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OBJECTIVE This study compared relapse prevention and acceptability of long-acting injectable (LAI) antipsychotics in the maintenance treatment of adults with nonaffective psychoses. METHODS The authors searched MEDLINE, Embase, PsycINFO, CINAHL, CENTRAL, and online registers for randomized controlled trials published until June 2020. Relative risks and standardized mean differences were pooled using random-effects pairwise and network meta-analysis. The primary outcomes were relapse rate and all-cause discontinuation ("acceptability"). The quality of included studies was rated with the Cochrane Risk of Bias tool, and the certainty of pooled estimates was measured with GRADE (Grading of Recommendations Assessment, Development, and Evaluation). RESULTS Of 86 eligible trials, 78 (N=11,505) were included in the meta-analysis. Regarding relapse prevention, most of the 12 LAIs included outperformed placebo. The largest point estimates and best rankings of LAIs compared with placebo were found for paliperidone (3-month formulation) and aripiprazole. Moderate to high GRADE certainty for superior relapse prevention compared with placebo was also found for (in descending ranking order) risperidone, pipothiazine, olanzapine, and paliperidone (1-month formulation). In head-to-head comparisons of LAIs, only haloperidol was inferior to aripiprazole, fluphenazine, and paliperidone. For acceptability, most LAIs outperformed placebo, with moderate to high GRADE certainty for (in descending ranking order) zuclopenthixol, aripiprazole, paliperidone (3-month formulation), olanzapine, flupenthixol, fluphenazine, and paliperidone (1-month formulation). In head-to-head comparisons, only LAI aripiprazole had superior acceptability to other LAIs (bromperidol, fluphenazine, paliperidone [1-month formulation], pipothiazine, and risperidone). CONCLUSIONS LAI formulations of paliperidone (3-month formulation), aripiprazole, olanzapine, and paliperidone (1-month formulation) showed the highest effect sizes and certainty of evidence for both relapse prevention and acceptability. Results from this network meta-analysis should inform frontline clinicians and guidelines.

Carotid endarterectomy (CEA) has a wide range of approaches based on personal expertise and preference. We evaluated our outcome with CEA with modified eversion technique (meCEA) under local anesthesia and whether the surgeon's experience could influence it.at our Institution, 837 patients underwent CEA across 8 years. Although the surgical technique was standardized, 2 groups were considered further: meCEA performed by a single Senior Operator (Group A) and meCEA performed by 4 young Consultants (Group B).A selective shunting policy was needed in 5.1%, together with general anesthesia. Overall operative time was 63.9 ± 15.1 minutes (61.4 ± 12.5 and 66 ± 16.9 minutes in Group A and Group B respectively; P 0.001) and cross-clamp time 19.3 ± 2.9 minutes (19.0 ± 3.2 vs. 19.5 ± 2.8, P = 0.009). At 30 days, 0.7% TIA and 0.8% strokes were recorded. No differences (p = N.S.) between the 2 study groups in terms of postoperative neurological complications, with postoperative ipsilateral strokes always 1%. At a median imaging follow-up of 22.5 months, the overall percentage of restenosis was 3.7%, with no difference between the 2 groups (P = 0.954). Twenty-two patients (2.6%) underwent reintervention for significant restenosis, and none of them had an ipsilateral stroke or TIA. Freedom from reintervention for restenosis at 24 months was 97.9% in Group A and 95.9% in Group B, with no between-group difference (P = 0.14). At the median survival follow-up of 37 months, the overall survival rate at 24 months was 97.9%in Group A, and 97.9% in Group B, with no between-group difference (P = 0.070).In our experience, CEA with a modified technique is safe and achieves comparable outcomes to those of other established techniques. The reported short cross-clamp time, also in less experienced hands, is an additional strength.

Results of three rapid immunochromatographic tests (ICTs) were compared with those obtained with two automated immunoassays for evaluation of their usefulness. One hundred fifty-nine patients and 67 healthy volunteers were included. Different assays demonstrate 41-45% of diagnostic sensitivities and 91-98% of specificities, with substantial agreement (89.3-91.2%), but a high percentage of weak positive results (13-22%) was observed with ICTs. ICTs performances were comparable to those of automated immunoassays. ICTs could have a role as screening approach due to their easy usability. Subjective interpretation, significant rate of uncertain results, uncertainty on viral antigens source are undoubtedly drawbacks.

In recent years, there have been significant developments in rapid diagnostic techniques (RDTs) in microbiology for the diagnosis of infectious diseases. By providing a more rapid diagnosis, RDTs have the potential to affect diagnostic algorithms and therapeutic decisions. In addition to “antibiotic stewardship,” the term “diagnostic stewardship” has recently been coined in clinical practice and denotes the promotion of a rational implementation of diagnostic tests with a view to improving the quality of care and safely reducing cost. This review explores the advancement of diagnostic and antibiotic stewardship in the implementation of RDTs and describes the most relevant related clinical applications in Clostridioides difficile infections (CDIs), bloodstream infections (BSIs), and respiratory infections. An innovative evidence-based RDT diagnostic algorithm that varies according to the presence of pre-agreed institutional criteria significantly increases testing accuracy for differentiating CDIs from carriage status. Evidence on BSIs reveals that pairing RDTs and antibiotic stewardship eases timely and appropriate utilization of RDTs results that may improve the clinical outcomes by optimizing antibiotic use. Data on clinical implications of RDTs targeting antibiotic-resistant Gram-negative and respiratory infections are scarce and inconclusive. Intertwining the role of diagnostic and antibiotic stewardship is crucial to optimizing RDTs utilization, by ensuring that RDTs are rationally selected and implemented, and results correctly interpreted and applied to clinical practice. Further research is needed to explore the clinical implications of RDT implementation.

The COVID-19 pandemic is affecting healthcare services worldwide. We investigated the impact of a strict lockdown policy on the characteristics of neonatal and pediatric attendances to our pediatric emergency department (PED). The clinical features of PED visits in March–April 2020 (COVID-19) and March–April 2019 (non-COVID-19) were analyzed. During the COVID-19 lockdown period, visits reduced by 67%, from 3159 to 1039. Neonatal access decreased from 78 to 59, mainly due to fewer pathological conditions, with a complete disappearance of respiratory infections. On the other hand, minor neonatal clinical conditions rose from 44 (56.4%) to 48 (81.4%), mostly due to feeding-related issues. Communicable diseases, particularly respiratory infections and gastroenteritis, dropped from 1552 (49.1%) to 288 (27.7%). Accident-related visits also decreased during COVID-19, from 535 (16.9%) to 309 (29.7%), becoming the most common cause of PED access. Hospital admissions reduced from 266 to 109, while PICU (pediatric intensive care unit) admissions decreased from 27 to 11, with a comparable rate of 10.1% in both periods. The lockdown due to COVID-19 had a substantial impact on our PED visits, which markedly decreased, mainly due to fewer respiratory infections. Unexpectedly, neonatal visits for minor conditions did not decline, but rather slightly increased. Among the children admitted to the PICU, none had respiratory disease.

ObjectiveTo determine burn-out levels and associated factors among healthcare personnel working in a tertiary hospital of a highly burdened area of north-east Italy during the COVID-19 pandemic.DesignObservational study conducted from 21 April to 6 May 2020 using a web-based questionnaire.SettingResearch conducted in the Verona University Hospital (Veneto, Italy).ParticipantsOut of 2195 eligible participants, 1961 healthcare workers with the full range of professional profiles (89.3%) completed the survey.Primary outcome measureLevels of burn-out, assessed by the Maslach Burnout Inventory-General Survey (MBI-GS). Multivariable logistic regression analysis was performed to identify factors associated with burn-out in each MBI-GS dimension (emotional exhaustion, EX; professional efficacy, EF; cynicism, CY).ResultsOverall, 38.3% displayed high EX, 46.5% low EF and 26.5% high CY. Burn-out was frequent among staff working in intensive care units (EX 57.0%; EF 47.8%; CY 40.1%), and among residents (EX 34.9%; EF 63.9%; CY 33.4%) and nurses (EX 49.2%; EF 46.9%; CY 29.7%). Being a resident increased the risk of burn-out (by nearly 2.5 times) in all the three MBI subscales and being a nurse increased the risk of burn-out in the EX dimension in comparison to physicians. Healthcare staff directly engaged with patients with COVID-19 showed more EX and CY than those working in non-COVID wards. Finally, the risk of burn-out was higher in staff showing pre-existing psychological problems, in those having experienced a COVID-related traumatic event and in those having experienced interpersonal avoidance in the workplace and personal life.ConclusionsBurn-out represents a great concern for healthcare staff working in a large tertiary hospital during the COVID-19 pandemic and its impact is more burdensome for front-line junior physicians. This study underlines the need to carefully address psychological well-being of healthcare workers to prevent the increase of burn-out in the event of a new COVID-19 healthcare emergency.

Background Asthma control and monitoring still represents a challenge worldwide. Although the international guidelines suggest the interplay between secondary and primary care services as an effective strategy to control the disease, community pharmacies’ are seldom involved in asthma control assessment. The present cross-sectional study aimed at providing a picture of the relationship between asthma severity and control in community pharmacies within the health district of the city of Verona (Veneto Region, North-Eastern Italy). Methods A call for participation was launched through the Pharmacists’ Association of Verona. Patients referring to the participating pharmacies with an anti-asthmatic drug medical prescription and an asthma exemption code were asked to complete the Asthma Control Test (ACT) and a brief questionnaire collecting information on their age, sex, smoking status, aerobic physical exercise and usual asthma therapy, which also defined asthma severity. A multinomial logistic regression model was fitted to investigate the risk of uncontrolled as well as poorly controlled vs. controlled asthma (base). Results were expressed as relative risk ratios (RRR) with 95% confidence interval (95%CI). Results Fifty-seven community pharmacies accepted to participate and 584 asthmatic patients (54% females; mean-age: 51 ± 19 years) were consecutively recruited from 1st January to 30th June 2018 (6 months). Based upon ACT score 50.5% patients had a controlled asthma, 22.3% a poorly controlled and 27.2% uncontrolled. A variable proportion of patients with uncontrolled asthma were observed for every level of severity, although more frequently with mild persistent form of asthma. Most patients (92%) self-reported regular compliance with therapy. At multinomial regression analysis, patients under regular asthma treatment course (RRR = 0.33; 95%CI: 0.15; 0.77) were less likely to have an ACT Conclusions Overall, our findings highlighted an unsatisfactory asthma control in the general population, independently of the severity level of the disease. Community pharmacies could be a useful frontline interface between patients and the health care services, supporting an effective asthma management plan, from disease assessment and monitoring treatment compliance to referral of patients to specialist medical consultancies.

Background The current management guidelines recommend that patients with borderline resectable pancreatic adenocarcinoma (BRPC) should initially receive neoadjuvant chemotherapy. The addition of advanced radiation therapy modalities, including stereotactic body radiation therapy (SBRT) and intraoperative radiation therapy (IORT), could result in a more effective neoadjuvant strategy, with higher rates of margin-free resections and improved survival outcomes. Methods/design In this single-center, single-arm, intention-to-treat, phase II trial newly diagnosed BRPC will receive a “total neoadjuvant” therapy with FOLFIRINOX (5-fluorouracil, irinotecan and oxaliplatin) and hypofractionated SBRT (5 fractions, total dose of 30 Gy with simultaneous integrated boost of 50 Gy on tumor-vessel interface). Following surgical exploration or resection, IORT will be also delivered (10 Gy). The primary endpoint is 3-year survival. Secondary endpoints include completion of neoadjuvant treatment, resection rate, acute and late toxicities, and progression-free survival. In the subset of patients undergoing resection, per-protocol analysis of disease-free and disease-specific survival will be performed. The estimated sample size is 100 patients over a 36-month period. The trial is currently recruiting. Trial registration NCT04090463 at clinicaltrials.gov.

Biologics for severe asthma can significantly impact on the burden of disease and also have the potential to reduce asthma mortality. By reviewing the literature and contacting the pharmaceutical companies, the present paper aims at providing a worldwide snapshot of biologic drugs availability, related with the trend of asthma mortality rate, as a marker of the burden of the disease. A decline in the global rate of annual asthma mortality was observed until the 1980s, but overall no further reduction occurred, and the current mortality estimation is 0.19 deaths per 100.000 people. A higher mortality rate has been registered in low and middle-income countries (LMICs), where poor socioeconomic conditions and lack of access to the medical resources are more relevant. The availability of monoclonal antibodies is mainly limited to the developed and high-income countries. Furthermore the overall “asthma management system” in LMICs suffers from a number of restrictions that hamper the widespread availability of biologics besides their costs. The availability of generic drugs in the field of biologics for severe asthma could contribute to facilitate their widespread accessibility. But before that, awareness and expertise regarding severe asthma, and proper tools to assess and manage it, deserve to be shared worldwide. Collaboration projects involving physicians from all the countries through the scientific Academies network and with the support of the Companies active in the field may provide an initial concrete opportunity.

Previous studies showed a significant association between lower plasma adiponectin levels and higher risk of adverse cardiovascular outcomes in patients with and without type 2 diabetes mellitus (T2DM). Presently, it is uncertain whether lower plasma adiponectin levels are associated with greater plasma thrombin generation in patients with T2DM. We studied 82 middle-aged men with non-insulin-treated T2DM [mean age ± SD: 64.1 ± 8 years; median duration of diabetes: 12.5 (inter-quartile range 6–19) years; mean hemoglobin A1c 7.0 ± 0.7%], consecutively attending our diabetes outpatient service over a 6-month period. Using the newly developed fully automated thrombin generation analyzer ST Genesia®, we measured the plasma parameters lag time (LT), time to peak (TP), peak height (PH) and endogenous thrombin potential (ETP) in all participants. In univariable linear regression analyses, lower plasma adiponectin levels were significantly associated with higher plasma thrombin generation parameters, as reflected by higher values of PH (Pearson’s r coefficient = − 0.228, p = 0.039) and EPT (r = − 0.293, p = 0.007). Plasma adiponectin levels were not significantly associated with other thrombin generation parameters (LT and TP). Notably, the significant associations of plasma adiponectin levels with thrombin PH and EPT values persisted after adjustment for age and adiposity measures, but they were lost after additional adjustment for plasma triglycerides. Our findings show for the first time the existence of a significant association between lower levels of plasma adiponectin and greater plasma thrombin generation (as assessed by the ST Genesia® analyzer) in men with non-insulin-treated T2DM, which appears to be largely mediated by plasma triglycerides.

Objectives The COVID-19 pandemic is putting a huge strain on the provision and continuity of care. The length of sickness absence of the healthcare workers as a result of SARS-CoV-2 infection plays a pivotal role in hospital staff management. Therefore, the aim of this study was to explore the timing of COVID-19 recovery and viral clearance, and its predictive factors, in a large sample of healthcare workers. Study design Retrospective cohort study. Methods The analysis was conducted on data collected during the hospital health surveillance programme for healthcare staff at the University Hospital of Verona; healthcare workers were tested for SARS-CoV-2 through RT-PCR with oro-nasopharyngeal swab samples. The health surveillance programme targeted healthcare workers who either had close contact with SARS-CoV-2 infected patients or were tested as part of the screening-based strategy implemented according to national and regional requirements. Recovery time was estimated from the first positive swab to two consecutive negative swabs, collected 24 hours apart, using survival analysis for both right-censored and interval-censored data. Cox proportional hazard was used for multivariate analysis. Results During the health surveillance programme, 6455 healthcare workers were tested for SARS-CoV-2 and 248 (3.8%, 95% confidence interval [CI] 3.4–4.3) reported positive results; among those who tested positive, 49% were asymptomatic, with a median age of 39.8 years, which is significantly younger than symptomatic healthcare workers (48.2 years, p < 0.001). Screening tests as part of the health surveillance programme identified 31 (12.5%) of the positive cases. Median recovery time was 24 days (95% CI 23–26) and 21.5 days (95% CI 15.5–30.5) in right- and interval-censoring analysis, respectively, with no association with age, sex or presence of symptoms. Overall, 63% of participants required >20 days to test negative on two consecutive swabs. Hospitalised healthcare workers (4.8%) were older and had a significantly longer recovery time compared with non-hospitalised healthcare workers in both analyses (33.5 vs 24 days, p = 0.005). Conclusions Recovery from COVID-19 and viral clearance may take a long time, especially in individuals who are hospitalised. To detect asymptomatic cases, screening programmes for healthcare workers is recommended.

Background People living in 'humanitarian settings' in low‐ and middle‐income countries (LMICs) are exposed to a constellation of physical and psychological stressors that make them vulnerable to developing mental disorders. A range of psychological and social interventions have been implemented with the aim to prevent the onset of mental disorders and/or lower psychological distress in populations at risk, and it is not known whether interventions are effective. Objectives To compare the efficacy and acceptability of psychological and social interventions versus control conditions (wait list, treatment as usual, attention placebo, psychological placebo, or no treatment) aimed at preventing the onset of non‐psychotic mental disorders in people living in LMICs affected by humanitarian crises. Search methods We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMD‐CTR), the Cochrane Drugs and Alcohol Review Group (CDAG) Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), Embase (OVID), PsycINFO (OVID), and ProQuest PILOTS database with results incorporated from searches to February 2020. We also searched the World Health Organization's (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov to identify unpublished or ongoing studies. We checked the reference lists of relevant studies and reviews. Selection criteria All randomised controlled trials (RCTs) comparing psychological and social interventions versus control conditions to prevent the onset of mental disorders in adults and children living in LMICs affected by humanitarian crises. We excluded studies that enrolled participants based on a positive diagnosis of mental disorder (or based on a proxy of scoring above a cut‐off score on a screening measure). Data collection and analysis We calculated standardised mean differences for continuous outcomes and risk ratios for dichotomous data, using a random‐effects model. We analysed data at endpoint (zero to four weeks after therapy) and at medium term (one to four months after intervention). No data were available at long term (six months or longer). We used GRADE to assess the quality of evidence. Main results In the present review we included seven RCTs with a total of 2398 participants, coming from both children/adolescents (five RCTs), and adults (two RCTs). Together, the seven RCTs compared six different psychosocial interventions against a control comparator (waiting list in all studies). All the interventions were delivered by paraprofessionals and, with the exception of one study, delivered at a group level. None of the included studies provided data on the efficacy of interventions to prevent the onset of mental disorders (incidence). For the primary outcome of acceptability, there may be no evidence of a difference between psychological and social interventions and control at endpoint for children and adolescents (RR 0.93, 95% CI 0.78 to 1.10; 5 studies, 1372 participants; low‐quality evidence) or adults (RR 0.96, 95% CI 0.61 to 1.50; 2 studies, 767 participants; very low quality evidence). No information on adverse events related to the interventions was available. For children's and adolescents' secondary outcomes of prevention interventions, there may be no evidence of a difference between psychological and social intervention groups and control groups for reducing PTSD symptoms (standardised mean difference (SMD) −0.16, 95% CI −0.50 to 0.18; 3 studies, 590 participants; very low quality evidence), depressive symptoms (SMD −0.01, 95% CI −0.29 to 0.31; 4 RCTs, 746 participants; very low quality evidence) and anxiety symptoms (SMD 0.11, 95% CI −0.09 to 0.31; 3 studies, 632 participants; very low quality evidence) at study endpoint. In adults' secondary outcomes of prevention interventions, psychological counselling may be effective for reducing depressive symptoms (MD −7.50, 95% CI −9.19 to −5.81; 1 study, 258 participants; very low quality evidence) and anxiety symptoms (MD −6.10, 95% CI −7.57 to −4.63; 1 study, 258 participants; very low quality evidence) at endpoint. No data were available for PTSD symptoms in the adult population. Owing to the small number of RCTs included in the present review, it was not possible to carry out neither sensitivity nor subgroup analyses. Authors' conclusions Of the seven prevention studies included in this review, none assessed whether prevention interventions reduced the incidence of mental disorders and there may be no evidence for any differences in acceptability. Additionally, for both child and adolescent populations and adult populations, a very small number of RCTs with low quality evidence on the review's secondary outcomes (changes in symptomatology at endpoint) did not suggest any beneficial effect for the studied prevention interventions. Confidence in the findings is hampered by the scarcity of prevention studies eligible for inclusion in the review, by risk of bias in the studies, and by substantial levels of heterogeneity. Moreover, it is possible that random error had a role in distorting results, and that a more thorough picture of the efficacy of prevention interventions will be provided by future studies. For this reason, prevention studies are urgently needed to assess the impact of interventions on the incidence of mental disorders in children and adults, with extended periods of follow‐up., Plain language summary Do psychological and social interventions prevent mental health disorders in low‐ and middle‐income countries affected by humanitarian crises? Mental health during a humanitarian crisis A humanitarian crisis is an event, or series of events, that threaten the health, safety, security or well‐being of a community or large group of people, usually over a wide area. Examples include: wars, famine, and natural disasters such as earthquakes, hurricanes and floods. People living through a humanitarian crisis may experience physical and mental distress that make them vulnerable to developing mental health disorders. These include post‐traumatic stress disorder, depression and anxiety. What are psychological and social interventions? Psychological interventions of a preventive nature usually offer people support and practical help to develop ways of coping, a sense of hope, and focus on building resilience. Social interventions of a preventive nature usually aim to strengthen social support systems and help people to feel more connected. Why we did this Cochrane Review We wanted to know if psychological and social interventions (psychosocial interventions) could help to stop mental health disorders developing in people living through humanitarian crises in low‐ and middle‐income countries. We were interested in: 1)·how many people developed a mental health disorder after taking part in an intervention; and 2) how many people dropped out of a programme or had unwanted effects related to the intervention. What did we do? We searched for studies that looked at the preventive effects of psychosocial interventions on people's mental health in low‐ and middle‐income countries affected by humanitarian crises. We looked for randomised controlled studies, in which the interventions people received were decided at random. This type of study usually gives the most reliable evidence about the effects of an intervention. Search date We included evidence published up to February 2020. What we found We found seven prevention studies with a total of 2398 participants. Five studies were in children and adolescents (aged 7 to 18 years), and two were in adults (aged over 18 years). Two studies were done in Nepal, and one study each in Democratic Republic of Congo, Haiti, Syria, Uganda and Sri Lanka. Six different psychosocial interventions were studied. The studies measured symptoms of depression, anxiety and post‐traumatic stress disorder in children and adolescents, and anxiety and depression symptoms in adults, at the beginning of the study, the end of the intervention, and after four weeks and up to four months later. They compared the results with symptoms measured in people on a waiting list to take part in the intervention. What are the results of our review? None of the studies measured how many people developed a mental disorder after taking part in a psychosocial intervention, and none measured any unwanted effects of the interventions. There may be little to no difference in how many children and adolescents dropped out of an intervention while taking part, compared with being on a waiting list (5 studies). We were uncertain if there was any difference in the number of adults who dropped out (2 studies). In children and adolescents, only very small differences in symptoms of post‐traumatic stress disorder, depression and anxiety were seen at the end of an intervention, compared with being on a waiting list, suggesting no evidence of a difference. However, we are not confident that these results are reliable: the results are likely to change when further evidence is available. In adults, results from one prevention study showed that psychological counselling may lower depression and anxiety symptoms; but this result is from only one study and we are not confident the result is reliable. This result will probably change when more evidence becomes available. Conclusions We did not find any randomized evidence whether psychosocial interventions can stop mental health disorders developing in people living through humanitarian crises in low‐ to middle‐income countries. We did not find enough reliable evidence about the benefits of these interventions in reducing mental health symptoms. Larger, well‐conducted studies are needed to give more reliable evidence about the short‐ and long‐term effects of psychosocial interventions to prevent mental disorders in people living in low‐ and middle‐income countries affected by humanitarian crises.

The 2019 coronavirus disease (COVID-19) outbreak could result in higher levels of psychological distress, especially among people suffering from pre-existing mental health conditions. Young individuals with autism spectrum disorders (ASD) are particularly at risk due to their vulnerability to unpredictable and complex changes. This study aimed to investigate the impact of the COVID-19 pandemic on ASD individuals, whether any pre-pandemic sociodemographic or clinical characteristics would predict a negative outcome, and to narratively characterize their needs. Parents and guardians of ASD individuals filled out an online survey consisting of 40 questions investigating socio-demographic and clinical characteristics of their children, impact of the COVID-19 outbreak on their wellbeing and needs to deal with the emergency. Data were available on 527 survey participants. The COVID-19 emergency resulted in a challenging period for 93.9% of families, increased difficulties in managing daily activities, especially free time (78.1%) and structured activities (75.7%), and, respectively, 35.5% and 41.5% of children presenting with more intense and more frequent behavior problems. Behavior problems predating the COVID-19 outbreak predicted a higher risk of more intense (odds ratio (OR) = 2.16, 95% confidence interval (CI) 1.42&ndash, 3.29) and more frequent (OR = 1.67, 95% CI 1.13&ndash, 2.48) disruptive behavior. Even though ASD children were receiving different types of support, also requiring specialist (19.1%) or emergency (1.5%) interventions in a relatively low proportion of cases, a number of needs emerged, including receiving more healthcare support (47.4%), especially in-home support (29.9%), as well as interventions to tackle a potentially disruptive quarantine (16.8%). The COVID-19 outbreak has undoubtedly resulted in increased difficulties among ASD individuals.

Keywords: STAT3, mTOR, Bone Marrow Failure Syndromes, lymphocytes

Current data show that maternal mental conditions affect about 10% of pregnant women worldwide. Assessing timing and patterns of mental health illness, therefore, is critical to ensure the wellbeing of the mother, the new-born and the whole family. The aim of this review is to summarize the latest evidence linking maternal mental disorders and adverse reproductive outcomes. Following the PRISMA guidelines for systematic reviews, a literature search was conducted to ascertain the possible impact of mental health conditions on reproductive outcomes before and during pregnancy. The comprehensive strategy included cohort studies, randomised controlled trials and literature reviews on women with Primary Maternal Mental Illness (PMMI) and Secondary Maternal Mental Illness (SMMI) considering periconceptional, obstetric and foetal-neonatal outcomes. PubMed, WoS, CINAHL and Google scholar were used for the search. Cross-referencing in bibliographies of the selected papers ensured wider study capture. Evidence linking depressive disorders and infertility among PMMI is weak. Given this, women with prior mental conditions experience additional distress when undergoing fertility treatments. Primary mental disorders may also increase the risk of miscarriage and other pregnancy complications (e.g., gestational diabetes). For SMMI, there is more robust evidence correlating Preterm Birth (PTB) and Low Birth Weight (LBW) with common mental disorders which develop during pregnancy. Prevention and management of maternal mental health diseases and minor mental conditions within the first 1000 days’ timeframe, should have a place in the holistic approach to women going through reproductive decisions, infertility treatment and pregnancy.

Background The osmotic fragility test (OFT), conventionally used for assisting the diagnosis of many erythrocyte disorders, is a manual and time-consuming analysis not daily performed in many medical laboratories. This study was aimed at defining the stability of whole blood samples used for assessing erythrocyte osmotic resistance. Methods Twenty-one consecutive routine whole blood samples collected into 5.4 mg K2EDTA were tested immediately after collection (day 0) and at different time intervals afterward (day 1, 2, 3, 4, 7, 10 and 14) after storage at 4 °C. The OFT was performed with the Osmored Monotest (1.3% glycerol; Eurospital, Trieste, Italy). Results at the different time points were compared with those obtained at day 0 and with the reference change value (i.e., 33%). Results The median value of both hyperosmolar and hyposmolar resistance increased from baseline, reaching statistical significance at day 7 for hyperosmolar resistance and at day 1 for hyposmolar resistance, respectively. The median relative increase of hemolysis percentage values become greater than the reference change value at day 3 for hyposmolar resistance, while this limit was never overcome for hyperosmolar resistance. A significant inverse association was found between the mean increase in hyperosmolar resistance and the baseline value of hyperosmolar resistance (r = −0.92), mean corpuscular volume (MCV; r = −0.46) or mean corpuscular hemoglobin (MCH; r = −0.44), as well as between the mean increase in hyposmolar resistance and the baseline value of hyposmolar resistance (r = −0.86), or patient age (r = −0.56). Conclusions The sample stability seems critical for the OFT. Whole blood specimens should not be stored refrigerated at 4 °C for >2 days before testing.

The aim of this study was to analyze the immunological response to SARS-CoV-2 using novel fully automated chemiluminescence immunoassays (CLIAs) The direct comparison by receiver operating characteristic (ROC) curve analysis of MAGLUMI 2019-nCoV IgG positive/negative vs Euroimmun Anti-SARS-CoV-2 IgG positive/negative results yielded an overall concordance of 88% (kappa statistics, 0 47;95% CI, 0 26-0 68;p=1 30 AU/mL Despite being different immunoglobulin classes, an analogous analysis between MAGLUMI 2019-nCoV IgM positive/negative vs Euroimmun Anti-SARS-CoV-2 IgA positive/negative results yielded an overall concordance of 90% (kappa statistics, 0 39;95% CI, 0 14-0 65;p=0 001), AUC of 0 64 (95% CI, 0 53-0 75;p=0 001) and Spearman correlation (absorbance) of 0 26 (95% CI, 0 09-0 41;p=0 003) The ROC curve, recalculated using MAGLUMI 2019-nCoV IgM absorbance data vs Euroimmun Anti-SARS-CoV-2 positive/negative IgA results, yielded a substantial increase in the AUC (0 87;95% CI, 0 77-0 97;p

Less than half of severe asthmatic patients show a >80% adherence rate to inhaled treatment just before and during biologic therapy. This has implications in biologic treatment sustainability and disease prevalence estimation. http://bit.ly/3cRTJB0.

Antibiotic resistance is increasing worldwide. The implementation of antibiotic stewardship programmes (ASPs) is of utmost importance to optimize antibiotic use in order to prevent resistance development without harming patients. The emergency department (ED), cornerstone between hospital and community, represents a crucial setting for addressing ASP implementation; however, evidence data on ASP in ED are poor. In this study, a 4-year, non-restrictive, multi-faceted ASP was implemented in a general ED with the aim to evaluate its impact on antibiotic use and costs. Secondly, the study focused on assessing the impact on length of hospital stay (LOS), Clostridioides difficile infection (CDI) incidence rate, and mortality in the patients’ group admitted from ED to medical wards. The ASP implementation was associated with a reduction of antibiotic use and costs. A mild but sustained LOS decrease in all medical wards and a significant downward trend of CDI incidence rate were observed, while mortality did not significantly change. In conclusion, the implementation of our ED-based ASP has demonstrated to be feasible and safe and might clinically benefit the hospital admitted patients’ group. Further research is needed to identify the most suitable ASP design for ED and the key outcome measures to reliably assess its effectiveness.

Background: Although it is known that glucose concentration exhibits a time-dependent decay in uncentrifuged serum and lithium-heparin blood tubes, no evidence exists on how this variation may depend on blood cell counts (CBC) and volumes. Methods: Venous blood was drawn from 30 non fasting healthy volunteers into three serum and three lithium-heparin tubes. One serum and lithium-heparin tubes were centrifuged within 15 min after collection and glucose was measured with a hexokinase assay. The second and third serum and lithium-heparin tubes were maintained at room temperature for 1 and 2 h after the first tubes were centrifuged. These other tubes were then centrifuged and glucose was measured. CBC was performed in the first lithium-heparin tube, before centrifugation. Results: The mean decrease of glucose was higher in lithium-heparin plasma than in serum (0.33 vs. 0.24 mmol/L/h; p Conclusions: Glucose concentration decrease in uncentrifuged lithium-heparin and serum tubes depends on the baseline number of RBC, WBC, neutrophils and monocytes within the tubes.

Background: Asthma still represents a cause of death and hospital admissions worldwide. Our study aimed at analyzing the trend of Emergency Room (ER) asthma admissions in Northeast Italy in order to investigate the relevance of specific patient-related determinants and environmental triggers (pollens, mold spores, and pollutants). Methods: Retrospective data from admissions for asthma exacerbations registered between the years 2013 and 2015 in two main ERs in Northeast Italy were collected. Data about patients' age, sex and nationality were recorded. Classification of disease severity followed the current Italian ER triage scoring system (white: no need for emergency treatment; green: need for fast treatment; yellow: severe condition; red: life-threatening condition). Data on pollen/mold spore counts and pollutants were analyzed. Results: Overall, 1745 ​ER admissions for asthma were registered, with a persistent and significant increase year by year. A slight prevalence of females and patients over 50 years old was observed. Immigrants accounted for 32%, 36% and 26% of admissions respectively in 2013, 2014 and 2015. The prevalence of immigrants' admissions was significantly higher when comparing the relative ratio of immigrant populations/Italian nationals (p ​

Background The prevalence of pure stress urinary incontinence (P-SUI) and the role of urodynamic investigation (UDI) prior to surgery for stress urinary incontinence (SUI) is debated. Since the exact prevalence of P-SUI is not clear, its clinical and economic impact is not well defined. The aims of this study were to evaluate the prevalence of P-SUI in a population of women who underwent UDI for urinary incontinence (UI), also assessing: 1) the correspondence between clinical diagnosis of P-SUI and urodynamic findings; 2) the analysis of costs in terms of UDI and eventually post-UDI avoided surgical procedures. Methods A single cohort of women who underwent UDI for UI between January 2012 and July 2016 was prospectively collected and retrospectively analyzed. Clinical P-SUI was defined by the strict criteria of the International Continence Society. For each patient, history, physical examination and UDI were collected. The correspondence between clinical and urodynamic findings of P-SUI was analyzed. The rate of clinical P-SUI changed after performing UDI and the number of unnecessary intervention after UDI were reported. A wide cost analysis of UDIs, and the amount of surgical procedures that were believed unnecessary after UDI was reported. Results Stress urinary incontinence was present in 323/544 (59.4%) patients. The prevalence of clinical P-SUI was 20.7% (67/323), while the prevalence of complicated SUI (C-SUI) was 79.3% (256/323). After UDI, diagnosis of P-SUI decreased to 18.3% (59/232). In 10.2% of cases (6/59) the scheduled middle urethral sling (MUS) was suppressed after the UDI results because 3/6 cases had detrusor overactivity and urge incontinence, in 2/6 cases SUI was treated with a conservative management, in 1/6 case an important voiding dysfunction was detected. Considering the national reimbursement in our country, the cost of each UDI was 296.5 euros and the total amount was 17,493.5 euros. So far the surgery-related savings covered 61.7–105.0% of the costs of total number of UDIs performed in the uncomplicated patients. Conclusions The prevalence of clinical P-SUI is relevant, involving about 20% of women with clinical SUI. Although the correspondence between clinical and urodynamic diagnosis was high, we demonstrated that UDI may help in some cases to avoid an inappropriate surgical treatment. Therefore, UDI prior to SUI surgery should be considered to achieve a correct diagnosis and a proper therapeutic strategy.

Flinn et al . have reported the results of the long-term follow-up for the BRIGHT trial, an international study which compared the efficacy and the safety of bendamustine plus rituximab (BR) with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) for treatment-naive patients with indolent non-Hodgkin lymphoma (iNHL) or mantle-cell lymphoma (MCL).

Paternal health and behavioral lifestyles affect reproductive and neonatal outcomes and yet the magnitude of these effects remain underestimated. Even though these impacts have been formally recognized as a central aspect of reproductive health, health care services in Europe often neglect the involvement of fathers in their reproductive programs. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic reviews, a literature search was carried out to assess the possible impact of paternal health on reproductive outcomes. The comprehensive strategy included cohort studies and meta-analysis available on PubMed, Web of Science, CINAHL, and Google scholar. Cross-referencing of bibliographies of the selected papers ensured wider study capture. Paternal factors were grouped into two categories respectively identified with the terms “Biological Paternal Factors” and “Lifestyle Paternal Factors”. Advanced age may impair male fertility and affect early pregnancy stages. Increased body mass index, smoking, alcohol and recreational drugs, all alter seminal fluid parameters. Hazardous alcohol use correlates with low birthweight in pregnancy and harmful behavioral lifestyles have been linked to congenital heart defects, metabolic and neurodevelopmental disorders in the offspring. Measures targeting paternal health and lifestyle within the first 1,000 days' timeframe need to be implemented in couples undergoing reproductive decisions. Health professionals, as well as future fathers, must be aware of the benefits for the offspring associated with correct paternal behaviors. More research is needed to build guidelines and to implement specific programs aiming at reproductive health promotion.

// Andrea Mafficini 1,* , Michele Simbolo 1,* , Alice Parisi 2 , Borislav Rusev 1,2 , Claudio Luchini 1,2 , Ivana Cataldo 1 , Elena Piazzola 2 , Nicola Sperandio 1 , Giona Turri 2 , Massimo Franchi 3 , Giampaolo Tortora 4 , Chiara Bovo 5 , Rita T. Lawlor 1,2 and Aldo Scarpa 1,2 1 ARC-Net Research Centre, University and Hospital Trust of Verona, Verona, Italy 2 Department of Pathology & Diagnostics, University and Hospital Trust of Verona, Verona, Italy 3 Department of Gynecology, University and Hospital Trust of Verona, Verona, Italy 4 Comprehensive Cancer Centre, University and Hospital Trust of Verona, Verona, Italy 5 Board of Directors, University and Hospital Trust of Verona, Verona, Italy * Shared first authors Correspondence to: Rita T. Lawlor , email: // Keywords : BRCA1-BRCA2 , ovarian carcinoma, next generation sequencing, PARP inhibitor, olaparib Received : November 10, 2015 Accepted : December 29, 2015 Published : January 07, 2016 Abstract BRCA mutated ovarian cancers respond better to platinum-based therapy and to the recently approved PARP-inhibitors. There is the need for efficient and timely methods to detect both somatic and germline mutations using formalin-fixed paraffin-embedded (FFPE) tissues and commercially available technology. We used a commercial kit exploring all exons and 50bp exon-intron junctions of BRCA1 and BRCA2 genes, and semiconductor next-generation sequencing (NGS) on DNA from 47 FFPE samples of high-grade serous ovarian cancers. Pathogenic mutations were found in 13/47 (28%) cancers: eight in BRCA1 and five in BRCA2 . All BRCA1 and two BRCA2 mutations were germline; three BRCA2 mutations were somatic. All mutations were confirmed by Sanger sequencing. To evaluate the performance of the NGS panel, we assessed its capability to detect the 6,953 variants described for BRCA1 and BRCA2 in ClinVar and COSMIC databases using callability analysis. 6,059 (87.1%) variants were identified automatically by the software; 829 (12.0%) required visual verification. The remaining 65 (0.9%) variants were uncallable, and would require 15 Sanger reactions to be resolved. Thus, the sensitivity of the NGS-panel was 99.1%. In conclusion, NGS performed with a commercial kit is highly efficient for detection of germline and somatic mutations in BRCA genes using routine FFPE tissue.

Highlights • So far, the prevalence of COVID-19 in multiple sclerosis patients are unknown. • The prevalence in an MS cohort from the Veneto region, Italy, was higher than in the general population. The disease course was mild to moderate. • MS-population based studies could be a good way to investigate indirectly the infection prevalence in the general population., Neurologists are interested in understanding whether patients with multiple sclerosis (pwMS) undergoing immunomodulatory/immunosuppressive therapy are more susceptible to developing COVID-19 or have worse outcomes. Currently, there are no conclusive data in this regard. We report the prevalence and severity of COVID-19 (confirmed and possible) in pwMS followed at the Veneto Regional MS Center in Verona (Italy), an area most stricken by COVID-19. In our sample size, the prevalence of COVID-19 seems to be much higher than that officially reported at the regional level on the general population, but it also characterized by a favourable course.

Patient: Female, 39-year-old Final Diagnosis: Goiter with periprocedural complication Symptoms: None Medication:— Clinical Procedure: Fine-needle aspiration cytology Specialty: Radiology Objective: Challenging differential diagnosis Background: The complications of fine-needle aspiration cytology (FNAC) are rare but can be challenging for performing physicians to diagnose and manage. This type of procedure is perceived as routine and devoid of substantial risks, but uncommon complications can occur and need to be addressed with careful workup. Case Report: A FNAC procedure for a young female patient with multiple thyroid nodules was requested by her general practitioner. After the FNAC thyroid procedure, a carotid wall hematoma was suspected and could not be excluded with ultrasound (US) alone. Thus, the patient underwent a computed tomography angiogram (CTA) that excluded blood extravasation from the carotid, confirming the suspicion of perivascular blood accumulation. As a precaution, the patient was hospitalized, with US follow-up; she was dismissed the day after her hospital admission with a diagnosis of a benign thyroid nodule in multinodular goiter according to SIAPEC-IAP classification. Conclusions: This case highlights how a routine-perceived procedure such as FNAC could present a challenge to the performing physicians, pathologist, and radiologist, raising the suspicion of a severe complication that needs to be addressed with a readily available emergency service that may be accessible only within a central hospital-level organization. This case reinforces the point that more careful adherence to clinic-radiological guidelines is needed to avoid potentially inappropriate and harmful procedures. A review of the literature concerning guidelines for FNAC procedure, diagnostic classifications, and reported complications is provided as part of this case report.

Objectives: The aims of this cross-sectional study were to describe the incidence of haemorrhages and adverse drug events related to different classes of drugs as cause of emergency department admission. Methods: Adult patients (≥ 18 years) visiting two emergency departments of the University Hospital in Verona (Italy) over a twelve-month period in 2015-2016 were included. The study takes into consideration non-traumatic haemorrhages defined through an International Classification of Diseases, Clinical Modification (ICD-9 CM) diagnosis code and classified into five groups (cerebral haemorrhage, gastrointestinal bleeding, epistaxis, haematuria and other haemorrhages). Demographic data, clinical data and outcome of hospitalization were extrapolated from computerized medical records. Drugs were grouped into six categories and linked to the prescription data of the Verona population during the study period. Results: Overall, 117,019 admissions to emergency departments related to 101,053 patients occurred. According to selection criteria, 1,614 admissions for bleeding, which concerned 1,391 patients (1.4% of the total patients, 59.6% male, 45.7% ≥ 75 years old) were analysed. Out of 1,391 patients, 873 had taken at least one drug (62.8%). Patients were admitted more frequently for epistaxis and gastrointestinal bleeding (27.5% and 23.9%, respectively), and the most reported drugs were antiplatelet (38.8% and 37.7%, respectively) followed by anticoagulants (23.5%), heparins (8.4%), corticosteroids (6.2%), SSRI (5.6%) and NSAIDs (3.0%). About 37% of the visiting patients were subsequently hospitalized, and death was the outcome in 4.2% of cases. Conclusion: In emergency department about 1.4% of admitted patients had an haemorrhage, of these 37% have been hospitalized and 4.2% died during hospitalization. About one third of patients with haemorrhages did not use any drugs. The majority of hospitalized patients had gastrointestinal bleedings and cerebral haemorrhages. To the best of our knowledge, this study is new in the literature, since it takes into consideration all non-traumatic bleedings, and also all drugs known to be associated with haemorrhagic events mentioned on the clinical records.

Background: The use of mobile phones has been associated with an increased risk of developing certain type of cancer, especially in long term users. Therefore, this study was aimed to investigate the potential genotoxic effect of mobile phone radiofrequency exposure on human peripheral blood mononuclear cells in vitro. Methods: The study population consisted in 14 healthy volunteers. After collection of two whole blood samples, the former was placed in a plastic rack, 1 cm from the chassis of a commercial mobile phone (900 MHz carrier frequency), which was activated by a 30-min call. The second blood sample was instead maintained far from mobile phones or other RF sources. The influence of mobile phone RF on DNA integrity was assessed by analyzing γ-H2AX foci in lymphocytes using immunofluorescence staining kit on AKLIDES. Results: No measure of γ-H2AX foci was significantly influenced by mobile phone RF exposure, nor mobile phone exposure was associated with significant risk of genetic damages in vitro (odds ratio comprised between 0.27 and 1.00). Conclusions: The results of this experimental study demonstrate that exposure of human lymphocytes to a conventional 900 MHz RF emitted by a commercial mobile phone for 30 min does not significantly impact DNA integrity.

Background: Prevention of transmission of malignancy from donors to recipients is an aim of donor assessment. We report the most stringent interpretation of the Italian National Guidelines. Methods: A two- step ALERT process was used: ALERT1 consisting of clinical, radiological, and laboratory tests; ALERT2, consisting of intraoperative assessment in suspicious lesions. Results: Four hundred of 506 potential deceased donors entered the ALERT system. Forty- one of 400 (10%) donors were excluded due to unacceptable risk of transmission. Of the remaining 359 193 required histopathology, which excluded malignancy or determined acceptable risk in 161/193 (83%). Thirty- five malignancies were identified: 19 (54%) at ALERT1, four (11%) at ALERT2, nine (26%) picked up at ALERT1 and confirmed by ALERT2. Three (9%) were missed by ALERT and diagnosed at postmortem examination. Prostate (n=12%, 34%) and renal cell (n=7%, 20%) were the most frequent carcinomas. The majority (92%) of prostate adenocarcinomas were of low risk and donation proceeded compared to 43% of renal carcinomas. Four renal carcinomas, two breast carcinomas, and a single case of nine different malignancies excluded donation. Positive ALERT donors had statistically more malignant reports than negative ALERT donors (P=

Identification errors have emerged as critical issues in health care, as testified by the ample scientific literature on this argument. Despite available evidence suggesting that the frequency of misidentification in vitro laboratory diagnostic testing may be relatively low compared to that of other laboratory errors (i.e., usually comprised between 0.01 and 0.1% of all specimens received), the potential adverse consequences remain particularly worrying, wherein 10-20% of these errors not only would translate into serious harm for the patient, but may also erode considerable human and economic resources, so that the entire healthcare system should be re-engineered to act proactively and limiting the burden of this important problem. The most important paradigms for reducing the chance of misidentification in healthcare entail the widespread use of more than two unique patient identifiers, the accurate education and training of healthcare personnel, the delivery of more resources for patient safety (i.e., implementation of safer technological tools), and the use of customized solutions according to local organization and resources. Moreover, after weighing advantages and drawbacks, labeling blood collection tubes before and not after venipuncture may be considered a safer practice for safeguarding patient safety and optimizing phlebotomist's activity.

Introduction : This study investigated the values of red blood cell distribution width (RDW), an emerging and independent predictor of morbidity and mortality, in patients with limb, chest and head trauma. Material and methods : The study sample consisted of all patients who attended the emergency department (ED) of the University Hospital of Parma for limb, chest and head traumas requiring admission to hospital wards during the year 2014. The controls consisted of outpatients living in the same geographical area and undergoing routine laboratory testing for health check-up. Results : The final study sample consisted of 290 patients with limb (n = 97), chest (n = 49) or head (n = 144) trauma and 967 outpatients. Significantly increased RDW values at admission were observed in all trauma patients compared with controls. Although the frequency of increased RDW (> 14.6%) was higher in all trauma patients than in controls, a subanalysis revealed that increased RDW values were significantly more frequent in patients with head trauma than in controls, but not in those with limb or chest trauma. In multivariate analysis, a significant association was found between head trauma and hemoglobin (p < 0.001) or RDW (p = 0.005). Head trauma patients had a ~3-fold higher likelihood of increased RDW values than controls. The negative and positive predictive values of increased RDW for predicting the presence of head trauma were 0.90 (95% CI: 0.88–0.92) and 0.24 (95% CI: 0.19–0.30). Conclusions : The results of this study highlight that RDW is increased in patients admitted to the ED with head trauma.

Background Asthma mortality has declined since the 1980s. Nevertheless the World Health Organization (WHO) identified asthma as responsible for 225.000 deaths worldwide in 2005, and 430.000 fatal cases are expected by 2030. Some unexpected and concentrated fatal asthma events all occurred between 2013 and 2015 in Veneto, a North Eastern region of Italy, which prompted a more in-depth investigation of characteristics and risk factors.Methods A web search including key words related to fatal asthma in Italy between 2013 and 2015 has been performed. Concerning the cases that occurred in Veneto, subjects’ clinical records have been evaluated and details about concomitant weather conditions, pollutants and pollen count have been collected.Results Twenty-three cases of asthma deaths were found in Italy; 16 of them (69%) occurred in the Veneto Region. A prevalence of male and young age was observed. Most of patients were atopic, died in the night-time hours and during the weekends. The possible risk factors identified were the sensitization to alternaria, previous near fatal asthma attacks and the incorrect treatment of the disease. Weather condition did not appear to be related to the fatal exacerbations, whereas among the pollutants only ozone was detected over the accepted limits. Smoking habits, possible drug abuse and concomitant complementary therapies might be regarded as further risk factors.Discussion Although not free from potential biases, our web search and further investigations highlight an increasing asthma mortality trend, similarly to what other observatories report. The analysis of available clinical data suggests that the lack of treatment more than a severe asthma phenotype characterizes the fatal events.Conclusions Asthma mortality still represents a critical issue in the management of the disease, particularly in youngsters. Once more the inadequate treatment and the lack of adherence seem to be not only related to the uncontrolled asthma but also to asthma mortality. Keywords: Fatal asthma, Asthma mortality, Asthma exacerbations, Alternaria

Background Recent evidence suggests that microRNAs play an important role in cancer diagnostics. We assessed plasma microRNA-21 levels in patients with colorectal cancer (CRC) at different stages and in patients with benign polyps. Methods Plasma levels of miR-21 were assessed by quantitative reverse transcription polymerase chain reaction assay in plasma samples of 76 CRC patients and in 20 patients with benign polyps. Differences between groups were evaluated with Mann-Whitney and Kruskal-Wallis tests. Results No significant differences of miR-21 plasma levels were observed between CRC patients and subjects with benign polyps (p > 0.05). Also, no significant differences were found between CRC patients with advanced (III-IV) or early cancer stages (I-II) (p > 0.05). Conclusions These results do not support the hypothesis that circulating miR-21 expression is increased in adenoma-carcinoma-advanced carcinoma sequence. Accordingly, plasma miR-21 assessment does not appear to be a useful biomarker for diagnosing and staging CRC.

The value of red blood cell distribution width (RDW), a simple and inexpensive measure of anisocytosis, has been associated with the outcome of many human chronic disorders. Therefore, this retrospective study was aimed to investigate whether RDW may be associated with medium-term mortality and major adverse cardiac events (MACE) after an acute coronary syndrome (ACS).A total number of 979 patients diagnosed with ACS were enrolled from June 2014 to November 2014, and followed-up until June 2015.The RDW value in patients with 3-month MACE and in those who died was significantly higher than that of patients without 3-month MACE (13.3% vs. 14.0%; P0.001) and those who were still alive at the end of follow-up (13.4% vs. 14.4%; P0.001). In univariate analysis, RDW was found to be associated with 3-month MACE [odds ratio (OR), 1.70; 95% CI, 1.44-2.00, P0.001]. In multivariate analysis, RDW remained independently associated with 3-month MACE (adjusted OR, 1.36; 95% CI, 1.19-1.55; P0.001) and death (adjusted OR, 1.34; 95% CI, 1.05-1.71; P=0.020). The accuracy of RDW for predicting 3-month MACE was 0.67 (95% CI, 0.66-0.72; P0.001). The most efficient discriminatory RDW value was 14.8%, which was associated with 3.8 (95% CI, 2.6-5.7; P0.001) higher risk of 3-month MACE. Patients with RDW14.8% exhibited a significantly short survival than those with RDW ≤14.8% (331 vs. 465 days; P0.001).The results of this study confirm that RDW may be a valuable, easy and inexpensive parameter for stratifying the medium-term risk in patients with ACS.

Background The appropriate therapeutic management of patients with wasp-induced allergic reactions necessitates an accurate allergologic workup, entailing differentiation between sensitization against Vespula or Polistes venoms. Materials and methods We studied 52 consecutive adult subjects diagnosed with hypersensitivity to wasp venoms. Cap inhibition was performed using UniCAP Specific IgE. The concentration of serum IgE against two recombinant constituents of Antigen 5 (rVes v 5 and rPol d 5) was also measured using Immuno CAP 250. The ratio between values of specific IgE against recombinant allergens was calculated and a percentage difference > 50% was considered significant for specific immunization against one of the two venoms. Results The diagnostic agreement between recombinant allergens testing and CAP inhibition was 54% (kappa statistics, 0.34; 95% CI, 0.18–0.50) in the whole study population. In the 24 patients with recombinant allergens ratio > 50% and non dubious results of CAP inhibition assay the diagnostic agreement was perfect (100%; kappa of agreement, 1.00; 95% CI; 1.00–1.00). Discussion The results of this study show that the assessment of specific IgE against rVes v 5 and rPol d 5 may be regarded as a low-cost screening, providing valuable diagnostic information for differentiating the sensitization against Vespula or Polistes venoms. In patients with suggestive clinical history and ratio > 50% between specific IgE against rVes v 5 and specific IgE against and rPol d 5, the CAP inhibition assay may be safely withheld, thus allowing to achieve an early diagnosis at lower cost.

Introduction: Whole-slide imaging (WSI) technology can be used for primary diagnosis and consultation, including intraoperative (IO) frozen section (FS). We aimed to implement and validate a digital system for the FS evaluation of cancer and transplant specimens following recommendations of the College of American Pathologists. Materials and Methods: FS cases were routinely scanned at ×20 employing the 'Navigo' scanner system. IO diagnoses using glass versus digital slides after a 3-week washout period were recorded. Intraobserver concordance was evaluated using accuracy rate and kappa statistics. Feasibility of WSI diagnoses was assessed by the way of sensitivity, specificity, as well as positive and negative predictive values. Participants also completed a survey denoting scan time, time spent viewing cases, preference for glass versus WSI, image quality, interface experience, and any problems encountered. Results: Of the 125 cases submitted, 121 (436 slides) were successfully scanned including 93 oncological and 28 donor-organ FS biopsies. Four cases were excluded because of failed digitalization due to scanning problems or sample preparation artifacts. Full agreement between glass and digital-slide diagnosis was obtained in 90 of 93 (97%, κ = 0.96) oncology and in 24 of 28 (86%, κ = 0.91) transplant cases. There were two major and one minor discrepancy for cancer cases (sensitivity 100%, specificity 96%) and two major and two minor disagreements for transplant cases (sensitivity 96%, specificity 75%). Average scan and viewing/reporting time were 12 and 3 min for cancer cases, compared to 18 and 5 min for transplant cases. A high diagnostic comfort level among pathologists emerged from the survey. Conclusions: These data demonstrate that the 'Navigo' digital WSI system can reliably support an IO FS service involving complicated cancer and transplant cases.

Appropriateness of diagnostic testing can be conventionally described as prescription of the right test, using the right method, at the right time, to the right patient, with the right costs and for producing the right outcome. There is ongoing debate about the real burden of inappropriateness in laboratory diagnostics. The media coverage of this issue has also recently led to either over- or under-emphasizing the clinical, organizational and economic consequences. This is quite problematic, inasmuch as some reliable data are available in the current scientific literature, showing that inappropriateness of laboratory testing can be as high as 70%. This is especially evident for, though not limited to, cancer biomarkers testing, in which the practice of avoidable tests ordering is dramatically magnified. The reasons beyond inappropriateness are many and multifaceted, entailing wrong habits, resistance to changes, poor culture, insufficient education and healthcare inefficiencies. There are many unfavorable consequences attributable to avoidable testing, including unjustified incremental costs, derangement of laboratory efficiency and potential patient safety issues. The tentative solutions to this important problem necessitate that policymakers, local hospital administrators, laboratory professionals, clinicians, patients' associations and diagnostic companies join the efforts and embark in the same landmark effort for disseminating a better culture of appropriateness.

This retrospective study was planned to establish potential associations between circulating values of cardiac troponins and those of conventional blood lipids.The study population consisted of patients attending an inpatient clinic of the University Hospital of Verona during the year 2015 as part of routine cardiovascular risk assessment. No exclusion criteria were applied. Serum lipids including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were measured using reference enzymatic techniques, whereas troponin T (TnT) was measured using a high-sensitivity (HS) immunoassay. A second analysis was also performed in the General Hospital of Verona, extracting data from the local laboratory database of all patients in whom troponin I (TnI) and blood lipids were simultaneously measured during the same year.In univariate analysis, HS-TnT was found to be associated with age, sex, TC, LDL-C, HDL-C, but not with TG. In multivariate linear regression analysis, age (positive correlation; P0.001) and HDL-C (negative correlation; P=0.032) remained significantly associated with HS-TnT. The frequency of HS-TnT values50 ng/L was higher in subjects with HDL-C1 mmol/L than in those with HDL-C ≥1 mmol/L [odds ratio (OR), 1.84; 95% confidence interval (CI), 1.03-3.32]. The frequency of HS-TnT values50 ng/L was also higher in elderly subjects than in younger ones (OR, 2.10; 95% CI, 1.15-3.84). The combination of age and HDL-C explained 35% of overall variability of TnT concentration. In the second analysis, HDL-C was also found to be an independent and negative predictor of TnI in multivariate linear regression analysis (P=0.010). The combination of age and HDL-C explained approximately 28% of the overall variability of TnI concentration.Our study suggests that HDL-C values inversely predict cardiac troponins concentration irrespective of age, sex and other blood lipids.

The rather short history of diagnostic algorithms for investigating patients with a suspected acute coronary syndrome (ACS) has led to a constantly evolving and unquestionably chaotic scenario. Although the recent development and introduction of high-sensitivity immunoassays for the measurement of cardiac troponins has represented a paradigm shift for dispersing part of the overwhelming fog, many uncertainties remain, especially concerning the appropriate timing for serial testing and the interpretation of cardiac troponin variations over time. Therefore, the aim of this article is to review the available evidence about diagnostic algorithms for ACS which incorporate the measurement of cardiac troponins, and generate a final algorithm attempting to integrate and harmonize the many clinical and laboratory findings emerged from the recent scientific literature.