Use of eltrombopag for patients 65 years old or older with immune thrombocytopenia

Background Eltrombopag is useful for immune thrombocytopenia (ITP). However, results of clinical trials may not accurately mirror clinical practice reality. Here we evaluated eltrombopag for primary and secondary ITP in our ≥65‐year‐old population. Methods A total of 106 primary ITP patients (16 with newly diagnosed ITP, 16 with persistent ITP, and 74 with chronic ITP) and 39 secondary ITP patients (20 with ITP secondary to immune disorders, 7 with ITP secondary to infectious diseases, and 12 with ITP secondary to lymphoproliferative disorders [LPD]) were retrospectively evaluated. Results Median age of our cohort was 76 (interquartile range, IQR, 70‐81) years. 75.9% of patients yielded a platelet response including 66.2% complete responders. Median time to platelet response was 14 (IQR, 8‐21) days. Median time on response was 320 (IQR, 147‐526) days. Sixty‐three adverse events (AEs), mainly grade 1‐2, occurred. The most common were hepatobiliary laboratory abnormalities (HBLAs) and headaches. One transient ischemic attack in a newly diagnosed ITP and two self‐limited pulmonary embolisms in secondary ITP were the only thrombotic events observed. Conclusion Eltrombopag showed efficacy and safety in ITP patients aged ≥65 years with primary and secondary ITP. However, efficacy results in LPD‐ITP were poor. A relatively high number of deaths were observed

The Prostate Specific Membrane Antigen Regulates the Expression of IL-6 and CCL5 in Prostate Tumour Cells by Activating the MAPK Pathways1

The interleukin-6 (IL-6) and the chemokine CCL5 are implicated in the development and progression of several forms of tumours including that of the prostate. The expression of the prostate specific membrane antigen (PSMA) is augmented in high-grade and metastatic tumors. Observations of the clinical behaviour of prostate tumors suggest that the increased secretion of IL-6 and CCL5 and the higher expression of PSMA may be correlated. We hypothesized that PSMA could be endowed with signalling properties and that its stimulation might impact on the regulation of the gene expression of IL-6 and CCL5. We herein demonstrate that the cross-linking of cell surface PSMA with specific antibodies activates the small GTPases RAS and RAC1 and the MAPKs p38 and ERK1/2 in prostate carcinoma LNCaP cells. As downstream effects of the PSMA-fostered RAS-RAC1-MAPK pathway activation we observed a strong induction of NF-κB activation associated with an increased expression of IL-6 and CCL5 genes. Pharmacological blockade with specific inhibitors revealed that both p38 and ERK1/2 participate in the phenomenon, although a major role exerted by p38 was evident. Finally we demonstrate that IL-6 and CCL5 enhanced the proliferative potential of LNCaP cells synergistically and in a dose-dependent manner and that CCL5 functioned by receptor-mediated activation of the STAT5-Cyclin D1 pro-proliferative pathway. The novel functions attributable to PSMA which are described in the present report may have profound influence on the survival and proliferation of prostate tumor cells, accounting for the observation that PSMA overexpression in prostate cancer patients is related to a worse prognosis

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

Influência do butorfanol sobre os períodos de latência e de ação da ropivacaína pela via peridural na ovariossalpingo-histerectomia em cadelas

Avaliaram-se os períodos de latência e de duração do efeito do butorfanol associado à ropivacaína aplicados pela via peridural e a possibilidade de uso dessa associação como protocolo anestésico para realização de ovariossalpingo-histerectomia (OSH) em cadelas. Utilizaram-se 16 cadelas pré-medicadas com acepromazina e midazolam compondo dois grupos: no grupo 1 (n=8) aplicou-se ropivacaína isolada (0,3mL/kg) e no grupo 2 (n=8), butorfanol (0,1mg/kg) e ropivacaína (até o volume de 0,3mL/kg), pela via peridural. Consideraram-se nove momentos (M): M0 - animal sem anestesia, M1 - 15 minutos após medicação pré-anestésica; M2 - 30 minutos após a aplicação peridural; M3, M4 e M5 - correspondentes ao início do procedimento e ao pinçamento dos pedículos esquerdo e direito, respectivamente; M6 - ligadura da cérvix uterina; e M7 e M8 - início da laparorrafia e fim da sutura de pele, respectivamente. Foram avaliados os períodos de latência e ação do bloqueio, além da viabilidade de realização do procedimento cirúrgico por meio do bloqueio efetuado. O que recebeu ropivacaína + butorfanol apresentou sedação pronunciada e permitiu a realização de OSH em 75% dos animais, sem indução anestésica. Não houve diferença entre os grupos quanto aos períodos de latência e duração. A associação do butorfanol à ropivacaína proporcionou bloqueio anestésico compatível com a realização de OSH e período de latência curto, com duração de efeito suficiente para o procedimento cirúrgico.The periods of latency and duration of butorphanol associated with ropivacaine used via epidural, and this combination as anesthetic protocol for carrying out ovariosalpingohysterectomy (OSH) in bitches were evaluated. Sixteen animals pre-medicated with acepromazine and midazolam were used composing two groups that received: 1 (n=8) ropivacaine (0.3mL/kg) and 2 (n=8) butorphanol (0.1mg/kg) and ropivacaine (up to the volume of 0.3ml/kg) via epidural. Nine moments were studied: M1 - 15 minutes after pre-anesthetic medication; M2 - 30 minutes after the epidural medication; M3, M4, and M5 - at the beginning of surgery and at clamping left and right pedicles, respectively; M6 - at ligation of the uterine cervix; and M7 and M8 - at laparorhaphy and end of skin suture, respectively. Periods of latency and blocking the action of random double-covert manner were evaluated as well as the feasibility of carrying out the surgery performed by the blockade. It was observed that the group receiving ropivacaine + butorphanol allowed the execution of OSH in 75% of animals without the need for anesthesia. There was no statistical difference between the periods of latency and duration. It was concluded that the combination of butorphanol to ropivacaine provides, in bitches, block compatible with the implementation of OSH with short period of latency and duration of effect sufficient for the surgical procedure.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Pessoas com úlceras vasculogênicas em atendimento ambulatorial de enfermagem: estudo das variáveis clínicas e sociodemográficas

Objetivou-se analisar características sociodemográficas e clínicas de pessoas com úlceras vasculogênicas e investigar a associação entre estas variáveis. Realizou-se um estudo clínico observacional transversal, em salas de curativo de serviços municipais de saúde, de fevereiro a agosto de 2009. Realizou-se entrevista, exame clínico, aplicação da escala Pressure Ulcer Scale Healing (PUSH) e registro fotográfico das lesões. Participaram 42 indivíduos, com média de 60 anos (± 12), 73,8% do sexo masculino, com lesões únicas (66,7%), decorrentes de alteração da circulação venosa (90,5%), duração de até um ano (55,5%). Houve associação entre o escore da PUSH (p=0,019) e profundidade da lesão (p=0,027) com exercício de atividade ocupacional na atualidade, assim como entre o histórico de tabagismo e o gênero (p=0,049). As características sociodemográficas evidenciadas são semelhantes às de outros, com exceção do gênero masculino, o que indica a necessidade de maiores investigações na população goianiense

Use of eltrombopag for secondary immune thrombocytopenia in clinical practice.

Eltrombopag is a second-line treatment in primary immune thrombocytopenia (ITP). However, its role in secondary ITP is unknown. We evaluated the efficacy and safety of eltrombopag in secondary ITP in daily clinical practice. Eighty-seven secondary ITP patients (46 with ITP secondary to autoimmune syndromes, 23 with ITP secondary to a neoplastic disease subtype: lymphoproliferative disorders [LPDs] and 18 with ITP secondary to viral infections) who had been treated with eltrombopag were retrospectively evaluated. Forty-four patients (38%) had a platelet response, including 40 (35%) with complete responses. Median time to platelet response was 15 days (95% confidence interval, 7-28 days), and was longer in the LPD-ITP group. Platelet response rate was significantly lower in the LPD-ITP than in other groups. However, having achieved response, there were no significant differences between the durable response of the groups. Forty-three patients (49·4%) experienced adverse events (mainly grade 1-2), the commonest being hepatobiliary laboratory abnormalities. There were 10 deaths in this case series, all of which were related to pre-existing medical conditions. In routine clinical practice, eltrombopag is effective and well-tolerated in unselected patients with ITP secondary to both immune and infectious disorders. However, the response rate in LPD-ITP is low

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

ObjectiveTo estimate risk of necrotizing enterocolitis (NEC) for extremely low birth weight (ELBW) infants as a function of preterm formula (PF) and maternal milk intake and calculate the impact of suboptimal feeding on the incidence and costs of NEC.Study designWe used aORs derived from the Glutamine Trial to perform Monte Carlo simulation of a cohort of ELBW infants under current suboptimal feeding practices, compared with a theoretical cohort in which 90% of infants received at least 98% human milk.ResultsNEC incidence among infants receiving ≥98% human milk was 1.3%; 11.1% among infants fed only PF; and 8.2% among infants fed a mixed diet (P = .002). In adjusted models, compared with infants fed predominantly human milk, we found an increased risk of NEC associated with exclusive PF (aOR = 12.1, 95% CI 1.5, 94.2), or a mixed diet (aOR 8.7, 95% CI 1.2-65.2). In Monte Carlo simulation, current feeding of ELBW infants was associated with 928 excess NEC cases and 121 excess deaths annually, compared with a model in which 90% of infants received ≥98% human milk. These models estimated an annual cost of suboptimal feeding of ELBW infants of $27.1 million (CI$24 million, $30.4 million) in direct medical costs,$563 655 (CI $476 191,$599 069) in indirect nonmedical costs, and $1.5 billion (CI$1.3 billion, $1.6 billion) in cost attributable to premature death.ConclusionsAmong ELBW infants, not being fed predominantly human milk is associated with an increased risk of NEC. Efforts to support milk production by mothers of ELBW infants may prevent infant deaths and reduce costs

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

Head and neck cancer surgery during the COVID-19 pandemic: An international, multicenter, observational cohort study

Background: The aims of this study were to provide data on the safety of head and neck cancer surgery currently being undertaken during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This international, observational cohort study comprised 1137 consecutive patients with head and neck cancer undergoing primary surgery with curative intent in 26 countries. Factors associated with severe pulmonary complications in COVID-19–positive patients and infections in the surgical team were determined by univariate analysis. Results: Among the 1137 patients, the commonest sites were the oral cavity (38%) and the thyroid (21%). For oropharynx and larynx tumors, nonsurgical therapy was favored in most cases. There was evidence of surgical de-escalation of neck management and reconstruction. Overall 30-day mortality was 1.2%. Twenty-nine patients (3%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 30 days of surgery; 13 of these patients (44.8%) developed severe respiratory complications, and 3.51 (10.3%) died. There were significant correlations with an advanced tumor stage and admission to critical care. Members of the surgical team tested positive within 30 days of surgery in 40 cases (3%). There were significant associations with operations in which the patients also tested positive for SARS-CoV-2 within 30 days, with a high community incidence of SARS-CoV-2, with screened patients, with oral tumor sites, and with tracheostomy. Conclusions: Head and neck cancer surgery in the COVID-19 era appears safe even when surgery is prolonged and complex. The overlap in COVID-19 between patients and members of the surgical team raises the suspicion of failures in cross-infection measures or the use of personal protective equipment. Lay Summary: Head and neck surgery is safe for patients during the coronavirus disease 2019 pandemic even when it is lengthy and complex. This is significant because concerns over patient safety raised in many guidelines appear not to be reflected by outcomes, even for those who have other serious illnesses or require complex reconstructions. Patients subjected to suboptimal or nonstandard treatments should be carefully followed up to optimize their cancer outcomes. The overlap between patients and surgeons testing positive for severe acute respiratory syndrome coronavirus 2 is notable and emphasizes the need for fastidious cross-infection controls and effective personal protective equipment

Behavioral Deficits at 18-22 Months of Age Are Associated with Early Cerebellar Injury and Cognitive and Language Performance in Children Born Extremely Preterm

To investigate associations in toddlers born extremely preterm (<28 weeks) between neonatal neuroimaging and 18- to 22-month developmental and behavioral outcomes. Cohort analysis from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Trial Neuroimaging and Neurodevelopmental Outcomes Study of infants born extremely preterm. Subjects underwent cranial ultrasonography and near-term magnetic resonance imaging (MRI). At 18-22 months of corrected age, the assessment included the Brief Infant Toddler Social Emotional Assessment (BITSEA) Problem and Competence Scale scores and the Bayley Scales of Infant Development, Third Edition (Bayley-III). The BITSEA Problem Scale assesses dysregulation; the Competence Scale assesses social-emotional competence. We examined associations of Problem and Competence scores and positive screen rates with cranial ultrasonography and near-term MRI. Mean BITSEA and Bayley-III scores were compared using ANOVA and positive screen rates with the χ2 test. We computed correlations between BITSEA and Bayley-III scores. Of the 397 children, positive BITSEA screens were found in 34% for the Problem score and 26% for the Competence score. Presence of lesions on near-term MRI that included cerebellar lesions were significantly associated with lower BITSEA Competence but not with Problem scores; Competence scores were inversely related to the presence/significance of lesions. Positive screens on Competence scores and on both Competence and Problem scores were significantly associated with Bayley-III cognitive and language scores <85 (P < .001). Social–emotional competence contributes to deficits in cognitive and language development. Presence of injury on near-term MRI that includes cerebellar lesions is associated with later social–emotional competence and may be a useful predictor to guide early assessment and intervention. ClinicalTrials.gov: NCT00063063 and NCT00233324