Search

Hypothesis: The possibility to use hexamethylenediamine (HMDA) to impart film forming ability to natural polymers including eumelanins and plant polyphenols endowed with biological activity and functional properties has been recently explored with the aim to broaden the potential of polydopamine (PDA)-based films overcoming their inherent limitations. 5,6-dihydroxyindole-2-carboxylic acid, its methyl ester (MeDHICA) and eumelanins thereof were shown to exhibit potent reducing activity. Experiments: MeDHICA and HMDA were reacted in aqueous buffer, pH 9.0 in the presence of different substrates to assess the film forming ability. The effect of different reaction parameters (pH, diamine chain length) on film formation was investigated. Voltammetric and AFM /SEM methods were applied for analysis of the film redox activity and morphology. HPLC, MALDI-MS and 1HNMR were used for chemical characterization. The film reducing activity was evaluated in comparison with PDA by chemical assays and using UV stressed human immortalized keratinocytes (HaCat) cells model. Findings: Regular and homogeneous yellowish films were obtained with moderately hydrophobic properties. Film deposition was optimal at pH 9, and specifically induced by HMDA. The film consisted of HMDA and monomeric MeDHICA accompanied by dimers/small oligomers, but no detectable MeDHICA/HMDA covalent conjugation products. Spontaneous assembly of self-organized networks held together mainly by electrostatic interactions of MeDHICA in the anion form and HMDA as the dication is proposed as film deposition mechanism. The film displayed potent reducing properties and exerted significant protective effects from oxidative stress on HaCaT

Background: Digital dermoscopy monitoring (DDM) helps to recognize melanomas lacking specific dermoscopic features at baseline, but the number of melanomas eventually developing specific features is still unknown. Objective: To assess how many melanomas are identified because they develop melanoma-specific criteria over time compared with melanomas recognized by side-by-side image comparison. Methods: A case-control study was conducted collecting 206 melanomas: 103 melanomas diagnosed during DDM follow-up and 103 melanomas diagnosed at baseline. The control group was composed of 309 benign lesions consisting of 103 nevi excised for diagnostic reasons, 103 not excised nevi, and 103 not excised seborrheic keratoses. Dermoscopic images of all 515 lesions were randomly presented to 2 blinded experts to give a diagnosis and to score the criteria of the 7-point checklist. Results: Of the 103 melanomas diagnosed at baseline, 78.6% (n = 81) were correctly identified compared with only 40.8% (n = 42) of melanomas diagnosed after DDM (P

Contrast-enhanced ultrasound scan (CEUS) is the application of ultrasound contrast agents (UCAs) to traditional ultrasound. Our aim is to report the use of CEUS for a prompt assessment of a suspected secondary splenic lymphoma in a child, which, in our experience, has allowed an accurate description of the parenchymal perfusion and vascularization pattern, leading to a confident diagnosis. We suggest that CEUS will replace Magnetic resonance imaging (MRI) or Computed tomography (CT) as standard imaging option for differential diagnosis of spleen lesions in pediatric population. As a result this will lead to decreasing the overall use of ionizing radiation and reducing the time interval to a certain diagnosis.

Background A recently introduced dermoscopic method for the diagnosis of early lentigo maligna (LM) is based on the absence of prevalent patterns of pigmented actinic keratosis and solar lentigo/flat seborrheic keratosis. We term this the inverse approach. Objective To determine whether training on the inverse approach increases the diagnostic accuracy of readers compared to classic pattern analysis. Methods We used clinical and dermoscopic images of histopathologically diagnosed LMs, pigmented actinic keratoses, and solar lentigo/flat seborrheic keratoses. Participants in a dermoscopy masterclass classified the lesions at baseline and after training on pattern analysis and the inverse approach. We compared their diagnostic performance among the 3 timepoints and to that of a trained convolutional neural network. Results The mean sensitivity for LM without training was 51.5%; after training on pattern analysis, it increased to 56.7%; and after learning the inverse approach, it increased to 83.6%. The mean proportions of correct answers at the 3 timepoints were 62.1%, 65.5, and 78.5%. The percentages of readers outperforming the convolutional neural network were 6.4%, 15.4%, and 53.9%, respectively. Limitations The experimental setting and the inclusion of histopathologically diagnosed lesions only. Conclusions The inverse approach, added to the classic pattern analysis, significantly improves the sensitivity of human readers for early LM diagnosis.

Background Timely recognition of malignant melanoma (MM) is challenging for dermatologists worldwide and represents the main determinant for mortality. Dermoscopic examination is influenced by dermatologists’ experience and fails to achieve adequate accuracy and reproducibility in discriminating atypical nevi (AN) from early melanomas (EM). Objective We aimed to develop a Deep Convolutional Neural Network (DCNN) model able to support dermatologists in the classification and management of atypical melanocytic skin lesions (aMSL). Methods A training set (630 images), a validation set (135) and a testing set (214) were derived from the idScore dataset of 979 challenging aMSL cases in which the dermoscopic image is integrated with clinical data (age, sex, body site and diameter) and associated with histological data. A DCNN_aMSL architecture was designed and then trained on both dermoscopic images of aMSL and the clinical/anamnestic data, resulting in the integrated “iDCNN_aMSL” model. Responses of 111 dermatologists with different experience levels on both aMSL classification (intuitive diagnosis) and management decisions (no/long follow-up; short follow-up; excision/preventive excision) were compared with the DCNNs models. Results In the lesion classification study, the iDCNN_aMSL achieved the best accuracy, reaching an AUC = 90.3 %, SE = 86.5 % and SP = 73.6 %, compared to DCNN_aMSL (SE = 89.2 %, SP = 65.7 %) and intuitive diagnosis of dermatologists (SE = 77.0 %; SP = 61.4 %). Conclusions The iDCNN_aMSL proved to be the best support tool for management decisions reducing the ratio of inappropriate excision. The proposed iDCNN_aMSL model can represent a valid support for dermatologists in discriminating AN from EM with high accuracy and for medical decision making by reducing their rates of inappropriate excisions.

Background: Chronic nodular prurigo (CNPG) is a multifactorial skin disease characterized by itchy papules and nodules, usually resistant to standard treatment and associated with markedly impaired quality of life. Objective: To describe dupilumab effectiveness and tolerability in treating adult patients with CNPG refractory to both topical and systemic therapies. Methods: Retrospective, multicenter study including adult patients affected by CNPG, who were treated with dupilumab for at least 16 weeks. Results: Twenty-seven CNPG patients showed clinical improvement in terms of skin lesions, itch, sleeplessness, and quality of life. A consistent proportion of patients (24/27; 88.9%) had at least 16-week continuous treatment and achieved Investigator Global Assessment score 1 (11/24; 45.8%). An increased number of patients achieved at least a 2-grade reduction in Investigator Global Assessment score (19/24; 79.2%). Numeric rating scale values for itch and sleeplessness decreased from 8.9 to 2.7 and from 8.2 to 1.7, respectively (P

Objective(s) The authors aimed to assess whether the introduction of a tailored Analgesia Prescription Guideline would decrease the amount of unused opioid following discharge from cardiac surgery. Design Prospective, observational, before and after study. Setting Quaternary care university hospital. Participants A total of 191 participants who underwent cardiac surgery requiring midline sternotomy and cardiopulmonary bypass. There were 99 participants in the before cohort (prior to introduction of the Analgesia Prescription Guideline), and 92 participants in the after cohort (after introduction of the Analgesia Prescription Guideline). Interventions Using prospectively collected observational data on participant opioid consumption in the before cohort, a tailored Analgesia Prescription Guideline was developed. This guideline then was introduced to all opioid-prescribing providers in the cardiothoracic surgery department. Prospective data then were collected in the after cohort of participants. Opioid prescription practices and opioid consumption between the two groups then were compared. Measurements and Main Results Opioid prescriptions were given to 62/99 participants (63%) in the before cohort, and 48/92 (52%) in the after cohort (rate difference 0.1, CI 95% -0.26, 0.046). In the before cohort, the mean (± standard deviation) number of opioid tablets prescribed, used, and leftover was 26 (±10), 11 (±10), and 15 (±12), respectively. In the after cohort, the mean number of opioid tablets prescribed, used, and leftover was 18 (mean difference -8, CI 95% -12, -5), 10 (mean difference -1, CI 95% -5, 3), and 8 (mean difference -7, CI 95% -11, -3), respectively. There were 110/191 (58%) participants using no opioids following discharge, and 10/191 (5%) still using opioids two weeks after discharge. There were no differences between groups with regard to demographics, opioid-related side effects, pain scores, satisfaction, opioid storage. and disposal practices. Conclusions The development and implementation of a tailored Analgesia Prescription Guideline decreased the amount of opioids prescribed after cardiac surgery and resulted in lower numbers of unused leftover opioid tablets in the community. Patient comfort and satisfaction scores remained high.

In this paper, the strategy of Intermediate Isolation System (IIS) is proposed for the vertical extension of an aggregate of masonry buildings located in Pozzuoli, south Italy. The effectiveness of IIS working as a nonconventional Tuned Mass Damper (TMD) for the existing construction is assessed in terms of reduction of seismic demand and damage in the masonry structure undergoing inelastic deformation under seismic input. For this aim, a general step-by-step procedure is first defined and then applied to the case study building. In particular, the characterization of dynamic behaviour and seismic capacity of the building aggregate is first addressed through modal and push over analyses. Elastic parametric analyses are then carried out on lumped mass models to derive the so-called nonconventional TMD design spectrum and to define the design configurations of the isolated vertical addition that minimize the global seismic response of the overall structure. The effectiveness of the retrofit solutions is evaluated and compared to the AS-IS structure through nonlinear time history analyses; structural performance indexes accounting for both peak response and accumulated damage are defined and utilised for this purpose. The results of the time history analyses show that when the masonry structure rests in the elastic field, the displacements in the existing structure decrease, particularly for IIS solutions characterised by low-medium periods. When the masonry exhibits nonlinear behaviour, the effectiveness in terms of displacement reduction is not as significant as in the elastic range but the accumulated damage in the masonry structure is always mitigated.

Background: Cutaneous warts are an extremely common problem, whose eradication can be challenging. Topical PDT involves applying a porphyrin precursor, 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) to the affected area. ALA-PDT has been well documented to be successful in the treatment of recalcitrant warts. PDT has a limited role in the treatment of thicker lesions because the photosensitizer does not penetrate keratotic lesions well, though this is vehicle dependent. Objective: The aim of this study was to evaluate the efficacy and safety of curettage + microneedling + ALA-PDT for the treatment of resistant acral warts. We hypothesized that microneedling may increase the efficacy of PDT, providing a channel to deliver the ALA to deeper areas of warts. Methods: Our study was carried out between November 2017 and July 2018. Eligible participants had one or more resistant plantar or palmar warts. Thirteen patients were recruited. They underwent a thorough curettage, followed by the application of 5-ALA 10% cream on the wart, and by microneedling. Later, the pricked skin was covered for three hours by an occlusive polyurethane dressing, and finally irradiated with a red-light source. Patients performed one session every three weeks for a total of three cycles. Results:After 3 treatments of curettage + microneedling + ALA-PDT, 11 patients (84.6%) showed complete remission (defined as complete disappearance of their warts). One patient (7.7%) showed partial remission (defined as greater than 50% decrease in the wart area) after 3 sessions; this patient needed other 2 sessions to achieve complete remission. The mean follow-up period after healing was 4.3 months. Adverse effects were recorded. Conclusion: We have demonstrated, for the first time to our knowledge, that the combination of curettage + microneedling + topical ALA-PDT may offer an effective and safe alternative for the treatment of acral resistant warts, even when PDT alone has already been insufficient.

Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain.The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery.Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years.Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04).After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).

Left-sided staphylococcal, streptococcal, and enterococcal infective endocarditis (IE) is associated with poor clinical outcomes. Our primary aim is to compare clinical outcomes of staphylococcal, streptococcal, and enterococcal IE patients who undergo valve replacement surgery and outcomes of patients who are treated solely with antibiotics.All patients were treated medically or surgically for left-sided staphylococcal, streptococcal, or enterococcal IE at our institution from 1998 to 2014 and were retrospectively studied. The primary outcome of interest was 30-day and 1-year mortality, and secondary outcomes included posttreatment septic shock, embolic events, stroke, and end-stage renal disease at 30 days. Inverse probability treatment weights, derived from propensity scores, were used to balance the medical and surgical cohorts across clinical risk factors, The Society of Thoracic Surgeon scores, and pathogens. Outcomes were compared comprehensively and in a staphylococcal-only subanalysis.Study population consisted of 245 surgical patients and 164 medical patients. Mortality at 30 days was higher in the medical cohort, both in aggregate and for staphylococcal only (all, 7% vs 16%, P.001; staphylococcal only, 7% vs 22%, P.001). Surgical patients had a higher incidence of septic shock and renal dysfunction; however, stroke and embolic events at 30 days were not different between cohorts. Cox survival analysis demonstrated that surgical treatment provided a 1-year survival benefit, with a hazard ratio of 0.48 (95% confidence interval, 0.36 to 0.64) that was robust regardless of pathogen.Compared with medical management, valve replacement surgery in patients with left-sided staphylococcal, streptococcal, or enterococcal IE appears to confer a survival advantage at 30 days and 1 year.

The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days.Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life.By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01).Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Urban densification represents one of the biggest universal challenges of contemporary cities: the increase of urban population requires new spaces to accommodate the growing demand for housing, working and tertiary activities. However, the land available for new constructions in highly urbanized areas is very limited. In this framework, the vertical extension of existing buildings is the most sustainable strategy and fascinating. Masonry structures , constituting a major part of the built stock in the historical city centres of several European countries, are particularly suitable for vertical addition of extra-floors, since they generally exhibit an adequate overstrength for bearing an increase of gravity loads, although seismic retrofit interventions are usually required. In this paper, starting from the case study of the historical town of Pozzuoli, in South Italy, an “antifragile” approach, based on the intermediate isolation system, is suggested to rise the height of the masonry building , while reducing the global seismic demand. For this aim, in this paper are analysed the architectural-functional and structural design issues related to a vast-scale application of vertical additions isolated on the top of existing structures. Further, the feasibility and effectiveness of the strategy are discussed, and benefits in terms of seismic performance are evaluated.