Exploring the influence of baseline rheumatoid factor levels on TNF inhibitor retention rate in patients with rheumatoid arthritis: a multicentre and retrospective study.

OBJECTIVE: To assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels. METHODS: Longitudinal, retrospective and multicentre study including patients with RA who were treated with any TNFi (monoclonal antibodies (mAB), etanercept (ETA) or CZP). Log-rank test and Cox regressions were conducted to evaluate the retention rate in the three groups according to the level of RF, with the third quartile of the baseline levels used as cut-off: <200 (

Organ Transplant From SARS-CoV-2-Positive Donors: A Brazilian Experience.

Since March 2022, donors with detectable SARS-CoV-2 RNA have been accepted for extrapulmonary organ transplants in Brazil. In this report, we described 11 successful organ transplants (6 kidney, 5 liver) from 5 asymptomatic infected donors.

Real-life experience of venetoclax and hypomethylating agents in acute myeloid leukemia patients not candidates for intensive chemotherapy or who are refractory/relapsed: A single-centre experience.

We report our experience with venetoclax/hypomethylating agents (Ven/HMA) in 8 AML patients not candidates for intensive CT or refractory/relapsed with limited treatment options. The response rate was 50%. Venetoclax was well-tolerated in 62.5% of the patients. Ven/HMA provides a benefit particularly when used in patients without prior HMA exposure.

Real-world analysis of main clinical outcomes in patients with polycythemia vera treated with ruxolitinib or best available therapy after developing resistance/intolerance to hydroxyurea.

BACKGROUND: Ruxolitinib is approved for patients with polycythemia vera (PV) who are resistant/intolerant to hydroxyurea, but its impact on preventing thrombosis or disease-progression is unknown. METHODS: A retrospective, real-world analysis was performed on the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to subsequent treatment with ruxolitinib (n = 105) or the best available therapy (BAT; n = 272). Survival probabilities and rates of thrombosis, hemorrhage, acute myeloid leukemia, myelofibrosis, and second primary cancers were calculated according to treatment. To minimize biases in treatment allocation, all results were adjusted by a propensity score for receiving ruxolitinib or BAT. RESULTS: Patients receiving ruxolitinib had a significantly lower rate of arterial thrombosis than those on BAT (0.4% vs 2.3% per year; P = .03), and this persisted as a trend after adjustment for the propensity to have received the drug (incidence rate ratio, 0.18; 95% confidence interval, 0.02-1.3; P = .09). There were no significant differences in the rates of venous thrombosis (0.8% and 1.1% for ruxolitinib and BAT, respectively; P = .7) and major bleeding (0.8% and 0.9%, respectively; P = .9). Ruxolitinib exposure was not associated with a higher rate of second primary cancers, including all types of neoplasia, noncutaneous cancers, and nonmelanoma skin cancers. After a median follow-up of 3.5 years, there were no differences in survival or progression to acute leukemia or myelofibrosis between the 2 groups. CONCLUSIONS: The results suggest that ruxolitinib treatment for PV patients with resistance/intolerance to hydroxyurea may reduce the incidence of arterial thrombosis. LAY SUMMARY: Ruxolitinib is better than other available therapies in achieving hematocrit control and symptom relief in patients with polycythemia vera who are resistant/intolerant to hydroxyurea, but we still do not know whether ruxolitinib provides an additional benefit in preventing thrombosis or disease progression. We retrospectively studied the outcomes of 377 patients with resistance/intolerance to hydroxyurea from the Spanish Registry of Polycythemia Vera according to whether they subsequently received ruxolitinib (n = 105) or the best available therapy (n = 272). Our findings suggest that ruxolitinib could reduce the incidence of arterial thrombosis, but a disease-modifying effect could not be demonstrated for ruxolitinib in this patient population.

Evolução de crianças asmáticas com tratamento homeopático / Evolution in asthmatic children through homeopatic treatment

Estudando 43 crianças asmáticas, atendidas no ambulatório de asma da Associação Paulista de Homeopatia, pudemos observar boa evolução na intensidade e no número de crises com o tratamento, bem como constatar a importância dos fatores físicos e climáticos na etiologia asmática e na busca do remédio adequado. (AU)

The aim of the present paper is to describe the results of a study on the progression of 43 cases of asthmatic children subjected to homeopathic treatment at the asthma outpatient clinic, São Paulo Homeopathic Medical Association, from march to December 1985. Improvement in the intensity and frequency of attacks was observed. The results further demonstrate, based on the preset statistical criteria, the relevance of investigating mental, physical and climate-related factors. (AU)

Artritis reumatoide y nódulos pulmonares: un diagnóstico final inesperado / Rheumatoid arthritis and pulmonary nodules: a unexpected final diagnosis

Se presenta el caso de una mujer de 50 años, fumadora, con artritis reumatoide seropositiva (FR y CCP) de 11 años de evolución en tratamiento con triple terapia, y aparición de nódulos pulmonares con diagnóstico final de histiocitosis de células de Langerhans por biopsia pulmonar. No hemos encontrado casos descritos de la coexistencia de ambas enfermedades. La abstinencia tabáquica llevó a la resolución radiológica sin necesidad de modificar la terapia inmunosupresora (AU)

We report the case of a 50-year-old female smoker with an 11-year history of seropositive rheumatoid arthritis (rheumatoid factor and anti-cyclic citrullinated peptide antibodies) receiving triple therapy. She developed pulmonary nodules diagnosed as Langerhans cell histiocytosis by lung biopsy. We found no reported cases of the coexistence of these two diseases. Smoking abstinence led to radiologic resolution without modifying the immunosuppressive therapy (AU)

Pseudohipertrofia gemelar / Calf pseudohipertrophy

La pseudohipertrofia gemelar secundaria a una radiculopatía es un fenómeno excepcional raramente descrito. Presentamos el caso de una mujer de 67 años con antecedentes de cirugía discal lumbar que consultaba por aumento progresivo de más de un año de evolución, no doloroso, de la región gemelar derecha con ligera pérdida de fuerza asociada. Los hallazgos electromiográficos evidenciaron una radiculopatía crónica S1 y radiológicamente se apreciaba, en territorio del gastrocnemio medial y sóleo derechos, una sustitución del tejido muscular normal por tejido adiposo, sin evidencia de miopatía o degeneración sarcomatosa (AU)

Calf pseudohypertrophy due to radiculopathy is an exceptional phenomenon rarely described. We report a 67 year old woman with a previous history of lumbar disc surgery consulting by progressive increase for more than a year of evolution painless right calf associated loss of strength. Electromyographic findings showed chronic S1 radiculopathy and radiologically was appreciated in the medial gastrocnemius and soleus rights substitution of normal muscle tissue by adipose tissue without evidence of myopathy or sarcomatous degeneration (AU)

Calf pseudohipertrophy. / Pseudohipertrofia gemelar.

Calf pseudohypertrophy due to radiculopathy is an exceptional phenomenon rarely described. We report a 67 year old woman with a previous history of lumbar disc surgery consulting by progressive increase for more than a year of evolution painless right calf associated loss of strength. Electromyographic findings showed chronic S1 radiculopathy and radiologically was appreciated in the medial gastrocnemius and soleus rights substitution of normal muscle tissue by adipose tissue without evidence of myopathy or sarcomatous degeneration.

Rheumatoid arthritis and pulmonary nodules: An unexpected final diagnosis. / Artritis reumatoide y nódulos pulmonares: un diagnóstico final inesperado.

We report the case of a 50-year-old female smoker with an 11-year history of seropositive rheumatoid arthritis (rheumatoid factor and anti-cyclic citrullinated peptide antibodies) receiving triple therapy. She developed pulmonary nodules diagnosed as Langerhans cell histiocytosis by lung biopsy. We found no reported cases of the coexistence of these two diseases. Smoking abstinence led to radiologic resolution without modifying the immunosuppressive therapy.

Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion-dependent anemia and thrombocytopenia.

BACKGROUND: CC-486 is an oral formulation of the epigenetic modifier azacitidine. In an expanded phase 1 trial, CC-486 demonstrated clinical and biological activity in patients with International Prognostic Scoring System (IPSS) lower-risk (low- and intermediate-1-risk) myelodysplastic syndromes (MDS) with poor prognostic features including anemia and/or thrombocytopenia who may have required red blood cell or platelet transfusions. The overall response rate was 40 %, including hematologic improvement in 28 % of patients and RBC transfusion independence sustained for 56 days in 47 % of patients with baseline transfusion dependence. Based on the results of this study, the randomized, placebo-controlled phase 3 QUAZAR Lower-Risk MDS trial (AZA-MDS-003) was initiated. The design and rationale for this trial comparing CC-486 with placebo for the treatment of patients with IPSS lower-risk MDS with poor prognostic features are described. METHODS: Patients must have IPSS lower-risk MDS with red blood cell (RBC) transfusion-dependent anemia and thrombocytopenia. Eligible patients are randomized 1:1 to receive 300 mg of CC-486 or placebo once daily for the first 21 days of 28-day treatment cycles. Disease status assessments occur at the end of cycle 6 and patients may continue to receive treatment unless there is evidence of progressive disease, lack of efficacy, or unacceptable toxicity. The primary endpoint is RBC transfusion independence for ≥ 84 days, assessed according to International Working Group 2006 criteria. Secondary endpoints include overall survival, hematologic response including platelet response and erythroid response, RBC transfusion independence for ≥ 56 days, duration of RBC transfusion independence, time to RBC transfusion independence, rate of acute myeloid leukemia (AML) progression, time to AML progression, clinically significant bleeding events, safety, health-related quality of life, and healthcare resource utilization. CONCLUSIONS: This study will provide data on the efficacy and safety of CC-486 in the treatment of IPSS lower-risk MDS with poor prognosis due to the presence of both RBC transfusion-dependent anemia and thrombocytopenia. Positive results of the AZA-MDS-003 study may expand treatment options for patients with IPSS lower-risk MDS. TRIAL REGISTRATION: ClinicalTrials.gov NCT01566695, registered March 27, 2012.

Response to erythropoietic-stimulating agents in patients with chronic myelomonocytic leukemia.

BACKGROUND: The efficacy of erythropoietic-stimulating agents (ESA) in chronic myelomonocytic leukemia (CMML) is unknown. Our objective was to analyze erythroid response (ER) and overall survival (OS) in a series of 94 patients with CMML treated with ESA. METHODS: We analyzed a series of 94 patients with CMML treated with ESA included in the Spanish and Düsseldorf-MDS registries. FINDINGS: ER was observed in 64% of patients and red blood cell (RBC) transfusion independence in 31%. The median duration of ER was 7 months (range, 0-88). CPSS and EPO level were significantly associated with ER in multivariate analysis (P = 0.003). Considering only patients with CPSS low- or intermediate-1-risk group, the absence of RBC transfusion dependence and erythropoietin (EPO) level predicted ER (P = 0.003 and P = 0.008, respectively). In multivariate analysis, only the EPO level retained its prognostic value (P = 0.029). Achievement of ER correlated with a better survival since ER evaluation (P = 0.016). INTERPRETATION: The CPSS and EPO levels are adequate tools to select CMML patients with symptomatic anemia who may benefit from treatment with ESA. A significant ER to ESA is expected in anemic patients with low/intermediate-1 CMML risk by the CPSS and a low endogenous serum EPO level.

Avaliação da qualidade de vida de idosos em hemodiálise pelo questionário KDQOL / Evaluation of quality of life in elderly patients on hemodialysis using KDQOLquestionnaire

JUSTIFICATIVA: A expectativa média de vida no Brasil aumentou e observa-se um crescimento no número de idosos com doença renal crônica. OBJETIVO: Avaliar a qualidade de vida obtida através do questionário KDQOL (Kidney Disease Qualityof Life) em idosos em hemodiálise, correlacionando os dados desse questionário com idade e condições socioeconômicas.MÉTODOS: Trata-se de um estudo transversal em pacientes com idade maior que 60 anos, portadores de doença renal crônica em hemodiálise em dois centros da cidade de São Paulo(Hospital do Servidor Público Estadual de São Paulo e Hospital Samaritano). Para mensurar os indicadores de qualidade de vida, foi aplicado o questionário KDQOL uma hora antes da realização da sessão de hemodiálise. RESULTADOS: Foram estudados 18 pacientes com média de idade de 71,3±6,8 anos,sendo 61,1% do sexo masculino, 77,7% brancos, com tempo de tratamento hemodialítico de 29,2±27,6 meses, todos realizando3 sessões semanais, com duração de 3,8±0,4h por sessão ea grande maioria (61%) realizando sessões por fistula arterio-venosa.Os escores pior avaliados foram saúde geral, função sexual,funcionamento físico e efeitos da doença renal. Foi encontrada correlação negativa de idade com o estímulo por parte da equipe de diálise e com saúde geral, sendo esses efeitos mais perceptíveis nos pacientes com maior escolaridade. CONCLUSÃO:A importância de mensurar a qualidade de vida em pacientes idosos em hemodiálise justifica-se pela real possibilidade de atuação multidisciplinar e melhoria de muitos escores, como o da função emocional.

IMPORTANCE: The average life expectancy in Brazil has increased and there has been a growth in the number ofelderly patients with chronic kidney disease. OBJECTIVE: Toevaluate quality of life obtained through the KDQOL (KidneyDisease Quality of Life) questionnaire in elderly patients onhemodialysis, correlating the data with age and socioeconomic status. METHODS: This was a cross-sectional study in patientsaged 61 years and older, with chronic kidney disease on hemodialysis in two centers of São Paulo (Hospital do Servidor Público Estadual de São Paulo Hospital Samaritano). Tomeasure the indicators of quality of life, KDQOL questionnaire(Kidney Disease Quality of Life) was applied one hour prior tothe hemodialysis session. RESULTS: We studied 18 patients with a mean age of 71.3±6.8 years, 61.1% male, 77.7% whites, in hemodialysis treatment for 29.2±27.6 months, eachdoing 3 weekly sessions, lasting 3.8±0.4 h per session andthe vast majority (61%) holding sessions for arterio-venousfistula. The worst scores were assessed general health, sexual function, physical functioning and effects of kidney disease.Age showed a negative correlation with stimulation by dialysisstaff and overall health, these being most noticeable effects in patients with higher education levels. CONCLUSION:The importance of measuring the quality of life in elderlypatients on hemodialysis is justified by the real possibility of multidisciplinary work and improvement of many scores, suchas the emotional function.

Bone marrow mesenchymal stem cells from patients with aplastic anemia maintain functional and immune properties and do not contribute to the pathogenesis of the disease.

Aplastic anemia is a life-threatening bone marrow failure disorder characterized by peripheral pancytopenia and marrow hypoplasia. The majority of cases of aplastic anemia remain idiopathic, although hematopoietic stem cell deficiency and impaired immune responses are hallmarks underlying the bone marrow failure in this condition. Mesenchymal stem/stromal cells constitute an essential component of the bone marrow hematopoietic microenvironment because of their immunomodulatory properties and their ability to support hematopoiesis, and they have been involved in the pathogenesis of several hematologic malignancies. We investigated whether bone marrow mesenchymal stem cells contribute, directly or indirectly, to the pathogenesis of aplastic anemia. We found that mesenchymal stem cell cultures can be established from the bone marrow of aplastic anemia patients and display the same phenotype and differentiation potential as their counterparts from normal bone marrow. Mesenchymal stem cells from aplastic anemia patients support the in vitro homeostasis and the in vivo repopulating function of CD34(+) cells, and maintain their immunosuppressive and anti-inflammatory properties. These data demonstrate that bone marrow mesenchymal stem cells from patients with aplastic anemia do not have impaired functional and immunological properties, suggesting that they do not contribute to the pathogenesis of the disease.

Combined liver-kidney transplantation: experience at a Brazilian university hospital.

BACKGROUND: Combined liver-kidney transplant is a routine procedure in many transplant centers. The increase in its number coincided with the introduction in 2002 of the MELD (Model for End-stage Liver Disease) score for allocation of livers, prioritizing patients with renal dysfunction. Aim : To analyze the experience with combined liver-kidney transplantation in a liver transplant center in Brazil. METHOD: A retrospective review was conducted. All transplants were performed using grafts from deceased donors. RESULTS: Sixteen combined liver-kidney transplantations were performed in the same period, which corresponds to 2.7% and 2.5% of the kidney and liver transplants, respectively. Fourteen patients were male (87.5 %) and two were female (12.5%). The average patients and donors age was 57.3 ± 9.1 and 32.7 ± 13.1, respectively. The MELD score mean was 23.6 ± 3.67. The main cause of liver dysfunction were chronic hepatitis C virus (n=9). As for renal dysfunction, diabetic nephropathy (n=4) was the most frequent. There were six deaths, two of them by severe dysfunction of the liver graft and four by infectious causes. The 1, 3 and 5 years survival rate in patients undergoing liver-kidney transplantations was 68.8%, 57.3% and 57.3%, respectively. CONCLUSION: The survival rates achieved in this series are considered satisfactory and show that this procedure has an acceptable morbidity and survival.

Combined liver-kidney transplantation: experience at a brazilian university hospital / Transplante combinado figado-rim: experiencia de um hospital universitario brasileiro

Background: Combined liver-kidney transplant is a routine procedure in many transplant centers. The increase in its number coincided with the introduction in 2002 of the MELD (Model for End-stage Liver Disease) score for allocation of livers, prioritizing patients with renal dysfunction. Aim : To analyze the experience with combined liver-kidney transplantation in a liver transplant center in Brazil. Method : A retrospective review was conducted. All transplants were performed using grafts from deceased donors. Results : Sixteen combined liver-kidney transplantations were performed in the same period, which corresponds to 2.7% and 2.5% of the kidney and liver transplants, respectively. Fourteen patients were male (87.5 %) and two were female (12.5%). The average patients and donors age was 57.3±9.1 and 32.7±13.1, respectively. The MELD score mean was 23.6±3.67. The main cause of liver dysfunction were chronic hepatitis C virus (n=9). As for renal dysfunction, diabetic nephropathy (n=4) was the most frequent. There were six deaths, two of them by severe dysfunction of the liver graft and four by infectious causes. The 1, 3 and 5 years survival rate in patients undergoing liver-kidney transplantations was 68.8%, 57.3% and 57.3%, respectively. Conclusion : The survival rates achieved in this series are considered satisfactory and show that this procedure has an acceptable morbidity and survival. .

Racional: O transplante combinado fígado-rim é procedimento de rotina em muitos centros de transplante. O aumento no seu número coincidiu com a introdução em 2002 do escore MELD (Model for End-stage Liver Disease) para alocar fígados, priorizando pacientes com disfunção renal. Objetivo : Mostrar a experiência em transplante combinado fígado-rim de um centro de transplante hepático. Método : Foi realizado estudo retrospectivo de pacientes adultos tratados com transplante combinado fígado-rim. Todos foram feitos com enxertos de doadores cadáveres. Resultados : Dezesseis transplantes combinados fígado-rim foram realizados no período, correspondendo a 2,7% e 2,5% dos transplantes de rim e fígado, respectivamente. Quatorze eram homens (87,5%) e duas mulheres (12,5%). A média de idade dos pacientes e doadores foi 57,3±9,1 e 32,7±13,1, respectivamente. A média do escore MELD foi 23.6±3.67. A principal causa de disfunção hepática foi hepatite crônica pelo vírus C (n=9). Para a disfunção renal, nefropatia diabética (n=4) foi a mais frequente. Houve seis mortes, duas por disfunção grave do enxerto hepático e quatro por causas infecciosas. A taxa de sobrevida dos pacientes submetidos ao transplante combinado fígado-rim no 1º, 3º e 5º anos foi 68.8%, 57.3% e 57.3%, respectivamente. Conclusão : As taxas de sobrevida alcançadas nesta série são consideradas satisfatórias e mostram que este procedimento tem morbidade e sobrevida aceitáveis. .

Pollination of rapeseed (Brassica napus) by Africanized honeybees (Hymenoptera: Apidae) on two sowing dates.

In this study, performed in the western part of the state of Paraná, Brazil, two self-fertile hybrid commercial rapeseed genotypes were evaluated for yield components and physiological quality using three pollination tests and spanning two sowing dates. The treatments consisted of combinations of two rapeseed genotypes (Hyola 61 and Hyola 433), three pollination tests (uncovered area, covered area without insects and covered area containing a single colony of Africanized Apis mellifera honeybees) and two sowing dates (May 25th, 2011 and June 25th, 2011). The presence of Africanized honeybees during flowering time increased the productivity of the rapeseed. Losses in the productivity of the hybrids caused by weather conditions unfavorable for rapeseed development were mitigated through cross-pollination performed by the Africanized honeybees. Weather conditions may limit the foraging activity of Africanized honeybees, causing decreased cross-pollination by potential pollinators, especially the Africanized A. mellifera honeybee. The rapeseed hybrids respond differently depending on the sowing date, and the short-cycle Hyola 433 hybrid is the most suitable hybrid for sowing under less favorable weather conditions.

Implementation of a geographic information system (GIS) for the planning of beekeeping in the west region of Paraná.

This study aimed to develop a Geographic Information System (GIS), for storage of information and geographic location of apiaries in eight counties in western Paraná; study the local flora; the land used; and the honey productivity in the harvest of 2010 in two of these areas: Marechal Cândido Rondon and Santa Helena. In order to do so we used the software SPRING, delimiting a radius of action of bees of three kilometers around the apiaries. We interviewed and registered 126 beekeepers with 383 apiaries. By using the images we selected areas with greater and lower overlap of hives in Marechal Cândido Rondon (144 and 44 hives, respectively) and Santa Helena (165 and 40 hives, respectively), in a three kilometers radius, selecting 15 colonies in each area, for the study of the parameters cited. In the multivariate analysis of the grouping, five groups were formed, by their similarity of management, indicating the higher average production in the hives of the most populated area of Santa Helena and lower average production in the most populated of Marechal Cândido Rondon. The grouping of hives, the differences in the production of honey and floristic survey indicated that these differences could be associated with management, floristic and climatic differences recorded in the period of production, in the areas studied.

Obesity short-circuits stemness gene network in human adipose multipotent stem cells.

The discovery of adipose multipotent stem cells has provided new insights to explore cellular mechanisms involved in adipose tissue function. In the present work, we aimed to evaluate how the adipogenic environment influences the stemness of the resident multipotent stem cells. To achieve this goal, human omental multipotent stem cells (hO-MSCs) were isolated, expanded, and characterized in both healthy lean and morbidly obese individuals. We observed decreased cell proliferation, premature senescence, and increased cytokine secretion associated with increasing body mass index of the patients. Consistent with the latter finding, the hO-MSCs derived from patients with morbid obesity lose their multilineage differentiation capacity associated with a dysregulation in the Wnt, Notch, and Sonic Hedgehog signaling pathways. Moreover, microRNAs involved in the regulation of stemness, cell differentiation, and senescence were also up-regulated in obese individuals. Altogether, our data show that obesity causes a general short circuit in the stemness gene network of hO-MSCs.

Cytomegalovirus myopericarditis and hepatitis in an immunocompetent adult: successful treatment with oral valganciclovir.

Primary infection by cytomegalovirus (CMV) commonly occurs subclinically or manifested by a self-limited mononucleosis-like syndrome in immunocompetent subjects. Severe clinical pictures are uncommon. We present a case of acute myopericarditis and hepatitis in a previously healthy 32-year-old man with primary CMV infection, assessed by serology and positive pp65 antigenemia. He was successfully treated with a course of oral valganciclovir therapy, with an immediate clinical response and normalization of laboratory tests. The literature on simultaneous presentation of CMV pericarditis and hepatitis in immunocompetent hosts, as well as the role of oral valganciclovir in this clinical setting, is reviewed.