Axilla management in sentinel node positive breast cancer patients at Mater Dei Hospital : an audit and literature review

BACKGROUND: In breast cancer patients with a positive SLN, surgical axillary clearance and axillary radiation therapy (ART) provide comparable locoregional control and survival, according to a 10-year follow-up of the large European Organisation for Research and Treatment of Cancer AMAROS trial. ART has the advantage of causing less complications with significantly lower rates of lymphoedema. The aim of this audit is to review clinical practice of axillary management of breast cancer patients in Malta following identification of positive SLN and compare results with international criteria. The possibility of de-escalating therapy might improve the morbidity of our patients without compromising their outcomes.METHODS: A retrospective and quantitative analysis of 329 breast cancer patients who underwent an axillary SLN procedure at Mater Dei Hospital (MDH) between January 2019 and 2020 was performed. The inclusion criteria were patient demographics, pre-/post-operative staging, tumour size, and treatment given. Data was analysed and compared to International randomised trials. The San Matteo Criteria based on the AMAROS trial, were reviewed, and used as a standard and compared to local practice.RESULTS: 329 patients were analysed, of which 284 patients fulfilled the inclusion criteria. 70 patients had a positive SLN with 74% having one SLN positive, of which 40% underwent ALND, 6% had ART, 2% refused ART and 52% received no treatment. 26% had 2 positive SLNs of which 44% underwent ALND, none received ART and 56% received no treatment in those with two positive SLN. Patients with more than 2 positive SLNs were excluded.CONCLUSION: We have determined that ALND is the accepted management for breast cancer patients with positive SLN in MDH. ART should be considered as a more favourable treatment option in patients with positive SLN being treated as it provides comparable results with significantly lower morbidity than ALND.peer-reviewe

Лечебно-диагностический алгоритм при очаговых тиреопатиях

Представлены современные данные о возможности развития тиреоидного рака на фоне доброкачественной патологии щитовидной железы, определены группы риска по развитию тиреоидных карцином. Разработан диагностический алгоритм своевременной и ранней диагностики рака щитовидной железы, предложены терапевтические подходы, направленные на предупреждение развития тиреоидного рака.Contemporary data about the possibility of thyroid carcinoma development against a background of thyroid pathology are presented. Risk groups of thyroid carcinoma development were determined. A diagnostic algorithm of timely and early diagnosis of thyroid carcinoma was worked out. Therapeutic approaches to prevention of thyroid cancer are suggested

The Characterization of Varicella Zoster Virus–Specific T Cells in Skin and Blood during Aging

Reactivation of the varicella zoster virus (VZV) increases during aging. Although the effects of VZV reactivation are observed in the skin (shingles), the number and functional capacity of cutaneous VZV-specific T cells have not been investigated. The numbers of circulating IFN-γ-secreting VZV-specific CD4+ T cells are significantly decreased in old subjects. However, other measures of VZV-specific CD4+ T cells, including proliferative capacity to VZV antigen stimulation and identification of VZV-specific CD4+ T cells with an major histocompatibility complex class II tetramer (epitope of IE-63 protein), were similar in both age groups. The majority of T cells in the skin of both age groups expressed CD69, a characteristic of skin-resident T cells. VZV-specific CD4+ T cells were significantly increased in the skin compared with the blood in young and old subjects, and their function was similar in both age groups. In contrast, the number of Foxp3+ regulatory T cells and expression of the inhibitory receptor programmed cell death -1 PD-1 on CD4+ T cells were significantly increased in the skin of older humans. Therefore, VZV-specific CD4+ T cells in the skin of older individuals are functionally competent. However, their activity may be restricted by multiple inhibitory influences in situ

Enhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase-induced inflammation

Background Immunity decreases with age, which leads to reactivation of varicella zoster virus (VZV). In human subjects age-associated immune changes are usually measured in blood leukocytes; however, this might not reflect alterations in tissue-specific immunity. Objectives We used a VZV antigen challenge system in the skin to investigate changes in tissue-specific mechanisms involved in the decreased response to this virus during aging. Methods We assessed cutaneous immunity based on the extent of erythema and induration after intradermal VZV antigen injection. We also performed immune histology and transcriptomic analyses on skin biopsy specimens taken from the challenge site in young (65 years) subjects. Results Old human subjects exhibited decreased erythema and induration, CD4+ and CD8+ T-cell infiltration, and attenuated global gene activation at the site of cutaneous VZV antigen challenge compared with young subjects. This was associated with increased sterile inflammation in the skin in the same subjects related to p38 mitogen-activated protein kinase–related proinflammatory cytokine production (P < .0007). We inhibited systemic inflammation in old subjects by means of pretreatment with an oral small-molecule p38 mitogen-activated protein kinase inhibitor (Losmapimod; GlaxoSmithKline, Brentford, United Kingdom), which reduced both serum C-reactive protein levels and peripheral blood monocyte secretion of IL-6 and TNF-α. In contrast, cutaneous responses to VZV antigen challenge were increased significantly in the same subjects (P < .0003). Conclusion Excessive inflammation in the skin early after antigen challenge retards antigen-specific immunity. However, this can be reversed by inhibition of inflammatory cytokine production that can be used to promote vaccine efficacy and the treatment of infections and malignancy during aging

Еволюція підходів до виділення факторів зміцнення конкурентних позицій підприємств

В статье исследовано развитие теоретической базы дисциплин, которые рассматривают конкурентное позиционирование предприятий. На основе обобщения дисциплинарных подходов к определению факторов укрепления конкурентных позиций предприятий выделено и охарактеризовано этапы развития последних. Сформулированы выводы относительно пригодности использования различных подходов для формирования адекватного современным условиям функционирования предприятий механизма достижения, поддержки и укрепления их конкурентных позиций.У статті досліджено розвиток теоретичної бази дисциплін, що розглядають конкурентне позиціонування підприємств. На основі узагальнення дисциплінарних підходів до визначення факторів зміцнення конкурентних позицій підприємств виділено та охарактеризовано етапи розвитку останніх. Сформульовано висновки відносно придатності використання різних підходів для формування адекватного сучасним умовам функціонування підприємств механізму досягнення, підтримки і зміцнення їх конкурентних позицій.Development of theoretical base of disciplines which examine the competition positioning is explored in the article. On the basis of generalization of disciplinary approaches to determination of factors of competition positions of enterprises it is selected and described the stages of development of it. Conclusions are formulated in relation to the fitness of the use of different approaches for forming of functioning of enterprises of mechanism of achievement, support and strengthening of their competition positions adequate to the modern terms

Decreased TNF-α synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging

Immunity declines during aging, however the mechanisms involved in this decline are not known. In this study, we show that cutaneous delayed type hypersensitivity (DTH) responses to recall antigens are significantly decreased in older individuals. However, this is not related to CC chemokine receptor 4, cutaneous lymphocyte-associated antigen, or CD11a expression by CD4+ T cells or their physical capacity for migration. Instead, there is defective activation of dermal blood vessels in older subject that results from decreased TNF-α secretion by macrophages. This prevents memory T cell entry into the skin after antigen challenge. However, isolated cutaneous macrophages from these subjects can be induced to secrete TNF-α after stimulation with Toll-like receptor (TLR) 1/2 or TLR 4 ligands in vitro, indicating that the defect is reversible. The decreased conditioning of tissue microenvironments by macrophage-derived cytokines may therefore lead to defective immunosurveillance by memory T cells. This may be a predisposing factor for the development of malignancy and infection in the skin during aging

The education and registration of European Fluency Specialists

The European Clinical Specialization Fluency (ECSF) consortium has been running courses for qualified SLTs since 2008 with an annual intake of around 20 students. Currently more than 200 students from 27 EU and non-EU countries have graduated from the program. Members of this consortium are specialist therapists, researchers and lecturers working in the area of fluency disorders, drawn from 13 universities and colleges in 9 EU countries, along with two associate partners from Centers of Excellence for working the people with fluency disorders. The program is a well-designed combination of lectures, clinical practice and home assignments. Lectures are provided during two intensive weeks (September & February), scheduled during the academic year. These modules are combined with several lectures and follow up sessions in the home country of the participant. The local sessions take place outside the intensive weeks. Preparatory reading and home assignments form an integral part of the course. The specialized clinical training, under supervision of a fluency specialist, can begin after the first intensive week. Evaluation is based on permanent evaluation, portfolio, and specific evaluation moments. The curriculum consists of two components: theoretical knowledge and specific therapeutic skills along with specialized clinical training and portfolio. The one-year intensive course leads to a qualification as an ECSF-recognized Fluency Therapist, a significant step towards becoming a European Fluency Specialist (EFS). During this presentation, we will (1) elaborate how the course has evolved over time in order to create an ideal learning curve and optimal learning environment for participants; and (2) report on the results of an online survey of our graduates re. the learning outcomes and perceived benefits. This European group has now developed an additional stepwise procedure to become a European Fluency Specialist. This is open to ECSF graduates as well as eligible clinicians and academics with special interest in fluency disorders. The process involves documentation re. clinical and/or academic activities, continued professional development activities, and informal discussion groups, within a time frame of three years. The EFS Board reviews the documentation, approves applications in accordance with stated criteria and registers the applicant accordingly. Once approved, the certification process is complete and the person can use the title of European Fluency Specialist. To maintain certification, candidates must provide proof of accomplishments of the required activities annually; every three years the EFS Board will review the documented required activities for candidates to maintain certification. This recently developed EU model, active from 2016, shows similarities to ASHA’s (American Board of Fluency and Fluency Disorders) recognition procedure for becoming a ‘Board certified specialist in fluency’, and might be a useful model for other SLT domains