PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study.

BACKGROUND: Pro-protein convertase subtilisin/kexin 9 (PCSK9) is a proenzyme primarily known to regulate low-density lipoprotein receptor re-uptake on hepatocytes. Whether PCSK9 can concurrently trigger inflammation or not remains unclear. Here, we investigated the potential association between circulating levels of PCSK9 and mortality in patients with severe sepsis or septic shock. METHODS: Plasma PCSK9 levels at days 1, 2 and 7 were measured in 958 patients with severe sepsis or septic shock previously enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. Correlations between levels of PCSK9 and pentraxin 3 (PTX3), a biomarker of disease severity, were evaluated with ranked Spearman's coefficients. Cox proportional hazards models were used to assess the association of PCSK9 levels at day 1 with 28- and 90-day mortality. RESULTS: Median plasma PCSK9 levels were 278 [182-452] ng mL-1 on day 1. PCSK9 correlated positively with PTX3 at the three time-points, and patients with septic shock within the first quartile of PCSK9 showed higher levels of PTX3. Similar mortality rates were observed in patients with severe sepsis across PCSK9 quartiles. Patients with septic shock with lower PCSK9 levels on day 1 (within the first quartile) showed the highest 28- and 90-day mortality rate as compared to other quartiles. CONCLUSION: In our sub-analysis of the ALBIOS trial, we found that patients with septic shock presenting with lower plasma PCSK9 levels experienced higher mortality rate. Further studies are warranted to better evaluate the pathophysiological role of PCSK9 in sepsis.

Resistin is associated with overall survival in non-small cell lung cancer patients during nivolumab treatment.

PURPOSE: Since the role of resistin was evaluated only in patients with non-small cell lung cancer (NSCLC) not treated with immunotherapy, we aimed to evaluate levels of resistin during immunotherapy (nivolumab) and its prognostic role with regard to OS. METHODS/PATIENTS: From a cohort of 78 patients with advanced NSCLC enrolled in a prospective study at Ospedale Policlinico San Martino in Genoa (Italy), 43 patients have been considered for this sub-analysis because of the availability of samples. Before and during nivolumab administration, clinical information and blood samples were collected and resistin, matrix metalloproteinase (MMP)-8, MMP-9, and myeloperoxidase were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Median age was 71 with a prevalence of males and former smokers. Median resistin levels presented a peak at cycle 2 and then dropped down until the last cycle. Resistin correlated with all neutrophil degranulation products at cycle 1 (except for MMP-9) and at cycle 2 as well as with white blood cells and neutrophils. By a ROC curve analysis, a resistin value at cycle 2 of 19 ng/mL was tested as the best cut-off point for OS. Kaplan-Meier analysis demonstrated that patients above the resistin cut-off experienced a reduced OS (median OS 242.5 vs. 470 days, p = 0.0073), as confirmed by Cox proportional hazards regression analysis. CONCLUSIONS: Resistin levels > 19 ng/mL at the time of the second cycle of nivolumab treatment independently predict a reduced OS in patients with advanced NSCLC.

Respiratory allergy in immigrants to a highly industrialised area in Italy according to area of origin and time period

BACKGROUND: Migrants from developing to Western countries tend to become more sensitised to host than to origin country allergens, although substantial changes in migration patterns have occurred in recent decades. Methods We investigated adult immigrants with respiratory allergy, first tested for allergic sensitisation between 1985 and 2012 in a highly industrialised area in Italy. A comparison was made of the sensitisation pattern between immigrants and a random sample of native-born subjects affected by a respiratory allergy, and among immigrants according to macro-region of origin and time period. RESULTS: Between 1985 and 2012, 480 immigrants with respiratory allergy had a first positive allergy test. Immigrants were sensitised mainly to grass (67.1%), house dust mites (HDM) (38.5%) and birch (27.5%), with a pattern of sensitisation very similar to that observed in Italians (native-born). An increase in the proportion of subjects with asthma and of subjects with polysensitisation was observed from the first (1985-2002) to the middle (2003-2007) and the most recent period (2008-2012). In recent years, the proportion of subjects with polysensitisation in immigrants is higher than in Italians (native-born) (53.3% vs. 40.1%). Among immigrants, the risk of sensitisation to grass was higher in those from Sub-Saharan Africa (odds ratio, OR = 2.76) and Latin America (OR = 2.49), whereas risk of sensitisation to HDM was higher among immigrants from South Asia (OR = 2.71), compared to immigrants from Eastern Europe. CONCLUSIONS: Immigrants develop multiple sensitisations more frequently than native-born people, and are especially sensitised to local allergens; the country of origin seems to play a role

No disponible

Respiratory allergy in immigrants to a highly industrialised area in Italy according to area of origin and time period.

BACKGROUND: Migrants from developing to Western countries tend to become more sensitised to host than to origin country allergens, although substantial changes in migration patterns have occurred in recent decades. METHODS: We investigated adult immigrants with respiratory allergy, first tested for allergic sensitisation between 1985 and 2012 in a highly industrialised area in Italy. A comparison was made of the sensitisation pattern between immigrants and a random sample of native-born subjects affected by a respiratory allergy, and among immigrants according to macro-region of origin and time period. RESULTS: Between 1985 and 2012, 480 immigrants with respiratory allergy had a first positive allergy test. Immigrants were sensitised mainly to grass (67.1%), house dust mites (HDM) (38.5%) and birch (27.5%), with a pattern of sensitisation very similar to that observed in Italians (native-born). An increase in the proportion of subjects with asthma and of subjects with polysensitisation was observed from the first (1985-2002) to the middle (2003-2007) and the most recent period (2008-2012). In recent years, the proportion of subjects with polysensitisation in immigrants is higher than in Italians (native-born) (53.3% vs. 40.1%). Among immigrants, the risk of sensitisation to grass was higher in those from Sub-Saharan Africa (odds ratio, OR=2.76) and Latin America (OR=2.49), whereas risk of sensitisation to HDM was higher among immigrants from South Asia (OR=2.71), compared to immigrants from Eastern Europe. CONCLUSIONS: Immigrants develop multiple sensitisations more frequently than native-born people, and are especially sensitised to local allergens; the country of origin seems to play a role.

Italian study on buckwheat allergy: prevalence and clinical features of buckwheat-sensitized patients in Italy.

Buckwheat allergy is considered a rare food allergy outside of Asia. In Europe, buckwheat has been described mainly as a hidden allergen. Data on the prevalence of buckwheat hypersensitivity in non-Asian countries is very poor. The aim of this multicenter study was to evaluate the prevalence of buckwheat sensitization and its association with other sensitizations among patients referred to allergy clinics in different geographic areas of Italy. All patients referred to 18 Italian allergy clinics from February through April 2011 were included in the study and evaluated for sensitization to buckwheat and other allergens depending on their clinical history. A total of 1,954 patients were included in the study and 61.3 percent of them were atopic. Mean prevalence of buckwheat sensitization was 3.6 percent with significant difference between Northern (4.5 percent), Central (2.2 percent) and Southern (2.8 percent) regions. This is, to our knowledge, the largest epidemiological survey on buckwheat allergy reported outside of Asia. Buckwheat is an emerging allergen in Italy, being more frequently associated to sensitization in Northern regions.

Effects of acute ethanol intoxication during pregnancy on central dopaminergic system in male rats.

Pregnant albino rats received 2 IP injections, spaced by 4 h, of either ethanol (2.9 g/kg in 24% v/v saline solution) or saline, on gestational day (GD) 8. During adulthood, male rats prenatally exposed to alcohol exhibited an increased stereotyped behavioral response to 12 mg/kg of amphetamine (AMPH) or 1 mg/kg of apomorphine (APO), whereas the stereotypy induced by 6 mg/kg of AMPH showed no difference between control and experimental animals. Also, the hypoactivity response elicited by small doses of APO was not significantly affected by the prenatal treatment with alcohol. Analysis of dopaminergic function in the striatum and nucleus accumbens demonstrated no change on dopamine (DA) levels in both structures in alcohol pre-exposed 55- and 180-day-old rats. A reduction in striatum 3-4 dihydroxyphenylacetic acid levels was observed at both ages. These results indicate that an acute intoxication with alcohol on GD 8 induces a long-lasting decrease in striatal but not in nucleus accumbens DA metabolism. As a consequence, a lower striatal DA release might produce a compensatory supersensitivity of postsynaptic DA sites. This interpretation is consistent and correlates with behavioral results.

Acute ethanol intoxication during pregnancy: postnatal effects on the behavioral response to serotonin agents.

Pregnant wistar rats were treated on the eighth day of gestation (GD 8) with two IP injections, spaced by 4 h, of either ethanol (2.9 g/kg in 24% v/v saline solution, EG) or saline (SG). Other pregnant females did not received any type of IP injections (absolute control group, ACG). Offspring were tested at 45 or 90 days of age. At 45 days of age, EG showed an increased behavioral response (forepaw treading and hindlimb abduction) to the 5-HT1 agonist, 5-methoxy-N,N-dymethyltryptamine. In addition, an enhanced "wet-dog" shakes behavioral response to 5-HT2 agonist, 5-hydroxy-L-tryptophan, was also observed in EG as compared to ACG and SG. On the contrary, at 90 days, EG exhibited a diminished behavioral reactivity to 5-HT1 and 5-HT2 agonists as compared to SG. These results demonstrated that acute administration of ethanol on GD 8 induced long-lasting changes in the functioning of central serotonergic systems.

Sexual receptivity of adult female rats prenatally intoxicated with alcohol on gestational day 8.

On gestational day 8 (GD 8), pregnant albino rats received two IP injections, spaced by 4 hours, of either ethanol (2.9 g/kg in 24% v/v saline solution) or saline. Adult females exposed to ethanol in utero showed greater sensitivity to estrogen, but not to estrogen plus progesterone, for induction of lordotic response. The 5-HT1 receptor agonist 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT) had a significantly smaller effect in inhibiting lordosis response in experimental rats. The greater sensitivity to estrogen and lower sensitivity to the receptor agonist could be a consequence of long-term changes in central neurotransmitter systems induced by acute intoxication with ethanol on GD 8.

Mass poisoning by sodium arsenite.

An acute massive epidemic of arsenic poisoning in Argentina involved 718 subjects. Urine samples were obtained from 307. The 49 with urine arsenic 76-500 micrograms/dl and 12 with urine arsenic greater than 500 micrograms/dL received dimercaprol treatment. Symptomatology increased with the urine arsenic with increased diarrhea, vomiting and systemic symptoms at urine arsenic greater than 75 micrograms/dL.

Acute ethanol exposure during pregnancy in rats: effects upon a multiple learning task.

Pregnant rats received 4.8 g/kg of 20% (v/v) ethanol IP or identical volume of saline during gestational Day 8. No signs of gross physical teratogenesis were evident in the offspring as expressed by litter size, weight and external malformations at birth. However, when offspring were subjected to a multiple fixed ratio-4/differential reinforcement of low rate of responding 10-sec ( FR 4/DRL 10 sec) schedule of reinforcement at 60 days of age, significant differences were observed in the performance of DRL 10-sec schedule that required visual discrimination and response inhibition, but not in the FR 4 schedule that required a relatively simple nondiscrimination task of active-response. Bar press rates were unaffected by prenatal treatment since no differences between groups were found in the number of total responses performed on either component of the multiple schedule. Present results are discussed in terms of either response perseveration or a lower aptitude to deal with low rates of responding-discrimination learning tasks on the animals prenatally exposed to alcohol.

The effects of practice on 8-10-yr-old children using the Staggered Spondaic Word Test.

Katz' Staggered Spondaic Word (SSW) Test was given at 50 db re SRT to 20 normal right-handed children aged 8 - 10 yrs. Half the Ss heard items 1 - 40 in that order, half heard the order Items 21-40, 1-20. Groups yielded similar total scores. For both groups there were no significant L-R ear differences. Practice on a prior 20 items had a significant effect on later responses to competing stimuli in a later 20-item test. There were too few errors on non-competing stimuli for meaningful analysis. Four practice items as provided by a standard version of this test were determined to be too few with children of this age.