RIT with Y90-Ibritumomab Tiuxetan in Follicular Non-Hodgkin Lymphoma: Evaluation of Recent Outcomes in a Single Institution

Background. Based on historical data we reviewed our hospital clinical database to analyse our updated information and therapy outcomes of follicular non-Hodgkin lymphoma (F-NHL) patients treated with 90Y-Ibritumomab tiuxetan. Patients and Methods. Between 2005 and 2011, 56 F-NHL patients were included in a clinical protocol conducted by a multidisciplinary team and treated in the same centre. All patients received 0.3 or 0.4 mCi/kg IV (88%) of 90Y-IT; response evaluation was performed 12 weeks after. Results. M/F 44.6%/55.4%, mean age 61.45 years (30–85); ECOG 0-1 96.9%. According to FLIPI score, distribution were good: 58.5%, intermediate: 29.2%, and poor: 12.3%. Previous therapies: >2: 40% (26). ORR was 94.6% (53/56). CR: 85.7%; CR according to previous disease: relapsed disease: 90% (27/30), refractory disease: 42.85% (3/7), consolidation with CR: 92.85% (13/14), and consolidation with PR: 100% (5/5). Global PR and NR were 8.9% (5) and 5.3% (3), respectively. Mean OS 63.86 months with a mean follow-up time of 57 months (2–73). Mean TTP: 52.65 months (95% CI: 43.83–61.48). Median OS and TTP were not achieved. No hospital submissions or deaths were registered. Conclusions. This study confirms the safety and high efficacy of 90Y-IT in F-NHL patients, RIT in early stage of disease could improve outcomes

Cell-Free DNA for Genomic Analysis in Primary Mediastinal Large B-Cell Lymphoma

High-throughput sequencing of cell-free DNA (cfDNA) has emerged as a promising noninvasive approach in lymphomas, being particularly useful when a biopsy specimen is not available for molecular analysis, as it frequently occurs in primary mediastinal large B-cell lymphoma (PMBL). We used cfDNA for genomic characterization in 20 PMBL patients by means of a custom NGS panel for gene mutations and low-pass whole-genome sequencing (WGS) for copy number analysis (CNA) in a real-life setting. Appropriate cfDNA to perform the analyses was obtained in 18/20 cases. The sensitivity of cfDNA to detect the mutations present in paired FFPE samples was 69% (95% CI: 60-78%). The mutational landscape found in cfDNA samples was highly consistent with that of the tissue, with the most frequently mutated genes being B2M (61%), SOCS1 (61%), GNA13 (44%), STAT6 (44%), NFKBIA (39%), ITPKB (33%), and NFKBIE (33%). Overall, we observed a 75% concordance to detect CNA gains/losses between DNA microarray and low-pass WGS. The sensitivity of low-pass WGS was remarkably higher for clonal CNA (18/20, 90%) compared to subclonal alterations identified by DNA microarray. No significant associations between cfDNA amount and tumor burden or outcome were found. cfDNA is an excellent alternative source for the accurate genetic characterization of PMBL cases

Relato de dois casos consecutivos de derivação biliodigestiva pela técnica de Couinaud-Soupault, no tratamento de icterícia obstrutiva por neoplasia de via biliar / Report of two consecutive cases of biliodigestive shunt by the Couinaud-Soupault technique, in the treatment of obstructive jaundice due to biliary tract neoplasia

A anastomose Biliodigestiva com técnica de Couinaud-Soupault foi realizada como tratamento paliativo de ictéricia obstrutiva em dois casos de neoplasias em via biliar intra-hepática no Hospital Municipal Lourenço Jorge (HMLJ)

Position statement of the Brazilian Academy of Rhinology on the use of antihistamines, antileukotrienes, and oral corticosteroids in the treatment of inflammatory sinonasal diseases

Introduction: Inflammatory conditions of the nose and paranasal sinuses are very prevalent in the general population, resulting in marked loss of quality of life in affected patients, as well as significant work, leisure, and social activity losses. These patients require specific and specialized treatment. A wide range of oral medications are available. Objective: The present document is aimed to clarify, for professionals treating patients with inflammatory sinonasal diseases, both specialists and general practitioners, specific oral therapies in noninfectious nasal inflammatory conditions. Methods: The methodology used to create this article included the search for the key words: oral corticosteroids, antihistamines, antileukotrienes, rhinitis, rhinosinusitis in the MEDLINE and EMBASE databases in the last 5 years. Since no relevant article was found for the text on the subject of interest in the last 5 years, the search was extended for another 5 years, and so on, according to the authors' needs. Results: Relevant literature was found regarding the use of antihistamines, antileukotrienes and oral corticosteroids in these conditions. The Brazilian Academy of Rhinology emphasizes, after extensive discussion by the collegiate, key points in the treatment with these drugs. Conclusion: There is support in the literature for the use of these drugshowever, final considerations about the role of each of them have been made. (C) 2017 Published by Elsevier Editora Ltda. on behalf of Associacao Brasileira de Otorrino-laringologia e Cirurgia Cervico-Facial.Univ Sao Paulo, Disciplina Otorrinolaringol, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Dept Otorrinolaringol, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Otorrinolaringol, Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Ciencias Saude, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Otorrinolaringol, Sao Paulo, SP, BrazilUniv Fed Minas Gerais, Fac Med, Belo Horizonte, MG, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, SP, BrazilUniv Fed Bahia, Fac Med, Disciplina Otorrinolaringol, Salvador, BA, BrazilHosp Inst Paranaense Otorrinolaringol, Centro Rinite & Alergia, Curitiba, PR, BrazilUniv Estado Rio De Janeiro, Rio De Janeiro, RJ, BrazilUniv Brasilia, Fac Med, Brasilia, DF, BrazilUniv Fed Sao Paulo, Dept Otorrinolaringol & Cabeca & Pescoco, Sao Paulo, SP, BrazilUniv Luterana Brasil, Fac Med, Otorrinolaringol, Canoas, RS, BrazilMt Sinai Hosp, Dept Othorhinolaryngol, Toronto, ON, CanadaUniv Sao Paulo, Fac Med, Ciencias, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Oftalmol Otorrinolaringol & Cirurgia Cabeca, Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Ciencias Saude, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Otorrinolaringol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Otorrinolaringol & Cabeca & Pescoco, Sao Paulo, SP, BrazilWeb of Scienc

Biological effects of trans, trans-farnesol in Leishmania amazonensis

IntroductionFarnesol, derived from farnesyl pyrophosphate in the sterols biosynthetic pathway, is a molecule with three unsaturations and four possible isomers. Candida albicans predominantly secretes the trans, trans-farnesol (t, t-FOH) isomer, known for its role in regulating the virulence of various fungi species and modulating morphological transition processes. Notably, the evolutionary divergence in sterol biosynthesis between fungi, including Candida albicans, and trypanosomatids resulted in the synthesis of sterols with the ergostane skeleton, distinct from cholesterol. This study aims to assess the impact of exogenously added trans, trans-farnesol on the proliferative ability of Leishmania amazonensis and to identify its presence in the lipid secretome of the parasite.MethodsThe study involved the addition of exogenous trans, trans-farnesol to evaluate its interference with the proliferation of L. amazonensis promastigotes. Proliferation, cell cycle, DNA fragmentation, and mitochondrial functionality were assessed as indicators of the effects of trans, trans-farnesol. Additionally, lipid secretome analysis was conducted, focusing on the detection of trans, trans-farnesol and related products derived from the precursor, farnesyl pyrophosphate. In silico analysis was employed to identify the sequence for the farnesene synthase gene responsible for producing these isoprenoids in the Leishmania genome.ResultsExogenously added trans, trans-farnesol was found to interfere with the proliferation of L. amazonensis promastigotes, inhibiting the cell cycle without causing DNA fragmentation or loss of mitochondrial functionality. Despite the absence of trans, trans-farnesol in the culture supernatant, other products derived from farnesyl pyrophosphate, specifically α-farnesene and β-farnesene, were detected starting on the fourth day of culture, continuing to increase until the tenth day. Furthermore, the identification of the farnesene synthase gene in the Leishmania genome through in silico analysis provided insights into the enzymatic basis of isoprenoid production.DiscussionThe findings collectively offer the first insights into the mechanism of action of farnesol on L. amazonensis. While trans, trans-farnesol was not detected in the lipid secretome, the presence of α-farnesene and β-farnesene suggests alternative pathways or modifications in the isoprenoid metabolism of the parasite. The inhibitory effects on proliferation and cell cycle without inducing DNA fragmentation or mitochondrial dysfunction raise questions about the specific targets and pathways affected by exogenous trans, trans-farnesol. The identification of the farnesene synthase gene provides a molecular basis for understanding the synthesis of related isoprenoids in Leishmania. Further exploration of these mechanisms may contribute to the development of novel therapeutic strategies against Leishmania infections

408 Cases of Genital Ambiguity Followed by Single Multidisciplinary Team during 23 Years: Etiologic Diagnosis and Sex of Rearing

Objective. To evaluate diagnosis, age of referral, karyotype, and sex of rearing of cases with disorders of sex development (DSD) with ambiguous genitalia. Methods. Retrospective study during 23 years at outpatient clinic of a referral center. Results. There were 408 cases; 250 (61.3%) were 46,XY and 124 (30.4%) 46,XX and 34 (8.3%) had sex chromosomes abnormalities. 189 (46.3%) had 46,XY testicular DSD, 105 (25.7%) 46,XX ovarian DSD, 95 (23.3%) disorders of gonadal development (DGD), and 19 (4.7%) complex malformations. The main etiology of 46,XX ovarian DSD was salt-wasting 21-hydroxylase deficiency. In 46,XX and 46,XY groups, other malformations were observed. In the DGD group, 46,XY partial gonadal dysgenesis, mixed gonadal dysgenesis, and ovotesticular DSD were more frequent. Low birth weight was observed in 42 cases of idiopathic 46,XY testicular DSD. The average age at diagnosis was 31.7 months. The final sex of rearing was male in 238 cases and female in 170. Only 6.6% (27 cases) needed sex reassignment. Conclusions. In this large DSD sample with ambiguous genitalia, the 46,XY karyotype was the most frequent; in turn, congenital adrenal hyperplasia was the most frequent etiology. Malformations associated with DSD were common in all groups and low birth weight was associated with idiopathic 46,XY testicular DSD