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In a laboratory that uses a web-based building management system to run equipment, critical records from this system must be compliant with good laboratory practices (GLPs) regarding data integrity. GLPs [...]

Objective and design: Glucocorticoids (GCs) have been widely used in symptomatic patients for the treatment of COVID-19. The risk for adrenal insufficiency must be considered after GC withdrawal given that it is a life-threatening condition if left unrecognized and untreated. Our study aimed to diagnose adrenal insufficiency early on through a GC reduction schedule in patients with COVID-19 infection. Patients and measurements: From November 2021 to May 2022, 233 patients were admitted to the Geriatric Division of the University Hospital of Padova with COVID-19 infection. A total of 122 patients were treated with dexamethasone, after which the GC tapering was performed according to a structured schedule. It consists of step-by-step GC tapering with prednisone, from 25 mg to 2.5 mg over 2 weeks. Morning serum sodium, potassium, and cortisol levels were assessed 3 days after the last dose of prednisone. Results: At the end of GC withdrawal, no adrenal crisis or signs/symptoms of acute adrenal insufficiency were reported. Median serum cortisol, sodium, and potassium levels after GC discontinuation were, respectively, 427 nmol/L, 140 nmol/L, and 4 nmol/L (interquartile range 395–479, 138–142, and 3.7–4.3). A morning serum cortisol level below the selected threshold of 270 nmol/L was observed in two asymptomatic cases (respectively, 173 and 239 nmol/L, reference range 138–690 nmol/L). Mild hyponatremia (serum sodium 132 to 134 nmol/L, reference range 135–145 nmol/L) was detected in five patients, without being related to cortisol levels. Conclusions: A structured schedule for the tapering of GC treatment used in patients with severe COVID-19 can reduce the risk of adrenal crisis and acute adrenal insufficiency.

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Introduction: Since COVID-19 pandemic spread, strict preventive measures were adopted to reduce the risk of transmission. Antiseptic dispensers for hand hygiene were diffusely available for patients and hospital staff. To investigate the prophylactic role played by the strict antiseptic rules adopted during pandemic, the rates of nosocomial urinary infections in 2019 and 2020 were compared.Materials and methods: Patients’ clinical pre-operative characteristics, symptoms, fever, and laboratory data were recorded pre- and post-operatively. Urological surgery was classified in five categories: 1. major surgery 2. upper urinary tract endoscopy, 3. lower urinary tract endoscopy, 4. minor surgery, and 5. Nephrostomy and ureteral stenting. Clavien-Dindo complication score was used. Statistical analysis was performed with R 3.4.2 software.Results: Out of 495 patients, 383 (57.1%) underwent surgical intervention in pre-pandemic March–May 2019 period and 212 (42.9%) in the same pandemic 2020 interval. Preoperatively, 40 (14.1%) and 11 (5.2%) and 77 (27.3%) and 37 (17.5%) patients had fever (p< 0.003) and leukocytosis (p< 0.02), in 2019 and 2020 respectively. Urine culture was positive in 29 (10.2%) and 13 (6.2%) patients respectively (p= 0.22). Post-operatively, 54 (19.1%) and 22 (10.4%) patients and 17 (6.1%) and 2 (0.6%) patients showed fever (p< 0.003) and positive urineculture (p< 0.03), in 2019 and 2020 respectively.Discussion and conclusion: Preoperative and post-operative clinical and laboratory signs of nosocomial urinary infection showed a statistically significant lower incidence during the pandemic period in 2020. This observation could be ascribed to the strong preventive measures, to the medical staff high adherence to hygiene and the diffuse availability of hand sanitizers.

In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, a central committee of heart failure (HF) specialists optimized guideline-directed medical therapies (GDMT) and documented medication and goal dose intolerances before patient enrollment.

Objectives: Learning and performing new routines are difficult for children with neurodevelopmental disorders. Studies have shown that consistency in child reinforcement and parental support are effective. For example, digital solutions such as serious games can be used to support parents and children in developing these life skills. The objective of this study was to evaluate the effect of a serious game on the performance of daily routines by autistic and ADHD children. Methods: A total of 201 families (parents and children) participated in the study. The study used a combined 3 (intervention) × 3 (diagnosis) × 3 (time) research design with repeated measures. Participants were randomly assigned to three intervention groups (serious game, parental support, and a combination of serious game and parental support) based on their diagnosis (ASD, ADHD, neurotypical). Latent growth modeling and repeated ANOVAS were performed to analyze routine scores collected at three moments (baseline, midpoint, persistence) over an 8-week period. Results: Results show a moderating effect of diagnosis on child routine trajectory. For ADHD participants, we observed a very important significant clinical effect for two interventions (parental support alone and combination of serious game and parental support) where for ASD children, this effect is observed for only one treatment (combination of serious game and parental support). For neurotypical children, results indicate a very important and significant clinical effect when they use the serious game alone. Conclusions: Results show that the serious game can improve children’s routines. However, for some neurodevelopmental profiles (ASD or ADHD), the addition of parental support produces greater clinical improvements.

BackgroundThe role of bridging intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) in the treatment of acute ischemic stroke (AIS) remains debatable. Atrial fibrillation (AF) associated strokes may be associated with reduced treatment effect from IVT. This study compares the effect of bridging IVT in AF and non-AF patients.MethodsThis retrospective cohort study comprised anterior circulation large vessel occlusion (LVO) AIS patients receiving EVT alone or bridging IVT plus EVT within 6 hours of symptom onset. Primary outcome was good functional outcome defined as modified Rankin Scale (mRS) 0–2 at 90 days. Secondary outcomes were successful reperfusion defined as expanded Thrombolysis In Cerebral Infarction (eTICI) grading ≥2b flow, symptomatic intracerebral hemorrhage (sICH), and in-hospital mortality.ResultsWe included 705 patients (314 AF and 391 non-AF patients). The mean age was 68.6 years and 53.9% were male. The odds of good functional outcomes with bridging IVT was higher in the non-AF (adjusted odds ratio (aOR) 2.28, 95% CI 1.06 to 4.91, P=0.035) compared with the AF subgroups (aOR 1.89, 95% CI 0.89 to 4.01, P=0.097). However, this did not constitute a significant effect modification by the presence of AF on bridging IVT (interaction aOR 0.12, 95% CI −1.94 to 2.18, P=0.455). The rate of successful reperfusion, sICH, and mortality were similar between bridging IVT and EVT for both AF and non-AF patients.ConclusionThe presence of AF did not modify the treatment effect of bridging IVT. Further individual patient data meta-analysis of randomized trials may shed light on the comparative efficacy of bridging IVT in AF versus non-AF LVO strokes.

The directed assembly of nanomaterials into 3D architectures is a powerful tool to produce macroscopic materials with tailored physical properties. We show in this article that such a process can be advantageously performed for the fabrication of lightweight electrically conductive materials. Silver nanowire aerogels (AgNWAs) with very low densities (down to ∼6 mg cm–3) were ice-templated and freeze-dried, leading to 3D shaped cellular materials based on one-dimensional nanoscopic building blocks. Due to their intrinsic moderate mechanical resistance, the potential use of pure AgNWAs in real life applications appears rather limited. We demonstrate that the addition of carboxymethylcellulose (CMC) in a 1:1 weight ratio leads to the fabrication of hybrid aerogels with highly improved mechanical properties. The molecular weight of the CMC is shown to be a critical parameter to ensure a good dispersion of the AgNWs, and thus to reach excellent performances such as a very low resistivity (0.9 ± 0.2 Ω·cm at 99.2 vol % porosity). The combination of silver nanowires with CMC-700k results in a gain higher than 7100% of the Young’s modulus, from 10.4 ± 0.9 kPa (at very low density, i.e., 12 mg cm−3) for the AgNWAs to 740 ± 40 kPa for the AgNW:CMC aerogel. Electromechanical characterizations allowed us to quantify the piezoelectric properties of these hybrid aerogels. The very good elasticity and the piezoelectric behavior stability up to 100 cycles of compression under high (50%) deformation were revealed, which may be of interest for various applications such as pressure sensors.

An important research question examined in the credit risk literature focuses on the proportion of corporate yield spreads attributed to default risk. This topic is reexamined in light of the [...]

Background: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are long-chain polyunsaturated fatty acids (LCPs) that play pivotal roles in growth and neurodevelopment. Objective: We aimed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs. Design: Twenty-two preterm infants were randomly assigned to either the no-LCP group (fed formula without LCPs; n = 11) or the LCP group (fed formula with LCPs; n = 11). Dietary LCPs had higher [sup.13]C content than did the endogenously synthesized LCPs, which were derived from linoleic and [alpha]-linolenic acids. The [sup.13]C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1, 3, and 7 mo. Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated. Results: Percentage AA synthesis was 67.2 [+ or -] 7.8%, 35.9 [+ or -]9.8%, and 29.0 [+ or -] 10.3%, and that of DHA was 41.7 [+ or -] 14.9%, 10.5 [+ or -] 8.1%, and 7.4 [+ or -] 6.2% at 1, 3, and 7 mo old, respectively. Absolute AA synthesis was 26.7 [+ or -] 4.2, 14.4 [+ or -] 3.9, and 11.6 [+ or -] 4.1 mg x [kg.sup.-1] x [d.sup.-1] and that of DHA was 12.6 [+ or -] 4.5, 3.2 [+ or -] 2.5, and 2.3 [+ or -] 1.9 mg x [kg.sup-1] x [d.sup.-1] at 1, 3, and 7 mo old, respectively. AA and DHA synthesis decreased significantly (P < 0.01) with time, and AA synthesis was significantly (P < 0.01) greater than DHA synthesis. Conclusions: By this novel approach, we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods. By age 7 mo, LCP synthesis was dramatically lower in preterm infants fed LCPs. KEY WORDS Preterm infant, long-chain polyunsaturated fatty acids, LCPs, natural abundance, endogenous synthesis

A modified lattice approach to option pricing is proposed.

An efficient method for determining prices of financial options is obtained by combining decision trees and a moments of cumulative return formula.

Background The Silk Vista Baby (SVB) flow diverter (FDS) is the only FDS deliverable via a 0.017 inch microcatheter and is specifically designed for the distal vasculature. We sought to evaluate the safety and efficacy of the SVB.Materials and Methods We performed a retrospective review to identify SVB cases at 4 tertiary neurosurgical centres within the U.K. Clinical, procedural, angiographic and follow-up data were collected.Results We identified 60 patients (35 female, 58%) of average age 54 ± 10.5 (range 30–72) with 61 aneurysms, 50 (81.9%) located in the anterior circulation. The majority of the aneurysms treated were unruptured (46, 75.4%) and saccular (46, 75.4%). Dome size was 6.2 ± 6.2 mm (range 1–36mm) and parent vessel diameter was 2.3 ± 0.4 mm (range 1.2-3.3 mm). An average number of 1.07 devices were implanted. Coils or other devices were implanted in 14 aneurysms (23.3%). At last angiographic follow-up (n = 55), 7.5 ± 4.2 months post-procedure, 32 aneurysms (57.1%) were graded as RRC I, 7 (12.5%) RRC II, and 17 RRC III (30.4%). Clinical complications, excluding death, were seen in 4 patients (6.8%) including 1 delayed aneurysm rupture and 3 symptomatic ischaemic events. Only one patient had permanent morbidity (mRS 1). 3 patients died during follow-up (5.1%); 2 deaths were related to the aneurysms (3.4%) – one ruptured dissecting MCA aneurysm, and one giant partially thrombosed posterior circulation aneurysm. 93% of patients were mRS ≤ 2 at last follow-up.Conclusion The SVB has high rates of technical success and an acceptable safety profile. Distal aneurysms may occlude slower due to relative oversizing of the devices.

IMPORTANCE: The outcome and interpretation of noninferiority trials depend on the magnitude of the noninferiority margin and whether a relative or absolute noninferiority margin is used and may be affected by imprecision in event rate estimation. OBJECTIVE: To assess the consequence of imprecise event rate estimations on interpretation of peer-reviewed randomized clinical trials. DATA SOURCES: PubMed/MEDLINE was searched for articles published between January 1, 2015, and April 30, 2021. STUDY SELECTION: Noninferiority randomized clinical trials of coronary stents published in selected journals with clinical events as the primary end point. DATA EXTRACTION AND SYNTHESIS: Two reviewers (M.S. and F.V.) independently extracted data on trial characteristics, noninferiority assumptions, primary end point clinical outcomes, and study conclusions. Overestimation or underestimation of the control event rate was evaluated by dividing the assumed control event rate by the observed control event rate. For noninferiority end points with absolute margins, the assumed corresponding relative margin was defined as the ratio of the absolute margin and the assumed event rate, and the observed corresponding relative margin as the ratio between the absolute margin and the observed event rate in the control arm. Noninferiority comparisons with absolute margins were reanalyzed using the assumed corresponding relative margin and the Farrington-Manning score test for relative risk. MAIN OUTCOMES AND MEASURES: Overestimation or underestimation, assumed and observed corresponding relative margins, and relative reanalysis of the primary end points of trials with absolute margins. RESULTS: A total of 106 989 patients from 58 trials were included. The event rate in the control arms was overestimated by a median (IQR) of 28% (2%-74%). Most noninferiority trials used absolute rather than relative margins (55 of 58 trials [94.8%]). Owing to overestimation, absolute noninferiority margins became more permissive than originally assumed (median [IQR] of observed relative noninferiority margin, 1.62 [1.50-1.80] vs assumed relative noninferiority margin, 1.47 [1.39-1.55]; P &lt; .001). Among trial comparisons that met noninferiority with an absolute noninferiority margin, 17 of 50 trials (34.0%) would not have met noninferiority with a corresponding assumed relative noninferiority margin. CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, assumed event rates were often overestimated in noninferiority coronary stent trials. Because most of these trials use absolute margins to define noninferiority, such overestimation results in excessively permissive relative noninferiority margins.

Introduction: BCG and MMC shortage and Covid-19 pandemic, more recently, limit accessibility to maintenance regimen in intravesical prophylaxis against recurrence of non-muscle invasive bladder cancer (NMIBC). Ellagic acid (EA) and Annona muricata (AM) exert antitumor activity against different human tumours. An observational prospective study on the prophylactic effect of oral administration of EA+AM in patients avoiding maintenance regimen is presented.Materials and methods: Patients affected by NMIBC and not undergoing maintenance after a 6-week course of intravesical prophylaxis with MMC or BCG were entered. Tis and very high-risk tumours were excluded. After informed consent, the patients were subdivided in relation to the oral assumption or not of EA (100 mg) plus AM (100 mg), daily for 6 months. All patients were submitted to 3-month cytology and cystoscopy.Results: 162 (90%) of 180 entered patients are evaluable, 90 and 72 receiving or not EA+AM. No difference emerged in patients’ characteristics between the two groups. BCG was given in 86 (54%) and chemotherapy in 74 (46%) patients. The recurrence free rate at 3, 6 and 12 months in patients assuming or not EA was 96.5% versus 84.6% (p= 0.003), 85.4% versus 64.8% (p= 0.005) and 74.2% versus 60.6% (p= 0.246), respectively. The recurrence free survival at 12 months in patients assuming or not EA was 63.0% versus 34.5% (p< 0.0001).Discussion and conclusions: Our study suffers several limits: not randomized trial although prospective, limited number of patients and short follow-up, nevertheless it shows the prophylactic effect of oral EA+AM in absence of maintenance after intravesical chemotherapy or immunotherapy induction.

Background and purposeCone-beam CT angiography (CB-CTA) provides a three-dimensional spatial resolution which is, so far, unmatched in clinical practice compared with other conventional techniques such as two-dimensional digital subtracted angiography. We aimed to assess the distribution of symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) using CB-CTA.Methods30 consecutive patients with aSAH undergoing vasospasm percutaneous balloon angioplasty (PBA) were recruited and underwent CB-CTA in this single-center prospective cohort series. Intracranial arteries were systematically analyzed by two independent observers from the large trunks to the distal cortical branches and perforators using a high-resolution reconstruction protocol. Intermediate and severe cerebral vasospasm was defined as 30–50% and >50% narrowing in the diameter of the vessel, respectively.Results35 arterial cervical artery territories were analyzed, of which 80% were associated with clinical or radiological signs of delayed cerebral ischemia. The median spatial resolution was 150 µm (range 100–250 µm). Intermediate or severe vasospasm was observed in the proximal (86%, 95% CI 74% to 97%), middle (89%, 95% CI 78% to 99%), and distal (60%, 95% CI 44% to 76%) segments of the large trunks, as well as the cortical branches (11%, 95% CI 1% to 22%). No vasospasm was observed in basal ganglia or cortical perforators, or in arteries smaller than 900 µm. Vasospasm was more severe in middle or distal segments compared with proximal segments in 43% (95% CI 26% to 59%) of cases.ConclusionsOur study demonstrated that symptomatic cerebral vasospasm following aSAH did not involve arteries smaller than 900 µm, and frequently predominated in middle or distal segments. These results offer new insights into the potential management options for vasospasm using PBA.

Background: An association between exposure to environmental tobacco smoke (ETS) and lung cancer risk has been suggested. To evaluate this possible association better, researchers need more precise estimates of risk, the relative contribution of different sources of ETS, and the effect of ETS exposure on different histologic types of lung cancer. To address these issues, we have conducted a case-control study of lung cancer and exposure to ETS in 12 centers from seven European countries. Methods: A total of 650 patients with lung cancer and 1542 control subjects up to 74 years of age were interviewed about exposure to ETS. Neither case subjects nor control subjects had smoked more than 400 cigarettes in their lifetime. Results: ETS exposure during childhood was not associated with an increased risk of lung cancer (odds ratio [OR] for ever exposure = 0.78; 95% confidence interval [CI] = 0.64-0.96). The OR for ever exposure to spousal ETS was 1.16 (95% CI = 0.93-1.44). No clear dose-response relationship could be demonstrated for cumulative spousal ETS exposure. The OR for ever exposure to workplace ETS was 1.17 (95% CI = 0.94-1.45), with possible evidence of increasing risk for increasing duration of exposure. No increase in risk was detected in subjects whose exposure to spousal or workplace ETS ended more than 15 years earlier. Ever exposure to ETS from other sources was not associated with lung cancer risk. Risks from combined exposure to spousal and workplace ETS were higher for squamous cell carcinoma and small-cell carcinoma than for adenocarcinoma, but the differences were not statistically significant. Conclusions: Our results indicate no association between childhood exposure to ETS and lung cancer risk. We did find weak evidence of a dose-response relationship between risk of lung cancer and exposure to spousal and workplace ETS. There was no detectable risk after cessation of exposure. [J Natl Cancer Inst 1998;90:1440-50]

Introduction: The current scenario of the COVID-19 pandemic is significantly different from that of the first, emergency phase. Several countries in the world are experiencing a second, or even a third, wave of contagion, while awaiting the effects of mass vaccination campaigns. The aim of this report was to provide an update of previously released recommendations on prioritization and restructuring of urological activities.Methods: A large group of Italian urologists directly involved in the reorganization of their urological wards during the first and second phase of the pandemic agreed on a set of updated recommendations for current urology practice.Results: The updated recommendations included strategies for the prioritization of both surgical and outpatient activities, implementation of perioperative pathways for patients scheduled for elective surgery, management of urological conditions in infected patients. Future scenarios with possible implementation of telehealth and reshaping of clinical practice following the effects of vaccination are also discussed.Conclusion: The present update may be a valid tool to be used in the clinical practice, may provide useful recommendations for national and international urological societies, and may be a cornerstone for further discussion on the topic, also considering further evolution of the pandemic after the recently initiated mass vaccination campaigns.

As part of the cost reduction of proton exchange membrane fuel cells, the substitution of the standard platinum catalyst by iron active sites for the oxygen reduction reaction (ORR) appears as a promising route. Herein, we report Pt-free catalysts prepared through an Fe–N-doped carbon cryogel synthesis process. By tuning selected parameters such as the initial pH and precursor molar ratios, various new structures with different chemical compositions and catalytic activities were synthesized and characterized. Carbon cryogels are porous materials, and the achieved hierarchical structures proved favorable for the accessibility of the active sites for O2and H+. The value of the pH medium was identified as a key parameter to control the structure of N-rich carbon cryogels, leading to a specific pH range to diphasic hydrogels. These materials are described and characterized for the first time, and they show promising catalytic activity for the ORR.

Estimates of the proportion of lung and bladder cancer cases attributable to occupational exposure vary widely. For example, in published reports, the proportion of all cancers that could be prevented by better workplace hygiene ranges between 1 percent and 38 percent. This high variability results from different study methodologies, as well as from the variation in exposure to carcinogens among different populations. To learn more concerning these sources of variability, a systematic evaluation was carried out of several published studies. Only case-control studies were selected for inclusion in which the subject's smoking status was known. Case-control studies use an approach which matches an affected person with an unaffected subject (control) for age, sex, or other relevant criteria; cases and controls are then compared to see if differences in the variable suspected of elevating risk (in this case, occupation) can be detected. Other selection criteria are discussed. Results showed that between 1 and 40 percent of lung cancers, and between 0 and 24 percent of bladder cancers, could be attributed to occupational exposure. This variability seems to result from the wide fluctuation in exposure by different geographic regions. For instance, five studies of lung cancer in the US used data from workers in shipyards in four geographic areas. As such, risk estimates cannot be generalized to the population as a whole, and are specific to location and time. (Consumer Summary produced by Reliance Medical Information, Inc.), Proportion of Lung and Bladder Cancers in Males Resulting From Occupation: A Systematic Approach ACCORDING to previous estimates, the proportion of cancers that could be prevented with occupational hygiene measures [...]

La sclérose en plaques (SEP) est la première cause de handicap non traumatique de l’adulte jeune. L’hypersomnolence diurne a été rapportée chez ces patients, altérant la qualité de vie.

Les patients atteints de sclérose en plaques (SEP) sont plus fréquemment atteints de troubles du sommeil que la population générale. Notre étude avait pour objectif d’évaluer la prévalence de l’hypersomnolence chez des patients atteints de SEP et d’en analyser les étiologies.

Onset of many forms of epilepsy occurs after an initial epileptogenic insult or as a result of an identified genetic defect. Given that the precipitating insult is known, these epilepsies are, in principle, amenable to secondary prevention. However, development of preventive treatments is difficult because only a subset of individuals will develop epilepsy and we cannot currently predict which individuals are at the highest risk. Biomarkers that enable identification of these individuals would facilitate clinical trials of potential anti-epileptogenic treatments, but no such prognostic biomarkers currently exist. Several putative molecular, imaging, electroencephalographic and behavioural biomarkers of epileptogenesis have been identified, but clinical translation has been hampered by fragmented and poorly coordinated efforts, issues with inter-model reproducibility, study design and statistical approaches, and difficulties with validation in patients. These challenges demand a strategic roadmap to facilitate the identification, characterization and clinical validation of biomarkers for epileptogenesis. In this Review, we summarize the state of the art with respect to biomarker research in epileptogenesis and propose a five-phase roadmap, adapted from those developed for cancer and Alzheimer disease, that provides a conceptual structure for biomarker research.

Pumps used in professional appliances process a solution of water, soils residues and detergents. These affect vapor tension, viscosity and rheology of the solution, mainly due to the presence of surfactants and polymers. Only a few studies have been found on how these substances can influence pump performances. Therefore, an experimental analysis has been carried out with aqueous solutions of a detergent component, the Polyox WSR 301, in the concentration range of 100–7000 ppm, to evaluate their influence on pump performances and cavitation. Some properties of the solutions have been preliminary characterized with a rheometer. Then, each solution has been tested in a dedicated test rig, to compare the performance curves of a centrifugal pump used in professional warewashing machines with those obtained with pure water. A non-intrusive method, based on the investigation of high frequency vibrations and noise signals, has been developed to detect cavitation at its early stage of inception. It was observed that polymer mitigates cavitating pump vibrations, with a reduction of the acceleration to less than one g. The analysis has provided the data necessary for the successive development of a control strategy for pump operation in professional appliances.

BackgroundWhile anatomic features associated with the risk of posterior communicating artery (PcoA) occlusion after embolization of aneurysms of the PcoA segment of the internal carotid artery (ICA) are well known, the link between perforator origin and perforator infarction has only been reported following neurosurgical clipping. The aim of this study was to determine the origin of anterior thalamic perforators and correlate it with risk of perforator infarction after embolization of PcoA segment aneurysms.MethodsOne-hundred-and-ninety consecutive patients treated for PcoA segment aneurysms between 2017 and 2019 were included. PcoA and anterior thalamic perforator origin anatomy was assessed with computed tomography (CT) angiography, digital subtracted angiography, and high-resolution three-dimensional rotational cone-beam CT angiography (CBCT-A) by two independent interventional neuroradiologists. The presence of perforator infarction after embolization was ascertained from the patient’s notes and follow-up imaging.ResultsCBCT-A was superior in demonstrating the origin of perforators (P<0.001). The prevalence of perforator origin was estimated at 86% (95% CI 81%–92%) for PcoA, 8% (95% CI 4%–13%) for aneurysm wall, and 5% (95% CI 2%–9%) for ICA. The aneurysm wall origin was exclusively associated with PcoA agenesis, as well as higher risk of perforator infarction after aneurysm coiling compared with other variants (OR=14, 95% CI 2–88, P=0.006).ConclusionsOur study suggests that anterior thalamic perforators may arise from aneurysm wall when there is no PcoA. Anatomic association between PcoA agenesis and perforator arising from ICA could underlie such findings, and careful consideration is essential before aneurysm repair to anticipate the risk of thalamic infarction in such cases.

This systematic review was conducted to identify the literature examining the prevalence of problematic internet use (PIU) in individuals with autism spectrum disorder (ASD), the difference in prevalence of PIU between those with and without ASD, and the correlates of PIU in ASD. Ten studies were identified. The eight studies with comparison groups reported that individuals with ASD had more symptoms of or scored higher on PIU. Correlates of PIU included time spent online and age at which individuals first went online, as well as depression, inattention, hyperactivity, impulsivity, opposition, and escapism. Results indicate that additional research is needed to examine PIU in adults with ASD and the causal relation of factors related to PIU in ASD through longitudinal studies.

ABSTRACTThree new species of Luticolaare described from lotic ecosystems in Andakí Municipal Natural Park, located in the Andean-Amazon region on the eastern flank of the eastern Andes mountain range in Colombia. Size and morphological features of the three new species, L. caquetensisKociolek, Simonato & Núñez-Avellaneda sp. nov., L. andakiesiorumSimonato, Kociolek & Plata Díaz sp. nov., and L. sinchiiSala, Kociolek & Simonato sp. nov. are provided, based on light and scanning electron microscopical observations, and compared with similar congeners. Species of the genus are organized into groups depending upon whether they possess or lack marginal channels and/or pseudosepta. All the new species possess pseudosepta and L. caquetensisand L. andakiesiorumlack marginal channels. The two latter species share this combination of features with Luticola affinisLevkov et al.,a species described from Brazil. These species thus form a unique group within the genus, offering additional evidence for the unique biodiversity found in this region.

In pediatric acute myeloid leukemia (AML), intensive chemotherapy and allogeneic hematopoietic stem cell transplantation are the cornerstones of treatment in high-risk cases, with severe late effects and a still high risk of disease recurrence as the main drawbacks. The identification of targeted, more effective, safer drugs is thus desirable. We performed a high-throughput drug-screening assay of 1280 compounds and identified thioridazine (TDZ), a drug that was highly selective for the t(6;11)(q27;q23) MLL-AF6 (6;11)AML rearrangement, which mediates a dramatically poor (below 20%) survival rate. TDZ induced cell death and irreversible progress toward the loss of leukemia cell clonogenic capacity in vitro. Thus, we explored its mechanism of action and found a profound cytoskeletal remodeling of blast cells that led to Ca2+ influx, triggering apoptosis through mitochondrial depolarization, confirming that this latter phenomenon occurs selectively in t(6;11)AML, for which AF6 does not work as a cytoskeletal regulator, because it is sequestered into the nucleus by the fusion gene. We confirmed TDZ-mediated t(6;11)AML toxicity in vivo and enhanced the drug’s safety by developing novel TDZ analogues that exerted the same effect on leukemia reduction, but with lowered neuroleptic effects in vivo. Overall, these results refine the MLL-AF6 AML leukemogenic mechanism and suggest that the benefits of targeting it be corroborated in further clinical trials.

ABSTRACTCoronary obstruction is a major complication of transcatheter aortic valve replacement (TAVR). Rapid and growing demand for TAVR procedures is accompanied by interest in techniques that may prevent this life-threatening adverse event. BASILICA (Bioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Iatrogenic Coronary Artery Obstruction) is a transcatheter technique that may effectively prevent coronary obstruction. Formal proctorship and assistance by operators already experienced with the performance of BASILICA is beneficial to ensure good clinical outcomes. This review describes the BASILICA procedure and outlines selected technical considerations and pitfalls.AbbreviationsTAVR: transcatheter aortic valve replacement; BASILICA: Bioprosthetic or Native Aortic Scallop Intentional Laceration to Prevent Iatrogenic coronary Artery Obstruction; THV: transcatheter heart valve; VTC: virtual valve to coronary distance; ViV: valve-in-valve; VIVID: valve in valve international data.

Valve-in-valve transcatheter aortic valve replacement (ViV TAVR) is an established alternative to conventional surgical reoperation for failed aortic bioprosthetic valves. The technique has undergone significant refinements in recent years, aiming to tackle pain points of the procedure such as subpar hemodynamics and coronary obstruction. In this state-of-the-art review, we aim to discuss these refinements, including novel surgical valves, transcatheter heart valve positioning, bioprosthetic valve fracture, prevention of coronary obstruction, among others. We also summarize key updates on clinical trial data and contemporary outcomes of ViV TAVR.

Early ischemic recurrence (EIR) following the diagnosis of acute spontaneous cervical artery dissection (CeAD) has been little investigated. We aimed to determine the prevalence and determinants on admission of EIR in a large single-center retrospective cohort study of patients with CeAD.

All-polymeric flexible transparent heaters (THs) are demonstrated for the first time. Thin films of four poly(3,4-ethylenedioxythiophene) (PEDOT)-based materials embedding different dopants exhibit low sheet resistances, down to 57 Ω sq–1associated with good transparencies (>87%) and a haze lower than 1%. These transparent thin films show excellent heating properties, with high heating rates (up to 1.6 °C s–1) and steady-state temperatures exceeding 100 °C when subjected to 12 V bias. Very high areal power densities were also measured, reaching almost 10 000 W m–2. The temperature increase is finely fitted to a thermal model. It is further demonstrated that these new THs can be efficiently integrated for applications in thermochromic displays and visor deicers.

Local tetanus develops when limited amounts of tetanus neurotoxin (TeNT) are released by Clostridium tetanigenerated from spores inside a necrotic wound. Within days, a spastic paralysis restricted to the muscles of the affected anatomical area develops. This paralysis follows the retrograde transport of TeNT inside the axons of spinal cord motoneurons and its uptake by inhibitory interneurons with cleavage of VAMP, a synaptic vesicle protein required for neurotransmitter release. Consequently, incontrollable excitation of motoneurons causes contractures of innervated muscles and to local spastic paralysis.

A limit of peripheral veno-arterial Extracorporeal Membrane Oxigenator (VA-ECMO) is the inadequate unloading of the left ventricle. The increase of end-diastolic pressure reduces the possibility of a recovery and may cause severe pulmonary edema. In this study, we evaluate our results after implantation of VA-ECMO and Transapical Left Ventricular Vent (TLVV) as a bridge to recovery, heart transplantation or long-term left ventricular assit devices (LVAD). From 2011 to 2014, 24 consecutive patients with profound cardiogenic shock were supported by peripheral VA-ECMO as bridge to decision. In all cases, TLVV was implanted after a mean period of 12.2 ± 3.4 hours through a left mini-thoracotomy and connected to the venous inflow line of the VA-ECMO. Thirty-day mortality was 37.5% (9/24). In all patients, hemodynamics improved after TLVV implantation with an increased cardiac output, mixed venous saturation and a significant reduced heart filling pressures (p< .05). Recovery of the cardiac function was observed in 11 patients (11/24; 45.8%). Three patients were transplanted (3/24; 12.5%) and three patients (3/24; 12.5%) underwent LVAD implantation as destination therapy, all these patients were discharged from the hospital in good clinical conditions. In these critical patients, systematic TLVV improved hemodynamic seemed to provide better in hospital survival and chance of recovery, compared to VA-ECMO results in the treatment of cardiogenic shock reported in the literature . TLVV is a viable alternative to standard VA-ECMO to identify the appropriate long-term strategy (heart transplantation or long-term VAD) reducing the risk of treatment failure. A larger and multicenter experience is mandatory to validate these hypothesis.

ABSTRACTBackground:The management of patients with asymptomatic, severe aortic stenosis (AS) is controversial. We performed a meta-analysis to examine the impact on outcomes of early aortic valve replacement (AVR) in patients with severe asymptomatic AS versus a watchful-waiting (WW) approach.Methods:Databases were searched for studies published until April 2019. Main outcome of interest was death during follow-up.Results:The search yielded 1,889 studies for inclusion. Of these, seven articles were analyzed and their data extracted. The total number of patients included was 3,839. The overall HR (95% CI) for death showed a statistically significant difference between the groups, with lower risk in the “early AVR” group (random effect model: HR 0.280; 95% CI 0.159–0.494, P< 0.001). There was evidence of significant statistical heterogeneity of treatment effect among the studies for death. Funnel plot analysis disclosed no asymmetry around the axis for the outcome of interest, which means that we have low risk of publication bias related to this outcome. Sensitivity analysis showed that none of the studies had a particular impact on the results. The meta-regression coefficients for the modulating factors age, male sex, presence of hypertension and presence of diabetes were significant for mortality, showing that the early intervention becomes even more protective in comparison with the conservative approach when we take these factors into consideration.Conclusion:Early AVR seems to be a better approach than WW in the treatment of asymptomatic patients with severe AS, but we would still advocate a case-by-case decision-making process.

To evaluate the functional results and complications of the lingual mucosal graft (LMG) urethroplasty and to sum up the current state of the art of this surgical technique.

Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults. This neurological disorder is characterized by focal seizures originating in the temporal lobe, often with secondary generalization. A variety of pharmacological treatments exist for patients suffering from focal seizures, but systemically administered drugs offer only symptomatic relief and frequently cause unwanted side effects. Moreover, available drugs are ineffective in one third of the epilepsy patients. Thus, developing more targeted and effective treatment strategies for focal seizures, originating from, e.g., the temporal lobe, is highly warranted. In order to deliver potential anti-epileptic agents directly into the seizure focus we used encapsulated cell biodelivery (ECB), a specific type of ex vivo gene therapy. Specifically, we asked whether unilateral delivery of glial cell line-derived neurotrophic factor (GDNF), exclusively into the epileptic focus, would suppress already established spontaneous recurrent seizures (SRS) in rats. Our results show that GDNF delivered by ECB devices unilaterally into the seizure focus in the hippocampus effectively decreases the number of SRS in epileptic rats. Thus, our study demonstrates that focal unilateral delivery of neurotrophic factors, such as GDNF, using ex vivo gene therapy based on ECB devices could be an effective anti-epileptic strategy providing a bases for the development of a novel, alternative, treatment for focal epilepsies.

Aortic valve-in-valve is a less invasive alternative to surgical redo in the treatment of failed bioprosthetic valves. While only inoperable patients underwent the procedure before, operators currently offer it to those at lower risk and worldwide experience is in the thousands. Early mortality has diminished in recent analyses and improvements in symptoms and quality of life have been documented. Main considerations with aortic valve-in-valve include elevated postprocedural gradients, coronary obstruction and leaflet thrombosis. Risk factors for each of these adverse events have been described at length. Aortic valve-in-valve offers a safe and effective option in the management of failed bioprosthetic valves.

Fabrication of silver nanowires (AgNWs) with fine and independent control of both the diameter (from 30 to 120 nm) and length (from 5 to 120 μm) by concomitant addition of co-nucleants and temperature control is demonstrated, and used for the preparation of size standards. Percolating random networks were fabricated using these standards and their optoelectronic properties were measured and compared with regard to the nanowire dimensions. The transparent electrodes appear suitable for various applications and exhibit excellent performances (e.g.16 ohm sq−1at 93% transparency), with haze values varying from 1.6 to 26.2%. Besides, in vitrotoxicological studies carried out on murine macrophages with the same size standards revealed that AgNWs are weakly toxic (no toxicity observed below 50 μg mL−1Ag), in particular compared to other silver nanoparticles. Short AgNWs (4 μm) appeared to be slightly more toxic than longer AgNWs (10 and 20 μm). Conversely, long AgNWs (20 μm) induced a more prolonged pro-inflammatory response in murine macrophages. These results contribute, in a safer by design approach, to promoting the use of short AgNWs. The global knowledge dealing with the combination of nanowire dimensions associated with optoelectronic performances and related toxicity should encourage the rational use of AgNWs, and guide the choice of the most adequate AgNW dimensions in an integrated approach.

Aim: Assessing the incidence of immediate postoperative complications and 90-day mortality in high-risk patients who have undergone radical cystectomy; evaluating the correlation between preoperative conditions and surgery outcomes.Materials and methods: This is a monocentric retrospective observational study in which data of 65 patients have been analyzed.High-risk criteria: (a) Age ≥75 years, (b) obesity, (c) age-adjusted Charlson Comorbidity Index ≥8, (d) anemic status, and (e) pT ≥3. More than 50% of patients had two or more “high-risk” indicators. Postoperative complications were assessed through Clavien–Dindo classification.Results: Average age of patients was 70.4 years, average age-adjusted Charlson Comorbidity Index was 5.8, and average body mass index was 27.5. In 28% of patients, no complications arose, while in 46% grades I–II complications according to Clavien–Dindo occurred, in 23% grades III–IV complications occurred, and in 3% of the patients, death arose in the immediate postoperative period (grade V). Overall, 90-day mortality rate after surgery was 12.3%. The age ≥75 years and an age-adjusted Charlson Comorbidity Index score ≥8 have shown to be risk factors for the onset of severe complications (odds ratio = 3.54, p= 0.028 and odds ratio = 4.7, p= 0.026), while preoperative anemic status was a risk factor for complications in general (odds ratio = 4.1, p= 0.015). No analyzed parameter was a predictor of 90-day mortality (p > 0.05).Conclusion: Immediate postoperative complications and 90-day mortality in radical cystectomy in high-risk patients remain significant, but still in line with the data in the literature on comparable populations. Some of the preoperative parameters were able to predict the outcomes of the intervention with regard to the onset of complications but not to the 90-day mortality.

Electrical stability and homogeneity of silver nanowire (AgNW) networks are critical assets for increasing their robustness and reliability when integrated as transparent electrodes in devices. Our ability to distinguish defects, inhomogeneities, or inactive areas at the scale of the entire network is therefore a critical issue. We propose one-probe electrical mapping (1P-mapping) as a specific simple tool to study the electrical distribution in these discrete structures. 1P-mapping has allowed us to show that the tortuosity of the voltage equipotential lines of AgNW networks under bias decreases with increasing network density, leading to a better electrical homogeneity. The impact of the network fabrication technique on the electrical homogeneity of the resulting electrode has also been investigated. Then, by combining 1P-mapping with electrical resistance measurements and IR thermography, we propose a comprehensive analysis of the evolution of the electrical distribution in AgNW networks when subjected to increasing voltage stresses. We show that AgNW networks experience three distinctive stages: optimization, degradation, and breakdown. We also demonstrate that the failure dynamics of AgNW networks at high voltages occurs through a highly correlated and spatially localized mechanism. In particular the in situformation of cracks could be clearly visualized. It consists of two steps: creation of a crack followed by propagation nearly parallel to the equipotential lines. Finally, we show that current can dynamically redistribute during failure, by following partially damaged secondary pathways through the crack.

BackgroundIn children with congenital heart disease (CHD), altered pulmonary circulation compromises gas exchange. Moreover, pulmonary dysfunction is a complication of cardiac surgery with cardiopulmonary bypass (CPB). No data are available on the effect of different CHDs on lung injury. The aim of this study was to analyze epithelial lining fluid (ELF) surfactant composition in children with CHD.MethodsTracheal aspirates (TAs) from 72 CHD children (age 2.9 (0.4–5.7) months) were obtained before and after CPB. We measured ELF phospholipids, surfactant proteins A and B (SP-A, SP-B), albumin, and myeloperoxidase activity. TAs from 12 infants (age 1.0 (0.9–2.9) months) with normal heart/lung served as controls.ResultsHeart defects were transposition of great arteries (19), tetralogy of Fallot (TOF, 20), atrial/ventricular septal defect (ASD/VSD, 22), and hypoplastic left heart syndrome (11). Increased levels of ELF SP-B were found in all defects, increased myeloperoxidase activity in all except the TOF, and increased levels of ELF albumin and SP-A only in ASD/VSD patients. Postoperatively, ELF findings remained unchanged except for a further increase in myeloperoxidase activity.ConclusionELF composition has distinctive patterns in different CHD. We speculate that a better knowledge of the ELF biochemical changes may help to prevent respiratory complications.

Bioprostheses are prone to structural valve degeneration, resulting in limited long-term durability. A significant challenge when comparing the durability of different types of bioprostheses is the lack of a standardized terminology for the definition of a degenerated valve. This issue becomes especially important when we try to compare the degeneration rate of surgically inserted and transcatheter bioprosthetic valves. This document, by the VIVID (Valve-in-Valve International Data), proposes practical and standardized definitions of valve degeneration and provides recommendations for the timing of clinical and imaging follow-up assessments accordingly. Its goal is to improve the quality of research and clinical care for patients with deteriorated bioprostheses by providing objective and strict criteria that can be utilized in future clinical trials. We hope that the adoption of these criteria by both the cardiological and surgical communities will lead to improved comparability and interpretation of durability analyses.

ObjectiveWe aimed to analyse the incidence of prosthesis–patient mismatch (PPM) and elevated gradients after aortic valve in valve (ViV), and to evaluate predictors and associations with clinical outcomes of this adverse event.MethodsA total of 910 aortic ViV patients were investigated. Elevated residual gradients were defined as ≥20 mm Hg. PPM was identified based on the indexed effective orifice area (EOA), measured by echocardiography, and patient body mass index (BMI). Moderate and severe PPM (cases) were defined by European Association of Cardiovascular Imaging (EACVI) criteria and compared with patients without PPM (controls).ResultsModerate or greater PPM was found in 61% of the patients, and severe in 24.6%. Elevated residual gradients were found in 27.9%. Independent risk factors for the occurrence of lower indexed EOA and therefore severe PPM were higher gradients of the failed bioprosthesis at baseline (unstandardised beta −0.023; 95% CI −0.032 to –0.014; P<0.001), a stented (vs a stentless) surgical bioprosthesis (unstandardised beta −0.11; 95% CI −0.161 to –0.071; P<0.001), higher BMI (unstandardised beta −0.01; 95% CI −0.013 to –0.007; P<0.001) and implantation of a SAPIEN/SAPIEN XT/SAPIEN 3 transcatheter device (unstandardised beta −0.064; 95% CI −0.095 to –0.032; P<0.001). Neither severe PPM nor elevated gradients had an association with VARC II-defined outcomes or 1-year survival (90.9% severe vs 91.5% moderate vs 89.3% none, P=0.44).ConclusionsSevere PPM and elevated gradients after aortic ViV are very common but were not associated with short-term survival and clinical outcomes. The long-term effect of poor post-ViV haemodynamics on clinical outcomes requires further evaluation.