A prospective, international phase 2 study of bortezomib retreatment in patients with relapsed multiple myeloma.

Multiple myeloma (MM) typically follows a relapsing course with many patients requiring multiple therapies. This single-arm phase 2 study prospectively evaluated the efficacy and safety of bortezomib retreatment in MM patients who had relapsed after achieving at least a partial response (≥ PR) to prior bortezomib-based therapy. Patients aged ≥ 18 years, with measurable, secretory MM, who relapsed ≥ 6 months after prior bortezomib treatment were eligible. Patients received up to eight cycles of bortezomib (± dexamethasone). The primary endpoint was best confirmed response at retreatment; secondary endpoints included duration of response (DOR), time to progression (TTP), and safety. Adverse events (AEs) were graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. A total of 130 patients (median of two prior lines of therapy) were enrolled and received retreatment. At retreatment, 28% and 72% of patients received bortezomib and bortezomib-dexamethasone, respectively. Overall response rate was 40%. In patients who achieved ≥ PR, median DOR and TTP were 6.5 and 8.4 months, respectively. Thrombocytopenia was the most common grade ≥ 3 AE (35%). Forty percent of patients experienced neuropathy events, which improved and resolved in a median of 1.5 and 8.9 months, respectively. In conclusion, bortezomib retreatment was effective and tolerable in relapsed MM patients, with no evidence of cumulative toxicities.

Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial.

BACKGROUND: Bortezomib and rituximab have shown additive activity in preclinical models of lymphoma, and have been shown to be active and generally well tolerated in a randomised phase 2 study in patients with follicular and marginal zone lymphoma. We compared the efficacy and safety of rituximab alone or combined with bortezomib in patients with relapsed or refractory follicular lymphoma in a phase 3 setting. METHODS: In this multicentre phase 3 trial, rituximab-naive or rituximab-sensitive patients aged 18 years or older with relapsed grade 1 or 2 follicular lymphoma were randomly assigned (1:1) to receive five 35-day cycles consisting of intravenous infusions of rituximab 375 mg/m(2) on days 1, 8, 15, and 22 of cycle 1, and on day 1 of cycles 2-5, either alone or with bortezomib 1·6 mg/m(2), administered by intravenous injection on days 1, 8, 15, and 22 of all cycles. Randomisation was stratified by FLIPI score, previous use of rituximab, time since last therapy, and region. Treatment assignment was based on a computer-generated randomisation schedule prepared by the sponsor. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival analysed by intention to treat. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00312845. FINDINGS: Between April 10, 2006, and Aug 12, 2008, 676 patients were randomised to receive rituximab (n=340) or bortezomib plus rituximab (n=336). After a median follow-up of 33·9 months (IQR 26·4-39·7), median progression-free survival was 11·0 months (95% CI 9·1-12·0) in the rituximab group and 12·8 months (11·5-15·0) in the bortezomib plus rituximab group (hazard ratio 0·82, 95% CI 0·68-0·99; p=0·039). The magnitude of clinical benefit was not as large as the anticipated prespecified improvement of 33% in progression-free survival. Patients in both groups received a median of five treatment cycles (range 1-5); 245 of 339 (72%) and 237 of 334 (71%) patients in the rituximab and bortezomib plus rituximab groups, respectively, completed five cycles. Of patients who did not complete five cycles, most discontinued early because of disease progression (77 [23%] patients in the rituximab group, and 56 [17%] patients in the bortezomib plus rituximab group). Rates of adverse events of grade 3 or higher (70 [21%] of 339 rituximab-treated patients vs 152 [46%] of 334 bortezomib plus rituximab treated patients), and serious adverse events (37 [11%] patients vs 59 [18%] patients) were lower in the rituximab group than in the combination group. The most common adverse events of grade 3 or higher were neutropenia (15 [4%] patients in the rituximab group and 37 [11%] patients in the bortezomib plus rituximab group), infection (15 [4%] patients and 36 [11%] patients, respectively), diarrhoea (no patients and 25 [7%] patients, respectively), herpes zoster (one [<1%] patient and 12 [4%] patients, respectively), nausea or vomiting (two [<1%] patients and 10 [3%] patients, respectively) and thrombocytopenia (two [<1%] patients and 10 [3%] patients, respectively). No individual serious adverse event was reported by more than three patients in the rituximab group; in the bortezomib plus rituximab group, only pneumonia (seven patients [2%]) and pyrexia (six patients [2%]) were reported in more than five patients. In the bortezomib plus rituximab group 57 (17%) of 334 patients had peripheral neuropathy (including sensory, motor, and sensorimotor neuropathy), including nine (3%) with grade 3 or higher, compared with three (1%) of 339 patients in the rituximab group (no events of grade ≥3). No patients in the rituximab group but three (1%) patients in the bortezomib plus rituximab group died of adverse events considered at least possibly related to treatment. INTERPRETATION: Although a regimen of bortezomib plus rituximab is feasible, the improvement in progression-free survival provided by this regimen versus rituximab alone was not as great as expected. The regimen might represent a useful addition to the armamentarium, particularly for some subgroups of patients. FUNDING: Johnson & Johnson Pharmaceutical Research & Development and Millennium Pharmaceuticals, Inc.

Age and experience with dental operating microscope: Do these factors influence on the post space preparation and adhesion of glass fiber posts?

This study evaluated the influence of operator's age and experience with dental operating microscope (DOM) on the cleaning of post space walls and on bond strength of glass fiber posts associated with self-adhesive resin cement. Sixty bovine roots were selected. Root canal preparation was performed and roots were filled using gutta-percha/AH Plus. For post space preparation, specimens were divided into four groups (n = 15), according to operator's age and the use of DOM: (1) ≥40 years; (2) ≥40 years with magnification; (3) <40 years; (4) <40 years with magnification. Next, a high-speed bur of the post system and torque-controlled round burs were used for cleaning of post space. Five roots in each group were evaluated for the degree of cleanliness under a stereo microscope using a scoring system. In the remaining 10 specimens from each group, glass fiber posts were cemented with RelyX U200. Two slices (1 ± 0.1 mm) prepared on each root third of all specimens were evaluated by push-out analysis. The scoring system was analyzed using Kruskal-Wallis and push-out data using ANOVA. Significance level was set at 5%. No significant difference was observed in cleaning scores among groups (p > .05). There was no significant difference when comparing the groups and the root thirds (p > .05). The adhesive failure between dentin, cement, and post predominated in all groups. Operator's age and experience with DOM did not influence the cleanliness of root canal walls or the bond strength of glass fiber posts associated with self-adhesive resin cement for post space preparation. RESEARCH HIGHLIGHTS: Although magnification is considered part of Endodontics, little is known about the variables associated. Operator's age and experience with microscope on cleaning of canals and on push-out of posts with self-adhesive resin cement were evaluated.

Analysis of the impact of coronavirus disease 19 on hospitalization rates for chronic non-communicable diseases in Brazil.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has impacted health services and healthcare systems worldwide. Studies have shown that hospital admissions for causes related to chronic non-communicable diseases (NCDs) have decreased significantly during peak pandemic periods. An analysis of the impact of the COVID-19 pandemic on hospital admissions for NCDs is essential to implement disability and mortality mitigation strategies for these groups. Therefore, this study aimed to analyze the impact of the COVID-19 pandemic on hospital admissions for NCDs in Brazil according to the type of NCD, sex, age group, and region of Brazil. METHODS: This is an ecological study conducted in Brazil. Data on hospital admissions from January 1, 2017 to May 31, 2021 were extracted from the Unified Health System's Hospital Admissions Information System. The hospital admission rates per 100,000 thousand inhabitants were calculated monthly according to the type of NCD, sex, age group, and region of Brazil. Poisson regression models were used to analyze the impact of the COVID-19 pandemic on the number of hospital admissions. In this study, the pre-pandemic period was set from January 1, 2017 to February 29, 2020 and the during-pandemic from March 1, 2020 to May 31, 2021. RESULTS: There was a 27.0% (95.0%CI: -29.0; -25.0%) decrease in hospital admissions for NCDs after the onset of the pandemic compared to that during the pre-pandemic period. Decreases were found for all types of NCDs-cancer (-23.0%; 95.0%CI: -26.0; -21.0%), diabetes mellitus (-24.0%; 95.0%CI: -25.0%; -22.0%), cardiovascular diseases (-30.0%; 95.0%CI: -31.0%; -28.0%), and chronic respiratory diseases (-29.0%; 95.0%CI: -30.0%; -27.0%). In addition, there was a decrease in the number of admissions, regardless of the age group, sex, and region of Brazil. The Northern and Southern regions demonstrated the largest decrease in the percentage of hospital admissions during the pandemic period. CONCLUSIONS: There was a decrease in the hospitalization rate for NCDs in Brazil during the COVID-19 pandemic in a scenario of social distancing measures and overload of health services.

Cohort study protocol of the Brazilian collaborative research network on COVID-19: strengthening WHO global data.

INTRODUCTION: With the COVID-19 pandemic, hospitals in low-income countries were faced with a triple challenge. First, a large number of patients required hospitalisation because of the infection's more severe symptoms. Second, there was a lack of systematic and broad testing policies for early identification of cases. Third, there were weaknesses in the integration of information systems, which led to the need to search for available information from the hospital information systems. Accordingly, it is also important to state that relevant aspects of COVID-19's natural history had not yet been fully clarified. The aim of this research protocol is to present the strategies of a Brazilian network of hospitals to perform systematised data collection on COVID-19 through the WHO platform. METHODS AND ANALYSIS: This is a multicentre project among Brazilian hospitals to provide data on COVID-19 through the WHO global platform, which integrates patient care information from different countries. From October 2020 to March 2021, a committee worked on defining a flowchart for this platform, specifying the variables of interest, data extraction standardisation and analysis. ETHICS AND DISSEMINATION: This protocol was approved by the Research Ethics Committee (CEP) of the Research Coordinating Center of Brazil (CEP of the Hospital Nossa Senhora da Conceicao), on 29 January 2021, under approval No. 4.515.519 and by the National Research Ethics Commission (CONEP), on 5 February 2021, under approval No. 4.526.456. The project results will be explained in WHO reports and published in international peer-reviewed journals, and summaries will be provided to the funders of the study.

Multicentricity in the thyroid differentiated carcinoma.

UNLABELLED: The treatment of choice for the well differentiated thyroid carcinoma has always been controversial. AIM: to analyze tumor invasion of the thyroid gland's contralateral lobe in cases of differentiated carcinoma, correlating risk/benefit with the complications of a second surgical approach. MATERIALS AND METHODS: Retrospective study, from 1998 to 2006, of 27 patients undergoing less than total thyroidectomy: lobectomy (21), subtotal thyroidectomy (5) or isthmusectomy (1). Gender, age, type of surgery, complications, histopathological analysis and invasion of the contralateral lobe were analyzed. Patients' ages varied from 17 to 89; the most frequent histopathological pattern was the classical papillary carcinoma (18 cases), followed by follicular carcinoma (6); the follicular variant of the papillary carcinoma (2) and the Hürthle cell carcinoma (1). Twenty-one patients underwent full thyroidectomies, from 15 to 30 days after the first intervention. RESULTS: the contralateral lobe analysis was negative for carcinoma in 16 (76.5%) and positive in the other 5 (23.8%) patients. The complications observed were temporary dysphonia (3 cases) and hypoparathyroidism (2 cases, one permanent). CONCLUSIONS: total thyroidectomy is important in the treatment of differentiated thyroid carcinomas, because there is a high contralateral spread rate (23.8%). It is a procedure without mortality, which bears few complications.

Nutritional screening in hospitalized pediatric patients: a systematic review.

OBJECTIVE: This systematic review aimed to verify the available scientific evidence on the clinical performance and diagnostic accuracy of nutritional screening tools in hospitalized pediatric patients. DATA SOURCE: A search was performed in the Medline (National Library of Medicine United States), LILACS (Latin American and Caribbean Health Sciences), PubMed (US National Library of Medicine National Institutes of Health), in the SCIELO (Scientific Electronic Library Online), through CAPES portal (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), bases Scopus e Web of Science. The descriptors used in accordance with the Descriptors in Health Sciences (DeCS)/Medical Subject Headings (MeSH) list were "malnutrition", "screening", and "pediatrics", as well as the equivalent words in Portuguese. SUMMARY OF THE FINDINGS: The authors identified 270 articles published between 2004 and 2014. After applying the selection criteria, 35 were analyzed in full and eight articles were included in the systematic review. We evaluated the methodological quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Five nutritional screening tools in pediatrics were identified. Among these, the Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) showed high sensitivity, almost perfect inter-rater agreement and between the screening and the reference standard; the Screening Tool Risk on Nutritional Status and Growth (STRONGkids) showed high sensitivity, lower percentage of specificity, substantial intra-rater agreement, and ease of use in clinical practice. CONCLUSIONS: The studies included in this systematic review showed good performance of the nutritional screening tools in pediatrics, especially STRONGkids and STAMP. The authors emphasize the need to perform for more studies in this area. Only one tool was translated and adapted to the Brazilian pediatric population, and it is essential to carry out studies of tool adaptation and validation for this population.

Eversão da cartilagem da terceira pálpebra em um gato / Eversion of the third eyelid cartilage in a cat

Background: Eversion of the cartilage of the third eyelid is a rare congenital disease in cats. It is caused by the anterioreversion of the cartilage edge of the third eyelid. Clinical signs may be associated with secondary keratoconjunctivitis,third eyelid gland protrusion, and ocular surface irritation. The diagnosis is made by ophthalmic examination, and treatment consists of surgical resection of the everted cartilage portion. The goal of the present study was to report a case ofeversion of third eyelid cartilage in a cat, given that it is an unusual abnormality in this animal species, and an importantdifferential diagnosis to be considered in the disorders of the third eyelid.Case: A 6-year-old neutered female Persian cat was presented with a presumptive diagnosis of protrusion of the thirdeyelid gland, history of ocular irritation, and epiphora in the left eye. The disorder had been intermittently present sincethe animal was 1-year-old, with spontaneous disappearance after approximately 15 days. The owner related the reappearance of the disorder to stressful situations, with no previous history of trauma or other ocular alteration. During theophthalmic examination, suspended solute was observed through biomiscroscopic examination in both eyes, as well asan increase in volume of the third eyelid in the left eye, without other changes. A thorough examination, under generalanesthesia, indicated the protruding volume of the cartilage of the everted third eyelid. The third eyelid was pleated inits upper portion, demonstrating that the cartilage of the third eyelid was folded instead of following the curvature of theocular surface. Under general anesthesia, the cartilage was partially removed through two parallel incisions on the bulbarconjunctival surface, divulsioning 5 mm in length in the vertical portion of the cartilage in a ‘T shape, and separating the...(AU)

Eversão da cartilagem da terceira pálpebra em um gato / Eversion of the third eyelid cartilage in a cat

Background: Eversion of the cartilage of the third eyelid is a rare congenital disease in cats. It is caused by the anterioreversion of the cartilage edge of the third eyelid. Clinical signs may be associated with secondary keratoconjunctivitis,third eyelid gland protrusion, and ocular surface irritation. The diagnosis is made by ophthalmic examination, and treatment consists of surgical resection of the everted cartilage portion. The goal of the present study was to report a case ofeversion of third eyelid cartilage in a cat, given that it is an unusual abnormality in this animal species, and an importantdifferential diagnosis to be considered in the disorders of the third eyelid.Case: A 6-year-old neutered female Persian cat was presented with a presumptive diagnosis of protrusion of the thirdeyelid gland, history of ocular irritation, and epiphora in the left eye. The disorder had been intermittently present sincethe animal was 1-year-old, with spontaneous disappearance after approximately 15 days. The owner related the reappearance of the disorder to stressful situations, with no previous history of trauma or other ocular alteration. During theophthalmic examination, suspended solute was observed through biomiscroscopic examination in both eyes, as well asan increase in volume of the third eyelid in the left eye, without other changes. A thorough examination, under generalanesthesia, indicated the protruding volume of the cartilage of the everted third eyelid. The third eyelid was pleated inits upper portion, demonstrating that the cartilage of the third eyelid was folded instead of following the curvature of theocular surface. Under general anesthesia, the cartilage was partially removed through two parallel incisions on the bulbarconjunctival surface, divulsioning 5 mm in length in the vertical portion of the cartilage in a ‘T’ shape, and separating the...

An update on the epigenetics of glioblastomas.

Glioblastomas, also known as glioblastoma multiforme (GBM), are the most aggressive and malignant type of primary brain tumor in adults, exhibiting notable variability at the histopathological, genetic and epigenetic levels. Recently, epigenetic alterations have emerged as a common hallmark of many tumors, including GBM. Considering that a deeper understanding of the epigenetic modifications that occur in GBM may increase the knowledge regarding the tumorigenesis, progression and recurrence of this disease, in this review we discuss the recent major advances in GBM epigenetics research involving histone modification, glioblastoma stem cells, DNA methylation, noncoding RNAs expression, including their main alterations and the use of epigenetic therapy as a valid option for GBM treatment.

Fake news colocam a vida em risco: a polêmica da campanha de vacinação contra a febre amarela no Brasil / Fake News put human life at risk: the controversy of the yellow fever vaccination campaign in Brazil / Fake News ponen en riesgo la vida: la controversia de la campaña de vacunación contra la fiebre amarilla en Brasil

Este artigo faz a leitura das notícias falsas que circulam conteúdo sobre saúde pública em redes digitais e aplicativos de troca de mensagens. Para enumerar os argumentos utilizados pelos divulgadores de fake news na disputa pela enunciação da verdade, no campo do discurso, os autores escolheram a campanha de vacinação contra a febre amarela, lançada em um surto da doença no Brasil, no final de 2016. Selecionamos os textos de posts e áudios que se multiplicaram no WhatsApp, especificamente no ano de 2018, para a análise ancorada nas teses sobre produção de verdade e poder de Michel Foucault e de Nikolas Rose. Iniciamos, assim, uma reflexão sobre a ação das fake news em defesa da vida e que, ao mesmo tempo, colocam a vida em risco. A Organização Mundial da Saúde já aponta as fake news como uma das responsáveis pela baixa nos níveis internacionais de imunização.

This article analyses the fake news that spread contents of public health using digital networks and crossplatform messaging applications. To list the arguments used by those people whom spread fake news to dispute the utterance of the truth, in the discourse field, the authors have chosen the yellow fever vaccination campaign, launched in the outbreak of the disease in Brazil, in late 2016. We selected the texts of posts and audios that multiplied via WhatsApp, specifically in 2018, for analysis based on the theses on the production of truth and power by Michel Foucault and Nikolas Rose. Thus, we started a reflection on the action of fake news in defense of life while themselves put many lives at risk. The World Health Organization already points out fake news as one of the factors responsible for the drop in international levels of immunization.

Este artículo hace un análisis de las fake news que difunden contenido sobre salud pública por medio de redes digitales y aplicaciones de mensajería. Para enumerar los argumentos utilizados por las personas que hacen la divulgación de las fake news en la disputa por la expresión de la verdad, en el campo del discurso, los autores eligieron la campaña de vacunación contra la fiebre amarilla, lanzada en el brote de la enfermedad en Brasil, a fines de 2016. Seleccionamos los textos de publicaciones y audios que se multiplicaron en el WhatsApp, especialmente en 2018, para el análisis basado en las tesis sobre la producción de verdad y poder de Michel Foucault y de Nikolas Rose. Comenzamos así a reflexionar sobre la acción de las fake news en defensa de la vida y que al mismo tiempo la ponen en riesgo. La Organización Mundial de la Salud ya señala las fake news como uno de los factores responsables de la bajada de los niveles internacionales de inmunización.

Fake news colocam a vida em risco: a polêmica da campanha de vacinação contra a febre amarela no Brasil / Fake news put human life at risk: the controversy of the yellow fever vaccination campaign in Brazil

Este artigo faz a leitura das notícias falsas que circulam conteúdo sobre saúde pública em redes digitais e aplicativos de troca de mensagens. Para enumerar os argumentos utilizados pelos divulgadores de fake news na disputa pela enunciação da verdade, no campo do discurso, os autores escolheram a campanha de vacinação contra a febre amarela, lançada em um surto da doença no Brasil, no final de 2016. Selecionamos os textos de posts e áudios que se multiplicaram no WhatsApp, especificamente no ano de 2018, para a análise ancorada nas teses sobre produção de verdade e poder de Michel Foucault e de Nikolas Rose. Iniciamos, assim, uma reflexão sobre a ação das fake news em defesa da vida e que, ao mesmo tempo, colocam a vida em risco. A Organização Mundial da Saúde já aponta as fake news como uma das responsáveis pela baixa nos níveis internacionais de imunização.

Relationship between the action of reactive oxygen and nitrogen species on bilayer membranes and antioxidants.

Membrane lipid peroxidation (LPO) induced by hydroxyl (*OH) and ascorbyl (*Asc) radicals and by peroxynitrite (ONOO-) was investigated in asolectin (ASO), egg phosphatidylcholine (PC) and PC/phosphatidic acid mixtures (PC:PA) liposomes and rat liver microsomes (MC). Enthalpy variation (DeltaH) of PC:PA at different molar ratios were obtained by differential scanning calorimetry. It was also evaluated the LPO inhibition by quercetin, melatonin and Vitamin B6. The oxidant effect power follows the order *OH approximately *Asc > ONOO- on PC and MC; whilst on ASO liposomes, it follows *Asc > *OH approximately ONOO-. Increasing amounts of PA in PC liposomes resulted in lower levels of LPO. The DeltaH values indicate a more ordered membrane arrangement as a function of PA amount. The results were discussed in order to provide a complete view involving the influence of membranes, oxidants and antioxidants intrinsic behavior on the LPO dynamics.

What determines therapeutic choices for elderly patients with DLBCL? Clinical findings of a multicenter study in Portugal.

BACKGROUND: Age is a negative prognostic factor in lymphomas, and elderly patients are often undertreated because of toxicity concerns. The pattern of treatment in elderly patients with diffuse large B-cell lymphoma (DLBCL) in Portugal has not been previously described. PATIENTS AND METHODS: We conducted a multicenter retrospective study including 378 elderly patients with DLBCL receiving alkylating agent-containing regimens between 2003 and 2010. We compared the outcome of patients aged 60 to 79 years with patients > 79 years and analyzed the second group according to treatment. RESULTS: R-CHOP (rituximab, cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], prednisolone) was prescribed in only 60% of patients and was prescribed significantly less in patients > 79 years, despite no significant differences being found in comorbidities between the 2 age groups. Similarly, dose reductions frequently were instituted because of chronologic age and not always because of toxicity. When different regimens were compared, multivariate analysis showed an independent beneficial effect of R-CHOP in treatment outcomes. Additionally, treatment with anthracyclines and rituximab predicted a better progression-free survival (PFS) and time to progression (TTP) in patients > 79 years. CONCLUSION: This was the first characterization of the clinical care of elderly Portuguese patients with DLBCL. We showed that R-CHOP is effective even in patients > 79 years, emphasizing that treatment decisions based on age alone can compromise treatment efficacy and outcome in fit patients.

Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

PURPOSE: Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. EXPERIMENTAL DESIGN: A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. RESULTS: In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. CONCLUSIONS: Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab.

A possible role for oxidation stress in lymphoid leukaemias and therapeutic failure.

The aim of this study was to evaluate the role of oxidative stress in the pathobiology of lymphoid leukaemias and its involvement in leukaemic relapse. For this purpose the generation of peroxides by mononuclear cells, the erythrocyte activity of superoxide-dismutase (SOD) and glutathione peroxidase (GL-PX), and the plasma levels of reduced glutathione (GSH) and vitamin E (VIT E) were determined in 52 patients with two different types of lymphoid leukaemias, chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL), 36 prior to chemotherapy and 16 treated patients. A decrease in SOD and GL-PX activities was observed in ALL patients prior to therapy, while a decrease in GSH and VIT E plasma levels was observed in untreated CLL, as compared to age-matched controls. An increase in peroxides formation occurred in both types of leukaemia, as compared to age-matched controls. There are significant differences for GSH, VIT E and peroxides generation between the different types of leukaemias. In relapsed ALL patients a decrease in peroxides generation was observed which may be due to the increase of the non-enzymatic defences GSH and VIT E. These data suggest the involvement of oxidative stress in acute and chronic lymphoid leukaemias and leukaemic relapse.

Nutritional screening in hospitalized pediatric patients: a systematic review / Triagem nutricional em pacientes pediátricos hospitalizados: uma revisão sistemática

Abstract Objective: This systematic review aimed to verify the available scientific evidence on the clinical performance and diagnostic accuracy of nutritional screening tools in hospitalized pediatric patients. Data source: A search was performed in the Medline (National Library of Medicine United States), LILACS (Latin American and Caribbean Health Sciences), PubMed (US National Library of Medicine National Institutes of Health), in the SCIELO (Scientific Electronic Library Online), through CAPES portal (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), bases Scopus e Web of Science. The descriptors used in accordance with the Descriptors in Health Sciences (DeCS)/Medical Subject Headings (MeSH) list were “malnutrition”, “screening”, and “pediatrics”, as well as the equivalent words in Portuguese. Summary of the findings: The authors identified 270 articles published between 2004 and 2014. After applying the selection criteria, 35 were analyzed in full and eight articles were included in the systematic review. We evaluated the methodological quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Five nutritional screening tools in pediatrics were identified. Among these, the Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) showed high sensitivity, almost perfect inter-rater agreement and between the screening and the reference standard; the Screening Tool Risk on Nutritional Status and Growth (STRONGkids) showed high sensitivity, lower percentage of specificity, substantial intra-rater agreement, and ease of use in clinical practice. Conclusions: The studies included in this systematic review showed good performance of the nutritional screening tools in pediatrics, especially STRONGkids and STAMP. The authors emphasize the need to perform for more studies in this area. Only one tool was translated and adapted to the Brazilian pediatric population, and it is essential to carry out studies of tool adaptation and validation for this population.

Resumo Objetivo: Esta revisão sistemática tem por objetivo verificar as evidências científicas disponíveis sobre o desempenho clínico e acurácia diagnóstica dos instrumentos de triagem nutricional em pacientes pediátricos hospitalizados. Fonte de dados: Realizou-se busca nas bases de dados Medline (National Library of Medicine United States), LILACS (Latin American and Caribbean Health Sciences), PubMed (US National Library of Medicine National Institutes of Health), na biblioteca eletrônica SCIELO (Scientific Electronic Library Online), através do portal de periódicos da CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior), bases Scopus e Web of Science. Os descritores utilizados conforme lista do DeCS (Descritores em Ciências da Saúde)/MeSH (Medical Subject Headings) foram “desnutrição”, “triagem” e “pediatria”, bem como, “malnutrition”, “screening” e “pediatrics”, respectivamente. Síntese dos dados: Identificou-se 270 artigos, publicados entre 2004 e 2014. Após aplicação dos critérios de seleção, 35 foram analisados na íntegra, sendo incluídos 8 artigos na revisão sistemática. Avaliou-se a qualidade metodológica dos estudos utilizando-se o QUADAS (Quality Assessment of Diagnostic Accuracy Studies). Verificou-se 05 instrumentos de triagem nutricional em pediatria. Dentre estes, o STAMP (Screening Tool for the Assessment of Malnutrition in Pediatrics) apresentou sensibilidade elevada, concordância quase perfeita inter-avaliador e entre a triagem e padrão de referência; o STRONGkids (Screening Tool Risk on Nutritional Status and Growth) evidenciou sensibilidade elevada, menor percentual de especificidade, concordância intra-avaliador substancial e facilidade de uso na prática clínica. Conclusões: Os estudos incluídos nesta revisão sistemática demonstraram um bom desempenho dos instrumentos de triagem nutricional em pediatria, principalmente STRONGkids e STAMP. Evidencia-se a necessidade de mais pesquisas nessa área. Apenas um instrumento foi traduzido e adaptado para a população pediátrica brasileira, sendo imprescindível a realização de estudos de adaptação e validação de instrumentos para essa população.

[Economic analysis of rituximab in combination with cyclophosphamide, vincristine and prednisolone in the treatment of patients with advanced follicular lymphoma in Portugal]. / Análise económica de rituximab em associação com ciclofosfamida, vincristina e prednisolona no tratamento de doentes com linfoma folicular avançado em Portugal.

OBJECTIVE: Evaluate costs and benefits of rituximab in combination with cyclophosphamide/vincristine/prednisolone chemotherapy regimen (R-CVP), in previously untreated patients with indolent non-Hodgkin lymphoma (NHL), compared to CVP alone from a Portuguese National Health System (NHS) perspective. METHODS: Cost-effectiveness (Life Years Gained--LYG) and cost-utility analysis (Quality Adjusted Life Years--QALYs) were performed for a time horizon of 10 years, according to a Markov economic model with three health states (progression free survival, progression and death) and monthly cycles for a population of previously untreated patients with indolent NHL. Data from a phase III clinical trial was used and expanded to include unpublished 53-month median follow-up data. Survival after first-line therapy was estimated from the Scotland and Newcastle Lymphoma Group registry data and utilities were derived from a study in the UK performed in patients with follicular lymphoma. Resource consumption was estimated by a Portuguese expert panel (Delbecq Panel). Costs were calculated from the Portuguese NHS perspective through official data with prices updated to 2008. Only direct medical costs were considered. Costs and clinical outcomes were discounted at 5% per annum. Deterministic and probabilistic sensitivity analysis were performed around assumptions on the time horizon, costs, utilities and excess mortality rate due to progression applied in the base-case analysis. RESULTS: The 10-year base-case analysis showed a lower total cost per patient with CVP alone (€ 85,838) in comparison with R-CVP (€ 87,774). Life expectancy and Quality adjusted life expectancy per patient were higher with R-CVP (6.361 and 4.166, respectively) than with CVP alone (5.557 and 3.438, respectively), representing increases of 0.804 in LYG and 0.728 (8.7 months) in QALYs gained. The incremental cost per LYG was € 2,407 and the incremental cost per QALY gained was € 2,661. The probabilistic sensitivity analysis confirmed the robustness of the base-case analysis results. CONCLUSIONS: This study demonstrates that the combination R-CVP in previously untreated indolent NHL patients improves life expectancy and is a cost-effective alternative to CVP in Portugal.

[Biosimilars in oncology]. / Biossimilares em oncologia.

The development of biotechnology drugs represents one of the great advances in medical therapy and it was observed an exponential growth in its use. The resource to these drugs in Oncology and Hematology is no exception and it soon became an essential element of an integrated and directed therapy strategy. The expiry of the first biotechnology drugs patents has opened the door for the development and marketing of biosimilars, which entry in the Portuguese market was recently approved. This article was built on the analysis of the available state-of-the-art information on biotechnology drugs, biosimilars and current legislation and it expresses the opinion of Oncology and Hematology experts about the substituition of biological drugs by biosimilars in clinical practice.

[Use of granulocyte growth factors: recommendations of the Portuguese Society of Hematology]. / Uso de factores de crescimento de granulócitos: recomendações da Sociedade Portuguesa de Hematologia.

The administration of cytotoxic chemotherapy may be complicated by the emergence of neutropenia and febrile neutropenia, frequently determining hospital admission and intravenous treatment with broad spectrum antibiotics. Frequently, it is necessary to reduce the dose or to delay the administration of the cytotoxic drugs reducing the relative dose intensity of the chemotherapy regimen. Granulocyte growth factors stimulate the proliferation and differentiation of neutrophils and reduce the number of days of severe neutropenia and febrile neutropenia associated with cytotoxic chemotherapy. They are also indicated for the collection of hematopoietic progenitors for autologous and allogeneic transplantation, as well as in non malignant diseases associated with chronic neutropenia. This article reviews the evidence supporting the use of granulocyte growth factors in Hematology.