Acalabrutinib-based regimens in frontline or relapsed/refractory higher-risk CLL: pooled analysis of 5 clinical trials.

ABSTRACT: Before targeted therapies, patients with higher-risk chronic lymphocytic leukemia (CLL), defined as del(17p) and/or TP53 mutation (TP53m), unmutated immunoglobulin heavy chain variable region genes (uIGHV), or complex karyotype (CK), had poorer prognosis with chemoimmunotherapy. Bruton tyrosine kinase inhibitors (BTKis) have demonstrated benefit in higher-risk patient populations with CLL in individual trials. To better understand the impact of the second-generation BTKi acalabrutinib, we pooled data from 5 prospective clinical studies of acalabrutinib as monotherapy or in combination with obinutuzumab (ACE-CL-001, ACE-CL-003, ELEVATE-TN, ELEVATE-RR, and ASCEND) in patients with higher-risk CLL in treatment-naive (TN) or relapsed/refractory (R/R) cohorts. A total of 808 patients were included (TN cohort, n = 320; R/R cohort, n = 488). Median follow-up was 59.1 months (TN cohort) and 44.3 months (R/R cohort); 51.3% and 26.8% of patients in the TN and R/R cohorts, respectively, remained on treatment at last follow-up. In the del(17p)/TP53m, uIGHV, and CK subgroups in the TN cohort, median progression-free survival (PFS) and median overall survival (OS) were not reached (NR). In the del(17p)/TP53m, uIGHV, and CK subgroups in the R/R cohort, median PFS was 38.6 months, 46.9 months, and 38.6 months, respectively, and median OS was 60.6 months, NR, and NR, respectively. The safety profile of acalabrutinib-based therapy in this population was consistent with the known safety profile of acalabrutinib in a broad CLL population. Our analysis demonstrates long-term benefit of acalabrutinib-based regimens in patients with higher-risk CLL, regardless of line of therapy.

Follicular Unit Excision-Linear Ellipse Donor Harvesting Technique: Combining Standard Follicular Unit Excision with Follicular Unit Excision inside a Linear Strip (Modified Linear Strip Excision) to Optimize Graft Yield.

Follicular unit excision (FUE) graft dissection has become the dominant method of donor harvesting globally, however, only a percentage of donor hair can be excised inside the safe donor area before visible donor thinning occurs. Compared to linear strip excision (LSE) where all follicular units inside the harvested ellipse of hair are used, FUE poses substantial limitations for lifetime graft yield and, therefore, cosmetic coverage in patients with advanced pattern hair loss. This paper reviews how combining the donor harvesting methods of FUE and LSE has been shown to optimize graft yield while minimizing the risk of donor depletion from overharvesting. It then describes a surgical technique called FUE-Linear Ellipse (FUE-LE) where FUE dissection of grafts inside a demarcated linear ellipse eliminates the need for a large dissection team which has posed a barrier for many new practices that offer both the donor harvesting methods. For practices that currently offer only FUE, the addition of the LSE method by the modified FUE-LE technique is possible without specialized staff training or associated equipment costs. In this paper, surgery practices that have adopted this technique will report on their experiences. Hair restoration surgeons are encouraged to provide both methods of donor harvesting (FUE and LSE using FUE-LE) in order to optimize graft yield for patients and avoid long-term donor depletion. Based on limited experience, it appears the technique of FUE-LE will help achieve this goal.

2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

Detailed safety profile of acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia in the ELEVATE-RR trial.

ELEVATE-RR demonstrated noninferior progression-free survival and lower incidence of key adverse events (AEs) with acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia. We further characterize AEs of acalabrutinib and ibrutinib via post hoc analysis. Overall and exposure-adjusted incidence rate was assessed for common Bruton tyrosine kinase inhibitor-associated AEs and for selected events of clinical interest (ECIs). AE burden scores based on previously published methodology were calculated for AEs overall and selected ECIs. Safety analyses included 529 patients (acalabrutinib, n = 266; ibrutinib, n = 263). Among common AEs, incidences of any-grade diarrhea, arthralgia, urinary tract infection, back pain, muscle spasms, and dyspepsia were higher with ibrutinib, with 1.5- to 4.1-fold higher exposure-adjusted incidence rates. Incidences of headache and cough were higher with acalabrutinib, with 1.6- and 1.2-fold higher exposure-adjusted incidence rate, respectively. Among ECIs, incidences of any-grade atrial fibrillation/flutter, hypertension, and bleeding were higher with ibrutinib, as were exposure-adjusted incidence rates (2.0-, 2.8-, and 1.6-fold, respectively); incidences of cardiac events overall (the Medical Dictionary for Regulatory Activities system organ class) and infections were similar between arms. Rate of discontinuation because of AEs was lower for acalabrutinib (hazard ratio, 0.62; 95% confidence interval, 0.41-0.93). AE burden score was higher for ibrutinib vs acalabrutinib overall and for the ECIs atrial fibrillation/flutter, hypertension, and bleeding. A limitation of this analysis is its open-label study design, which may influence the reporting of more subjective AEs. Overall, event-based analyses and AE burden scores demonstrated higher AE burden overall and specifically for atrial fibrillation, hypertension, and hemorrhage with ibrutinib vs acalabrutinib. This trial was registered at www.clinicaltrials.gov as #NCT02477696.

Doxorubicin Interaction with Lipid Monolayers Leads to Decreased Membrane Stiffness when Experiencing Compression-Expansion Dynamics.

Physical membrane models permit to study and quantify the interactions of many external molecules with monitored and simplified systems. In this work, we have constructed artificial Langmuir single-lipid monolayers with dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylethanolamine (DPPE), dipalmitoylphosphatidylserine (DPPS), or sphingomyelin to resemble the main lipid components of the mammalian cell membranes. We determined the collapse pressure, minimum area per molecule, and maximum compression modulus (Cs-1) from surface pressure measurements in a Langmuir trough. Also, from compression/expansion isotherms, we estimated the viscoelastic properties of the monolayers. With this model, we explored the membrane molecular mechanism of toxicity of the well-known anticancer drug doxorubicin, with particular emphasis in cardiotoxicity. The results showed that doxorubicin intercalates mainly between DPPS and sphingomyelin, and less between DPPE, inducing a change in the Cs-1 of up to 34% for DPPS. The isotherm experiments suggested that doxorubicin had little effect on DPPC, partially solubilized DPPS lipids toward the bulk of the subphase, and caused a slight or large expansion in the DPPE and sphingomyelin monolayers, respectively. Furthermore, the dynamic viscoelasticity of the DPPE and DPPS membranes was greatly reduced (by 43 and 23%, respectively), while the reduction amounted only to 12% for sphingomyelin and DPPC models. In conclusion, doxorubicin intercalates into the DPPS, DPPE, and sphingomyelin, but not into the DPPC, membrane lipids, inducing a structural distortion that leads to decreased membrane stiffness and reduced compressibility modulus. These alterations may constitute a novel, early step in explaining the doxorubicin mechanism of action in mammalian cancer cells or its toxicity in non-cancer cells, with relevance to explain its cardiotoxicity.

Quality-adjusted survival time without symptoms or toxicity of acalabrutinib with or without obinutuzumab in patients with treatment-naive chronic lymphocytic leukemia.

Acalabrutinib monotherapy (A) and acalabrutinib plus obinutuzumab (A + O) demonstrated improved efficacy and safety versus chlorambucil plus obinutuzumab (C + O) among treatment-naive patients with chronic lymphocytic leukaemia (CLL) in the ELEVATE-TN trial. The relative risk-benefit at a median follow-up of 47 months was assessed using Quality-adjusted Time Without Symptoms and Toxicity (Q-TWiST) methodology. Patient data were partitioned into 3 states: time with toxicity (TOX); time without symptoms or toxicity (TWiST); and time after relapse (REL). Mean Q-TWiST was estimated by summing the mean time in each state, multiplied by its respective utility weight. Patients receiving A or A + O experienced significantly longer Q-TWiST versus C + O when toxicity was defined as grade 3-4 adverse events (AEs) (41.79 vs 34.56 months; 42.07 vs 34.56 months) and grade 2-4 AEs (35.07 vs 30.64 months; 34.21 vs 30.64 months). Overall, patients with treatment-naive CLL treated with A or A + O experienced significant gains in Q-TWiST compared with C + O.

"Anti-obesity medications" or "medications to treat obesity" instead of "weight loss drugs" - why language matters - an official statement of the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) and the Brazilian Society of Endocrinology and Metabolism (SBEM)

ABSTRACT Obesity is largely undertreated, in part because of the stigma surrounding the disease and its treatment. The use of the term "weight loss drugs" to refer to medications for the treatment of obesity may contribute to this stigma, leading to the idea that anyone who wants to lose weight could use them and that short-term use, only in the active weight loss phase would be enough. On the contrary, the use of terms such as "medications to treat obesity" or "anti-obesity medications" conveys the idea that the treatment is directed at the disease rather than the symptom. This joint statement by the Brazilian Association for the Study of Obesity and Metabolic Syndrome (ABESO) and the Brazilian Society of Endocrinology and Metabolism (SBEM) intends to alert the press, healthcare professionals and scientific community about the importance of the appropriate use of language, with the aim of improving obesity care.

Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso)

ABSTRACT Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up, 14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusions: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

The gut microbial metabolite formate exacerbates colorectal cancer progression.

The gut microbiome is a key player in the immunomodulatory and protumorigenic microenvironment during colorectal cancer (CRC), as different gut-derived bacteria can induce tumour growth. However, the crosstalk between the gut microbiome and the host in relation to tumour cell metabolism remains largely unexplored. Here we show that formate, a metabolite produced by the CRC-associated bacterium Fusobacterium nucleatum, promotes CRC development. We describe molecular signatures linking CRC phenotypes with Fusobacterium abundance. Cocultures of F. nucleatum with patient-derived CRC cells display protumorigenic effects, along with a metabolic shift towards increased formate secretion and cancer glutamine metabolism. We further show that microbiome-derived formate drives CRC tumour invasion by triggering AhR signalling, while increasing cancer stemness. Finally, F. nucleatum or formate treatment in mice leads to increased tumour incidence or size, and Th17 cell expansion, which can favour proinflammatory profiles. Moving beyond observational studies, we identify formate as a gut-derived oncometabolite that is relevant for CRC progression.

Primary results of STRONG: An open-label, multicenter, phase 3b study of fixed-dose durvalumab monotherapy in previously treated patients with urinary tract carcinoma.

BACKGROUND: Prior durvalumab (anti-PD-L1 agent) studies in platinum-refractory metastatic urothelial carcinoma evaluated a dose of 10 mg/kg administered every two weeks. The nonrandomised phase 3b STRONG study (NCT03084471) evaluated the safety and efficacy of fixed-dose durvalumab at a more convenient dosing schedule in a previously treated patient population, more similar to a real-world clinical setting. PATIENTS AND METHODS: 867 patients with urothelial or nonurothelial urinary tract carcinoma (UTC) who progressed on or after platinum or nonplatinum chemotherapy were treated with durvalumab 1500 mg every four weeks; 87% had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, and 13% had an ECOG PS of 2. The primary end-point was the incidence of adverse events of special interest (AESIs), including immune-mediated AEs (imAEs). Secondary and exploratory end-points included overall survival (OS), objective response rate (ORR) and disease control rate (at six and 12 months) (DCR). RESULTS: AESIs of any grade were reported in 51% of patients (8% grade ≥ 3). The incidence of imAEs was 11% (2% grade ≥ 3). The median OS was 7.0 months (95% confidence interval [CI]: 6.4-8.2) and ORR was 18% (95% CI: 14.8-20.6), with complete responses in 5% of patients and a DCR at six months of 19% (95% CI: 16.1-22.1). CONCLUSION: Fixed-dose durvalumab monotherapy every four weeks has an acceptable safety profile and yields durable clinical activity in previously chemotherapy-treated patients with UTC. Safety and efficacy are consistent with previous durvalumab studies and other anti-PD-1/PD-L1 agents in this setting. CLINICALTRIALS. GOV IDENTIFIER: NCT03084471https://clinicaltrials.gov/ct2/show/NCT03084471.

Fibrohistiocitoma maligno de face: uma apresentação rara / Malignant fibrohistiocytoma of face: a rare presentation

Contexto: O fibrohistiocitoma maligno é um sarcoma de tecidos moles muito agressivo, com rara apresentação limitada à pele e tecido subcutâneo em face. O diagnóstico é anatomopatológico com auxílio da imuno-histoquímica. Descrição do caso: Este artigo relata o caso de um paciente com diagnóstico de fibrohistiocitoma maligno restrito à face com boa resposta terapêutica após exérese cirúrgica. Discussão: Tendo em vista a raridade dessa afecção, dificuldade diagnóstica devido ao quadro inespecífico e com rápida evolução, é importante lembrar desse possível diagnóstico e atuar precocemente. Conclusões: O diagnóstico precoce interfere de forma significativa na evolução do quadro, sendo necessária a manutenção do acompanhamento oncológico e dermatológico com o intuito de detectar precocemente recidivas locais e metástases a distância.

Processos grupais com adolescentes em situação de vulnerabilidade social / Group processes with social vulnerability teenagers / Procesos grupales con adolescentes en situación de vulnerabilidad social

O presente relato de experiência visa problematizar a prática com grupos de adolescentes em situação de vulnerabilidade social. Realizou-se cinco grupos entre agosto e dezembro de 2019. Os grupos eram fechados e com duração de 1 hora e 40 minutos cada. Como método e forma de manejo grupal utilizou-se a estratégia de coordenação cartográfica. Os resultados e discussão apontam rizomaticamente para diferentes direções: a alta disponibilidade dos adolescentes em participar dos grupos; a importância do delineamento e da sensibilização ao setting grupal; o modo como os vetores macropolíticos e institucionais incidem nos processos grupais; os efeitos da sub-apropriação da língua formal na dinâmica dos grupos e na circulação social; a importância de dar lugar ao que não tem lugar; e, o mapeamento de expressões com camadas de sentido. Por fim, aponta-se o grupo como dispositivo potente para a instauração de novas formas de vida.(AU)

The present experience report aims to problematize the practice with groups of adolescents in situations of social vulnerability. Five groups were held between August and December 2019. The groups were closed and lasting 1 hour and 40 minutes each. As a method and as a form of group management was used the strategy of cartographic coordination. The results and discussion indicate rhizomatically to different directions: the high availability of adolescents to participate in groups; the importance of design and sensation by the participants of the group setting; the macro-political and institutional vectors converging on group processes; the effects of the sub-appropriation of formal language in the groups dynamics and social mobilities; the importance of step up a place for what has no place; and, the mapping of expressions with layers of meaning. Finally, the group is pointed out as a powerful device for the creation of new forms of life.(AU)

El presente informe de experiencia tiene como objetivo problematizar la práctica con grupos de adolescentes en situaciones de vulnerabilidad social. Se realizaron cinco grupos entre agosto y diciembre de 2019. Los grupos fueron cerrados y ocurrieron durante 1 hora y 40 minutos cada uno. Como método y forma de seguimiento grupal se utilizó la estrategia de coordinación cartográfica. Los resultados y la discusión apuntan rizomaticamente a diferentes direcciones: la alta disponibilidad de adolescentes para participar de los grupos; la importancia del diseño y de la sensibilización del espacio grupal; los vectores macropolíticos y institucionales en los procesos grupales; los efectos de la sub-apropiación de la lengua formal sobre la dinámica grupal y la circulación social; la importancia de producir lugar para lo que no tiene lugar; y, el mapeo de expresiones con capas de sentido. Finalmente, se señala el grupo como un fuerte dispositivo para la producción de nuevas formas de vida.(AU)

Management of hypopituitarism: a perspective from the Brazilian Society of Endocrinology and Metabolism.

Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.

Management of hypopituitarism: a perspective from the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.

Perfil clínico, histopatológico e tricoscópico da alopecia frontal fibrosante: estudo retrospectivo de casos de um serviço de referência de dermatologia / Clinical, histopathological and trichoscopic of frontal alopecia fibrosing: retrospective study of cases of a service of dermatology reference

Contexto: Alopecia frontal fibrosante (AFF) é uma alopecia cicatricial que acomete a região frontotemporal, e predomina em mulheres pós-menopausadas. Objetivo: Descrever o perfil clínico, histopatológico e tricoscópico de pacientes com diagnóstico de AFF. Desenho e local: Estudo de coorte retrospectivo observacional que foi desenvolvido no ambulatório de tricologia do departamento de dermatologia do Hospital Santa Casa de Misericórdia de Vitória, Vitória (ES), Brasil. Métodos: O estudo foi realizado por meio da análise de prontuários e de revisão histopatológica de pacientes com diagnóstico de AFF atendidos entre 1 de março de 2019 a 29 de fevereiro de 2020. Resultados: No período, 17 pacientes do sexo feminino foram diagnosticadas com AFF, 76,5% delas na pós-menopausa. Todas apresentavam alopecia frontotemporal e madarose. À tricoscopia, ausência de pelos velus, aberturas foliculares reduzidas, hiperceratose folicular e eritema perifolicular foram encontrados na maioria dos casos. Todas as biópsias mostraram aspectos microscópicos compatíveis com AFF. O tratamento mais utilizado foi tacrolimo 0,1%. Discussão: A patogênese da AFF ainda não é compreendida. A associação com doenças autoimunes sugere a influência da imunidade no quadro. A tricoscopia é uma ferramenta de fácil acesso e não invasiva que pode auxiliar no diagnóstico. Histopatologicamente a AFF é indistinguível do líquen plano pilar. O tratamento objetiva reduzir a inflamação e retardar a progressão da doença. Conclusões: Embora apresentações clínicas e tricoscópicas tenham sido descritas ao longo dos anos, a patogênese, a histologia e os tratamentos eficazes para AFF ainda são debatidos. O reconhecimento e o tratamento precoce da doença permitiriam a redução da progressão da doença.

Psicologia nos cras: uma análise do dissenso e dos processos de coletivização / Psicología en los cras: un análisis de los procesos de disensión y colectivización / Psychology in brazil's social assistence reference centers (cras): an analisis of dissense and collectivization processes

Resumo O presente trabalho busca analisar os modos como se organizam os Centros de Referência em Assistência Social (CRAS), a partir de experiências coletivas e práticas comunitárias realizadas pelas equipes-território, destacando os processos de dissensos e consensos nas relações de trabalho. Metodologicamente, com base na análise de discurso, foram realizadas coletivamente 14 entrevistas semiestruturadas com cada equipe dos CRAS de dois estados da macrorregião sul do Brasil. Os resultados apontam que trabalhar as divergências internas sem tentar homogeneizá-las, compondo práticas transdisciplinares e horizontalizantes, se mostrou um modo potente de organização das equipes de trabalho. Ademais, foi relatado também a potência na produção dos fazeres de territorialização, com e a partir do território, por meio de seus significantes e possibilidades singulares. Finalmente, apontam-se as práticas comunitárias com grupos e coletivos nos CRAS como um dos vetores potentes no enfrentamento ao sofrimento ético-político produzido pelas desigualdades sociais.

Resumen El presente trabajo busca analizar las formas en que se organizan los Centros de Referencia de Asistencia Social (CRAS), a partir de experiencias colectivas y prácticas comunitarias realizadas por los equipos del territorio, destacando los procesos de desacuerdos y consensos en las relaciones laborales. Metodológicamente, con base en el análisis del discurso, se realizaron colectivamente 14 entrevistas semiestructuradas con cada equipo de los CRAS de dos estados del macrorregión sur del Brasil. Los resultados muestran que trabajar las diferencias internas sin tratar de homogeneizarlas, componiendo prácticas transdisciplinarias y horizontales, resultó ser una forma poderosa de organizar equipos de trabajo. Además, también se informó del poder en la producción de actividades de territorialización, con y desde el territorio, a través de sus significantes y posibilidades singulares. Finalmente, las prácticas comunitarias con grupos y colectivos en los CRAS se señalan como uno de los vectores poderosos para enfrentar el sufrimiento ético-político que producen las desigualdades sociales.

Abstract This paper analyzes the ways through which the Social Assistance Reference Centers (CRAS) is organized, based on collective experiences and community practices carried out by the territory-teams, highlighting the processes of dissent and consensus in working relations. Methodologically, based on discourse analysis, 14 semi-structured interviews were conducted collectively with each CRAS team from two states of the Brazilian southern region. The results indicate that working internal differences without trying to homogenize them, composing transdisciplinary and horizontal practices, proved to be a powerful way of organizing the work teams. Besides, the power in the production of territorialization actions, with and from the territory, was also reported through its significant and singular possibilities. Finally, the community practices with groups and collectives in CRAS are pointed as one of the potent vectors in facing the ethical-political suffering produced by social inequalities.

Percepção de pessoas com hipertensão arterial sobre aspectos que influenciam a adesão ao tratamento' / Percepción de las personas con hipertensión arterial sobre aspectos que influyen en la adherencia al tratamento / Perception of people with arterial hypertension about aspects that influence treatment adherence

Objetivo: descrever a percepção de pessoas com hipertensão arterial sobre aspectos que facilitam e dificultam a adesão ao tratamento. Método: estudo qualitativo descritivo desenvolvido com 16 pessoas atendidas em consultas de enfermagem. Realizaram-se entrevistas com roteiro semiestruturado e utilizou-se a técnica de análise de conteúdo. Os dados foram coletados entre os meses de janeiro e agosto de 2017. Resultados: observou-se que ter força de vontade, apoio familiar e multiprofissional, conhecimento sobre a patologia e formas de prevenção e medo da morte facilitou a adesão; por outro lado, pouco conhecimento, preguiça, falta de infraestrutura urbana e condições climáticas, hábito de consumir alimentos não saudáveis, bebidas alcoólicas e tabaco, custo do tratamento e esquecimento de tomar a medicação dificultaram a adesão. Conclusão: o tratamento da hipertensão acarreta mudanças na dinâmica da vida para as quais é fundamental ter força de vontade, apoio familiar e profissional, além de superar hábitos não saudáveis.

Objective: to describe the perception of people with arterial hypertension of the aspects that facilitate and hinder treatment adherence. Method: descriptive qualitative study developed with 16 people met in Nursing consultations. Interviews were conducted with a semi-structured guide and the content analysis technique was used. Data were collected between January and August 2017. Results: having willpower, family and multidisciplinary support, knowledge about the pathology and forms of prevention and fear of death facilitated adherence; on the other hand, little knowledge, laziness, lack of urban infrastructure and climatic conditions, habit of consuming unhealthy foods, alcoholic beverages and tobacco, cost of treatment and forgetfulness of taking the medication hindered adherence. Conclusion: the treatment of hypertension causes changes in the dynamics of life, being essential to have willpower, family and professional support, in addition to overcoming unhealthy habits.

Objetivo: describir la percepción de las personas con hipertensión arterial sobre los aspectos que facilitan y dificultan la adherencia al tratamiento. Método: estudio cualitativo descriptivo desarrollado con 16 personas atendidas en consultas de enfermería. Se realizaron entrevistas con un guion semiestructurado y se utilizó la técnica de análisis de contenido. Los datos se recopilaron entre enero y agosto de 2017. Resultados: se observó que tener fuerza de voluntad, apoyo familiar y multidisciplinario, conocimiento sobre la patología y las formas de prevención y miedo a la muerte facilitaba la adherencia; por otro lado, poco conocimiento, pereza, falta de infraestructura urbana y condiciones climáticas, hábito de consumir alimentos no saludables, bebidas alcohólicas y tabaco, costo de tratamiento y olvido de tomar el medicamento obstaculizaba la adherencia. Conclusión: el tratamiento de la hipertensión provoca cambios en la dinámica de la vida para los que es esencial contar con fuerza de voluntad, apoyo familiar y profesional, además de superar hábitos poco saludables.

Correlation between human papillomavirus infection and histopathological diagnosis of women in Northeast Brazil.

Cervical carcinoma is the fourth leading cause of death among women worldwide. Epidemiological studies claim that human papillomavirus (HPV) infection is a necessary condition for cervical cancer development. Knowledge of the geographic distribution of HPV is important in guiding the introduction of prophylactic vaccines. This study analyzed the prevalence of HPV infection in cervical samples obtained from women with abnormal cervical histopathological diagnosis in Northeast Brazil. The study included an analysis of 211 women whose diagnosis was confirmed for cervical intraepithelial neoplasia type 1 (CIN-1), cervical intraepithelial neoplasia type 2 (CIN-2), cervical intraepithelial neoplasia type 3 (CIN-3), and cancer. The identification of the HPV genotypes was based on the polymerase chain reaction-restriction fragment length polymorphism technique. A total of 42.7% of the samples showed a single HPV infection, while 57.3% showed multiple infections. The most common genotypes detected were HPV-16, HPV-18, and HPV-31. HPV-16, HPV-31, HPV-35, and HPV-18 were the most common types in CIN-1 with a single infection. HPV-16 and HPV-18 were the most often found in CIN-2 with a single infection. HPV-16, HPV-18, and HPV-31 were the most detected in CIN-3 with a single infection. HPV-16 and HPV-31 were the most frequent in cancer with a single infection. Multiple infection with HPV-16 shows a 2.7 times greater risk of CIN-3 (P = .04). Multiple infections for HPV with HPV-16 and excluding the HPV18/31 types, were associated with CIN-3 (P = .01). The results allowed the detection and genotyping of HPV types circulating in the population studied. These findings must be taken into account when devising vaccination strategies against HPV.

Clinical evidence for the first-line treatment of advanced urothelial carcinoma: Current paradigms and emerging treatment options.

BACKGROUND: Patients with advanced urothelial carcinoma (UC) have poor outcomes, with 5-year survival rates of <5% for those with metastatic, stage IV disease. We have reviewed current treatment paradigms and emerging treatment options for these patients. METHODS: The websites of seven national or international organizations were searched for metastatic UC treatment guidelines. Systematic literature reviews were conducted to identify evidence from randomized controlled trials (RCTs) of chemotherapy for patients with previously untreated, unresectable, stage IV UC. Searches included congress databases and articles published between 1990 and 2018. In order to align with the latest treatment paradigms in first-line advanced UC, a focused literature search was conducted to identify evidence supporting immuno-oncology (IO) agents. RESULTS: For advanced UC, guidelines universally recommend cisplatin-based chemotherapy as first-line treatment for eligible patients and carboplatin-based regimens for those unfit to receive cisplatin. Despite the evaluation of a number of different cytotoxic regimens over the years, including triplet combinations, survival outcomes have not improved markedly with chemotherapy. Median overall survival with standard of care chemotherapy is ~13 months. Based on the results of single-arm, phase II studies, recent treatment guidelines have included atezolizumab (anti-PD-L1) and pembrolizumab (anti-PD-1) as first-line options for cisplatin-ineligible patients whose tumors express high levels of PD-L1. However, emerging evidence from RCTs of IO agents, including both cisplatin-eligible and cisplatin-ineligible patients, suggest that survival times exceeding 20 months are possible. CONCLUSIONS: After having reached a plateau with chemotherapy, the treatment landscape for advanced UC is evolving. Survival outcomes for patients with advanced UC are improving with treatment modalities involving IO agents.