Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial.

OBJECTIVE: To determine whether tocilizumab improves clinical outcomes for patients with severe or critical coronavirus disease 2019 (covid-19). DESIGN: Randomised, open label trial. SETTING: Nine hospitals in Brazil, 8 May to 17 July 2020. PARTICIPANTS: Adults with confirmed covid-19 who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase, or ferritin). The data monitoring committee recommended stopping the trial early, after 129 patients had been enrolled, because of an increased number of deaths at 15 days in the tocilizumab group. INTERVENTIONS: Tocilizumab (single intravenous infusion of 8 mg/kg) plus standard care (n=65) versus standard care alone (n=64). MAIN OUTCOME MEASURE: The primary outcome, clinical status measured at 15 days using a seven level ordinal scale, was analysed as a composite of death or mechanical ventilation because the assumption of odds proportionality was not met. RESULTS: A total of 129 patients were enrolled (mean age 57 (SD 14) years; 68% men) and all completed follow-up. All patients in the tocilizumab group and two in the standard care group received tocilizumab. 18 of 65 (28%) patients in the tocilizumab group and 13 of 64 (20%) in the standard care group were receiving mechanical ventilation or died at day 15 (odds ratio 1.54, 95% confidence interval 0.66 to 3.66; P=0.32). Death at 15 days occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group (odds ratio 6.42, 95% confidence interval 1.59 to 43.2). Adverse events were reported in 29 of 67 (43%) patients who received tocilizumab and 21 of 62 (34%) who did not receive tocilizumab. CONCLUSIONS: In patients with severe or critical covid-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT04403685.

Degree of knowledge of health care professionals about pain management and use of opioids in pediatrics.

OBJECTIVE: To evaluate the degree of knowledge about pain management and opioids use by professionals working at three pediatric units. DESIGN: This is a cross-sectional study. SETTING: This study was carried out at three pediatric units (pediatrics, intensive care unit, and oncology) of Hospital de Clínicas de Porto Alegre, which is a university hospital located in southern Brazil. SUBJECT: The subjects of this study include physicians, pharmacists, physiotherapists, nurses, nursing technicians, and nursing assistants. METHODS: Cross-sectional study carried out in a university hospital in southern Brazil. A self-applicable semi-structured questionnaire was handed out to 182 professionals from December 2011 to March 2012. RESULTS: The response rate was 67% (122); the average percentage of correct answers was 63.2 ± 1.4%. The most frequent errors were: an opioid must not be used if the cause of pain is unknown (47%; 54/115); patients often develop respiratory depression (42.3%; 22/52); and confusion about symptoms of withdrawal, tolerance, and dependency syndromes (81.9%; 95/116). Only 8.8% (10/114) reported the use of pain scales to identify pain in children. The most often cited hindrance to control pain was the difficulty to measure and spot pain in pediatric patients. Finally, 50.8% (62/122) of them did not have any previous training in pain management. CONCLUSIONS: Problems in the processes of pain identification, measurement, and treatment have been found. Results suggest that there is a need for both an investment in continuing education of professionals and the development of protocols to optimize the analgesic therapy, thus preventing increased child suffering.

The effect of bone marrow transplantation on oxidative stress in X-linked adrenoleukodystrophy.

Oxidative stress plays an important role in the pathophysiology of neurodegenerative diseases, including X-linked adrenoleukodystrophy (X-ALD). In the present work, we evaluated lipid (malondialdehyde [MDA] content) and protein (sulfhydryl and carbonyl contents) oxidative damage parameters in plasma from X-ALD patients before and after bone marrow transplant (BMT), in order to verify if this treatment is capable to alter the oxidative parameters studied. We also evaluated the plasma concentration of hexacosanoic acid (C26:0) from X-ALD patients and correlated it with the oxidative damage parameters investigated. We observed that MDA content was significantly increased in plasma of X-ALD patients before BMT and after BMT when compared to controls, and that it was significantly reduced in plasma of X-ALD after BMT when compared to the before BMT group. These results indicate that lipid peroxidation is stimulated in X-ALD patients but there is a significant reduction of lipid peroxidation after BMT. Next, we observed a significant reduction of sulfhydryl content in plasma of X-ALD patients before BMT compared to controls indicating protein oxidative damage and that this measurement was increased in these patients after BMT as compared to before BMT. We found no significant differences in plasma carbonyl content in X-ALD patients before and after BMT as compared to controls. However, we observed a significant reduction in this parameter in X-ALD patients after BMT compared to before BMT. Finally, C26:0 plasma concentration was significantly reduced in X-ALD patients after BMT when compared to before BMT. We found no significant correlations between MDA and carbonyl values with C26:0 levels of the patients before BMT and after BMT, but a significant inverse correlation between sulfhydryl content and C26:0 levels was detected. In conclusion, the present study reinforces the hypothesis that lipid peroxidation and protein damage are induced in plasma of X-ALD patients and, in addition, demonstrates that BMT treatment is capable to reduce this pathogenic process. Taken together, the data obtained from plasma of X-ALD patients before and after BMT showing induction and protection, respectively, of oxidative stress, allowed to suggest that BMT, when well succeeded and under the recommendations, is effective to reduce C26:0 plasma levels and the increased lipid and protein oxidative damage in X-ALD.

Safety of general anesthesia for lumbar puncture and bone marrow aspirate/biopsy in pediatric oncology patients.

INTRODUCTION: Painful short duration procedures such as bone marrow aspiration/biopsy and the lumbar puncture with or without intrathecal chemotherapy are frequently performed during the treatment of children with cancer. This study evaluated the frequency and severity of complications of bone marrow aspiration biopsy and lumbar puncture/intrathecal chemotherapy under general anesthesia. PATIENTS AND METHODS: A prospective observational study was performed from November 2003 to August 2005. Patients with cancer younger than 21 years old, receiving treatment at the Pediatric Oncology Unity of Hospital de Clínicas de Porto Alegre, undergoing diagnostic and/or therapeutic short duration procedures carried out under general anesthesia in the outpatient surgery unit. RESULTS: One hundred and thirty-seven patients were submitted to 423 procedures under general anesthesia. There were 61% boys, mean age of 7.5 years (0.2 to 21) and ASA II 98%. Eighty seven percent of the procedures were carried out in patients with leukemia or lymphoma. The majority of the procedures had no adverse events during intraoperative and postoperative periods. No procedure had to be suspended after it had begun. One patient had lumbar pain after the procedure and was admitted to the ward with suspected subdural bleeding, but this was not confirmed. No patient needed cardiopulmonary reanimation or treatment in the intensive care unit. CONCLUSIONS: General anesthesia for short duration painful procedures in children undergoing treatment for malignancies is safe when carried out by trained professionals in outpatient clinical surgery unit.

Influence of low-energy laser in the prevention of oral mucositis in children with cancer receiving chemotherapy.

BACKGROUND: This study assessed the use of low-energy laser in the prevention or reduction of the severity of oral mucositis. PROCEDURE: A randomized clinical trial was carried out. Patients from 3 to 18 years of age treated with chemotherapy or hematopoietic stem-cell transplantation between May, 2003 and February, 2005 were eligible. The intervention group received laser application for 5 days following the start of chemotherapy. The grade of oral mucositis was assessed by the WHO per NCI-CTC common toxicity criteria and the assessments were made on days 1, 8 and 15 by a trained examiner blind to the intervention. RESULTS: Sixty patients were evaluable for analysis; thirty-nine (65%) were males, 35 (58%) patients had a diagnosis of leukemia or lymphoma, and 25 (42%) had solid tumors. The mean age was 8.7 +/- 4.3 years. Twenty-nine patients were randomized in the laser group and 31 in the control group. On day 1, no patients presented with mucositis. On day 8, of 20 patients (36%) who developed mucositis, 13 of them were from the laser group and 7 from the control group. On day 15, of 24 patients (41%) who developed mucositis, 13 of them were from the laser group and 11 from the control group. There was no significant difference between groups concerning the grades of mucositis on day 8 (P = 0.234) or on day 15 (P = 0.208). CONCLUSIONS: This study showed no evidence of benefit from the prophylactic use of low-energy laser in children and adolescents with cancer treated with chemotherapy when optimal dental and oral care was provided.

Estudo retrospectivo do tratamento de leucemia mielóide aguda com o transplante de medula óssea: a experiência brasileira / Retrospective study of stem cell transplantation for acute myeloid leukemia (AML): the Brazilian experience

Dados do Registro Internacional de Transplante de Medula Óssea, International Bone Marrow Transplant Registry (IBMTR) contribuem para o progresso do transplante de medula óssea (TMO) em todo o mundo. Neste artigo relatamos a experiência brasileira em leucemia mielóide aguda e comparamos os resultados do TMO com os dados internacionais. Foi realizado um estudo retrospectivo com dados de tratamento de LMA com o TMO de 16 instituições brasileiras. A análise estatística dos transplantes da modalidade autogênica (TMO auto) e alogênica (TMO alo) foi realizada com o método de Kaplan-Meier e log-rank. Todos os valores de p foram bicaudados. Foram avaliados os dados de 731 pacientes (205 TMO auto e 526 TMO alo). A mediana de sobrevida global dos pacientes submetidos ao TMO auto foi superior à dos submetidos ao TMO alo (1.035 vs 466 dias, p=0,0012). A origem das células-tronco (OCT) no TMO alo em 73% dos pacientes foi de medula óssea (CTMO), em 23% de sangue periférico (CTSP) e em 4% de cordão umbilical. No TMO auto, a OCT foi 63% de CTSP, 22% CTMO e 15% de ambas as fontes. A OCT não teve impacto na sobrevida global (SG). Não houve diferença na SG também entre os pacientes segundo a classificação FAB no TMO alo, mas os pacientes com LMA M3 com o TMO auto tiveram SG longa. Como esperado, a principal causa de óbito entre os pacientes do TMO auto foi relacionada à recidiva de doença (60%), enquanto no TMO alo as principais causas foram a doença enxerto versus hospedeiro e infecções (38%). Em ambos os grupos foi observada SG mais longa nos pacientes tratados em primeira remissão completa (1RC) quando comparados aos de segunda remissão (2RC) e outras fases (p<0,0001), tendo sido observado SG mais longa nos pacientes com LMA de novo quando comparados aos de LMA secundária. No TMO alo a SG foi mais longa com doadores aparentados (538 versus 93 dias p=0,001). A SG foi mais curta nos pacientes que utilizaram irradiação corpórea total no regime de condicionamento (p=0,0001)...

Data from the International Bone Marrow Transplant Registry (IBMTR) contribute for the improvement of Bone Marrow Transplant (BMT) worldwide. We studied the Brazilian experience in BMT for AML to compare this with international data. We performed a retrospective study by sending questionnaires to 16 BMT centers regarding clinical and treatment variables. Statistical analyses concerning autologous BMT (autoBMT) and allogeneic BMT (alloBMT) were performed using the Kaplan-Meier method and the log-rank test. All p-values were two-tailed. We collected data from 731 patients (205 autoBMT and 526 alloBMT). Median overall survival (OS) for autoBMT patients was longer than alloBMT patients (1035 vs. 466 days, p=0.0012). AlloBMT stem cell source (SCS): 73% bone marrow stem cell (BMSC), 23% peripheral blood stem cells (PBSC) and 4% umbilical cord blood. Among the autoBMT patients, the SCS was 63% PBSC, 22% BMSC and 15% both. The SCS did not impact on OS. There was no difference in OS between different FAB classifications in the alloBMT group, but in the autoBMT the M3 patients had longer survival. As expected, the main cause of mortality among autoBMT patients was related to disease relapse (60%), while in the alloBMT, to infection (38%). In both groups we found longer OS in first complete remission (1CR) compared to second (2CR) and other (p<0.0001), and longer OS in de novo AML than in secondary...

[Clinical features in osteosarcoma and prognostic implications]. / Características clínicas do osteossarcoma na infância e sua influência no prognóstico.

OBJECTIVE: To identify the clinical features in osteosarcoma and to investigate their influence on the prognosis of children and adolescents presenting this disease. MATERIAL AND METHODS: The records of children and adolescents with osteosarcoma treated by the Bone Tumors Group of the state of Rio Grande do Sul, Brazil, between January 1992 and December 2001 were reviewed. RESULTS: Fifty consecutive patients were included in this study. Mean age at diagnosis was 13 years (3-22); 68% of the patients were males. The primary site of disease was the femur in 50% of the patients, tibia in 30%, pelvis in 4%, humerus in 10%, fibula in 2% and other sites in 4%. Nineteen patients presented metastases at diagnosis (38%). All patients received chemotherapy and were treated with three different schemes. As for surgical treatment, 26 patients (52%) had an amputation and 17 (34%) received conservative surgery. Serum lactic dehydrogenase > 1,000 UI/ml (p = 0.0159, log rank), tumor necrosis < 90% and presence of metastases had a negative influence on prognosis. The overall 5-year survival was of 33.2+/-7.2% with mean follow-up of 36 months (6-126). Event-free survival was 29.7+/-7%. The 5-year event-free survival in non-metastatic patients was 45+/-10.7%, and zero in metastatic patients (follow-up of 78.4 and 18.7 months, respectively). Only two out of 19 metastatic patients are alive and free of disease at 18 and 30 months respectively. CONCLUSION: Metastatic disease at diagnosis, serum levels of serum lactic dehydrogenase > 1,000 UI/ml and tumor necrosis < 90% are predictors of unfavorable prognosis. The excessively high incidence of metastatic patients may suggest the presence of an aggressive pattern of disease in our population, or may indicate late diagnosis.