Sarcoid-like Reactions to Immune Checkpoint Inhibitors. / Reacciones sarcoideas relacionadas con inhibidores de puntos de control inmunitario.

Immune checkpoint inhibitors (ICIs) can cause immune-mediated cutaneous adverse events, including sarcoid-like reactions. The aim of this study was to retrospectively analyze clinical and histologic data from patients who developed cutaneous sarcoid-like reactions between 2019 and 2022 while under treatment with ICIs. We studied 7 patients (6 women and 1 man) with a median age of 65years. Median time to onset of symptoms was 4months. The most common presentation was papular sarcoidosis of the knees followed by subcutaneous sarcoidosis. Diagnosis was confirmed histologically in all cases, and no differences were observed relative to idiopathic sarcoidosis. Discontinuation of ICI therapy was required in just two patients. ICI-induced sarcoid-like reactions tend to be mild and generally do not require treatment discontinuation. Histologic confirmation is essential for distinguishing these reactions from tumor progression.

[Translated article] Sarcoid-like Reactions to Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) can cause immune-mediated cutaneous adverse events, including sarcoid-like reactions. The aim of this study was to retrospectively analyze clinical and histologic data from patients who developed cutaneous sarcoid-like reactions between 2019 and 2022 while under treatment with ICIs. We studied 7 patients (6 women and 1 man) with a median age of 65years. Median time to onset of symptoms was 4months. The most common presentation was papular sarcoidosis of the knees followed by subcutaneous sarcoidosis. Diagnosis was confirmed histologically in all cases, and no differences were observed relative to idiopathic sarcoidosis. Discontinuation of ICI therapy was required in just two patients. ICI-induced sarcoid-like reactions tend to be mild and generally do not require treatment discontinuation. Histologic confirmation is essential for distinguishing these reactions from tumor progression.

Extracorporeal membrane oxygenation during pregnancy and peripartal. An international retrospective multicenter study.

INTRODUCTION: Extracorporeal Membrane Oxygenation (ECMO) may be used in the setting of pregnancy or the peripartal period, however its utility has not been well-characterized. This study aims to give an overview on the prevalence of peripartel ECMO cases and further assess the indications and outcomes of ECMO in this setting across multiple centers and countries. METHODS: A retrospective, multicenter, international cohort study of pregnant and peripartum ECMO cases was performed. Data were collected from six ECMO centers across three continents over a 10-year period. RESULTS: A total of 60 pregnany/peripartal ECMO cases have been identified. Most frequent indications are acute respiratory distress syndrome (n = 30) and pulmonary embolism (n = 5). Veno-venous ECMO mode was applied more often (77%). ECMO treatment during pregnancy was performed in 17 cases. Maternal and fetal survival was high with 87% (n = 52), respectively 73% (n = 44). CONCLUSIONS: Various emergency scenarios during pregnancy and at time of delivery may require ECMO treatment. Peripartal mortality in a well-resourced setting is rare, however emergencies in the labor room occur and knowledge of available rescue therapy is essential to improve outcome. Obstetricians and obstetric anesthesiologists should be aware of the availability of ECMO resource at their hospital or region to ensure immediate contact when needed.

Prevalence and morphometric analysis of the retromolar canal in a Spanish population sample: a helical CT scan study.

BACKGROUND: The retromolar canal (RMC) is an anatomical variation of the mandibular canal (MC) whose identification and study should be considered given its implication in the surgical procedures of the retromolar area. The prevalence of the RMC widely varies according to previous studies and may be influenced by the followed study method. This work aimed to evaluate the prevalence of the RMC in a Spanish population sample. MATERIAL AND METHODS: For this purpose, 225 CT scan images (with a higher resolution than the cone beam CT used in other previous studies) from the Hospital Clínico Universitario de Valencia were analyzed. The Osirix MD® radiological image analysis system was applied to analyse the dimensions, location in the retromolar area and morphologic characteristics of the RMC by classifying them according to their typology. Furthermore, the relations between the RMC and gender, age and laterality were studied. RESULTS: RMC prevalence was 23.1%. No significant relation between the presence of the canal and gender, age or laterality was found. Type Ia was the commonest type with a prevalence of 40.8%. CONCLUSIONS: Based on the results of this study, the RMC should be considered a frequent anatomical variation whose complete study is very important in daily clinical practice.

Primary Angioplasty in a Catastrophic Presentation: Acute Left Main Coronary Total Occlusion-The ATOLMA Registry.

OBJECTIVES: To determine the outcome predictors of in-hospital mortality in acute total occlusion of the left main coronary artery (ATOLMA) patients referred to emergent angioplasty and to describe the clinical presentation and the long-term outcome of these patients. BACKGROUND: ATOLMA is an uncommon angiographic finding that usually leads to a catastrophic presentation. Limited and inconsistent data have been previously reported regarding true ATOLMA, yet comprehensive knowledge remains scarce. METHODS: This is a multicenter retrospective cohort that includes patients presenting with myocardial infarction due to a confirmed ATOLMA who underwent emergency percutaneous coronary intervention (PCI). RESULTS: In the period of the study, 7930 emergent PCI were performed in the five participating centers, and 46 of them had a true ATOLMA (0.58%). At admission, cardiogenic shock was present in 89% of patients, and cardiopulmonary resuscitation was required in 67.4%. All the patients had right dominance. Angiographic success was achieved in 80.4% of the procedures, 13 patients (28.2%) died during the catheterization, and the in-hospital mortality rate was 58.6% (27/46). At one-year and at the final follow-up, 18 patients (39%) were alive, including four cases successfully transplanted. Multivariate analysis showed that postprocedural TIMI flow was the only independent predictor of in-hospital mortality (OR 0.23, (95% CI 0.1-0.36), p < 0.001). CONCLUSIONS: Our study confirms that the clinical presentation of ATOLMA is catastrophic, presenting a high in-hospital mortality rate; nevertheless, primary angioplasty in this setting is feasible. Postprocedural TIMI flow resulted as the only independent predictor of in-hospital mortality. In-hospital survivors presented an encouraging outcome. ATOLMA and left dominance could be incompatible with life.

Multivariate factor analysis of milk fatty acid composition in relation to the somatic cell count of single udder quarters.

The present study investigated whether the fatty acid composition of milk changes in relation to an increase in the milk somatic cell count (SCC) of separate udder quarters. We investigated the potential of multivariate factor analysis to extract metabolic evidence from data on the quantity and quality of milk of quarters characterized by different SCC levels. We collected data from individual milk samples taken from single quarters of 49 Italian Holstein cows from the same dairy farm. Factor analysis was carried out on 64 individual fatty acids. In line with a previous study on multivariate factor analysis, a variable was considered to be associated with a specific factor if the absolute value of its correlation with the factor was ≥0.60. Seven factors were extracted that explained the following groups of fatty acids or functions: de novo synthesis, energy balance, uptake of dietary fatty acids, biohydrogenation, short-chain fatty acids, very long chain fatty acids, and odd- and branched-chain fatty acids. An ANOVA of factor scores highlighted the significant effects of the SCC level on de novo fatty acids and biohydrogenation. The de novo fatty acid factor decreased significantly with a high level of SCC, from just 10,000 cells/mL, whereas the biohydrogenation factor showed a significantly higher level in quarters with SCC levels greater than 400,000 cells/mL. This statistical approach enabled us to reduce the number of variables to a few latent factors with biological significance and to represent groups of fatty acids with a common origin and function. Multivariate factor analysis could therefore be key to studying the influence of SCC on the lipid metabolism of single quarters. This approach also demonstrated the metabolic differences between quarters of the same animal showing a different level of SCC.

Contralateral surgery in patients scheduled for total thyroidectomy with initial loss or absence of signal during neural monitoring.

BACKGROUND: Staged total thyroidectomy has been advised to prevent bilateral recurrent laryngeal nerve paralysis when loss of the signal from neural monitoring is observed after dissection of the initial thyroid lobe. This is supported by expert opinion but hard evidence is lacking. A lost signal can return during surgery or, even if it persists, its positive predictive value is only in the range 60-70 per cent. The aim of the present study was to investigate the clinical outcome of patients in whom total thyroidectomy was performed following loss of signal after dissection of the first thyroid lobe. METHODS: This was a prospective observational study of adult patients scheduled for neural monitoring during total thyroidectomy. The prevalence of first-side absence or loss of signal was recorded. The contralateral thyroid lobe was approached routinely. The vagus and recurrent laryngeal nerves on the first side were retested during and at the end of the contralateral procedure. RESULTS: Some 462 patients were included. Loss (32 patients) or initial absence (8) of signal at dissection of the first thyroid lobe was noted in 40 patients (8·7 per cent). Total thyroidectomy was completed in 29 patients, and a change of surgical strategy adopted in 11 patients with benign disease. At retesting, 15 of 37 initially silent nerves recovered electromyographic signal after a mean(s.d.) interval of 30(14) min. Postoperative vocal cord palsy/paresis was demonstrated in 24 of 40 patients. One patient developed a bilateral paresis that could be managed conservatively. CONCLUSION: After an absence or loss of signal of the recurrent laryngeal nerve following dissection of the first thyroid lobe, contralateral thyroidectomy can be performed safely, avoiding the expense, psychological burden and potential complications of a second procedure.

Invited review: Plant polyphenols and rumen microbiota responsible for fatty acid biohydrogenation, fiber digestion, and methane emission: Experimental evidence and methodological approaches.

The interest of the scientific community in the effects of plant polyphenols on animal nutrition is increasing. These compounds, in fact, are ubiquitous in the plant kingdom, especially in some spontaneous plants exploited as feeding resources alternative to cultivated crops and in several agro-industry by-products. Polyphenols interact with rumen microbiota, affecting carbohydrate fermentation, protein degradation, and lipid metabolism. Some of these aspects have been largely reviewed, especially for tannins; however, less information is available about the direct effect of polyphenols on the composition of rumen microbiota. In the present paper, we review the most recent literature about the effect of plant polyphenols on rumen microbiota responsible for unsaturated fatty acid biohydrogenation, fiber digestion, and methane production, taking into consideration the advances in microbiota analysis achieved in the last 10 yr. Key aspects, such as sample collection, sample storage, DNA extraction, and the main phylogenetic markers used in the reconstruction of microbial community structure, are examined. Furthermore, a summary of the new high-throughput methods based on next generation sequencing is reviewed. Several effects can be associated with dietary polyphenols. Polyphenols are able to depress or modulate the biohydrogenation of unsaturated fatty acids by a perturbation of ruminal microbiota composition. In particular, condensed tannins have an inhibitory effect on biohydrogenation, whereas hydrolyzable tannins seem to have a modulatory effect on biohydrogenation. With regard to fiber digestion, data from literature are quite consistent about a general depressive effect of polyphenols on gram-positive fibrolytic bacteria and ciliate protozoa, resulting in a reduction of volatile fatty acid production (mostly acetate molar production). Methane production is also usually reduced when tannins are included in the diet of ruminants, probably as a consequence of the inhibition of fiber digestion. However, some evidence suggests that hydrolyzable tannins may reduce methane emission by directly interacting with rumen microbiota without affecting fiber digestion.

Oral administration of chestnut tannins to reduce the duration of neonatal calf diarrhea.

BACKGROUND: Neonatal calf diarrhea is generally caused by infectious agents and is a very common disease in bovine practice, leading to substantial economic losses. Tannins are known for their astringent and anti-inflammatory properties in the gastro-enteric tract. The aim of this study was to evaluate the effect of the oral administration of chestnut tannins (Castanea sativa Mill.) in order to reduce the duration of calf neonatal diarrhea. Twenty-four Italian Friesian calves affected by neonatal diarrhea were included. The duration of the diarrheic episode (DDE) was recorded and the animals were divided into a control group (C), which received Effydral® in 2 l of warm water, and a tannin-treated group (T), which received Effydral® in 2 l of warm water plus 10 g of extract of chestnut tannins powder. A Mann-Whitney test was performed to verify differences for the DDE values between the two groups. RESULTS: The DDE was significantly higher in group C than in group T (p = 0.02), resulting in 10.1 ± 3.2 and 6.6 ± 3.8 days, respectively. CONCLUSIONS: Phytotherapic treatments for various diseases have become more common both in human and in veterinary medicine, in order to reduce the presence of antibiotic molecules in the food chain and in the environment. Administration of tannins in calves with diarrhea seemed to shorten the DDE in T by almost 4 days compared to C, suggesting an effective astringent action of chestnut tannins in the calf, as already reported in humans. The use of chestnut tannins in calves could represent an effective, low-impact treatment for neonatal diarrhea.

A canonical discriminant analysis to study the association between milk fatty acids of ruminal origin and milk fat depression in dairy cows.

Although milk fat depression (MFD) has been observed and described since the beginning of the last century, all the molecular and biochemical mechanisms involved are still not completely understood. Some fatty acids (FA) originating during rumen biohydrogenation have been proposed as causative elements of MFD. However, contradictory results were obtained when studying the effect of single FA on MFD. An alternative could be the simultaneous evaluation of the effect of many FA using a multivariate approach. The aim of this study was to evaluate the relationship between individual milk FA of ruminal origin and MFD using canonical discriminant analysis, a multivariate technique able to distinguish 2 or more groups on the basis of a pool of variables. In a commercial dairy herd, a diet containing 26% starch on a DM basis induced an unintentional MFD syndrome in 14 cows out of 40. Milk yielded by these 14 animals showed a fat content lower than 50% of the ordinary value, whereas milk production and protein content were normal. The remaining 26 cows secreted typical milk fat content and therefore were considered the control group, even though they ate the same diet. The stepwise discriminant analysis selected 14 milk FA of ruminal origin most able to distinguish the 2 groups. This restricted pool of FA was used, as variables, in a run of the canonical discriminant analysis that was able to significantly discriminate between the 2 groups. Out of the 14 FA, 5 conjugated linoleic acid isomers (C18:2 trans-10,trans-12, C18:2 trans-8,trans-10, C18:2 trans-11,cis-13, C18:2 cis-9,cis-11, C18:2 cis-10,cis-12) and C15:0 iso were more related to the control group, whereas C18:2 trans-10,cis-12, C16:1 trans-6-7, C16:1 trans-9, C18:1 trans-6-8, C18:1 trans-9, C18:1 trans-10, C18:1 cis-11, and C18:3n-3 were positively associated with the MFD group, allowing a complete discrimination. On the basis of these results, we can conclude that (1) the shift of ruminal biohydrogenation from C18:1 trans-11 to C18:1 trans-10 seemed to be strongly associated with MFD; (2) at the same time, other C18:1 trans isomers showed a similar association; (3) on the contrary, conjugated linoleic acid isomers other than C18:2 trans-10,cis-12 seemed to be associated with a normal fat secretion. Results confirmed that MFD is the consequence of a combined effect of the outflow of many ruminal FA, which collectively affect mammary fat synthesis. Because the animals of the 2 groups were fed the same diet, these results suggested that factors other than diet are involved in the MFD syndrome. Feeding behavior (i.e., ability to select dietary ingredients in a total mixed ration), rumen environment and the composition of ruminal bacteria are additional factors able to modify the products of rumen biohydrogenation. Results of the present work confirmed that the multivariate approach can be a useful tool to evaluate a metabolic pathway that involves several parameters, providing interesting suggestions about the role of some FA involved in MFD. However, results about the MFD syndrome obtained in the present research require a deep molecular investigation to be confirmed.

Dietary linseed supplementation affects the fatty acid composition of the sn-2 position of triglycerides in sheep milk.

In the human intestine, lipids are absorbed as sn-2 monoglycerides (sn-2, also named ß-position), produced mainly by pancreatic lipases, which hydrolysate the triglyceride molecule in positions 1 and 3 (sn-1,3, α-position). The fatty acids esterified in sn-2 are thus preferentially absorbed, which means that the bioavailability of a single fatty acid is affected by its position on the triglyceride. This experiment is carried out with the milk used to make cheese applied in a study with 42 human volunteers. In that study the authors detected an improvement in the blood lipid profile. The aim of the present study was to examine the effectiveness of this kind of cheese in improving human health by studying how linseed supplementation affects the milk fatty acid composition of the 3 different triglyceride positions and thus the fatty acid bioavailability. The sn-2 were obtained by reacting total milk lipids with swine pancreatic lipase. The milk came from 24 sheep fed a control diet and 24 sheep fed a diet containing 200 g of extruded linseed per day. The sn-2 were separated by thin-layer chromatography. The fatty acid composition of total lipids and sn-2 was obtained by a gas chromatography-flame ionization detector apparatus equipped with a high polar 100 m length capillary column. The bioavailability of the fatty acids was evaluated by a putative preferential intestinal absorption index (PPIAi), where PPIAi <0 indicated a disadvantageous nutritional condition and PPIAi >0 indicated a preferential intestinal absorption. With regard to the fatty acid composition of triglycerides, the linseed group showed a significantly higher content of both linolenic acid and rumenic acid compared with the control. As a consequence of linseed supplementation, the linolenic and rumenic acid content esterified in the ß-position increased greatly. This was highlighted by the PPIAi. The results of the present study suggest that the linolenic acid and conjugated linoleic acid affinity for lyso-phosphatidic acid acyl-transferase increased with its tissue availability.

Solar photo-Fenton with simultaneous addition of ozone for the treatment of real industrial wastewaters.

Simultaneous application of solar photo-Fenton and ozonation (SPFO) for the efficient treatment of real wastewaters was studied. Four different industrial effluents were selected for the study: landfill leachate, pharmaceutical effluent and two textile wastewaters, in order to demonstrate the effectiveness and versatility of the proposed technology. SPFO performance was compared with individual processes (either solar photo-Fenton or ozonation), as well as the hybrid Fenton and ozonation treatment. In highly polluted wastewaters, combined strategies led to higher organic matter removal than O3 and photo-Fenton processes applied individually. Solar light favoured catalyst regeneration, allowing removal efficiencies up to 67% of chemical oxygen demand (COD) and 62% of total organic carbon (TOC) (in the case of textile wastewaters) using an initial concentration of only 10 mg Fe2+ L-1. The reduction of catalyst consumption, along with the absence of sludge production (since Fe2+ removal from the effluent is not required), led to a significant decrease in operational costs (up to 1.22 € kg-1 COD removed) when combined Fenton and ozonation was applied under solar light. SPFO results in a versatile, effective and economically efficient technology, thus postulating as a promising alternative for reducing the organic load of highly polluted industrial effluents prior to biological treatment.

Painful skin lesions and squamous cell carcinoma predict overall mortality risk in organ transplant recipients: a cohort study.

BACKGROUND: Organ transplant recipients (OTRs) have a highly increased risk of cutaneous squamous cell carcinomas (SCCs). Sensation of pain in cutaneous tumours is a powerful patient-reported warning signal for invasive SCCs in OTRs. OBJECTIVES: To investigate the impact of painful vs. painless skin lesions and SCC vs. other skin lesions on the overall mortality risk in OTRs. METHODS: We followed 410 OTRs from 10 different centres across Europe and North America between 2008 and 2015. These patients had been enrolled in an earlier study to define clinically meaningful patient-reported warning signals predicting the presence of SCC, and had been included if they had a lesion requiring histological diagnosis. Cumulative incidences of overall mortality were calculated using Kaplan-Meier survival analysis, and risk factors were analysed with Cox proportional hazard analysis. RESULTS: There was an increased overall mortality risk in OTRs who reported painful vs. painless skin lesions, with a hazard ratio (HR) of 1·6 [95% confidence interval (CI) 0·97-2·7], adjusted for age, sex and other relevant factors. There was also an increased overall mortality risk in OTRs diagnosed with SCC compared with other skin lesions, with an adjusted HR of 1·7 (95% CI 1·0-2·8). Mortality due to internal malignancies and systemic infections appeared to prevail in OTRs with SCC. CONCLUSIONS: We suggest that OTRs have an increased overall mortality risk if they develop painful skin lesions or are diagnosed with cutaneous SCC.

Effects of early administration of acetazolamide on the duration of mechanical ventilation in patients with chronic obstructive pulmonary disease or obesity-hypoventilation syndrome with metabolic alkalosis. A randomized trial.

BACKGROUND: Metabolic alkalosis (MA) inhibits respiratory drive and may delay weaning from mechanical ventilation (MV). MA is common in CO2-retainer patients that need MV. Acetazolamide (ACTZ) decreases serum bicarbonate concentration and stimulates respiratory drive. This study evaluated the effects of ACTZ on the duration of MV in patients with MA and COPD or obesity hypoventilation syndrome (OHS) intubated with acute respiratory failure. METHODS: Multicenter, randomized, controlled, double-blind study, with COPD or OHS patients with MV < 72 h and initial bicarbonate >28 mmol/L and pH > 7.35. Test-treatment, ACTZ 500 mg or placebo, was daily administered if pH > 7.35 and bicarbonate >26 mmol/L. Clinical, respiratory and laboratory parameters were recorded. RESULTS: 47 patients (36 men) were randomized. There were no significant differences between groups in comorbidities, baseline characteristics or arterial blood gases at inclusion. The mean difference in the duration of MV between placebo and ACTZ group was 1.3 days (95%CI, -2.1-4.8; p = 0.44). Kaplan-Meier curves showed no differences in the duration of MV (Log-Rank p = 0.41). Between-group comparison of estimated marginal means (CI 95%) during MV were, respectively: PaCO2 55 (51-59) vs 48 (47-50) mm Hg, p = 0.002; bicarbonate concentration 34 (32-35) vs 29 (28-30) mmol/L, p < 0.0001; and minute volume 9.7 (8.9-10.4) vs 10.6 (9.2-12.0) L/min, p = 0.26. There were no severe adverse effects with ACTZ administration. CONCLUSIONS: Among patients with MA and COPD or OHS, early treatment with ACTZ did not shorten significantly the duration of MV compared with placebo. TRIAL REGISTRY: clinical.trials.gov; NCT01499485; URL:.www.clinicaltrials.gov.

Clinical significance and outcome of Aeromonas spp. infections among 204 adult patients.

The objectives of this investigation were to analyze the clinical patterns, risk groups, prognostic factors, and mortality of infections caused by Aeromonas spp. This was a retrospective study of adult patients with Aeromonas spp. isolates attended at the Hospital del Mar in Barcelona, Spain, between January 2006 and December 2012. Epidemiological data, antimicrobial susceptibility, clinical patterns, underlying illnesses, type of infection, admission to the intensive care unit (ICU), number of episodes, coinfection, antimicrobial therapy, and evolution were analyzed. A total of 221 clinical samples from 204 patients were positive for Aeromonas spp. The mean age of the patients was 67.6 years. The main clinical form of presentation was gastrointestinal (78.4%). Malignancy was the main risk group in 69 (33.8%) patients, and 48 (23.5%) were previously healthy. Twenty-one patients (10.3%) were admitted to the ICU. Infections were acquired in the hospital in 52.5% of the patients, and 28.9% were polymicrobial. The overall mortality (after 1 year of follow-up from the first positive culture) was 26.5%. Univariate analysis identified an association between increased mortality and the following variables: age ≥80 years, hospitalization, admission to the ICU, malignancy, extraintestinal infection, and appropriate antimicrobial therapy. In the multivariate analysis, age ≥80 years [odds ratio (OR), 4.37 [95% confidence interval (CI), 1.68-11.35; p = 0.002]], admission to the ICU (OR, 6.59 [95% CI, 2.17-19.99; p = 0.001]), and malignancy (OR, 3.62 [95% CI, 1.32-9.90; p = 0.012]) were significantly associated with mortality. Aeromonas infections are mainly gastrointestinal. The 1-year follow-up mortality rate was high. Old age (age ≥80 years), admission to the ICU, and malignancy were identified as independent risk factors for mortality.

Multicenter prospective crossover study on new prosthetic opportunities in post-laryngectomy voice rehabilitation.

The aim of this study was to assess the clinical experience of three Italian centers using the third generation Provox Vega prosthesis, in terms of device life and voice outcome, comparing the results with the second generation Provox 2 prosthesis in the same sample. A prospective multicenter crossover study was performed in three phases. In the first phase we performed a reassessment, for enrollment purposes, of patients who were categorized into four different groups [normal ­ group A; radio-treated ­ group B; gastroesophageal reflux disease (GERD) ­ group C; and elderly subjects ­ group D]. In the second and third phases, all patients were monitored for prosthetic device life and assessed for objective and subjective voice characteristics after introducing Provox 2 and Provox Vega prostheses. In patients with Provox 2 prosthesis, the mean life was 165 days in group A, 148 days in group B, 91 days in group C and 188 days in group D. In Provox Vega patients, mean in situ prosthesis life was 213 days in group A, 182 days in group B, 118 days in group C and 227 days in group D. The perceptual voice data showed a better rating across all parameters for the Provox Vega samples compared to those of Provox 2. In this paper, we report the first multicenter crossover study comparing different prosthetic models in the same patients, categorized in relation to different typologies of tracheoesophageal rehabilitative status. Result analyses confirmed an optimal stability of the Provox Vega compared to the Provox 2, in terms of device life and perceptual voice parameters.

Efficacy and safety of omalizumab in paediatric age: an update of literature data.

Immunoglobulin E (IgE) was discovered in 1966 and was found responsible for immune defense against helminths, type I hypersensitivity and allergic diseases. IgE mediates allergic responses by binding to Fc receptors (the high affinity Fc-epsilon receptor I and the low affinity Fc-epsilon receptor II or CD23) expressed on tissue mast cells and blood basophils. This binding leads to degranulation and release of pro-inflammatory mediators. Considering the pivotal role of IgE in allergic diseases, antibodies against IgE potentiate an array of new therapeutic strategies and in this regard omalizumab (rhuMAb-E25, Xolair) has been developed as a monoclonal biologic drug to block serum IgEs. Although the use of omalizumab has been studied vigorously in many adult populations with allergic diseases, there are few heterogenous studies on children. There are very few ongoing clinical trials with omalizumab exclusively on children, although some adult studies have concluded pediatric patients as a part of their studies. Nevertheless, in pediatric clinical trials omalizumab has been demonstrated to be effective and safe also in this age group. Herein, the authors present a systematic review of extensive literature data on the use of omalizumab in children and adolescents.

Parasympathetic nervous system involvement in food allergy: description of a paediatric case.

The latest research data emphasize the interaction between the nervous and the immune systems. It has been demonstrated that the central nervous system (CNS) can be involved secondarily due to blood brain barrier (BBB) disruption via pro-inflammatory cytokines released in allergy. More recently it was demonstrated that the parasympathetic nervous system (PNS) could also be equally involved in models of peripheral inflammation such as food allergy; although this last clinical presentation has rarely been described. Herein, the authors report the case of a five-year-old Caucasian female who was admitted to our Pediatric Acute and Emergency Operative Unit for cyclic vomiting. Her vomiting, which was preceded by objective torque vertigo, headache and weakness, had been recurring with constant frequency every two months since she was 3 years old. After a complex diagnostic flow-chart, it was found that this spectrum of neurologic symptoms was due to a food allergy syndrome, which postulates some etiopathogenic hypotheses to explain the relationship between the two mentioned diseases.

Redox modulation of cellular stress response and lipoxin A4 expression by Hericium Erinaceus in rat brain: relevance to Alzheimer's disease pathogenesis.

BACKGROUND: There has been a recent upsurge of interest in complementary medicine, especially dietary supplements and foods functional in delaying the onset of age-associated neurodegenerative diseases. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as antitumor, antioxidant, antiviral, antibacterial and hepatoprotective agent also capable to stimulate host immune responses. RESULTS: Here we provide evidence of neuroprotective action of Hericium Herinaceus when administered orally to rat. Expression of Lipoxin A4 (LXA4) was measured in different brain regions after oral administration of a biomass Hericium preparation, given for 3 month. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, Heme oxygenase -1 and Thioredoxin. In the brain of rats receiving Hericium, maximum induction of LXA4 was observed in cortex, and hippocampus followed by substantia Nigra, striatum and cerebellum. Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is a fundamental cause in neurodegenerative diseases. As prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and Lipoxin A4. Emerging interest is now focussing on molecules capable of activating the vitagene system as novel therapeutic target to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. LXA4 is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. In addition, Hsp system is emerging as key pathway for modulation to prevent neuronal dysfunction, caused by protein misfolding. CONCLUSIONS: Conceivably, activation of LXA4 signaling and modulation of stress responsive vitagene proteins could serve as a potential therapeutic target for AD-related inflammation and neurodegenerative damage.

EFSUMB statement on medical student education in ultrasound [short version].

The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) recommends that ultrasound should be used systematically as an easy accessible and instructive educational tool in the curriculum of modern medical schools. Medical students should acquire theoretical knowledge of the modality and hands-on training should be implemented and adhere to evidence-based principles. In this paper we summarise EFSUMB policy statements on medical student education in ultrasound.