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Introduction: Immune checkpoint blockade of programmed death-1 (PD-1) receptor and its ligand (PD-L1) has contributed to efficacy in many tumor types, with clinical responses observed in a proportion of patients (pts) with Hodgkin lymphoma and rare non-Hodgkin lymphoma subtypes. A recent study demonstrated that combination treatment with anti-PD-L1 and anti-CD38 agents contributed to a stronger anti-tumor immune response compared with anti-PD-L1 monotherapy. Isatuximab, an anti-CD38 monoclonal antibody, is approved for use in multiple myeloma. Cemiplimab, an anti-PD-1 monoclonal antibody, is approved for use in cutaneous squamous cell carcinoma, basal cell carcinoma, and non-small cell lung cancer. Methods: This Phase 1/2 open-label study (NCT03769181) was designed to assess the safety, tolerability, and efficacy of isatuximab in combination with cemiplimab (Isa+Cemi) in pts with relapsed and refractory classic Hodgkin's lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), and peripheral T-cell lymphoma (PTCL). The primary objectives of Phase 1 were to characterize the safety and tolerability of Isa+Cemi and to confirm the recommended Phase 2 dose. Phase 2 used a Simon's 2-stage design to assess the complete response rate in Cohort A1 (anti-PD-1/PD-L1 naïve cHL; n=18; median age, 36 years; 55.6% male; ≥2 prior regimens, 100%) and to assess the objective response rate in Cohorts A2 (cHL progressing after PD-1/PD-L1 therapy; n=12; median age, 33 years; 58.3% male; ≥2 prior regimens, 100%), B (DLBCL; n=17; median age, 64 years; 70.6% male; ≥2 prior regimens, 100%), and C (PTCL; n=11; median age, 69 years; 63.6% male; ≥2 prior regimens, 9.1%). Pts received Isa+Cemi for up to 96 weeks. In Phase 1, the isatuximab dose was 10 mg/kg every week (Cycle 1), every 2 weeks (Cycle 2-6), or every 3 weeks (Cycle 7+). The cemiplimab dose was 250 mg every 2 weeks (Cycle 1-6) or 350 mg every 3 weeks (Cycle 7+). An interim analysis was performed when the last pt in Phase 2 was followed up for 24 weeks. The efficacy evaluation was based on Simon's 2-stage design with 85% power at a 5% 1-sided alpha level for each cohort. At least 8 (44.4%) and 3 (30.0%) responses were required in Cohorts B and C, respectively, in Phase 2 Stage 1 to advance to Phase 2 Stage 2. Results: Isa+Cemi demonstrated a manageable safety profile with no new safety signals. No dose-limiting toxicities were observed, confirming the recommended Phase 2 dose. Treatment-emergent adverse events (TEAEs) were reported in 83.3% (Cohort A1) and 100% (Cohorts A2, B, C) of pts. Grade ≥3 TEAEs occurred in 5.6%, 8.3%, 70.6%, and 81.8% of pts in Cohorts A1, A2, B, and C, respectively. There were no pts in Cohorts A1 or A2 who reported TEAEs leading to definitive discontinuation; 5.9% and 27.3% of pts in Cohorts B and C experienced TEAEs leading to definitive discontinuation. No Grade 5 TEAEs with fatal outcome were reported in Cohorts A1 or A2. There were 4 deaths reported during the on-treatment period in Cohort B (progressive disease, n=2; intestinal perforation, n=1; urinary tract infection, n=1) and 2 in Cohort C (unknown, n=1; progressive disease, n=1). Infusion reactions were reported in 38.9%, 75.0%, 52.9%, and 72.7% of pts in Cohorts A1, A2, B, and C, respectively; there was 1 (9.1%) Grade ≥3 infusion reaction reported in Cohort C. Pharmacokinetics (PK) analyses suggested no effect of cemiplimab on isatuximab PK, and vice versa. Based on Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of pts in the all-treated population achieved a complete or partial response. Median progression-free survival was 8.38 months (95% CI: 2.72-not calculable [NC]), 8.28 months (95% CI: 2.6-NC), 2.37 months (95% CI: 0.46-2.69), and 2.66 months (95% CI: 0.43-2.99) in Cohorts A1, A2, B, and C, respectively. Conclusion: In this study, Isa+Cemi had a manageable safety profile. Clinical efficacy was observed in pts with cHL, with increased responses observed in pts who had not previously received anti-PD-1/PD-L1 therapy compared with those who progressed on anti-PD-1/PD-L1 therapy. For Cohorts B (DLBCL) and C (PTCL), results of the interim efficacy analysis did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Most pts with DLBCL were primary refractory/bulky and discontinued rapidly, which may have contributed to the lack of activity with this combination. Disclosures Carlo-Stella: ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Oncology: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Research Funding. Zinzani: TG Therapeutics Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ImmuneDesign: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sureda: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; Roche: Other: Support for attending meetings and/or travel; Bluebird: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Casasnovas: TAKEDA: Consultancy, Research Funding; Gilead/Kite: Consultancy, Research Funding; BMS: Consultancy; Janssen: Consultancy; Amgen: Consultancy; ROCHE: Consultancy, Research Funding. Carpio: Regeneron, TAKEDA, Celgene, Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travels and accommodation. Bouabdallah: Abbvie: Honoraria; Sandoz: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Takeda: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Kim: Celltrion: Research Funding; Dong-A Pharmaceutical: Research Funding; Kyowa Kirin: Research Funding; Sanofi: Research Funding; IGM Biosciences: Research Funding; Eisai: Research Funding; Johnson & Johnson: Research Funding; Roche: Research Funding. Cordoba: Incyte: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADCTherapeutics: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Koh: Pfizer: Consultancy; Jassen: Honoraria; AstraZeneca: Honoraria; Novartis: Honoraria; GSK: Honoraria; Roche: Honoraria; Takeda: Honoraria. Alves: Janssen, Cilag, Gilead, Takeda, Astrazeneca, Roche, Abbvie: Consultancy, Honoraria. Chamuleau: Gilead: Research Funding; Genmab: Research Funding; Celgene: Research Funding. Lopez-Guillermo: Roche, Gilead/Kite, Celgene, Novartis, Janssen, AbbVie, Spectrum: Consultancy, Honoraria, Research Funding. Van Der Poel: Roche, Janssen, Abbvie: Honoraria. Abbadessa: Sanofi: Current Employment. Meng: Sanofi: Current Employment. Ji: Sanofi: Current Employment. Lepine: Sanofi: Other: Contractual relationship. Saleem: Sanofi: Current Employment. Ribrag: PharmaMar: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Research Funding; Epizyme: Honoraria, Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; MSD Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Argen-X: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Based on the Phase III ICARIA-MM study, isatuximab (Sarclisa) is approved in a number of countries in combination with pomalidomide and dexamethasone for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. Based on the Phase III IKEMA study, isatuximab in combination with carfilzomib and dexamethasone is approved in the United States for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy, and in the European Union for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Cemiplimab (Libtayo) is an anti-PD-1 antibody approved for the treatment of the following: 1) patients with metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation; 2) patients with locally advanced or metastatic basal cell carcinoma previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate; and 3) patients with NSCLC and high tumor PD-L1 expression as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations, and is locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or metastatic.

High‐dose methylprednisolone plus rituximab (R‐HDMP) is a useful treatment in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) patients unfit for chemo‐immunotherapy and has proven its utility on the treatment of CLL/SLL complicated by auto‐immune cytopenias. We performed a retrospective, single‐centre study, of CLL/SLL patients treated with R‐HDMP for 9 years. Thirty‐nine patients were included, median age at time of treatment was 77 years. Most patients had stage Rai III/IV and Binet C disease. Twenty‐eight patients had relapsed/refractory disease at time of treatment with a median of 1 previous line of therapy; 53.8% had prior exposure to fludarabine and 25% to rituximab. Grade 3–4 neutropenia and thrombocytopenia were recorded in 10.2% and 17.9% patients, respectively. While on treatment, 51.3% had documented infectious complications, but no other non‐haematological toxicities grades 3–4 were identified. Overall response rate was 64%. Median overall survival and progression‐free survival were 24 and 13 months, respectively. Twenty four patients relapsed and 16 received another line of treatment after R‐HDMP, with median time to next treatment of 13.5 months. Thirteen out of the 24 patients improved performance status and were subsequently considered fit for chemo‐immunotherapy. R‐HDMP is a valuable option for elderly and frail patients, with low risk of severe myelotoxicity and other severe adverse events. It was shown to work as a bridge to other lines of treatment, including chemo‐immunotherapy., High dose methylprednisolone plus rituximab (R‐HDMP) is a useful treatment in chronic lymphocytic leukaemia/small lymphocytic lymphoma patients unfit for chemo‐immunotherapy. We present a cohort of patients with median age of 77 years, most with stage Rai III/IV and Binet C disease. Overall response rate was 64% and median overall survival and progression‐free survival were 24 and 13 months, respectively, with an acceptable toxicity profile, highlighting R‐HDMP utility for elderly and frail patients.

Background Vitiligo is a muco-cutaneous, autoimmune, localized, or disseminated disease, which manifests through hypochromic or achromic macules, with loss in quality of life. The prevalence of vitiligo in Brazil was determined to be 0.54%. There is no on-label medication for its treatment. To date, no Brazilian consensus on the treatment of vitiligo had been written. Objectives The objective of this group of Brazilian dermatologists with experience in the treatment of this disease was to reach a consensus on the clinical and surgical treatment of vitiligo, based on articles with the best scientific evidence. Methods Seven dermatologists were invited, and each was assigned two treatment modalities to review. Each treatment (topical, systemic, and phototherapy) was reviewed by three experts. Two experts reviewed the surgical treatment. Subsequently, the coordinator compiled the different versions and drafted a text about each type of treatment. The new version was returned to all experts, who expressed their opinions and made suggestions for clarity. The final text was written by the coordinator and sent to all participants to prepare the final consensus. Results/Conclusion The experts defined the following as standard treatments of vitiligo: the use of topical corticosteroids and calcineurin inhibitors for localized and unstable cases; corticosteroid minipulse in progressive generalized vitiligo; narrowband UVB phototherapy for extensive forms of the disease. Surgical modalities should be indicated for segmental and stable generalized vitiligo. Topical and systemic anti-JAK drugs are being tested, with promising results.

Introduction Treatment of Splenic (SMZL) and Nodal (NMZL) Marginal Zone Lymphoma is not consensual. Histologic transformation (HT) to aggressive lymphoma is a poorly understood event, with an unfavorable outcome. Objectives Describe the clinical characteristics, treatment, outcomes and incidence of HT. Methods Characteristics of patients with SMZL and NMZL consecutively diagnosed in 8 Portuguese centers were retrospectively reviewed. Endpoints were overall survival (OS), time to first systemic treatment (TTFST), frequency of HT and time to transformation (TTT). Results This study included 122 SMZL and 68 NMZL, most of them received systemic treatment: 55.4% and 76.5%, respectively. Splenectomy was performed in 58.7% of patients with SMZL. Different treatment protocols were used. OS or TTFST did not differ significantly according to treatments. Given the small sample size, no conclusion can be made concerning the role of Rituximab in the treatment of NMZL and SMZL based in these results. HT was documented in 18 patients, mainly in SMZL, with a cumulative incidence at 5 years of 4.2%. We confirmed that age is a prognostic factor. Conclusion Randomized prospective trials are needed to standardize treatment in MZL. Patients with HT did appear to have shorter OS in comparison with those who did not experience HT (OS 5 years of 68.4% vs. 80.4%), but the number of HT was too small to reach statistical significance.

© 2021 the International Society of Dermatology, A 66-year-old man presented with a 10-month history ofmultiple pruritic flesh-colored translucent papules on both eye-brows. Two of the lesions were located on the left eyebrowand four grouped on the right eyebrow (Fig. 1a,b). He had noother symptoms or signs. Clinical examination showed noother skin lesions nor evidence of lymphadenopathy. A punchbiopsy specimen revealed a dense nodular infiltrate ofmonomorphic small to medium-sized B lymphocytes involvingthe superficial and deep dermis (Fig. 2a–c). Immunohistochem-ical studies disclosed immunoreactivity of the lymphoid cellsfor CD5, CD20, and CD23 (Fig. 2d). The complete blood cellcount was normal, but the flow cytometry of the peripheralblood, the myelogram, and the osteomedullary biopsy wereconsistent with B-cell chronic lymphocytic leukemia (B-CLL)diagnosis. Fluorescence in situ hybridization (FISH) analysisperformed on peripheral blood and bone marrow disclosed nochromosomal abnormalities. Imaging studies showed no signifi-cant alterations. The patient was treated with local irradiationof lesions (total cumulative dose of 12 Gray), with completeclinical resolution. There were no complications or recurrenceat 12 months follow-up.

Introduction: Brazil has presented alarming and growing data on infection and deaths from SARS-CoV-2. There are more than 4 500 000 confirmed cases and more than 137 000 deaths ranking second in the world ranking of infected people. In addition to the involvement of the respiratory, cardiovascular, renal and neurological systems, this virus also causes non-specific skin lesions in same patients. Little is known about the pathophysiology of cutaneous involvement. At this moment, we cannot predict a difference in prognosis based on skin lesions. Methods: We conducted an observational case study of 25 patients affected by SARS-CoV-2 who had dermatological lesions. We described the clinical and epidemiological characteristics of each case, demonstrating the polymorphism of the skin lesions and also making a correlation with the chronology of presented systemic symptoms. Results: Twenty five cases of COVID-19 with cutaneous manifestations (urticaria, erythematous rash, maculopapular eruption, pruritus, erythema multiforme-like lesions, dyshidrotic eczema) were observed during, after and before systemic symptoms. A few cases with skin involvement were also observed as isolated symptoms of the viral infection. These data demonstrate the clinical polymorphism related to skin involvement of patients infected with SARS-CoV-2, emphasizing the importance of clinical suspicion by dermatologists when handling suspected cases in the current epidemiological scenario. Conclusion: Although the number of cases in the world stage seems to be regressing, infection by SARS-CoV-2 will be part of the dermatologist's daily routine. As long as we do not have a widely available vaccine and the pandemic takes on an endemic profile, we need to be aware of these manifestations, not only for the proper diagnosis, indication of patient isolation, as well as all the necessary biosafety procedures in dermatology clinics.

Objectives Since physicians play an important role in antibiotic usage, it is vital to understand their antibiotic-prescribing behaviour and knowledge on antimicrobial resistance in order to develop and implement effective antibiotic stewardship interventions. The aim of this study was to evaluate Portuguese physicians’ knowledge and to understand prescription behaviours, difficulties and barriers in their antibiotic prescription process in order to promote better and well-adapted antibiotic stewardship policies. Methods This study was conducted in 2016 using a self-administered questionnaire to physicians in two tertiary public hospitals from two different regions in Portugal. Results Participating physicians [response rate 47.6% (30/63)] identified antibiotic resistance as a global problem; however, one-third did not recognise antibiotic resistance as a major problem on their own hospital. Factors that most influenced antibiotic prescription were ‘microbiology laboratory results’, ‘patient clinical situation’ and patient ‘co-morbidities’. On the other hand, ‘colleagues’ opinion’ and ‘costs control’ were considered as less determining factors. Regarding difficulties and bottlenecks in the antibiotic prescription process, participant physicians reported ‘lack of (or delayed) microbiological results’ and ‘no access to antibiotic susceptibility patterns’ as major barriers. ‘Education and training’ was considered the most effective intervention to improve antibiotic prescription. Conclusion These results suggest that the design and implementation of antibiotic stewardship interventions should provide better data management and sharing tools between physicians and the microbiology laboratory, especially through the creation of antimicrobial prescribing guidelines according to hospital epidemiology, and easy access to hospital antibiotic susceptibility patterns and epidemiological data.

Passive transfer of antibodies secondary to intravenous immunoglobulin infusion is a rare but important side effect that can lead to the wrong diagnosis and therapeutic decisions. It has never been reported in a newborn. A male newborn, vaccinated against hepatitis B and diagnosed with dilated cardiomyopathy, presented positive hepatitis B core antibodies at 12 days of life. Exclusion of hepatitis B infection was mandatory as it would be a contraindication to heart transplant. Passive transfer of antibodies was confirmed at 44 days of age, after seroreversion of hepatitis B core antibodies. Passive transfer of antibodies after intravenous immunoglobulin infusion can lead to a misleading diagnosis if not recognized. In our patient it could have been especially harmful had it prevented heart transplant. Screening for hepatitis B should be performed at least 1 month after intravenous immunoglobulin infusion.

Background: The development of two different non-Hodgkin lymphomas in the same patient is an unlikely coincidence due to the low prevalence of each malignancy. However, a significantly increased risk of developing a second lymphoma was observed in patients with cutaneous T-cell lymphoma (CTCL) in both population-based and clinic-based data [ 1 ]. Most cases reported describe the occurrence of concomitant lymphomas of discordant B- and T-cell phenotypes, mainly MF and chronic lymphocytic leukemia [ 2 ]. On the opposite, few cases of concomitant systemic and cutaneous B-cell lymphomas have been reported [ 3 , 4 ]. Case 1: A young woman with the diagnosis of three B-cell lymphomas. At 37 years-old, primary cutaneous marginal zone lymphoma (pcMZL) was diagnosed on a right cervical cutaneous nodule and relapsed 3 years later on the temporal region; both lesions were excised. One year later, diffuse large B-cell lymphoma (DLBCL) diagnosis was made on an isolated cervical right lymphadenopathy. She was staged as Ann Arbor stage I and treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) regimen for 6 cycles with complete response (CR). Two years later, the diagnosis of follicular lymphoma was made on a lymph node biopsy. The patient remained with asymptomatic cervical and inguinal lymph node enlargement for 10 years until extra-nodal involvement ensued. At that time, treatment with R-FC (rituximab-fludarabine and cyclophosphamide) followed by radiotherapy achieved partial response (PR). In the following 3 years, follicular lymphoma progressed twice and was retreated with radiotherapy with PR. After 5 years of follow-up, the patient remains asymptomatic without further treatment. Case 2: A patient with two lymphomas of discordant phenotype. The 51 years-old Caucasian man presented at our dermatology clinic with a 10-years history of cutaneous erythematous patches and plaques on the abdomen and upper limbs. The 3 cutaneous biopsies made were consistent with the diagnosis of mycosis fungoides and workup excluded systemic involvement. As such, a diagnosis of mycosis fungoides (MF) stage IB was made. The patient had been observed on another hospital facility 3 months before, when he presented bilateral inguinal lymph node enlargement. The excisional biopsy revealed follicular lymphoma but the pathology examination review of the sample at our hospital diagnosed DLBCL, non-germinal center type, that was staged as Ann Arbor II. He started chemoimmunotherapy with R-CHOP regimen for 6 cycles, leading to CR and a mild improvement on MF (downstaging to IB). The patient is currently on topical steroids for MF and DLBC lymphoma is still on remission after 1 year of follow-up. Conclusions: The occurrence of concomitant systemic and cutaneous lymphomas of discordant or concordant lineages may represent a diagnostic challenge. As the treatment of each lymphoma is often different, their correct identification is critical for optimal management of both diseases.

Understanding whether cannabidiol (CBD) is useful and safe for the treatment of psychiatric disorders is essential to empower psychiatrists and patients to take good clinical decisions. Our aim was to conduct a systematic review regarding the benefits and adverse events (AEs) of CBD in the treatment of schizophrenia, psychotic disorders, anxiety disorders, depression, bipolar disorder and substance-use disorders.We conducted a literature search in PubMed, Scielo, and Clinicaltrials.gov databases. Evidence was classified according to the WFSBP task forces standards.Bibliographic research yielded 692 records. After analysis, we included six case reports and seven trials, comprising 201 subjects. Most the studies published presented several drawbacks and did not reach statistical significance. We have not found evidence regarding major depressive and bipolar disorders. The level of evidence for cannabis withdrawal is B; cannabis addiction is C2; treatment of positive symptoms in schizophrenia and anxiety in social anxiety disorder is C1. Discrete or no AEs were reported. The most frequently reported AEs are sedation and dizziness.The evidence regarding efficacy and safety of CBD in psychiatry is still scarce. Further larger well-designed randomised controlled trials are required to assess the effects of CBD in psychiatric disorders.

Resumo: O objetivo foi avaliar o efeito da exposição e do tempo de exposição ao aleitamento materno na ocorrência de transtornos mentais comuns (TMC) entre adolescentes escolares brasileiros. Este trabalho analisou dados do Estudo de Riscos Cardiovasculares em Adolescentes (ERICA), avaliando aqueles que tiveram o questionário referente ao aleitamento materno respondido pelos pais ou responsáveis. A presença de TMC foi identificada pelo General Health Questionnaire, versão 12 itens (GHQ-12), considerando-se dois pontos de corte (escores ≥ 3 e ≥ 5). As associações foram testadas em análises bivariadas e por meio de modelos de regressão logística múltipla, com ajustes por variáveis potenciais de confusão. Dentre os 41.723 adolescentes avaliados, a maioria foi composta por estudantes do sexo feminino (54,6%), que tinham idades entre 12 e 15 anos (71%), estudavam em escolas públicas (83,1%), residiam na Região Sudeste (51,9%) e eram das classes econômicas B (53,8%) e C (34,1%). Cerca de metade das mães dos adolescentes não tinha o ensino médio completo (51,7%). O grupo de adolescentes com mais de seis meses de aleitamento materno (51,8%) apresentou uma menor prevalência de TMC para os dois pontos de corte do GHQ-12 avaliados, quando comparado com o grupo que não recebeu aleitamento materno ou que o recebeu por período ≤ 1 mês (RI = 0,82; IC95%:0,69-0,97 e RI = 0,74; IC95%: 0,59-0,91 para 3 e 5 pontos, respectivamente). O aleitamento materno prolongado parece desempenhar um papel protetor para a ocorrência de TMC na adolescência. Abstract: This article sought to evaluate the effect of exposure, and exposure time, to breastfeeding on the occurrence of common mental disorders (CMD) among Brazilian adolescents enrolled in school. This study analyzed data from the Study of Cardiovascular Risk in Adolescents (ERICA), evaluating those whose questionnaire regarding breastfeeding had been filled out by parents or guardians. The presence of CMD was identified using the General Health Questionnaire, version 12 items (GHQ-12), and we considered two cutoff points (scores ≥ 3 and ≥ 5). We tested the associations in bivariate analyses and through multiple logistical regression models, adjusting for potential confounding variables. Of the 41,723 adolescents we evaluated, most were students of the female sex (54.6%), aged between 12 and 15 years (71%), attended public schools (83.1%), resided in the Southeastern region (51.9%) and belonged to the economic classes B (53.8%) and C (34.1%). Around half of the adolescents’ mothers had not completed their secondary education (51.7%). The group of adolescents who were breastfed for more than six months (51.8%) had a lower CMD prevalence for both GHQ-12 cutoff points, when compared with the group who were not breastfed or who were breastfed for ≤ 1 month (IR = 0.82; 95%CI: 0.69-0.97 and IR = 0.74; 95%CI: 0.59-0.91 for 3 and 5 points, respectively). Prolonged breastfeeding seems to play a protective role on the occurrence of CMD in adolescence. Resumen: El objetivo fue evaluar el efecto de la exposición y del tiempo de exposición a la lactancia materna en la ocurrencia de trastornos mentales comunes (TMC) entre adolescentes escolares brasileñas. Este trabajo analizó datos del Estudio de Riesgos Cardiovasculares en Adolescentes (ERICA), evaluando aquellos, cuyo cuestionario -referente a la lactancia materna- había sido respondido por los padres o responsables legales. La presencia de TMC fue identificada por el General Health Questionnaire, versión 12 ítems (GHQ-12), considerándose dos puntos de corte (puntuaciones ≥ 3 y ≥ 5). Las asociaciones fueron probadas en análisis bivariados, y a través de modelos de regresión logística múltiple, con ajustes por variables potenciales de confusión. Entre los 41.723 adolescentes evaluados, la mayoría estuvo compuesta por estudiantes que eran del sexo femenino (54,6%), que tenían una edad entre 12 y 15 años (71%), estudiaban en escuelas públicas (83,1%), residían en la región Sudeste (51,9%) y eran de las clases económicas B (53,8%) y C (34,1%). Cerca de la mitad de las madres de los adolescentes no contaba con la enseñanza media completa (51,7%). El grupo de adolescentes con más de seis meses de lactancia materna (51,8%) presentó una menor prevalencia de TMC para los dos puntos de corte del GHQ-12 evaluados, cuando se comparan con el grupo que no recibió lactancia materna o que la recibió durante un período ≤ 1 mes (RI = 0,82; IC95%: 0,69-0,97 y RI = 0,74 y IC95%: 0,59-0,91 para 3 y 5 puntos, respectivamente). La lactancia materna prolongada parece desempeñar un papel protector para la ocurrencia de TMC en la adolescencia.

IntroductionStudies which focus on the process of acculturation in the lifestyles, nutritional status and health of immigrants from the Community of Portuguese-Speaking Countries (CPLP) in the Iberian Peninsula are still scarce. This study aims to explore the influence of the acculturation process and dietary acculturation on the lifestyle and nutritional and health status of CPLP immigrants in Portugal and Spain, focusing on two Iberian contexts: Lisbon Metropolitan Area and the Basque Country.Methods and analysisA mixed methods sequential explanatory design, combining cross-sectional studies and semistructured interviews. Official data will also be analysed. Primary data will be collected through a questionnaire and assessment of nutritional status and body composition. The estimated samples sizes are 1061 adults (≥18 years old) in the Lisbon Metropolitan Area and 573 in the Basque Country. Time-location sampling will be used for the quantitative component and non-probabilistic sampling for the qualitative component. If safety conditions are not guaranteed due to the COVID-19 pandemic, online studies will be conducted. The semistructured interviews will complement the questionnaire data and extend knowledge about the process of acculturation of CPLP immigrants and their relationship with eating habits and physical activity. Thematic analysis will be used for qualitative data. Triangulation of data derived from different methods will be carried out. An integrative approach will be used to address potential discrepancies in findings and limitations inherent to the study design. As inter-method discrepancies may occur, triangulation protocol will be used, elaborating a ‘convergence coding matrix’ to display findings emerging from each component of the study.Ethics and disseminationEthical approval was obtained through the IHMT Ethics Council (Doc No 20/2020), Portugal, and it was submitted to the Ethics Committee of the UPV/EHU (Doc No under revision), Spain.

Introduction Acute Promyelocytic Leukemia (APL) prognosis has largely improved over the past decades and is now the acute leukemia with the highest cure rates. However, its early death rate, which reaches 30% in several real-world studies, is the main obstacle to achieving lifelong remission in most patients. Several reports have suggested a potential role of the Disseminated Intravascular Coagulation (DIC) Score of the International Society of Thrombosis and Hemostasis as a marker of bleeding and death in APL. Since the APL-induced coagulopathy and hyperfibrinolysis are responsible for most early deaths, a method to assess the severity of the coagulopathy could guide the daily patient management and the intensity of the blood products used. We aimed to test the hypothesis of whether the improvement of the DIC Score through coagulopathy support can improve the rate of early death in APL. Methods This retrospective, single-center study, included consecutively admitted patients with newly diagnosed genetically confirmed Acute Promyelocytic Leukemia between 2000 and 2020, who were treated with ATRA + anthracycline protocols and prednisolone 0.5 mg/kg differentiation syndrome prophylaxis. All patients received platelets, fibrinogen, and/or fresh frozen plasma according to published clinical indications. Baseline demographics and clinical data were collected, and the DIC Score was calculated at diagnosis and after 48 hours for each patient, using fibrinogen, platelets, prothrombin time and d-dimers. "DIC Score improvement" was defined as an increase of ≥1 point in the calculated score at 48 hours; a stable or decreasing score were considered "no-improvement". A 30-day follow-up for each patient was conducted, and any death during this period was considered in the early-death group. Statistical analysis was performed using Stata, with chi-square test and Mann-Whitney test for differences between groups, and logistic regression for the analysis of predictors of early death. Results A total of 67 patients were included, after excluding 9 patients for missing coagulation values, 8 for first-line arsenic trioxide treatment, and 7 patients for death within 48 hours of hospital admission. The median age was 53 years (25-82), and 29.9% of patients were aged >60 years old. The 30-day mortality rate for this cohort was 31.3%. Comparing the baseline differences between the two groups, the only statistically significant difference detected was a less frequent improvement of the DIC Score over 48 hours in the early-death group (42.86% versus 76.09% in the remaining patients, p=0.008). There was no difference in the Sanz Risk distribution nor age between the two groups. The univariate analysis of predictors of death in 30 days (logistic regression) yielded age >60 years and 48h-improvement of the DIC Score as potential predictors of death. A multivariate analysis model was built incorporating these 2 variables with the Sanz Risk (the number of events in this study permitted only a 3-variable prognostic model), and it identified age>60 years (OR 4.84 [1.37-17.10]; p=0.014) and the lack of a 48-hour improvement in the DIC Score (OR 5.46 [1.61-18.47]; p=0.006) as independent predictors of early death. In patients under 60 years old, having no improvement in the DIC Score over 48 hours is still associated with almost five times superior odds of 30-day mortality (OR 4.55; p=0.038). Conclusion In this cohort, we identified a lack of DIC Score improvement and age>60 years as independent predictive factors of early death in APL. These findings identified a new independent predictor of early death using a dynamic DIC Score assessment, which is easily accessible and calculated, and illustrate how this score can be applied daily in the clinical care of APL patients. Together with the current APL treatment strategies, the intensification of measures to control the leukemia-associated coagulopathy in patients who do not show a DIC Score improvement in the first 48 hours after diagnosis could decrease the early death rate in this otherwise highly-curable leukemia. Disclosures Brioso Infante: Astellas: Speakers Bureau; Novartis: Speakers Bureau.

Esta carta traz uma reflexão surgida a partir da palestra da professora Fatimata Ly, da University Cheikh Diop de Dakar (África), no último Congresso da Academia Europeia de Dermatologia, em Paris. A professora F. Ly proferiu a palestra Depigmentation: when, where and how. O tom de pele uniforme é um dos critérios de beleza. Esta carta não diz respeito aos pacientes que chegam ao consultório médico e que são cuidadosamente acompanhados e monitorados por dermatologistas criteriosos. Ela quer chamar a atenção para os indivíduos que não chegam aos consultórios, que repetem prescrições de conhecidos ou que mantêm por tempo indefinido uma prescrição realizada por dermatologista numa consulta pontual. Recentemente, participei, de forma anônima, de fóruns de “discussão” na internet de pessoas leigas sobre melasma. A intensidade e a velocidade do compartilhamento em relação àquilo que eles aconselham são expressivas. A criatividade é enorme ao sugerirem usar produtos que podem causar algum dano. Entre os clareadores mais utilizados estão esteroides, hidroquinona, mercúrio e ácidos. Há que se realizar uma campanha de conscientização da população em relação aos perigos de se utilizarem despigmentantes cutâneos sem indicação precisa do médico dermatologista.

© Springer Science+Business Media, LLC, part of Springer Nature 2018, Chemotherapy-induced cardiotoxicity is a growing concern. The cardiotoxic impact of new drugs such as tyrosine kinase inhibitors is unknown, especially the ones used for chronic myeloid leukemia. We aim to evaluate nilotinib- and imatinib-induced cardiotoxicity. Single-center prospective study of consecutive patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors was conducted during 2015. Patients underwent an initial clinical, laboratorial and echocardiographic evaluation, repeated after 1 year. Eleven patients were included [60.0 (11) years, 63.6% of males; seven patients treated with imatinib and four with nilotinib]. After 1 year of follow-up, all patients remained in functional NYHA class I, with a similar Minnesota quality of life score. Also there was no difference in the biomarkers evaluated (cystatin-C and NT-proBNP). Likewise, no modification in systolic or diastolic function evaluated by echocardiography was observed. All patients presented normal values of longitudinal, circumferential and radial strain in the baseline study, without changes during follow-up. In addition, there were no differences between the two tyrosine kinase inhibitors used, considering all the aforementioned variables. No clinical, laboratory or echocardiographic evidence of nilotinib- and imatinib-induced cardiotoxicity was observed. However, these results should be confirmed in multicenter studies given the low incidence of chronic myeloid leukemia.

Introduction: Quality control programs are required to ensure the effectiveness of Pap smear, which still remain a key strategy for control of cervical cancer worldwide. Objective: This study was based on the retrospective and quantitative analysis of the post-analytical phase indicators from the internal quality monitoring (IQM) program for cytopathology laboratories, such as: positivity rate, atypical squamous cell (ASC)/satisfactory exams ratio, ASC/abnormal test results ratio, ASC/squamous intraepithelial lesions (SIL) ratio, percentage of tests compatible with high-grade squamous intraepithelial lesion (HSIL), and total of false negative. Materials and methods: The information was extracted from the computerized system of the Section for Integrated Technology in Cytopathology (Seção Integrada de Tecnologia em Citopatologia [SITEC]), a reference institution for cancer cytopathology, from July 2013 to June 2014. From a total of 156,888 Pap smears, 157,454 were considered satisfactory for indicator analysis and 566 were excluded because they were considered unsatisfactory and/or rejected for analysis. The data was organized in tables using Microsoft Excel 2010 software, and categorized as indicators. Results: The averages for the indicators were: 7.2% for positivity rate, 56.9 for ASC/abnormal test ratio, 4.1 for ASC/satisfactory tests ratio, 1.4 for ASC/SIL ratio, 0.6% percentage for tests compatible with HSIL, and 2.1% for false-negative rate. Conclusion: The results show that an Internal Quality Monitoring Program is essencial to ensure quality for cytopathology laboratories, and a randomized review of at least 10% of the negative exams, as recommended by the Brazilian Ministry of Health/Instituto Nacional de Câncer (INCA), since is an effective method, especially for large laboratories.

Lateral meningocele syndrome (LMS, OMIM%130720), also known as Lehman syndrome, is a very rare skeletal disorder with facial anomalies, hypotonia and meningocele-related neurologic dysfunction. The characteristic lateral meningoceles represent the severe end of the dural ectasia spectrum and are typically most severe in the lower spine. Facial features of LMS include hypertelorism and telecanthus, high arched eyebrows, ptosis, midfacial hypoplasia, micrognathia, high and narrow palate, low-set ears and a hypotonic appearance. Hyperextensibility, hernias and scoliosis reflect a connective tissue abnormality, and aortic dilation, a high-pitched nasal voice, wormian bones and osteolysis may be present. Lateral meningocele syndrome has phenotypic overlap with Hajdu–Cheney syndrome. We performed exome resequencing in five unrelated individuals with LMS and identified heterozygous truncating NOTCH3 mutations. In an additional unrelated individual Sanger sequencing revealed a deleterious variant in the same exon 33. In total, five novel de novo NOTCH3 mutations were identified in six unrelated patients. One had a 26 bp deletion (c.6461_6486del, p.G2154fsTer78), two carried the same single base pair insertion (c.6692_93insC, p.P2231fsTer11), and three individuals had a nonsense point mutation at c.6247A > T (pK2083*), c.6663C > G (p.Y2221*) or c.6732C > A, (p.Y2244*). All mutations cluster into the last coding exon, resulting in premature termination of the protein and truncation of the negative regulatory proline-glutamate-serine-threonine rich PEST domain. Our results suggest that mutant mRNA products escape nonsense mediated decay. The truncated NOTCH3 may cause gain-of-function through decreased clearance of the active intracellular product, resembling NOTCH2 mutations in the clinically related Hajdu–Cheney syndrome and contrasting the NOTCH3 missense mutations causing CADASIL. © 2014 Wiley Periodicals, Inc.

This study aimed to evaluate long-term atrophy in contralateral hippocampal volume after surgery for unilateral MTLE, as well as the cognitive outcome for patients submitted to either selective transsylvian amygdalohippocampectomy (SelAH) or anterior temporal lobe resection (ATL).We performed a longitudinal study of 47 patients with MRI signs of unilateral hippocampal sclerosis (23 patients with right-sided hippocampal sclerosis) who underwent surgical treatment for MTLE. They underwent preoperative/postoperative high-resolution MRI as well as neuropsychological assessment for memory and estimated IQ. To investigate possible changes in the contralateral hippocampus of patients, we included 28 controls who underwent two MRIs at long-term intervals.The volumetry using preoperative MRI showed significant hippocampal atrophy ipsilateral to the side of surgery when compared with controls (p0.0001) but no differences in contralateral hippocampal volumes. The mean postoperative follow-up was 8.7 years (± 2.5 SD; median=8.0). Our patients were classified as Engel I (80%), Engel II (18.2%), and Engel III (1.8%). We observed a small but significant reduction in the contralateral hippocampus of patients but no volume changes in controls. Most of the patients presented small declines in both estimated IQ and memory, which were more pronounced in patients with left TLE and in those with persistent seizures. Different surgical approaches did not impose differences in seizure control or in cognitive outcome.We observed small declines in cognitive scores with most of these patients, which were worse in patients with left-sided resection and in those who continued to suffer from postoperative seizures. We also demonstrated that manual volumetry can reveal a reduction in volume in the contralateral hippocampus, although this change was mild and could not be detected by visual analysis. These new findings suggest that dynamic processes continue to act after the removal of the hippocampus, and further studies with larger groups may help in understanding the underlying mechanisms.

O dedo azul não-isquémico espontâneo é uma entidade rara e benigna, caracterizada pela alteração da coloração isolada de um dedo, com aparecimento e resolução espontânea. Este artigo relata o caso de uma mulher de 88 anos, que após algumas horas de permanência no serviço de urgência desenvolveu, sem trauma associado uma coloração violácea do terceiro dedo da mão direita, com pulsos mantidos, sem alteração da temperatura e indolor. A pesquisa etiológica realizada foi negativa. A doente foi reavaliada uma semana após o evento e mostrava regressão total da lesão. Apesar de existirem várias patologias que partilham sinais e sintomassemelhantes, o diagnóstico baseia-se no aparecimento espontâneo, na coloração violácea característica que poupa a polpa do dedo, e na resolução rápida sem necessidade de tratamento. Mesmo sendo um fenómeno benigno necessita de avaliação precoce para que o diagnóstico diferencial com patologias mais graves seja feito atempadamente.

This study aimed to evaluate the prevalence of dyslipidemias and related factors, in Brazilian adolescents from rural and urban areas. This is a cross-sectional study with 182 adolescents aged 10 to 13 years, students, residing in the rural and urban area of Brazil; grouped according to age, gender and socioeconomic class. Sexual maturation, physical activity, blood pressure, nutritional status and body composition were evaluated. Total cholesterol, LDL, HDL and serum triglycerides were dosed. The food frequency questionnaire was applied, quantifying energy, carbohydrates, proteins, lipids, full fat and fibers. Bivariate and multiple analyses were carried out, by logistic regression. It was verified that 84.6% (n = 154) adolescents presented some lipid profile alteration. There was no difference in the lipid profile between adolescents for residence place. However, as for gender, it was noticed that girls presented higher levels of total cholesterol and HDL (p < 0.05). In addition, adolescents with excess weight and body fat showed lower HDL and higher triglycerides values compared with eutrophic and with those with appropriate body fat percentage (p < 0.05). In the multiple analyses, it was observed that gender and signs of sexual maturation were associated with total cholesterol; fiber intake remained associated with HDL and signs of sexual maturation with LDL (p < 0.05). For triglycerides the related factors were gender, nutritional status and protein intake (p < 0.05). The elevated prevalence of dyslipidemias found between adolescents from rural and urban areas reinforces the importance of monitoring these alterations and information as for the related risk factors, with programs for correction of changeable factors.

CONTEXT AND OBJECTIVE: Uterine fibroids (UF), also known as leiomyomas, are the most prevalent gynecological tumors. The Uterine Fibroid Symptoms and Quality of Life (UFS-QOL) is the only specific questionnaire that assesses symptom intensity and quality-of-life issues for women with symptomatic UF; however, it only exists in the English language. Thus, we aimed to translate and culturally validate the UFS-QOL questionnaire for the Brazilian Portuguese language. DESIGN AND SETTING: Cross-sectional study, Department of Gynecology and Obstetrics, FMRP-USP. METHODS: 113 patients with UF (case group) and 55 patients without UF (control group) were interviewed using the UFS-QOL questionnaire after translation and cultural adaptation. The Short Form-36 questionnaire was used as a control. Demographic and psychometric variables were analyzed. RESULTS: Women with UF presented higher mean age, body mass index, weight, parity and comorbidities than the control group (P < 0.05). The most prevalent complaints were abnormal uterine bleeding (93.8%), pelvic pain (36.3%) and extrinsic compression (10.6%) and these presented adequate construct validity regarding UFS-QOL severity (P < 0.05). The UFS-QOL questionnaire presented good internal consistency regarding symptom severity and quality-of-life-related domains (intraclass correlation coefficient, ICC = 0.82/0.88). Structural validity presented correlation coefficients ranging from 0.59 to 0.91. Test-retest comparison did not show differences among the UFS-QOL subscales. After treatment, women with UF presented improvements on all subscales. CONCLUSION: The UFS-QOL questionnaire presented adequate translation to the Brazilian Portuguese language, with good internal consistency, discriminant validity, construct validity, structural validity and responsiveness, along with adequate test-retest results. RESUMO CONTEXTO E OBJETIVO: O leiomioma uterino (LU) é o tumor ginecológico mais comum. Existe apenas um questionário específico que avalia a intensidade de sintomas e qualidade de vida de mulheres com LU sintomático, o Uterine Fibroid Symptom and Quality of Life (UFS-QOL), porém somente na língua inglesa. Dessa forma, objetivamos traduzir e validar culturalmente o questionário UFS-QOL para a língua portuguesa brasileira. TIPO DE ESTUDO E LOCAL: Estudo transversal, Departamento de Ginecologia e Obstetrícia da FMRP-USP. MÉTODOS: 113 pacientes portadoras de LU (grupo caso) e 55 pacientes-controle foram entrevistadas com o questionário UFS-QOL após tradução e adaptação cultural. O questionário Short Form-36 foi utilizado para controle. Variáveis demográficas e psicométricas foram analisadas. RESULTADOS: As mulheres com LU apresentaram maior média de idade, índice de massa corporal, peso, paridade e comorbidades do que o grupo controle (P < 0,05). As queixas mais prevalentes foram sangramento uterino anormal (93,8%), dor pélvica (36,3%) e compressão extrínseca (10,6%) e estas apresentaram adequada validade de constructo com a gravidade indicada pelo UFS-QOL (P < 0,05). O questionário UFS-QOL apresentou boa consistência interna com a gravidade dos sintomas e com os domínios relacionados a qualidade de vida (coeficiente de correlação intraclasse, CCI = 0,82/0,88). A validade estrutural mostrou coeficientes de correlação variando de 0,59 até 0,91. A comparação teste-reteste não mostrou diferença entre as subscalas do UFS-QOL. Depois do tratamento, as mulheres com LU apresentaram melhora em todas as subscalas. CONCLUSÃO: O questionário UFS-QOL apresentou adequada tradução para a língua portuguesa brasileira, com boa consistência interna, validade de constructo/discriminatória, estrutural e responsividade, assim como adequados resultados teste-reteste.

A 70-year-old man with a history of prostate cancer, previously submitted to surgical castration and trans-urethral resection of the prostate, was admitted to Accident and Emergency department. He had been suffering from osteoarticular and abdominal pain, and recent weight loss. An abdominal and a pelvic CT showed multiple hepatic metastases and a pelvic mass, but his prostate-specific antigen values were low (0.26 n/mL). A biopsy of a hepatic metastasis and of the pelvic mass revealed a small-cell neuroendocrine prostate cancer, a rare and aggressive androgen-independent form of prostate cancer with a poor prognosis. Our purpose was to report a clinical case of a rare and aggressive variant of a common disease. A high index of suspicion is required to make an early diagnosis and to ensure a proper therapeutic approach.

Pelvic floor disorders [urinary (UI) and/or fecal C (FI) incontinence, pelvic organ prolapse (POP)] may have a significant impact in womens’ quality of life (QoL). The Pelvic Floor Impact Questionnaire (PFIQ-7) and Pelvic Floor Distress Inventory (PFDI-20) help assess these disorders; however, we do not have them culturally translated in the Brazilian Portuguese language. A cross-sectional study was performed of 185 women with pelvic floor disorders (PFD group) and 65 healthy patients (control group). A translated, pilot-tested, Brazilian Portuguese version were given to these women. Internal consistency, construct validity, and floor/ceiling effect were assessed. Test–retest was performed in 79 patients after 4 weeks, and responsiveness was assessed in 42 patients after surgical treatment. Internal consistency (Cronbach’s alpha) was adequate between PFD and control groups on the PFDI-20 (0.816-0.844) and PFIQ-7 (0.823-0.846). Test–retest reliability was also adequate [intraclass correlation coefficient (ICC) 0.803-0.843]. Subscales [Pelvic Organ Prolapse Impact Questionnaire (POPIQ-7) and Colorectal–Anal Impact Questionnaire (CRAIQ-7) from the PFIQ-7 demonstrated floor effect (42.70, 60, and 18.38 %, respectively) in the PFD group, with no influence at total score. No ceiling effect was observed. Construct validity was adequate at all correlations between clinical symptoms and subscales in both questionnaires in both groups. Responsiveness was demonstrated by a statistically significant reduction in scale/subscale scores from PFDI-20 and PFIQ-7 after surgical treatment. The PFDI-20 and PFIQ-7 presented adequate cultural translation and are reliable and valid in the Brazilian Portuguese language.

OBJETIVOS: A obesidade representa importante fator de risco para alterações endometriais. O presente estudo teve por objetivo avaliar a prevalência de lesões endometriais, como pólipos, hiperplasia e câncer de endométrio em mulheres obesas assintomáticas, assim como reconhecer os fatores de risco associados. MÉTODOS: Entre dezembro de 2004 e fevereiro de 2006, em estudo transversal foram avaliadas 94 mulheres obesas (índice de massa corpóreo >30Kg/m²), divididas em dois grupos com 47 participantes cada: em idade reprodutiva e após a menopausa. Foram analisados: história clínica, exame físico (antropométrico/ginecológico), determinações bioquímicas e avaliação do endométrio por ultra-sonografia endovaginal, biópsia e histeroscopia (para confirmar patologia endometrial). RESULTADOS: Nas mulheres em idade reprodutiva foram encontrados 12,8% de casos de patologia endometrial, que se associaram significativamente com as elevações da idade, hipertensão arterial (HAS), colesterol e LDL-c. Após a menopausa, foram identificadas 40,4% de lesões endometriais que se associaram significativamente com pressão arterial sistólica (PAS) > 140mmHg, elevação do LDL-c e da estrona. Dois casos de câncer de endométrio foram constatados, sendo um em cada grupo. CONCLUSÃO: O aumento de incidência da obesidade nos últimos anos tem elevado os fatores de risco para o câncer de endométrio. Na idade reprodutiva tivemos um pequeno tamanho amostral de alterações endometriais; com isso, poderíamos apenas sugerir, uma maior atenção àquelas com idade superior a 40 anos, que apresentem HAS e/ou elevação do LDL-c. O status menopausal eleva o risco de lesão endometrial; associado com elevações da PAS, LDL-c e/ou estrona, elas se tornarão candidatas à biópsia de endométrio, visando o diagnóstico precoce do câncer, decisivo para o prognóstico favorável da mulher. OBJECTIVE: Obesity represents the most important risk factor for endometrial pathology. This study aimed to evaluate the prevalence of endometrial injuries, such as polyps, hyperplasia and endometrial cancer in asymptomatic obese women, as well as to recognize the associated risk factors . METHODS: A cross-sectional study was conducted between December 2004 and February 2006. Ninety-four obese (body mass index > 30 kg/m²) women were evaluated, divided in two groups of 47 participants each: pre-menopausal and postmenopausal women. Clinical characteristics, physical exams (anthropometric and gynecological), blood count and endometrial assessment by vaginal ultrasonography, biopsy, and hysteroscopy (only for confirmed endometrial pathology), were the variables appraised. RESULTS: In pre-menopausal women, 12.8% of cases had endometrial pathology statistically associated to age, hypertension, hypercholesterolemia and LDL-c increase. In the post-menopausal women, 40.4% of cases had a pathology identified as statistically associated with hypertension, LDL-c and estrone increase. Two cases of endometrial cancer were identified, one in each group. CONCLUSIONS: The increased incidence of obesity over recent years has increased risk factors of endometrial cancer. In pre-menopausal women only a small number of cases with endometrial alterations was observed. Therefore, it is suggested that greater attention be given to those over 40 years of age, associated with hypertension and/or higher LDL-c . The menopausal status increases risk of endometrial injury, and when associated with hypertension, LDL-c and/or estrone increase, women become candidates to biopsy aiming for an early diagnosis of cancer, a decisive factor for a favorable prognosis.

The purpose of this study was to investigate the prevalence of migraine in medical students, as well as its clinical aspects and impact. All 595 medical students of Santa Casa School of Medicine of São Paulo, Brazil were asked if they had experienced any kind of headache in the past year. Those who responded positively were further investigated by an appropriate questionnaire. Diagnosis of migraine was based on the International Headache Society criteria of 1988. Forty percent of students suffered from some kind of headache; 40.2% of these headaches were migraine. The prevalence of migraine was 54.4% in women and 28.3% in men. Migraine headaches were unilateral in 24.2%, had a gradual onset in 69%, and were of a throbbing type in 88.3%. Migraine was considered incapacitating by 53.9% of students. Migraine with aura caused more disability than migraine without aura. Women experienced more intense migraine than men, and migraine with aura was especially more severe than migraine without aura. Photophobia, phonophobia, and nausea were more commonly encountered in migraine with aura. Despite the high prevalence, the high rate of disability, and the need for analgesic medication, only 7.1% of students with migraine had sought medical treatment.

Objetivo: Identificar as principais alteracoes no quotidiano da pessoa com ulcera de perna e como estas afetam a sua qualidade de vida. Metodologia: Utilizou-se a metodologia PI[C]OD tendo sido selecionados quatro artigos de investigacao, retirados da EBSCO, PubMed e EWMA. Resultados: As principais alteracoes identificadas no quotidiano da pessoa com ulcera de perna sao: fisicas (dor, diminuicao da mobilidade, presenca de exsudado, mau odor da ulcera e alteracao no estilo de roupa), psicologicas (alteracoes do sono, depressao, ansiedade, sentimentos de repulsa e baixa autoestima), sociais (isolamento, restricao nas atividades de lazer, incapacidade de realizar tarefas domesticas). Conclusoes: A literatura sobre qualidade de vida na pessoa com ulcera de perna relata um impacto significativo no quotidiano da mesma. Os cuidados prestados pelo enfermeiro deverao ser centrados na pessoa, integrando todas as suas necessidades, nao sendo a ulcera de perna o unico foco de cuidados. Descritores: Qualidade de vida, ulcera de perna cronica, ulcera. ABSTRACT Objective: To identify the main changes in the daily life of people with leg ulcer and how that affects the person’s life’s quality. Methodology: We used the methodology PI [C] OD and were selected four research articles, taken from EBSCO, PubMed, and EWMA. Results: The main changes identified in the people’s daily live with leg’s ulcers are physical (pain, decreased mobility, presence of exudate, bad smell from the wound and change in the style of clothing), psychological (sleep disorders, depression, anxiety, feelings of rejection and low self-esteem), social (isolation, restriction in leisure activities, inability to perform household chores). Conclusions: The literature about person’s life’s quality with leg ulcer reported a significant impact in the daily life of that person. The care provided by nurses should be centred on the person itself, integrating all the kind of needs and the leg ulcer mustn’t be the sole focus of care. Descriptors: Quality of life, Chronic leg ulceration, wound

Objetivo: Esta revisao sistematica da literatura pretende esclarecer as indicacoes do uso da alimentacao enterica na pessoa com demencia. As dificuldades na alimentacao da pessoa com demencia podem surgir em qualquer fase da doenca, manifestando-se por desnutricao, perda de peso, decrescimo da qualidade de vida, entre outras. A alimentacao enterica por sonda pode ser uma das opcoes para minorar o seu efeito, onde ainda se discute os seus beneficios. Metodos: Foram incluidos 8 estudos de natureza qualitativa: 5 artigos de fonte primaria, 3 artigos de revisao sistematica da literatura, publicados no horizonte temporal de 2008 a 2013. Resultados: A alimentacao enterica por sonda na pessoa com demencia pode ter efeitos na sobrevivencia/taxa de mortalidade (sem evidencia de beneficio), estado nutricional (sem melhorias), estado funcional e cognitivo (sem melhorias), aspiracao (nao reduz o risco de aspiracao), ulceras de pressao (sem evidencia de beneficio na incidencia e na evolucao das ulceras), qualidade de vida (sem dados concretos na maioria dos estudos). Conclusoes: A evidencia que a alimentacao por sonda nas pessoas com demencia proporciona beneficios nao foi conclusivo, podendo ate ter o efeito oposto. Faltam ainda dados sobre os efeitos adversos destas intervencoes. Descritores: Cuidados paliativos; Demencia; Nutricao enteral; Indicacoes terapeuticas. Abstract Objective: With this systematic literature review aims to clarify the indications for the use of enteral feeding in the person with dementia. The difficulties in feeding the person with dementia, may arise at any stage of the disease and can include malnutrition, weight loss, decreased quality of life, among others. Enteral feeding by tube may be an option, where there is debate about its benefits. Methods: Were included eight qualitative studies: 5 primary source articles, 3 articles systematic literature review, published in the timeframe 2008-2013. Results: Enteral feeding in the person with dementia may have effects in several areas: survival/mortality rate (no evidence of benefit), nutritional status (no improvement), functional status and cognitive development (no improvement), aspiration (enteral feeding does not reduce the risk of aspiration), pressure ulcers (no evidence of benefit in the incidence and progression of ulcers), quality life (without hard data in most studies). Conclusion: Evidence that tube feeding in people with dementia provides benefits was not conclusive, and may even have the opposite effect. There are still data on the adverse effects of these interventions. Key words: Palliative care; Dementia; Enteral nutrition; Therapeutic Use.

Background: Obesity is a public health problem and it is necessary to identify if non-symptomatic obese women must be submitted to endometrial evaluation. Aims: To determine the prevalence of endometrial hyperplasia and cancer in non-symptomatic overweight or obese women. Methods: A cross-sectional study was carried out in 193 women submitted to an endometrial biopsy using a Pipelle de Cornier. The findings were classified as normal, hyperplasia or cancer, and the results were compared to body mass index (BMI; kg/m2). For the purpose of statistical analysis, women were divided into two groups: women of reproductive age and postmenopausal women, and according to BMI as overweight or obese. Results: The prevalence of endometrial cancer and hyperplasia was 1.0% and 5.8% in women of reproductive age and 3.0% and 12.1% in postmenopausal women, respectively. According to logistic regression, being in the postmenopause increased the risk of endometrial hyperplasia and cancer to 1.19 (95% confidence interval (CI): 0.36–3.90), while being postmenopausal and severely obese increased the odds ratio (OR) to 1.58 (95%CI: 0.30–8.23) and being postmenopausal and morbidly obese increased the OR to 2.72 (95%CI: 0.65–11.5). No increase in risk was found in women of reproductive age who were either overweight or obese. Discussion: Our results show that non-symptomatic, severe or morbidly obese postmenopausal women have a high risk of developing endometrial hyperplasia or cancer; however, no such risk was found for women of reproductive age.

Introduction MM is characterized by the presence of a monoclonal immunoglobulin in the serum and/or urine, produced by malignant plasma cells. MM has a highly uncertain evolution and prognostic depending on age, stage and cytogenetic abnormalities. FLC is a readily available laboratory test and has independent prognostic significance in all the plasma cell disease entities helping to clarify International Staging System (ISS). Its value in the era of new therapeutic drugs is to be proved. Purpose To determine the prognostic value of baseline serum FLCr in patients with newly diagnosed MM, consecutively treated with thalidomide or bortezomib based regimens. Methods This is a retrospective study, from July 2004 to December 2012. We studied the relationship of baseline FLCr with outcome and its contribution to clarify the prognostic value of ISS. Serum FLC levels were measured in frozen sera at initial diagnosis, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK) on a Beckman Coulter nephelometric analyzer. FLCr was calculated as k/λ (reference range: 0,26-1,65). Abnormal FLCr was defined of < 0,03 or > 32,00 and standard FLCr of 0,03-32. Patients have been staged by ISS and Mayo Clinic stratification. All patients received at least two cycles of a thalidomide based regimen, 91 patients (38,9%): thalidomide, doxorubicin, dexamethasone (TAD), 37 patients (15,8%) and melphalan/cyclophosphamide, thalidomide, prednisone (M/CTP), 54 patients (23,0%) or bortezomib based regimens, 143 patients (61,1%): bortezomib, doxorubicin and dexamethasone (PAD), 53 patients (22,6%), bortezomib, cyclophosphamide and dexamethasone (Cy-Bor-D), 7 patients (2,9%) and melphalan/cyclophosphamide, bortezomib, prednisone (M/CVP), 83 patients (35,6%). Median follow-up from diagnosis was 25 months. Follow-up was through the review of each patient’s complete medical records at our center. Statistical analysis was performed with SPSS 20 ®. Results We reviewed 234 patients consecutively treated. Male gender was 46,6% and median age was 67 years (22-84y). The Ig type was IgG in 59,4%, IgA in 22,2%, IgD in 1,7%, light chains MM in 15,4% and non-secretory MM in 1,3%. The median Hb level was 10,7g/dL (4,9-16,7g/dL) and serum albumin was 27,4 g/L (9,0-50-0g/L). Twenty five percent of patients had a creatinine clearance 32,00) and 49,1% had standard FLCr 0,03-32,00. FISH was performed in 74,4% patients: 26,0% presented high-risk features. Overall survival (OS) and progression free survival (PFS) were significantly different according the patients presented 0, 1, 2 or 3 Mayo Clinic risk factors, with median survival times of 83, not reached (NR), 39 and 36 months, for OS, p=0,000, and 41, 41, 17 and 17 months for PFS, p=0,000. Patients with abnormal FLCr had similar outcome of standard FLCr. Patients in ISS II had significant different OS according the FLCr: 77 and 39 months for standard and abnormal FLCr, respectively, P=0,015. There was no such correlation on stages I and III. Conclusions Baseline serum FLCr associated to others risk-factors like serum β2-microglobuline and albumin is a powerful prognostic factor for survival in newly diagnosed MM treated with thalidomide or bortezomib-based therapies. FLCr helps to clarify the outcome of ISS stage II patients identifying a subgroup with clearly inferior outcome. Disclosures: Esteves: Yassen: Consultancy; Celgene: Consultancy. Raposo:Roche; lymphoproliferative diseases: Consultancy. Guerra:Novartis, Bristol-Myers Squibb and Amgen. Advisory bord meetings. Areas involved: Myeloproliferative neoplasms and acute leukaemia: Consultancy.

Introduction MM is a B cell malignancy characterized by the presence of a monoclonal immunoglobulin (Ig) in the serum and/or urine produced by clonal plasma cells. MM has a variable outcome depending on age, stage and cytogenetic abnormalities. FLCr is a readily available laboratory test and has independent prognostic significance in all the plasma cell disease entities, helping to clarify International Staging System (ISS), namely the heterogeneous stage II. In the era of new therapeutic agents trending to personalized therapy, its prognostic value needs to be proved. Purpose To evaluate the prognostic value of baseline serum FLCr on outcome of patients with newly diagnosed MM eligible for HDM treated with thalidomide or bortezomib based regimens. Methods This is a retrospective study, from January 2005 to December 2012. We analyzed the relationship of baseline FLCr with outcome and its contribution to clarify the prognostic value of ISS. Serum FLC levels were measured in frozen sera drew at diagnosis before treatment, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK) on a Beckman Coulter nephelometric analyzer. FLCr was calculated as k/λ (reference range: 0,26-1,65). Abnormal FLCr was defined of 32,00 and standard FLCr of 0,03-32. Patients have been staged by ISS and Mayo Clinic stratification. All patients received at least two cycles of a bortezomib based regimen (64,7%), with doxorubicin and dexamethasone (PAD) in 55 patients (53,9%), with cyclophosphamide and dexamethasone (Cy-Bor-D) in 11 patients (10,8%) or thalidomide, doxorubicin and dexamethasone (TAD) in 36 patients (35,3%). Median follow-up from diagnosis was 30 months. Follow-up was through the review of each patient’s complete medical records at our center. Statistical analysis was performed with SPSS 20 ®. Results We reviewed 102 patients treated with thalidomide or bortezomib based-regimens eligible for HDM. Fifty one percent of patients were male and median age was 52 years (22-70y). The Ig type was IgG in 62,7%, IgA in 14,7%, IgD in 3,9%, light chains MM in 17,7% and non-secretory MM in 1,0% of patients. The median Hb level was 9,8 g/dL (5,3-16,7mg/L) and median serum albumin was 31,5 g/L (22,3-48,3g/L). Creatinine clearance 32,00). Cytogenetic FISH analysis was performed in 86,3% of patients: 32,4% presented high-risk features. We observed a significant difference on overall survival (OS) and progression free survival (PFS) according to Mayo Clinic risk-factors: 0, not reached (NR), 1, NR, 2, 49 months and 3, 71 months for OS (P=0,000) and 0, 68 months, 1, 55 months, 2, 16 months and 3, 24 months for PFS (P=0,000). According the FLCr there was a significant advantage on OS for standard FLCr: NR vs 71 months (P=0,035). A trend to a better OS (P=0,061) was observed in stage II patients with standard FLCr but no significant difference at any stage. Conclusions Baseline serum FLCr associated to others risk-factors like serum β2-microglobuline and albumin is a powerful prognostic factor for survival in newly diagnosed MM eligible for HDM treated with thalidomide or bortezomib-based therapies. We fail to fully demonstrate FLCr prognostic value on ISS stage II patients, only a trend for better outcome with standard FLCr. Disclosures: Esteves: Janssen-Cylag and Celgene. Consultancy on the area of multiple myeloma and acute myeloid leukaemia: Consultancy. Raposo:Roche; lymphoproliferative diseases: Consultancy. Guerra:Novartis, Bristol-Myers Squibb and Amgen. Advisory bord meetings. Areas involved: Myeloproliferative neoplasms and acute leukaemia: Consultancy.

Introduction Tuberculosis remains an infectious disease with a high prevalence worldwide and represents a major public health issue. Although venous thromboembolism is a rare complication of this disease, it may be a potentially life-threatening event. Case series presentation We report two cases of severe pulmonary tuberculosis associated with venous thromboembolism. A 38 year-old caucasian male that had a thromboembolic event as an unsual presentation form of tuberculosis and a 51 year-old caucasian male that developed deep venous thrombosis later in the course of the disease. Conclusion An association between inflamation induced by tuberculosis and a hypercoagulable state has been described. Therefore, the occurence of deep venous thrombosis or pulmonary embolic episods, should be considered in patients with tuberculosis particulary during the first weeks of treatment. The physician's awarness of these phenomena is important to an early diagnostic suspicion and prompt treatment in order to prevent fatal outcomes.

We describe seven patients from five different families with GM 2 gangliosidosis, variant B 1 . To our knowledge these are the first juvenile cases reported in the literature

There is a lack of knowledge on the epidemiology of fungal infections worldwide because there are no reporting obligations. The aim of this study was to estimate the burden of fungal disease in Portugal as part of a global fungal burden project. Most published epidemiology papers reporting fungal infection rates from Portugal were identified. Where no data existed, specific populations at risk and fungal infection frequencies in those populations were used in order to estimate national incidence or prevalence, depending on the condition. An estimated 1,510,391 persons develop a skin or nail fungal infection each year. The second most common fungal infection in Portugal is recurrent vulvovaginal candidiasis, with an estimated 150,700 women (15-50 years of age) suffering from it every year. In human immunodeficiency virus (HIV)-infected people, oral or oesophageal candidiasis rates were estimated to be 19.5 and 16.8/100,000, respectively. Candidaemia affects 2.19/100,000 patients, in a total of 231 cases nationally. Invasive aspergillosis is less common than in other countries as chronic obstructive pulmonary disease (COPD) is uncommon in Portugal, a total of 240 cases annually. The estimated prevalence of chronic pulmonary aspergillosis after tuberculosis (TB) is 194 cases, whereas its prevalence for all underlying pulmonary conditions was 776 patients. Asthma is common (10% in adults) and we estimate 16,614 and 12,600 people with severe asthma with fungal sensitisation and allergic bronchopulmonary aspergillosis, respectively. Sixty-five patients develop Pneumocystis pneumonia in acquired immune deficiency syndrome (AIDS) and 13 develop cryptococcosis. Overall, we estimate a total number of 1,695,514 fungal infections starting each year in Portugal., info:eu-repo/semantics/publishedVersion