Functional Divergence in Solute Permeability between Ray-Finned Fish-Specific Paralogs of aqp10.

Aquaporin (Aqp) 10 is a member of the aquaglyceroporin subfamily of water channels, and human Aqp10 is permeable to solutes such as glycerol, urea, and boric acid. Tetrapods have a single aqp10 gene, whereas ray-finned fishes have paralogs of this gene through tandem duplication, whole-genome duplication, and subsequent deletion. A previous study on Aqps in the Japanese pufferfish Takifugu rubripes showed that one pufferfish paralog, Aqp10.2b, was permeable to water and glycerol, but not to urea and boric acid. To understand the functional differences of Aqp10s between humans and pufferfish from an evolutionary perspective, we analyzed Aqp10s from an amphibian (Xenopus laevis) and a lobe-finned fish (Protopterus annectens) and Aqp10.1 and Aqp10.2 from several ray-finned fishes (Polypterus senegalus, Lepisosteus oculatus, Danio rerio, and Clupea pallasii). The expression of tetrapod and lobe-finned fish Aqp10s and Aqp10.1-derived Aqps in ray-finned fishes in Xenopus oocytes increased the membrane permeabilities to water, glycerol, urea, and boric acid. In contrast, Aqp10.2-derived Aqps in ray-finned fishes increased water and glycerol permeabilities, whereas those of urea and boric acid were much weaker than those of Aqp10.1-derived Aqps. These results indicate that water, glycerol, urea, and boric acid permeabilities are plesiomorphic activities of Aqp10s and that the ray-finned fish-specific Aqp10.2 paralogs have secondarily reduced or lost urea and boric acid permeability.

Polycystic Liver Disease: Pathophysiology, Diagnosis and Treatment.

Polycystic liver disease (PLD) is a clinical condition characterized by the presence of more than 10 cysts in the liver. It is a rare disease Of genetic etiology that presents as an isolated disease or assoc\iated with polycystic kidney disease. Ductal plate malformation, ciliary dysfunction, and changes in cell signaling are the main factors involved in its pathogenesis. Most patients with PLD are asymptomatic, but in 2-5% of cases the disease has disabling symptoms and a significant reduction in quality of life. The diagnosis is based on family history of hepatic and/or renal polycystic disease, clinical manifestations, patient age, and polycystic liver phenotype shown on imaging examinations. PLD treatment has evolved considerably in the last decades. Somatostatin analogues hold promise in controlling disease progression, but liver transplantation remains a unique curative treatment modality.

Effectiveness of Open Fenestration for Autosomal Dominant Polycystic Liver Disease.

Autosomal dominant polycystic liver disease (ADPLD) is a rare disease with variable clinical presentations, characterized by cystic enlargement of the liver. The diagnosis is made based on family history, patient's age, and liver phenotype and is confirmed by imaging tests. The treatment aims to reduce symptoms caused by the increased liver volume and can be performed by aspiration with sclerotherapy, fenestration, and liver resection. Although ADPLD is a rare disease, it is an important differential diagnosis of cystic diseases such as polycystic kidney disease; therefore, the aim of this article was to present the diagnostic and therapeutic approach of a case of ADPLD and conducting a literature review. This is the case of a 32-year-old male patient, who was hospitalized due to abdominal pain, hepatomegaly, lack of appetite, and weight loss. Imaging propaedeutics showed a significant increase in the liver volume due to hepatic cysts. After a multidisciplinary evaluation, given the clinical changes and the location of the hepatic cysts, fenestration was performed by laparotomy. The postoperative period was uneventful. The treatment was efficient in promoting symptomatic relief and improving the quality of life in this patient. Case reports on this disease are quite limited in the currently available literature, and there are gaps in knowledge with regard to the diagnosis and management of ADPLD. The importance of this article is that it will highlight the limitations in treatment options and allow physicians to make a more informed decision when diagnosing and treating a patient with ADPLD in the future.

Placental Mammals Acquired Functional Sequences in NRK for Regulating the CK2-PTEN-AKT Pathway and Placental Cell Proliferation.

The molecular evolution processes underlying the acquisition of the placenta in eutherian ancestors are not fully understood. Mouse NCK-interacting kinase (NIK)-related kinase (NRK) is expressed highly in the placenta and plays a role in preventing placental hyperplasia. Here, we show the molecular evolution of NRK, which confers its function for inhibiting placental cell proliferation. Comparative genome analysis identified NRK orthologs across vertebrates, which share the kinase and citron homology (CNH) domains. Evolutionary analysis revealed that NRK underwent extensive amino acid substitutions in the ancestor of placental mammals and has been since conserved. Biochemical analysis of mouse NRK revealed that the CNH domain binds to phospholipids, and a region in NRK binds to and inhibits casein kinase-2 (CK2), which we named the CK2-inhibitory region (CIR). Cell culture experiments suggest the following: 1) Mouse NRK is localized at the plasma membrane via the CNH domain, where the CIR inhibits CK2. 2) This mitigates CK2-dependent phosphorylation and inhibition of PTEN and 3) leads to the inhibition of AKT signaling and cell proliferation. Nrk deficiency increased phosphorylation levels of PTEN and AKT in mouse placenta, supporting our hypothesis. Unlike mouse NRK, chicken NRK did not bind to phospholipids and CK2, decrease phosphorylation of AKT, or inhibit cell proliferation. Both the CNH domain and CIR have evolved under purifying selection in placental mammals. Taken together, our study suggests that placental mammals acquired the phospholipid-binding CNH domain and CIR in NRK for regulating the CK2-PTEN-AKT pathway and placental cell proliferation.

Pulmonary Tuberculosis After Therapy with Anti-Tumor Necrosis Factor (TNF) for Crohn Disease: A Case Report.

BACKGROUND Adalimumab is a biological anti-tumor necrosis factor (TNF) agent which induces and maintains remission in patients with moderate-to-severe Crohn disease (CD). An adverse effect of its use is reactivation of latent infections, such as tuberculosis (TB). TB is caused by Mycobacterium tuberculosis and continues to be an important public health problem in some developing countries, such as Brazil. The present report describes the case of a patient with CD who developed pulmonary TB while receiving adalimumab therapy. CASE REPORT A 38-year-old penitentiary worker presented with colonic CD that was intolerant to azathioprine and was started on adalimumab. After 3 months, he experienced coughing, fever, and weight loss, and was diagnosed with pulmonary TB. A chest X-ray and tuberculin skin test performed before he started taking adalimumab were negative for latent TB. The patient was treated for 9 months to cure his infection. The use of adalimumab was suspended while the TB was investigated and he took mesalazine to achieve clinical and endoscopic remission of CD. CONCLUSIONS Adequate screening and chemoprophylaxis for latent TB are indicated in patients at high risk of infection. In patients with inflammatory bowel disease, after anti-TNF therapy is started, strict monitoring is required so that opportunistic infections can be detected early and morbidity and mortality reduced in this population.

Comparisons of plasma aldosterone and renin data between an automated chemiluminescent immunoanalyzer and conventional radioimmunoassays in the screening and diagnosis of primary aldosteronism.

Determining values of plasma renin activity (PRA) or plasma active renin concentration (ARC), plasma aldosterone concentration (PAC), and aldosterone-to-renin ratio (ARR) is essential to diagnose primary aldosteronism (PA), but it takes several days with conventional radioimmunoassays (RIAs). Chemiluminescent enzyme immunoassays for PAC and ARC using the Accuraseed® immunoanalyzer facilitated the determination, but relations between Accuraseed® immunoanalyzer-based and RIA-based values in samples of PA confirmatory tests and adrenal venous sampling remained to be elucidated. We addressed this issue in the present study. This is a prospective, cross-sectional study. ARC and PAC values were measured by the Accuraseed® immunoanalyzer in samples, in which PRA and PAC values had been measured by the PRA-FR® RIA and SPAC®-S Aldosterone kits, respectively. The relations between Accuraseed® immunoanalyzer-based and RIA-based values were investigated with regression analyses. The optimal cutoff of Accuraseed® immunoanalyzer-based ARR for PA screening was determined by the receiver operating characteristic analysis. After log-log transformations, linear relations with high coefficients of determination were observed between Accuraseed® immunoanalyzer-based and RIA-based data of renin and aldosterone. Following the PA guidelines of Japan Endocrine Society, Accuraseed® immunoanalyzer-based cutoffs were calculated from the regression equations: the basal PAC for PA screening >12 ng/dL, PAC for the saline infusion test >8.2 ng/dL, ARC for the furosemide-upright test <15 pg/mL, and ARR for the captopril challenge test >3.09 ng/dL per pg/mL. The optimal cutoff of Accuraseed® immunoanalyzer-based ARR for PA screening was >2.43 ng/dL over pg/mL not to overlook bilateral PA patients. The present study provided conversion formulas between Accuraseed® immunoanalyzer-based and RIA-based values of renin, aldosterone, and ARR, not only in basal samples but also in samples of PA confirmatory tests and adrenal venous sampling. Although validation studies are awaited, the present study will become priming water of harmonization of renin and aldosterone immunoassays.

Dosing Optimization of Ampicillin-Sulbactam Based on Cystatin C in Elderly Patients with Pneumonia.

Ampicillin-sulbactam is a first-line therapy for pneumonia and is mainly excreted by the kidney. It is important to optimize the dose and dosing interval of ampicillin-sulbactam because in patients with decreased renal function and low skeletal muscle mass, such as the elderly, excess drug may burden renal function. In this study, we evaluated indices of renal function and optimized the dose and dosing interval of ampicillin-sulbactam based on pharmacokinetics (PK) and pharmacodynamics theory in elderly patients. The serum concentrations of ampicillin and sulbactam were measured by HPLC, and PK parameters were calculated. Correlations between the clearance of ampicillin or sulbactam and renal function were evaluated, and dosing optimization was calculated based on PK parameters. The PK parameters of ampicillin were CL = 6.5 ± 4.0 L/h, Vd = 19.3 ± 0.2 L, Ke = 0.4 ± 0.2, and t1/2 = 2.7 ± 1.6 h. The most correlated renal function index was estimated glomerular filtration rate (eGFRcys-c) calculated by serum cystatin-c (r = 0.7374, correlation formula; CL of ampicillin = 0.1937 × eGFRcys-c-0.6726). Based on this formula, we calculated the clearance of ampicillin and developed dosing regimens for the elderly. Serum cystatin-c concentration is an ideal index to optimize ampicillin-sulbactam antimicrobial therapy in elderly patients with pneumonia.

Mixed and disseminated paracoccidioidomycosis after liver transplantation: Case report.

Paracoccidioidomycosis (PCM) is a systemic granulomatous fungal infection rarely associated with solid organ transplantation. We report the second case of PCM in an adult after liver transplantation. A 47-year-old woman who had undergone liver transplantation was hospitalized for flu-like symptoms and multiple erythematous ulcerated skin papules. There was lymphadenopathy, pulmonary compromise, and quickly progression to septic shock. PCM was confirmed by skin biopsy and serologic tests, and a satisfactory response to amphotericin B was achieved.

Extraction of corn germ oil with supercritical CO2 and cosolvents.

The aim of this work was to investigate corn germ oil extraction using supercritical CO2 and cosolvents addition (hexane, acetone and ethanol). The effects of temperature (45-85 °C) and pressure (15-25 MPa) on the extract yield were evaluated for the tests conducted only with supercritical CO2. The addition of cosolvents to supercritical CO2 was also examined at 25 MPa and 60 °C. The conventional Soxhlet extraction with different organic solvents was also performed for comparison purposes. The results of extraction with supercritical fluid showed that the yields increased with pressure at each temperature, but decreased with temperature increase. Mathematical modeling was applied to describe extraction curves, with very good fits. The addition of cosolvents led to higher yield, with a maximum yield of 13.81% using ethanol. The analysis of fatty acids profile did not present significant differences among the evaluated methods. On the other hand, the antioxidant activity of the extracts obtained by supercritical CO2 extraction was higher than the ones verified for the extracts collected after conventional Soxhlet extraction. Therefore, the use of supercritical CO2 extraction could be an interesting way to preserve antioxidant properties of this oil in order to use it for pharmaceutical purposes.

Atendimento às vítimas de acidentes de trânsito pelo serviço pré-hospitalar: estudo transversal / Assistance to victims of traffic accidents through the prehospital service: a cross-sectional study / Atención del servicio pre-hospitalario a las víctimas de accidentes de tráfico: estudio transversal

OBJETIVO: avaliar o perfil dos atendimentos de acidentes de trânsito realizados pelo Serviço de Atendimento Móvel de Urgência (SAMU) de uma cidade da região Sul do Brasil. MÉTODO: estudo transversal, retrospectivo e quantitativo, desenvolvido com dados de 342 vítimas de acidentes de trânsito atendidos pelo SAMU no ano de 2015, analisados estatisticamente. RESULTADOS: entre as vítimas, prevaleceram os homens (71,3%); com idades de 15 a 44 anos (65,7%); e que se envolveram em acidentes de automóveis com motos (29,2%). As lesões mais frequentes foram as escoriações (48,2%) e as corto-contusas (33,0%); e as que acometeram múltiplos locais do corpo (50,6%) e os membros inferiores e superiores (85,1%). O suporte avançado atendeu 75,1% das ocorrências. CONCLUSÃO: constatou-se associação estatística entre os mecanismos do acidente com os grupos etários, com as fraturas abertas e fechadas e com as lesões nos membros superiores e inferiores

AIM: to evaluate the profile of traffic accident assistance performed by the Mobile Emergency Service (Serviço de Atendimento Móvel de Urgência ­ SAMU) of a city in the South of Brazil. METHOD: a cross-sectional, retrospective and quantitative study, developed with data from 342 victims of traffic accidents attended by SAMU in 2015, statistically analyzed. RESULTS: among the victims, men prevailed (71.3%); ages ranged from 15 to 44 years (65.7%); and who were involved in automobile accidents with motorcycles (29.2%). The most frequent lesions were bruises (48.2%) and short-bruises (33.0%); and those involving multiple body sites (50.6%) and lower and upper limbs (85.1%). Advanced support accounted for 75.1% of incidents. CONCLUSION: it was found a statistical association between the mechanisms of accident with age groups, with open and closed fractures and lesions in the upper and lower limbs

OBJETIVO: evaluar el perfil de la atención a los accidentes de tráfico realizada por el Servicio de Atención Móvil de Urgencia (SAMU) de una ciudad de la región Sur de Brasil MÉTODO: estudio transversal, retrospectivo y cuantitativo, desarrollado con los datos de 342 víctimas de accidentes de tráfico atendidos por el SAMU en el 2015, analizados estadísticamente. RESULTADOS: entre las víctimas, prevalecieron los hombres (71,3%); con edades de 15 a 44 años (65,7%); involucrados en accidentes de motos (29,2%). Las lesiones más frecuentes fueron las laceraciones (48,2%) y las cortopunzantes (33,0%); y las que ocurren en varios lugares del cuerpo (50,6%) y los miembros inferiores e superiores (85,1%). El soporte avanzado atendió 75,1% de las ocurrencias. CONCLUSIÓN: se constató que hay asociación estadística entre los mecanismos del accidente con los grupos etarios, con las fracturas abiertas y cerradas y con las lesiones en los miembros superiores e inferiores

Conventional and volatile salts as precipitating agents for recombinant antiviral protein / Sais convencionais e voláteis como agentes de precipitação para proteína recombinante com ação antiviral

Recombinant proteins expressed in cell culture have been shown to be relevant in the biopharmaceutical production focusing human health. The current work investigated the precipitation process of recAVLOEc protein, synthesized by E. coli BL21 (DE3) pLysS cells. The system is used for the AVLO expression that shown antiviral activity and it was found in the hemolymph of Lonomia obliqua caterpillar. The precipitation was conducted by the use of conventional salts (ammonium sulfate and sodium sulfate) and the volatile ammonium carbamate salt. Initially, the precipitated protein obtained from bacterial lysate was added to L929 cells to evaluate the cytotoxic effect; and besides Vero cells were infected with measles virus to verify the antiviral action of the precipitated recombinant protein. Toxic effect on the culture of L929 cells was observed for the precipitate obtained by the use of ammonium sulfate and sodium sulfate. In addition, tests in L929 cell cultures infected with EMC virus showed that samples of precipitated protein by salts did not show antiviral action. In Vero cell cultures, the precipitated protein by sodium sulfate showed antiviral action for measles virus.

Proteínas recombinantes expressas em culturas celulares têm se mostrado importantes na produção de fármacos de interesse para a saúde humana. Este estudo investigou a precipitação da proteína recAVLOEc, sintetizada por células de E. coli BL21 (DE3) pLysS, utilizadas como sistema de expressão da AVLO, proteína com atividade antiviral, originalmente encontrada na hemolinfa da lagarta Lonomia obliqua. A precipitação foi conduzida por meio do uso de sais convencionais (sulfato de amônio e de sódio) e do sal volátil carbamato de amônio. Inicialmente o precipitado proteico obtido do lisado bacteriano foi administrado em culturas de células L929 para avaliar o efeito citotóxico e posteriormente em células Vero infectadas com o vírus do sarampo, para a verificação da ação antiviral. Um efeito tóxico em culturas de L929 foi observado para os precipitados obtidos pelo uso de sulfato de amônio e de sódio. Testes em culturas de L929 infectadas com o vírus EMC foram também efetuados e as amostras de proteínas precipitadas com os sais convencionais e o sal volátil não resultaram em ação antiviral. Em culturas de células Vero, o uso do sulfato de sódio como agente de precipitação das proteínas contidas no lisado bacteriano resultou em ação antiviral para o sarampo.

The pharmacokinetics of ampicillin-sulbactam in anuric patients: dosing optimization for prophylaxis during cardiovascular surgery.

Background The administration of antibiotic prophylaxis during cardiothoracic surgery can reduce the rate of surgical site infections. Trials of cardiothoracic antibiotic prophylaxis have found it to be beneficial in preventing postoperative wound infections. Objective To determine the more appropriate timing of repeated doses of ampicillin-sulbactam to maintain adequate antibiotic concentrations during cardiovascular surgery in anuric patients. Method Five adult anuric dialysis patients who received ampicillin-sulbactam during cardiovascular surgery at Kagoshima University Hospital, the total plasma concentrations of ampicillin and sulbactam were monitored after ampicillin (1 g)-sulbactam (0.5 g) administration. Pharmacokinetic parameters were estimated and used to predict the free plasma concentrations of ampicillin and sulbactam. Results The mean values for the volume of distribution, total clearance, elimination rate constant and the elimination half-life for ampicillin were 8.9 ± 2.4 L, 1.69 ± 0.93 L/h, 0.180 ± 0.059 h(-1) and 4.23 ± 1.48 h, respectively. The pharmacokinetic parameters were similar to those of sulbactam. When ampicillin (1 g)-sulbactam (0.5 g) was intravenously administered at 8, 12 and 24 h intervals, the predicted free trough plasma concentrations of ampicillin were 28.72, 12.06 and 1.25 µg/mL, respectively. Conclusion We suggest that ampicillin (1 g)-sulbactam (0.5 g) should be intravenously administered every 12 h in order to maintain a free ampicillin concentration of more than 12 µg/mL in anuric patients during cardiovascular surgery.

Pharmacokinetics of Prophylactic Ampicillin-Sulbactam and Dosing Optimization in Patients Undergoing Cardiovascular Surgery with Cardiopulmonary Bypass.

UNLABELLED: Antibiotic concentrations must be maintained at an adequate level throughout cardiovascular surgery to prevent surgical site infection. This study aimed to determine the most appropriate timing for intraoperative repeated dosing of ampicillin-sulbactam, a commonly used antibiotic prophylaxis regimen, to maintain adequate concentrations throughout the course of cardiovascular surgery with cardiopulmonary bypass (CPB). The total plasma concentrations of ampicillin were monitored in 8 patients after ampicillin (1 g)-sulbactam (0.5 g) administration via initial intravenous infusion and subsequent CPB priming. Pharmacokinetic parameters were estimated and used to predict the free plasma concentrations of ampicillin. The mean values for the volume of distribution, elimination rate constant, elimination half-life, and total clearance of ampicillin were 15.8±4.1 L, 0.505±0.186 h(-1), 1.52±0.47 h, and 7.72±2.72 L/h, respectively. When ampicillin (1 g)-sulbactam (0.5 g) was intravenously administered every 3, 4, 6, and 12 h after the start of CPB, the predicted free trough plasma concentrations of ampicillin were 15.20, 8.25, 2.74, and 0.13 µg/mL, respectively. Therefore, an every-6-h regimen was needed to maintain the free ampicillin concentration at more than 2 µg/mL during cardiovascular surgery with CPB. We suggest that the dose and dosing interval for ampicillin-sulbactam should be adjusted to optimize the efficacy and safety of treatment, according to the minimum inhibitory concentrations for methicillin-sensitive Staphylococcus aureus isolates at each institution. REGISTRATION NUMBER: UMIN000007356.

Trough level monitoring of intravenous busulfan to estimate the area under the plasma drug concentration-time curve in pediatric hematopoietic stem cell transplant recipients.

Optimizing systemic busulfan exposure, the area under the concentration-time curve (AUC), improves the outcomes for hematopoietic stem cell transplantation (HSCT). The AUC is conventionally calculated using six plasma concentrations (AUC(0-∞)) drawn after the first of 16 intravenous busulfan doses given as a 2-h infusion every 6 h. The aim of the present study was to develop limited sampling strategies using three or fewer busulfan concentrations to reliably calculate AUC(0-∞) in patients undergoing HSCT. We investigated the pharmacokinetics of busulfan 46 times in 29 pediatric patients receiving intravenous busulfan. Limited sampling strategies using one, two, or three plasma busulfan concentrations were developed by multiple linear regression that showed excellent agreement with AUC(0-∞). In single-point sampling strategies, the AUC(0-∞) predicted based on C(6) (trough level: busulfan plasma concentration 6 h after the start of the infusion) was significantly correlated with, and not statistically different from, actual values as follows: AUC(0-∞) = 2556.5 C6 + 320.9 (r(2) = 0.929, P < 0.0001, mean bias 0.282 %, precision 7.91 %). In contrast, the predicted AUCs derived from the other sampling single points did not meet the criteria. The trough level well correlated with actual AUC(0-∞), suggesting that this time-point is acceptable for busulfan monitoring.

Impacto das infecções relacionadas à assistência à saúde em pacientes acometidos por trauma / Impact of health care-related infections in trauma patients

As infecções relacionadas à assistência hospitalar impactam negativamente a saúde de pacientes hospitalizados, e refletem em elevados índices de morbimortalidade. Este estudo epidemiológico descritivo teve como objetivo caracterizar as infecções e avaliar seu impacto na saúde de pacientes acometidos por trauma, em um hospital universitário, no período de um ano. Os resultados mostraram que a prevalência das infecções nos pacientes do estudo foi elevada (15,6%), acometendo principalmente o sexo masculino (80,0%), com idade entre 18 e 40 anos (47,5%), período de internação maior que 15 dias(78,6%), mais frequente no trauma fechado (54,0%) e nas queimaduras (32,5%). Os principais sítios de infecção foram a pneumonia (49,5%) seguida pela infecção do trato urinário (23,8%). A intubação orotraqueal e o cateterismo vesical de longa permanência estiveram significativamente relacionados à maioria das pneumonias (60,3%; p<0,001) e infecções do trato urinário (77,3%; p<0,001), aumentando os riscos para tais infecções em 20 e 6 vezes, respectivamente. A sepse acometeu 44,7% dos pacientes.Ampla gama de microrganismos apresentou resistência aos antimicrobianos, sendo Acinetobacter baumannii (92,7%, p<0,001) e Klebsiella pneumoniae (70,5%, p<0,001) os mais prevalentes. Evoluíram a óbito 28,8% dos pacientes, e 96,8% das mortes relacionavam-se às infecções. A relação das infecções com o óbito foi estatisticamente significativa em pacientes com pneumonia (37,8%, p<0,001) e sepse(54,2%, p<0,001). A relação das infecções com a maioria dos óbitos evidenciou o impacto negativo desta complicação na saúde das vítimas de traumas.

Healthcare associated infections have an impact on the health of hospitalized patients and are reflected inhigh rates of morbidity and mortality. The aim of this descriptive study is to characterize the infections andevaluate their impact on trauma patient health at a University Hospital over a 1-year period. The resultsshowed that the prevalence of infections in trauma patients was elevated (15.6%), affecting mainly males(80.0%), ages between 18 and 30 years (47.5%), more than 15 days hospitalization (78.6%), more frequentin blunt trauma (54.0%) and in burns (32.5%). The principal sites of infection were pneumonia (49.5%) followed by urinary tract infection (23.8%). The tracheal intubation and long-term vesical catheterization were significantly related to most pneumonias (60.3%; p<0.001) and urinary tract infection (77.3%; p<0.001), increasing the risk for such infections on 20 and 6 times, respectively. Sepsis occurred in 44.7% of patients. A wide range of microorganisms showed resistance to antimicrobials, and Acinetobacter baumannii (92.7%, p <0.001) and Klebsiella pneumoniae (70.5%, p <0.001) were the most prevalent. 28.8% of the patients evolved to death, and 96.8% of deaths were related to infections. The relation between infections and death was statistically significant in pneumonia patients (37.8%, p <0.001) and sepsis (54.2%, p <0.001). The association of infections with the death showed the negative impact of this health complication in trauma patients.

Comparação da técnica de radioterapia em arco modulada volumetricamente (VMAT) em relação à técnica de radioterapia de intensidade modulada (IMRT) para tumores de próstata e cabeça e pescoço / [131]

As técnicas de radioterapia vem sendo constantemente modificadas com a implementação de novas tecnologias visando aumentar a eficiência e diminuir a toxicidade dos tratamentos com radiação ionizante. Esse trabalho visa comparar as técnicas de radioterapia de intensidade modulada (IMRT) e a radioterapia em arco modulada volumetricamente (VMAT) em termos dosimétricos para o alvo e órgãos em risco além de avaliar a diferença do tempo de tratamento utilizando cada técnica. Para assegurar que os planejamentos seguiriam um padrão aceitável para ambas as técnicas, realizou-se primeiramente os planejamentos sugeridos pelo TG 119 da Associação Americana de Física Médica e compatibilidade dos resultados obtidos comparados com os dados da literatura. Tal comparação permitiu prosseguir para uma próxima etapa que consistiu da utilização de imagens de pacientes reais que foram submetidos a tratamentos de próstata e cabeça e pescoço, para a realização dos planejamentos utilizando as técnicas de IMRT e VMAT. A qualidade dosimétrica dos planejamentos utilizando ambas as técnicas foi avaliada em termos de conformidade e homogeneidade da dose no alvo e para os casos de pacientes com câncer de próstata, foram investigados os limites de dose em reto, bexiga e cabeça de fêmur, sendo avaliada a associação entre o volume de intersecção de reto e bexiga com o alvo. Para os casos de pacientes com câncer de cabeça e pescoço, em termos dos limites de dose em medula, tronco cerebral e parótidas. Os planejamentos nos quais fez se uso da técnica de VMAT apresentaram valores semelhantes aos dos planos de IMRT. A análise dos tempos de tratamento para cada técnica avaliada mostrou que a VMAT reduz significativamente o tempo, até 67% para os casos de pacientes com câncer de próstata e até 36% para os casos de pacientes com câncer de cabeça e pescoço.

The goal of this study was to compare the dosimetric aspects of volumetric-modulated arc therapy (VMAT) with those of intensity-modulated radiotherapy (IMRT) and to evaluate the delivery time and monitor unit differences between the two techniques, for applications in prostate and head and neck cancer treatment. First of all, to assure an acceptable pattern of treatment planning using both techniques, the TG119 of American Association of Medical Physics instructions were followed and the results of plans were compared to TG119 published data. The next step consisted of using real patients' images, whose underwent prostate radiotherapy or head and neck radiotherapy, to planning IMRT and VMAT. The dosimetric quality of plans using both techniques was evaluated in terms of target dose conformity and target dose homogeneity The dose constraints for rectum, bladder and femoral head were analyzed and the association between the rectum intersection volume and bladder intersection volume to the target volume were evaluated for the prostate cases. The dose constraints for spinal cord, brainstem and parotids were investigated for the head and neck cases. Best or similar values were obtained for the VMAT plans in relation to IMRT plans. The analysis of treatment time indicated a significant reduction using VMAT, until 67% to the prostate cases and 36% to the head and neck cases.

Pharmacokinetics of ampicillin-sulbactam and the renal function-based optimization of dosing regimens for prophylaxis in patients undergoing cardiovascular surgery.

UNLABELLED: Surgical site infections are a major cause of postoperative morbidity and mortality in cardiovascular surgery. Proper antibiotic prophylaxis can reduce the rate of such infections, but the concentration of antibiotic must be maintained at an adequate level throughout the operation. This study aimed to use renal function to determine the most appropriate timing for intraoperative repeated dosing of ampicillin-sulbactam, a commonly used prophylactic antibiotic, to maintain adequate concentrations throughout the course of surgery. The mean volume of distribution, elimination rate constant, elimination half-life, and total clearance of ampicillin were 13.2 l, 0.652 h⁻¹, 1.32 h, and 8.45 l/h, respectively. A statistically significant (P < 0.0001) correlation (r = 0.771) was observed between the total clearance of ampicillin and creatinine clearance of the patients. Plasma concentrations of ampicillin were simulated with the pharmacokinetic parameters obtained. We developed a nomogram for adjusting the dosing interval according to renal function and predicted ampicillin trough concentrations. We revealed the best dosage and dosing interval for cardiovascular surgery by analyzing the perioperative pharmacokinetics of ampicillin-sulbactam administered prophylactically. We suggest that the dosage and dosing interval for ampicillin-sulbactam should be adjusted to optimize treatment efficacy and safety, on the basis of the MIC90 of methicillin-sensitive Staphylococcus aureus (MSSA) in each institution. TRIAL REGISTRATION: UMIN000007356.

Caracterização dosimétrica de feixes de fótons com detector de diamante / Dosimetric characterization of photon beams using a diamond detector

OBJETIVO: Este trabalho foi realizado com o objetivo de caracterizar o detector de diamante, bem como observar seu comportamento. MATERIAIS E MÉTODOS: As características dosimétricas de feixes de fótons de 6 MV de energia foram medidas utilizando o sistema automático de varredura MP3 da PTW com um detector de diamante e foram comparadas com medidas usando uma câmara de ionização 31010 da PTW. RESULTADOS: As características dosimétricas do detector de diamante foram observadas por meio de medidas de linearidade com a dose, dependência com a taxa de dose e distribuições de dose em profundidade, bem como perfis. CONCLUSÃO: Algumas medidas com diamante e câmara de ionização foram validadas com resultados publicados na literatura, o que demonstrou um bom comportamento do detector de diamante na comparação com a câmara de ionização, muito utilizada para dosimetria em radioterapia, evidenciando que o diamante é uma boa escolha de detector para dosimetria de campos pequenos.

OBJECTIVE: The present study was aimed at characterizing a diamond detector and observing its behavior. MATERIALS AND METHODS: The dosimetric characteristics of 6 MV photon beams were measured by utilizing an automatic PTW MP3 scanning system with a diamond detector, and compared with measurements performed with a PTW 31010 ion chamber. RESULTS: Measurements of dose linearity, dose rate dependence and depth dose distribution as well as dose profiles demonstrated the dosimetric characteristics of the diamond detector. CONCLUSION: Some measurements with diamond detector and ion chamber were validated with results published in the literature, demonstrating a good behavior of the diamond detector as compared with the ionization chamber that is widely utilized for dosimetry in radiotherapy, indicating that the diamond detector is a good choice for small field dosimetry.