Double-Blind, Randomized, Placebo-Controlled, Dose-Response Study of the Safety and Efficacy of Botulinum Toxin Type A in Subjects with Crow''s Feet

BACKGROUND: Published evidence suggests that botulinum toxin type A (BTX-A) is an effective treatment for crow's feet. However, few dose-ranging studies have been performed. OBJECTIVES: To assess the safety and efficacy of a single treatment with one of four doses of BTX-A (Botox/Vistabel, Allergan Inc) compared with placebo for the improvement of crow's feet. METHODS: Subjects received a single bilateral treatment of 18, 12, 6, or 3 U of BTX-A or placebo injected into the lateral aspect of the orbicularis oculi muscle (parallel-group, double-blind design). Investigators and subjects rated crow's feet severity at maximum smile on day 7 and at 30-day intervals from days 30 to 180. RESULTS: As observed by both investigators and subjects, all doses of BTX-A resulted in improvements in crow's feet severity when compared with placebo. A dose-dependent treatment effect for efficacy was observed, with higher doses having an increased magnitude and duration of effect. However, a clear differentiation between the 18 U and 12 U doses was not apparent. Few adverse events were reported, with no statistically significant differences between BTX-A and placebo in the incidence of subjects experiencing adverse events. CONCLUSION: BTX-A is safe and effective in decreasing the severity of crow's feet, with 12 U per side suggested as the most appropriate dose.     

Botulinum A Toxin (BOTOX) in the Lower Eyelid: Dose-Finding Study

BACKGROUND: Botulinum toxin type A (BTX-A, BOTOX) is an excellent therapeutic option for hyperkinetic facial lines. It improves wrinkles by relaxing the muscles of facial expression, which underlie the rhytids. Periocular wrinkles such as lateral orbital rhytids respond well to treatment. BOTOX can be used in the lower eyelid to improve wrinkles and widen the eye. OBJECTIVE: To determine whether there is additional benefit in using more than 2 U of BTX-A to improve infraorbital wrinkles and widen the eye. METHODS: Nineteen women had BTX-A injected into the orbicularis oculi muscle. Eleven women had 4 U injected into the lower eyelid bilaterally, 3 mm below the ciliary margin, and 12 U of BTX-A injected into one lateral orbital (crow's feet) area. Eight patients had 8 U injected bilaterally into the lower eyelid and 12 U placed unilaterally into the crow's feet. Physicians and patients independently evaluated the degree of improvement (grade 3=dramatic improvement, grade 2=moderate improvement, grade 1=mild improvement, and grade 0=no improvement). Single investigator analysis was used to measure, in actual millimeters, the amount of increase in palpebral aperture. Side effects were noted. RESULTS: Improvement was noted in lower eyelid wrinkles by both physicians and patients at both dose groups. When only the lower lid was injected, patients reported an improvement of 1.18 with 4 U and a grade of 1.63 with 8 U. When both the lower eyelid the lateral orbital area were treated, an improvement of 1.73 was reported with 4 U and a grade of 2.25 reported with 8 U in the lower eyelid. Physician evaluations had grades of 1.85 for 4 U alone and 1.85 with 8 U alone. Grades of 2.35 and 2.25 were obtained for 4 U plus 12 U and 8 U plus 12 U, respectively. An increase in palpebral aperture (IPA) occurred in all subjects. Subjects who received 4 U in the lower eyelid alone had a 1.8-mm IPA at rest and a 2.6-mm increase at full smile. Subjects who received 8 U of BTX-A alone in the lower lid had an IPA of 2.2 mm at rest and 2.9 mm at full smile. Eyes treated with 12 U in the bilateral orbital area plus 4 U in the lower eyelid had an IPA of 2.2 at rest and 4.5 mm at full smile. Those treated with 8 U in the lower lid plus the crow's feet had an IPA of 1.5 at rest and 4.0 at full smile. Side effects increased with dosage, with eight of eight subjects in the 8-U dose groups reporting bothersome side effects such as lower eyelid edema and incomplete sphincter function. CONCLUSION: A dose-response curve is seen with increasing doses of BTX-A used in the lower eyelid. Treatment of the lateral orbital area in combination with the lower lid produces a synergistic response at lower doses, but at higher doses, a plateau effect is suggested. Although increasing doses of BTX-A increases eye widening, unattractive results and side effects are seen at higher doses. The authors recommend that lower 2- or 4-U doses of BTX-A be used in the lower eyelid and specifically discuss techniques.     

Radiographic classification of osteoarthritis in commonly affected joints of the foot

OBJECTIVE: To develop a radiographic atlas for the classification of osteoarthritis (OA) in commonly affected joints of the foot based on observations of osteophytes and joint space narrowing, and to assess its intra- and inter-examiner reliability. DESIGN: Weightbearing dorso-plantar and lateral foot radiographs from people aged over 65 years were examined, and an atlas was developed incorporating characteristic OA features of five foot joints: the first metatarsophalangeal joint, the first cuneo-metatarsal joint (1(st) CMJ), the second cuneo-metatarsal (2(nd) CMJ), the navicular-first cuneiform joint and the talonavicular joint. To assess the reliability of the atlas, two examiners independently rated 50 radiographs on two separate occasions. RESULTS: Observations using the atlas demonstrated moderate to excellent reliability within examiners (percentage agreement from 86 to 99% and weighted kappa from 0.45 to 0.95), and, with the exception of joint space narrowing of the 2(nd) CMJ from the lateral projection, fair to excellent reliability between examiners (percentage agreement from 86 to 97% and weighted kappa from 0.32 to 0.87). Intra-class correlation coefficients for the overall foot OA score (representing the sum of observations for all joints from both feet) ranged between 0.83 and 0.89 for intra-examiner comparisons, and between 0.72 and 0.74 for inter-examiner comparisons. CONCLUSION: Radiographic features of OA in commonly affected foot joints can be documented with high levels of agreement within examiners and moderate levels of agreement between examiners. Provided single examiners or consensus gradings are used, the atlas appears to be a useful tool to assist in the standardization of foot OA assessment for epidemiological and clinical studies.     

The Effect of Full-Face Broadband Light Treatments Alone and in Combination With Bilateral Crow''s Feet Botulinum Toxin Type A Chemodenervation

BACKGROUND: Broadband light (BBL; Intense Pulsed Light; Lumenis Ltd., Yokneam, Israel) is a powerful, nonablative, light-based technology that targets melanin and hemoglobin and stimulates the formation of collagen and elastin. Botulinum toxin type A (BTX-A; BOTOX; Allergan Inc., Irvine, CA) treatment of the lateral periocular region relaxes the vertical fibers of the orbicularis oculi and results in softening of the lateral orbital crow's feet rhytides and widening of the palpebral aperture. OBJECTIVE: To compare the effects of full-face BBL in combination with BTX-A and BBL alone in female subjects with Fitzpatrick I-III skin types, Glogau II-III rhytides, and significant associated facial lentigines and telangiectasia. METHODS: This was a prospective, randomized study of 30 women with moderate to severe crow's feet rhytides. Half of the subjects were treated with BTX-A and BBL and the other half with BBL alone. Their response was assessed clinically and photographically. Skin biopsies of the temporal skin were taken from two subjects in each group and were stained with Masson trichrome. RESULTS: Patients treated with a combination of BTX-A and BBL experienced a better response to treatment, both at rest and on maximum smile, as well as a slightly improved response in associated lentigines, telangiectasia, pore size, and facial skin texture compared with patients who received BBL treatment alone. Skin biopsies showed an increase in dermal collagen in each group. CONCLUSIONS: The patients in this study benefited from both treatments. Although BBL led to a remarkable improvement in full-face telangiectasias, lentigines, and skin texture, the improvement increased in all categories with combination therapy. In addition, an added improvement in the full-face aesthetic with both BTX-A and BBL therapy combined was obvious. These results suggest that both treatments--although evidently complementary--may also act synergistically to produce optimal clinical effects, revolutionizing the treatment of facial aging.     

正常汉族青年人微笑特征的计算机测量研究

目的：研究汉族正常he青年人的微笑特征，为正畸临床提供参考。方法：在头颅定位仪辅助定位下，利用数码相机采集90名18～24岁学生(男44人，女46人)正面休息位及微笑位照片，进行计算机辅助测量分析，得到29项有关微笑特征的测量指标。结果：正常he男女面部软组织特征有显著差异，软组织动态变化无明显差异；下唇上缘与上切牙切缘距．微笑线比率及左上中切牙临床冠长三项反映微笑时唇齿关系的指标，男女之间有显著性差异；微笑类型具有性别差异。结论：姿势性微笑位是研究微笑的标准像位；微笑特征中的部分指标显示出性别差异，因此男女应分别进行研究；正常he女性的中位微笑更接近理想微笑的标准。     

微笑特征计算机测量分析系统的研制和开发

目的：开发实用性强、重复性好的微笑特征计算机测量分析系统，为正畸临床及相关研究提供有效工具。方法：利用数码照相机采集患者休息位及微笑位的正面像；在Windows 2000 Professional环境下应用Microsoft Visual C^ 6．0语言开发系统；使用该系统对患者正面像进行定点测量，其中休息位有10个标志点，微笑位有21个标志点，可得到29项微笑特征指标。结果：该系统具有良好的重测性并具有以下特点：测量数据准确；测量项目丰富；使用方便快捷；数据处理功能完善；兼容性较好。结论：该系统可为正畸临床病例诊断、矫治计划制定及疗效评价提供指导，同时也是相关科学研究的有效工具。     

Validation of a self-report instrument for assessment of hallux valgus

OBJECTIVES: To validate an instrument for self-reported hallux valgus (HV). METHODS: The self-report instrument consists of five line drawings for each foot depicting a sequential increase in HV angle of 15 degrees developed from a photograph of a normal foot. Participants were asked to select the picture which best represented their left and right feet in turn. Four hundred and fifty-nine subjects completed the self-report instrument: 100 attending a hospital rheumatology clinic and 359 who participated in a community questionnaire study. Three hundred and eighty-four completed it on two occasions (1-2 months apart in 71 subjects and 3-6 months apart in 313) and were assessed once by a blinded observer. Twenty-five subjects were assessed by the blinded observer on two occasions. Validity of the instrument was assessed by the weighted kappa statistic for subject-observer agreement and reliability by the weighted kappa statistics for subject repeatability and observer repeatability. These analyses were repeated for HV dichotomised as present or absent. RESULTS: For the five-grade HV scale, weighted kappa scores (left and right feet combined) were 0.45 for subject-observer agreement, 0.53 at 1-2 months and 0.51 at 3-6 months for subject repeatability, and 0.82 for observer repeatability. For the dichotomised scale (left and right feet combined), sensitivity was 75% and specificity was 82%: kappa scores were 0.55 for subject-observer agreement, 0.63 at 1-2 months and 0.61 at 3-6 months for subject repeatability and 0.83 for observer repeatability. CONCLUSIONS: The HV self-report instrument provides a valid and reliable assessment of the presence and severity of HV and appears suitable for use in epidemiological studies.     

Long-term effects of botulinum toxin type A (Botox) on facial lines: a comparison in identical twins

OBJECTIVE: To evaluate the presence of imprinted facial lines in identical twin sisters, one of whom had received botulinum toxin type A (Botox) treatment in the forehead and glabellar region regularly for 13 years and one of whom had not. Crow's feet were also compared. METHODS: One twin received Botox in the forehead and glabellar region (approximately 2 to 3 times each year over the past 13 years) and in the crow's feet (twice in past 2 years). Her twin received Botox only twice (in the forehead and glabellar region, 3 and 7 years ago). RESULTS: Imprinted forehead and glabellar lines were not evident in the regularly treated twin but were evident in the minimally treated twin. Crow's feet were less noticeable when the regularly treated twin smiled (even at 7 months after treatment) than when the minimally treated twin smiled. Untreated facial areas (eg, nasolabial folds) showed comparable aging in both twins. Neither twin experienced adverse effects. CONCLUSIONS: Long-term treatment with Botox can prevent the development of imprinted facial lines that are visible at rest. Botox treatment can also reduce crow's feet. Treatment is well tolerated, with no adverse events reported during 13 years of regular treatment in this study.     

Screening for hand osteoarthritis (OA) using a postal survey.

OBJECTIVE: The aim of this study was to determine the feasibility of screening for hand osteoarthritis (OA) using a postal survey. METHODS: Men and women aged 40-79, selected at random from a general practice in Nottingham, were sent a postal survey concerning arm pain. Subjects were asked to identify presence of any nodes, based on a diagrammatic example, and to document specific distal (DIP) and proximal (PIP) nodes. One hundred and thirty-nine subjects were subsequently assessed by a nurse metrologist, blinded to the subjects assessment. Subject-observer agreement was measured by calculating unweighted kappa (kappa). In addition, sensitivity and specificity were calculated, taking observer-identified nodes as the 'gold standard'. Intraobserver reproducibility was assessed on 10 subjects with nodes. RESULTS: Intraobserver reproducibility was reasonable at all sites (kappa>/=0.59). Of the 56 subjects with observer-identified 'any nodes', 40 subjects had correctly identified them (sensitivity 71.4%); with three subjects incorrectly identifying nodes (specificity 96.4%). Corresponding kappa was 0.70. Subject-observer agreement was higher for presence/absence of any DIP nodes than PIP nodes (kappa=0.67 and 0.36 respectively). As with nodes overall, specificity was high (100% and 96.6% respectively). Agreement was generally poor for specific joint involvement. CONCLUSION: A postal survey is a useful screening tool for identifying subjects with nodes. Although sensitivity may not be sufficient to permit assessment of prevalence of hand OA in the community, it has potential applications in terms of identifying and defining cases for further study.     

Definitive Treatment for Crow’s Feet Wrinkles by Total Myectomy of the Lateral Orbicularis Oculi

BACKGROUND: A common dissatisfaction after rhytidoplasty are the remaining lateral eyelid wrinkles also known as crow's feet. METHODS: This article presents an analysis of the enlarged myectomy of the orbicularis oculi muscle used for the definitive treatment of crow's feet in 105 patients during face lifting. Myectomy involved all the lateral portion of the orbicularis oculi muscle exposed after the undermining of the face, corresponding to about one third of the whole orbital extension of the muscle. To avoid depression in the area of the excision, a free graft from the superficial musculoaponeurotic system was performed with the blepharoplasty. RESULTS: The reduction of the crow's feet was significant during the subsequent 5 years of follow-up. CONCLUSION: The enlarged myectomy allowed the treatment of a larger area in the wrinkled region without increasing the complications and with excellent results.     

Botulinum Toxin A Can Positively Impact First Impression

BACKGROUND First impression is influenced by facial appearance and improved by cosmetic surgery.
OBJECTIVE We wanted to determine if treatment with botulinum toxin A (BTxnA) would improve first impression.
MATERIALS AND METHODS Women received BTxnA in the forehead. Photos were taken prior to, and 1 week after, final BTxnA injection in smiling and relaxed poses. Photos were divided into books with each subject represented only once. Evaluators completed a survey rating first impression on various measures of success for each photo.
RESULTS No differences were seen for social skills, financial, or relationship success scales. A significant decrease in first impression scores between treatment photos was seen for academic performance and occupational success. However, analysis of between-subject effects found that "smile/relax" accounted for the decreased score in both scales. Significant increases in first impression scores were seen for dating success, attractiveness, and athletic success scales where smile/relax and BTxnA contributed significantly to the improved scores.
CONCLUSIONS BTxnA improved first impression scores for dating success, attractiveness, and athletic success scales. Academic performance and occupational success scores were not affected by BTxnA when the smile/relax variable was included. The smile/relax variable was a more important predictor for academic performance and occupational success scores.     

Single-Center, Double-Blind, Randomized Study to Evaluate the Efficacy of 4% Lidocaine Cream versus Vehicle Cream During Botulinum Toxin Type A Treatments

BACKGROUND: Botulinum toxin type A (BTX-A) injections are overwhelmingly safe and effective treatment in cosmetic treatment, but some patients are apprehensive about pain associated with injection. OBJECTIVE: To determine whether preprocedural application of lidocaine 4% topical anesthetic cream to the injection site will reduce pain on injection of BTX-A for the treatment of crow's feet. METHODS: Twenty-four participants receiving bilateral injections for crow's feet were enrolled. Subjects were randomized to one of four study groups. Prior to BTX-A injection, group 1 (n = 6) received lidocaine 4% cream on the right side of the face and vehicle cream on the left side of the face; group 2 (n = 6) received vehicle cream on the right side and lidocaine 4% on the left side; group 3 (n = 6) received lidocaine 4% on both sides; and group 4 (n = 6) received vehicle cream on both sides. RESULTS: We observed a statistically significant reduction in subject-reported procedural pain in participants pretreated with lidocaine 4% on both sides of the face compared with controls. CONCLUSION: Lidocaine 4% cream is effective in reducing the pain associated with BTX-A injection for crow's feet. We encourage further study to clarify the optimal use of topical anesthetics in the practice of cosmetic dermatology.     

Reliability and reproducibility of dens fracture classification with use of plain radiography and reformatted computer-aided tomography

BACKGROUND: The classification system of dens fractures by Anderson and D'Alonzo has been widely used in clinical studies. Of the three types of fractures, Type II and Type III are of particular importance because the distinction between them may affect treatment decisions. The purposes of this study were to assess whether this classification is reliable and reproducible and to determine whether computed tomography can improve its reliability and reproducibility. METHODS: Plain radiographs and spiral computed tomography images of dens fractures in eleven patients were assessed, and the fractures were assigned a classification of Type II or Type III at two readings, separated by six months, by two spine surgeons and three neuroradiologists. Kappa coefficients of agreement between the raters as well as the reproducibility of the classifications made by the individual raters were calculated independently for the fracture classifications based on the plain radiographs and those based on the reformatted computed tomography scans. RESULTS: The kappa coefficient for classifications based on plain radiographs was 0.30 and 0.25 (fair agreement) at the first and second readings, respectively. For classifications based on computed tomography scans, the corresponding kappa coefficients were 0.46 (moderate agreement) and 0.67 (substantial agreement). The kappa coefficients for intrarater reliability among the five raters averaged 0.56 (moderate agreement) when computed tomography scans were used and 0.28 (fair agreement) when plain radiographs were used. CONCLUSIONS: Substantial variation with regard to the classification of dens fractures was found within our group of raters. Greater agreement occurred when reformatted computed tomography scans rather than plain radiographs were used as the basis for classification. When classifying dens fractures according to the system of Anderson and D'Alonzo, one should consider using reformatted computed tomography scans and reaching a consensus with multiple raters.     

Interobserver and intraobserver reliability of two classification systems for intra-articular calcaneal fractures

BACKGROUND: For a fracture classification to be useful it must provide prognostic significance, interobserver reliability, and intraobserver reproducibility. Most studies have found reliability and reproducibility to be poor for fracture classification schemes. The purpose of this study was to evaluate the interobserver and intraobserver reliability of the Sanders and Crosby-Fitzgibbons classification systems, two commonly used methods for classifying intra-articular calcaneal fractures. METHODS: Twenty-five CT scans of intra-articular calcaneal fractures occurring at one trauma center were reviewed. The CT images were presented to eight observers (two orthopaedic surgery chief residents, two foot and ankle fellows, two fellowship-trained orthopaedic trauma surgeons, and two fellowship-trained foot and ankle surgeons) on two separate occasions 8 weeks apart. On each viewing, observers were asked to classify the fractures according to both the Sanders and Crosby-Fitzgibbons systems. Interobserver reliability and intraobserver reproducibility were assessed with computer-generated kappa statistics (SAS software; SAS Institute Inc., Cary, North Carolina). RESULTS: Total unanimity (eight of eight observers assigned the same fracture classification) was achieved only 24% (six of 25) of the time with the Sanders system and 36% (nine of 25) of the time with the Crosby-Fitzgibbons scheme. Interobserver reliability for the Sanders classification method reached a moderate (kappa = 0.48, 0.50) level of agreement, when the subclasses were included. The agreement level increased but remained in the moderate (kappa = 0.55, 0.55) range when the subclasses were excluded. Interobserver agreement reached a substantial (kappa = 0.63, 0.63) level with the Crosby-Fitzgibbons system. Intraobserver reproducibility was better for both schemes. The Sanders system with subclasses included reached moderate (kappa = 0.57) agreement, while ignoring the subclasses brought agreement into the substantial (kappa = 0.77) range. The overall intraobserver agreement was substantial (kappa = 0.74) for the Crosby-Fitzgibbons system. CONCLUSIONS: Although intraobserver kappa values reached substantial levels and the Crosby-Fitzgibbons system generally showed greater agreement, we were unable to demonstrate excellent interobserver or intraobserver reliability with either classification scheme. While a system with perfect agreement would be impossible, our results indicate that these classifications lack the reproducibility to be considered ideal.     

Proposal of a modified, treatment-oriented classification of odontoid fractures.

BACKGROUND CONTEXT: The classification scheme of odontoid fractures described by Anderson and D'Alonzo is the one most commonly used. However, uncertainty exists in the distinction between Type II and "shallow" Type III fractures. Moreover, fractures at the base of the odontoid (Anderson and D'Alonzo Type II) include a spectrum of injury patterns. PURPOSE: To modify the Anderson and D'Alonzo classification of odontoid fractures based on current clinical treatment options. STUDY DESIGN: Proposal of a modified classification system for odontoid fractures. METHODS: A more precise distinction between Type II and III fractures based on the presence/absence of C1-C2 facet involvement is proposed. A modified classification of Type II fractures based on fracture line obliquity, displacement and comminution is then proposed, because these are factors deemed to influence management. To evaluate the reproducibility of this classification, 52 odontoid fractures were reviewed and classified by four attending spine surgeons and three spine fellows. RESULTS: There was substantial agreement (at least five of seven respondents) in 70% of cases. The overall kappa value for the modified classification system was 0.48, indicating moderate agreement, and there were no differences in kappa values between attending spine surgeons and fellows. CONCLUSIONS: The reproducibility of this system was demonstrated by the moderate agreement observed when applied to odontoid fractures at our institution. The proposed utility of this system is its ability to guide clinical decision making in the treatment of odontoid fractures. Prospective application of this modified classification system and suggested treatment options is now required.     

Problems in grading of prostatic carcinoma: interobserver reproducibility of five different grading systems

Summary In order to investigate the reproducibility of grading systems for prostatic carcinoma currently in use, a comparative histological grading study was done. These studies were carried out on tissue sections from radical prostatectomy specimens (N=50) stained with hematoxylin and eosin. Five pathologists with varying professional experience participated in the study, using five different grading systems: those of Broders, Brawn, Gleason (for statistical compilation the modified version), Mostofi, and a modified Mostofi grading method recently described by Schroeder and Mostofi. Weighted kappa coefficients ranged from 0.21 to 0.52. None of the systems investigated demonstrated a high degree of reproducibility (k>0.70). Reproducibility of the systems described by Broders and Brawn was reasonably good (k=0.52 and 0.41, respectively). With the modified Gleason method (rearrangement of Gleason scores into 3 grades), a considerable difference was noted between the numerical agreement score (among at least 3 observers) and the measured kappa value (100% and 0.30, respectively). The methods described by Mostofi and Schroeder-Mostofi revealed only limited reproducibility (k=0.21 and 0.34, respectively).     

FACE-Q量表评估全面部除皱术的近期和远期效果

目的:探讨全面部除皱术的手术方法并进行FACE-Q量表评估。方法:2010年1月至2016年12月,北京大学第三医院成形外科对接受全面部除皱提升术女性患者126例(年龄27~64岁,平均43.3岁)进行FACE-Q系列14个量表的评估。结果:共44例患者完成FACE-Q量表,随访6~86个月,平均27.9个月。面部整体...     

Inter-observer reliability and intra-observer reproducibility of the Weber classification of ankle fractures

Our aim was to assess the reproducibility and the reliability of the Weber classification system for fractures of the ankle based on anteroposterior and lateral radiographs. Five observers with varying clinical experience reviewed 50 sets of blinded radiographs. The same observers reviewed the same radiographs again after an interval of four weeks. Inter- and intra-observer agreement was assessed based on the proportion of agreement and the values of the kappa coefficient. For inter-observer agreement, the mean kappa value was 0.61 (0.59 to 0.63) and the proportion of agreement was 78% (76% to 79%) and for intra-observer agreement the mean kappa value was 0.74 (0.39 to 0.86) with an 85% (60% to 93%) observed agreement. These results show that the Weber classification of fractures of the ankle based on two radiological views has substantial inter-observer reliability and intra-observer reproducibility.     

In Search of a Gold Standard Scoring System for the Subjective Evaluation of Cosmetic Outcomes Following Breast‐Conserving Therapy

The absence of a widely accepted method for aesthetic evaluation following breast‐conserving surgery for breast cancer limits the ability to evaluate cosmetic outcomes. In this study, two different panel scoring approaches were compared in an attempt to identify a gold standard scoring system for subjectively assessing cosmetic outcomes following breast‐conserving therapy. Standardized photographs of each participant were evaluated independently by twelve health care professionals involved in breast cancer diagnosis and treatment using the Danoff four‐point scale. Individual Danoff scores were combined using two methods, a random sample “three‐panel” score and an iterative “Delphi‐panel” score, in order to create a final cosmetic score for each patient. Agreement between these two aggregative approaches was assessed with a weighted kappa (wk) statistic. Patient and professional recruitment occurred at two separate tertiary care multi‐disciplinary breast health centers. Women with unilateral breast cancer who underwent breast‐conserving therapy (segmental mastectomy or lumpectomy and radiotherapy) and were at least 2 years after radiotherapy were asked to participate. Ninety‐seven women were evaluated. The Delphi approach required three rounds of evaluation to obtain greater than 50% agreement in all photographs. The wk statistic between scores generated from the “three‐panel” and “Delphi‐panel” approaches was 0.80 (95% CI: 0.71–0.89), thus demonstrating substantial agreement. Evaluation of cosmetic outcomes following breast‐conserving therapy using a “three‐panel” and “Delphi‐panel” score provide similar results, confirming the reliability of either approach for subjective evaluation. Simplicity of use and interpretation favors the “three‐panel” score. Future work should concentrate on the integration of the three‐panel score with objective and patient‐reported scales to generate a comprehensive cosmetic evaluation platform.     

Interassay and interobserver comparability study of four programmed death-ligand 1 (PD-L1) immunohistochemistry assays in triple-negative breast cancer

Different immunohistochemical programmed death-ligand 1 (PD-L1) assays and scorings have been reported to yield variable results in triple-negative breast cancer (TNBC). We compared the analytical concordance and reproducibility of four clinically relevant PD-L1 assays assessing immune cell (IC) score, tumor proportion score (TPS), and combined positive score (CPS) in TNBC. Primary TNBC resection specimens (n = 104) were stained for PD-L1 using VENTANA SP142, VENTANA SP263, DAKO 22C3, and DAKO 28–8. PD-L1 expression was scored according to guidelines on virtual whole slide images by four trained readers.The mean PD-L1 positivity at IC-score ≥1% and CPS ≥1 ranged between 53% and 75% with the highest positivity for SP263 and comparable levels for 22C3, 28–8, and SP142. Inter-assay agreement was good between 28–8 and 22C3 across all scores and cut-offs (kappa 0.68–0.74) and for both assays with SP142 at IC-score ≥1% and CPS ≥1 (kappa 0.61–0.67). The agreement between SP263 and all other assays was substantially lower for all scores. Inter-reader agreement for each assay was good to excellent for IC-score ≥1% (kappa 0.73–0.78) and CPS ≥1 (kappa 0.68–0.74), fair to good for CPS ≥10 (kappa 0.52–0.67) and TPS ≥1% (kappa 0.53–0.72). The percentage of overlapping cases in the positive/negative category was >90% between IC-score ≥1% and CPS ≥1 but below when comparing IC-score ≥1% with CPS ≥10. We demonstrate an overall good inter-reader agreement for all PD-L1 assays in TNBC along with assay specific differences in positivity and concordances, which may aid to select the right test strategy in routine diagnostics.