epinephrine. The surgery consisted of the extraction of the impacted mandibular third molar by performing a procedure following the same repeatable scheme. The visual analogue scale (VAS) was used to analyse postoperative pain. Results: Groups were homogeneous, without significant differences related to epidemiological variables. Postoperative pain among the first, second, and seventh postoperative days was statistically significantly lower in the experimental group compared to the control group (p < 0.001). Drug consumption was lower in the experimental group throughout the study period (p < 0.04). Conclusion: Bupivacaine is an alternative to articaine in oral surgery, being more effective in reducing postoperative pain by reducing patients' scores on the VAS as well as their consumption of analgesic drugs after surgery.

Ultrasound patterns of different dermal filler materials used in aesthetics.

Background Hyaluronic acid (HA) injection procedures has experienced an unprecedented increase. Aims To assess and determine, by using ultrasound examinations, the patterns corresponding to different dermal fillers. Patients/Methods Observational and retrospective bicenter study conducted on patients who underwent previous aesthetic treatments with dermal fillers. Ultrasound examinations were performed, at each study center, by one experienced observer. Results Sixty patients were included in the analysis. Among them, 48 patients showed a well-defined ultrasound pattern, while 12 exhibited a mixed one. According to ultrasound images, 4 different patterns were identified: [1] Heterogeneous, characterized by alternating hyperechoic and anechoic areas, which are visualized in the tissue in a heterogeneous way. This pattern is associated with healthy skin/subcutaneous cellular tissue and with fully integrated HA fillers. [2] Fine grain snowfall, characterized by alternating hyperechoic imaging, with posterior echogenic shadows. It is typical of liquid injectable silicone. [3] Coarse grain snowfall, characterized by hyperechoic images distributed all over the tissue. This is typical of calcium hydroxyapatite and polymethyl methacrylate-based fillers. [4] Globular, typical "cystic" imaging, with anechoic images indicative of liquid semi-liquid content. This pattern is characteristic of polyalkylamides and polyacrylamides, and HA-based fillers immediately after their injection. The presence of "mixed" patterns is mainly due to different aesthetic procedures performed at different times. Conclusions Ultrasound imaging may be a valuable tool for assessing the nature of former dermal filler procedures in daily practice. The identification of these patterns will allow specialists to choose the best therapeutic approach in patients who underwent previous aesthetictreatments.

Ultrasound assessment of tissue integration of the crosslinked hyaluronic acid filler VYC-25L in facial lower-third aesthetic treatment: A prospective multicenter study.

BACKGROUND: Dermal fillers have become an integral part of any aesthetic physician's intervention. AIMS: To assess, by means of ultrasounds, the tissue integration of the hyaluronic acid (HA) dermal filler VYC-25L in chin and jaw. METHODS: Prospective, noncomparative, open-label, and multicenter study conducted on healthy subjects, with age comprised between 30 and 60 years old, who attended to the clinic to perform a facial rejuvenation treatment of the lower third of the face. VYC-25L was injected using a 27G needle (supraperiosteal bolus, from 0.2 to 0.3 mL per bolus) in the chin and with canula (retrograde threads, from 0.4 to 0.6 mL) in the jaw. Ultrasound examinations (UE) were performed at each study center by the same experienced observer at baseline, immediately after injection, 48 hours, and 30 days after treatment. RESULTS: Thirty patients (10 per center) were included in the study. At baseline, UE found a characteristic heterogeneous pattern of subcutaneous cellular tissue, with alternation of soft anechoic and hyperechoic images. The UE, performed immediately after treatment, showed a poorly defined globular ultrasound pattern, with anechoic images indicative of liquid content. Forty-eight hours after treatment, UE are still showing a globular pattern, with well-defined anechoic areas. Thirty days after treatment, a thickening of the subcutaneous cellular tissue was observed in all the evaluated zones, with a total integration of the HA into the tissue. CONCLUSION: VYC-25L might represent a significant advance in volumization/restoration of the lower face. Its biointegration was total at day 30 and practically complete at 48 hours of treatment.

Correction to: Concomitant Use of Hyaluronic Acid and Laser in Facial Rejuvenation.

The article Concomitant Use of Hyaluronic Acid and Laser in Facial Rejuvenation written by Urdiales-Gálvez et al. was originally published electronically on the publisher's internet portal (currently SpringerLink) on May 9, 2019, without open access.

Different Pathological Complete Response Rates According to PAM50 Subtype in HER2+ Breast Cancer Patients Treated With Neoadjuvant Pertuzumab/Trastuzumab vs. Trastuzumab Plus Standard Chemotherapy: An Analysis of Real-World Data.

Background: Double blockade with pertuzumab and trastuzumab combined with chemotherapy is the standard neoadjuvant treatment for HER2-positive early breast cancer. Data derived from clinical trials indicates that the response rates differ among intrinsic subtypes of breast cancer. The aim of this study is to determine if these results are valid in real-world patients. Methods: A total of 259 patients treated in eight Spanish hospitals were included and divided into two cohorts: Cohort A (132 patients) received trastuzumab plus standard neoadjuvant chemotherapy (NAC), and Cohort B received pertuzumab and trastuzumab plus NAC (122 patients). Pathological complete response (pCR) was defined as the complete disappearance of invasive tumor cells. Assignment of the intrinsic subtype was realized using the research-based PAM50 signature. Results: There were more HER2-enriched tumors in Cohort A (70 vs. 56%) and more basal-like tumors in Cohort B (12 vs. 2%), with similar luminal cases in both cohorts (luminal A 12 vs. 14%; luminal B 14 vs. 18%). The overall pCR rate was 39% in Cohort A and 61% in Cohort B. Better pCR rates with pertuzumab plus trastuzumab than with trastuzumab alone were also observed in all intrinsic subtypes (luminal PAM50 41 vs. 11.4% and HER2-enriched subtype 73.5 vs. 50%) but not in basal-like tumors (53.3 vs. 50%). In multivariate analysis the only significant variables related to pCR in both luminal PAM50 and HER2-enriched subtypes were treatment with pertuzumab plus trastuzumab (Cohort B) and histological grade 3. Conclusions: With data obtained from patients treated in clinical practice, it has been possible to verify that the addition of pertuzumab to trastuzumab and neoadjuvant chemotherapy substantially increases the rate of pCR, especially in the HER2-enriched subtype but also in luminal subtypes, with no apparent benefit in basal-like tumors.

Concomitant Use of Hyaluronic Acid and Laser in Facial Rejuvenation.

BACKGROUND: Facial aging is a process that involves many different changes. Therefore, in many patients, it may be necessary to perform a combined treatment. Botulinum toxin A and dermal fillers are the two most popular nonsurgical cosmetic procedures performed globally to treat age-associated changes. However, there are not many studies reporting the concomitant use of dermal fillers and laser technology for facial rejuvenation. This review aims to assess the concomitant use of dermal hyaluronic acid (HA) fillers and laser technology for facial rejuvenation. METHODS: The present updated consensus recommendations are based on the experience and opinions of the authors and on a literature search. RESULTS: If a combined procedure (HA and light treatments) is to be performed, on the same day, the panel recommends starting always with the light treatments, avoiding skin manipulations after having injected HA. To customize the therapeutic management, it is crucial to establish a precise diagnosis of the photodamage and loss of volumes suffered by the patients. CONCLUSIONS: The currently available scientific evidence about the combined use of HA fillers and laser-radiofrequency-intense pulsed light (laser/RF/IPL) is limited and encompasses mainly small and nonrandomized studies. Nevertheless, most of these studies found that, on average, the concomitant use (same day) of laser and HA fillers for facial rejuvenation represents an effective and safe strategy which improves clinical results and patient's satisfaction. Future well-designed clinical studies are needed regarding the effectiveness and safety of combination filler/laser treatments. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Treatment of Soft Tissue Filler Complications: Expert Consensus Recommendations.

BACKGROUND: Dermal fillers have been increasingly used in minimally invasive facial esthetic procedures. This widespread use has led to a rise in reports of associated complications. The aim of this expert consensus report is to describe potential adverse events associated with dermal fillers and to provide guidance on their treatment and avoidance. METHODS: A multidisciplinary group of experts in esthetic treatments convened to discuss the management of the complications associated with dermal fillers use. A search was performed for English, French, and Spanish language articles in MEDLINE, the Cochrane Database, and Google Scholar using the search terms "complications" OR "soft filler complications" OR "injectable complications" AND "dermal fillers" AND "Therapy". An initial document was drafted by the Coordinating Committee, and it was reviewed and modified by the experts, until a final text was agreed upon and validated. RESULTS: The panel addressed consensus recommendations about the classification of filler complications according to the time of onset and about the clinical management of different complications including bruising, swelling, edema, infections, lumps and bumps, skin discoloration, and biofilm formation. Special attention was paid to vascular compromise and retinal artery occlusion. CONCLUSIONS: Clinicians should be fully aware of the signs and symptoms related to complications and be prepared to confidently treat them. Establishing action protocols for emergencies, with agents readily available in the office, would reduce the severity of adverse outcomes associated with injection of hyaluronic acid fillers in the cosmetic setting. This document seeks to lay down a set of recommendations and to identify key issues that may be useful for clinicians who are starting to use dermal fillers. Additionally, this document provides a better understanding about the diagnoses and management of complications if they do occur. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Biomarkers of Aryl-hydrocarbon Receptor Activity in Gulf Killifish (Fundulus grandis) From Northern Gulf of Mexico Marshes Following the Deepwater Horizon Oil Spill.

Following the Deepwater Horizon oil spill, shorelines throughout the Barataria Basin of the northern Gulf of Mexico in Louisiana were heavily oiled for months with Macondo-252 oil, potentially impacting estuarine species. The Gulf killifish (Fundulus grandis) has been identified as a sentinel species for the study of site-specific effects of crude oil contamination on biological function. In November and December 2010, 4-5 months after the Macondo well was plugged and new oil was no longer spilling into the Gulf waters, Gulf killifish were collected across the Barataria Basin from 14 sites with varying degrees of oiling. Fish collected from oiled sites exhibited biological indications of exposure to oil, including increase in cytochrome P4501A (CYP1A) mRNA transcript and protein abundances in liver tissues. Immunohistochemistry revealed increases in gill, head kidney, and intestinal CYP1A protein at heavily oiled sites. Intestinal CYP1A protein was a sensitive indicator of exposure, indicating that intestinal tissue plays a key role in biotransformation of AHR ligands and that ingestion is a probable route of exposure, warranting additional consideration in future studies.

Preventing the Complications Associated with the Use of Dermal Fillers in Facial Aesthetic Procedures: An Expert Group Consensus Report.

BACKGROUND: The use of dermal fillers in minimally invasive facial aesthetic procedures has become increasingly popular of late, yet as the indications and the number of procedures performed increase, the number of complications is also likely to increase. Paying special attention to specific patient characteristics and to the technique used can do much to avoid these complications. Indeed, a well-trained physician can also minimize the impact of such problems when they do occur. METHODS: A multidisciplinary group of experts in aesthetic treatments reviewed the main factors associated with the complications that arise when using dermal fillers. A search of English, French and Spanish language articles in PubMed was performed using the terms "complications" OR "soft filler complications" OR "injectable complications" AND "dermal fillers". An initial document was drafted that reflected the complications identified and recommendations as to how they should be handled. This document was then reviewed and modified by the expert panel, until a final text was agreed upon and validated. RESULTS: The panel addressed consensus recommendations about the preparation, the procedure and the post-procedural care. The panel considered it crucial to obtain an accurate medical history to prevent potential complications. An additional clinical assessment, including standardized photography, is also crucial to evaluate the outcomes and prevent potential complications. Furthermore, the state of the operating theatre, the patient's health status and the preparation of the skin are critical to prevent superficial soft tissue infections. Finally, selecting the appropriate technique, based on the physician's experience, as well as the characteristics of the patient and filler, helps to ensure successful outcomes and limits the complications. CONCLUSIONS: This consensus document provides key elements to help clinicians who are starting to use dermal fillers to employ standard procedures and to understand how best to prevent potential complications of the treatment. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .