Postoperative Cognitive Dysfunction (POCD) and Inflammatory Markers in Elderly Patients

Introduction: Particularly in elderly patients, the brain responds to a systemic inflammatory response with an increased production of inflammatory mediators. This has hypothetically been linked to the development of postoperative cognitive dysfunction (POCD). Methods: We investigated 31 patients aged >65 yrs undergoing elective major surgery under standardized general anaesthesia (thiopental, sevoflurane, fentanyl, atracurium). Cognitive function was measured preoperatively and 7 days postoperatively using the extended version of the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery (CERAD-NAB, validated German version) for which we developed a diagnostic cut-off in healthy elderly volunteers. Systemic C-reactive protein (CRP) and interleukin 6 (IL-6) were measured preoperatively, 2 days postoperatively, and 7 days postoperatively. Values for CRP, IL-6, operative characteristics and hospital length of stay in patients with POCD and without POCD were compared using the Mann- Whitney U test and are shown as median [range]. Results: Fourteen patients (45%) developed POCD. Values for CRP were not statistically different in patients with POCD and without POCD but tended to be higher in patients with POCD 2 days postoperatively. Patients with POCD had significantly higher IL-6 values on postoperative days 2 and 7 (table 1). These patients also had a significantly longer duration of anaesthesia (305 [195-620] vs.190 [150-560] min, p = 0.034), larger intraoperative blood loss (425 [0-1600] vs. 100 [0-1500] ml, p = 0.018) and longer hospital stays (15 [8-45] vs. 8 [4-40] days, p = 0.008). Table 1 POCD (n = 14) No POCD (n = 17) p value CRP (mg/dl) preop. 4.0 [1.0-245] 4.2 [0.3-36.2] 0.6 2 days postop. 223 [20-318] 98 [4.5-384] 0.07 7 days postop. 58 [15-147] 44 [11-148] 0.2 IL-6 (U/ml) preop. 2[2-28.1] 2 [2-7.3] 0.8 2 days postop. 56 [17-315] 20 [2-123] 0.009 7 days postop. 9[2-77] 4 [2-16] 0.03 Interpretation: In this small group of patients, high IL-6 values postoperatively were associated with POCD supporting a role for systemic inflammation in the development of POCD. In patients with POCD, duration of anaesthesia was significantly longer, and intraoperative blood losses were larger. These risk factors will need to be confirmed in a larger group of patients. The difference in length of stay may be indicative of postoperative complications, which have been linked to POCD earlier.

Effect of 15n-labeled hairy vetch and nitrogen fertilization on maize nutrition and yield under no-tillage¹

This study evaluated the effect of hairy vetch (Vicia villosa Roth) as cover crop on maize nutrition and yield under no tillage using isotope techniques. For this purpose, three experiments were carried out: 1) quantification of biological nitrogen fixation (BNF) in hairy vetch; 2) estimation of the N release rate from hairy vetch residues on the soil surface; 3) quantification of 15N recovery by maize from labeled hairy vetch under three rates of mineral N fertilization. This two-year field experiment was conducted on a sandy Acrisol (FAO soil classification) or Argissolo Vermelho distrófico arênico (Brazilian Soil Classification), at a mean annual temperature of 18 ºC and mean annual rainfall of 1686 mm. The experiment was arranged in a double split-plot factorial design with three replications. Two levels of hairy vetch residue (50 and 100 % of the aboveground biomass production) were distributed on the surface of the main plots (5 x 12 m). Maize in the sub-plots (5 x 4 m) was fertilized with three N rates (0, 60, and 120 kg ha-1 N), with urea as N source. The hairy vetch-derived N recovered by maize was evaluated in microplots (1.8 x 2.2 m). The BFN of hairy vetch was on average 72.4 %, which represents an annual input of 130 kg ha-1 of atmospheric N. The N release from hairy vetch residues was fast, with a release of about 90 % of total N within the first four weeks after cover crop management and soil residue application. The recovery of hairy vetch 15N by maize was low, with an average of 12.3 % at harvest. Although hairy vetch was not directly the main source of maize N nutrition, the crop yield reached 8.2 Mg ha-1, without mineral fertilization. There was an apparent synergism between hairy vetch residue application and the mineral N fertilization rate of 60 kg ha-1, confirming the benefits of the combination of organic and inorganic N sources for maize under no tillage.

Sistemas de manejo e os estoques de carbono e nitrogênio em latossolo de cerrado com a sucessão soja-milho

Os estoques de C e N no solo são determinados pelo balanço entre adição e perda no sistema, sendo o preparo do solo e o sistema de culturas determinantes nesse processo. Este estudo teve por objetivo avaliar o efeito de sistemas de manejo do solo baseados em sistemas de preparo, plantas de cobertura e adubação fosfatada nos estoques de C e N em frações físicas da matéria orgânica do solo e na biomassa e respiração microbiana em um solo cultivado por 11 anos na sucessão soja-milho. O experimento foi iniciado em 1999 em um Latossolo Vermelho argiloso com teor de P adequado para obtenção de 80 a 90 % de rendimentos potenciais de culturas anuais. O delineamento experimental foi o de blocos ao acaso com parcelas divididas, tendo três sistemas de manejo baseados em preparo do solo e plantas de cobertura (sistema de preparo convencional com milheto, sistema plantio direto com milheto e sistema plantio direto com mucuna-preta) nas parcelas e duas doses de P (0 e 100 kg ha-1 ano-1 de P2O5 na forma de superfosfato triplo, aplicados no sulco de semeadura) nas subparcelas. Amostras de solo foram retiradas no enchimento de grãos da soja (março de 2010), nas camadas de 0-5, 5-10 e 10-20 cm de profundidade, e submetidas ao fracionamento físico da matéria orgânica do solo e a análises microbianas. O sistema plantio direto promoveu estratificação de C orgânico e N total, enquanto o preparo convencional promoveu distribuição mais homogênea na camada de 0 a 20 cm de profundidade. A adubação fosfatada por 11 anos promoveu acúmulo de C orgânico e N total em solos com adequada disponibilidade inicial de P, com relação àquele que não recebeu adubação com P, independentemente do sistema de preparo e das plantas de cobertura. O sistema plantio direto apresentou maior estoque de C orgânico e N total, maior C biomassa microbiana e menor respiração microbiana em relação ao sistema de preparo convencional, ambos tendo o milheto como planta de cobertura. Quando sob plantio direto, maior estoque de C orgânico e N total, semelhante C biomassa microbiana e maior respiração microbiana foram obtidos com o milheto como planta de cobertura, em relação à mucuna. A taxa de conversão do C adicionado pelas culturas em C orgânico do solo foi de 4,0, 8,2 e 14,3 % para sistema de preparo convencional com milheto, sistema plantio direto com milheto e com mucuna, respectivamente.

Feasibility of radiotherapy or chemoradiotherapy after taxane-based induction chemotherapy for nonoperated locally advanced head and neck squamous cell carcinomas.

To assess the use of radiotherapy (RT) or concurrent chemoradiotherapy (CRT) following taxane-based induction chemotherapy (T-ICT) in locally advanced head and neck squamous cell carcinoma (LAHNSCC) and to evaluate the tolerability of CRT after T-ICT. From 01/2006 to 08/2012, 173 LAHNSCC patients treated as a curative intent by T-ICT, followed by definitive RT/CRT were included in this analysis. There was an 86% objective response (OR) after ICT among 154 evaluable patients. Forty-four patients received less than three cycles (25%) and 20 received only one cycle of T-ICT. The 3-year actuarial overall survival (OS) was 49% and there was no OS difference according to the type of ICT (regimen or number of cycle) or the addition of concurrent CT (cisplatin, carboplatin, or cetuximab) to RT. In multivariate analysis (MVA), clinically involved lymph node (cN+), age more than 60 years, the absence of OR after ICT, and performance status of at least 1 predicted for a decreased OS, with hazard ratios (HR) of 2.8, 2.2, 2.1, and 2, respectively. The 3-year actuarial locoregional control (LRC) and distant control (DC) rates were 52 and 73%, respectively. In MVA, the absence of OR after ICT (HR: 3.2), cN+ (HR: 3), and age more than 60 years (HR: 1.7) were prognostic for a lower LRC whereas cN+ (HR: 4.2) and carboplatin-based T-ICT (HR: 2.9) were prognostic for a lower DC. The number of cycles (≤ 2) received during ICT was borderline significant for DC in the MVA (P=0.08). Among patients receiving less than or equal to three cycles of ICT, higher outcomes were observed in patients who received cisplatin-based T-ICT (vs. carboplatin-based T-ICT) or subsequent CRT (vs. RT). T-ICT in our experience, followed by RT or CRT, raises several questions on the role and type of induction, and the efficacy of CRT over RT. The role of RT or CRT following induction, although feasible in these advanced patients, awaits answers from randomized trials.

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolism.

Background: In haemodynamically stable patients with acute symptomatic pulmonary embolism (PE), studies have not evaluated the usefulness of combining the measurement of cardiac troponin, transthoracic echocardiogram (TTE), and lower extremity complete compression ultrasound (CCUS) testing for predicting the risk of PE-related death. Methods: The study assessed the ability of three diagnostic tests (cardiac troponin I (cTnI), echocardiogram, and CCUS) to prognosticate the primary outcome of PE-related mortality during 30 days of follow-up after a diagnosis of PE by objective testing. Results: Of 591 normotensive patients diagnosed with PE, the primary outcome occurred in 37 patients (6.3%; 95% CI 4.3% to 8.2%). Patients with right ventricular dysfunction (RVD) by TTE and concomitant deep vein thrombosis (DVT) by CCUS had a PE-related mortality of 19.6%, compared with 17.1% of patients with elevated cTnI and concomitant DVT and 15.2% of patients with elevated cTnI and RVD. The use of any two-test strategy had a higher specificity and positive predictive value compared with the use of any test by itself. A combined three-test strategy did not further improve prognostication. For a subgroup analysis of high-risk patients, according to the pulmonary embolism severity index (classes IV and V), positive predictive values of the two-test strategies for PE-related mortality were 25.0%, 24.4% and 20.7%, respectively. Conclusions: In haemodynamically stable patients with acute symptomatic PE, a combination of echocardiography (or troponin testing) and CCUS improved prognostication compared with the use of any test by itself for the identification of those at high risk of PE-related death.

Transport of the organic cation N1-methylnicotinamide by the rabbit proximal tubule. I. Accumulation in the isolated nonperfused tubule.

Isolated nonperfused rabbit renal proximal tubules were used to investigate the basolateral step of transport of the organic cation N1-methylnicotinamide (NMN). NMN accumulation was highest and saturable in S2 and S3 segments, but lowest and nonsaturable in S1 segments. In S1 segments, accumulation of [3H]-NMN (0.5-8 microM in the bath) resulted in an average tubular water/medium concentration ratio (T/M) of 8.2, whereas in S2 and S3 segments T/M averaged 19.5 and 18.6, respectively. At these concentrations, about 30% of the label was attached in all segments to a metabolite comigrating with nicotinamide. KCN (10(-2) M) or ouabain (10(-4) M) reduced T/M to about 8 for all segments. NMN accumulation was inhibited (to a T/M of about 3 with mepiperphenidol) by other organic cations (10(-5)-10(-3) M) with the potency sequence mepiperphenidol greater than tetraethylammonium = quinine greater than morphine, these organic cations having no effect on p-aminohippurate accumulation, except for the highest concentration of quinine (10(-3) M). After correction for metabolism, NMN accumulation could be accounted for by simple electrochemical equilibrium across the basolateral membrane. The basolateral step of NMN transport appears therefore to be a carrier-mediated diffusion, in opposition to the active basolateral accumulation described for tetraethylammonium.

Beta-adrenoceptor stimulation increases neuropeptide Y release from sympathetic nerves in intact rats.

This study was undertaken to assess in conscious normotensive rats the effects of beta-adrenoceptor stimulation on plasma neuropeptide Y (NPY) levels. Wistar rats were subjected to adrenal demedullation on the right side and were either adrenalectomized or sham-operated on the left side. Eleven days later, the conscious rats were infused i.v. for 30 min with either isoproterenol (10 ng/min) or its vehicle. Plasma NPY levels were significantly lower (23.8 +/- 2.6 pM, means +/- S.E.M., n = 12, P < 0.01) in vehicle-treated medullectomized rats than in corresponding sham-operated controls (36.7 +/- 4.1 pM, n = 12). The medullectomized rats infused with isoproterenol showed plasma NPY levels (36.7 +/- 3.3 pM, n = 11) comparable to those of sham-operated rats having received the vehicle. These data therefore demonstrate that plasma NPY levels are lower in rats without adrenal medulla and that in these animals isoproterenol increases NPY release, most likely by activating pre-synaptic beta-adrenoceptors.

Pregnancy outcome following exposure to topical retinoids: a multicenter prospective study.

Concerns have been raised about the use of topical retinoids since the publication of isolated cases of characteristic retinoid embryopathy, originally described after oral use. A collaborative study of the European Network of Teratology Information Services was carried out to evaluate the rate of congenital malformations following first-trimester topical retinoid exposure. A population of 235 exposed pregnant women was compared with 444 controls. No significant differences were observed between groups with regard to the rates of spontaneous abortion (odds ratio [95% confidence interval], 1.5 [0.8-2.7]), minor birth defects (1.3 [0.4-3.7]), and major birth defects (1.8 [0.6-5.4]). No child showed features of retinoid embryopathy. The rate of elective termination in the exposed group was increased 3-fold (3.4 [1.5-7.8]). In conclusion, these results do not suggest an increased risk of retinoid embryopathy. However, according to current knowledge, topical retinoids cannot be advised for use during pregnancy because their risk/benefit ratio remains questionable.