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Malnutrition is a major issue in gastrointestinal perioperative situations, as only 40% of malnourished patients are finally treated. This literature review investigates the inconsistencies regarding the diagnostic approach to both preoperative and postoperative patients and the various underlying causes, as well as the efficiency of the various therapeutic regimens. A literature search was conducted until August 2023 in MEDLINE and Scopus. Clinical studies involving perioperative nutritional assessment in adult gastrointestinal surgery patients during the last 10 years were included in the present review. Finally, 19 articles were included in the study. Preoperative nutritional therapy is increasingly recognized as a key component of surgical care. Malnourished patients who are hospitalized and operated on, have significantly worse clinical results. Gastrointestinal postoperative malnutrition coexists with metabolic stress, as patients usually suffer from minor chronic inflammations; therefore, postoperative malnutrition is the result of a combination of the effects of inflammation and a lack of food intake. Postoperative malnutrition leads to prolonged hospitalizations and hospital complications and therefore the need to treat it is essential. There are many recognized tools for detecting malnutrition. However, all tools showed inconsistent results regarding their validity. Per os feeding after surgery, and dietary supplements when necessary, have been recommended. Therefore, it is very important to reduce malnutrition and define clear strategies towards that direction.
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Introduction and objectives Bacterial translocation (BT) is the passage of viable bacteria or endotoxins from the gastrointestinal lumen to extra-luminal tissues and is usually observed after intestinal ischaemia-reperfusion injury. The aim of this study was to investigate post-resuscitation BT after cardiac arrest and resuscitation in a swine anaesthetized with propofol-based total intravenous anaesthesia. Materials and methods Eighteen female Landrace/Large White piglets were randomly divided into control (CON), cardiac arrest (CA) and cardiac arrest-cardiopulmonary resuscitation (CA-CPR) groups. In the CON group, the animals were only monitored for two hours. In the CA group, the animals were not resuscitated and underwent necropsy immediately after cardiac arrest. In the CA-CPR group, the animals were resuscitated until the return of spontaneous circulation (ROSC) and were monitored for two hours. The animals of the CON and CA-CPR groups underwent necropsy 24 hours later. Bacterial translocation was assessed by blood and tissue cultures and endotoxin measurement in the portal and systemic circulation. Malondialdehyde content calculation and histological analysis of the intestine were performed in order to estimate ischemia and reperfusion (I/R) tissue damage. Results Malondialdehyde content, an indicator of oxidative stress, was significantly higher in the CA-CPR group compared to the CA in homogenized ileum (p=0.016). Malondialdehyde content in homogenized colon revealed significantly higher levels in the CA-CPR group compared to the CON (p=0.004) and the CA group (p=0.016). We found significantly higher levels of portal endotoxin in the CA-CPR group compared to the CON (p=0.026) and the CA group (p=0.026). The number of positive mesenteric lymph nodes cultures for E. coli was greater in the CA-CPR group, followed by the CA and CON groups, although the difference was not significant (67%, 33%, and 33%, respectively; p=0.407). Conclusions Malondialdehyde content and portal endotoxin levels do not increase during the cardiac arrest interval, but only after CPR and ROSC. Although the number of positive MLNs cultures was greater in the CA-CPR animals, no statistically significant differences were observed between the three groups due to the short monitoring period.
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Cancer accounts for approximately 13 % of all deaths worldwide. Development of stratification biomarkers, for cancer screening, diagnosis, monitoring, and treatment optimization, is a vital concept to facilitate disease prevention and drug development. The advent of stratified medicine should result in the safer, more effective use of therapeutic drugs to treat cancer, and in reducing the cost associated with inappropriate therapeutic regimens; however, many barriers delay the use of biomarkers in drug development and clinical practice. Since the incorporation of biomarkers in clinical practice might have additional initial costs, the question arises regarding whether the improvement in outcomes is reached at a realistic additional cost. This review presents an overview of economic issues surrounding biomarkers in cancer treatment optimization.
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Neoplasias/diagnóstico , Antineoplásicos/uso terapêutico , Análise Custo-Benefício , Detecção Precoce de Câncer/métodos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/cirurgia , Neoplasias/terapiaRESUMO
To address the value of qRT-PCR and IHC in accurately detecting lymph node micrometastasis in gynecological cancer, we performed a systematic approach, using a set of dual molecular tumor-specific markers such as cytokeratin 19 (CK19) and carbonic anhydrase 9 (CA9), in a series of 46 patients (19 with cervical cancer, 18 with endometrial cancer, and 9 with vulvar cancer). A total of 1281 lymph nodes were analyzed and 28 were found positive by histopathology. Following this documentation, 82 lymph nodes, 11 positive and 71 negative, were randomly selected and further analyzed both by IHC and qRT-PCR for CK19 and CA9 expression. All 11 (100%) expressed CK19 by IHC, while only 6 (54.5%) expressed CA9. On the contrary, all the histologically negative for micrometastases lymph nodes were also negative by IHC analysis for both markers. The comparative diagnostic efficacy of the two markers using qRT-PCR, however, disclosed that the analysis of the same aliquots of the 82 lymph nodes led to 100% specificity for the CK19 biomarker, while, in contrast, CA9 failed to recapitulate a similar pattern. These data suggest that qRT-PCR exhibits a better diagnostic accuracy compared to IHC, while CK19 displays a consistent pattern of detection compared to CA9.
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Neoplasias do Endométrio/genética , Micrometástase de Neoplasia/genética , Neoplasias do Colo do Útero/genética , Neoplasias Vulvares/genética , Antígenos de Neoplasias/biossíntese , Biomarcadores Tumorais/biossíntese , Anidrase Carbônica IX , Anidrases Carbônicas/biossíntese , Neoplasias do Endométrio/patologia , Feminino , Humanos , Queratina-19/biossíntese , Linfonodos/metabolismo , Linfonodos/patologia , Micrometástase de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/patologia , Neoplasias Vulvares/patologiaRESUMO
The pharmacokinetics of tobramycin was studied in adult patients (N = 151) admitted either for initial suspicion of Gram-negative infection or for prophylaxis. In addition to age, weight, height and creatinine clearance (CrCL), a range of other covariates were also analysed, including type of pathology, co-medication, fever, sex and ethnicity (Basque or not). All patients received 100mg tobramycin every 8 h and samples were collected at three time points after the first dose and at two time points after the fourth dose and assayed with a fluorescence polarisation immunoassay. The population mixed effects bicompartmental parameters were obtained from 725 concentration measurements using NONMEM, FOCE method, and were: systemic clearance, CL = 6.03 L/h (between-subject coefficient of variation (CV) %, 29.4%); volume of distribution, V = 15.04 L (7.3%); and intercompartmental constants, k(12) = 0.192 h(-1) (56%) and k(21) = 0.55 h(-1) (no CV% determined). Covariate modelling was performed within NONMEM. Two alternative significant covariate models (Models 1 and 2) are proposed, with functions of CrCL and/or sex (Model 2). However, for clinical purposes, differentiation by sex is insignificant. Model 1 is for CL = 3.1 + 0.05.CrCLL/h (17.3%); V = 14.6 L (12%); k(12) = 0.224 h(-1) (63%) and k(21) = 0.468 h(-1). Stochastic simulation was used to predict the expected concentration 95th percentiles after the recommended 7 mg/kg dose and for minimum inhibitory concentration (MIC) = 1 mg/L, as well as alternative once-daily dosing regimens for MIC = 2 mg/L. It is seen that once-daily high-dose tobramycin is an appropriate strategy with respect to pharmacodynamic indices, C(peak)/MIC or AUC/MIC (where C(peak) is the peak plasma concentration and AUC is the area under the concentration-time curve).
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Antibacterianos/farmacocinética , Infecções por Bactérias Gram-Negativas/metabolismo , Tobramicina/farmacocinética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Método de Monte CarloRESUMO
PURPOSE: Research data have recently emphasized an intriguing association of JC polyoma virus with colon carcinogenesis. Tumorigenicity of JC virus is attributed to the T-antigen of its Mad-1 variant. Controversy arose when another research group did not confirm this association. The purpose of this study was to detect JC virus in a series of colon neoplasms from Greek patients. METHODS: A nested polymerase chain reaction assay was used to detect JC virus in 80 cancerous, 25 adenomatous specimens of large bowel, and 20 colonoscopic biopsy samples from normal patients without colorectal neoplasia. Quantitation of JC virus DNA was performed by real-time polymerase chain reaction. RESULTS: JC polyoma virus nucleotide sequence was detected in 61 percent of colon adenocarcinomas and in 60 percent of adenomas, at a viral load of 9 x 10(3) to 20 x 10(3) copies/microg DNA. Adjacent normal mucosa in 35 positive colon adenocarcinoma specimens, and normal mucosa from six patients of the control group, had low viral loads (50-450 copies/microg DNA). CONCLUSIONS: JC polyoma virus genome is present in colon neoplasms. JC virus detection in adenomas at comparable viral loads to malignant tumors suggests its implication at early steps of colonic carcinogenesis. Taking into consideration other published data, infection of colonic epithelium with JC virus might be a prime candidate for a role in chromosomal and genomic instability.
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Adenocarcinoma/virologia , Adenoma/virologia , Neoplasias do Colo/virologia , Vírus JC/patogenicidade , Infecções Tumorais por Vírus/complicações , Adenocarcinoma/etiologia , Adenoma/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Neoplasias do Colo/etiologia , Colonoscopia , DNA Viral/análise , Feminino , Humanos , Vírus JC/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
PURPOSE: Better dosing is needed for antibiotics, including teicoplanin (TEI), to prevent emergence of resistant bacterial strains. Here, we assess the TEI pharmacokinetics (PK) related to a 10 mg/l minimum inhibitory concentration (MIC) target in ICU children (4 to 120 months; n = 20) with gram+ infections. METHODS: Standard administration of TEI was with three 10 mg/kg Q12h, loading infusions, and maintainance with 10 mg/kg or 15 mg/kg Q24h. During maintenance, 9 samples (3/day) were collected per patient and the PK analyzed with Nonlinear Mixed Effects Model (NONMEM). RESULTS: Thirty-five percent of concentrations in older children (> or =2 months) vs. 8% in younger infants (<12 months) were below the target MIC. The global bicompartmental population PK parameters were [mean (interindividual CV%)] CL = 0.23 l/h [72%], V = 3.16 l [58%], k12 = 0.23 h(-1), and k21 = 0.04 h(-1). Two PK subpopulations were identified. The older children had CL = 0.29 [23%] l/h, V = 3.9 l and the younger infants, CL = 0.09 [37%] l/h, V = 1.05 l. Residual error was reduced from 52% to around 30% in the final models. CONCLUSIONS: Older children in the ICU may require relatively higher doses of teicoplanin. However, a study in a larger population is needed.