KRD (carfilzomib and lenalidomide plus dexamethasone) for the treatment of relapsed or refractory multiple myeloma in the real-life: a retrospective survey in 123 patients.

From April 2016, carfilzomib, in combination with lenalidomide and dexamethasone (KRD), became available for use in the daily practice in Italy for patients with relapsed or refractory multiple myeloma (RRMM). We performed a retrospective survey at 14 different institutions from Southern Italy in order to evaluate patient characteristics and treatment results from an unselected series of patients treated accordingly so far. One hundred and twenty-three consecutive patients were included, with a median of 2 previous lines of therapy (range 1-9) and a median age of 63 years (range 39-82). At the time of analysis, median number of courses administered is 11 (range 1-34), and all patients are evaluable for response. Overall response rate including complete remission, very good partial remission, and partial remission is 85%. After a median follow-up of 27 months, median overall and progression-free survival are 33 and 23 months, respectively. Sixty-three patients are alive and between them, 45 (37%) are in continuous remission. Sixty patients have died (49%), mainly from progressive disease. There were 6 treatment-related deaths (5% of the whole patient population). Overall, hematological and non-hematological toxicity were manageable, mostly on outpatient basis. Arterial hypertension has been observed in 43 cases (35%) but did not lead to treatment interruption. Our data demonstrate that in real life, KRD is highly effective and well tolerated in the majority of patients with RRMM.

Inflammation and oxidative stress transcription profiles due to in vitro supply of methionine with or without choline in unstimulated blood polymorphonuclear leukocytes from lactating Holstein cows.

Neutrophils are the most important polymorphonuclear leukocytes (PMNL), representing the front-line defense involved in pathogen clearance upon invasion. As such, they play a pivotal role in immune and inflammatory responses. Isolated PMNL from 5 mid-lactating Holstein dairy cows were used to evaluate the in vitro effect of methionine (Met) and choline (Chol) supplementation on mRNA expression of genes related to the Met cycle and innate immunity. The target genes are associated with the Met cycle, cell signaling, inflammation, antimicrobial and killing mechanisms, and pathogen recognition. Treatments were allocated in a 3 × 3 factorial arrangement, including 3 Lys-to-Met ratios (L:M, 3.6:1, 2.9:1, or 2.4:1) and 3 levels of supplemental Chol (0, 400, or 800 µg/mL). Three replicates per treatment group were incubated for 2 h at 37°C and 5% atmospheric CO2. Both betaine-homocysteine S-methyltransferase and choline dehydrogenase were undetectable, indicating that PMNL (at least in vitro) cannot generate Met from Chol through the betaine pathway. The PMNL incubated without Chol experienced a specific state of inflammatory mediation [greater interleukin-1ß (IL1B), myeloperoxidase (MPO), IL10, and IL6] and oxidative stress [greater cysteine sulfinic acid decarboxylase (CSAD), cystathionine gamma-lyase (CTH), glutathione reductase (GSR), and glutathione synthase (GSS)]. However, data from the interaction L:M × Chol indicated that this negative state could be overcome by supplementing additional Met. This was reflected in the upregulation of methionine synthase (MTR) and toll-like receptor 2 (TLR2); that is, pathogen detection ability. At the lowest level of supplemental Chol, Met downregulated GSS, GSR, IL1B, and IL6, suggesting it could reduce cellular inflammation and enhance antioxidant status. At 400 µg/mL Chol, supplemental Met upregulated PMNL recognition capacity [higher TLR4 and L-selectin (SELL)]. Overall, enhancing the supply of methyl donors to isolated unstimulated PMNL from mid-lactating dairy cows leads to a low level of PMNL activation and upregulates a cytoprotective mechanism against oxidative stress. Enhancing the supply of Met coupled with adequate Chol levels enhances the gene expression of PMNL pathogen-recognition mechanism. These data suggest that Chol supply to PMNL exposed to low levels of Met effectively downregulated the entire repertoire of innate inflammatory-responsive genes. Thus, Met availability in PMNL during an inflammatory challenge may be sufficient for mounting an appropriate biologic response.

Far-off and close-up dry matter intake modulate indicators of immunometabolic adaptations to lactation in subcutaneous adipose tissue of pasture-based transition dairy cows.

The common practice of increasing dietary energy density during the close-up dry period (last ∼3 wk prepartum) has been recently associated with a higher incidence of metabolic disorders after calving. Despite these reports, over-feeding of metabolizable energy (ME) during the far-off, nonlactating period is a common management policy aimed at achieving optimum calving body condition score (BCS) in pasture-based systems, as cows are generally thinner than total mixed ration cows at the end of lactation. Our hypothesis was that both far-off and close-up overfeeding influence the peripartum adipose tissue changes associated with energy balance and inflammatory state. Sixty mid-lactation, grazing dairy cows of mixed age and breed were randomly allocated to 1 of 2 groups that were managed through late lactation to achieve a low and high BCS (approximately 4.25 and 5.0 on a 10-point scale) at dry-off. The low BCS cows were then overfed ME to ensure that they achieved the same BCS as the higher BCS group by calving. Within each rate of BCS gain treatment, cows were offered 65, 90, or 120% of their pre-calving ME requirements for 3 wk pre-calving in a 2 × 3 factorial arrangement of treatments (i.e., 10 cows/treatment). Subcutaneous adipose tissue was collected via biopsy at -1, 1, and 4 wk relative to parturition. Quantitative PCR was used to measure mRNA and microRNA expression of targets related to adipogenesis and inflammation. Cows overfed in the far-off period had increased expression of miR-143 and miR-378 prepartum (-1 wk) indicating greater adipogenesis, consistent with their rapid gain in BCS following dry-off. Furthermore, the lower postpartum expression of IL6, TNF, TLR4, TLR9, and miR-145, and a higher abundance of miR-99a indicated lower body fat mobilization in early lactation in the same group. In the close-up period, feeding either 65 or 120% of ME requirements caused changes in FASN, IL1B, IL6R, TLR9, and the microRNA miR-143, miR-155, and miR-378. Their respective expression patterns indicate a tentative negative-feedback mechanism in metabolically compromised, feed-restricted cows, and a possible immune-related stimulation of lipolysis in apparently static adipocytes in overfed cows. Data from cows fed 90% of ME requirements indicate the existence of a balance between lipolytic (inflammatory-related) and anti-lipolytic signals, to prime the mobilization machinery in light of imminent lactation. Overall, results indicate that far-off dry cow nutrition influences peripartum adipose tissue metabolism, with neither strategy negatively affecting the physiological adaptation to lactation. Furthermore, to ensure a favorable transition, cows should be subjected to a small feed restriction in the close-up period, irrespective of far-off nutritional management.

Fresh Insights into Disease Etiology and the Role of Microbial Pathogens.

Pathogens have been implicated in the initiation and/or promotion of systemic sclerosis (scleroderma, SSc); however, no evidence was found to substantiate the direct contribution to this disease in past years. Recently, significant advances have been made in understanding the role of the innate immune system in SSc pathogenesis, supporting the idea that pathogens might interact with host innate immune-regulatory responses in SSc. In light of these findings, we review the studies that identified the presence of pathogens in SSc, along with studies on pathogens implicated in driving the innate immune dysregulation in SSc. The goal of this review is to illustrate how these pathogens, specifically viruses, may play important role both as triggers of the innate immune system, and critical players in the development of SSc disease.

Growth performance, carcass characteristics and meat composition of Milanino chickens fed on diets with different protein concentrations.

Milanino is a heavy Italian chicken breed included in a conservation project of the University of Milan and is an important genetic resource for alternative production systems. This research was aimed to study the effect of the dietary protein concentration on growth, slaughter performance and meat composition in free-range reared Milanino chickens. A total of 120 Milanino chickens were fed on different protein concentrations (HP = 20% CP and LP = 16% CP), reared according to a free-range system and slaughtered at 150 and 180 d of age. Growth, slaughter performance and meat (breast and thigh) composition were recorded. The protein concentration of the diet did not affect the overall Milanino mean body weight recorded in the straight-run group in the whole rearing period. However, the growth rate within sex was significantly different between the dietary treatments: heavier females were found in the HP group from 125 d onwards, while no differences were recorded in male body weights. The protein concentration of the diet did not affect carcass weight data or meat composition. The present results suggest the use of a low-protein diet for rearing straight-run Milanino chickens for long rearing periods. However, in females, a high-protein diet is recommended from 125 d of age onwards.

Value of KRAS as prognostic or predictive marker in NSCLC: results from the TAILOR trial.

BACKGROUND: The prognostic and predictive role of KRAS mutations in advanced nonsmall-cell lung cancer (NSCLC) is still unclear. TAILOR prospectively assessed the prognostic and predictive value of KRAS mutations in NSCLC patients treated with erlotinib or docetaxel in second line. PATIENTS AND METHODS: NSCLC patients from 52 Italian hospitals were genotyped for KRAS and EGFR mutational status in two independent laboratories. Wild-type EGFR patients (N = 218) received first-line platinum-based chemotherapy and were randomly allocated at progression to erlotinib or docetaxel. Overall survival (OS) according to KRAS mutational status was the primary end point. RESULTS: KRAS mutations were present in 23% of TAILOR randomized cases. The presence of a KRAS mutation did not adversely affect progression-free (PFS) or overall (OS) survival [hazard ratio (HR) PFS = 1.01, 95% confidence interval (CI) 0.71-1.41, P = 0.977; OS = 1.24, 95% CI 0.87-1.77, P = 0.233], nor influenced treatment outcome (test for interaction: OS P = 0.965; PFS P = 0.417). Patients randomized to docetaxel treatment experienced longer survival independently from the KRAS mutational status of their tumors (HR: mutated KRAS 0.81, 95% CI 0.45-1.47; wild-type KRAS 0.79, 95% CI 0.57-1.10). CONCLUSION: In TAILOR, KRAS was neither prognostic nor predictive of benefit for either docetaxel or erlotinib. Docetaxel remains superior independently from KRAS status for second-line treatment in EGFR wild-type advanced NSCLC patients. CLINICAL TRIAL REGISTRATION: NCT00637910.

Rice and soy protein isolate in pre-starter diets for broilers.

Although most industries use a specific diet for the pre-starter phase, ingredients are used in the later phases, primarily corn and soybean meal, which at this stage do not have high digestibility. Three experiments : Exp : were carried out to evaluate the substitution of corn by white or parboiled rice : WR, PR : and the inclusion of 6% soy protein isolate : SPI : in pre-starter diets (1 to 7 d). In Exp 1 (1 to 21 d), WR, PR, and SPI were added to the diets until the birds were 21-day-old, whereas in Exps 2 and 3 (1 to 33 d), only until birds were 7-day-old. Birds were fed a basal diet based on corn and soybean meal until the end of the experimental period. In Exp 1, the coefficients of total tract apparent retention : CTTAR : of the pre-starter and the starter diets, ileal and jejunal digestibility of starch in the starter diets, and broiler performance were measured. Subsequently, the same pre-starter diets Exp 1 were evaluated in pellet (Exp 2) or mash (Exp 3) form and different oil percentage (Exp 2) or not (Exp 3). We hypothesized that the ingredients particle size (Exp 2) and fat content (Exp 3) could influence feed intake. There was no interaction among the evaluated factors (P > 0.05). Rice (WR or PR) promoted better results than corn in terms of CTTAR of dietary components, jejunal and ileal starch digestibility, and broiler performance (P < 0.01). In Exp 1, diets with 6% SPI presented better CTTAR, except Nitrogen ( N: ), but lower feed intake, which negatively affected broiler performance (P < 0.01). In Exps 1, 2, and 3, the inclusion of SPI did not improve broiler performance (P > 0.05), so that SPI may not be the best choice for pre-starter diets. The study also suggests that better growth performance and nutrient digestibility can be obtained in broiler chickens if corn is replaced by rice in pre-starter diets.

Global chemokine expression in systemic sclerosis (SSc): CCL19 expression correlates with vascular inflammation in SSc skin.

OBJECTIVE: To characterise global chemokine expression in systemic sclerosis (SSc) skin in order to better understand the relationship between chemokine expression and vascular inflammation in this disease. METHODS: We investigated chemokine mRNA expression in the skin through quantitative PCR analysis comparing patients with diffuse cutaneous (dcSSc) or limited cutaneous (lcSSc) disease with healthy controls. We tested correlations between the most regulated chemokines and vascular inflammation and macrophage recruitment. CCL19 expression was examined in human primary immune cells treated with innate immune activators. RESULTS: The chemokines, CCL18, CCL19 and CXCL13, were upregulated in dcSSc skin, and CCL18 in lcSSc skin. Expression of CCL19 in dcSSc skin correlated with markers of vascular inflammation and macrophage recruitment. Immunofluorescence data showed CCL19 colocalisation with CD163 macrophages in dcSSc skin. In vitro studies on human primary cells demonstrated that CCL19 expression was induced after toll-like receptor activation of peripheral blood mononuclear cells and separated populations of CD14 monocytes. CONCLUSIONS: CCL18, CCL19 and CXCL13-chemoattractants for macrophage and T cell recruitment-were three of six chemokines with the highest expression in dcSSc skin. Increased CCL19 expression in the skin suggests a role for CCL19 in the recruitment of immune cells to the peripheral tissue. Induction of CCL19 in macrophages but not structural cells indicates a role for skin-resident or recruited immune cells in perivascular inflammation. This study demonstrates that CCL19 is a sensitive marker for the perivascular inflammation and immune cell recruitment seen in dcSSc skin disease.

Comparison of methods to homogenize ricotta cheese samples for total solids determination.

Ricotta cheese is an Italian dairy product obtained by heat-coagulation of the proteins in whey, resulting from cheese production. The homogenization method applied to collect ricotta cheese samples could affect the total solids (TS) contents of the products. The aim of this study was to determine the effects of 5 different homogenization methods of the samples collection applied for the accuracy in TS determination in ricotta cheese, including un-homogenized method (UNH), un-homogenized combined with the Ultra-Turrax (IKA-Werke GmbH & Co. KG) method (UNH-UTX), spoon-homogenized method (SPN), spoon-homogenized combined with Ultra-Turrax method (SPN-UTX), and Ultra-Turrax homogenized method (UTX). The repeatability and the standard deviation of repeatability are indicators of agreement between repeated measures for TS contents. Results reported that UNH ricotta cheese samples showed large variation in TS content with values ranging from 18.31% to 25.85% and a standard deviation of repeatability higher than 1%; SPN samples showed repeatability values higher than 0.35% and standard deviation of repeatability ranged until 1.36%, suggesting large variability even in this case; the Ultra-Turrax homogenization reported repeatability values lower than 0.1% and standard deviation of repeatability lower than 0.05%, indicating that this method provides repeatable measurements that may reduce the sources of uncertainty in TS determination.

Integration of ventricular remodeling, synchrony and filling rate parameters to improve the assessment of left ventricular systolic function.

INTRODUCTION AND OBJECTIVES: The aim of this study is to assess the relationship between structural, remodeling, synchrony, and systolic left ventricular (LV) function parameters using gated-SPECT myocardial-perfusion-images (gSPECT-MPI). In addition, obtaining the cut-off values for end-diastolic LV-shape-index (EDLVsi), end-systolic LV-shape-index (ESLVsi), ECC (eccentricity-index) and PER, and developing a new index to evaluate different patterns of the LV systolic function. METHODS: The study was approved by the Hospital's Ethical-Committee (PR[AG]168.2010), and all patients gave their informed consent. We analyzed prospectively 238 patients (age 63.4 ±â€¯13 years) who underwent stress-rest gSPECT-MPI (control-group, n = 148; patients with previous myocardial infarction [MI], n = 90). RESULTS: In the control group, with regard to remodeling parameters: the end-diastolic-volume-index (EDV) and the ECC were the parameters that influenced the EDLVsi (r2: 0.52, p < 0.001). EDV, PER, men, and the ECC were the parameters (r2: 0.44; p < 0.001) which influenced the ESLVsi. EDLVsi, ESLVsi, LVEF and the stroke-volume were the parameters (r2: 0.62; p < 0.001) which influenced the ECC. With regards to PER: LVEF, heart-rate, bandwidth, and the standard-deviation were the influencing parameters (r2: 0.76; p < 0.001). The cut-off values for EDLVsi, ESLVsi, ECC, and PER were 0.59, 0.42, 0.87, and 3.3, respectively. The PER, the ESLVsi and the bandwidth were the parameters related to patients with previous MI (AUC: 0.89); and they allow the assessment of different patterns of systolic function (PERRS-index: peak-emptying-rate, left ventricular-remodeling and synchrony). CONCLUSIONS: The remodeling, synchrony and the systolic function parameters of the LV should be interpreted together (PERRS-index). In this way, we obtain different patterns of LV systolic function.

Quality of Life and Psychiatric Symptoms in Wilson's Disease: the Relevance of Bipolar Disorders.

INTRODUCTION: Wilson's disease is an inherited disorder caused by a gene located on chromosome 13, which involved copper transportation across cell membranes. The disease can cause a reduced incorporation of copper into ceruloplasmin resulting in accumulation of this metal in the liver, central nervous system, kidneys and other organs. The objective is to define the frequencies of psychiatric disorders in WD, the amount of impairment of Quality of Life [QoL] in patients with WD and the relevance of the psychiatric disorders in the QoL of people suffering by WD. METHODS: This is a systematic review. The search of the significant articles was carried out in PubMed using specific key words. RESULTS: Such other neurological diseases, WD is characterized by chronic course and need of treatments, impairment of functional outcomes and high frequency of psychiatric symptoms, although a specific association between Bipolar Disorders and WD was recently found. Despite this, since today few studies are carried on WD patients' quality of life related to psychiatric symptoms. Some new reports showed a link between presence of Bipolar Disorders diagnosis, cerebral damage and low Qol. CONCLUSION: Prospective studies on large cohorts are required to establish the effective impact of psychiatric disorders comorbidity, particularly Bipolar Disorders, on quality of life in WD and to clarify the causal link between brain damage, psychiatric disorders and worsening of QoL.

Effect of dietary tannin supplementation on cow milk quality in two different grazing seasons.

Extensive farming systems are characterized by seasons with different diet quality along the year, as pasture availability is strictly depending on climatic conditions. A number of problems for cattle may occur in each season. Tannins are natural polyphenolic compounds that can be integrated in cows' diet to overcome these seasonal problems, but little is known about their effect on milk quality according to the season. This study was designed to assess the effects of 150 g/head × day of tannin extract supplementation on proximate composition, urea, colour, cheesemaking aptitude, antioxidant capacity, and fatty acid (FA) profile of cow milk, measured during the wet season (WS) and the dry season (DS) of Mediterranean climate. In WS, dietary tannins had marginal effect on milk quality. Conversely, in DS, the milk from cows eating tannins showed 10% lower urea and slight improvement in antioxidant capacity, measured with FRAP and TEAC assays. Also, tannin extract supplementation in DS reduced branched-chain FA concentration, C18:1 t10 to C18:1 t11 ratio and rumenic to linoleic acid ratio. Tannins effect on rumen metabolism was enhanced in the season in which green herbage was not available, probably because of the low protein content, and high acid detergent fibre and lignin contents in diet. Thus, the integration of tannin in the diet should be adapted to the season. This could have practical implications for a more conscious use of tannin-rich extracts, and other tannin sources such as agro-industrial by-products and forages.

[Short exercise-rest versus long myocardial perfusion gated SPECT protocols in patients with ischemic cardiomyopathy]. / Protocolo corto esfuerzo reposo frente a protocolo largo en la gated-SPECT de perfusión miocárdica de pacientes con miocardiopatía isquémica.

OBJECTIVE: The purpose of this study was to analyze left systolic ventricular function and myocardial perfusion characteristics between short one day exercise-rest and long two days gated SPECT (Single Photon Emission Computed Tomography) protocols in patients with ischemic cardiomyopathy (ICM). METHODS: A prospective study of 40 patients (59.6±8.9 years, 3 women) with IHD (left ventricular ejection fraction (EF) ≤40%) was performed with myocardial perfusion gated SPECT. From 5 to 10 days after a one-day exercise-rest study (gated SPECT-1), patients were called back for a second rest study (gated SPECT-2) in order to compare EF and differences in perfusion summed rest score (ΔSRS=SRS1-SRS2) and summed difference score (ΔSDS=SDS1-SDS2) between both protocols. RESULTS: Between rest-gated SPECT-1 (short protocol) and rest-gated SPECT-2 (long protocol) EF increased (34% vs 37%, P= 0.008) in 26 patients (65%), and in 11 patients (27.5%) the increase was ≥5%. There were no significant differences in clinical and coronary angiography variables between patients with and without increase of the EF ≥5%. In the multivariate analysis, ΔSRS (95% CI: -1.1 to -29.2) and ΔSDS (0.179-1.236) were predictors for this EF increase between both studies. CONCLUSIONS: Exercise-rest short protocol can underestimate EF in patients with CM. Stunning but also contamination of rest images by previous exercise images in a short protocol could explain these results.

Cost-effectiveness of myocardial perfusion SPECT and stress test according to coronary revascularization therapy, cardiac events and total mortality: Register of 8,496 patients. / Coste-efectividad de la SPECT de perfusión miocárdica y de la prueba de esfuerzo en relación con la revascularización coronaria, eventos cardíacos y mortalidad total. Registro de 8.496 pacientes.

OBJECTIVE: The aim was to analyze the cost-effectiveness ratio (CER) of stress electrocardiogram (ES) and stress myocardial perfusion imaging (SPECT-MPI) according to coronary revascularization (CR) therapy, cardiac events (CE) and total mortality (TM). MATERIAL AND METHODS: A total of 8,496 consecutive patients who underwent SPECT-MPI were followed-up (mean 5.3±3.5years). Cost-effectiveness for coronary bypass (CABG) or percutaneous CR (PCR) (45.6%/54.4%) according to combined electrocardiographic ischemia and scintigraphic ischemia were evaluated. Effectiveness was evaluated as TM, CE, life-year saved observed (LYSO) and CE-LYSO; costs analyses were conducted from the perspective of the health care payer. A sensitivity analysis was performed considering current CABG/PCR ratios (12%/88%). RESULTS: When electrocardiogram and SPECT approaches are combined, the cost-effectiveness values for CABG ranged between 112,589€ (electrocardiographic and scintigraphic ischemia) and 2,814,715€ (without ischemia)/event avoided, 38,664 and 2,221,559€/LYSO; for PCR ranged between 18,824€ (electrocardiographic and scintigraphic ischemia) and 46,377€ (without ischemia)/event avoided, 6,464 and 36,604€/LYSO. To CE: the cost-effectiveness values of the CABG and CPR in presence of electrocardiographic and scintigraphic ischemia were 269,904€/CE-avoided and 24,428€/CE-avoided, respectively; and the €/LYSO of the CABG and PCR were 152,488 and 13,801, respectively. The RCE was maintained for the current proportion of revascularized patients (12%/88%). CONCLUSIONS: Combined ES and SPECT-MPI results, allows differentiation between patient groups, where the PCR and CABG are more cost-effective in different economic frameworks. The major CER in relation to CR, CE and TM occurs in patients with electrocardiographic and scintigraphic ischemia. PCR is more cost-effective than CABG.

Cartilage oligomeric matrix protein expression in systemic sclerosis reveals heterogeneity of dermal fibroblast responses to transforming growth factor beta.

OBJECTIVE: Cartilage oligomeric matrix protein (COMP) accumulates in systemic sclerosis (SSc) skin and is upregulated by transforming growth factor (TGF)beta. To further characterise the response to TGFbeta in SSc, we investigated TGFbeta1 and COMP expression and myofibroblast staining in SSc skin. METHODS: Skin biopsies from patients with diffuse cutaneous SSc (dSSc), limited cutaneous SSc (lSSc) and healthy controls were evaluated for COMP mRNA expression using real-time PCR. COMP, alpha-smooth muscle actin (SMA) and TGFbeta were assessed in skin sections and in cultured fibroblasts by immunohistochemistry. Clinical disease status was assessed by the modified Rodnan skin score (mRSS). RESULTS: Myofibroblasts expressing SMA and COMP were found coexpressed in many cells in dSSc dermis, but each also stained distinct cells in the dermis. Cultured SSc dermal fibroblasts also showed heterogeneity for COMP and SMA expression, with cells expressing SMA, COMP, both or neither. TGFbeta treatment increased COMP and SMA-expressing cells. COMP mRNA expression in lesional skin from patients with dSSc correlated with the mRSS and TGFbeta1 staining. CONCLUSION: These findings suggest that TGFbeta upregulation of COMP and/or SMA expression in subpopulations of fibroblasts contributes to different pathways of fibrosis and that multiple TGFbeta regulated genes may serve as biomarkers for the degree of SSc skin involvement.

[Analysis of the number of patients needed to treat by coronary revascularisation in relation to the presence of myocardial viability in gated SPECT images: a prospective cohort study from a nuclear cardiology unit]. / Análisis del número de pacientes que es necesario tratar mediante revascularización coronaria en relación con la presencia de viabilidad miocárdica en las imágenes de la gated-SPECT: estudio de cohorte prospectivo desde una unidad de cardiología nuclear.

OBJECTIVE: To evaluate the number of patients needed to treat (NNT) to assess the magnitude of benefit of coronary revascularisation (CR) in patients with ischaemic cardiomyopathy (IC) in relation to the presence or absence of myocardial viability in myocardial perfusion gated-SPECT (single photon emission computed tomography) images. METHOD: We studied 198 consecutive patients with IC using rest gated-SPECT with technetium-based agents. The cardiac mortality was analysed in four groups: viable with CR (n = 50), viable with medical treatment (MT) (n = 90), non-viable with CR (n = 18), and non-viable with medical treatment (n = 40). RESULTS: During 2.3 +/- 1.2 years of follow-up, the cardiac mortality rate in patients with scintigraphic viability criteria undergoing revascularisation was 5.9/100 patients/year and 12.9/100 patients/year in those who received medical treatment. In patients without viability who underwent revascularisation, the cardiac mortality rate was 6.2/100 patients/year and in those who received MT it was 1.9/100 patients/year. In patients with myocardial viability the NNT was 4, while in patients without myocardial viability, the NNT was 24. CONCLUSIONS: In patients with scintigraphic viability criteria, the NNT to obtain one survival with CR was 6 times lower with respect to patients without viability, with lower cost and mortality.

The effects of superoxide dismutase-rich melon pulp concentrate on inflammation, antioxidant status and growth performance of challenged post-weaning piglets.

Piglets can often suffer impaired antioxidant status and poor immune response during post-weaning, especially when chronic inflammation takes place, leading to lower growth rates than expected. Oral administration of dietary antioxidant compounds during this period could be a feasible way to balance oxidation processes and increase health and growth performance. The aim of the trial was to study the effects of an antioxidant feed supplement (melon pulp concentrate) that contains high concentration of the antioxidant superoxide dismutase (SOD) on inflammation, antioxidant status and growth performance of lipopolysaccharide (LPS) challenged weaned piglets. In total, 48 weaned piglets were individually allocated to four experimental groups in a 2×2 factorial design for 29 days. Two different dietary treatments were adopted: (a) control (CTR), fed a basal diet, (b) treatment (MPC), fed the basal diet plus 30 g/ton of melon pulp concentrate. On days 19, 21, 23 and 25 half of the animals within CTR and MPC groups were subjected to a challenge with intramuscular injections of an increasing dosage of LPS from Escherichia coli (serotype 0.55:B5) (+) or were injected with an equal amount of PBS solution (-). Blood samples were collected at the beginning of the trial and under the challenge period for interleukin 1ß, interleukin 6, tumour necrosis factor α, haptoglobin, plasma SOD activity, total antioxidant capacity, reactive oxygen species, red blood cells and plasma resistance to haemolysis, and 8-oxo-7, 8-dihydro-2'-deoxyguanosine. Growth performance was evaluated weekly. A positive effect of melon pulp concentrate was evidenced on total antioxidant capacity, half-haemolysis time of red blood cells, average daily gain (ADG) and feed intake, while LPS challenge increased pro-inflammatory cytokines and haptoglobin serum concentrations, with a reduced feed intake and gain : feed (G : F). The obtained results show that oral SOD supplementation with melon pulp concentrate ameliorates the total antioxidant capacity and the half-haemolysis time in red blood cell of post-weaning piglets, with positive results on growing performance.

A study of the process of apoptosis in animals infected with the contagious ecthyma virus.

Contagious ecthyma virus (CEV) is a disease caused by a parapoxvirus, also is a potent genetic carrier with the capacity for regulating apoptosis in the cells of infected skin, a mechanism that serves for evading the immune response of the host. It has been suggested that the virus may remain in the skin and be able to cause repeated infections in the same flock. The effect of infection as well as the presence of contagious ecthyma virus was evaluated in terms of lesions and apoptosis in the skin of animals, infected both naturally and experimentally. Samples used were obtained from a naturally infected sheep, 5 goats inoculated with CEV and a negative control. Samples obtained were longitudinally sectioned and processed using photon and electron microscopy, and embedded in paraffin and araldite. Samples embedded in paraffin were sectioned in 5 microm of thickness and dyed with orange eosin-hematoxilin G and Gomori's trichrom stain, apoptosis was demonstrated by the TUNEL assay, the viral antigen was revealed using polyclonal antibodies, and the presence of lymphocytes CD4+ and CD8+, with monoclonal antibodies. The samples processed in resin were cut to obtain semi-fine sections and dyed with toluidine blue-borax, and the ultra-fine sections were impregnated with lead citrate and uranyl acetate. Observations were similar in both, the natural infected animal and the experimental group. Infiltration was observed as well as images suggestive of a process of apoptosis. The TUNEL assay demonstrated that the number of epithelial cells undergoing apoptosis diminished during the process and increased among defense cells, until they almost disappeared at the beginning of healing. Cells undergoing apoptosis were located near the sebaceous glands and pilose follicles. The infiltrated lymphocytes gradually diminished. The viral antigen was observed in cells with morphology suggestive of apoptosis, located in sebaceous glands and pilose follicles. Using electron microscopy, cells with morphology compatible with that of lymphocytes were observed to be undergoing apoptosis, but there was little evidence of viral particles.

Cerebral CO2 reactivity in severe head injury. A transcranial Doppler study.

BACKGROUND: Cerebral circulation is profoundly affected by changes in PaCO2. CO2 manipulation plays a basic role in the management of intracranial hypertension; CO2 reactivity (CO2R) defines the changes in CBF in response to changes in PaCO2. Transcranial Doppler has allowed exploring its effects "on line". MATERIALS AND METHODS: We conducted a prospective clinical trial, with the objective of studying CO2R in severe head injury patients. Sixteen severe traumatic brain injury patients, mechanically ventilated, were included. Monitoring of MAP, ICP, CPP, SjO2, ETCO2, and cerebral blood flow velocity (CBFV) was performed. Taking into account basal cerebral hemodynamic pattern, minute ventilation was modified to attain a negative ("A") or positive ("B") deltaPCO2. CO2R was calculated as: CO2R = % deltaCBFV/deltaETCO2 in mmHg (normal value 3.7 +/- 1%/mmHg). CO2R was compared with deltaICP/ deltaPCO2 in each patient. FINDINGS: Three patients were excluded because the change in ETCO2 was too low (deltaETCO2 < 3 mmHg). The median value of CO2R in the total group of 13 patients was 3.38. In "A" the values tended to be lower than in "B". There were four low CO2R values in "A" and none in "B". There was no significant correlation between CO2R and deltaICP/deltaPCO2. CONCLUSIONS: The different "A" and "B" behavior might be due to dissimilar mechanisms involved in the basis of vasodilatation and vasoconstriction. Changes in ventilation must be performed with caution, avoiding sudden increases in CO2 that may increase ICP. The absence of correlation between CO2R and deltaICP/deltaPCO2 is explained, at least partially, by different cranio-cerebral compliance in each patient. Therefore, induced blood volume changes are not directly transmitted to ICP, but their effects depend on the shape of the pressure-volume curve and the position on the curve in which each situation is working.