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The interventional treatment of coronary artery disease (CAD) has undergone significant improvements thanks to technological innovations. Nowadays, percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is the standard of care for the treatment of CAD. Nevertheless, the non-negligible incidence of in-stent restenosis (ISR) and suboptimal results in various anatomical settings has led to the development of drug-coated balloons (DCBs). DCBs are catheter-based balloons whose surface is coated with an anti-proliferative drug (mainly Paclitaxel or Sirolimus) loaded onto the balloon surface with different technologies and dose concentrations. In the beginning, these devices were used for the treatment of ISR showing an excellent efficacy profile in the inhibition of intimal hyperplasia. Subsequently, several studies evaluated their use in other angiographical and clinical contexts such as de novo lesions, small vessel disease, diffuse coronary disease, bifurcation lesions, acute coronary syndromes, high-bleeding risk and diabetic patients. This comprehensive review aims to describe the main DCB platforms on the market, their fields of application with the main supporting studies and their future perspectives. [ABSTRACT FROM AUTHOR]

Determinants of health are important drivers of health states, yet there is little work examining their role in the relationship between HIV stigma and health. This study uses moderation analysis to examine how determinants of health affect the relationship between enacted, internalized, and anticipated stigma and mental health. Quantitative data was collected on 337 participants in Ontario, Canada at baseline (t1) between August 2018 and September 2019 and at follow-up (t2) between February 2021 and October 2021. Separate moderation models were created with each determinant of health (age, gender, sexual orientation, ethnicity, geographic region, education, employment, and basic needs) acting as the moderator between types of stigma at t1 and mental health at t2. Age was a significant moderator for the relationship between internalized and enacted stigma at t1 and mental health at t2. Region was a moderator for enacted and anticipated stigma and mental health. Sexual orientation was a moderator for anticipated stigma and mental health. Lastly, having basic needs was a moderator for enacted and anticipated stigma and mental health. Our findings suggest that intervention strategies may be more effective by incorporating supports for these determinants of health in addition to stigma reduction to improve mental health. [ABSTRACT FROM AUTHOR]

Granular hydrogels have emerged as a promising class of biomaterials in medical research, enabling independent control of matrix stiffness within a porous biomaterial. Such microgel packings comprise interconnected pores and high surface‐to‐volume ratios. These features facilitate cell viability and nutrient diffusion, which are critical in enabling tissue regeneration. Despite the current interest in granular hydrogels for tissue engineering applications, only a few in vitro platforms are used to investigate cell interactions, limiting their design, and translation. In this study, microfluidic platforms able to reproducibly confine and immobilize microgels without the need for secondary cross‐linking are developed. Protocols are established for the generation of human bone marrow‐derived mesenchymal stem/stromal cells (hBM‐MSC)‐infiltrated microporous substrates and early‐time responses of cells to their environment are studied. Further, a tissue invasion assay is established, where cells infiltrate granular materials at different rates depending on growth factor presence or material properties. This platform is compatible with a range of different granular materials, and it is envisioned to have significant utility as a pre‐clinical tool for the rational design of materials for tissue healing applications. [ABSTRACT FROM AUTHOR]

The SoccerNet 2023 challenges were the third annual video understanding challenges organized by the SoccerNet team. For this third edition, the challenges were composed of seven vision-based tasks split into three main themes. The first theme, broadcast video understanding, is composed of three high-level tasks related to describing events occurring in the video broadcasts: (1) action spotting, focusing on retrieving all timestamps related to global actions in soccer, (2) ball action spotting, focusing on retrieving all timestamps related to the soccer ball change of state, and (3) dense video captioning, focusing on describing the broadcast with natural language and anchored timestamps. The second theme, field understanding, relates to the single task of (4) camera calibration, focusing on retrieving the intrinsic and extrinsic camera parameters from images. The third and last theme, player understanding, is composed of three low-level tasks related to extracting information about the players: (5) re-identification, focusing on retrieving the same players across multiple views, (6) multiple object tracking, focusing on tracking players and the ball through unedited video streams, and (7) jersey number recognition, focusing on recognizing the jersey number of players from tracklets. Compared to the previous editions of the SoccerNet challenges, tasks (2-3-7) are novel, including new annotations and data, task (4) was enhanced with more data and annotations, and task (6) now focuses on end-to-end approaches. Our report indicates performance trends across tasks: (1) Action spotting is nearing saturation, while (2) ball action spotting improved significantly with advanced end-to-end models. (3) Dense video captioning also saw substantial enhancements aligned with Large Language Models advancements. (4) Camera calibration, redefined end-to-end, demonstrated a significant performance boost. In contrast, (5) player re-identification showed only minor improvements, reflecting decreasing interest. The new (6) multiple object tracking task exhibited notable advances, underscoring the maturity of current techniques. (7) Jersey number recognition received the most focus, achieving impressive results. More information on the tasks, challenges, and leaderboards are available on https://www.soccer-net.org. Baselines and development kits can be found on https://github.com/SoccerNet. [ABSTRACT FROM AUTHOR]

Introduction: Children and adolescents receiving inpatient psychiatric services have disproportionately high levels of exposure to trauma and adversity. The National Child Traumatic Stress Network Trauma-Informed Organizational Assessment (TIOA) is a comprehensive tool intended to guide implementation of trauma-informed care, but it has not yet been applied in inpatient settings. Aims: The purpose of this quality improvement project was to describe trauma-informed care in inpatient child/adolescent psychiatry with the TIOA, examine relatedness among trauma-informed care domains, and explore barriers or facilitators to applying trauma-informed care. Methods: This quality improvement project used mixed methods. We conducted a web-based survey in Summer 2022 with staff members (clinical and administrative) at two inpatient child/adolescent psychiatric units in California to assess trauma-informed care practices with the TIOA (87 items). Qualitative follow-up interviews were offered to interested participants. A correlation matrix and cluster analyses were used to examine relationships among TIOA domains; qualitative data were analyzed thematically. Results: There were 69 survey respondents and seven qualitative interviews. TIOA domain scores ranged from a low of 2.3 to a high of 3.2, indicating that practices were occurring only "rarely" to "sometimes." There were two major themes identified from qualitive interviews: (a) barriers to trauma-informed care in an inpatient context that can be resource-constrained or coercive; and (b) discovering strategies to provide trauma-informed care despite structural barriers. Conclusion: Organizational interventions targeting any domains of trauma-informed care are needed in inpatient settings given limited uptake of trauma-informed care. [ABSTRACT FROM AUTHOR]

Background: UVA‐1 phototherapy was first used to treat atopic dermatitis and afterwards to several other skin diseases. The contribution of UVA‐1 in human photocarcinogenesis, skin photoaging, immune suppression, and hyperpigmentation is now well established. The actual contribution of UVA‐1 radiation to the development of malignant melanoma (MM) in humans cannot be excluded. Purpose: The aim of the study is to evaluate the risk of developing skin cancers (non‐melanoma skin cancers (NMSCs) and MM) in patients treated with UVA‐1 phototherapy with a 5‐year dermatological follow‐up. Methods: We conducted a retrospective cohort study with 31 patients with morphea and atopic dermatitis treated with medium dose UVA‐1 phototherapy (34 J/cm2). All enrolled patients underwent an oncologic prevention visit annually with a 5‐year follow‐up with clinical evaluation of the entire skin surface. Results: During the 5‐year follow‐up, we recorded a case of basal cell carcinoma (BCC) in the cervical region and one case of MM on the back (pT1a). In both cases, the patients were female and affected by morphea. The Glogau 3 group is prevalent (42%), which is consistent with moderate to severe aging; the data appear to be compatible with the age. Conclusions: This study attests that medium‐dose UVA‐1 phototherapy does not increase the risk of developing skin tumors and that UVA‐1 phototherapy is not a worsening factor of facial photoaging. The main limitation of the study is the small sample size, avoiding to obtain statistically significant values. It was not possible to analyze individually the actual daily sun exposure during the 5‐year observation period and to correlate it in terms of time and tumor development. Further studies with large sample sizes will be needed to confirm our data. Our study reaffirms how the dermatological examination performed annually is essential in the follow‐up of patients undergoing this type of therapy. [ABSTRACT FROM AUTHOR]

Patients with atopic dermatitis (AD) experience decreased quality of life (QoL). Here we describe the relationship between severity and QoL-related scores in patients with moderate-to-severe AD treated with dupilumab. Patients and Methods: This was a real-life, retrospective, and observational study involving patients with AD treated with dupilumab. Treatment effectiveness was evaluated based on the changes in the eczema area and severity index (EASI), sleep quality numerical rating scale, and pruritus numerical rating scale (PNRS), as well as the dermatology life quality index (DLQI). The relationship between each of them was analyzed. After the first data collection at baseline, patients were re-evaluated at 3 subsequent follow-ups (4, 8, and 12 months). Results: A total of 52 patients were enrolled in the study. At 4 months, the change in DLQI is more correlated with PNRSs (r = 0.643, P < 0.001) than the other scores considered. At 8 months, however, the change in DLQIs correlates similarly both with PNRSs (r = 0.644, P < 0.001) and with the change in EASIs (r = 0.633, P < 0.001). At 12 months of treatments, however, the trend reverses and the correlation with EASIs becomes higher (r = 0.735, P < 0.001) than PNRSs (r = 0.0.659, P < 0.001). Conclusions: The results of our study show that the reduction in the impact on QoL for AD patients in the first months of therapy with dupilumab correlates more with the control of pruritus than with the disappearance of skin lesions. [ABSTRACT FROM AUTHOR]

Background: Aortic valve stenosis (AS) is the most common valvular heart disease worldwide. When timely intervention is performed, aortic valve replacement can improve patients' quality and duration of life. Load‐independent left ventricular (LV) functional assessments, such as myocardial work indices (MWIs) and LV diastolic function parameters, could help clinicians decide on the optimal timing of intervention. Aims: To evaluate the reliability of MWI in AS patients and the changes in MWI and LV diastolic function after transcatheter aortic valve replacement (TAVR). Methods: We enrolled 53 consecutive patients with severe AS undergoing TAVR admitted between March 2021 and November 2021. MWIs and LV diastolic function were assessed before and after TAVR for each patient. Results: All MWIs and LV diastolic function indices improved after TAVR. The degree of MWIs improvement was higher in patients with lower prior‐TAVR MWI values, while the more severe the impairment of diastolic function, the greater the post‐TAVR benefit. Conclusion: The introduction of myocardial work parameters into the routine assessment of patients with AS could improve our understanding of cardiac performance and aid in identifying the optimal timing for surgical or percutaneous treatment. [ABSTRACT FROM AUTHOR]

Levels of HIV stigma remain high, however there is a limited understanding around how different types of stigma interact to impact health. This study uses data from two time points to examine how enacted and internalized stigma lead to worse health through anticipated stigma as a mediator. We recruited 341 participants in Ontario, Canada to complete the HIV Stigma Index survey at baseline (t1) from September 2018 to August 2019 and follow up (t2) approximately two years later. Mediation models were created with enacted and internalized stigma at t1 as the antecedents, anticipated stigma at t2 as the mediator, and physical health, mental health, and overall health at t2 as the outcomes. Only the model with internalized stigma (t1) as the antecedent had anticipated stigma (t2) as a significant mediator contributing to both decreased mental and overall health. This highlights the need to address internalized stigma and the potential for anticipated stigma interventions to be effective at improving the health and wellbeing of people living with HIV. [ABSTRACT FROM AUTHOR]

Super-high (×400) magnification dermoscopy (D400) is a new non-invasive imaging technique that has been shown to add information for the differential diagnosis of melanocytic lesions in a pilot study. Our study aimed to confirm if D400 can add details for the discrimination of clinically atypical nevus and melanoma. This is a retrospective observational, multicentric study enrolling patients who received ×20 (D20) and ×400 (D400) magnification dermoscopic examinations of pigmented skin lesions. Dermoscopic images were retrospectively evaluated by three observers for the presence/absence of nine D20 and twenty D400 dermoscopic features defined in the previous pilot study. Univariate and multivariate analyses were carried out to find predictors of benign and malignant behaviors. At D20, an atypical pigment network, blue-whitish veil, atypical vascular pattern, regression, and homogenous pattern were more frequent in melanoma than in nevi (p < 0.001). At D400, melanoma showed more frequently than benign lesions, melanocytes with an irregular arrangement and irregular in shape and size (p < 0.001). A network with edged papillae was more frequent in benign lesions than melanomas (p < 0.001). Our study confirms that D400 can identify melanocytes with an irregular arrangement, and irregularities in shape and size in melanomas, adding information to the conventional D20 examination. [ABSTRACT FROM AUTHOR]

Atrioventricular reentrant tachycardia (AVRT) is the most common form of supraventricular tachycardia in newborns. AVRT is sometimes refractory to conventional antiarrhythmic therapy. We describe our experience about the use of the triple combination of flecainide + propranolol + amiodarone as third-line regimen for refractory and recurrent AVRT in newborns. We considered a series of 14 patients who had failed both first-line and second-line therapy and were treated using the combination of flecainide + propranolol + amiodarone. Transoesophageal electrophysiologic study (TES) was performed to test the effectiveness of medical therapy during hospitalization and to try to reduce the amount of therapy, after amiodarone wash-out, before 1 year of age. TES was repeated at 1 year of age to test the spontaneous resolution of the arrhythmia after treatment discontinuation. Rhythm control was achieved in all 14 patients. At a mean age of 9.3 ± 2 months, AVRT was not inducible by TES in 11/12 amiodarone-free patients. At a mean age of 14.1 ± 3 months, AVRT was still inducible in 7/12 patients after interrupting the entire antiarrhythmic therapy (58.3%). Triple combination was effective as third-line option to suppress AVRT refractory to single and double antiarrhythmic therapy, with no significant adverse events. Our experience suggests that triple therapy could be maintained for a short-term treatment, discontinuing amiodarone before 1 year of age to avoid long-term side effects. Newborns who needed triple therapy appear to have a lower chance of accessory pathway disappearance at 1 year of age. TES could be useful for risk stratification of recurrences at the time of drug discontinuation in infants considered to be at higher risk of recurrent AVRT. [ABSTRACT FROM AUTHOR]

L-Arginine (L-Arg), is a semi-essential amino acid involved in the formation of nitric oxide. The functional relevance of L-Arg in diabetes mellitus has been evaluated both in animal models and in human subjects. In the literature there are several lines of evidence indicating that L-Arg has beneficial effects in diabetes and numerous studies advocate its administration to attenuate glucose intolerance in diabetic patients. Here we present a comprehensive overview of the main studies exploring the effects of L-Arg in diabetes, including preclinical and clinical reports on this topic. [ABSTRACT FROM AUTHOR]

Carotid artery stenting (CAS) is usually performed through a femoral vascular access using 6–9 Fr guiding catheters. We investigated whether a systematic distal radial approach using 5 Fr guiding sheaths was a safe and effective alternative to transfemoral approach for CAS. From July 2020 to October 2022, two operators at our center systematically performed CAS using a 5 Fr distal radial approach in consecutive patients. The main endpoints of the study were procedural success via distal radial and via proximal or distal radial access. The learning curve was evaluated by comparing the first half of patients versus the second half of patients enrolled. Procedural data and 30-day clinical outcomes were collected. Fifty-one patients were prospectively enrolled. CAS was effectively performed via distal radial access in 45 patients (88%). Overall radial artery success was 92%. Distal radial CAS was successfully performed in 20 out of the first 25 patients enrolled (80%), and in 25 of the last 26 patients enrolled (96%; p = 0.07). Significantly less contrast was administered in the last 26 patients compared to the first 25 enrolled (110 (70, 140) mL vs. 120 (107, 150) mL; p = 0.045). Radial artery occlusion was reported in 1 patient (2%). Only 1 minor stroke (2%) was reported in-hospital and at 30-day follow-up. In conclusion, distal radial CAS using 5 Fr catheters was a safe procedure with a high success rate. The procedure had a relatively short learning curve in operators familiar with transfemoral CAS. [ABSTRACT FROM AUTHOR]

In this paper, we propose an innovative Federated Learning-inspired evolutionary framework. Its main novelty is that this is the first time that an Evolutionary Algorithm is employed on its own to directly perform Federated Learning activity. A further novelty resides in the fact that, differently from the other Federated Learning frameworks in the literature, ours can efficiently deal at the same time with two relevant issues in Machine Learning, i.e., data privacy and interpretability of the solutions. Our framework consists of a master/slave approach in which each slave contains local data, protecting sensible private data, and exploits an evolutionary algorithm to generate prediction models. The master shares through the slaves the locally learned models that emerge on each slave. Sharing these local models results in global models. Being that data privacy and interpretability are very significant in the medical domain, the algorithm is tested to forecast future glucose values for diabetic patients by exploiting a Grammatical Evolution algorithm. The effectiveness of this knowledge-sharing process is assessed experimentally by comparing the proposed framework with another where no exchange of local models occurs. The results show that the performance of the proposed approach is better and demonstrate the validity of its sharing process for the emergence of local models for personal diabetes management, usable as efficient global models. When further subjects not involved in the learning process are considered, the models discovered by our framework show higher generalization capability than those achieved without knowledge sharing: the improvement provided by knowledge sharing is equal to about 3.03% for precision, 1.56% for recall, 3.17% for F 1 , and 1.56% for accuracy. Moreover, statistical analysis reveals the statistical superiority of model exchange with respect to the case of no exchange taking place. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Ischemia with nonobstructive coronary arteries (INOCA) is a prevailing finding in patients with angina. However, the main factors underlying the risk of being rehospitalized for chest pain in patients with INOCA remain mostly unknown. RESEARCH DESIGN AND METHODS: We evaluated INOCA patients referred to the "Casa di Cura Montevergine" in Mercogliano (Avellino), Italy, from January 2016 to January 2021 for percutaneous coronary intervention (PCI). In these subjects, we assessed the impact of the stress hyperglycemia ratio (SHR), defined as the ratio of mmol/L blood glucose and % HbA1c, on the risk of rehospitalization for chest pain. RESULTS: A total of 2,874 patients with INOCA successfully completed the study. At the 1-year follow-up, the risk of rehospitalization for chest pain was significantly higher (P < 0.001) in INOCA patients with SHR >1 compared to patients with SHR ≤1. These findings were confirmed by multivariable analyses (adjusting for potential confounders, including age, BMI, blood pressure, heart rate, chronic kidney disease, and cholesterol), propensity score matching, and inverse probability of treatment weighting. CONCLUSIONS: Our data indicate, to our knowledge for the first time, that SHR on hospital admission significantly and independently increases the risk of rehospitalization for chest pain in INOCA patients. [ABSTRACT FROM AUTHOR]

Background: Many community-based HIV research studies incorporate principles of greater involvement and meaningful engagement of people living with HIV (GIPA/MEPA) by training people with HIV as peer researchers. Unfortunately, there are still some aspects of research (e.g., quantitative data analysis and interpretation) where many projects fall short in realizing GIPA/MEPA principles. To address these gaps, we developed an eight-week training course that aimed to build the capacity of peer researchers around the understanding and interpretation of quantitative data and incorporating lived experience to increase the impact of the knowledge transfer and exchange phase of a study. Methods: Peer researchers (n = 8) participated from British Columbia, Alberta, and Ontario and lessons learned from the training were implemented throughout the dissemination of research findings from the People Living with HIV Stigma Index study. This paper presents the curriculum and main training components, course evaluation results, and challenges and lessons learned. The manuscript was created in collaboration with and includes the perspectives of both the peer researchers involved in the training, as well the course facilitators. Results: Throughout the course, peer researchers' self-assessed knowledge and understanding of quantitative research and data storytelling improved and, through interactive activities and practice, they gained the confidence to deliver a full research presentation. This improved their understanding of research findings, which was beneficial for discussing results with community partners and study participants. The peer researchers also agreed that learning about integrating lived experience with quantitative data has helped them to make research findings more relatable and convey key messages in a more meaningful way. Conclusions: Our training curriculum provides a template for research teams to build capacity in areas of research where peer researchers and community members are less often engaged. In doing so, we continue to uphold the principles of GIPA/MEPA and enhance the translation of research knowledge in communities most greatly affected. Plain English Summary: Engaging patient groups or community members is commonplace in HIV research where people living with HIV are trained as peer researchers. There are still however some gaps where community members are less engaged, especially in quantitative data analysis. This presents a barrier preventing them from being meaningfully engaged in research about them. To build capacity in these areas, we designed an eight-week online course that taught peer researchers about quantitative data analysis and interpretation with a focus on concepts that would be important for talking about key messages from research findings. This was used to enhance the knowledge translation and dissemination initiatives for the People Living with HIV Stigma Index study—a survey tool containing quantitative measures examining stigma and related health factors. Peer researchers agreed that their knowledge and understanding of the key quantitative data concepts improved significantly throughout the course. This increased understanding helped them discuss quantitative data with community members and study participants, which was important to ensure that research findings reach the affected communities. Peer researchers also agreed that incorporating their new data analysis knowledge with existing lived experience helped them to make findings more relatable and understandable which is critical for translating knowledge to other researchers and policy makers. Overall, our training curriculum gave peer researchers the confidence to talk about quantitative data and improve their capacity to disseminate research. This work also provides guidelines for training peer researchers and ensuring that they are meaningfully engaged in research studies they are a part of. [ABSTRACT FROM AUTHOR]

Diabetes is a heterogeneous group of diseases that share a common trait of elevated blood glucose levels. Insulin lowers this level by promoting glucose utilization, thus avoiding short- and long-term organ damage due to the elevated blood glucose level. A patient with diabetes uses an insulin pump to dose insulin. The pump uses a controller to compute and dose the correct amount of insulin to keep blood glucose levels in a safe range. Insulin-pump controller development is an ongoing process aiming at fully closed-loop control. Controllers entering the market must be evaluated for safety. We propose an evaluation method that exploits an FDA-approved diabetic patient simulator. The method evaluates a Cartesian product of individual insulin-pump parameters with a fine degree of granularity. As this is a computationally intensive task, the simulator executes on a distributed cluster. We identify safe and risky combinations of insulin-pump parameter settings by applying the binomial model and decision tree to this product. As a result, we obtain a tool for insulin-pump settings and controller safety assessment. In this paper, we demonstrate the tool with the Low-Glucose Suspend and OpenAPS controllers. For average ± standard deviation, LGS and OpenAPS exhibited 1.7 ± 0.6% and 3.2 ± 1.8% of local extrema (i.e., good insulin-pump settings) out of all the entire Cartesian products, respectively. A continuous region around the best-discovered settings (i.e., the global extremum) of the insulin-pump settings spread across 4.0 ± 1.1% and 4.1 ± 1.3% of the Cartesian products, respectively. [ABSTRACT FROM AUTHOR]

In particular, the tinnitus symptoms were still present after I T. pallidum i clearing and resolved only after resolution of platelets' alteration.[[3]] In conclusion, physicians should be aware of such a rare presentation of secondary syphilis with mucocutaneous and sensorineural findings. A case of polycythemia vera accompaning hearing loss, tinnitus and dizziness. [Extracted from the article]

This article, published in Dermatology Reports, discusses a case study of a 55-year-old male with a recurrent infiltrative basal cell carcinoma of the right nasal ala. The patient had previously undergone incomplete excision, resulting in a contracted ala with columellar deviation and nostril asymmetry. After three stages of Mohs surgery, a full-thickness defect was present. The authors performed a Spear flap surgical revision, which involved incising the flap, elevating it, and suturing it to the mucosal aspect of the defect. However, after two months, an unnatural lateral alar base insertion occurred, leading to a surgical revision through an alar rotation flap. The outcome of the procedure was successful, with corrections maintained after two years of follow-up. The article also discusses the potential pitfalls and techniques for achieving satisfactory results in similar cases. [Extracted from the article]

Soccer videos are a rich playground for computer vision, involving many elements, such as players, lines, and specific objects. Hence, to capture the richness of this sport and allow for fine automated analyses, we release SoccerNet-v3, a major extension of the SoccerNet dataset, providing a wide variety of spatial annotations and cross-view correspondences. SoccerNet's broadcast videos contain replays of important actions, allowing us to retrieve a same action from different viewpoints. We annotate those live and replay action frames showing same moments with exhaustive local information. Specifically, we label lines, goal parts, players, referees, teams, salient objects, jersey numbers, and we establish player correspondences between the views. This yields 1,324,732 annotations on 33,986 soccer images, making SoccerNet-v3 the largest dataset for multi-view soccer analysis. Derived tasks may benefit from these annotations, like camera calibration, player localization, team discrimination and multi-view re-identification, which can further sustain practical applications in augmented reality and soccer analytics. Finally, we provide Python codes to easily download our data and access our annotations. Measurement(s) Localization of soccer features Technology Type(s) Manual annotations [ABSTRACT FROM AUTHOR]

The point at which clinical development programs transition from early phase to pivotal trials is a critical milestone. Substantial uncertainty about the outcome of pivotal trials may remain even after seeing positive early phase data, and companies may need to make difficult prioritization decisions for their portfolio. The probability of success (PoS) of a program, a single number expressed as a percentage reflecting the multitude of risks that may influence the final program outcome, is a key decision‐making tool. Despite its importance, companies often rely on crude industry benchmarks that may be "adjusted" by experts based on undocumented criteria and which are typically misaligned with the definition of success used to drive commercial forecasts, leading to overly optimistic expected net present value calculations. We developed a new framework to assess the PoS of a program before pivotal trials begin. Our definition of success encompasses the successful outcome of pivotal trials, regulatory approval and meeting the requirements for market access as outlined in the target product profile. The proposed approach is organized in four steps and uses an innovative Bayesian approach to synthesize all relevant evidence. The new PoS framework is systematic and transparent. It will help organizations to make more informed decisions. In this paper, we outline the rationale and elaborate on the structure of the proposed framework, provide examples, and discuss the benefits and challenges associated with its adoption. [ABSTRACT FROM AUTHOR]

There are several steps to confirming the safety and efficacy of a new medicine. A sequence of trials, each with its own objectives, is usually required. Quantitative risk metrics can be useful for informing decisions about whether a medicine should transition from one stage of development to the next. To obtain an estimate of the probability of regulatory approval, pharmaceutical companies may start with industry‐wide success rates and then apply to these subjective adjustments to reflect program‐specific information. However, this approach lacks transparency and fails to make full use of data from previous clinical trials. We describe a quantitative Bayesian approach for calculating the probability of success (PoS) at the end of phase II which incorporates internal clinical data from one or more phase IIb studies, industry‐wide success rates, and expert opinion or external data if needed. Using an example, we illustrate how PoS can be calculated accounting for differences between the phase II data and future phase III trials, and discuss how the methods can be extended to accommodate accelerated drug development pathways. [ABSTRACT FROM AUTHOR]

Performing transcatheter aortic valve implantation with high implantation technique, i.e. with an aorto-ventricular ratio > 60/40, reduces the need of permanent pacemaker implantation. Valve calcification and prosthesis oversizing are predictors of permanent pacemaker implantation, but there are no available data on their role when transcatheter aortic valve implantation is performed with an aorto-ventricular ratio > 60/40. The aim of this study was to evaluate the effect of leaflets/annulus calcification and prosthesis oversizing on the incidence of permanent pacemaker implantation after transcatheter aortic valve implantation with a high implantation technique. Transcatheter aortic valve implantation was performed in 48 patients implanting a balloon-expandable transcatheter heart valve with an aorto-ventricular ratio > 60/40. Calcium burden was assessed by preprocedural multidetector computed tomography. An invasive electrophysiological study was performed before and after transcatheter aortic valve implantation. Five patients (10.4%) needed permanent pacemaker implantation. At univariate analysis, baseline right bundle branch block and postprocedural PR, QRS and His-ventricular interval elongation significantly predicted permanent pacemaker implantation (p < 0.05). Receiver-operating characteristic curve analysis showed a correlation between transcatheter heart valve oversizing and permanent pacemaker implantation need, with the best cut-off being 17% (AUC = 0.72, p = 0.033). Linear regression analysis demonstrated that QRS complex elongation was related to total, left and non-coronary leaflet calcification (p < 0.05). This study demonstrates that, when transcatheter aortic valve implantation is performed using a balloon-expandable transcatheter heart valve deployed with an aorto-ventricular ratio > 60/40, the presence of leaflets/annulus calcification or the need to oversize the prosthesis correlate with the occurrence of pathological cardiac conduction delays. [ABSTRACT FROM AUTHOR]

This article, published in Dermatology Reports, discusses a case of a 91-year-old woman with a recurrent cutaneous squamous cell carcinoma (CSCC) on her lower eyelid and cheek. The article describes the surgical procedure used to reconstruct the defects, including Mohs Micrographic Surgery (MMS) with frozen sections and the use of flaps for eyelid and cheek reconstruction. The outcome of the surgery was successful, with no complications and the correction of the ectropion maintained two years after the procedure. The article highlights the importance of MMS in treating CSCC and discusses the specific surgical techniques used in this case. [Extracted from the article]

Objective To keep patients healthy and safe during the pandemic, payers and the federal government temporarily relaxed restrictions, expanded the eligible provider list for providing telehealth services, and developed a reimbursement structure. Physical therapists were uniquely challenged during the pandemic, requiring a reassessment of techniques and strategies in order to best support patients. The purpose of this case report is to describe a musculoskeletal institution's experience with implementing telehealth physical therapy. Methods Previous telehealth experience enabled the infrastructure of a wide-scale adoption across institutions to respond to the COVID-19 pandemic. However, to fill in training gaps for Hospital for Special Surgery (HSS) outpatient physical therapists, HSS Rehabilitation developed a robust education and implementation program. This training was influenced by clinician and patient surveys as well as the development of a published HSS Rehabilitation telehealth guide. Prior to performing telehealth physical therapist visits, clinicians were required to complete all training material to ensure comfortability and confidence. Results The adoption of telehealth among clinicians was born out of necessaity; however, the speed with which HSS Rehabilitation pivoted was critical to avoid lapses in care. In a 4-week period after the New York City shelter in-place orders, 173 therapists were trained and performing virtual visits. HSS Rehabilitation determined telehealth physical therapy had quicker access to care, similar patient satisifaction, and increased geographical outreach compared with in-person care. Conclusion The transition to telehealth physical therapy included a multi-step process that provided clinician training, established protocols and guidelines, and obtained a better understanding of the patient experience. Telehealth physical therapy has shown early benefits such as improving patient access to care and better continuity of care for traveling patients. Even after the current public health emergency, there is a place for high-value telehealth physical therapy in caring for patients with musculoskeletal conditions. [ABSTRACT FROM AUTHOR]

A 55-year-old male presented with a recurrent infiltrative basal cell carcinoma of the right nasal ala. Previous incomplete excision was repaired with second intention healing resulting in a contracted ala with columellar deviation and nostril asymmetry. [...] [ABSTRACT FROM AUTHOR]

The expansion of coronavirus disease 2019 (COVID-19) prompted measures of disease containment by the Italian government with a national lockdown on March 9, 2020. The purpose of this study is to evaluate the rate of hospitalization and mode of in-hospital treatment of patients with chronic limb-threatening ischemia (CLTI) before and during lockdown in the Campania region of Italy. The study population includes all patients with CLTI hospitalized in Campania over a 10-week period: 5 weeks before and 5 weeks during lockdown (n = 453). Patients were treated medically and/or underwent urgent revascularization and/or major amputation of the lower extremities. Mean age was 69.2 ± 10.6 years and 27.6% of the patients were women. During hospitalization, 21.9% of patients were treated medically, 78.1% underwent revascularization, and 17.4% required amputations. In the weeks during the lockdown, a reduced rate of hospitalization for CLTI was observed compared with the weeks before lockdown (25 vs 74/100,000 inhabitants/year; incidence rate ratio: 0.34, 95% CI 0.32–0.37). This effect persisted to the end of the study period. An increased amputation rate in the weeks during lockdown was observed (29.3% vs 13.4%; p < 0.001). This study reports a reduced rate of CLTI-related hospitalization and an increased in-hospital amputation rate during lockdown in Campania. Ensuring appropriate treatment for patients with CLTI should be prioritized, even during disease containment measures due to the COVID-19 pandemic or other similar conditions. [ABSTRACT FROM AUTHOR]

Time-optimal control of robotic manipulators along specified paths is a well-known problem in robotics. It concerns the minimization of the trajectory-tracking time subject to a constrained path and actuator torque limits. Calculus of variations reveals that time-optimal control is of bang-bang type, meaning that at least one actuator is in saturation for every point on the path. Unfortunately, this rule is broken at singular points, where the enforcement of the maximal and/or minimal torque at the bounding actuator would cause the violation of the path constraint. At these particular points, and, sometimes, at critical ones too, the selection of the torques is cumbersome and may introduce jitters in the control references. In this paper, the time-optimal control is addressed in the phase plane with a genetic approach. Results of calculus of variations are ignored and bang-bang control is re-found for the most of the trajectory, while in the neighborhoods of singular points, torques are automatically selected in order to minimize the trajectory-tracking time. Compared to other techniques, the problem is solved directly, without intermediate steps requiring, for example, the explicit computation of the switching points and the management of torques at critical points. The algorithm is validated in simulation on a canonical 2R planar robot in order to ease the comparison with previous works. [ABSTRACT FROM AUTHOR]

The method of Semantic Background Subtraction (SBS), which combines semantic segmentation and background subtraction, has recently emerged for the task of segmenting moving objects in video sequences. While SBS has been shown to improve background subtraction, a major difficulty is that it combines two streams generated at different frame rates. This results in SBS operating at the slowest frame rate of the two streams, usually being the one of the semantic segmentation algorithm. We present a method, referred to as "Asynchronous Semantic Background Subtraction" (ASBS), able to combine a semantic segmentation algorithm with any background subtraction algorithm asynchronously. It achieves performances close to that of SBS while operating at the fastest possible frame rate, being the one of the background subtraction algorithm. Our method consists in analyzing the temporal evolution of pixel features to possibly replicate the decisions previously enforced by semantics when no semantic information is computed. We showcase ASBS with several background subtraction algorithms and also add a feedback mechanism that feeds the background model of the background subtraction algorithm to upgrade its updating strategy and, consequently, enhance the decision. Experiments show that we systematically improve the performance, even when the semantic stream has a much slower frame rate than the frame rate of the background subtraction algorithm. In addition, we establish that, with the help of ASBS, a real-time background subtraction algorithm, such as ViBe, stays real time and competes with some of the best non-real-time unsupervised background subtraction algorithms such as SuBSENSE. [ABSTRACT FROM AUTHOR]

The aim of this study is to assess the morbidity and mortality related to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colo-rectal carcinomatosis. A retrospective multi-institutional study from seven Italian Centers was performed. One hundred and seventy-two patients, submitted to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) to treat carcinomatosis of colorectal origin, were recorded. Postoperative morbidity was evaluated in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Post-operative mortality was evaluated as patients' death within 60 days from surgical procedures. Predictors of morbidity were evaluated with univariate and multivariate analyses. Post-operative morbidity occurred in 83 patients (48.3%): grades 1–2 in 29 cases (16.9%), and grades 3–4 in 54 (31.4%). Mortality occurred in four cases (2.3%). Number of anastomoses (OR 1.45; 95% CI 1.05–2.00; p = 0.024), number of blood transfusions (OR 1.31; 95% CI 1.11–1.54; p = 0.001) and chemotherapy regimen [Oxaliplatin (OX): OR 2.87; 95% CI 1.22–6.75; p = 0.015] remained, in multivariate analysis, in a statistically significant correlation with overall morbidity. The only variable that was proven to have statistically significant correlation with 3–4 morbidity was the number of blood transfusions (OR 1.25; 95% CI 1.07–1.46; p = 0.005). Morbidity and mortality do not preclude the use of CRS plus HIPEC in the treatment of peritoneal carcinomatosis of colorectal origin. [ABSTRACT FROM AUTHOR]

Background: A two‐incision technique, in association with inter‐muscular positioning of the subcutaneous defibrillator (S‐ICD), is now the most frequently adopted implantation approach in Europe. Ultrasound‐guided serratus anterior plane block (SAPB) has been proposed to provide anesthesia/analgesia during S‐ICD implantation. Objective: We performed a case‐control analysis in which a standardized SAPB approach was compared with the typical local anesthesia and sedation approach. Methods: Ninety‐one consecutive patients underwent implantation of an S‐ICD with the SAPB approach for anesthesia/analgesia at 10 centers. The control group consisted of 55 consecutive patients who underwent S‐ICD implantation with a standard local approach. Results: The mean procedure duration was 59 ± 15 minutes in the SAPB group and 76 ± 23 minutes in the control group (P <.001). No operative complications were reported in either group. During the procedure, 79 (87%) patients in the SAPB group and 25 (46%) patients in the control group (P <.001) remained awake. Lower values of pain intensity at the device pocket (P =.005) and the lateral tunneling site (P =.046) were reported in the SAPB group. The difference in static (P =.002) and dynamic (P =.007) pain intensity between the groups persisted at 1 hour, while no differences were observed 6 hours after the end of the procedure. Conclusions: SAPB is feasible and effective in providing anesthesia/analgesia during S‐ICD implantation. The procedures were successfully accomplished and no complications occurred in either group. However, SAPB was associated with lower pain levels, enabling the need for sedation to be reduced and more patients to remain awake. Moreover, it resulted in shorter procedure durations. [ABSTRACT FROM AUTHOR]

We propose tailored mucosectomy and haemorrhoidopexy (TM&H), a new surgical conservative treatment for grade III haemorrhoids with fibrous and redundant piles. TM&H is a valid conservative procedure in the treatment of grade III haemorrhoids avoiding external excisions. The IIIF piles were randomized versus FH or TM&H. All the procedures were performed using a tailored anaesthetic technique[4] that consisted of a levator ani nerve block and a Selvasekar anaesthesia[5] with submucosal infiltration of ropivacaine 5 mg/ml. [Extracted from the article]

Aims: Preliminary data on Sapien 3 valve (S3-THV) use for transcatheter aortic valve implantation have shown an increased permanent pacemaker implantation (PPMI) rate with respect to Sapien XT valve. Aim of this study was to investigate the role of S3-THV position in the left ventricular outflow tract (LVOT) on electrocardiographic changes suggestive of atrioventricular (ΔPR) and/or intraventricular (ΔQRS) conduction abnormalities and 30 days PPMI rate.Methods and results: Eighty-six consecutive patients treated with S3-THV were included in the study. All patients underwent clinical and electrocardiogram evaluation. Left ventricular outflow tract prosthesis depth was assessed by fluoroscopy and expressed quantitatively (mm) and as aorto-ventricular ratio (AVR). Eight patients (9.3%) needed PPMI at 30 days. A low AVR (≤60/40) predicted PPMI (OR = 6.09, 95% CI 1.19-31.01, P = 0.030) and resulted into higher PPMI rate, compared with higher AVR (30.0 vs. 6.6%, P = 0.017). For each millimetre increase in the LVOT prosthesis depth PPMI risk increased by 1.41 times (95% CI 1.06-1.87, P = 0.017). In patients with low AVR, ΔPR was higher than in those with higher AVR (33.4 ± 56.7 vs. 12.1 ± 19.4 ms, P = 0.021) and ΔPR was associated to LVOT prosthesis depth (β = 0.286, P = 0.009). Furthermore, ΔPR was associated with risk of PPMI (OR = 1.03, 95% CI 1.01-1.06, P = 0.024).Conclusions: A low AVR is associated to higher ΔPR and PPMI rates. The correlation between LVOT prosthesis depth with ΔPR and higher PPMI rate suggests the need of a careful S3-THV implantation. [ABSTRACT FROM AUTHOR]