Real-world Implications of Botulinum Neurotoxin A Immunoresistance for Consumers and Aesthetic Practitioners: Insights from ASCEND Multidisciplinary Panel.

Background: As long-term, regular aesthetic botulinum neurotoxin A (BoNT-A) use becomes more commonplace, it is vital to understand real-world risk factors and impact of BoNT-A immunoresistance. The first Aesthetic Council on Ethical Use of Neurotoxin Delivery panel discussed issues relating to BoNT-A immunoresistance from the health care professionals' (HCPs') perspective. Understanding the implications of BoNT-A immunoresistance from the aesthetic patient's viewpoint allows HCPs to better support patients throughout their aesthetic treatment journey. Methods: A real-world consumer study surveyed 363 experienced aesthetic BoNT-A recipients across six Asia-Pacific territories. The survey mapped participants' BoNT-A aesthetic treatment journey and characterized awareness and attitudes relating to BoNT-A immunoresistance and treatment implications. At the second Aesthetic Council on Ethical use of Neurotoxin Delivery meeting, panelists discussed survey findings and developed consensus statements relating to the impact of BoNT-A immunoresistance on the aesthetic treatment journey. Results: Aesthetic BoNT-A patients' depth of knowledge about BoNT-A immunoresistance remains low, and risk/benefit communications need to be more lay-friendly. The initial consultation is the most important touchpoint for HCPs to raise awareness of BoNT-A immunoresistance as a potential side effect considering increased risk with repeated high-dose treatments. HCPs should be cognizant of differences across BoNT-A formulations due to the presence of certain excipients and pharmacologically unnecessary components that can increase immunogenicity. Standardized screening for clinical signs of secondary nonresponse and a framework for diagnosing and managing immunoresistance-related secondary nonresponse were proposed. Conclusion: These insights can help patients and HCPs make informed treatment decisions to achieve desired aesthetic outcomes while preserving future treatment options with BoNT-A.

Emerging Trends in Botulinum Neurotoxin A Resistance: An International Multidisciplinary Review and Consensus.

Botulinum neurotoxin A (BoNT-A) injection is the most widely performed aesthetic procedure and a first-line therapeutic option for various medical conditions. The potential for BoNT-A immunoresistance and secondary nonresponse related to neutralizing antibody (NAb) formation warrants attention as the range of BoNT-A aesthetic applications continues to expand. Methods: An international multidisciplinary panel reviewed published evidence on BoNT-A immunoresistance in aesthetic and therapeutic applications and discussed best practices integrating clinical, ethical, and aesthetic considerations. Consensus statements relating to awareness, assessment, and management of the risk of NAb-related secondary nonresponse in aesthetic practice were developed. Results: There was a consensus that, as doses used in aesthetic practice become like those in therapeutics, rates of NAb formation may be expected to increase. However, the true extent of NAb formation in aesthetics is likely underestimated due to limitations of published evidence and variability in treatment patterns of aesthetic patients. Since BoNT-A therapy is often lifelong, practitioners need to recognize immunogenicity as a potential complication that might affect future therapeutic use and strive to minimize modifiable risk factors. The selection and use of a BoNT-A product with the least immunogenic potential from the beginning may thus be advantageous, especially when treatment with high doses is planned. Conclusions: In view of current trends in BoNT-A aesthetic use, it is essential for practitioners to conduct thorough clinical assessments, inform patients of treatment risks, and develop BoNT-A treatment plans to minimize immunogenicity. This can help preserve the option of continued or future BoNT-A treatment with satisfactory outcomes.

Cancer antigen 15/3: possible diagnostic use in veterinary clinical oncology. Preliminary study.

The cancer antigen 15/3 is a mucin that is associated with the cell membrane, encoded by the MUC1 gene, and recognized by the monoclonal-clone DF3 antibody. The latter antigen was discovered to be specific for both the identification of human mammary neoplasia and during patient follow-up evaluations. The aim of this study is to report and compare the results of the application of direct chemiluminescence in canine blood sera and the kit utilized in human medicine for the determination of Ca 15/3 to verify the diagnostic efficiency of the kit in cases presenting mammary tumors. Specifically, CA 15/3 has proven to be measurable in all samples assayed to distinguish clinically healthy subjects from those with mammary neoplasia.

Group size and composition of Guiana dolphins (Sotalia guianensis) (Van Bénèden, 1864) in the Paranaguá Estuarine Complex, Brazil.

The aim of the present study was to describe the characteristics of Guiana dolphins (S. guianensis) group size and composition in the Paranaguá Estuarine Complex (25 degrees 15'-25 degrees 36' S and 48 degrees 02'-48 degrees 45' W), Paraná State, as well as to verify the existence of relationships between a given environmental variable (water depth, salinity, transparency and temperature) and group size. An area of around 124 km(2) was surveyed by boat from April 2006 to February 2008 in the following subsets of the estuary: Canal do Superagui (approximately 28 km(2)), Pinheiros bay (approximately 34 km(2)), part of Laranjeiras bay, which included the Guaraqueçaba sub-estuary (approximately 38 km(2)), and part of the Mixture Section of the Paranaguá Estuarine Complex (approximately 24 km(2)). In 45 survey days, a total of 147 hours were spent observing 286 groups of S. guianensis. Groups varied from two individuals to aggregations of up to 90 individuals (mean +/- SD: 11.5 +/- 14.4 individuals). Solitary individuals were seen only on five occasions (1.7% of all observations). Groups with calves (n = 247) represented 86.4% overall and were more common in all sub-areas when compared to groups without calves. Groups without calves were found in all sub-areas and were usually smaller and composed of up to 12 individuals. A usual group composition of 70% of adults and 30% of calves was observed considering all sub-areas and seasons. No correlations were found between group size and water temperature (Spearman's rank test, r = 0.0059, p = 0.9338), transparency (Spearman's rank test, r = 0.0597, p = 0.9333), depth (Spearman's rank test, r = 0.1421, p = 0.4698), and salinity (Spearman's rank test, r = -0.1938, p = 0.0665). While Guiana dolphin groups were seen in the entire surveyed area, group size varied significantly among the three main surveyed sub-areas (Kruskal Wallis, H2,196 = 29.85, p = 0.0000). Groups were larger in Laranjeiras bay and smaller in Canal do Superagui. The physical environment, risk of predation, seasonal distribution and abundance of prey are the main possible factors driving larger groups in inner and protected waters.

Feeding associations between Guiana dolphins, Sotalia guianensis (Van Bénèden, 1864) and seabirds in the Lagamar estuary, Brazil.

The main objective of the present study was to describe the characteristics regarding interactions between Guiana dolphins, Sotalia guianensis and seabirds in feeding associations in two distinct areas of the Lagamar estuary, Brazil. Boat-based surveys directed towards photo-identification studies of S. guianensis were conducted in the Cananéia Estuary (CE) (25 degrees 01' S and 47 degrees 55' W) from July 2004 to March 2008, as well as in the Paranaguá Estuarine Complex (PEC) (25 degrees 24' S and 48 degrees 24' W) from April 2006 to February 2008. On all occasions when seabirds were observed engaging in multi-species feeding associations with S. guianensis, data on species involved and their numbers were gathered. From 435 observed groups of S. guianensis in the CE, 38 (8.7%) involved interactions with seabirds. In the PEC, from the 286 observed groups, 32 (11.2%) involved the mentioned interactions. The following seabirds were observed in feeding associations with S. guianensis: Fregata magnificens, Sula leucogaster, Phalacrocorax brasilianus, and Sterna sp. In the CE, S. leucogaster was more commonly observed in feeding associations with Guiana dolphins (chi2 = 22.84; d.f. = 3, p < 0.05), while in the PEC no differences were reported when comparing seabird species (chi2 = 5.78; d.f.=3, p = 0.1223). In the CE, feeding associations were significantly more frequent in inner waters (subset A0; chi2 = 9.52; d.f. = 2, p < 0.05), and in winter (chi2 = 12.46; d.f. = 1, p < 0.05). Within these events, 44.7% of the association groups were composed by more than one seabird species. Seasonality in feeding associations was also observed in the PEC (chi2 = 4.76; d.f. = 1, p < 0.05), with same patterns observed in the CE. Interactions were more frequent in inner waters of the Laranjeiras bay, PEC (chi2 = 11.65; d.f. = 2, p < 0.05). Within these events, 74.2% of the association groups were composed by more than one seabird species. Water transparency, prey and seabird abundance and distribution, cetacean group size, and the life cycle of prey and seabirds are listed as the main factors addressing multi-species feeding associations in the Lagamar estuary.

Evaluation of serum HER2 extracellular domain in early breast cancer patients: correlation with clinicopathological parameters and survival.

BACKGROUND: We explored the correlation between serum human epidermal growth factor receptor-2 (HER2) extracellular domain (ECD) and tissue HER2 status, their relationship with clinicopathological parameters and their impact on disease-free survival (DFS) and overall survival in early breast cancer patients. PATIENTS AND METHODS: This prospective trial included patients with stage I-III breast cancer. Serum HER2 ECD levels were measured by two enzyme-linked immunosorbent assays before surgical treatment. Tissue HER2 status was analyzed by immunohistochemistry (IHC) in all tumors; FISH assay was utilized in HER2 2+ tumors by IHC. RESULTS: From May 2000 to July 2005, 256 consecutive stage I-III breast cancer patients were included in this study. High serum HER2 ECD levels (>or=15 ng/ml) were reported in 23 patients (9.0%) and HER2-positive status in tumor tissue was observed in 42 patients (16.4%) with a concordance of 87.1%. High HER2 ECD levels were significantly associated with high histological grade (P = 0.003), stage III (P = 0.008), lymph node involvement (P = 0.035) and negativity of both estrogen (P = 0.016) and progesterone (P = 0.007) receptors. At multivariate analysis, high serum HER2 ECD levels were a significant independent prognostic factor of worse DFS (P = 0.009). CONCLUSIONS: A statistically significant association was observed between high serum HER2 ECD levels and worse DFS in early breast cancer patients.

Antiphospholipid antibodies in patients with cancer.

Antiphospholipid antibodies are generally associated with Antiphospholipid Syndrome, which can occur as a primary disorder or may be secondary to connective tissue disease or tumour. The presence of antiphospholipid antibodies in patients with tumour disease is responsible for thrombotic complications. In a population of 53 tumor patients with positive carcinoembryonic antigen CEA, carbohydrate antigen CA19.9, CA125 and CA15.3 markers, IgM and IgG anticardiolipin and antiphosphatidylinositol were detected by solid-phase immunoassays. Our results show that moderate or high levels of antiphospholipid antibodies are present in a great number of patients with CEA and CA19.9 markers, suggesting a specific association with gastroenteric tumors. By testing for antiphosphatidylinositol antibodies, many patients not evidenced by the standard anticardiolipin assay were found to be antiphospholipid-positive. The analysis of antiphosphatidylinositol antibodies as a diagnostic tool in gastroenteric cancer to highlight patients with the risk of thromboembolic complications is discussed.

Malignant schwannoma of the breast.

A case of rare, malignant schwannoma of the breast has been analysed with regard to its history and diagnostic problems, such as the mammographic pattern and the role of cytology in the preoperative mesenchymal suggestion.

Fine-needle cytology of the breast: a controlled study of aspiration versus nonaspiration.

We report on 534 breast masses examined by fine-needle aspiration cytology. Two samples were obtained from each mass, one with aspiration and the other without. Aspiration, equivalent to that obtained by a 20-ml syringe on full aspiration, was obtained by an automatic aspirator. The two sampling modalities did not differ apart from aspiration and were compared in terms of inadequate sampling rates. The inadequacy rate was the same in 166 cancers (6.6%), whereas a significant difference was recorded in favor of aspiration (13.6 versus 24.4%) in 368 benign masses. When inadequate results were excluded, the accuracy of the two modalities was almost the same. Sensitivity was 97.4% and 96.7% and specificity was 99.4% and 99.3% for sampling with and without aspiration, respectively. Reducing the rate of inadequate sampling from benign masses seems to be the major advantage of aspiration. Double sampling, independent of the specific techniques, reduced inadequacy rates to very low levels (1.2% for cancers; 5.9% for benign masses) and may be useful as a routine policy.

Diagnosis of endometrial carcinoma and its precursors by means of cytologic examination of jet-washing material.

Experience with cytologic examination of 138 consecutive jet washings showed the value of the technique as a method of screening for endometrial carcinoma in symptomatic and at-risk patients. In the 127 adequate specimens obtained (92%), all 16 endometrial carcinomas were diagnosed cytologically. The necessity of physician experience in sampling as well as good cytopreparatory techniques in the use of jet washings is emphasized. A dual preparatory routine, including the use of Millipore filter preparations to evaluate cellularity and the type of clusters and the use of smears on chilled slides to evaluate cellular details, was found to be optimal.

Rearrangements involving four chromosomes in a child with congenital abnormalities.

This report describes a complex structural rearrangement between chromosomes X and 1 and a 7;13 translocation (together involving six break points) in a child with multiple congenital defects. Both parents showed a normal chromosome complement, suggesting that the changes may have originated either in a gametic nucleus or at a very early stage of zygotic development.