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Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut-MYD88) and interleukin-10 (IL-10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n=36) and relapsed (n=27) PCNSL and 162 controls (118 CNS disorders and 44 extra-CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut-MYD88 was assessed by TaqMan-based polymerase chain reaction. IL-6 and IL-10 messenger RNA (mRNA) was assessed on PCNSL biopsies using RNAscope technology. IL levels in CSF were assessed by enzyme-linked immunosorbent assay. Mut-MYD88 was detected in 15/17 (88%) PCNSL biopsies, with an 82% concordance in paired tissue-CSF samples. IL-10 mRNA was detected in lymphomatous B cells in most PCNSL; expression of IL-6 transcripts was negligible. In CSF samples, mut-MYD88 and high IL-10 levels were detected, respectively, in 72% and 88% of patients with newly diagnosed PCNSL and in 1% of controls; conversely, IL-6 showed a low discriminating sensitivity and specificity. Combined analysis of MYD88 and IL-10 exhibits a sensitivity and specificity to distinguish PCNSL of 94% and 98% respectively. Similar figures were recorded in patients with relapsed PCNSL. In conclusion, high detection rates of mut-MYD88 and IL-10 in CSF reflect, respectively, the MYD88 mutational status and synthesis of this IL in PCNSL tissue. These biomarkers exhibit a very high sensitivity and specificity in detecting PCNSL both at initial diagnosis and relapse. Implications of these findings in patients with lesions unsuitable for biopsy deserve to be investigated.

Objectives In this study, we developed and evaluated the diagnostic accuracy of the Sepsis Index for early sepsis screening in the Emergency Department (ED). Methods Sepsis Index is based on the combination of monocyte distribution width (MDW) and mean monocyte volume (MMV). Sepsis Index≥1 was selected to define sepsis. We tested its diagnostic accuracy in an ED population stratified in four groups: controls, Systemic Inflammatory Response Syndrome (SIRS), infection, and sepsis, according to Sepsis-2 criteria. Results Patients with sepsis displayed higher median Sepsis Index value than patients without sepsis. At the receiver operating characterictis (ROC) curve analysis for the prediction of sepsis, the area under the curve (AUC) of MDW and Sepsis Index were similar: 0.966 (95%CI 0.947–0.984), and 0.964 (95%CI 0.942–0.985), respectively. Sepsis Index showed increased specificity than MDW (94.7 vs. 90.6%), without any decrease in sensitivity (92.0%). Additionally, LR+ increased from 9.8 (MDW) to 17.4 (Sepsis Index), without any substantial change in LR− (respectively 0.09 vs. 0.08). Finally, PPV increased from 0.286 (MDW) to 0.420 (Sepsis Index). Conclusions Sepsis Index improves the diagnostic accuracy of MDW alone for sepsis screening.

Objective In this study, we investigated the roles of presepsin (PSP) and midregional proadrenomedullin (mr-proADM) in children with febrile neutropenia (FN) due to chemotherapy. Methods We assessed 36 FN episodes in 26 children. Patients were classified into bacteremia (B) and fever of unknown origin (FUO) groups. We evaluated PSP and mr-proADM at admission (T0), after 24/48 h (T1), and after 5 days (T2). Results PSP and mr-proADM levels were elevated at T0 and significantly decreased at T2. mr-proADM levels did not significantly differ between the B and FUO groups. PSP levels significantly differed between the B and FUO groups only at T1. Both PSP and mr-proADM levels at T0 were a predictor of length of hospital stay but not of the duration of fever. Finally, receiver operating characteristic curve analysis showed that PSP and mr-proADM had low diagnostic accuracy for blood culture positivity. Conclusion PSP and mr-proADM display poor clinical usefulness for FN in oncologic children.

BACKGROUND: The use of umbilical venous catheters (UVCs) in the perinatal period may be associated with severe complications, including the occurrence of portal vein thrombosis (PVT). AIM: To assess the incidence of UVC-related PVT in infants with postnatal age up to three months. METHODS: A systematic and comprehensive database searching (PubMed, Cochrane Library, Scopus, Web of Science) was performed for studies from 1980 to 2020 (the search was last updated on November 28, 2020). We included in the final analyses all peer-reviewed prospective cohort studies, retrospective cohort studies and case-control studies. The reference lists of included articles were hand-searched to identify additional studies of interest. Studies were considered eligible when they included infants with postnatal age up to three months with UVC-associated PVT. Incidence estimates were pooled by using random effects meta-analyses. The quality of included studies was assessed using the Newcastle-Ottawa scale. The systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. RESULTS: Overall, 16 studies were considered eligible and included in the final analyses. The data confirmed the relevant risk of UVC-related thrombosis. The mean pooled incidence of such condition was 12%, although it varied across studies (0%-49%). In 15/16 studies (94%), diagnosis of thrombosis was made accidentally during routine screening controls, whilst in 1/16 study (6%) targeted imaging assessments were carried out in neonates with clinical concerns for a thrombus. Tip position was investigated by abdominal ultrasound (US) alone in 1/16 (6%) studies, by a combination of radiography and abdominal US in 14/16 (88%) studies and by a combination of radiography, abdominal US and echocardiography in 1/16 (6%) studies. CONCLUSION: To the best of our knowledge, this is the first systematic review specifically investigating the incidence of UVC-related PVT. The use of UVCs requires a high index of suspicion, because its use is significantly associated with PVT. Well-designed prospective studies are required to assess the optimal approach to prevent UVC-related thrombosis of the portal system.

The debate over coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) with stent placement for the treatment of stable multivessel coronary artery disease (CAD) continues in spite of numerous studies investigating the issue. This paper reviews the most recent randomized control trials (RCT) and meta-analyses of pooled RCT data to help address this issue. General trends demonstrated that CABG was superior in all-cause mortality and fulfilling the need for repeat revascularization. These advantages tended to be more pronounced in multivessel CAD and diabetes, and less so in left main CAD. PCI showed a consistently lower rate of cerebrovascular events. CABG continues to offer significant advantages over PCI, even as drug-eluting stent technology continues to evolve. The ideal endpoint for comparing PCI and CABG remains to be determined. Furthermore, additional research is required to further refine patient selection criteria for each intervention.

SummaryThe available tools and approaches to inform conservation decisions commonly assume detailed distribution data. We examine how well-established ecological concepts about patterns in local richness and community turnover can help overcome data limitations when planning future protected areas. To inform our analyses, we surveyed tree species in protected areas in the southern Appalachian Mountains in the eastern USA. We used the survey data to construct predictive models for alpha and beta diversity based on readily observed biophysical variables and combined them to create a heuristic that could predict among-site richness in trees (gamma diversity). The predictive models suggest that site elevation and latitude in this montane system explain much of the variation in alpha and beta diversity in tree species. We tested how well resulting protected areas would represent species if a conservation planner lacking detailed species inventories for candidate sites were to rely only on our alpha, beta and gamma diversity predictions. Our approach selected sites that, when aggregated, covered a large proportion of the overall species pool. The combined gamma diversity models performed even better when we also accounted for the cost of protecting sites. Our results demonstrate that classic community biogeography concepts remain highly relevant to conservation practice today.

Sepsis represents an important global health burden due to its high mortality and morbidity. The rapid detection of sepsis is crucial in order to prevent adverse outcomes and reduce mortality. However, the diagnosis of sepsis is still challenging and many efforts have been made to identify reliable biomarkers. Unfortunately, many investigated biomarkers have several limitations that do not support their introduction in clinical practice, such as moderate diagnostic and prognostic accuracy, long turn-around time, and high-costs. Complete blood count represents instead a precious test that provides a wealth of information on individual health status. It can guide clinicians to early-identify patients at high risk of developing sepsis and to predict adverse outcomes. It has several advantages, being cheap, easy-to-perform, and available in all wards, from the emergency department to the intensive care unit. Noteworthy, it represents a first-level test and an alteration of its parameters must always be considered within the clinical context, and the eventual suspect of sepsis must be confirmed by more specific investigations. In this review, we describe the usefulness of basic and new complete blood count parameters as diagnostic and prognostic biomarkers of sepsis.

Simple Summary Prostate-specific antigen and digital rectal examination, used to guide prostate biopsy, often result in overdiagnosis of indolent prostate cancer (PCa) while missing clinically significant PCa (csPCa). The aim of this study was to evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance imaging (mpMRI) in predicting PCa in prostate biopsies. SelectMDx was revealed to be a good predictor of PCa, while with regards to csPCa detection, it was demonstrated to be less effective, showing results similar to mpMRI. The best diagnostic strategy to avoid unnecessary biopsy is performing SelectMDx after an initial negative mpMRI. Biopsy could be proposed for all cases of positive mpMRI and to those with a negative mpMRI followed by a positive SelectMDx. Abstract Prostate-specific antigen (PSA) testing as the sole indication for prostate biopsy lacks specificity, resulting in overdiagnosis of indolent prostate cancer (PCa) and missing clinically significant PCa (csPCa). SelectMDx is a biomarker-based risk score to assess urinary HOXC6 and DLX1 mRNA expression combined with traditional clinical risk factors. The aim of this prospective multi-institutional study was to evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance (mpMRI) when predicting PCa in prostate biopsies. Overall, 310 consecutive subjects were included. All patients underwent mpMRI and SelectMDx prior to prostate biopsy. SelectMDx and mpMRI showed sensitivity and specificity of 86.5% vs. 51.9%, and 73.8% vs. 88.3%, respectively, in predicting PCa at biopsy, and 87.1% vs. 61.3%, and 63.7% vs. 83.9%, respectively, in predicting csPCa at biopsy. SelectMDx was revealed to be a good predictor of PCa, while with regards to csPCa detection, it was demonstrated to be less effective, showing results similar to mpMRI. With analysis of strategies assessed to define the best diagnostic strategy to avoid unnecessary biopsy, SelectMDx appeared to be a reliable pathway after an initial negative mpMRI. Thus, biopsy could be proposed for all cases of mpMRI PI-RADS 4–5 score, and to those with Prostate Imaging-Reporting and Data System (PI-RADS) 1–3 score followed by a positive SelectMDx.

Decision makers often cite data quality as a limitation in environmental management. Value of information approaches evaluate the benefit of new data collection for management outcomes. Pesticide exposure risk assessment for endangered species is one context where data limitations may affect decisions and a value of information type approach could be useful for identifying optimal data quality and resolution. Under the U.S. Federal Insecticide, Fungicide and Rodenticide Act, the U.S. Environmental Protection Agency (EPA) is responsible for registering pesticides before they can be sold and regularly reviewing pesticides. Section 7 of the Endangered Species Act requires that the EPA consider potential impacts of pesticides to listed endangered species and critical habitats in this process, and for the Services—U.S. Fish and Wildlife Service and National Marine Fisheries Service—to complete a formal Section 7 consultation if the EPA deems it necessary. The current process is time‐intensive, lacks transparency and confidence among stakeholders, and leaves hundreds of unreviewed pesticides on the market. Increasing the resolution of pesticide usage data could address these concerns by improving estimated overlaps between species ranges and pesticide usage. Thus, we evaluated the relative importance of different resolutions of pesticide usage data for assessing expected carbaryl exposure to endangered plant species endemic to California. We found that spatially explicit, township resolution usage data (~36 mile2) excluded 33% of terrestrial plants (55/168) and 51% their critical habitats (27/53) from requiring a Section 7 consultation, while coarser resolution data excluded none. In contrast, the EPA's biological evaluation for carbaryl only excludes 4% of terrestrial plants (nationally) from requiring formal Section 7 consultation. This suggests high‐resolution data could increase pesticide review efficiency and decrease the amount of time pesticides remain on the market without a formal evaluation.

Pericarditis is the most common form of pericardial disease. Its exact incidence remains unknown, probably because many cases resolve without diagnosis. Indications for pericardiectomy from the standpoint of the cardiac surgeon are based mainly on the physiopathology of 2 different entities that can overlap: inflammatory or relapsing pericarditis and constrictive pericarditis. Surgical indications are not always straightforward. Patients with inflammatory or relapsing pericarditis may undergo radical pericardiectomy because they experience severe symptoms despite maximal medical treatment or have sequelae from the medical treatment. Pericardiectomy is the standard treatment in patients with chronic constrictive pericarditis and persistent symptoms who are in New York Heart Association functional class III or IV and a class I recommendation in the European Society of Cardiology/European Association of Cardio-Vascular Surgery guidelines. The goal of surgery is always complete removal of any site of inflammation through a radical pericardiectomy.

(1) Background: The Italian Constitutional Court’s decision n. 99/2019 abolished the distinction between physical and psychological health care in the Italian prison system. However, this and other changes to the penitentiary system present challenges to prison staff, which may vary based on their roles and backgrounds, (2) Purpose: To create a process of dialogue and collaboration that include different points of view, needs, and proposals regarding mental health in prisons, this study collects and integrates the perspectives of 91 prison staff who work in various capacities in eight prisons in northeast Italy. (3) Methods: Each participant was involved in either a focus group or a semi-structured interview, and thematic analysis was used to process the resulting transcripts, (3) Results: Through this process, 10 themes were derived that highlight the difficulties of working with prisoners with psychiatric disorders or psychological distress, including lack of human and economic resources, lack of positive communication between prisoners and society and a sense of professional incompetency, (4) Conclusions: Based on these themes, the need for increased points of view, dialogue, and collaboration between prison professionals and between prison and society is discussed, and the current feasibility of treating psychiatric disorders in prison is considered.

Objective to evaluate the changes in daily voice production, analysed through the Ambulatory Phonation Monitoring (APM), and their relationship with Quality of Life (QOL) measurements in a group of profound deaf patients treated with Cochlear Implant (CI). Methods A total of 12 consecutive post-lingual deaf patients (8 females and 4 males) treated with CI for bilateral severe-to-profound hearing loss were enrolled. Each patient was evaluated before and after 6 months of CI use. In particular, the daily voice production evaluation was performed using the APM, while QOL information were gathered from the Italian version of the Nijmegen Cochlear Implant Questionnaire (I-NCIQ). Results Significant differences in the APM results obtained before and after CI were found. In particular, a significant decrease of the mean amplitude and a significant increase of the daily phonation time and percentage of phonation time were demonstrated after CI use in all the patients. A significant improvement in the I-NCIQ scores was demonstrated after CI use and significant correlations among I-NCIQ scores and the APM parameters were found. Conclusions The APM could be useful in the evaluation of the benefits of cochlear implantation and may represents an indicator of deaf patient participation. In addition, the daily voice production’s modifications after CI and their significant relations with the changes in QOL measurements could be useful in treatment planning as well as during pre- and post-operative counselling.

Background Sudden sensorineural hearing loss (SSNHL) is rare in children, and its etiology remains largely unknown, although viral infections seem to play an important role. The aim of this study is to report 5 children who experienced permanent SSNHL and had dual positivity of serum anti-Epstein-Barr virus (EBV) IgM and anti-Cytomegalovirus (CMV) IgM antibodies. Methods The study was conducted in a third-level referral audiological center. The medical charts of children under age 14 who experienced SSNHL without hearing recovery between September 1, 2017 and August 31, 2020, were reviewed. These children had undergone diagnostic evaluations, including brain magnetic resonance imaging, serological testing, thrombophilia and autoimmunity screening, to find possible causes of SSNHL. Results In all 5 patients identified, anti-EBV IgM, anti-CMV IgM and anti-CMV IgG antibodies were detected by chemiluminescent immunoassay (CLIA) immediately after the diagnosis of SSNHL, which occurred from 2 to 4 weeks after the onset of symptoms attributable to primary EBV infection. No abnormalities were demonstrated by coagulation and immunologic tests. Brain magnetic resonance imaging showed normal findings. Conclusions This study suggests that primary EBV infection should be considered one of the most likely causes of SSNHL without any hearing recovery in children. Therefore, a routine audiological examination should be recommended for children with virologically confirmed primary EBV infection at approximately 3-4 weeks after onset of symptoms and then repeated with periodic follow-up. Further studies on a wider number of children affected by SSNHL might clarify the possible pathogenetic role of this dual serological positivity.

This is a narrative review during the ongoing coronavirus disease 2019 (COVID-19) pandemic to streamline workflow of pediatric surgical patients in operating theaters and for theater teams involved in their management. Pediatric patient anxiety in theaters, aspects of communication, and optimizing vision during surgery during the pandemic have also been addressed. The COVID-19 pandemic has led to the creation of pathways in the surgical management of patients. As the pandemic progressed, hospitals developed pathways to offer increased protection to staff during procedures. This narrative review provides a clear perspective in the management of pediatric patients in operating theaters. Guidelines received from National Health Authorities and Societies affiliated with surgery, endoscopic surgery, anesthesiology, and endoscopy were carefully reviewed regarding their recommendations and data emerging from reports on COVID-19 were selected to compile the pathways specific for pediatric patients and staff. The workflow pathways have been successfully implemented during the pandemic and include a section on patients for endoscopy as well as approach to endoscopic surgery and open procedures. Theater room ergonomics that were successful during the pandemic have been outlined along with identification of areas specific to the pediatric patient anxiety, interteam communication/identification, and visor-related vision. The guidelines used successfully during the pandemic for pediatric theater teams can be used or adapted for formulating local hospital guidelines in other centers that could be valuable in patient management beyond the pandemic.

In this work, we propose to transfer a soil moisture-based wireless sensor network (SM-WSN) to support the reduction of irrigation water consume in the Tuscany region (Italy). The SM-WSN was designed and validated in a commercial pear orchard during two growing seasons (2019-2020) in which the smart irrigation strategy was implemented and applied.Initially, the micro irrigation system was assessed based on its performance in terms of water distribution uniformity (DU) evaluated with field measurements of emitter flow rates. Then, a zoning analysis was carried out to divide the orchard into homogeneous areas according to the normalized difference vegetation index (NDVI) detected with unmanned aerial vehicle (UAV) and GIS tools. These areas were used to define the topology of the SM-WSN and to investigate how water distribution uniformity can affect the vigour of the trees. A total of 6 “drill & drop” capacitance probes (Sentek Pty Ltd, Stepney, Australia) were installed in the field, after following a simplified laboratory calibration procedure. The hardware and the smartphone-based application, AgriNET, used to download from remote the sensors’ readings were provided by Tuctronics (Walla Walla, Washington, USA).Assuming that the zoning outcome was only associated with the soil spatial variability, the effect of DU on the vigour of the trees has been identified. Moreover, unlike the ordinary irrigation scheduling applied in the farm, the smart system allowed maintaining the soil water content within a pre-defined optimal range, in which the upper and lower limits corresponded respectively to the soil field capacity and the threshold below which water stress occurs. Based on the smart irrigation management, a water-saving up to 50% of the total water supplied with ordinary scheduling was achieved during both the investigated growing seasons. Moreover, the quality of the productions (i.e °Brix, fruit size and firmness) were in line with the standard required by the farmer. The adoption of the new technology, aiming at identifying the most appropriate irrigation management, has the potential to generate positive economic returns and to reduce the environmental impacts.

Background In clinical trials that assess novel therapeutic agents in patients with non-small-cell lung cancer (NSCLC), early endpoints (e.g. progression-free survival [PFS] and objective response rate) are often evaluated as indicators of biological drug activity, and are used as surrogate endpoints for overall survival (OS). Compiling trial-level data could help to develop a predictive framework to ascertain correlation trends between treatment effects for early (e.g. odds ratio [OR] for PFS at 6 months) and late endpoints (e.g. hazard ratio [HR] OS). Methods A dataset was compiled, which included 81 randomized, controlled trials (RCTs; Phase II–IV) of NSCLC (Stages I–IV), with 35 drugs and 156 observations. The dataset was collected from multiple source databases, including Citeline, TrialTrove, clinicaltrials.gov, and PubMed. We applied random-effects meta-analysis to correlate a variety of treatment effects for early endpoints with HR OS. We performed meta-regression analyses across different data-strata, stratified by the mechanism of action (MoA) of the investigational product (programmed death protein-1/programmed death-ligand 1 [PD-1/PD-L1], epidermal growth factor receptor [EGFR], vascular endothelial growth factor receptor, and DNA damage response). Results Low (Spearman’s rho 0.3– 1, indicate benefit with the investigational product. Conclusions Using a comprehensive summary data set in the NSCLC space, we observed low-to-moderate correlations between treatment effects for early endpoints and HR OS across RCTs of agents with different MoAs, including trials of PD-1/PD-L1 checkpoint inhibitors. Exploration of additional endpoints, beyond RECIST, is required to identify other early indicators of efficacy that might predict HR OS. By incorporating additional trial-level parameters and building composite biomarkers using machine intelligence methods, in collaboration with innovative trial design efforts, we envisage to improve the prediction of HR OS from early endpoints.

AIM This systematic review analyzed outcomes in thoracoscopic "primary" repair of type-C esophageal atresia. MATERIALS AND METHODS The Healthcare Database Advance Search, Embase, Medline, and Cochrane databases in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were researched by 2 independent reviewers. Non-English, mixed procedures (open/thoracoscopic) and staged-repair articles were excluded. RESULTS Between 2000 and 2018, 173 articles were identified of which 14 met the inclusion criteria and 382 neonates analyzed. Lowest reported age and weight were 28 gestational weeks and 830 g, respectively (gestational weeks: 28 to 41 wk; birth weight: 830 to 3960 g), with 136/382 (36%) having associated comorbidities. All procedures were performed in Cuschieri modified decubitus position with 3 ports (3.5 to 5 mm) and 30-degree scopes. Azygos vein sparing approach was reported in 4/14 (28.5%) articles; and if divided 70% preferred sealing/diathermy devices. Preferences for fistula ligation were sutures in 5/13 (38%) articles, clips or hemlock in 4/13 (30.7%), sutures with clips in 4/13 (30.7%) and no data in 1/14. Transanastomotic tubes placement was reported in 9/14 articles (others no data). Chest tube placement was preferred in 9/12 (75%) articles; 3/12 no chest tubes; and 2/14 no data. Intraoperative complications were reported in 9/382 (2.3%) neonates-respiratory instability (5/9), endoclip displacement (2/9), and anastomotic leak requiring conversion (2/9). Conversion to open thoracotomy was reported in 12/14 articles in 37/382 (9.6%) neonates. Postoperative complications were reported in 94/382 (25%); 79/94 (84%) anastomotic strictures, 40/94 (42.5%) anastomotic leaks and 5/94 (5.3%) recurrent fistulation. There were 17/382 (4.4%) lethal outcomes (cardiopulmonary failure, sepsis, and 1 intraoperative tracheal rupture). CONCLUSIONS Thoracoscopic "primary" repair of type-C esophageal atresia is feasible in premature/term neonates with a 1:10 conversion rate. Around one third surgeons prefer azygous sparing approach and three fourth placement of chest tubes, but there is no unanimity on the fistula ligation technique. The procedure has morbidity in one fourth patients and 5% mortality.

Objectives Beginning in December 2019, the 2019 novel coronavirus disease (COVID-19) has caused a pneumonia epidemic that began in Wuhan, China, and is rapidly spreading throughout the whole world. Italy is the hardest hit country after China. Considering the deleterious consequences of malnutrition, which certainly can affect patients with COVID-19, the aim of this article is to present a pragmatic protocol for early nutritional supplementation of non-critically ill patients hospitalized for COVID-19 disease. It is based on the observation that most patients present at admission with severe inflammation and anorexia leading to a drastic reduction of food intake, and that a substantial percentage develops respiratory failure requiring non-invasive ventilation or even continuous positive airway pressure. Methods High-calorie dense diets in a variety of different consistencies with highly digestible foods and snacks are available for all patients. Oral supplementation of whey proteins as well as intravenous infusion of multivitamin, multimineral trace elements solutions are implemented at admission. In the presence of 25-hydroxyvitamin D deficit, cholecalciferol is promptly supplied. If nutritional risk is detected, two to three bottles of protein-calorie oral nutritional supplements (ONS) are provided. If, Highlights • Novel coronavirus disease (COVID-19) is spreading throughout the world and if nutritional care is not promptly implemented, malnutrition will affect also patients with the disease. • Most infected patients present with severe inflammation and anorexia leading to a drastic reduction of food intake; a large percentage develop respiratory failure. • A pragmatic protocol for early nutritional supplementation of patients with COVID-19 not in the intensive care unit was implemented. • Every effort should be made to avoid or limit underfeeding in patients with COVID-19, even if it means struggling against insurmountable difficulties due to the emergency scenario.

(1) Background: The early detection of sepsis is still challenging, and there is an urgent need for biomarkers that could identify patients at a high risk of developing it. We recently developed an index, namely the Sepsis Index (SI), based on the combination of two CBC parameters: monocyte distribution width (MDW) and mean monocyte volume (MMV). In this study, we sought to independently validate the performance of SI as a tool for the early detection of patients at a high risk of sepsis in the Emergency Department (ED). (2) Methods: We enrolled all consecutive patients attending the ED with a request of the CBC. MDW and MMV were measured on samples collected in K3-EDTA tubes on the UniCel DxH 900 haematology analyser. SI was calculated based on the MDW and MMV. (3) Results: We enrolled a total of 703 patients stratified into four subgroups according to the Sepsis-2 criteria: control (498), infection (105), SIRS (52) and sepsis (48). The sepsis subgroup displayed the highest MDW (median 27.5, IQR 24.6–32.9) and SI (median 1.15, IQR 1.05–1.29) values. The ROC curve analysis for the prediction of sepsis showed a good and comparable diagnostic accuracy of the MDW and SI. However, the SI displayed an increased specificity, positive predictive value and positive likelihood ratio in comparison to MDW alone. (4) Conclusions: SI improves the diagnostic accuracy of MDW for sepsis screening.

Aim of the study Divided colostomy (DC) has been recommended in anorectal malformations (ARMs) with previously reported advantages of decreasing overflow into the distal limb and urinary tract infections (UTIs). Skin bridge loop colostomy (LC) is a technically easier alternative without an increase in these complications. We report our institutional experience of LC in ARM. Methods Retrospective study (Institution-approved Clinical Audit) reviewing the clinical records of all patients with ARM undergoing stoma formation in a single UK tertiary pediatric surgical center (2000–2015). Data collected included type of ARM, associated anomalies, type and level of colostomy, time to stoma closure, complications and UTIs. Results One hundred and eighty-two (95 female) patients underwent colostomy formation for ARM. The vast majority (171/ 94%) underwent LC; 9 (5%) had a divided colostomy (DC) and 2 (1%) had no available data. The spectrum of defects in girls included rectovestibular (62/65%), rectovaginal (4/4%) and cloaca (29/31%). In boys, 71 (82%) had a fistula to the urinary tract and 16 (18%) presented with a perineal fistula. Urological abnormalities coexisted in 87 (47.8%) patients. Thirty five (21%) patients developed UTIs. Among the 19 girls who developed UTI, 8 had rectovestibular fistula and 11 had cloaca. Of the 16 boys who developed UTI, 14 had a fistula to the urinary tract and 11 had an independent urological abnormality. The mean time from stoma formation to stoma closure was 10 (3–52) months. Complications were reported in 22 (12%) LCs. Fifteen patients (9%) developed a stoma prolapse following LC with 10 (6%) requiring surgical revision. Conclusions This is the largest reported series of outcomes following LC for ARM. LC is easier to perform and to close, requiring minimal surgical access, with comparable complications and outcomes to those published for DC. Type of study Retrospective comparative study. Level of evidence III.

Environmental managers regularly face decisions about how to counteract threats. These decisions require an understanding of both the conservation benefits and economic costs of candidate actions. However, transparent frameworks for how to accurately calculate costs for management are rare. We worked with island managers in Australia to develop eradication protocols for six invasive species- four mammals and two weeds. We used the protocols to create an accounting framework for invasive species eradications to produce realistic cost estimates for eradications across multiple locations. We also used our models to test common cost assumptions: (1) that costs scale linearly with area, (2) that terrain does not influence costs, and (3) that eradication costs stay constant through time. By explicating testing assumptions, we found that costs largely scaled linearly with area, that terrain influences costs, and that costs decline as populations decline in response to ongoing management. Estimated mammal eradication costs were driven in large part by the area of an island and the cost of transport. However, when area alone was used as a proxy for costs, the calculated costs deviated from our modelled costs by 40–56%. Weed eradication cost estimates were driven by the size and density of an infestation as well as the terrain of the island, with the effect of terrain becoming more pronounced as area to be treated increased. We provide a method to calculate realistic costs across several sites, which can be used to guide strategic management decision-making, including prioritisation, and on-ground management actions.

Achieving global targets for restoring native vegetation cover requires restoration projects to identify and work toward common management objectives. This is made challenging by the different values held by concerned stakeholders, which are not often accounted for. Additionally, restoration is time-dependent and yet there is often little explicit acknowledgment of the time frames required to achieve outcomes. Here, we argue that explicitly incorporating value and time considerations into stated objectives would help to achieve restoration goals. We reviewed the peer-reviewed literature on restoration of terrestrial vegetation and found that while there is guidance on how to identify and account for stakeholder values and time considerations, there is little evidence these are being incorporated into decision-making processes. In this article, we explore how a combination of stakeholder surveys and workshops can be used within a structured decision-making framework to facilitate the integration of diverse stakeholder values and time frame considerations to set restoration objectives. We demonstrate this approach with a case of restoration decision-making at a regional scale (southeast Queensland, Australia) with a view to this experience supporting similar restoration projects elsewhere.

Explicit articulation of values and objectives is critical

Background: The role erectile dysfunction (ED) coupled with low testosterone levels as early markers of atherosclerosis is not well understood. Objectives: To analyze the relationship between serum testosterone levels with both ED and brachial artery flow-mediated vasodilation (FMD), in a primary prevention sample of men. Methods: We enrolled 802 asymptomatic, intermediate CV risk patients, according to the Framingham Risk Score, aged 40e80 years, who underwent the ultrasound examination of FMD, the evaluation of ED and the assessment of total serum testosterone levels. Results: Testosterone levels correlated both with FMD (r ¼ 0.85; p < 0.0001) and IIEF-5 score (rs ¼ 0.65; p < 0.0001). Multivariable logistic regression analyses revealed that lower serum testosterone levels were strongly associated (p < 0.001) with severe (OR 0.78; 95% CI: 0.62e0.86), and moderate ED (OR 0.85; 95% CI: 0.72 e0.97), while impaired FMD percentages were strongly associated (p < 0.001) with severe (OR 0.68; 95% CI: 0.59e0.79), moderate (OR 0.76; 95% CI: 0.63e0.83) and mild to moderate ED (OR 0.8; 95% CI: 0.69 e0.94). Mild ED resulted statistically associated with lower FMD (OR 0.94; 95% CI: 0.82 e 1.07; p ¼ 0.03) but not with serum testosterone levels. These relations were not substantially affected by adjustments for further potential confounders including smoking status, hypertension, diabetes mellitus and body mass index. Conclusions: lower total serum testosterone levels are associated with impaired FMD and ED in this sample of intermediate CV risk men according to the Framingham Risk Score

Objective: Testosterone levels play a role in cardiac and vascular pathology. In the present study we investigated the prognostic significance of this hormone for cardiovascular outcome, in a 5-year follow-up. Materials and methods: Our cohort included 802 adult subjects, from 40 to 80 years. Patients were excluded if they had a past history of peripheral or coronary artery disease, and revascularization. A blood sample was drawn to valuate testosterone level, and we considered normal testosterone levels 300 ng/dl. FMD (flow mediated dilatation) of the brachial artery was assessed by measuring the increase of the brachial artery diameter during reactive hyperemia after transient forearm ischemia. B-mode longitudinal images of the brachial artery were obtained at the level of the antecubital fossa. The FMD was defined as the percentage change in the brachial artery diameter 60 s after releasing the ischemic cuff. Erectile dysfunction (ERD) was assessed by the International Index of Erectile Function-5 (IIEF-5) score questionnaire. We considered composite end points including the following major adverse cardiovascular events (MACEs) Results: Subjects with lower serum testosterone levels (n = 332) had higher prevalence of traditional cardiovascular risk factors, such as hypertension (p = 0.009), diabetes (p = 0.03), dyslipidemia (p < 0.0001), obesity (p = 0.002), and endothelial function score (p < 0.0001). AMI, death after AMI, major stroke and all clinical events were more frequent (p < 0.001) in patients with testosterone levels < 300 ng/dl. Further, by multiple logistic regression analysis we found that only dyslipidemia (p = 0,001), obesity (p = 0,007), testosterone < 300 ng/dl (p < 0,0001) and ED (p < 0,0001) were independent predictors of future events. Conclusions: A therapeutic intervention on testosterone may not only have a positive effect on the cardiovascular system but also an important role in preventing new cardiovascular events.

De-extinction technology that brings back extinct species, or variants on extinct species, is becoming a reality with significant implications for biodiversity conservation. If extinction could be reversed there are potential conservation benefits and costs that need to be carefully considered before such action is taken. Here, we use a conservation prioritization framework to identify and discuss some factors that would be important if de-extinction of species for release into the wild were a viable option within an overall conservation strategy. We particularly focus on how de-extinction could influence the choices that a management agency would make with regard to the risks and costs of actions, and how these choices influence other extant species that are managed in the same system. We suggest that a decision science approach will allow for choices that are critical to the implementation of a drastic conservation action, such as de-extinction, to be considered in a deliberate manner while identifying possible perverse consequences.

BackgroundIn 2007, a partnership was initiated between a small-volume paediatric cardiac surgery unit located in Las Palmas de Gran Canaria, Spain, and a large-volume cardiac surgery unit located in Milan, Italy. The main goal of this partnership was to provide surgical treatment to children with CHD in the Canary Islands.MethodsAn operative algorithm for performing surgery in elective, urgent, and emergency cases was adopted by the this joint programme. Demographic and in-hospital variables were collected from the medical records of all the patients who had undergone surgical intervention for CHD from January, 2009 to March, 2013. Data were introduced into the congenital database of the European Congenital Heart Surgeons Association Congenital Database and the database was interrogated.ResultsIn total, 65 surgical mission trips were performed during the period of this study. The European Congenital Heart Surgeons Association Congenital Database documented 214 total patients with a mean age at operation of 36.45 months, 316 procedures in total with 198 cardiopulmonary bypass cases, 46 non-cardiopulmonary bypass cases, 26 cardiovascular cases without cardiopulmonary bypass, 22 miscellaneous other types of cases, 16 interventional cardiology cases, six thoracic cases, one non-cardiac, non-thoracic procedure on a cardiac patient with cardiac anaesthesia, and one extracorporeal membrane oxygenation case. The 30-day mortality was 6.07% (13 patients).ConclusionsA joint programme between a small-volume centre and a large-volume centre may represent a valid and reproducible model for safe paediatric cardiac surgery in the context of a peripheral region.

Background Neuromodulation is the application of electrical stimulation on nerve fibers to modulate the neuronal activity. Its use for chronic constipation and fecal incontinence has increased in popularity over the past few years. Invasive and noninvasive techniques are currently available. We reviewed the current literature on the application of the neuromodulation techniques in the management of chronic constipation and fecal incontinence in children. Materials and Methods A search of Healthcare Database Advanced Search, Embase, Medline, and Cochrane database was performed in accordance with PRISMA guideline. Terms used in the search included neuromodulation, nerve stimulation, fecal/fecal incontinence, incontinence, constipation, children, and pediatric/pediatric. Results Two-hundred forty-one papers were screened. Fourteen papers were included for the systematic review: seven were selected for the ISNM (implantable sacral nerve modulation) technique, one for the transcutaneous tibial nerve stimulation), one for the transcutaneous sacral nerve modulation), and five for the transcutaneous interferential sacral nerve stimulation. Results showed an overall improvement in constipation symptoms in 79 to 85.7% of patients, resolution of symptoms in 40%, reduced use of ACE stoma/transanal irrigation system in 12.5 to 38.4%, and improvement in incontinence symptoms in 75%. High complication rate was reported (17–50%) in the ISNM group. No complications were reported in the non-invasive group. Conclusion Neuromodulation is a promising tool in the management of constipation refractory to medical treatment and fecal incontinence in children. Noninvasive techniques provide good results with no complications. A longer term follow-up will provide more information regarding patient compliance and sustainability of benefits of these new techniques.

Aim Regular anal dilatations are commonly recommended in the postoperative management following posterior sagittal anorectoplasty (PSARP) in anorectal malformations (ARM). We hypothesized that routine postoperative dilatations may not affect surgical outcomes following PSARP. We compare surgical outcomes of routine postoperative dilatations versus no routine postoperative dilatations from two United Kingdom tertiary pediatric surgical centers. Materials and Methods This is retrospective records review of patients undergoing definitive surgery for ARM in two tertiary surgical centers in the UK over 5 years. Center A used a protocol of routine postoperative dilatations, and center B used a protocol, which used dilatations only for clinical indications of stricture. Data collected included ARM type, operative procedures, and postoperative interventions. All post-operative interventions under general anesthesia (GA) were compared between groups. Results From 2011 to 2015, 49 procedures (46 PSARPs) were performed in center A and 54 (52 PSARPs) in center B. Median follow up period was 31 months (interquartile range [IQR] 18–48). The first postoperative anal calibration under GA was documented for 43 (86%) patients in center A and for 42 (78%) patients in center B. Following this, center A followed routine postoperative dilatation (RPD) at home, and center B reserved further dilatations for specific indications. RPD was performed for 100% of patients in center A versus 8% in center B. Further anal dilatations under GA were performed in 19 (38%) children in center A and in 17 (34%) children in center B (p = 0.68). In center A, 10 patients (22%) needed further surgery versus 14 (28%) in center B (p = 0.48). Conclusion The use of routine postoperative dilatations does not significantly improve surgical outcomes following PSARP in ARM.

The NCIQ is a quantifiable self-assessment health-related quality of life instrument specific for cochlear implant users. The aim of this study was to culturally adapt the NCIQ into Italian (I-NCIQ). A prospective instrument validation study was conducted. Cross-cultural adaptation and validation were accomplished. Cronbach α was used to test internal consistency in 51 CI users and in a control group composed by 38 post-lingual deaf adult on a waiting list for a CI. ICC test was used for test-retest reliability analysis. Kruskal-Wallis test with Mann-Whitney post hoc were used to compare the I-NCIQ scores in CI users before and after the cochlear implantation and in control patients. I-NCIQ scores obtained in CI users were compared with the results of Italian version of disyllabic testing without lip-reading and without masking. Good internal consistency and good test-retest reliability were found. I-NCIQ scores obtained in the 51 CI users after implantation were consistently higher than those obtained before implantation and in the control group. Moreover, no differences were found in the results of I-NCIQ obtained in the group of 51 CI users before implantation and in the group of control patients on post hoc Mann-Whitney analysis. Positive correlations between I-NCIQ scores and the results of disyllabic testing without lip-reading and without masking were found. The I-NCIQ is a reliable, valid, self-administered questionnaire for the measurement of QOL in CI users; its application is recommended.

The assessment of nutritional intakes during hospitalization is crucial, as it is known that nutritional status tends to worsen during the hospital stay, and this can lead to the negative consequences of malnutrition. International guidelines recommend the use of parenteral nutrition (PN) in hypophagic, non-surgical patients at nutritional risk, with contraindications to enteral nutrition. However, to date, there are no published data regarding either energy intake or objective measurements associated with it in this patient population. The aim of the present exploratory methodological study was to evaluate whether phase angle (PhA) and handgrip strength normalized for skeletal muscle mass (HG/SMM) are sensitive early markers of energy intake in hypophagic, non-surgical patients at nutritional risk, with contraindications to enteral nutrition. We evaluated 30 eligible patients, who were treated with personalized dietary modifications and supplemental PN for at least one week during hospitalization. In a liner regression model adjusted for age, gender, basal protein intake and the basal value of each variable, a trend toward improvement of PhA and preservation of HG/SMM was observed in patients satisfying the estimated calorie requirements (N = 20), while a significant deterioration of these parameters occurred in those who were not able to reach the target (N = 10). The mean adjusted difference and 95% CI were +1.4° (0.5–2.3) (p = 0.005) for PhA and +0.23 (0.20–0.43) (p = 0.033) for HG/SMM. A significant correlation between PhA and HG/SMM variations was also observed (r = 0.56 (95% CI, 0.23–0.77); p = 0.0023). PhA and HG/SMM were able to distinguish between hypophagic, non-surgical patients at nutritional risk who satisfied their estimated caloric requirements and those who did not after a one-week personalized nutritional support. Clinical studies are warranted, in order to verify these preliminary observations and to validate the role of PhA variations as early markers of anabolic/catabolic fluctuations.

Objective To document the imaging follow-up of laparoscopic partial nephrectomy (LPN) in children and to investigate the natural history of cystic lesions following LPN. Patients and methods We reviewed the ultrasonography (US) imaging reports performed during the follow-up of 125 children (77 girls, 48 boys; mean age 3.2 years) who underwent LPN in two centres of paediatric surgery in the period 2005-2015. Results A transperitoneal approach was adopted in 83 children and a retroperitoneal approach in 42. The mean follow-up was 4.2 years. At US, an avascular cyst related to the operative site was found after 61/125 procedures (48.8%). As for their appearance, 53/61 cysts were simple and anechoic, and eight of the 61 cysts appeared septated. The mean diameter of the cysts was 3.3 × 2.8 cm. As for their course, 13/61 cysts (21.3%) disappeared after a mean of 4 years, 26/61 (42.6%) did not significantly change in dimension, 17/61 (27.8%) decreased in size, and only five of the 61 cysts (8.3%) enlarged. The cysts were asymptomatic in 51 children (83.6%), while they were associated with urinary tract infections (UTIs) and abdominal pain in the remaining 10; none required a re-intervention. Conclusions The US finding of a simple cyst at the operative site after LPN is common during follow-up, with an incidence of ~50% in our series. In regard to aetiology, probably a seroma takes the place of the removed hemi-kidney. There was no correlation between cyst formation and type of surgical technique adopted. As there was no correlation between cysts and clinical outcomes, renal cysts after LPN can be managed conservatively, with periodic US evaluations.

LETTER TO EDITOR

The occurrence of left bundle branch block (LBBB) is quite common in clinical practice. The changes in cardiac repolarization, caused by this disorder of electric conduction, may mask the presence of an acute myocardial infarction (AMI), delaying the diagnostic-therapeutic iter, with an important impact on prognosis. We describe the case of a woman of 59 years with LBBB, came to our observation for a constrictive chest pain associated with dyspnea. The diagnostic workup for suspected acute coronary syndrome (ACS), initially conducted only on the analysis of the electrocardiogram (negative TnI at entry), showed the presence of coronary arteries free of stenosis. However, the diagnostic confirmation of AMI was completed after the rise of cardiac markers and the electrocardiographic changes. This case confirm the difficulty about the diagnosis of AMI in patients with LBBB and stresses, however, as the use of some criteria proposed in the literature [1-3] can guide to its identification, directing patient to an appropriate treatment.

Congenital Hernia of the cord is an uncommon abdominal wall defect anatomically and embriologically considered as a different entity from Gastroschisis and Omphalocoele with an estimated incidence of 1:5000. Its content can be various including: small and large bowel, gallbladder, liver lobes and omphalo-mesenteric remnants. Here we report the first case of a wandering spleen incarcerated within the congenital hernia of the cord in order to highlight the importance of the surgical exploration to prevent solid organs injury.

Purpose: This dose-escalation study evaluated the safety, tolerability, and pharmacokinetics (PK) of the oral Src inhibitor saracatinib (AZD0530) in patients with advanced solid malignancies. Tumor biopsy samples were taken to investigate the effect of saracatinib on Src activity in tumors. Experimental Design: Part A of the study followed a multiple-ascending dose design to establish the maximum tolerated dose (MTD) of saracatinib. Part B was a randomized, parallel-group, cohort-expansion phase to further assess tolerated doses. Safety, tolerability, and Src activity (immunohistochemistry and lysate-based methodologies) were assessed after 21 days of once-daily oral dosing. PK was assessed after single and multiple dosing. Results: In part A, 30 patients received once-daily saracatinib at doses of 60 to 250 mg; the MTD was established as 175 mg. In part B, 51 patients were randomized to receive 50 mg (n = 16), 125 mg (n = 16), or 175 mg (n = 19) of saracatinib. The most common grade ≥3 events considered to be treatment related were anemia, diarrhea, and asthenia. Tumor Src activity was reduced following saracatinib treatment. The area under the concentration-time curve and Cmax of saracatinib increased with increasing dose. Saracatinib accumulated 4- to 5-fold on once-daily dosing to reach steady-state exposure after 10 to 17 days of dosing. The half-life was ∼40 hours. Conclusions: Saracatinib was well tolerated in patients with advanced solid malignancies. A reduction in tumor Src activity was observed. PK data show that saracatinib is suitable for once-daily oral dosing. Based on this study, the recommended dose for the phase II studies was chosen to be 175 mg/d. Clin Cancer Res; 16(19); 4876–83. ©2010 AACR.

Background Paediatric urolithiasis is uncommon and severe complications, such as urinary tract infections and renal parenchymal scarring, occur in a minority of children with urinary calculi. The goals of management are to prevent additional renal damage, to expedite the passage of stones, and prevent new stone formation. The standard work-up for paediatric calculi includes ultrasonography followed by an abdominal x-ray. However complex calculi (for example staghorn calculi with extensive ramification in the renal collecting system) present a special diagnostic and therapeutic challenge. Methods At Great Ormond Street Hospital for Children a new imaging approach has been proposed in children presenting with complex renal calculi. This involves a Tc-99m-DMSA scan with planar and tomographic images for assessment of renal parenchymal function, followed by a low dose unenhanced CT KUB. The DMSA tomographic images are co-registered to the CT images. Results This technique enables assessment of the function of the renal parenchyma adjacent to the renal stones. It has thus been possible to manage the calculi taking parenchymal function into account. For example, in the case of a horseshoe kidney in which one of the two moieties contained numerous stones, the DMSA scan showed very poor parenchymal function of that moiety: it was therefore decided to surgically resect the moiety instead of extracting the stones individually with percutaneous nephro-lithotomy (PCNL). Conversely, in a duplex kidney with stones in the lower moiety, the DMSA scan showed good parenchymal function of the lower moiety; as a result, this was not resected and the stones were extracted with PCNL. The radiation dose from this approach was no higher than the standard imaging protocol. Conclusion Preliminary results of this imaging approach in a selected patients’ population of more than 30 children with complex paediatric renal stones are encouraging and warrant further evaluation.

Biodiversity conservation projects confront immediate and escalating threats with limited funding. Conservation theory suggests that the best response to the species extinction crisis is to spend money as soon as it becomes available, and this is often an explicit constraint placed on funding. We use a general dynamic model of a conservation landscape to show that this decision to “front-load” project spending can be suboptimal if a delay allows managers to use resources more strategically. Our model demonstrates the existence of temporal efficiencies in conservation management, which parallel the spatial efficiencies identified by systematic conservation planning. The optimal timing of decisions balances the rate of biodiversity decline (e.g., the relaxation of extinction debts, or the progress of climate change) against the rate at which spending appreciates in value (e.g., through interest, learning, or capacity building). We contrast the benefits of acting and waiting in two ecosystems where restoration can mitigate forest bird extinction debts: South Australia’s Mount Lofty Ranges and Paraguay’s Atlantic Forest. In both cases, conservation outcomes cannot be maximized by front-loading spending, and the optimal solution recommends substantial delays before managers undertake conservation actions. Surprisingly, these delays allow superior conservation benefits to be achieved, in less time than front-loading. Our analyses provide an intuitive and mechanistic rationale for strategic delay, which contrasts with the orthodoxy of front-loaded spending for conservation actions. Our results illustrate the conservation efficiencies that could be achieved if decision makers choose when to spend their limited resources, as opposed to just where to spend them.

Background Right atrial area (RAA) is a prognostic factor in human patients with pulmonary arterial hypertension (PAH). Reference intervals for RAA have been described in healthy dogs. Objectives To evaluate RAA indexed to the body surface area in dogs with PAH as an indicator of right atrial size, PAH severity and right‐sided congestive heart failure (R‐CHF). Animals A total of 119 client‐owned dogs, 48 dogs with PAH and 71 control dogs. Methods Prospective observational study. Pulmonary arterial hypertension was classified according to the tricuspid regurgitation pressure gradient (TRPG) as mild (36–50 mmHg), moderate (51–75 mmHg), or severe (>75 mmHg). The RAA index was calculated as the RAA divided by body surface area. Results The RAA index was higher in dogs with moderate PAH (13.3 cm2/m2; range, 3.4–24.7 cm2/m2) and severe PAH (12.1 cm2/m2; range, 5.4–21.8 cm2/m2) than in those with mild PAH (6.7 cm2/m2; range, 4.8–10.7 cm2/m2) or in controls (7.3 cm2/m2; range, 4.2–10.2 cm2/m2; P 12.3 cm2/m2 (sensitivity, 100%; specificity, 89.5%). In dogs with PAH, severity of tricuspid regurgitation (TR) was the only independent predictor of RAA index based on multivariate analysis (P

Group-IV semiconductor nanowires (NWs) are attracting the interest of a wide scientific community as building blocks for a wide range of future nanoscaled devices. We used metal-assisted chemical etching of Si substrates to synthesize Si NWs with different length and nanometer-size diameter. NWs obtained by this technique have exactly the same structure and doping of the substrate and present quantum confinement effects. Photoluminescence (PL) emission at room temperature from Si NWs is reported. We observed an increasing behaviour of the PL intensity as a function of the NWs length. The fabrication of light emitting devices based on Si NWs, showing electroluminescence emission at room temperature under low voltage excitation, is also reported. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Decolonizing the mind: the politics of language in African Literature,1986, Kenia (NgugiWa’ Thiong’O); De Vulgari Eloquentia(“About Eloquence in the Vulgar”), 1303-05, Tuscany-Italy (Dante Alighieri); Half of a yellow sun, 2007, Nigeria (Chimanda Ngozie Adichie); Canale Mussolini(“Mussolini Canal”), 2010, Italy (Antonio Pennacchi). As you can see from the rough scheme above, the following will be a “horizontal” presentation rather than a “vertical” one. I will not talk extensively of the life and activity of the four mentioned writers, so “distant” each other either in time or in space but I will make talk, for them, their own mentioned works (a collection of essays, a middle age treatise and two novels). I will try to assume, synthetize and summarize the political and artistic role these four authors played, only through their direct speech and words, extracted from some sample works of theirs. I will also try to understand the social and political context which they belonged to from what they have said or told in the analyzed works.

Introduction: Early diagnosis remains a major concern in pts with primary diffuse large B-cell lymphoma (DLBCL) of the CNS (PCNSL). Diagnostic delay leads to severe neurological impairment due to prolonged exposure of CNS tissues to tumor infiltration, and protracted steroid therapy, which causes immunodepression and infective complications, the main reasons for treatment interruptions. A few molecular markers have been proposed as diagnostic tools, but reliable parameters that can be easily incorporated in routine practice are still needed. Near 70% of PCNSLs display MYD88 L265P mutation and release high levels of interleukin-10 (IL10). These two parameters are widely used for routine diagnosis of different disorders, but are hardly detectable in peripheral blood of PCNSL pts; accordingly, cerebrospinal fluid (CSF) may be an attractive alternative for their evaluation. Thus, we investigated the sensitivity and specificity of MYD88 L265P mut and IL10 levels in CSF samples to distinguish PCNSL from other neurological disorders, and to identify earlier relapsing lymphomas. Methods: MYD88 mutational status and IL6 and IL10 levels were assessed by TaqMan RT-PCR assay and ELISA, respectively, on CSF samples from 198 HIV-neg adults with 1) histologically-confirmed PCNSL at presentation (pPCNSL; n= 27) or relapse (rPCNSL; n= 26); 2) neurological disorders currently entering in differential diagnosis with PCNSL (n= 105; degenerative and inflammatory disorders, toxic or infective encephalitis, gliomas, and others); 3) systemic DLBCL at high-risk of CNS dissemination (n= 40). MYD88 status was assessed in 85 neurological controls and interleukins in 78; both parameters were assessed in 58. Differences in MYD88 status (categorical variable) and IL10 levels (continuous variables) among pts subgroups were assessed by Fisher exact and Mann-Whitney U tests, respectively. Predictive accuracy of IL6 & IL10 was evaluated in terms of sensitivity and specificity by means of ROC curves. Associations between PCNSL features (site and number of lesions; CSF protein level and cytological status) and analyzed molecules were addressed by Spearman's correlation. Results: Demographic characteristics of analyzed subgroups were similar, with a median (range) age of 62 (39-81) ys for PCNSLs and 63 (28-89) ys for controls (p= 0.42); with 27 (51%) and 69 (48%) males (p= 0.70), respectively. MYD88 L265P mut was detected in 19 (70%) of 27 pPCNSL, in 11 (42%) of 26 rPCNSL, in 1 (1%) of 85 neurological controls and in 1 (3%) of 40 systemic DLBCL (p< 0.00001), with a sensitivity and specificity for pPCNSL detection of 70% and 98%, respectively. Median IL6 concentration was 4.62 pg/mL (0-157.7) for the 53 PCNSLs and 2 pg/mL (0-200) for the 118 assessed controls (p= 1.0). High IL6 levels (>12 pg/mL) were recorded in 5 (18%) of 27 pPCNSL, in 7 (27%) of 26 rPCNSL, in 7 (9%) of 78 neurological controls, and in 0 (0%) of 40 systemic DLBCL. The ROC curve showed a low sensitivity and specificity of IL6 to distinguish PCNSL from other disorders and DLBCL, with an area under the curve of 0.66 (poor accuracy). Median IL10 concentration was 53.3 pg/mL (0-400) for PCNSLs and 0 pg/mL (0-10) for controls (p< 0.00001). Increased IL10 levels were recorded in 20 (91%) of 22 assessed pPCNSL, in 20 (91%) of 23 assessed rPCNSL, in 1 (1%) of 78 neurological controls, and in 1 (2%) of 40 systemic DLBCL, with a sensitivity and specificity for PCNSL detection of 91% and 98%, respectively, and an area under the ROC curve of 0.95 (high accuracy). At least one of analyzed parameters (MYD88 L265P mut & high IL10 level) was recorded in 26 (96%) of 27 pPCNSL, in 23 (88%) of 26 rPCNSL, in 1 (1%) of 58 neurological controls and in 2 (5%) of 40 systemic DLBCL, with a sensitivity and specificity to detect PCNSL of 96% and 97%, respectively. Both MYD88 L265P mut and IL10 levels were independent of lymphoma features. Conclusions: The occurrence of MYD88 L265P mut and high IL10 level in CSF samples are associated with very high sensitivity and specificity in PCNSL pts. These simple and fast procedures, currently used in routine practice, are reliable tools to generate early and strong suspicion of PCNSL at both diagnosis and relapse. These results support the use of MYD88 L265P mut and high IL10 level as diagnostic tools in pts with suspected PCNSL localized in areas unsuitable for biopsy (i.e., brain stem). The role of these parameters in monitoring lymphoma behavior should be addressed in prospective trials. Disclosures No relevant conflicts of interest to declare.

EHR 2.0 is an evolution of current Electronic Health Records (EHR) which provides an intelligent support for all healthcare providers and patients in the National Health System with the benefit of improving the quality of care and increasing patient involvement in the health care and prevention process. At the center of the EHR 2.0 the paper puts the Virtual Health Record (VHR), an intelligent resource in network that contains all the digital information available about the patient health. How the main services of the VHR were derived from the analysis of some innovative healthcare scenarios is presented.

The paper presents the prototype of a Personal Health System (PHS) realized during the Smart Health 2.0 Project. This implementation, called 'LiSE', represents an evolution with respect to the Citizen's Personal Notebook, introduced and specified by the EHR Italian regulations. The PHR provides some features that simplify the relationships between key players in NHS, like health care workers and patients. The PHR tools, such as the clinical dossier, the virtual medical assistant, or the GP/patient communication system, make the patient 'closer' to the health system, improving the own knowledge about her/his illness and, consequently, making him/her part active and conscious in the care processes. The PHS is able to enrich the EHR with information on the patient's health state and, at the same time, to take advantage of information extracted from the EHR content and supplied in a language and a format accessible to the patient. The proposed PHS, equipped with its own business logic to support patient empowerment, is the key element for the construction of a health care model based on a patient-centered vision of the healthcare.