SAPHO: has the time come for tailored therapy?

SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a heterogeneous condition combining osteoarticular and cutaneous manifestations. Conventional treatments are mostly ineffective. We hereby report two patients, the first with an aggressive form of disease and the second with an incomplete response to two different anti-TNF-α agents. Both were successfully treated with tocilizumab and ustekinumab, respectively, over a long period of time. A narrative review of a biological therapy in SAPHO syndrome yielded very little information on the specific use of these agents. We highlight the advantages of personalising therapy and describe emerging promising treatments for this disease.info:eu-repo/semantics/publishedVersio

A new phage-display tumor-homing peptide fused to antiangiogenic peptide generates a novel bioactive molecule with antimelanoma activity

Phage-display peptide libraries have been widely used to identify specific peptides targeting in vivo tumor cells and the tumor vasculature and playing an important role in the discovery of antitumor bioactive peptides. In the present work, we identified a new melanoma-homing peptide, (-CVNHPAFAC-), using a C7C phage-display library directed to the developing tumor in syngeneic mice. Phage were able to preferentially target melanoma in vivo, with an affinity about 50-fold greater than that with normal tissue, and the respective synthesized peptide displaced the corresponding phage from the tumor. A preferential binding to endothelial cells rather than to melanoma cells was seen in cell ELISA, suggesting that the peptide is directed to the melanoma vasculature. Furthermore, the peptide was able to bind to human sonic hedgehog, a protein involved in the development of many types of human cancers. Using a new peptide approach therapy, we coupled the cyclic peptide to another peptide, HTMYYHHYQHHL-NH(2), a known antagonist of VEGFR-2 receptor, using the GYG linker. The full peptide CVNHPAFACGYGHTMYYHHYQHHL-NH(2) was effective in delaying tumor growth (P < 0.05) and increasing animal survival when injected systemically, whereas a scramble-homing peptide containing the same antagonist did not have any effect. This is the first report on the synthesis of a tumor-homing peptide coupled to antiangiogenic peptide as a new anticancer therapeutics

Avaliação e tratamento do doente com acne – Parte I: Epidemiologia, etiopatogenia, clínica, classificação, impacto psicossocial, mitos e realidades, diagnóstico diferencial e estudos complementares

O Portuguese Acne Advisory Board (PAAB), grupo de dermatologistas portugueses que, à semelhança de grupos congéneres internacionais, tem dedicado particular atenção à definição de linhas de orientação para o tratamento da acne, pretende que o presente documento constitua uma ferramenta útil na abordagem dos doentes com esta patologia. Elaborou-se um dossier, para educação médica contínua, subdividido em 2 partes: Parte I – etiopatogenia e clínica; Parte II – abordagem terapêutica. Nesta Parte I, revêem-se os principais aspectos da clínica e da fisiopatogenia da acne à luz dos conhecimentos actuais. Discute-se a importância do impacto psicológico e social desta entidade e analisam-se os principais mitos e realidades com ela relacionados. Descrevem-se, sucintamente, as patologias mais relevantes no diagnóstico diferencial das lesões de acne. Enumeram-se as indicações para estudo hormonal, bem como os exames a efectuar nos doentes com esta patologia. The Portuguese Acne Advisory Board (PAAB), a group of Portuguese dermatologists with a special interest in acne, develop, as other international groups in this field, consensus recommendations for the treatment of acne. Overall, the goal is to provide a practice guideline to all physicians dealing with this entity. The continuing medical education dossier was divided in two parts: Part I – etiopathogeny and clinical features; Part II – therapy. This Part I reviews acne pathophysiology, clinical aspects, psychological and social impact and several myths surrounding this disease. Some other entities relevant for the differential diagnosis are described. The need of hormonal evaluation is also discusse

Avaliação e tratamento do doente com acne - Parte II: tratamento tópico, sistémico e cirúrgico, tratamento da acne na grávida, algoritmo terapêutico

O Portuguese Acne Advisory Board (PAAB), grupo de dermatologistas portugueses que, à semelhança de grupos congéneres internacionais, tem dedicado particular atenção à definição de linhas de orientação para o tratamento da acne, pretende que o presente documento constitua uma ferramenta útil na abordagem dos doentes com esta patologia. Elaborou-se um dossier, para educação médica contínua, subdividido em 2 partes: Parte I – etiopatogenia e clínica; Parte II – abordagem terapêutica. Nesta Parte II discute-se a abordagem terapêutica – tópica e sistémica – em cada forma clínica de acne, dando particular ênfase aos retinóides e aos antimicrobianos, e salientam-se as estratégias a adoptar para limitar a crescente resistência bacteriana aos antibióticos. Referem-se as indicações específicas para terapêutica hormonal e analisam-se as particularidades do tratamento da acne na grávida e lactante. Descrevem-se algumas técnicas para correcção das cicatrizes da acne. Por último, publica-se um algoritmo que pretende ilustrar a classificação da acne e definir, para cada tipo clínico, a abordagem terapêutica consensualmente recomendada

Brazilian smokers are ready for the ban on flavour additives in tobacco to be implemented

Brazil became the first country to approve a national policy to ban all flavour additives in all tobacco leaf products in 2012. However, as of February 2022, the policy remained to be implemented. Cross-sectional data come from the International Tobacco Control (ITC) Brazil Wave 3 Survey among adult smokers (N = 1216) in 2016–2017. The majority of smokers supported a ban on menthol (56.0%; 95%CI: 51.7–60.2%) and a ban on all additives (61.7%; 57.5–65.8%), with no significant differences across sociodemographic groups in adjusted logistic regression models. More than half of menthol smokers reported they would either quit or reduce the amount they smoked if menthol cigarettes were banned. Findings suggest that there is support for Brazil's ban on flavour additives, which is a determinant of successful policy implemented. Continued delays will postpone an important measure with demonstrated public health gains

Immunomodulatory Protective Effects of Rb9 Cyclic-Peptide in a Metastatic Melanoma Setting and the Involvement of Dendritic Cells

The cyclic VHCDR3-derived peptide (Rb9) from RebMab200 antibody, directed to a NaPi2B phosphate-transport protein, displayed anti-metastatic melanoma activity at 50-300 mu g intraperitoneally injected in syngeneic mice. Immune deficient mice failed to respond to the peptide protective effect. Rb9 induced increased CD8+ T and low Foxp3+ T cell infiltration in lung metastases and high IFN-gamma and low TGF-beta in lymphoid organs. The peptide co-localized with F-actin and a nuclear site in dendritic cells and specifically bound to MIF and CD74 in a dot-blot setting. Murine bone-marrow dendritic cells preincubated with Rb9 for 6 h were treated with MIF for short time periods. The modulated responses showed stimulation of CD74 and inhibition of pPI3K, pERK, and pNF-kappa B as compared to MIF alone. Rb9 in a melanoma-conditioned medium, stimulated the M1 type conversion in bone marrow-macrophages. Functional aspects of Rb9 in vivo were studied in therapeutic and prophylactic protocols using a melanoma metastatic model. In both protocols Rb9 exhibited a marked anti-melanoma protection. Human dendritic cells were also investigated showing increased expression of surface markers in response to Rb9 incubation. Rb9 either stimulated or slightly inhibited moDCs submitted to inhibitory (TGF-beta and IL-10) or activating (LPS) conditions, respectively. Lymphocyte proliferation was obtained with moDCs stimulated by Rb9 and tumor cell lysate. In moDCs from cancer patients Rb9 exerted immunomodulatory activities depending on their functional status. The peptide may inhibit over-stimulated cells, stimulate poorly activated and suppressed cells, or cause instead, little phenotypic and functional alterations. Recently, the interaction MIF-CD74 has been associated to PD-L1 expression and IFN-gamma, suggesting a target for melanoma treatment. The effects described for Rb9 and the protection against metastatic melanoma may suggest the possibility of a peptide reagent that could be relevant when associated to modern immunotherapeutic procedures

A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus

<p>Abstract</p> <p>Background</p> <p>Neramexane is a new substance that exhibits antagonistic properties at α₉α₁₀cholinergic nicotinic receptors and <it>N</it>-methyl-D-aspartate receptors, suggesting potential efficacy in the treatment of tinnitus.</p> <p>Methods</p> <p>A total of 431 outpatients with moderate to severe subjective tinnitus (onset 3-18 months before screening) were assigned randomly to receive either placebo or neramexane mesylate (25 mg/day, 50 mg/day and 75 mg/day) for 16 weeks, with assessment at 4-week intervals. The primary (intention-to-treat) efficacy analysis was based on the change from baseline in Week 16 in the total score of the adapted German short version of the validated Tinnitus Handicap Inventory questionnaire (THI-12).</p> <p>Results</p> <p>Compared with placebo, the largest improvement was achieved in the 50 mg/d neramexane group, followed by the 75 mg/d neramexane group. This treatment difference did not reach statistical significance at the pre-defined endpoint in Week 16 (<it>p </it>= 0.098 for 50 mg/d; <it>p </it>= 0.289 for 75 mg/d neramexane), but consistent numerical superiority of both neramexane groups compared with placebo was observed. Four weeks after the end of treatment, THI-12 scores in the 50 mg/d group were significantly better than those of the controls. Secondary efficacy variables supported this trend, with <it>p </it>values of < 0.05 for the 50 mg/d neramexane group associated with the functional-communicational subscores of the THI-12 and the assessments of tinnitus annoyance and tinnitus impact on life as measured on an 11-point Likert-like scale. No relevant changes were observed for puretone threshold, for tinnitus pitch and loudness match, or for minimum masking levels. The 25 mg/d neramexane group did not differ from placebo. Neramexane was generally well tolerated and had no relevant influence on laboratory values, electrocardiography and vital signs. Dizziness was the most common adverse event and showed a clear dose-dependence.</p> <p>Conclusions</p> <p>This study demonstrated the safety and tolerability of neramexane treatment in patients with moderate to severe tinnitus. The primary efficacy variable showed a trend towards improvement of tinnitus suffering in the medium- and high-dose neramexane groups. This finding is in line with consistent beneficial effects observed in secondary assessment variables. These results allow appropriate dose selection for further studies.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00405886</p

Social representations of needlestick injuries

OBJECTIVES: understand the Social Representations about needlestick injuries elaborated by Nursing Technicians and analyze how these representations influence their conducts. METHOD: the data, obtained by interviews, were processed using ALCESTE software and their analysis was based on Serge Moscovici's Social Representations Theory. RESULTS: it was evidenced that, after the accident, these professionals take care of the affected area. Then, they report the accident, motivated by the fear of catching HIV and hepatitis. The different feelings experienced are due to this fear and the way they were forwarded by the institution, reflecting in the cause they attribute to their accident. CONCLUSIONS: it was verified that knowledge about the accident as a whole is very incipient in this professional group, demanding continuing education and greater emphasis on this subject in professional training. It is expected that this study draws public authorities and health institutions' attention to the problem and that it modifies Nursing Technicians' Social Representations about percutaneous exposure.OBJETIVOS: Comprender las Representaciones Sociales de los accidentes con materiales corto-punzantes, elaboradas por Técnicos de Enfermería, así como analizar de que modo esas representaciones influencian las conductas de eses profesionales. MÉTODO: Los datos, logrados por medio de entrevistas, fueron procesados por el software ALCESTE y el análisis de los mismos fue basado en la Teoría de las Representaciones Sociales de Serge Moscovici. RESULTADOS: se evidenció que, después de accidentarse, los Técnicos de Enfermería cuidan del área afectada. Enseguida, notifican el accidente, motivados por el miedo de que contraigan HIV y hepatitis. Los diversos sentimientos vividos son consecuentes de ese miedo y de la manera como fueron encaminados por la institución, reflejando en la causa que ellos atribuyen a su accidente. CONCLUSIONES: se constató que hay un conocimiento bastante incipiente por parte de esa clase profesional sobre el accidente como un todo, habiendo necesidad de una educación continuada y mayor énfasis en cuanto a ese asunto durante la formación profesional. Se espera que ese estudio llame la atención de los órganos gubernamentales e instituciones de salud sobre el problema y modifique las Representaciones Sociales de la exposición percutánea de los Técnicos de Enfermería.OBJETIVOS: compreender as representações sociais dos acidentes com materiais perfurocortantes, elaboradas por técnicos de enfermagem, bem como analisar de que modo essas representações influenciam as condutas desses profissionais. MÉTODO: os dados, obtidos por meio de entrevistas, foram processados pelo software Alceste e a análise dos mesmos foi baseada na Teoria das Representações Sociais de Serge Moscovici. RESULTADOS: evidenciou-se que, após se acidentarem, os técnicos de enfermagem cuidam da área afetada. Em seguida, notificam o acidente, motivados pelo medo de contraírem HIV e hepatite. Os diversos sentimentos vivenciados são decorrentes desse medo e da forma como foram encaminhados pela instituição, refletindo na causa que eles atribuem ao seu acidente. CONCLUSÕES: constatou-se que há conhecimento bastante incipiente por parte dessa classe profissional sobre o acidente, como um todo, havendo necessidade de educação continuada e maior ênfase quanto a esse assunto, durante a formação profissional. Espera-se que este estudo chame a atenção dos órgãos governamentais e instituições de saúde sobre o problema e modifique as representações sociais da exposição percutânea dos técnicos de enfermagem