Evaluación de la efectividad del tratamiento con glucocorticoides intravenosos en la oftalmopatía de Graves

ObjectiveTo assess the efficacy of intermittent, high-dose treatment with intravenous glucocorticoids (IV GCs) in moderate to severe Graves’ ophthalmopathy (GO).Materials and methodsPatients with GO treated with IV GCs from August 2007 to August 2011 at the Endocrinology Department of Reina Sofía Hospital were enrolled into the study. IV pulse prednisolone (7.5 mg/kg/day) was administered twice weekly every two weeks for 6 weeks, and at half the dose for 6 additional weeks.ResultsEighteen patients (mean age, 43+/-11 years) with moderate to severe GO were analyzed (83.3% females). Four were active smokers, five former smokers, and the rest had never smoked. Hyperthyroidism due to Graves’ disease was found in 66.7% of patients, 41.6% of whom had received radioiodine therapy. Response to treatment was satisfactory in 72.2%, partial in 11.1%, and poor in 16.7%. Mild side effects were reported by 5 patients. Before treatment, 83.3% had diplopia, 33.3% eyelid retraction, 72.2% eye pain, and 44.4% exophthalmos. After treatment, only 33.3% had diplopia (P = .004), 5.6% eyelid retraction (P = .063), 16.7% eye pain (P = .002), and 11.1% exophthalmos (P = .031). Response to treatment was not related to the underlying disease (P = .866), prior radioiodine treatment (P = .447), or smoking status (P = .368).ConclusionsIntravenous glucocorticoid therapy decreased activity in patients with moderate to severe active GO, with major improvement occurring in diplopia, eye pain, and exophthalmos. Side effects were mild and uncommon. Treatment response was independent from the underlying disease, prior radioiodine treatment, or smoking status.     

Effect of suplemental nitrogen source and feeding frequency on nutrient supply to lambs fed a kikuyu grass (Pennisetum clandestinum) hay-based diet

Eight castrated male lambs (35 ± 4 kg live weight), fed a basal diet of kikuyu grass hay, were used in a replicated 4 × 4 Latin Square experiment with a 2 × 2 factorial arrangement of treatments to evaluate the effect of supplemental feeding frequency and source of rumen degradable N on intake, digestibility, ruminal fermentation, and microbial protein yield. Treatments were supplementation with cassava meal plus calcium caseinate or cassava meal plus urea offered at a rate of 7 g/kg live weight daily in one or two meals per day. Lambs were fed twice daily in such manner to allow ad libitum comsumption of forage. There was significant feeding frequency by N source interaction on variables of intake. In general, intake of feed components was higher (P ≤ 0.05) by lambs offered the caseinate-supplement twice daily over intake observed in lambs given the others diet treatments. Digestibility of feed components was neither affected by supplemental N source (DM, P = 0.541; OM, P = 0.585; NDF, P = 0.828) nor by feeding frequency (DM, P = 0.122; OM, P = 0.175; NDF, P = 0.591). Urinary excretion of N increased (P ≤ 0.05) in lambs supplemented twice daily whereas N retention was similar for all treatments (N source, P = 0.748; feeding frequency, P = 0.418). Microbial protein entering into the small intestine was affected by the interaction between feeding frequency and N source such as an increasing (P < 0.10) in this variable was observed when lambs received the caseinate but not the urea supplement twice daily. Efficiency of microbial protein synthesis, however, was not affected by treatments (N source, P = 0.588; feeding frequency, P = 0.334). Rumen pH averaged 6.70 and it was neither affected by N source (P = 0.827) nor by feeding frequency (P = 0.740). Ruminal concentration of ammonia N was not affected by feeding frequency (P = 0.144) while it increased (P < 0.05) when urea rather than caseinate was the supplemental N source (mean of 7.61 mg/dl vs. 6.00 mg/dl). Concentration of sugars in rumen fluid was higher (P ≤ 0.05) in lambs supplemented once a day compared to twice daily (mean of 49.4 mg/dl vs. 34.4 mg/dl) for both N sources. A significant (P ≤ 0.05) N source by feeding frequency interaction effect was observed for ruminal concentrations of α-amino N compounds. In urea treatment α-amino N concentration increased (P ≤ 0.05) in lambs receiving the supplement twice daily compared to once a day (mean of 4.59 mg/dl vs. 3.70 mg/dl) while in caseinate treatment it was higher (P ≤ 0.05) in lambs offered the supplement in one meal per day compared to twice daily (mean of 5.29 mg/dl vs. 4.07 mg/dl). In conclusion, for ruminants fed a tropical grass-based diet, starch-rich supplement containing non-protein N as N source may be offered only once a day whereas the supply of nutrients may be improved if degradable true protein is included as N source and supplement is offered in two meals per day.     

Association of urinary 15-F2t-isoprostane level with oxygen desaturation and carotid intima–media thickness in nonobese sleep apnea patients

Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may unbalance oxidative stress, increasing atherosclerosis. Among oxidative stress markers, 15-F_2t-isoprostane is considered one of the most sensitive and specific metabolites of lipid peroxidation. To explore the relationship between urinary 15-F_2t-isoprostane with sleep apnea severity and carotid modifications in nonobese OSA patients, 31 nonobese sleep apnea patients were studied, along with 10 lean subjects without OSA. Patients were assessed by polysomnography, blood pressure measurement, and ultrasonography to determine the carotid intima–media thickness (IMT). Urinary 15-F_2t-isoprostanes were measured by liquid chromatography–tandem mass spectrometry. Urinary 15-F_2t-isoprostane concentrations were increased in severe OSA patients compared to control subjects (20.2 ± 7.3 vs 12.3 ± 2.8 ng/mmol creatinine; P = 0.020). Mean carotid IMT was correlated with 15-F_2t-isoprostane (r = 0.532; P < 0.001) and with the apnea–hypopnea index (r = 0.345; P = 0.029). 15-F_2t-Isoprostane level was related to the night time spent at SaO₂ < 90% (r = 0.478; P = 0.002), the apnea–hypopnea index (r = 0.465; P = 0.003), and the mean nocturnal SaO₂ (r = ? 0.424; P = 0.007). These results showed a relationship between lipid peroxidation, carotid intima–media thickness, and intermittent hypoxia in nonobese OSA patients, thus reinforcing the hypothesis that oxidative stress could be involved in the early atherosclerotic process.     

Tri-axial accelerometer analysis techniques for evaluating functional use of the extremities

Activity monitors provide an objective mechanism for evaluating patient function. It is unclear what similarities or unique information may be yielded using different analyses. Fifteen patients scheduled to undergo shoulder arthroplasty and fifteen matched control subjects wore tri-axial accelerometer activity monitors bilaterally at the lower (wrist) and upper (biceps) arm for 3 days. Measures of central tendency, variance, sample entropy, and asymmetry were calculated. A novel technique to evaluate time distribution of activity intensity was also performed. Within both groups there was a difference in central tendency and variance when comparing dominant and non-dominant limbs for both the lower (Controls: Mean Activity, P < 0.001; Max Activity, P < 0.001; Patients: Mean Activity, P = 0.044; Max Activity, P = 0.009) and upper (Controls: Mean Activity, P < 0.001; Max Activity, P = 0.046; Patients: Mean Activity, P = 0.002; Max Activity, P = 0.049) arm. Within group differences were also present for lower arm entropy in both groups (Controls, P < 0.001; Patients P = 0.041), and at the upper arm for patients (P = 0.003). There were differences between groups for the asymmetry index for both the lower (P = 0.033) and upper arm (P = 0.005), and maximum activity level of the lower arm (P = 0.05). Between group differences were present for time distribution of activity intensity, as the involved upper arm of patients was inactive for a greater time than controls (P = 0.013). These results highlight unique information provided by multiple analysis methods, and include a novel approach of evaluating the distribution of time spent across variable intensity activities.     

Increased serum 2-oxoglutarate associated with high myocardial energy expenditure and poor prognosis in chronic heart failure patients

Myocardial energy expenditure (MEE) and 2-oxoglutarate are elevated in chronic heart failure (CHF) patients compared with healthy controls. To explore whether 2-oxoglutarate could reflect the levels of MEE and predict the prognosis of CHF, 219 CHF patients and 66 healthy controls were enrolled. 2-Oxoglutarate was assayed with Liquid Chromatography–Mass Spectrometry/Mass Spectrometry (LC/MS/MS). CHF patients were divided into 4 groups according to interquartile range of MEE and followed for death or recurrent hospital admission due to CHF for the mean follow-up time 6.64 ± 0.16 months. 2-Oxoglutarate was increased in CHF patients compared with controls (P < 0.01) and correlated with estimated glomerular filtration rate (r = 0.142, P = 0.036), age (r = − 0.269, P < 0.01) and MEE levels (r = 0.307, P < 0.01) in a multiple linear correlation analysis in CHF patients. Furthermore, 2-oxoglutarate (OR = 3.470, 95% CI = 1.557 to 7.730, P = 0.002), N-terminal pro-B-type natriuretic peptide (OR = 4.013, 95% CI = 1.553 to 10.365, P = 0.004), age (OR = 1.611, 95% CI = 1.136 to 2.283, P = 0.007) and left ventricular ejection fraction (OR = 7.272, 95% CI = 3.110 to 17.000, P < 0.001) were independently associated with MEE on multiple logistic regression analysis. Kaplan–Meier event curves showed that high 2-oxoglutarate levels were associated with adverse outcomes (Log Rank, Chi² = 4.026, P = 0.045). This study showed that serum 2-oxoglutarate is associated with MEE levels, which can be used as potential biomarkers for MEE, and it can reflect the clinical severity and short-term outcome of CHF.     

Importance of IL-10 and IL-6 during chronic hepatitis c genotype-1 treatment and their relation with IL28B

This paper investigates serum levels of interleukin 10 (IL-10) and interleukin 6 (IL-6) in patients with chronic hepatitis C genotype 1 (CHC-GT1), the relation of each with clinical and virological characteristics, how they affect the response to combined therapy and their relation with the IL28B polymorphisms rs12979860. Serum level expression and the polymorphism of IL-10, IL-6 and IL28B were determined in 138 CHC-GT1 patients, treated with pegylated interferon/ribavirin (pegIFN-α/RBV) for 48 weeks, in the following samples: baseline, week-12 (during treatment) and week-72 (post-treatment). 77 patients (56%) presented Sustained Virological Response (SVR) and 61 (44%) were non-SVR. Multivariate logistic regression showed that age ? 40 years (aOR = 3.7, 95%CI = 1.5–8.9, P = 0.004), low activity of gamma glutamyl transferase (GGT) (aOR = 0.9, 95%CI = 0.98–0.99, P = 0.028), CC genotype of IL28B polymorphim (aOR = 2.7, 95%CI = 1.0–7.2, P = 0.044) and low IL-6 (aOR = 0.5, 95%CI = 0.3–1.0, P = 0.038) were predictor factors of virological response. In all patients, following treatment, IL-6 decreased at week-12 (P = 0.004) from baseline and had returned to basal values at week-72. Serum IL-10 concentration was significantly decreased at week-72 only in SVR patients (P ? 0.001). When patients were stratified by IL28B polymorphisms rs12979860 CC vs non-CC patients, a statistically significant decrease in IL-10 at week-72 in both groups was observed (P = 0.003 and P ? 0.001, respectively). None of the polymorphisms of IL-10 or IL-6 studied were associated with SVR.ConclusionsCC genotype of IL28B and low IL-6 serum concentration are factors associated independently with SVR. Moreover, decreased IL-10 at week-72 is associated with SVR in both CC and non-CC patients, and both factors are important to determine the effectiveness of treatment.     

Plasma copeptin concentration and outcome after pediatric traumatic brain injury

Higher plasma copeptin level has been associated with poor outcomes of critical illness. The present study was undertaken to investigate the plasma copeptin concentrations in children with traumatic brain injury (TBI) and to analyze the correlation of copeptin with disease outcome. Plasma copeptin concentrations of 126 healthy children and 126 children with acute severe TBI were measured by enzyme-linked immunosorbent assay. Twenty-one patients (16.7%) died and 38 patients (30.2%) had an unfavorable outcome (Glasgow Outcome Scale score of 1–3) at 6 months. Plasma copeptin level was obviously higher in patients than in healthy children (46.2 ± 20.8 pmol/L vs. 9.6 ± 3.0 pmol/L, P < 0.001). Plasma copeptin level was identified as an independent predictor for 6-month mortality [odds ratio (OR) 1.261, 95% confidence interval (CI) 1.112–1.538, P = 0.005] and unfavorable outcome (OR 1.313, 95% CI 1.146–1.659, P = 0.003). The predictive value of copeptin was similar to that of Glasgow Coma Scale (GCS) score for 6-month mortality [area under curve (AUC) 0.832, 95% CI 0.755–0.892 vs. AUC 0.873, 95% CI 0.802–0.926, P = 0.412] and unfavorable outcome (AUC 0.863, 95% CI 0.790–0.918 vs. AUC 0.885, 95% CI 0.816–0.935, P = 0.596). Copeptin improved the AUC of GCS score for 6-month unfavorable outcome (AUC 0.929, 95% CI 0.869–0.967, P = 0.013), but not for 6-month mortality (AUC 0.887, 95% CI 0.818–0.936, P = 0.600). Thus, plasma copeptin level represents a novel biomarker for predicting 6-month clinical outcome in children with TBI.     

High TMPRSS4 expression is a predictor of poor prognosis in cervical squamous cell carcinoma

Objective The aim of this study was to clarify the clinical role of TMPRSS4 expression in cervical squamous cell carcinoma (CSCC) and to investigate the role of TMPRSS4 in predicting outcomes of patients with CSCC. Methods The retrospective study enrolled 87 patients diagnosed with CSCC between 2004 and 2006. TMPRSS4 expression in CSCC was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. The impact of TMPRSS4 expression on 5-year disease-free survival (DFS) and 5-year overall survival (OS) was assessed by Kaplan–Meier analysis and Cox proportional hazards modeling. Results The high expression of TMPRSS4 was 63.2% in 87 patients with CSCC, and 17.5% in 40 patients with benign cervical disease (P < 0.001). High TMPRSS4 expression was significantly associated with tumor grade (P = 0.005), lymph node metastasis (P = 0.004), and deep cervical stromal invasion (P = 0.025). Patients with high expression of TMPRSS4 had shorter OS and DFS than those with low expression (P = 0.0205 and P = 0.0318, respectively). In multivariate Cox regression analysis, high expression of TMPRSS4 was a potential prognostic indicator for OS (P = 0.041) and DFS (P = 0.015). Conclusion Our findings suggest that TMPRSS4 might play an important role in the progression of CSCC. TMPRSS4 could be a potential prognostic marker of CSCC.     

Interleukin-1 receptor antagonist gene (IL1RN) polymorphism possibly associated to severity of rheumatic carditis in a Brazilian cohort

Aims: To evaluate the IL1RN polymorphism as a possible marker for Rheumatic Fever (RF) susceptibility or disease severity. Methods: The genotypes of 84 RF patients (Jones criteria) and 84 normal race-matched controls were determined through the analysis of the number of 86-bp tandem repeats in the second intron of IL1RN. The DNA was extracted from peripheral-blood leukocytes and amplified with specific primers. Clinical manifestations of RF were obtained through a standardized questionnaire and an extensive chart review. Carditis was defined as new onset cardiac murmur that was perceived by a trained physician with corresponding valvae regurgitation or stenosis on echocardiogram. Carditis was classified as severe in the presence of congestive heart failure or upon the indication for cardiac surgery. The statistical association among the genotypes, RF and its clinical variations was determined. Results: The presence of allele 1 and the genotype A1/A1 were found less frequently among patients with severe carditis when compared to patients without this manifestation (OR = 0.11, p = 0.031; OR = 0.092, p = 0.017). Neither allele 1 nor allele 2 were associated with the presence of RF (p = 0.188 and p = 0.106), overall carditis (p = 0.578 and p = 0.767), polyarthritis (p = 0.343 and p = 0.313) and chorea (p = 0.654 and p = 0.633). Conclusion: In the Brazilian population, the polymorphism of the IL-1ra gene is a relevant factor for rheumatic heart disease severity.     

Perfil clínico y mortalidad a 90 días de los pacientes centenarios atendidos en servicios de urgencias hospitalarios

ObjectivesTo determine the clinical profile and to develop a model to predict 90-day mortality in centenarian patients attended in emergency departments (ED).MethodologyThis was an observational, retrospective, multicentre cohort study including patients > 99 years attended in 5 ED in the Community of Madrid from January to December 2012. Demographic variables were recorded, as well as, comorbidities, cognitive, functional, social basal status, geriatric syndromes, acute episode, and hospital and social resources use, and 90-day mortality.ResultsThe study included 209 patients aged 101 years (SD 1.7) of whom 161 (77.0%) were female. Sixty four (32.5%) had severe comorbidity (Charlson index ≥ 3), 101 (49.8%) on multiple medication, 100 (52.6%) had cognitive impairment, 82 (42.3%) had severe functional dependence, 85 (40.7%) were institutionalised, and 190 (94.5%) had a geriatric syndrome. Dyspnoea (26.8%), followed by falls (12.4%) were the most common causes of attendance. One hundred and eighteen (56.5%) were admitted, and 58 out of 174 (33.3%) died in the first 90 days. The model to predict 90-day overall mortality included male sex (OR 2.42 95% CI = 0.97-6.04; P = .059), emergency care in the previous 3 months (OR 4.08 95% CI = 1.26-13.16; P = .019) and the hospitalization by index event (OR 8.63 95% CI = 3.25-22.9; P < .001) and this model had an area under ROC curve of 0.776 (95% CI = 0.70-0.85; P < .001).ConclusionsCentenarian patients attended in ED had a significant frailty and one in three cases died in the first 90 days after being attended, and this was associated with male sex, emergency care in the previous 3 months, and hospitalisation.     

Polymorphisms of tumor-related genes IL-10, PSCA,MTRR and NOC3L are associated with the risk of gastric cancer in the Chinese Han population

BackgroundGastric cancer is the fourth most common cancer in the world. Environmental and genetic factors both play critical roles in the etiology of gastric cancer. Hundreds of SNPs have been identified to have association with the risk of gastric cancer in many races. In this study, 25 SNPs in genes for IL-10, IL-1B, MTRR, TNF-а, PSCA, PLCE1 and NOC3L were analyzed to further evaluate their associations with gastric cancer susceptibility in the Chinese Han population.MethodsTwo hundred and seventy nine gastric cancer patients and 296 healthy controls were recruited in this study. SNP genotyping was conducted using Sequenom MassARRAY RS1000. Data management and statistical analyses were conducted by Sequenom Typer 4.0 Software and Pearson's χ² test.ResultsOne protective allele and three risk alleles for gastric cancer patients were found in this study. The allele “G” of rs1801394 in MTRR showed an association with a decreased risk of gastric cancer: odds ratio (OR) = 0.74, 95% confidence interval (95% CI) = 0.57–0.97, P = 0.030 in the additive model; OR = 0.495, 95% CI = 0.26–0.95, P = 0.034 in the recessive model. The other three SNPs, the allele “C” of rs1800871 in IL10 (OR = 1.33, 95% CI = 1.04–1.90; P = 0.026 in the additive model; OR = 1.46, 95% CI = 1.04–2.06; P = 0.030 in the recessive model), the allele “A” of rs2976391 in PSCA (OR = 1.30, 95% CI = 1.01–1.66; P = 0.041 in the additive model and OR = 1.48, 95% CI = 1.04–2.11, P = 0.028 in the recessive model), and the allele “G” of rs17109928 in NOC3L gene (OR = 1.34, 95% CI = 1.01–1.78; P = 0.042 by additive model analysis; OR = 1.47, 95% CI = 1.04–2.07, P = 0.028 by dominant model analysis), showed an association with an increased risk of gastric cancer.ConclusionsThese results indicate the importance of four gastric cancer susceptibility polymorphisms of IL-10, NOC3L, PSCA and MTRR in the Chinese Han population, which could be used in the determination of gastric cancer risk in clinical practice.     

Incorporating sheep into dryland grain production systems: I. Impact on over-wintering larva populations of wheat stem sawfly,Cephus cinctus Norton (Hymenoptera: Cephidae)

Wheat stem sawfly (WSS), Cephus cinctus Norton (Hymenoptera: Cephidae) is the most damaging insect pest to Montana's $ 1 billion dollar per year grain industry. Current WSS control methods are either expensive, reduce wheat yields, or are not effective. Our objective was to compare burning, grazing, tilling, trampling and clipping wheat stubble fields on over-wintering WSS larval populations. Treatments were evaluated in three experiments using a randomized complete block design and four replications at each site. Eight, six, and two sites were used for Experiments 1, 2, and 3, respectively. Contrast statements were used to make pre-planned comparisons among treatments. For Experiment 1, treatments were fall tilled, fall grazed, spring grazed, fall and spring combined (Fall/Spr) grazed, and an untreated control. Five mature ewes were confined with electric fence to 111 m² plot for 24 h in the fall and spring grazed treatments resulting in a stocking rate of 452 sheep d/ha. For Fall/Spr, the stocking rate was 904 sheep d/ha. For Experiment 2, treatments were fall grazed, fall burned, fall tilled, and an untreated control. In Experiment 3, treatments were fall trampled, spring trampled, Fall/Spr trampled, hand clipped to a stubble height of 4.5 cm, and an untreated control. Trampled treatments were done at the same stocking rates as grazing treatments but sheep were muzzled to prevent intake. Wheat stem sawfly larval numbers were collected in the fall and spring, pre- and post-treatment, respectively, by collecting all plant material from three, 0.46 m lengths of row and counting the number of live larvae present. In Experiment 1, WSS mortality was greater (P < 0.01) for the mean of all grazed treatments (68.4%) than either control (43%) or tilled (47%) plots. Mortality did not differ (P = 0.75) between fall (67%) and spring (64%) grazed plots but was greater (P = 0.02) for Fall/Spr (74%). In Experiment 2, larva mortality was greater (P < 0.01) for fall grazed (63%) than burned plots (52%). In Experiment 3, WSS mortality was greater (P < 0.01) for the mean of all trampling treatments (57%) than either control (33%) or clipped (32%) plots. Mortality did not differ (P > 0.25) between fall (54%) and spring trampling (47%) but was greater (P = 0.01) for Fall/Spr (70.6%). No differences (P > 0.25) were detected for WSS mortality when grazing was compared to trampling. These results indicate the potential for using grazing sheep to control wheat stem sawfly infestations in cereal grain production systems.     

Impact of HLA-class I alleles on response to HCV treatment in a cohort of Egyptian patients

Extensive allele diversity is observed in HLA associations with response to HCV combined therapy (pegylated interferon + ribavitin) in different global ethnic populations. The aim of the study is to assess the frequency and association of certain HLA-class I alleles in Egyptian persons with persistent HCV and others with sustained viral response (SVR).Material and methodsThe study was a retrospective cohort study that included 246 HCV patients who received combined therapy; 106 cases responded to treatment (SVR) and 140 individuals did not respond to treatment (persistent HCV infection). Both groups are subjected to genotyping for HLA-class I.ResultsAccording to logistic regression analysis, Cw17 was considered as the most predictor allele as it was the highest significant allele (OR = 16.70; 95% CI: 2.64–105.58; P = 0.003), whereas the presence of the HLA-B45 and HLA-B27 alleles has a 19.35-fold risk and 15.7 fold risk, respectively of non-response to interferon therapy in chronic HCV patients (OR = 19.35; 95% CI: 1.05–357.24; P = 0.04) and (OR = 15.69; 95% CI: 1.179–208.9; P = 0.04) can act also as high predictor alleles, and the lowest significant predictor allele was B44 (OR = 6.535; 95% CI: 1.55–27.63; P = 0.01). The presence of the HLA-A alleles might have a limited role in prediction for the non-responders, as the A32 was significantly higher among the SVR patients, but, it cannot have a predictor role (OR: 0.161, CI: 0.03–1.056, P = 0.049).ConclusionCw17, HLA-B45, and HLA-B27 alleles can predict the nonresponders to HCV combined therapy.     

Cathepsin G activity lowers plasma LDL and reduces atherosclerosis

Cathepsin G (CatG), a serine protease present in mast cells and neutrophils, can produce angiotensin-II (Ang-II) and degrade elastin. Here we demonstrate increased CatG expression in smooth muscle cells (SMCs), endothelial cells (ECs), macrophages, and T cells from human atherosclerotic lesions. In low-density lipoprotein (LDL) receptor-deficient (Ldlr^–/–) mice, the absence of CatG reduces arterial wall elastin degradation and attenuates early atherosclerosis when mice consume a Western diet for 3 months. When mice consume this diet for 6 months, however, CatG deficiency exacerbates atherosclerosis in aortic arch without affecting lesion inflammatory cell content or extracellular matrix accumulation, but raises plasma total cholesterol and LDL levels without affecting high-density lipoprotein (HDL) or triglyceride levels. Patients with atherosclerosis also have significantly reduced plasma CatG levels that correlate inversely with total cholesterol (r = –0.535, P < 0.0001) and LDL cholesterol (r = –0.559, P < 0.0001), but not with HDL cholesterol (P = 0.901) or triglycerides (P = 0.186). Such inverse correlations with total cholesterol (r = –0.504, P < 0.0001) and LDL cholesterol (r = –0.502, P < 0.0001) remain significant after adjusting for lipid lowering treatments among this patient population. Human CatG degrades purified human LDL, but not HDL. This study suggests that CatG promotes early atherogenesis through its elastinolytic activity, but suppresses late progression of atherosclerosis by degrading LDL without affecting HDL or triglycerides.     

Intérêt pronostique et prédictif de la TEP-TDM au 18F-FDG au bilan initial des mélanomes de stade IIIB-C-D et IV avant traitement par anti-PD-1

PurposeThe advent of immunotherapy by checkpoint inhibitor has profoundly changed the prognosis of patients with metastatic melanoma. The objective of our study was to evaluate the prognostic and predictive performance of 18F-FDG PET/CT of the initial extension assessment of stage IIIB-C-D and IV melanomas.MethodsWe retrospectively included 57 patients who had 18F-FDG PET/CT prior to the introduction of anti-PD-1 immunotherapy. The parameters extracted were SUVmax, SUV peak, MTV and TLG of the lesion with highest uptake (MTV LM, TLG LM), as well as MTV total and TLG total, obtained by adaptive segmentation. The18F-FDG PET/CT were dichotomized using the optimal threshold measured according to the area under the curve in the ROC (Receiver Operation Characteristic) curves. These parameters were evaluated using a Cox model. Overall survival and progression-free survival analyses were performed using the Kaplan Meier model.ResultsThe median follow-up was 25.4 months, 38 patients had progressed or recurred, and 20 patients had died. TLG LM > 132.59 (P = 0.0011), MTV total > 12 cm³ (P = 0.0139), and TLG > 94.17 (P = 0.0084) were significantly associated with a shorter progression-free survival. TLG LM > 145.92 (P = 0.0062), MTV total > 10.16 cm³ (P = 0.0051), and a metastatic spread > 2 organs (P = 0.0001) were associated with a shorter overall survival.ConclusionWe confirm the potential prognostic interest of PET-TDM at 18FDG before immunotherapy of stage IIIB-C-D and IV melanomas on progression-free survival and overall survival. The combination of these metabolic markers reflecting tumor burden with clinical and biological prognostic factors could allow early identification of patients at high risk of anti-PD-1 failure.     

Delayed treatment with GnRH agonist,hCG and progesterone and reduced embryonic mortality in buffaloes

The present study examined the effect of delayed treatment with tropic hormones and progesterone (P₄) on embryonic mortality in buffaloes. Buffaloes with a conceptus on Day 25 after AI were assigned to the following treatments: Control (n = 41), i.m. physiological saline; GnRH agonist (n = 36), i.m. 12 μg buserelin acetate; hCG (n = 33), i.m. 1500 IU hCG; P₄ (n = 38), i.m. 341 mg P₄ every 4 days on three occasions. Control buffaloes had an embryonic mortality of 41.4% (17/41) between Days 25 and 45, and this was reduced (P < 0.01) by treatment with GnRH agonist (11.1%, 4/36), hCG (9.0%, 3/33) and P₄ (13.1%, 5/38). On Day 45, buffaloes treated with hCG and which ovulated had greater (P < 0.05) concentrations of P₄ in whey (453 ± 41 pg/ml) than buffaloes in the same treatment that did not ovulate (297 ± 32 pg/ml). A similar but non-significant trend was observed for buffaloes treated with GnRH agonist. It was concluded from the findings that the treatment of buffaloes on Day 25 after AI with tropic hormones or P₄ is beneficial to processes associated with embryonic implantation.     

Immune mobilization of autologous blood progenitor cells: direct influence on the cellular subsets collected

Background aimsA phase I trial examined the ability of immunotherapy to mobilize progenitor and activated T cells.MethodsInterleukin (IL)-2 was administered subcutaneously for 11 days, with granulocyte (G)-colony-stimulating factor (CSF) (5 mcg/kg/day) and granulocyte–macrophage (GM)-CSF (7.5 mcg/kg/day) added for the last 5 days. Leukapheresis was initiated on day 11. Thirteen patients were treated (myeloma n = 11, non-Hodgkin's lymphoma n = 2).ResultsToxicities were minimal. IL-2 was stopped in two patients because of capillary leak (n = 1) and diarrhea (n = 1). Each patient required 2.5 leukaphereses (median; range 1–3) to collect 3.2 × 10⁶ CD34⁺ cells/kg (median; range 1.9–6.6 × 10⁶/kg). Immune mobilization increased the number of CD3⁺ CD8⁺ T cells (P = 0.002), CD56⁺ natural killer (NK) cells (P = 0.0001), CD8⁺ CD56⁺ T cells (P = 0.002) and CD4⁺ CD25⁺ cells (P = 0.0001) compared with cancer patients mobilized with G-CSF alone. There was increased lysis of myeloma cells after 7 days (P = 0.03) or 11 days (P = 0.02). The maximum tolerated dose of IL-2 was 1 × 10⁶ IU/m²/day.ConclusionsImmune mobilization is well tolerated with normal subsequent marrow engraftment. As cells within the graft influence lymphocyte recovery, an increased number of functional lymphocytes may result in more rapid immune reconstitution.     

Recherche de facteurs de risque de la thrombopénie induite par le 177Lu-DOTATATE dans le bilan de suivi standard

PurposeThe thrombocytopenia induced by the ¹⁷⁷Lu-DOTATATE is one of its frequent, adverse effects. Its persistence causing problems in the subsequent management of patients, especially when the disease progression occurs, predicting it is a major issue. Due to the lack of knowledge about this subject, we searched to determine the existence of predisposing factors concerning the platelet toxicity in the standard follow-up.Material and methodsThis monocentric retrospective study included 20 patients with gastroenteropancreatic neuroendocrine tumors. Various parameters were analyzed, including: the standard blood analysis, the osteomedullary invasion factor, the spleen's volume and the estimated activity in the bone marrow or the spleen 24 hours post-injection.ResultsFour patients had a persistent grade 2 thrombocytopenia, one year after the last treatment. A decrease in platelet count after the first treatment above 30% and an osteomedullary invasion factor above 30% were highlighted as risk factors odds-ratio = ∞ (P = 0.0379) and odds-ratio = ∞ (P = 0.003) respectively. The initial platelet count, splenic length and estimated activity in the spleen after 24 h were correlated with platelet nadir value r = 0.5459 (P = 0.0128); r = − 0,8105 (P < 0,0001) and r = − 0.467; (P < 0.0001) respectively.ConclusionThis study has shown that the decrease of platelet's count after the first round of treatment and the scale of osteomedullary invasion are risk factors for thrombocytopenia and has brought to light that the spleen acts as a factor impacting the severity of this thrombocytopenia.     

Low serum interleukin-6 levels as a predictive marker of recurrence in patients with hepatitis B virus related hepatocellular carcinoma who underwent curative treatment

BackgroundWe aimed to investigate the use of novel serum biomarkers for predicting the recurrence and survival of patients with hepatitis B virus (HBV)-related early hepatocellular carcinoma (HCC) after hepatic resection or radiofrequency ablation (RFA).MethodsOne hundred and five patients with HBV-related HCC, who fulfilled the Milan criteria without vascular invasion and underwent hepatic resection or RFA, were followed-up for a median duration of 52 months. Pretreatment serum concentrations of 16 cytokines including interleukin-6 (IL-6) were measured by using a Luminex 200 system. The measured serum cytokines and several clinical factors were analyzed retrospectively.ResultsUnivariate analysis showed that patients with lower pretreatment serum levels of IL-10, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α had significantly shorter disease-free survival (DFS) than those with higher levels. Multivariate analysis revealed that a low serum IL-6 level (⩽33.00 pg/mL; hazard ratio [HR] = 5.39; 95% confidence interval [CI] = 1.27–22.93; P = 0.022), low platelet count (<100 × 10⁹/L; HR = 2.23; 95% CI = 1.28–3.89; P = 0.005), and low serum albumin level (⩽3.5 g/L; HR = 2.26; 95% CI = 1.28–3.97; P = 0.005) had a negative prognostic impact on DFS. In the analysis for overall survival, a low serum platelet level (<100 × 10⁹/L; HR = 2.80; 95% CI = 1.31–5.99; P = 0.008) and multiple tumor (⩾2; HR = 4.05; 95% CI = 1.56–10.48; P = 0.004) showed a negative prognostic impact on the overall survival.ConclusionA low serum IL-6 level is, in addition to low platelet count and low serum albumin level, an independent prognostic factor for DFS in patients with HBV-related early HCC who underwent hepatic resection or RFA with curative intention.