Neoadjuvant chemotherapy with dose-dense MVAC in muscle-invasive bladder cancer: a tertiary center experience.

PURPOSE: Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate. MATERIALS AND METHODS: In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported. RESULTS: Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65 years. All of them had ECOG 0-1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1-2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5 months, 33.3% of patients experienced disease recurrence. CONCLUSIONS: Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status.

ß-Glucosidase activity and antimicrobial properties of potentially probiotic autochthonous lactic cultures.

Background: The demand for lactic acid bacteria products, especially probiotics, has increased. Bacteria that increase polyphenol bioavailability and act as bio preservatives are sought after. This study aims to identify autochthonous lactic acid cultures from EMBRAPA that demonstrate ß-glucosidase activity and inhibitory effect on microbial sanitary indicators. Methods: Cell-free extracts were obtained by sonicating every 5 s for 40 min. The extracts were mixed with cellobiose and incubated at 50 °C. The reaction was stopped by immersing the tubes in boiling water. The GOD-POD reagent was added for spectrophotometer readings. Antimicrobial activity was tested against reference strains using the agar well diffusion method. Lactic cultures in MRS broth were added to 0.9 cm wells and incubated. The diameter of the inhibition zones was measured to determine the extension of inhibition. Results: Only L. rhamnosus EM1107 displayed extracellular ß-glucosidase activity, while all autochthonous strains except L. plantarum CNPC020 demonstrated intracellular activity for this enzyme. L. plantarum CNPC003 had the highest values. On the other hand, L. plantarum CNPC020, similarly to L. mucosae CNPC007, exhibited notable inhibition against sanitary indicators. These two strains significantly differed from the other five autochthonous cultures regarding S. enterica serovar Typhimurium ATCC 14028 inhibition (P < 0.05). However, they did not differ from at least one positive control in terms of inhibition against S. aureus ATCC 25923 and E. coli ATCC 25922 (P > 0.05). Therefore, it is advisable to consider these cultures separately for different technological purposes, such as phenolics metabolism or bio preservative activity. This will facilitate appropriate selection based on each specific property required for the intended product development.

Thymic alterations resulting from experimental visceral leishmaniasis in a Syrian hamster (Mesocricetus auratus).

BACKGROUND: The thymus is a lymphoid organ responsible for the development and maturation of T cells, which are part of the Th1, Th2, Th17, and Treg immune responses triggered by visceral leishmaniasis. The maturation and immunological development of T lymphocytes require a bidirectional interaction between the thymic microenvironment of epithelial cells, dendritic cells, and macrophages and the extracellular matrix with differentiating lymphocytes. OBJECTIVES: We evaluated the morphological characteristics and tissue distribution of hematopoietic and stromal cells in the thymuses of hamsters experimentally infected with Leishmania infantum, aiming to gain an insight into the pathophysiology of the disease. METHODS: Fifteen hamsters were subjected to intraperitoneal experimental infection with 107L. infantum promastigotes (MHOM/BR/1972/BH46). The animals were divided into three groups, each comprising five infected hamsters, and were then euthanized 15, 60, and 120 days postinfection. The control groups consisted of three groups of five healthy hamsters euthanized simultaneously with the infected ones. Thymic morphology was evaluated through histopathology and the cell composition through immunohistochemistry. We used antibodies to mark mesenchymal cells (anti-vimentin), epithelial cells (anti-cytokeratin), macrophages (anti-MAC387), B lymphocytes (anti-CD79a), and T lymphocytes (anti-CD3). Immunohistochemistry was also used to mark the parasite in the thymus. RESULTS: Infected and control hamsters showed no difference in thymic morphology and degree of atrophy. After 15 days of infection, CD3 + T lymphocytes in the thymus showed an increase that stabilized over time. At 120 days of infection, we detected a significant decrease in CD79a+ B lymphocytes. The parasite was present in the medullary and corticomedullary regions of 9 out of 15 hamsters. These findings confirm that the presence of a parasite can cause changes in a thymus cell population. However, further studies are needed to evaluate these changes' effects on the immune response of infected animals.

Biallelic deletion of 1p32 defines ultra-high-risk myeloma, but monoallelic del(1p32) remains a strong prognostic factor.

Cytogenetic abnormalities (CAs) are known to be the preponderant prognostic factor in multiple myeloma. Our team has recently developed a prognostic score based on 6 CAs, with which del(1p32) appears to be the second worst abnormality after del(17p). This study aimed to confirm the adverse effect of 1p32 deletion in patients with newly diagnosed multiple myeloma (NDMM). Among 2551 patients with newly diagnosed multiple myeloma, 11% were harboring del(1p32). Their overall survival (OS) was significantly inferior compared with patients without del(1p32) (median OS: 49 months vs 124 months). Likewise, progression-free survival was significantly shorter. More importantly, biallelic del(1p32) conferred a dramatically poorer prognosis than a monoallelic del(1p32) (median OS: 25 months vs 60 months). As expected, the OS of patients with del(1p32) significantly decreased when this abnormality was associated with other high-risk CAs [del(17p), t(4;14), or gain(1q)]. In the multivariate analysis, del(1p32) appeared as a negative prognostic factor; after adjustment for age and treatment, the risk of progression was 1.3 times higher among patients harboring del(1p32), and the risk of death was 1.9 times higher. At the dawn of risk-adapted treatment strategies, we have confirmed the adverse effect of del(1p32) in multiple myeloma and the relevance of its assessment at diagnosis.

Severe form of lymphocutaneous sporotrichosis: a case report

ABSTRACT Sporotrichosis is the most frequent subcutaneous mycosis in Latin America. It is caused by species of the genus Sporothrix. Infection in humans occurs through the entry of the fungus into the skin. Zoonotic outbreaks involving cats in the transmission of the disease have been frequently reported. The lymphocutaneous form is the most commonly observed and the upper limbs are the most affected sites. We report a case of a 64-year-old healthy female patient with a lymphocutaneous form with rapid progression of lesions, which was refractory to initial treatment with itraconazole. Treatment with liposomal amphotericin B was performed with a satisfactory resolution, but aesthetic and functional sequelae in the left upper limb were installed.

Cyclodextrin-based delivery systems in parenteral formulations: A critical update review.

Parenteral formulations are indispensable in clinical practice and often are the only option to administer drugs that cannot be administrated through other routes, such as proteins and certain anticancer drugs - which are indispensable to treat some of the most prevailing chronic diseases worldwide (like diabetes and cancer). Additionally, parenteral formulations play a relevant role in emergency care since they are the only ones that provide an immediate action of the drug after its administration. However, the development of parenteral formulations is a complex task owing to the specific quality and safety requirements set for these preparations and the intrinsic properties of the drugs. Amongst all the strategies that can be useful in the development of parenteral formulations, the formation of water-soluble host-guest inclusion complexes with cyclodextrins (CDs) has proven to be one of the most advantageous. CDs are multifunctional pharmaceutical excipients able to form water-soluble host-guest inclusion complexes with a wide variety of molecules, particularly drugs, and thus improve their apparent water-solubility, chemical stability, and bioavailability, to make them suitable for parenteral administration. Besides, CDs can be employed as building blocks of more complex injectable drug delivery systems with enhanced characteristics, such as nanoparticles and supramolecular hydrogels, that has been found particularly beneficial for the delivery of anticancer drugs. However, only a few CDs are considered safe when parenterally administered, and some of these types are already approved to be used in parenteral dosage forms. Therefore, the application of CDs in the development of parenteral formulations has been a more common practice in the last few years, due to their significant worldwide acceptance by the health authorities, promoting the development of safer and more efficient injectable drug delivery systems.

Primary plasma cell leukemias displaying t(11;14) have specific genomic, transcriptional, and clinical features.

Primary plasma cell leukemia (pPCL) is an aggressive form of multiple myeloma (MM) that has not benefited from recent therapeutic advances in the field. Because it is very rare and heterogeneous, it remains poorly understood at the molecular level. To address this issue, we performed DNA and RNA sequencing of sorted plasma cells from a large cohort of 90 newly diagnosed pPCL and compared with MM. We observed that pPCL presents a specific genomic landscape with a high prevalence of t(11;14) (about half) and high-risk genomic features such as del(17p), gain 1q, and del(1p32). In addition, pPCL displays a specific transcriptome when compared with MM. We then wanted to characterize specifically pPCL with t(11;14). We observed that this subentity displayed significantly fewer adverse cytogenetic abnormalities. This translated into better overall survival when compared with pPCL without t(11;14) (39.2 months vs 17.9 months, P = .002). Finally, pPCL with t(11;14) displayed a specific transcriptome, including differential expression of BCL2 family members. This study is the largest series of patients with pPCL reported so far.

The association of breastfeeding and other factors on respiratory virus positivity and severity in hospitalized children.

Acute respiratory infections (ARIs) are the most prevalent diseases in children under 5 years old, and viruses are the leading cause. ARIs arise due to numerous factors, including age, contact with siblings or other children in daycare centers, and environmental pollution. Breastfeeding reportedly confers protection against ARIs through bioactive components related to mucous epithelial immunity. This study aimed to evaluate the frequency and severity of viral ARIs in hospitalized children, together with the status and duration of exclusive breastfeeding (EBF) and other associated factors. It comprised an epidemiological surveillance study to investigate respiratory viruses in hospitalized children, in which demographic and clinical data were collected. Overall, 279 patients were included, 190 (68%) had positive viral results, and 132 (47%) were exclusively breastfed. In an adjusted analysis, it was observed that older children, the parents' educational level, and the presence of chronic disease were significantly related to EBF for more than 6 months. No significant differences were observed in viral positivity and disease severity concerning EBF. Whereas the EBF status was associated with a positive rate of virus detection, the significance did not remain after adjustment, and it was not considered a protective factor against ARIs. On the other hand, young age and exposure to tobacco were confirmed as risk factors of frequency and severity, respectively. Such confounding factors can impact the analysis and should be considered in future studies.

Toll-like receptor 4 selective inhibition in medullar microenvironment alters multiple myeloma cell growth.

Bone marrow (BM) mesenchymal stromal cells (MSCs) are abnormal in multiple myeloma (MM) and play a critical role by promoting growth, survival, and drug resistance of MM cells. We observed higher Toll-like receptor 4 (TLR4) gene expression in MM MSCs than in MSCs from healthy donors. At the clinical level, we highlighted that TLR4 expression in MM MSCs evolves in parallel with the disease stage. Thus, we reasoned that the TLR4 axis is pivotal in MM by increasing the protumor activity of MSCs. Challenging primary MSCs with TLR4 agonists increased the expression of CD54 and interleukin-6 (IL-6), 2 factors directly implicated in MM MSC-MM cell crosstalk. Then, we evaluated the therapeutic efficacy of a TLR4 antagonist combined or not with conventional treatment in vitro with MSC-MM cell coculture and in vivo with the Vk*MYC mouse model. Selective inhibition of TLR4 specifically reduced the MM MSC ability to support the growth of MM cells in an IL-6-dependent manner and delayed the development of MM in the Vk*MYC mouse model by altering the early disease phase in vivo. For the first time, we demonstrate that specific targeting of the pathological BM microenvironment via TLR4 signaling could be an innovative approach to alter MM pathology development.

As Escalas de Bem-Estar Infantil (EBI): Características Psicométricas da Versão Portuguesa / Child Well-Being Scales (CWBS): Psychometric Properties of the Portuguese Version

Resumo Em Portugal, existe escassez de instrumentos aferidos para avaliar os programas de proteção da infância. Este estudo analisou as características psicométricas das Escalas de Bem-Estar Infantil (EBI), destinadas à avaliação multidimensional de potenciais situações de maltrato e negligência, em 276 famílias em risco psicossocial. Foram também recolhidas medidas de eficácia, satisfação e sintomatologia parental. A análise fatorial exploratória sugere uma estrutura com três fatores, similar à versão original, com boa consistência interna (α entre 0,82 e 0,86) e bons indicadores de ajustamento (GFI = 0,97, RMSR = 0,06). Relativamente à validade de construto, foram encontradas correlações significativas que correspondiam à expectativa teórica. Os resultados sustentam a aplicabilidade das EBI para a avaliação e tomada de decisão nas medidas de proteção da criança.

Abstract There is a lack of validated instruments to evaluate child protection programs in Portugal. The present study analyzed the psychometric characteristics of the Child Well-Being Scales (CWBS), a multidimensional measure of potential situations of abuse and neglect, in 276 families at psychosocial risk. Measures of parental efficiency, satisfaction and parental symptomatology were also collected. Through exploratory factor analysis, a 3-factor solution, similar to the original version was identified, with high levels of internal consistency (α between 0.82-0.86) and good model fit (GFI = 0.97, RMSR = 0.06). Regarding construct validity, significant correlations were found that were in line with theoretical expectation. Our results support the utility of EBI as a guide to the assessment and decision-making regarding child protection measures.

HIV, syphilis, hepatitis B and C in key populations: results of a 10-year cross-sectional study, Southern Brazil

ABSTRACT Objective: Although the development of prevention and treatment strategies for sexually transmitted infections in key groups has improved over the years, they still remain a challenge for health systems worldwide. In this context, the objective of this study is to assess the seroprevalence in the tested population, with an emphasis on key populations, aiming at identifying the participants' profile and consequently the development of testing strategies. Methods: The present study analyzed the seroprevalence of HIV, syphilis, and hepatitis B and C, and the epidemiological profiles of key and general populations tested at a reference public health facility for sexually transmitted infections testing and counseling in the city of Curitiba, Southern Brazil. A cross-sectional study was conducted to report data from 2010 to 2019. Results: A total of 67,448 samples were analyzed, 9,086 of these tested positive, 3,633 (56%) for HIV, 4,978 (77%) for syphilis, 340 (5%) for hepatitis C virus (HCV), and 135 (2%) for hepatitis B virus (HBV). Overall, most of the participants were men (79 to 87%), and predominantly white. For HIV and syphilis, the predominant age groups were 21-30 years old (48 and 50%), HBV 21-40 years old (31%), and HCV 41-60 years old (25%). A high seroprevalence of HIV and syphilis was observed in the investigated key populations with a higher frequency in sex workers, men who have sex with men, and transgender. Conclusion: The progressive increase in syphilis cases emphasizes the need for effective interventions to enhance adherence to the use of condoms, and to expand diagnosis and treatment for these key populations.

A família do paciente com transtorno mental grave / The family of the patient with severe mental disorder

A atenção familiar é um componente essencial da Atenção Primária à Saúde (APS). É importante que equipes de APS se apoderem de instrumentos capazes de abordar integralmente as questões familiares envolvidas com o processo saúde-doença. O presente estudo teve como objetivo compreender a dinâmica de uma família que possui dois integrantes com doença mental (esquizofrenia) a partir da análise dos instrumentos Genograma, Ecomapa e Apgar Familiar. Além de evidenciar a importância do uso dessas ferramentas como vantagem para a amplificação da perspectiva sistêmica da doença, há auxílio na percepção da situação psicossocial pelos profissionais e família. A metodologia utilizada amparou-se nos princípios da abordagem familiar sistêmica, através de entrevistas familiares sucessivas com aplicação dos instrumentos mais comumente utilizados pela Medicina de Família e Comunidade, tendo como cenário o domicílio dos pacientes. Após análise das ferramentas, concluiu-se que a abordagem facilitou o autoconhecimento familiar, o entendimento da doença e ampliou/aprofundou o diálogo e relacionamento entre os membros do núcleo familiar. Alcances estes fundamentais à redução do sofrimento do paciente e sua família, e facilitadores da integralidade na atenção ofertada pelos profissionais da equipe de saúde.

Family care is an essential component of Primary Health Care (PHC). It is important that PHC teams seize instruments that can fully address the family issues involved in the health-disease process. The present study aimed to understand the dynamics of a family that has two members with mental illness (schizophrenia) from the analysis of the Genogram, Ecomap and Family Apgar instruments. In addition to highlighting the importance of using these instruments as an advantage for the amplification of the systemic perspective of the disease, there is an assistance in the perception of the psychosocial situation by health professionals and the family. The methodology used was based on the principles of the systemic family approach, through successive family interviews with application of the instruments most commonly used by Family and Community Medicine, based on the patient's home as a scenario. After analyzing the instruments, it was concluded that the approach facilitated family self-knowledge, the understanding of the disease and extended/ deepened the dialogue and relationship between the members of the family nucleus. These are fundamental achievements in order to reduce the suffering of the patients and their family, and facilitators of the integrality of the care offered by the health team professionals.

Carcinoma espinocelular avançado e imunoterápicos: novas perspectivas terapêuticas / Advanced squamous cell carcinoma and immunotherapy: new therapeutic perspectives

O carcinoma espinocelular (CEC) apresenta a segunda maior taxa de incidência entre os cânceres de pele não melanoma. Cerca de 5% desses casos evoluem para lesões localmente avançadas e/ou metastáticas, tornando a abordagem cirúrgica muitas vezes inviável. Com base nisso, foi realizada uma revisão na literatura sobre o uso de imunoterápicos no tratamento do CEC avançado. Observou-se, então, que a imunoterapia é uma potencial estratégia terapêutica devido à promoção da atividade antitumoral por meio da própria resposta imunológica individual, o que contribui para a redução dos efeitos colaterais de cirurgias, quimioterapias e radioterapias.

Squamous cell carcinoma (SCC) has the second highest incidence rate among non-melanoma skin cancers. About 5% of cases progress to locally advanced and/or metastatic lesions, making the surgical approach often unfeasible. Based on this, we performed a literature review on the use of immunotherapy drugs to treat advanced SCC. The results showed that immunotherapy is a potential therapeutic strategy due to the antitumor activity promotion through the individual immune response, reducing the adverse events of surgeries, chemotherapy, and radiotherapy

Cyclodextrin-based delivery systems for in vivo-tested anticancer therapies.

Cyclodextrins (CDs) are naturally occurring macromolecules widely used as excipients on pharmaceutical formulations, evidencing a large spectrum of applications in the pharmaceutical industry. Their unique ability to act as molecular containers by entrapping a wide range of guest molecules in their internal cavity makes them a remarkable excipient to improve drug apparent solubility, stability, and bioavailability, and a valuable tool for the assembly of new drug delivery systems. These features are especially useful when it comes to chemotherapy, as most of the anticancer drugs present both low permeability and reduced water solubility. Therefore, guest-host inclusion complexes offer several potential advantages not only regarding the improvement of pharmaceutical formulations characteristics but also considering the reduction of drug toxic side effects. The combination of CDs with additional technologies and materials constitutes a potential strategy towards the development of advanced and multifunctional CD-based delivery systems. Paclitaxel, curcumin, camptothecin, doxorubicin, and cisplatin are among the most studied molecules with anticancer activities and have been successfully incorporated in such nanosystems. Exciting results using CDs and CD-based delivery systems have been obtained so far, paving the way towards the attainment of intelligent delivery systems to possibly address cancer therapeutics' unmet needs. In this review, a comprehensive exposition concerning in vivo-tested CD and CD-based delivery systems for anticancer therapy is undertaken. Additionally, the authors address the multivalent functionalities of CD-based delivery systems, namely the incorporation of active target ligands, stimuli-responsiveness components, surface functionalization, or further associations with other delivery systems, aiming at improved in vivo anticancer therapies. Graphical abstract.

Perfil Epidemiológico da Febre Maculosa no Brasil / Epidemiological Profile of Spotted Fever in Brazil

Introdução: A Febre Maculosa é uma doença febril aguda, causada pela bactéria Rickettsia rickettsii e transmitida pela picada de carrapatos infectados. Atualmente, ocorre um aumento da incidência e das mortes pela doença em diversas áreas do Brasil, o que pode significar um surto e a necessidade de alerta. Metodologia: Estudo quantitativo, descritivo, transversal, que embasou sua busca nas plataformas de notificações brasileiras (DATASUS e SINAN) e boletins epidemiológicos no período de 2007 a 2019. Resultados: O número de casos e a mortalidade demonstraram valores maiores nos meses correspondentes à fase de ninfa do carrapato vetor, com incidência maior na zona rural, na região sudeste e durante o lazer. Além disso, a faixa etária mais atingida foi de 40 a 59 anos, com predominância da população masculina. Os valores maiores apresentados nas zonas rurais, assim como grupo etário e sexo se devem às atividades realizadas que expõem mais os indivíduos ao ambiente natural dos vetores, à sazonalidade dos carrapatos e à presença da Mata Atlântica. Nota-se a presença de grande subnotificação no Brasil. Conclusão: Constata-se a necessidade de desenvolver de políticas de prevenção e disseminar informações sobre o ciclo da doença, manifestações clínicas, prevenção e tratamento.

Introduction: Spotted Fever is an acute febrile disease, caused by the bacteria Rickettsia rickettsii and transmitted by the bite of infected ticks. Currently, there is an increase in the incidence and deaths from the disease in several areas of Brazil, which may mean an outbreak and the need for alert. Methodology: Quantitative, descriptive, cross-sectional study that based its search on the Brazilian notification platforms (DATASUS and SINAN) and newsletters. Results: The number of cases and mortality showed higher values in months corresponding to the vector tick nymph phase (from June to September), with a higher incidence in countryside, in southeast region and at moments of leisure practice. In addition, the most affected age group was 40 to 59 years old, in male population. Higher values presented in countryside, as well as age group and sex are due to activities that expose individuals more to natural environment of vectors, the seasonality of the ticks and the presence of the Atlantic Forest. In addition, there is a large underreporting in Brazil. Conclusion: It´s necessary to develop prevention policies, as well as disseminate information about disease cycle, clinical manifestations, prevention and treatment.

Imprinting of Mesenchymal Stromal Cell Transcriptome Persists even after Treatment in Patients with Multiple Myeloma.

INTRODUCTION: Multiple myeloma (MM) is a B-cell neoplasm characterized by clonal expansion of malignant plasma cells (MM cells) in the bone-marrow (BM) compartment. BM mesenchymal stromal cells (MSC) from newly diagnosed MM patients were shown to be involved in MM pathogenesis and chemoresistance. The patients displayed a distinct transcriptome and were functionally different from healthy donors' (HD) MSC. Our aim was to determine whether MM-MSC also contributed to relapse. METHODS: We obtained and characterized patients' MSC samples at diagnosis, two years after intensive treatment, without relapse and at relapse. RESULTS: Transcriptomic analysis revealed differences in gene expression between HD and MM-MSC, whatever the stage of the disease. An easier differentiation towards adipogenesis at the expense of osteoblatogeneis was observed, even in patients displaying a complete response to treatment. Although their transcriptome was similar, we found that MSC from relapsed patients had an increased immunosuppressive ability, compared to those from patients in remission. CONCLUSION: We demonstrated that imprinting of MSC transcriptome demonstrated at diagnosis of MM, persisted even after the apparent disappearance of MM cells induced by treatment, suggesting the maintenance of a local context favorable to relapse.

Functional Comparison between Healthy and Multiple Myeloma Adipose Stromal Cells.

Multiple myeloma (MM) is an incurable B cell neoplasia characterized by the accumulation of tumor plasma cells within the bone marrow (BM). As a consequence, bone osteolytic lesions develop in 80% of patients and remain even after complete disease remission. We and others had demonstrated that BM-derived mesenchymal stromal cells (MSCs) are abnormal in MM and thus cannot be used for autologous treatment to repair bone damage. Adipose stromal cells (ASCs) represent an interesting alternative to MSCs for cellular therapy. Thus, in this study, we wondered whether they could be a good candidate in repairing MM bone lesions. For the first time, we present a transcriptomic, phenotypic, and functional comparison of ASCs from MM patients and healthy donors (HDs) relying on their autologous MSC counterparts. In contrast to MM MSCs, MM ASCs did not exhibit major abnormalities. However, the changes observed in MM ASCs and the supportive property of ASCs on MM cells question their putative and safety uses at an autologous or allogenic level.

A Influência da Espiritualidade e da Religiosidade na Aceitação da Doença e no Tratamento de Pacientes Oncológicos: Revisão Integrativa da Literatura / The Influence of Spirituality and Religiosity in Acceptance of the Disease and Treatment of Oncologic Patients: an Integrative Literature Review / La Influencia de la Espiritualidad y la Religiosidad en la Aceptación de Enfermedad y Tratamiento de Pacientes con Cáncer: una Revisión Integradora de Literatura

Introdução: A religiosidade e a espiritualidade são fatores ímpares na saúde do ser humano. Elas servem de auxílio para lidar com o câncer em seu processo de história natural. Objetivo: Analisar a produção científica nacional e internacional, acerca dos temas espiritualidade, religiosidade e pacientes oncológicos. Método: Revisão integrativa de literatura sobre a influência da espiritualidade e da religiosidade em pacientes oncológicos, nas bases de dados SciELO, MEDLINE e EBSCO e nos idiomas português e inglês, que buscou artigos publicados entre janeiro de 2009 a janeiro de 2019. Resultados: Oito artigos relataram a influência da religiosidade e da espiritualidade desde o momento do diagnóstico do câncer até a aceitação do tratamento. Dez artigos relataram que ambas servem como apoio, chance de encarar a vida e a morte de forma diferentes e de melhorar a qualidade de vida e bem-estar do paciente. A religiosidade e a espiritualidade ajudam os pacientes com as consequências do câncer e influenciarão a sua vida e o seu modo de viver durante o tratamento. Além disso, constituem uma estratégia que legitima e ameniza a incerteza diante das questões de caráter moral, pessoal e social, relativas à condição oncológica crônica. Conclusão: O apego à espiritualidade e à religiosidade influencia positivamente na saúde biopsicossocial do paciente com câncer. Ademais, pacientes dotados de espiritualidade e religiosidade podem apresentar melhor maior aceitação do câncer do tratamento, além de maior esperança e positividade no decorrer da doença.

Introduction: Religiosity and spirituality are unique factors in human health. They are helpful in dealing with cancer in its natural course. Objective: Analyze the national and international scientific publications involving the themes of Spirituality and Religiosity in Cancer Patients. Method: Integrative literature review that searched SciELO, MEDLINE and EBSCO databases for articles published between January 2009 and January 2019, in Portuguese and in English, about the influence of spirituality and religiosity in cancer patients from. Results: Eight articles reported the influence of religiosity and spirituality from the moment of cancer diagnosis through acceptance of the treatment. 10 articles reported that both serve as support, chance of facing life and death differently and to improve the patient's quality of life and well-being. Religiosity and spirituality help patients with the consequences of cancer and will influence their life and lifestyle during and after treatment. Moreover, they constitute a strategy that legitimizes and mitigates uncertainty about moral, personal and social issues related to the chronic oncological condition. Conclusion: Attachment to spirituality and religiosity positively influences the biopsychosocial health of cancer patients. Moreover, patients endowed with spirituality and religiosity may have better acceptance of cancer treatment, in addition of greater hope and positiveness during the course of the disease.

Introducción: La religiosidad y la espiritualidad son factores únicos en la salud humana. Son útiles para tratar el cáncer en su proceso de historia natural. Objetivo: Analizar la producción científica nacional e internacional, sobre los temas Espiritualidad, Religiosidad y Pacientes con cáncer. Método: Revisión bibliográfica integradora sobre la influencia de la espiritualidad y la religión en pacientes con cáncer en las bases de datos SciELO, MEDLINE y EBSCO, en idiomas portugués e inglés, quienes buscaron artículos publicados entre enero de 2009 y enero de 2019. Resultados: Ocho de los artículos informaron la influencia de la religiosidad y la espiritualidad desde el momento del diagnóstico del cáncer hasta la aceptación del tratamiento. Diez artigos informaron que ambos sirven como apoyo, una oportunidad para enfrentar la vida y la muerte de manera diferente y para mejorar la calidad de vida y el bienestar del paciente.La religiosidad y la espiritualidad ayudan a los pacientes con las consecuencias del cáncer e influirán en su vida y estilo de vida durante el tratamiento. Además, constituyen una estrategia que legitima y mitiga la incertidumbre frente a cuestiones morales, personales y sociales relacionadas con la condición oncológica crónica. Conclusion: Attachment to spirituality and religiosity positively influences the biopsychosocial health of cancer patients. Moreover, patients with spirituality and religiosity may have better acceptance of cancer treatment, and greater hope and positivity during the course of the disease.

BMI, irAE, and gene expression signatures associate with resistance to immune-checkpoint inhibition and outcomes in renal cell carcinoma.

BACKGROUND: Clinical variables may correlate with lack of response to treatment (primary resistance) or clinical benefit in patients with clear cell renal cell carcinoma (ccRCC) treated with anti-programmed death 1/ligand one antibodies. METHODS: In this multi-institutional collaboration, clinical characteristics of patients with primary resistance (defined as progression on initial computed tomography scan) were compared to patients with clinical benefit using Two sample t-test and Chi-square test (or Fisher's Exact test). The Kaplan-Meier method was used to estimate the distribution of progression-free survival (PFS) and overall survival (OS) in all patients and the subsets of patients with clinical benefit or primary resistance. Cox's regression model was used to evaluate the correlation between survival endpoints and variables of interest. To explore clinical factors in a larger, independent patient sample, The Cancer Genome Atlas (TCGA) was analyzed. RNAseq gene expression data as well as demographic and clinical information were downloaded for primary tumors of 517 patients included within TCGA-ccRCC. RESULTS: Of 90 patients, 38 (42.2%) had primary resistance and 52 (57.8%) had clinical benefit. Compared with the cohort of patients with initial benefit, primary resistance was more likely to occur in patients with worse ECOG performance status (p = 0.03), earlier stage at diagnosis (p = 0.04), had no prior nephrectomy (p = 0.04) and no immune-related adverse events (irAE) (p = 0.02). In patients with primary resistance, improved OS was significantly correlated with lower International Metastatic RCC Database Consortium risk score (p = 0.02) and lower neutrophil:lymphocyte ratio (p = 0.04). In patients with clinical benefit, improved PFS was significantly associated with increased BMI (p = 0.007) and irAE occurrence (p = 0.02) while improved OS was significantly correlated with overweight BMI (BMI 25-30; p = 0.03) and no brain metastasis (p = 0.005). The cohort TCGA-ccRCC was examined for the correlations between gene expression patterns, clinical factors, and survival outcomes observing associations of T-cell inflammation and angiogenesis signatures with histologic grade, pathologic stage and OS. CONCLUSIONS: Clinical characteristics including performance status, BMI and occurrence of an irAE associate with outcomes in patients with ccRCC treated with immunotherapy. The inverse association of angiogenesis gene signature with ccRCC histologic grade highlight opportunities for adjuvant combination VEGFR2 tyrosine kinase inhibitor and immune-checkpoint inhibition.

Expansion of the Primrose syndrome phenotype through the comparative analysis of two new case reports with ZBTB20 variants.

Primrose syndrome (PRIMS), a rare genetic disorder with several clinical findings including intellectual disability, macrocephaly, typical facial features, and muscle wasting, is caused by heterozygous variants in the ZBTB20 gene. We report the cases of two males diagnosed with PRIMS at different ages, emphasizing the likely progressive nature of the disorder, as well as the differences and similarities of presentation during infancy and adulthood. Patient 1 is a 2-year-old American male with a medical history marked by impaired hearing, developmental delays, and fainting spells. Patient 2 is a 28-year-old Brazilian male, who presents with a phenotype similar to that seen in Patient 1 with additional features of ectopic calcifications and prominent muscular and skeletal abnormalities. Additionally, Patient 2 has a history of fainting spells and diminished body height and weight, with the latter features having only been reported in one PRIMS patient so far. Both Patients 1 and 2 were found to carry heterozygous likely pathogenic missense variants, detected in the last coding exon of ZBTB20 (c.1822T>C, p.Cys608Arg, de novo, and c.1873A>G, p.Met625Val, respectively), consistent with PRIMS. Overall, these case reports highlight PRIMS's likely progressive nature and contribute to the understanding of the natural history of this condition.