Fatal Viral and Bacterial Septicemia in a Seventeen-Year-Old Woman with Immunodepressive Influenza A H1N1: An Autopsy Case.

Abstract: The Influenza A H1N1 subtype can present with a wide spectrum of severity, from mild symptoms of influenza to severe respiratory distress. The morbidity and mortality connected to influenza are mostly associated with secondary bacterial infections. The influenza syndrome alone can cause a massive release of cytokines with dysregulation of the immune system, and it can act in synergy with other bacteria which can enhance cytokines secretion. This article deals with a case of severe pneumonia of H1N1 in a 17-year-old woman with bacterial superinfection with Staphylococcus aureus characterized by a high level of interleukine-6 (105900 pg/mL) and the appearance of severe leukopenia with immuno-suppression, such that HIV infection and hematological diseases were included in the initial differential diagnosis. After death, the autopsy confirmed the presence of severe pneumonia, in addition to an hepatic steatosis in absence of other risk factors. This case reports the rapid and lethal course of influenza A /H1N1 in a young and healthy subject without comorbidities, in an age group in which mortality is about 0.3 deaths per 100,000. The case underlines the importance of quickly diagnosis of viral infections and the differential diagnoses with other immunosuppressive diseases, which can be fatal even in adolescent and healthy subjects.

Spatio-temporal interactions between the red fox and the wolf in two contrasting European landscapes.

Relationships among carnivore species are complex, potentially switching from competition to facilitation on a context-dependent basis. Negative associations are predicted to increase with latitude, due to limited resources emphasising competition and/or intra-guild predation. Accordingly, a stronger negative correlation between large- and meso-carnivore abundances should be expected at higher latitudes, with a substantial spatio-temporal partitioning favouring interspecific coexistence. Human presence may influence spatio-temporal relationships between (meso)carnivore species, as it can be perceived as a risk factor, but anthropogenic food can also provide an important additional food resource. Using camera-trap data, we studied the spatio-temporal associations between two of the most widespread carnivores in Europe, i.e., the red fox and wolf. We compared their monthly/daily spatio-temporal partitioning between two different landscapes: Bialowieza Primeval Forest (Poland) and the Mediterranean Maremma Regional Park (Italy). We predicted a stronger interspecific partitioning, as well as more attraction of red foxes to humans in the northern site (Poland). Temporal activity patterns of the two carnivores overlapped in both sites, and their detection rates were positively associated, even though in weaker way in Poland. We observed a positive spatial association of red foxes with human activity in Bialowieza, but not in Maremma. This association occurred only at a monthly temporal scale and disappeared at a daily scale, suggesting some disturbance in the shorter term. Our results provided partial support to our predictions and suggest that, despite the ecological differences between our study areas, only weak differences in wolf-fox relations were observed, suggesting that red fox responses to wolves may be relatively comparable over large spatial scales.

A Literature Systematic Review with Meta-Analysis of Symptoms Prevalence in Covid-19: the Relevance of Olfactory Symptoms in Infection Not Requiring Hospitalization.

PURPOSE OF REVIEW: To investigate the association between the olfactory dysfunction and the more typical symptoms (fever, cough, dyspnoea) within the Sars-CoV-2 infection (COVID-19) in hospitalized and non-hospitalized patients. RECENT FINDINGS: PubMed, Scopus and Web of Science databases were reviewed from May 5, 2020, to June 1, 2020. Inclusion criteria included English, French, German, Spanish or Italian language studies containing original data related to COVID19, anosmia, fever, cough, and dyspnoea, in both hospital and non-hospital settings. Two investigators independently reviewed all manuscripts and performed quality assessment and quantitative meta-analysis using validated tools. A third author arbitrated full-text disagreements. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 of 135 studies fulfilled eligibility. Anosmia was estimated less prevalent than fever and cough (respectively rate difference = - 0.316, 95% CI: - 0.574 to - 0.058, Z = - 2.404, p < 0.016, k = 11 and rate difference = - 0.249, 95% CI: - 0.402 to - 0.096, Z = - 3.185, p < 0.001, k = 11); the analysis between anosmia and dyspnoea was not significant (rate difference = - 0.008, 95% CI: - 0.166 to 0.150, Z = - 0.099, p < 0.921, k = 8). The typical symptoms were significantly more frequent than anosmia in hospitalized more critical patients than in non-hospitalized ones (respectively [Q(1) = 50.638 p < 0.000, Q(1) = 52.520 p < 0.000, Q(1) = 100.734 p < 0.000). SUMMARY: Patient with new onset olfactory dysfunction should be investigated for COVID-19. Anosmia is more frequent in non-hospitalized COVID-19 patients than in hospitalized ones.

Enhancing adherence to antipsychotic treatment for bipolar disorders. Comparison of mobile app-based psychoeducation, group psychoeducation, and the combination of both: protocol of a three-arm single-blinded parallel-group multi-centre randomised trial.

Group Psychoeducation (PE) is an effective strategy to enhance adherence to antipsychotic treatment in Bipolar Disorders (BD). However, it requires attendance to weekly sessions during a period of about 6 months. This may impede its application for those patients living far from mental health centres, resulting inequality in access to evidence-based care. Therefore, there is an increasing need to find new efficient strategies to deliver and extend PE programs to a wider population of BD patients. Mobile apps are a cost-effective way to deliver PE. In the Italian healthcare context, no evidence about the use of apps is available. The current paper presents the protocol about the development of a smartphone app to deliver PE for BD and the protocol for a trial assessing its effectiveness. In euthymic BD patients, the study will compare the adherence rates to antipsychotics between PE delivered through Bipolar mobile Application (Bip.App), group PE and a combination of both, will investigate demographic, socio-cultural and clinical predictors of lower adherence in the arms, and will investigate whether PE combined with Bip.App is associated with lower risk of recurrence of (hypo)manic and depressive episodes than group PE alone, and assess the feasibility and satisfaction for Bip.App. Participants will be recruited from mental health centres and included if they are 18-65 year-old, have primary BD in the euthymic phase, they have been prescribed a second-generation oral antipsychotic as a maintenance/prophylactic therapy for at least 1 year, they have not undergone a structured protocol of PE for BD, they have access to a smartphone and sufficient competence in using it. Participants will be excluded if they have neurological disease, mental retardation or learning disability, psychosis, limited fluency in Italian. Adherence will be assessed through count pills, blood levels, and self-reported adherence. A single-blinded parallel-group superiority multi-centre randomised controlled trial design will be used.

Clinical risk management in High-Security Forensic Psychiatry Residences. Protecting patients and health professionals: perspectives and critical issues of the Law 81/2014.

The Italian Law n. 9/2012 provided the Italian Regions with a new decisional role by demanding the management/rehabilitation of prisoners judged as partially/fully mentally ill to care and protection delivered by the psychiatric services of the Regional Health Service. Healthcare has to be guaranteed by the so-called High-Security Forensic Psychiatry Residences (Italian: Residenze per l'Esecuzione delle Misure di Sicurezza: REMS) and by community mental health centres. Ensuring patients' and professionals' health and safety is a complex issue which requires effective strategies to cope with several structural, technological, and organisational problems. The present paper summarises the historical evolution of the Italian laws towards the development of the High-Security Forensic Psychiatry Residences in Italy, focusing specifically on the Tuscany Region situation. The paper also presents the key issues emerging after the implementation of the Law 81/2014 which complemented the Law 9/2012. Since these reforms included the need for assessing to what extent the patient may be considered as a danger to society and for ensuring the safety of National Health Service (NHS) professionals, they underscored the importance of a preventive use of specific clinical governance tools aimed to reduce risk of adverse events. The present work has the strength of proposing a new, evidence-based scientific approach to the implementation of assessment and care pathways in High-Security Forensic Psychiatry Residences.

The Workplace Health Promotion (WHP) programme in an Italian University Hospital.

INTRODUCTION: Description of the lifestyles of employees of the Siena University Hospital (Azienda Ospedaliera Universitaria Senese: AOUS), as assessed through a Workplace Health Promotion (WHP) project in the two-year period 2017-18; assessment of possible short-term effects of integrated health promotion interventions in the workplace, within the framework of the Tuscany WHP network, as applied in the AOUS and involving about 1,000 workers. METHODS: A cross-sectional study and a pre-post evaluation of data collected by means of anonymous questionnaires in two phases: before the beginning of the programme and after 12 months. RESULTS: Twelve months after the start of the programme regarding diet (consumption of fruit and vegetables) and physical activity, the positive effects that emerged were not statistically significant. No differences were observed between gender or professional categories. The employees' perception of the programme was satisfactory. CONCLUSIONS: Albeit within the methodological limits of the assessment, the results showed that the diffusion of some major risk factors for chronic diseases had not decreased after 12 months' exposure to the programme. However, monitoring of these risk factors needs to be continued over a longer period, in order to detect the appearance of the expected changes in the long term. Moreover, it is essential to continue monitoring by sex and professional category, in order to pick out any differences and, if possible, take remedial actions. Further studies, in collaboration with the pertinent physicians, are desirable, since integrating data collected during health surveillance with a limited set of indicators of general risk factors may help to promptly identify possible health needs among employees.

Development and validation of a new HPLC-MS method for meglumine impurity profiling.

We report a new High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) method to rapidly detect and quantify meglumine by-products (specifically reducing sugar(s) and nitrogen impurities) that could be present in the meglumine samples. Meglumine is a secondary amine obtained from glucose and it is an excipient used as counter-ion in several pharmaceutical formulations, especially when the concentration of the active pharmaceutical ingredient (API) is so high that the sodium is not a suitable option. Moreover, the increased use of meglumine is related to its ability to improve solubility in aqueous solutions due to the presence of a large number of hydroxyl groups. Thus, even if meglumine is widely used as excipient in pharmaceutical formulations, its impurity profile has never been fully evaluated. Here, we propose the use of a commercial agent that specifically reacts with carbonyl compounds, 1-(4-aminobenzyl)-1,2,4-triazole, with the aim of improving the detection of reducing sugars, such as glucose, after an easy derivatization procedure. Finally, we describe the method validation and the analysis of the impurity profile of meglumine samples from different manufacturers.

The development of episodic future thinking in middle childhood.

The ability to imagine future events (episodic future thinking-EFT) emerges in preschoolers and further improves during middle childhood and adolescence. In the present study, we focused on the possible cognitive factors that affect EFT and its development. We assessed the ability to mentally project forward in time of a large cohort of 135 6- to 11-year-old children through a task with minimal narrative demands (the Picture Book Trip task adapted from Atance and Meltzoff in Cogn Dev 20(3):341-361. doi:10.1016/j.cogdev.2005.05.001, 2005) in order to avoid potential linguistic effects on children's performance. The results showed that this task can be used to assess the development of EFT at least until the age of 8. Furthermore, EFT scores correlated with measures of phonological short-term and verbal working memory. These results support the possibility that cognitive factors such as working memory play a key role in EFT.

Healthcare Associated Infections: educational intervention by "Adult Learning" in an Italian teaching hospital.

BACKGROUND: An educational intervention for HAI prevention based on a combination of training, motivation and subsequent application in the current clinical practice in an Italian teaching hospital. METHODS: In 2015-2016 a pilot mandatory training on HAI targeted to HCWs was organized in the 450 bed teaching hospital Sant'Andrea in Rome. By adopting the "Impact/control matrix" prioritization tool, the relative level of impact (risk in causing or favoring HAI) and control (possibility for HCWs to prevent HAI) attributed by the participants to the issues associated to HAI during their working groups was evaluated. RESULTS: Overall, 34 physicians, 43 nurses and 15 non clinical professionals participated actively in seven courses, identifying 58 different issues related to HAI, which were reported 128 times. Results showed frequently that, within the same type of issue, HCW referred various levels of impact (risk in causing or favoring HAI) and personal control (possibility for HCW to prevent HAI). Overall staff shortage was the most reported problem by HCW in our hospital. Also hand washing was regarded as a main problem, but HCW expressed the feeling that individuals could act more successfully on this issue (high or medium control). Results showed that staff frequently did not know how to handle correctly visitors, similarly many colleagues expressed some difficulty in communicating information to patients and relatives on HAI. Surprisingly, "antimicrobial therapy" and "excessive invasive procedures" were not particularly highlighted by the personnel. HCW expressed satisfaction for the course approac. CONCLUSIONS: The study showed an overall good level of knowledge regarding the importance and principles of infection control in our teaching hospital HCW. However personnel perceived a variability in the impact of many issues on HAI and even more on the personal possibility to control their effect. In order to improve HCW compliance with HAI prevention programs, the "Adult Learning" model seems to be very useful.

Point prevalence surveys on healthcare acquired infections in medical and surgical wards of a teaching hospital in Rome.

BACKGROUND: Healthcare acquired infections (HAI) are an important cause of morbidity and mortality in hospitals worldwide. Aim of the study was to analyze nine years surveillance activity, carried out by point prevalence surveys from 2007 to 2015, in a 450-bed teaching hospital in Rome. METHODS: Point prevalence surveys were carried out every year in the medical and surgical wards following the same methodology. In accordance with definitions used by the Centers for Disease Control, all infections occurred more than 48 hours after hospital admission were considered HAI, and included in the study. Baseline characteristics, clinical features, isolated pathogens (only for the period 2011-2015) and antimicrobial resistance were recorded. RESULTS: During the nine years point prevalence surveys a total 2,840 patients were enrolled. Overall 136 (4.79%) patients developed 180 (6.34%) HAI. The most frequent HAI were respiratory tract infections (RTI), which accounted for 35.0% of all HAI, followed by surgical site infections (SSI) 22.2%, urinary tract infections (UTI) 19.4%, bloodstream infections (BSI) 17.2%, and others 6.1%. HAI related to major invasive risk procedures were also evaluated. SSI/patients undergoing surgery 3.99%, UTI/ patients with urinary catheter 4.17% and BSI/patients with CVC 9.42%. Over one-half of all patients surveyed (1,532, 53.9%) were receiving antibiotics at the time of our study. Among them 892 (58.2%) for treatment, 641 (41.8%) for prophylaxis. In the latter group, 109 (17.0%) underwent extra-short term, 89 (13.9%) short term and 443 (69.1%) a long term prophylaxis. During the period 2011-2015 out of 110 HAI episodes 71 (64.5%) were confirmed microbiologically. In total 106 pathogens were isolates, Gram-negative bacteria (63.2%) were isolated more frequently than Gram-positive bacteria (28.3%). CONCLUSIONS: The overall HAI prevalence in our hospital was consistent with those reported in other studies in Italy. The study underlined the role of Gram-negative bacteria in HAI and the need for antimicrobial stewardship. It also provided useful baseline data for rational priorities in allocation of resources, for further infection control activities.

Brief Report: Self-Based and Mechanical-Based Future Thinking in Children with Autism Spectrum Disorder.

This brief report is a partial replication of the study by Jackson and Atance (J Dev Disabil 14:40-45, 2008) assessing nonverbal Self-based and Mechanical-based future thinking (FT) in children with Autism Spectrum Disorder (ASD). In a first step, these tasks were administered to 30 children with ASD. The two Self-based tasks were then modified as a verbal component could not be completely ruled out. Consequently, 77 children with ASD and 77 children with typical development received the modified Self-based FT tasks and the Mechanical-based FT tasks. We partially replicated the previous findings. Participants with ASD had impaired FT in both kinds of tasks and both groups performed better on tasks assessing Mechanical-based FT than Self-based FT. These results suggest that impairments of FT in ASD are not limited to Self-Projection.

The overweight: a rare presentation of celiac disease.

We describe the nutritional status of a cohort of celiac disease (CD) children at presentation and during follow-up on gluten-free diet (GFD). Two Italian centers (Rome and Bari) prospectively enrolled 445 biopsy-confirmed CD children, diagnosed between 2009 and 2013. Body Mass Index was used as a measure of nutritional status according to Italian growth charts of Cacciari. The overweight/obese subject was 7.8% at onset and did not significantly increase during follow-up (9.8% at final assessment). The prevalence of overweight/obesity was significantly higher among males than females. Furthermore, overweight/obesity children as compared with those with normal weight were significantly older and had significantly lower levels of tTG antibodies. This study shows that some CD children are obese/overweight at diagnosis; therefore, overweight/obesity can be considered a rare but a possible mode of CD presentation. Thus, CD diagnosis must be considered even in overweight/obese children where this diagnosis can be easily missed.

A mechanistic investigation of the ruthenium porphyrin catalysed aziridination of olefins by aryl azides.

A mechanism for the aziridination of olefins by aryl azides (ArN3), promoted by ruthenium(ii) porphyrin complexes, is proposed on the basis of kinetic and theoretical studies. All the recorded data support the involvement of a mono-imido ruthenium complex as the active intermediate in the transfer of the nitrene moiety "ArN" to the olefin. The selectivity of the aziridination vs. the uncatalysed triazoline formation can be enhanced by fine-tuning the electronic features of the porphyrin ligand and the olefin/azide catalytic ratio. The DFT study highlights the importance of an accessible triplet ground state of the intermediate ruthenium mono-imido complex to allow the evolution of the aziridination process.

Detection of autoantibodies against actin filaments in celiac disease.

INTRODUCTION: Serum autoantibodies specifically directed toward intracellular cytoskeletal actin filaments (anti-actin antibodies, AAA) were found to be associated with intestinal villous atrophy (IVA) in celiac disease (CD). The aim of this study was to assess IgA-AAA with a commercial test that uses sections of rat intestinal epithelial cells in a well-selected cohort of patients and to evaluate the relationship between the presence of serum IgA-AAA and the severity of intestinal mucosa damage. MATERIALS AND METHODS: Serum samples from 70 CD patients and 150 controls subjects were analyzed retrospectively for the presence of IgA-AAA. RESULTS: The indirect immunofluorescence test that we used has a specificity of 100%; the sensitivity of the test is not high (25.7%). In this study we also show that serum AAA are more frequently positive in CD patients with total IVA (77.8%) and that this association is significant DISCUSSION: IgA-AAA certainly cannot take the place of much more sensitive tests such as a-tTG and EMA in the diagnosis of CD because of their low sensitivity; nonetheless, these antibodies could be determined in a-tTG and/or EMA positive patients who cannot undergo an intestinal biopsy because of a severe contraindication, or in the case of negative consensus regarding endoscopy, or when the histology interpretation is difficult. CONCLUSION: In conclusion, the IFI commercial test with intestinal epithelial cells as substrate offers a useful method for IgA-AAA determination. Serum IgA-AAA positivity is indicative of more severe intestinal histology damage and their assay could be a real help to the clinician, especially in the complicated cases.

Association between celiac disease and primary lactase deficiency.

Primary lactase deficiency (PLD) is a common inherited condition caused by a reduced activity of lactase. Two single-nucleotide polymorphisms C/T(-13910) and G/A(-22018) upstream of the lactase gene are associated with lactase nonpersistence. In celiac disease (CD) patients, lactose intolerance could be due to secondary lactase deficiency and to PLD. The aim of this study were to evaluate the association of PLD and CD using genetic test, and to define the prevalence of PLD in celiac subjects compared with a control population. A total of 188 controls and 92 biopsy-proven CD patients were included in the study. More than 70% of all subjects were found homozygous for the polymorphisms. Differences in the prevalence of PLD were not found between CD patients and controls.In conclusions, the hereditary lactase deficiency is frequent in Italian CD children as in control population.

[Neuroimaging and definition of transient ischemic attack]. / Neuroimaging e definizione di attacco ischemico transitorio.

AIM: Transient ischemic attack (TIA) has to be considered an "alarm bell" of a more or less severe organic or systemic vasculopathy. Positive findings at neuroimaging means tissue damage. The purpose of this retrospective study was to assess the role of neuroimaging in the management of patients presenting with TIA, and to consider the relative implications. METHODS: In a consecutive series of 82 patients (53 males, 29 females, mean age: 65.9±13.1 years) admitted for TIA, it was possible to review the history and the clinical data of 66 patients, including ABCD2 score, laboratory including plasmatic D-dimer, and neuroimaging data including computed tomography (CT) and magnetic resonance imaging including diffusion-weighted with apparent diffusion coefficient measure (DWI-ADC) obtained at diagnosis and by a week later (16 by CT, and 50 by DWI-ADC). Thirty-three patients underwent DWI-ADC within 24 hours from symptoms onset. Statistical analysis has been performed by non-parametric tests (χ2 and Mann-Whitney), and logistic regression by a commercially available software. RESULTS: CT and/or DWI-ADC showed signs of acute ischemic lesions in 23/66 (35%) patients. 12 out of the 35 patients with a 24-hour DWI-ADC follow-up were positive. Statistical analysis showed that positive neuroimaging was significantly associated only with familial history of cardiovascular diseases (P<0.012) and previous TIA/stroke (P<0.046). CONCLUSION: In this patients series, at least 35% of patients with TIA had a positive neuroimaging, especially DWI-ADC. Positive neuroimaging seems an independent factor. Patients with TIA need an early assessment by neuroimaging including DWI-ADC, in order to obtain a correct classification and prognosis.

The effectiveness of 124I PET/CT in patients with differentiated thyroid cancer.

AIM: Several studies consider 124I PET useful in the evaluation of differentiated thyroid cancer (DTC). The aim of this work was to evaluate the usefulness of 124I positron emission tomography (PET)/computed tomography (CT) for: 1) pretherapeutic staging; 2) optimizing the administering activity in case of remnants ablation; 3) individualizing a complex dosimetry case by case especially in plurimetastatic patients. METHODS: A total of 69 patients were studied in our department between September 2007 and June 2008: 17 male and 52 female, aged 17-83 (mean age 46.6) and, with a simplified method, an expectation dose with a distant therapeutic evaluation, in term of efficacy, was calculated. A total body 124I PET/CT and a whole body scan (WBS) were done, respectively, before and after radiometabolic therapy with 131I and then compared in double blind in 67/69. In 2/69 with a follicular plurimetastatic DTC (both female, aged 65 and 71), an individualized complex dosimetric study was done. RESULTS: PET/CT and WBS matched in 58/67 patients (86.6%). We obtained a complete ablation of the thyroid remnants in 60/67 patients (90%). The individualized complex dosimetry tells us that the administrable maximum activity is for: patient 1:13320 MBq and patient 2:9250 MBq. CONCLUSIONS: Iodine-124 PET/CT is a powerful diagnostic tool before administration of 131I therapeutic dose. It allows for a precise dosimetry in plurimetastatic patients. After an empiric dose estimation, the successful percentage in term of thyroid's remnants ablation was very elevated.

Dental magnetic resonance imaging: study of impacted mandibular third molars.

OBJECTIVES: To assess the usefulness of MRI in the evaluation of the relationships between the mandibular canal and impacted mandibular third molars. METHODS: 29 young patients from our hospital dental service, all with a unilateral impacted mandibular third molar, were investigated with MR and the anatomical details were evaluated in three dimensions by two MR-experienced radiologists from our radiology division. MR images were obtained by using a 1.0 T Siemens Magnetom Expert unit with a radiofrequency (RF) head coil. T(1) weighted axial oblique images and proton density-weighted sagittal/coronal oblique images were acquired in order to evaluate the anatomical details in the three dimensions. RESULTS: In all of the cases it was possible to evaluate the depth of the third molar in the alveolar bone, its inclination towards the occlusal plane and the relationships with the mandibular canal, but in 2 of 29 cases it was not possible to distinguish the mandibular canal from the third molar because of magnetic susceptibility artefacts. CONCLUSIONS: Owing to the possibility of inferior alveolar nerve injury during oral surgery, where dental panoramic radiography is not sufficient to demonstrate the relationships between mandibular third molar teeth and the mandibular canal, a dental CT scan is often needed; however, in young patients, to avoid high levels of radiation dose, MRI of the jaw may be useful.

[Theoric hints on the quality perception in health care services concept]. / Cenni teorici sul concetto di qualità percepita in sanità.

topic in healthcare services management. In this article we try to summarize the most relevant theoretical approaches, providing a general definition of "quality" and trying a possible generic relationship between the concepts of "perceived quality" and "client satisfaction". Finally, we examine some methodological problems, concerning surveys on quality perception in healthcare services. Through the analysis of some examples, we will compare two methodologies, coming from the University of Siena (Italy) and from the Picker Institute Europe in Oxford (United Kingdom).