Search

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.

Background: Nutritional derangements are common hallmarks of pancreatic cancer (PC). Their early detection and management are usually overlooked in routine practice. This study aimed to explore preoperative nutritional status and its prognostic value in patients undergoing surgery for PC. Methods: Data from 73 patients who underwent surgery for PC from November 2015 to January 2018 at the General and Pancreatic Surgery Unit, The Pancreas Institute, University Hospital of Verona Hospital, Verona, Italy, were retrospectively evaluated. The Nutritional Risk Screening (NRS)-2002 was used to evaluate the preoperative nutritional risk. Body composition was assessed using bioimpedance vectorial analysis (BIVA) on the day prior to surgery. The effect of clinical, pathological, and nutritional characteristics on overall survival (OS) was investigated using a Cox and logistic regression model. Kaplan–Meier curves were compared using the log-rank test. Results: Most patients (80.8%) were at preoperative risk of malnutrition (NRS-2002 ≥ 3) despite a mean BMI of 24.1kg/m2(± 4.3). Twenty-four patients (32.9%) received neoadjuvant therapy prior to surgery. Preoperative NRS-2002 was significantly higher in this subset of patients (p = 0.026), with a significant difference by chemotherapy regimens (in favor of FOLFIRINOX, p = 0.035). In a multivariate analysis, the only independent prognostic factor for OS was the NRS-2002 score (HR 5.24, p = 0.013). Particularly, the likelihood of 2-year survival was higher in NRS < 3 (p = 0.009). Conclusions: Our analysis confirms that preoperative malnutrition has a detrimental impact on OS in PC patients undergoing radical surgery for PC. Careful preoperative nutritional evaluation of PC patients should be mandatory, especially in those who are candidates for neoadjuvant therapy.

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.

IntroductionThe ongoing COVID-19 pandemic is heavily affecting healthcare services worldwide. We investigated the impact of a lockdown policy on the characteristics of patients attending a Paediatric Emergency Department (PED), in one of the first areas of COVID-19 outbreak in Europe.MethodsWe retrieved data of all PED visits in March-April 2020 (COVID-19) and March-April 2019 (non-COVID-19), comparing volume and characteristics of PED accesses in the two periods.ResultsIn COVID-19 period, total visits reduced by 67% if compared to 2019. White codes decreased from 45.8–35%. Green codes raised from 45.9–52.2%, while yellow and red codes were comparable. As a percentage, accidents increased during COVID-19, being the first cause of PED access (29.7%) (p

The purpose of the work described here was to evaluate the use of ultrasound fusion imaging (US-FI) in percutaneous ablation of hepatic malignancies with respect to its global usefulness, improvement of conspicuity, confidence increment, needle route changes, and time savings. Thirty-four hepatic tumors (28 hepatocellular carcinomas, 6 metastases) were prospectively ablated in 16 consecutive patients (64 ± 11 y, 75% males), first simulating B-mode-only planning and then synchronizing computed tomography/magnetic resonance images with US and proceeding to needle insertion and tumor ablation under US-FI guidance. Surveys were administered to the operators to evaluate their perception of US-FI advantages. First treatment and local recurrence were also compared. US-FI was judged useful in 91% of cases and more useful when the tumor was not conspicuous in B-mode (p0.001), in particular for ablation of local recurrences (p = 0.021). Forty-one percent of tumors were undetectable at B-mode evaluation, and 93% of them were completely ablated under US-FI guidance. The confidence of the operator was highly increased by US-FI in 68% of cases. In 71% of cases, the radiologist saved time using US-FI, especially in treatment of local recurrences (p = 0.024). In conclusion, US-FI significantly increases the detection of target tumors, improves the confidence of the operator and is a time-saving method, especially in the treatment of local recurrences.

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.

Background. Asthma control and monitoring still represents a challenge worldwide. Although the international guidelines suggest the interplay with primary care as an effective strategy, the community pharmacies’are rarely involved in asthma management.The present cross-sectional study aimed at providing a picture of the relationship between asthma severity and control according to the community pharmacies’ perspective of the health district of Verona (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 completethe Asthma Control Testand a brief questionnaire collecting information on their age, sex, smoking status, aerobic physical exercise and usual asthma therapy, which also defined the severity level of asthma.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.57 community pharmacies accepted to participate and 584 asthmatic patients (54% females; mean-age: 51 ± 19 years) were recruited. According to the ACT score 50.5% patients hada controlled asthma, 22.3% a poorly controlled and 27.2% uncontrolled. A variable proportion patients with uncontrolled asthma was observed at every level of severity, although more frequently in mild persistent form of disease. Most patients (92%) 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 ACTConclusions.Overall, our findings highlighted an unsatisfactory asthma control from the pharmacists’ perspective, independently of the asthma severity level. The relevance of community pharmacies as a first line interface suggest their involvement inan effective asthma management plan, from disease control and treatment compliance assessment to referral of asthmatic patients to medical consultancies.

The immunoassays methods need avoiding interferences that can influence result interpretation. Main sources of interference arise from either patient status, preparation and physiology or laboratory process and procedures. The aim of this non-systematic critical review is to highlight the preanalytical interferences on laboratory immunoassays. Blood hormone profile changes according with age and depending on sex: these are important variables, mainly in newborn, during both sexual maturation and childbearing. Gonadotropins FSH and LH show a sharp increase with age in females, whereas in males LH appears rather stable. With age both males and females show progressive decay of the hormone profile. Stress causes variations, as it influences GH, prolactin, Cortisol and the total/free ratio of thyroid hormone. Diurnal variations, day of cycle, influence by estrogens on thyroid hormone are relevant for result variability. Paraproteins and autoantibodies can interfere in some assays particularly drug, vitamin D and thyroid hormone. As regards the variables due to sample matrix, and to evacuated tubes components, some additives and anticoagulants have been reported to influence specific assays, e.g. thyroid hormone. Hemolysis, lipemia and bilirubin cause interferences on specific techniques/tests, e.g. ferritin, TSH, Vitamin B12, progesterone and folic acid. Nicotine and cocaine addictions interfere with some hormones. Thus, laboratory professionals should be aware of preanalytical problems particularly important when dealing with the immunoassays, by taking appropriate actions to avoid any relevant interferences.

Eligibility criteria for a biologic treatment for severe asthma include poor disease control despite a full medication plan according to Global Initiative for Asthma steps 4–5 [1]. Adherence to inhaled therapy should be verified as part of that prescription requirement [2]. In fact, it has been demonstrated that poor adherence is a major cause of uncontrolled asthma, regardless of its severity [3]. Furthermore, biologics do not exert a disease-modifying effect [4]; in contrast to allergen immunotherapy, which is able to permanently modulate the way the immune system reacts to allergens beyond the immunotherapy treatment course [5], biologic therapy withdrawal usually leads to asthma relapse [4]. Thus, a low adherence rate to inhaled treatment in patients undergoing biologic therapy raises some issues related to sustainability., 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

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: This study analyzed the Quality of Life (QoL) and cost-effectiveness of laparoscopic (LDP) versus robotic distal pancreatectomy (RDP). Method: All patients who underwent LDP or RDP from 2011 to 2017 and with a minimum postoperative follow-up of 12months were included in the study. To minimize bias, a propensity score-matched analysis (1:2) was performed. Two different questionnaires (EORTC QLQ-C30 and EQ-5D) were completed by the patients. The mean differential cost and mean differential Quality Adjusted Life Years (QALY) were calculated and plotted on a cost-utility plane. Results: The study population consisted of 152 patients. After having applied the propensity score matching, the final population included 103 patients divided into RDP group (n = 37, 36%) and LDP (n = 66, 64%). No differences were found between groups regarding the baseline, intraoperative, postoperative, and pathological variables (p > 0.05). The QoL analysis showed a significant improvement in the RDP group on the postoperative social function, nausea, vomiting, and financial status (p = 0.010, p = 0.050, and p = 0.030, respectively). As expected, the crude costs analysis confirmed that RDP was more expensive than LDP (12,053 Euros vs. 5519 Euros, p < 0.001). However, the robotic approach had a higher probability of being more cost-effective than the laparoscopic procedure when a willingness to pay of more than 4800 Euros/QALY was accepted. Conclusion: RDP was associated with QoL improvement in specific domains. Crude costs were higher relative to LDP. Cost-effectiveness threshold resulted to be 4800 euros/QALY. The increasing worldwide diffusion of the robotic technology, with easier access and possible cost reduction, could increase the sustainability of this procedure.

This retrospective observational study was carried out by searching the database of the laboratory information system for identifying all requests for alcohol testing placed from emergency departments and intensive care units of the University Hospital of Verona between June 29th, 2012 and December 31st, 2018. The study population consisted of 7488 patients. The number of alcohol tests was more than double in concomitance with New Year’s Eve than in the rest of the year (7.6±6.1 vs 3.1±2.8 requests/day; P0.1 g/L and >1.0 g/L was 1.9-fold and 1.6-fold higher in concomitance with New Year’s Eve. In multivariate analysis, younger age, female sex and alcohol testing during New Year’s Eve remained significant predictors of alcohol concentrations >0.1 g/L and >1.0 g/L. The requests for alcohol testing were similar in concomitance with Christmas Eve and in other periods of the year, whilst number of requests (4.0±3.2 vs 2.8±2.5 requests/day; P

Cerebrovascular accidents (CVA) represent a major complication in diabetes (DM). Real-life evidence as to whether modern management of CVA and DM have softened this relationship is currently limited. We assessed the prevalence of DM, previously known or newly-diagnosed, in all patients (N=542, males 51.5%) admitted for CVA at the Stroke Unit (SU) of Verona University Hospital from 1/1/2015 to 12/31/2016. DM was ascertained by previous diagnosis, glucose-lowering therapy at admission/discharge or admittance plasma glucose (PG) ≥11.1 mmol/L. Prevalence of DM was 21.03% (78.1% known-DM; 21.9% new-DM). In-hospital death rate was 10.5%. Compared to non-DM, patients with DM showed an increased risk of death (15.8 vs. 9.1%; OR 1.87 95% CI, 1.03-3.41) and complications (48.2 vs. 33.3%; 1.87, 1.22-2.86) with similar duration of hospitalization (mean±SEM, 9.14±1.06 vs. 8.80±0.39 days, p=0.72). All deaths occurred in the SU. The “survivors” with DM transferred to non-intensive ward had an out-of-SU hospital stay twice as longer than non-DM (2.32±1.02 vs. 0.98±0.19 days, p=0.038). After multivariable adjustment, DM remained predictor of complications (adj-OR 1.87, 1.22-2.86) but not mortality (1.79, 0.92-3.46). Patients in the highest PG quartile (≥6.55 mmol/L) displayed the highest risk of death (7.89, 2.73-22.79; PG In conclusion, these data highlight that DM frequently occurs in patients admitted for CVA and adds an excess burden of adverse clinical outcomes that urgently calls for strategies to anticipate DM diagnosis in high-risk individuals. Disclosure M. Dauriz: None. E. Tregnaghi: None. L. Santi: None. T. Lucianer: None. A. Altomari: None. E. Rinaldi: None. S. Tardivo: None. C. Bovo: None. E. Bonora: None.

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.

Transmission of Staphylococcus aureus along the dairy production chain is an emerging public health problem with human, veterinary, and food safety issues. The prevalence of multidrug-resistant, particularly methicillin-resistant S. aureus (MRSA), has steadily increased in several European countries. In this study, the prevalence of S. aureus in raw cow milk and farm workers was investigated, and the trajectories of MRSA transmission at the primary stage of the dairy chain were assessed. To this purpose, a longitudinal survey was conducted in 618 dairy farms in two contiguous regions with high livestock density in North-eastern Italy. S. aureus contamination of bulk tank milk (BTM) was observed in more than 80% of farms, while MRSA prevalence was 3.6% and 15.9% in BTM and farm workers, respectively. The majority of MRSA isolates from both BTM and farm workers were assigned to ST398, and showed a worrisome multidrug-resistant phenotype. Enterotoxin and Panton-Valentine leukocidin genes were detected in 11.5% and 4.9% of MRSA isolates from both sources. Nearly all MRSA isolates from workers belonged to the same epidemiological type as BTM isolates from the corresponding farm, denoting a bidirectional MRSA transmission pattern. A focus on the ST398 spa type t899 MRSA lineage in the Italian livestock system highlighted the presence of two major clusters whose dissemination was likely facilitated by the selective pressure imposed by antimicrobial use in animal farming. Our findings emphasize the need for continuous monitoring of MRSA along the dairy production chain, not only to avoid transmission between animals and exposed workers, but also to contain the risk of raw milk and dairy product contamination by multidrug resistant and toxigenic strain.

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.

Background Nutritional derangements are common hallmarks of non-small-cell lung cancer (NSCLC). Nevertheless, their early detection is overlooked in clinical routine. This study aimed to evaluate nutritional status and its correlation with outcome in NSCLC patients. Methods Data regarding NSCLC patients undergoing nutritional evaluation were prospectively collected (May 2016–October 2018). Nutritional risk was assessed by Nutritional Risk Screening 2002 (NRS-2002). Bilateral psoas major muscles were measured at L3 vertebrae level with routine staging-computed tomography and changes were evaluated using Wilcoxon signed-rank test. Clinico-pathological and nutritional data were correlated to progression-free/overall survival (PFS/OS) and response rate (ORR) using a Cox and logistic regression model. Kaplan–Meier curves were compared with log-rank test. Results Thirty-eight patients were included. The majority (65.8%) of them were at nutritional risk (NRS-2002 ≥3). At multivariate analysis for patients with advanced disease, age (HR 2.44, p=0.05), performance status (HR 2.48, p=0.043) and NRS-2002 (HR 1.74, p=0.001) were significant independent predictors for PFS and weight loss (HR 1.07, p=0.008) for OS. Patients with baseline NRS-2002

Objectives Liver transplant represents the criterion standard therapy for end-stage liver disease. Biliary complications after liver transplant have shown an increased trend and are characterized by anastomotic and nonanastomotic stenoses. Materials and methods This retrospective single-center observational study included 217 patients who underwent liver transplant between January 2004 and December 2014; 18 patients had anastomotic (8.3%) and 29 (13.4%) had non-anastomotic stenoses. Patients with and without biliary stenosis were compared with regard to their preoperative, intraoperative, and postoperative parameters and donor characteristics. Patients with biliary stenosis were divided into 3 cohorts according to the type of endoscopic treatment performed (single plastic, multiple plastic, and fully covered self-ex-pandable metal stents). We compared the patients with different types of endoscopic biliary drainages for length and type of stenosis, presence of stones, time of onset and treatment, number of procedures, complications, and success rate. Results Preoperative Child-Pugh and Model for End-Stage Liver Disease scores, complication and reoperation rates, and donor age were significantly higher in the stenosis group. We found no statistical differences other than length of stenosis between patients with multiple stents and self-expanding metal stents. Conclusions Preoperative recipient conditions and postoperative morbidities may represent risk factors for development of biliary strictures. Consequently, the optimal endoscopic treatment should be tailored to the type and the onset of stenosis and the patient's condition.

Prevalence of diabetes is increasing worldwide and outcomes after ACS are thought to improve. We assessed the prevalence of DM, previously known (known-DM) or newly-diagnosed (new-DM), in all patients (n=1,017, males 66.6%) admitted for ACS at the Intensive Coronary Care Unit of the Verona University Hospital from 1/1/2015 to 12/31/2016. DM was ascertained according to previous diagnosis, glucose-lowering therapy at admission/discharge or random plasma glucose ≥11.1 mmol/L. The association of DM with in-hospital death, infectious/cardiorespiratory complications, duration and costs of hospitalization was tested in all patients and separately in known-DM and new-DM. The prevalence of DM was 27.2% (74.1% known-DM; 25.9% new-DM). In-hospital death rate was 4.72%. Compared to nondiabetic patients, those with DM showed an increased risk of death (7.6 vs. 3.6%; OR 2.17 95% CI, 1.20-3.90) and complications (34.4 vs. 23.9%; OR 1.67, 1.23-2.28), a longer hospital stay (median[IQR], 11 [7-17] vs. 8 [6-13] days), higher hospitalization costs (mean±SD, € 10,033±7,626 vs. 8,513±6,363) and more need of rehabilitation at discharge (10.8 vs. 5.9%); P Disclosure M. Dauriz: None. L. Drezza: None. L. Santi: None. A. Altomari: None. E. Rinaldi: None. S. Tardivo: None. C. Bovo: None. F. Ribichini: None. E. Bonora: None.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the clinical effectiveness and safety of the combined Antiretroviral Treatment containing ABC relative to ABC‐sparing cART. A subgroup comparison will be performed in studies comparing Antiretroviral Treatment containing ABC relative to TDF containing cART.

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 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.

There is now consolidated evidence that the vast majority of laboratory errors occur in the extra-analytical phases of the total testing process, and especially in the preanalytical phase. Although development and dissemination of best practice recommendations for this crucial area of diagnostic testing have greatly contributed to reinforce error identification and reporting strategies, it is also undeniable that the combination of greater consciousness about preanalytical issues and technological advancements have helped decreasing the inherent vulnerability of many preanalytical activities, thus finally making the preanalytical phase less vulnerable to errors, slips and lapses. Many potential strategies can be adopted for reducing preanalytical errors, including education and training of healthcare staff on phlebotomy practice and preanalytical errors, greater observance of available phlebotomy guidelines, dissemination of specimen collection modules or phlebotomist check-lists, certification of phlebotomists, transmission of periodic preanalytical quality reports to phlebotomists, establishment of direct feed-back between laboratory professionals and phlebotomists, use of quality and validated blood collection systems for drawing blood, along with introduction of harmonized means for recording preanalytical errors.

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.

Summary Leucocyte alkaline phosphatase (L-ALP) is well known as leukemia marker, but recent results suggest its usefulness for the diagnosis of several diseases. The aim of this study was to develop a quantitative method to measure alkaline phosphatase activities in individualleukocytes by image analysis. We studied the reaction rate of L-ALP in human polymorphonuclear leucocytes by a microscope attached to a TV camera and a computerized image analyzer. The optical density (OD) measured was standardized by grey filters with known absorbance. We measured IOD for individual cells after a set incubation time by end-point measurements. Studies of kinetic parameters of L-ALP were performed by single-point measurements in the linear phase of the reaction and at increasing substrate concentrations. Cellular IOD increased proportionally with incubation time up to 10 min. The mean K M (mM) and V max (Δ IOD/min) values were 0.70 ± 0.11 and 1.76 ± 0.2 (mean ± SE, n = 5) respectively. Our findings are comparable to previous results using a polyvynil alcohol method in microphotometry analysis. The image analysis of cellular L-ALP activity appears a valuable tool for quantitative studies.

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.

Medical science has undergone a substantial revolution in recent years, wherein the traditional approach to diagnosing and treating many human diseases has gradually evolved from a generalized conception of health and disease to an individualized approach entailing decisions and interventions tailored to the single patient according to individual responses or risk of disease. This axiom has evolved from concept to practice, and has been translated into the notion of “personalized” or “precision” medicine. Although precision (personalized) medicine will be the core opportunity for effective care in the anticipatable future, many political, economic and cultural challenges need to be overwhelmed, and these include some ongoing healthcare reforms around the globe, cost containment strategies, consolidation of laboratories and in vitro diagnostic testing, as well as the impact of new technologies and tests on the existing laboratory organization. Therefore, the aim of this article is to discuss some of the several changes which may ultimately drive or challenge the future of laboratory medicine in the era of precision medicine.

Purpose: To assess prospectively the accuracy of diffusion-weighted magnetic resonance imaging (DWI) in differentiating between metastatic and benign axillary lymph nodes in patients with breast cancer. Materials and Methods: In all, 215 patients with histologically proven breast cancer, prior to axillary dissection, underwent breast and axillary 1.5 T MRI. In 102 patients in whom at least one axillary lymph node with a short axis of 6 mm or more was found the apparent diffusion coefficient (ADC) was measured in one lymph node per patient by means of an echo planar, parallel imaging DWI sequence. Forty-three lymph nodes were finally included which, on histological examination, either contained a metastasis larger than 5 mm or were metastasis-free; nodes with metastases smaller than 5 mm were excluded. Results: From histological examination, 19/43 lymph nodes had a metastasis at least 5 mm, while in 24/43 no malignant cells were found. The ADC values of the lymph nodes with metastases (mean: 0.878 × 10−3 mm2/s; range: 0.30 –1.20) were significantly lower (P < 0.001) than those of the benign lymph nodes (mean: 1.494; range: 0.60 –2.50). Adopting a threshold value of 1.09 × 10−3 mm2/s DWI resulted in 94.7% sensitivity, 91.7% specificity, and 93.0% accuracy in the identification of metastasis in this series of lymph nodes. Conclusion: From these preliminary data DWI seems a promising method in the differential diagnosis between metastatic and benign axillary lymph nodes in patients with breast cancer. J. Magn. Reson. Imaging 2012;36:858–864. © 2012 Wiley Periodicals, Inc.

Plasma levels of human leukocyte elastase, a serine proteinase stored in the azurophilic granules of polymorphonuclear granulocytes, increase in the early stages of several inflammatory diseases. We studied the intracellular enzyme activity by cytochemical quantitative image analysis and the amount of elastase released in plasma by an automatic immunoactivation immunoassay method in 66 patients with inflammatory diseases and in a control group. The patients were divided into two groups with infective disease (severe and moderate) and one group with non-infective inflammation. Intracellular activity and plasmatic levels of elastase were also compared with other inflammatory markers, i.e. erythrocyte sedimentation rate, C-reactive protein, alpha 1-antitrypsin, haptoglobin, alpha 1-acid glycoprotein and fibrinogen. Our studies suggest that plasma and leukocyte elastase are correlated both with etiology and with the severity of the inflammation.