Predictive comorbidities of hospital admission in 1,571 SARS- CoV-2 positive patients: analysis of administrative data from an Italian Local Health Autority.

Purpose: Globally, age and some comorbidities have been associ-ated with the risk of more severe outcomes of COVID-19. The purpose of this research is to calculate the hospitalization rate of SARS-CoV-2 positive patients in an Italian Local health Authority (LHA) and to examine whether medical comorbidities encoded through pharmaceutical administrative data are predictors of hospital admission in patients with a positive SARS-CoV-2 naso-pharyngeal swab. Methods: This retrospective observational study was conducted in a LHA of Pescara. Comorbidities were coded through the consumption of drugs, using the WHO's Anatomical Therapeutic Chemical (ATC) classification System. The admission was ascertained by checking the hospital discharge records where generated. Results: During the study period, 1571 patients were tested positive for SARS-CoV-2 oro-and-nasopharyngeal swab. Multivariable logistic analisys showed as predictors of admission an age ≥65 in the total sample (aOR 10.91; 95%CI 6.86-17.36) as well as in the male (aOR 12.64;95%CI 6.42-24.87) and female. (aOR 9.27; 95%CI 4.87-17.66) in SARS-CoV-2 positive patients. Comorbidities assiociated with admission were (GERD) in overall (AdjOR 1.58; 95% CI 1.06-2.34) and male (AdjOR 2.30; 95%CI 1.12-4.72) samples and anticoagulants drugs use in male (AdjOR 3.90; 95% 1.11-13.65) sample, the presence of congestive heart failure (CHF) in female (AdjOR 0.47;95%CI 0.27-0.83) sample results as protective factor. Conclusion: In conclusion, increasing age, male gender and PPI use are positively associated while female gender and CHF-related drug use are negatively associated with hospitalization in SARS-CoV-2 positive patients.

The Polygenic and Monogenic Basis of Paediatric Fractures.

PURPOSE OF REVIEW: Fractures are frequently encountered in paediatric practice. Although recurrent fractures in children usually unveil a monogenic syndrome, paediatric fracture risk could be shaped by the individual genetic background influencing the acquisition of bone mineral density, and therefore, the skeletal fragility as shown in adults. Here, we examine paediatric fractures from the perspective of monogenic and complex trait genetics. RECENT FINDINGS: Large-scale genome-wide studies in children have identified ~44 genetic loci associated with fracture or bone traits whereas ~35 monogenic diseases characterized by paediatric fractures have been described. Genetic variation can predispose to paediatric fractures through monogenic risk variants with a large effect and polygenic risk involving many variants of small effects. Studying genetic factors influencing peak bone attainment might help in identifying individuals at higher risk of developing early-onset osteoporosis and discovering drug targets to be used as bone restorative pharmacotherapies to prevent, or even reverse, bone loss later in life.

The sarcopenia and physical frailty in older people: multi-component treatment strategies (SPRINTT) project: description and feasibility of a nutrition intervention in community-dwelling older Europeans.

BACKGROUND: The "Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies" (SPRINTT) project sponsored a multi-center randomized controlled trial (RCT) with the objective to determine the effect of physical activity and nutrition intervention for prevention of mobility disability in community-dwelling frail older Europeans. We describe here the design and feasibility of the SPRINTT nutrition intervention, including techniques used by nutrition interventionists to identify those at risk of malnutrition and to carry out the nutrition intervention. METHODS: SPRINTT RCT recruited older adults (≥ 70 years) from 11 European countries. Eligible participants (n = 1517) had functional limitations measured with Short Physical Performance Battery (SPPB score 3-9) and low muscle mass as determined by DXA scans, but were able to walk 400 m without assistance within 15 min. Participants were followed up for up to 3 years. The nutrition intervention was carried out mainly by individual nutrition counseling. Nutrition goals included achieving a daily protein intake of 1.0-1.2 g/kg body weight, energy intake of 25-30 kcal/kg of body weight/day, and serum vitamin D concentration ≥ 75 mmol/L. Survey on the method strategies and feasibility of the nutrition intervention was sent to all nutrition interventionists of the 16 SPRINTT study sites. RESULTS: Nutrition interventionists from all study sites responded to the survey. All responders found that the SPRINTT nutrition intervention was feasible for the target population, and it was well received by the majority. The identification of participants at nutritional risk was accomplished by combining information from interviews, questionnaires, clinical and laboratory data. Although the nutrition intervention was mainly carried out using individual nutritional counselling, other assisting methods were used as appropriate. CONCLUSION: The SPRINTT nutrition intervention was feasible and able to adapt flexibly to varying needs of this heterogeneous population. The procedures adopted to identify older adults at risk of malnutrition and to design the appropriate intervention may serve as a model to deliver nutrition intervention for community-dwelling older people with mobility limitations.

Fibrin-based scaffolds for dental pulp regeneration: from biology to nanotherapeutics.

Tissue engineering-based endodontic therapies, designed to regenerate the dental pulp (DP) in the devitalised endodontic space, have been proposed to improve tooth longevity compared to conventional root-filling therapies. Their aim is to restore tooth vitality and major DP functions necessary to maintain tooth health such as immunosurveillance, sensitivity and healing/repair/regenerative capacities. Several formulations based on the use of fibrin, the main component of the blood clot matrix, recently gave valuable results in the regeneration of the human DP. This review describes recent fibrin-based scaffolds designed for that purpose. After having presented the various strategies for DP regeneration, the main fibrin-based scaffolds reported so far for clinical use in endodontics were reviewed. Particular emphasis was given to hydrogel devices that may be improved by incorporation of bioactive molecules that stimulate vascularisation and tissue neoformation or provide antibacterial properties. Data indicate that fibrin-based scaffolds constitute a highly favourable environment for mesenchymal stem cells, which is maintained upon functionalisation. Additional knowledge is needed to understand how fibrin and functionalising agents affect adhesion, survival, proliferation, migration and differentiation of cells incorporated in the scaffold or which will colonise it from neighbouring host tissues. This knowledge is needed to adapt the hydrogel formulation for various clinical conditions.

Development of an antibacterial nanocomposite hydrogel for human dental pulp engineering.

Hydrogel-based regenerative endodontic procedures (REPs) are considered to be very promising therapeutic strategies to reconstruct the dental pulp (DP) tissue in devitalized human teeth. However, the success of the regeneration process is limited by residual bacteria that may persist in the endodontic space after the disinfection step and contaminate the biomaterial. The aim of this work was to develop an innovative fibrin hydrogel incorporating clindamycin (CLIN)-loaded Poly (d,l) Lactic Acid (PLA) nanoparticles (NPs) to provide the hydrogel with antibacterial properties. CLIN-PLA-NPs were synthesized by a surfactant-free nanoprecipitation method and their microphysical properties were assessed by dynamic light scattering, electrophoretic mobility and scanning electron microscopy. Their antimicrobial efficacy was evaluated on Enteroccocus fæcalis by the determination of the minimal inhibitory concentration (MIC) and the minimal biofilm inhibition and eradication concentrations (MBIC and MBEC). Antibacterial properties of the nanocomposite hydrogel were verified by agar diffusion assays. NP distribution into the hydrogel and release from it were evaluated using fluorescent PLA-NPs. NP cytotoxicity was assessed on DP mesenchymal stem cells (DP-MSCs) incorporated into the hydrogel. Type I collagen synthesis was investigated after 7 days of culture by immunohistochemistry. We found that CLIN-PLA-NPs displayed a drug loading of 10 ± 2 µg per mg of PLA polymer and an entrapment efficiency of 43 ± 7%. Antibiotic loading did not affect NP size, polydispersity index and zeta potential. The MIC for Enterococcus fæcalis was 32 µg mL-1. MBIC50 and MBEC50 were 4 and 16 µg mL-1, respectively. CLIN-PLA-NPs appeared homogenously distributed throughout the hydrogel. CLIN-PLA-NP-loaded hydrogels clearly inhibited E. faecalis growth. DP-MSC viability and type I collagen synthesis within the fibrin hydrogel were not affected by CLIN-PLA-NPs. In conclusion, CLIN-PLA-NP incorporation into the fibrin hydrogel gave the latter antibacterial and antibiofilm properties without affecting cell viability and function. This formulation could help establish an aseptic environment supporting DP reconstruction and, accordingly, might be a valuable tool for REPs.

Health tourism: an opportunity for sustainable development.

In February 2017, the "Programma Mattone Internazionale Salute" (ProMis), that is the Italian Program for Internationalization of Regional Health Systems of the Ministry of Health (MoH), presented the first version of its Position Paper on Health Tourism, which embeds a first shared approach to the recommendations expressed by the European Committee of Regions (CoR) on "Age-Friendly" tourism. The CoR stresses the importance of local and regional authorities in the coordination of multi-sectoral policies such as healthcare, social assistance, transport, urban planning and rural development in relation to the promotion of mobility, security, accessibility of services, including health care and social services. "Age-friendly" tourism is an example of an innovative tourist offer that strives to meet the health needs of the entire "traveling" population, with an integrated and cross-sector approach that involves various organizations operating in sectors such as healthcare, accessibility and transport. The aim of the workshop was to explore the interest of the stakeholders to participate in a systemic action in the field of "health" tourism, and to identify priority implementation areas that offer opportunities to take advantage of validated, innovative experiences that strengthen the accessibility to health and social services in regional, national and international contexts. This effort provides the opportunity to take advantage of aligning the European Structural and Investment Funds (ESIF) to the development of tourism, coherently with the needs and resources of local and regional health authorities.

Nivolumab-refractory patients with advanced non-small-cell lung cancer.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionised cancer care especially in lung cancer. New response patterns have been described under ICIs such as pseudo-progression or hyper-progressive disease (HPD). The definition of HPD is yet to be consensual. The aim of this study was to suggest a clinical definition of nivolumab-refractory patients and find factors associated with this entity. METHODS: We performed a multi centric retrospective study including all patients who received nivolumab for the treatment of advanced non-small cell lung cancer (NSCLC) during the French authorisation for temporary use in 2015. RESULTS: 303 patients were included in the cohort and 292 had details on the number of nivolumab injections received. 57 patients (20%) were nivolumab-refractory. These patients had worse PS at nivolumab initiation (p < 0.0001), shorter duration of treatment before nivolumab (p = 0.028) and had dramatically shorter nivolumab overall survival (p < 0.0001) than patients who did not present with refractory disease. CONCLUSION: Nivolumab-refractory disease can affect up to 20% of patients treated with nivolumab for advanced NSCLC with dramatically shortened survival rates. Further studies are needed to understand the precise mechanisms leading to refractory disease as well as its management.

Early metabolic response to chemoradiotherapy by interim FDG PET/CT is associated with better overall survival and histological response in esophageal cancers.

BACKGROUND: Early assessment of response to neoadjuvant chemoradiotherapy (CRT) is crucial in determining the most suitable treatment strategy in locally advanced oesophageal cancer (LAEC). AIMS: We evaluated the impact of early metabolic response during CRT on overall survival (OS) and histological response. METHODS: Patients with biopsy-proven oesophageal carcinoma underwent FDG PET/CT with evaluation of the standardized uptake value (SUV) before any treatment and during CRT after 20 Gy. RESULTS: 116 patients (Male: 66.4%, Median age: 63; squamous cell carcinomas (SCC): 70%) met inclusion criteria. Median OS was 21.7 months. There was a significant positive correlation between interim metabolic response and OS. In multivariate analysis, only metabolic response using the 50% cut-off value remained significantly associated with OS (IC95% = 0.28-0.73; p = 0.001). In this statistical analysis, surgery (p = 0.007) and T stage (p = 0.023) were also correlated with OS. There was a significant correlation between early metabolic response and local recurrence (Chi-squared test p = 0.0001). CONCLUSIONS: Early metabolic response using FDG PET/CT is associated with better OS, disease-free survival, local control and pathological response in patients treated by CRT for LAEC.

Establishing the European Norm for the health-related quality of life domains of the computer-adaptive test EORTC CAT Core.

OBJECTIVE: The computer-adaptive test (CAT) of the European Organisation for Research and Treatment of Cancer (EORTC), the EORTC CAT Core, assesses the same 15 domains as the EORTC QLQ-C30 health-related quality of life questionnaire but with increased precision, efficiency, measurement range and flexibility. CAT parameters for estimating scores have been established based on clinical data from cancer patients. This study aimed at establishing the European Norm for each CAT domain based on general population data. METHODS: We collected representative general population data across 11 European Union (EU) countries, Russia, Turkey, Canada and the United States (n ≥ 1000/country; stratified by sex and age). We selected item subsets from each CAT domain for data collection (totalling 86 items). Differential item functioning (DIF) analyses were conducted to investigate cross-cultural measurement invariance. For each domain, means and standard deviations from the EU countries (weighted by country population, sex and age) were used to establish a T-metric with a European general population mean = 50 (standard deviation = 10). RESULTS: A total of 15,386 respondents completed the online survey (n = 11,343 from EU countries). EORTC CAT Core norm scores for all 15 countries were calculated. DIF had negligible impact on scoring. Domain-specific T-scores differed significantly across countries with small to medium effect sizes. CONCLUSION: This study establishes the official European Norm for the EORTC CAT Core. The European CAT Norm can be used globally and allows for meaningful interpretation of scores. Furthermore, CAT scores can be compared with sex- and age-adjusted norm scores at a national level within each of the 15 countries.

General population normative data for the EORTC QLQ-C30 health-related quality of life questionnaire based on 15,386 persons across 13 European countries, Canada and the Unites States.

OBJECTIVE: The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 health-related quality of life questionnaire is one of the most widely used cancer-specific health-related quality of life questionnaires worldwide. General population norm data can facilitate the interpretation of QLQ-C30 data obtained from cancer patients. This study aimed at systematically collecting norm data from the general population to develop European QLQ-C30 norm scores and to generate comparable norm data for individual countries in Europe and North America. METHODS: We collected QLQ-C30 data from the general population across 11 European Union (EU) countries, Russia, Turkey, Canada and United States (n ≥ 1000/country). Representative samples were stratified by sex and age groups (18-39, 40-49, 50-59, 60-69 and ≥ 70 years). After applying weights based on the United Nations population distribution statistics, we calculated QLQ-C30 domain scores to generate a 'European QLQ-C30 Norm' based on the EU countries. Further, we calculated QLQ-C30 norm scores for all 15 individual countries. RESULTS: A total of 15,386 respondents completed the online survey. For the EU sample, most QLQ-C30 domains showed differences by sex/age, with men scoring somewhat better health than women, while age effects varied across domains. Substantially larger differences were seen in inter-country comparisons, with Austrian and Dutch respondents reporting consistently better health compared with British and Polish respondents. CONCLUSIONS: This study is the first to systematically collect EORTC QLQ-C30 general population norm data across Europe and North America applying a consistent data collection method across 15 countries. These new norm data facilitate valid intra-country as well as inter-country comparisons and QLQ-C30 score interpretation.

First-line antiretroviral therapy with efavirenz plus tenofovir disiproxil fumarate/emtricitabine or rilpivirine plus tenofovir disiproxil fumarate/emtricitabine: a durability comparison.

OBJECTIVES: The aim of this study was to compare the durabilities of efavirenz (EFV) and rilpivirine (RPV) in combination with tenofovir/emtricitabine (TDF/FTC) in first-line regimens. METHODS: A multicentre prospective and observational study was carried out. We included all patients participating in the Italian Cohort Naive Antiretrovirals (ICONA) Foundation Study who started first-line combination antiretroviral therapy (cART) with TDF/FTC in combination with RPV or EFV, with a baseline viral load < 100 000 HIV-1 RNA copies/mL. Survival analyses using Kaplan-Meier (KM) curves and Cox regression with time-fixed covariates at baseline were employed. RESULTS: Overall, 1490 ART-naïve patients were included in the study, of whom 704 were initiating their first cART with EFV and 786 with RPV. Patients treated with EFV, compared with those on RPV, were older [median 36 (interquartile range (IQR) 30-43) years vs. 33 (IQR 27-39) years, respectively; P < 0.001], were more frequently at Centers for Disease Control and Prevention (CDC) stage C (3.1% vs. 1.4%, respectively; P = 0.024), and had a lower median baseline CD4 count [340 (IQR 257-421) cells/µL vs. 447 (IQR 347-580) cells/µL, respectively; P < 0.001] and a higher median viral load [4.38 (IQR 3.92-4.74) log10 copies/mL vs. 4.23 (IQR 3.81-4.59) log10 copies/mL, respectively], (P = 0.004). A total of 343 patients discontinued at least one drug of those included in the first cART regimen, more often EFV (26%) than RPV (13%), by 2 years (P < 0.0001). After adjustment, patients treated with EFV were more likely to discontinue at least one drug for any cause [relative hazard (RH) 4.09; 95% confidence interval (CI) 2.89-5.80], for toxicity (RH 2.23; 95% CI 1.05-4.73) for intolerance (RH 5.17; 95% CI 2.66-10.07) and for proactive switch (RH 10.96; 95% CI 3.17-37.87) than those starting RPV. CONCLUSIONS: In our nonrandomized comparison, RPV was better tolerated, less toxic and showed longer durability than EFV, without a significant difference in rates of discontinuation because of failures.

Childhood infectious diseases and risk of multiple myeloma: an analysis of the Italian multicentre case-control study.

Common childhood infectious diseases have been associated with a reduced risk of following haematopoietic malignancies, but investigations on multiple myeloma (MM) are scarce. Information about 213 MM cases and 1128 healthy controls were obtained from a multicentre population-based Italian case-control study. The association between chickenpox, measles, mumps, pertussis and rubella and the MM risk was estimated by unconditional logistic regression, adjusting for age, gender and residence area. No association was found between MM risk and any considered infectious disease. The number of infections was slightly inversely associated with the risk of MM, but statistical significance was not reached (OR 0.87, 95% CI 0.55-1.4 for 1-2 diseases vs. none and OR 0.68, 95% CI 0.41-1.1 for 3-5 diseases, respectively, P = 0.131). We did not find a clear evidence that common infections during childhood are associated with the subsequent risk of developing MM.

Phase III study of the European Organisation for Research and Treatment of Cancer satisfaction with cancer care core questionnaire (EORTC PATSAT-C33) and specific complementary outpatient module (EORTC OUT-PATSAT7).

Advances in cancer care delivery require revision and further development of questionnaires assessing patients' perceived quality of care. This study pre-tested the revised EORTC satisfaction with cancer care core questionnaire applicable in both the cancer inpatient and outpatient settings, and its new, outpatient-specific complementary module. The process of revision, development of the extended application, and pre-testing of these questionnaires was based on phases I to III of the "EORTC Quality of Life Group Module Development Guidelines." In phase III, patients in 11 countries in four European regions, South America and Asia completed provisional versions of the questionnaires. Fifty-seven relevant issues selected from literature reviews and input from experts were operationalized into provisional items, and subsequently translated into ten languages. Assessment of understanding, acceptability, redundancy and relevance by patients (n = 151) from oncology inpatient wards, and outpatient chemotherapy, radiotherapy and consultation settings, led to retention of, deletion of and merging of 40, 14 and 6 items respectively. Cronbach's alpha coefficients for hypothesized questionnaire scales were above 0.80. Our results provide preliminary support for the 33-item EORTC Satisfaction with cancer care core questionnaire and the 7-item complementary module specific for the outpatient care setting. A large scale phase IV cross-cultural psychometric study is now underway.

The international phase 4 validation study of the EORTC QLQ-SWB32: A stand-alone measure of spiritual well-being for people receiving palliative care for cancer.

The EORTC Quality of Life Group has just completed the final phase (field-testing and validation) of an international project to develop a stand-alone measure of spiritual well-being (SWB) for palliative cancer patients. Participants (n = 451)-from 14 countries on four continents; 54% female; 188 Christian; 50 Muslim; 156 with no religion-completed a provisional 36-item measure of SWB plus the EORTC QLQ-C15-PAL (PAL), then took part in a structured debriefing interview. All items showed good score distribution across response categories. We assessed scale structure using principal component analysis and Rasch analysis, and explored construct validity, and convergent/divergent validity with the PAL. Twenty-two items in four scoring scales (Relationship with Self, Relationships with Others, Relationship with Someone or Something Greater, and Existential) explained 53% of the variance. The measure also includes a global SWB item and nine other items. Scores on the PAL global quality-of-life item and Emotional Functioning scale weakly-moderately correlated with scores on the global SWB item and two of the four SWB scales. This new validated 32-item SWB measure addresses a distinct aspect of quality-of-life, and is now available for use in research and clinical practice, with a role as both a measurement and an intervention tool.

PLS3 sequencing in childhood-onset primary osteoporosis identifies two novel disease-causing variants.

Altogether 95 children with primary bone fragility were screened for variants in PLS3, the gene underlying X-linked osteoporosis. Two children with multiple peripheral and spinal fractures and low BMD had novel disease-causing PLS3 variants. Children with milder phenotypes had no pathogenic variants. PLS3 screening is indicated in childhood-onset primary osteoporosis. INTRODUCTION: The study aimed to determine the role of pathogenic PLS3 variants in children's bone fragility and to elucidate the associated phenotypic features. METHODS: Two cohorts of children with bone fragility were screened for variants in PLS3, the gene underlying X-linked osteoporosis. Cohort I comprised 31 patients with childhood-onset primary osteoporosis of unknown etiology. Cohort II comprised 64 children who had sustained multiple fractures but were otherwise healthy. Clinical and radiological data were reviewed. Peripheral blood DNA was Sanger sequenced for coding exons and flanking intronic regions of PLS3. RESULTS: In two patients of cohort I, where other common genetic causes had been excluded, we identified two novel disease-causing PLS3 variants. Patient 1 was a male with bilateral femoral fractures at 10 years, low BMD (Z-score -4.1; 18 years), and multiple vertebral compression fractures. He had a novel nonsense variant in PLS3. Patient 2 was a girl with multiple long bone and vertebral fractures and low BMD (Z-score -6.6 at 6 years). She had a de novo missense variant in PLS3; whole exome sequencing and array-CGH identified no other genetic causes. Iliac crest bone biopsies confirmed low-turnover osteoporosis in both patients. In cohort II, no pathogenic PLS3 variants were identified in any of the subjects. CONCLUSIONS: Two novel disease-causing variants in PLS3 were identified in a boy and a girl with multiple peripheral and spinal fractures and very low BMD while no pathogenic variants were identified in children with less severe skeletal fragility. PLS3 screening is warranted in male and female patients with childhood-onset primary osteoporosis.

The use of r-hFSH in treatment of idiopathic male factor infertility before ICSI.

OBJECTIVE: To evaluate the efficacy of pre-treatment of idiopathic oligozoospermic patients with r-hFSH to improve the clinical results of ICSI. PATIENTS AND METHODS: 82 infertile couples due to male factor who attended our center were included in the study. Thirty-six were randomized to the treatment group (group A) and forty-six to the control group (group B). The male partners in group A were treated with recombinant human FSH (r-hFSH; Gonal F®) 150 IU subcutaneously three times a week for a 3-months period. The control group (group B) did not receive any treatment. After the treatment couples of both groups underwent a cycle of ICSI. RESULTS: The fertilization rate was comparable in both groups. However, in the treatment group (group A), the clinical pregnancy rate was significantly higher (42%) compared to the control group (group B) (20%) (p < 0.02). Also, the implantation rate was significantly higher in treatment group (26%) compared to the control (15%) (p < 0.04). Miscarriage rate was lower (15.7%) in the treatment group than in the control (43.7%), and this difference was statistically significant (p < 0.05). CONCLUSIONS: Treatment of idiopathic male factor infertility with r-hFSH before ICSI improves clinical pregnancy rate, increases implantation rate and decreases the early pregnancy loss.

Italian Intersociety Recommendations on pain management in the emergency setting (SIAARTI, SIMEU, SIS 118, AISD, SIARED, SICUT, IRC).

BACKGRAUND: Pain is the primary reason for admission to the Emergency Department (ED). However, the management of pain in this setting is often inadequate because of opiophagia, fear of excessive sedation, and fear of compromising an adequate clinical assessment. METHODS: An intersociety consensus conference was held in 2010 on the assessment and treatment of pain in the emergency setting. This report is the Italian Intersociety recommendations on pain management in the emergency department setting. RESULTS: The list of level A recommendations includes: 1) use of IV acetaminophen for opioid sparing properties and reduction of opioid related adverse events; 2) ketamine-midazolam combination preferred over fentanyl-midazolam fentanyl-propofol in pediatric patients; 3) boluses of ketamine IV (particularly in the population under the age of 2 years and over the age of 13) can lead to impairment of the upper airways, including the onset of laryngospasm, requiring specific expertise and skills for administration; 4) the use of ketamine increases the potential risk of psychomotor agitation, which can happen in up to 30% of adult patients (this peculiar side effect can be significantly reduced by concomitant systemic use of benzodiazepines); 5) for shoulder dislocations and fractures of the upper limbs, the performance of brachial plexus block reduces the time spent in ED compared to sedation; 6) pain relief and the use of opioids in patients with acute abdominal pain do not increase the risk of error in the diagnostic and therapeutic pathway in adults; 7) in newborns, the administration of sucrose reduces behavioural responses to blood sampling from a heel puncture; 8) in newborns, breastfeeding or formula feeding during the procedure reduces the measures of distress; 9) in pediatric patients, non-pharmacological techniques such as distraction, hypnosis and cognitive-behavioural interventions reduce procedural pain caused by the use of needles; 10) in pediatric patients, preventive application of eutectic mixtures of prilocaine and lidocaine allows arterial and venous samples to be taken in optimum conditions; 11) in pediatric patients, the combination of hypnotics (midazolam) and N2O is effective for procedural pain, but may be accompanied by loss of consciousness. CONCLUSION: The diagnostic-therapeutic pathway of pain management in emergency should be implemented, through further interdisciplinary trials, in order to improve the EBM level of specific guidelines.

Effect of malolactic fermentation by Pediococcus damnosus on the composition and sensory profile of Albariño and Caiño white wines.

AIM: This study was aimed to investigate the influence of malolactic fermentation (MLF) on sensory profile and organoleptic characteristics of Albariño and Caiño white wines. METHODS AND RESULTS: Autochthonous bacteria were isolated from wines after alcoholic fermentation (AF) and further identified as Pediococcus damnosus by 16S rRNA gene sequence analysis. When a commercial Oenococcus oeni starter was inoculated into Albariño and Caiño white wines to perform MLF, which was checked by HPLC quantification of malic and lactic acids, it was shown that autochthonous Ped. damnosus strains were able to predominate over the commercial O. oeni starter and perform MLF in Caiño wine. By contrast, neither commercial strain nor indigenous Pediococcus carried out MLF in Albariño wine. However, MLF was achieved when autochthonous strains that predominated in Caiño were inoculated into Albariño. Sensory analysis showed that after the MLF Albariño increased its body and softness, while Caiño result a more mature wine. CONCLUSIONS: MLF can positively affect Albariño and Caiño wines giving them new attributes. Pediococci isolated and characterized in this work can successfully perform MLF without negative effects on the wine, because no production of biogenic amines or exopolysaccharides by the selected pediococcus strains was detected. SIGNIFICANCE AND IMPACT OF THE STUDY: The effect of MLF in the sensory profile of Albariño and Caiño wines has never been studied before. Results obtained in this work showed that Ped. damnosus strains can be considered as a new topic of investigation on malolactic starter.

Genotypic testing on HIV-1 DNA as a tool to assess HIV-1 co-receptor usage in clinical practice: results from the DIVA study group.

PURPOSE: We have developed a sequencing assay for determining the usage of the genotypic HIV-1 co-receptor using peripheral blood mononuclear cell (PBMC) DNA in virologically suppressed HIV-1 infected patients. Our specific aims were to (1) evaluate the efficiency of V3 sequences in B versus non-B subtypes, (2) compare the efficiency of V3 sequences and tropism prediction using whole blood and PBMCs for DNA extraction, (3) compare the efficiency of V3 sequences and tropism prediction using a single versus a triplicate round of amplification. RESULTS: The overall rate of successful V3 sequences ranged from 100 % in samples with >3,000 copies HIV-1 DNA/10(6) PBMCs to 60 % in samples with <100 copies total HIV-1 DNA /10(6) PBMCs. Analysis of 143 paired PBMCs and whole-blood samples showed successful V3 sequences rates of 77.6 % for PBMCs and 83.9 % for whole blood. These rates are in agreement with the tropism prediction obtained using the geno2pheno co-receptor algorithm, namely, 92.1 % with a false-positive rate (FPR) of 10 or 20 % and of 96.5 % with an FPR of 5.75 %. The agreement between tropism prediction values using single versus triplicate amplification was 98.2 % (56/57) of patients using an FPR of 20 % and 92.9 % (53/57) using an FPR of 10 or 5.75 %. For 63.0 % (36/57) of patients, the FPR obtained via the single amplification procedure was superimposable to all three FPRs obtained by triplicate amplification. CONCLUSIONS: Our results show the feasibility and consistency of genotypic testing on HIV-1 DNA tropism, supporting its possible use for selecting patients with suppressed plasma HIV-1 RNA as candidates for CCR5-antagonist treatment. The high agreement between tropism prediction by single and triple amplification does not support the use of triplicate amplification in clinical practice.

Fluorescent (rhodamine), folate decorated and doxorubicin charged, PEGylated nanoparticles synthesis.

PEGylated silica nanoparticles, giving very stable aqueous sols, were successfully functionalised with rhodamine, one of the more stable fluorophore; they were also decorated with the targeting agent folic acid (FA) and charged with the well known drug doxorubicin. Rhodamine functionalization required a modification of the synthesis route of the nanoparticles (NP). Functionalization with FA required activation with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride. Folate decorated NP were easily charged with doxorubicin. The experimental results proved the successfulness of the functionalization. The bond to the NP does not reduce the therapeutic efficacy of the drug. The calculated encapsulation efficiency (32 %) was only a little lower than the value (47 %) reported for the very popular PEGylated PLGA NP.