Search

Background and Aims: Post-surgical biliary leaks (PSBL) are one of the most prevalent and significant adverse events emerging after liver or biliary tract surgeries. Endoscopic retrograde cholangiopancreatography (ERCP) alone or combined with another approach (Rendez Vous) as treatment of PSBL obtains optimal outcomes due to the possibility of modifying the resistances in the biliary tree. Methods: A retrospective double-center study was conducted in two tertiary centers. Consecutive patients who underwent at least one attempt of PSBL correction by ERCP or Rendez Vous procedure between January 2018 and August 2023 were included. The primary outcome was overall endoscopic clinical success. In contrast, the secondary outcomes were hospital stay exceeding five days and endoscopic clinical success with the first endoscopic procedure at the tertiary center. Both univariate and multivariate analyses were used to assess outcomes. Results: 65 patients were included. Patients with one or multiple) leaks had more possibility to achieve the endoscopic clinical success compared to those affected by the association of leaks and stricture (96% vs 67%, pvalue 0.005). Leaks occurring in the main biliary duct had less probability (67%) to achieve the overall endoscopic clinical success compared to those in the end-to-end anastomosis (90%), in the resection plane or biliary stump (96%) or first or secondary order biliary branches (100%, pvalue 0.038). A leak-bridging stent positioning had more probability of achieving the endoscopic clinical success than a not leak-bridging stent (91% vs 53%, pvalue 0.005). Conclusions: ERCP and Rendez Vous procedures are safe and effective for treating PSBL, regardless of the type of preceding surgery, even if technical or clinical success was not achieved on the first attempt. A stent should be placed, if feasible, leak-bridging to enhance treatment efficacy. Graphical abstract:

Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia.

•The establishment of a clinical network led to significant and lasting advancements in the treatment outcomes of APL over a span of 15 years.•The overall survival rate for low-/intermediate-risk patients was 90%, similar to that reported in trials conducted in high-income countries.

Most patients with metastatic cancer eventually develop resistance to systemic therapy, with some having limited disease progression (ie, oligoprogression). We aimed to assess whether stereotactic body radiotherapy (SBRT) targeting oligoprogressive sites could improve patient outcomes.

Physicians work at a very tight schedule and need decision-making support tools to help on improving and doing their work in a timely and dependable manner. Examining piles of sheets with test results and using systems with little visualization support to provide diagnostics is daunting, but that is still the usual way for the physicians’ daily procedure, especially in developing countries. Electronic Health Records systems have been designed to keep the patients’ history and reduce the time spent analyzing the patient's data. However, better tools to support decision-making are still needed. In this article, we propose ClinicalPath, a visualization tool for users to track a patient's clinical path through a series of tests and data, which can aid in treatments and diagnoses. Our proposal is focused on patient's data analysis, presenting the test results and clinical history longitudinally. Both the visualization design and the system functionality were developed in close collaboration with experts in the medical domain to ensure a right fit of the technical solutions and the real needs of the professionals. We validated the proposed visualization based on case studies and user assessments through tasks based on the physician's daily activities. Our results show that our proposed system improves the physicians’ experience in decision-making tasks, made with more confidence and better usage of the physicians’ time, allowing them to take other needed care for the patients.

Social networks have become another resource for supporting mental health specialists in making inferences and finding indications of mental disorders, such as depression. This paper addresses the state-of-the-art regarding studies on recognition of depressive mood disorders in social networks through approaches and techniques of sentiment and emotion analysis. The systematic research conducted focused on social networks, social media, and the most employed techniques, feelings, and emotions were analyzed to find predecessors of a depressive disorder. Discussions on the research gaps identified aimed at improving the effectiveness of the analysis process, bringing the analysis close to the user’s reality. Twitter, Facebook, Blogs and Forums, Reddit, Live Journal, and Instagram are the most employed social networks regarding the identification of depressive mood disorders, and the most used information was text, followed by emoticons, user log information, and images. The selected studies usually employ classic off-the-shelf classifiers for the analysis of the available information, combined with lexicons such as NRC Word-Emoticon Association Lexicon, WordNet-Affect, Anew, and LIWC tool. The challenges include the analysis of temporal information and a combination of different types of information.

•TERRA is repressed in primary human hematopoietic cells (in the bone marrow and peripheral blood), regardless of their telomere lengths.•TERRA is dysregulated in a subset of AML characterized by higher R-loop formation and low TERTand RNAseH2expression.

This systematic review aimed to determine what existing job transition programs are evidence-based and methodologically founded. The PRISMA method was used for the review, and the inclusion criteria were to include studies where there were a description of transition programs and functional curriculum for acquiring employment competences; internship experiences in employment context; single-case or group-design studies with youths as participants; and diagnosis of intellectual disability. Forty-six studies were initially selected, and three final articles met all the criteria set for assessing the methodology quality. Although the review results show that more research is needed to provide empirical programs for enhancing the acquisition of employment capabilities, some evidence emerged from the analysis of studies. These concern mainly four aspects: curriculum contents facilitating the development of self-determination and the acquirement of job-related skills, chance to have individualized internships, support of job coaches, and technological solutions and programs anchored in community-based settings.

Objective The aim of this study was to document the survival rate in the middle-aged patient group up to 65 years old and to compare it with other age groups of patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis (OA).Design The Register of Orthopaedic Prosthetic Implants (RIPO) regional registry was used to analyze the results of patients <80 years old affected by primary OA and treated with TKA from 2000 to 2019. The database was investigated according to the age group: younger than 50 years, 50-65 years, or 66-79 years, with the aim to estimate revision surgeries and implant survivorship.Results A total of 45,488 TKAs for primary OA were included in the analysis (M: 11,388; F: 27,846). The percentage of patients <65 years old increased from 13.5% to 24.8% between 2000 and 2019 (P< 0.0001). The survival analysis showed an overall influence of age on the implant revision rate (P< 0.0001), with an estimated survival rate of 78.7%, 89.4%, and 94.8% at 15 years in the 3 groups, respectively. Compared with the older-aged group, the relative risk of failure was 3.1 (95% confidence interval [CI] = 2.2-4.3; P< 0.001) higher in patients <50 years old and 1.8 (95% CI = 1.6-2.0; P< 0.001) higher in patients 50-65 years old.Conclusions TKA use in the middle-aged patient population up to 65 years old increased significantly over time. These patients present a double risk of failure with respect to older patients. This is particularly important considering the increasing life expectancy and the emergence of new joint preserving strategies, which could postpone the need for TKA to an older age.

Introduction: The routine use of proximal femoral modularity was discouraged in total hip arthroplasties (THAs). However, titanium dual-taper (DT) implants may provide some advantages over single-taper (ST) stems in cases of complex deformity. A registry study comparing ST and DT stems in dysplasia was designed, aiming to assess: (1) survival rates at long-term; (2) reasons for revision; (3) the profile of failed implants.Methods: The arthroplasty registry RIPO was investigated for cementless THAs performed for dysplasia since 2000. ST implants were compared to titanium-on-titanium DT stems. Demographics and implant features were collected. Survival rates and reasons for revision were compared. The profile of DT stem failures in dysplasia was defined.Results: 6429 implants were included in the study, 3642 ST and 2787 DT. The demographic and implant features of the 2 cohorts were not comparable. The DT cohort achieved higher survival rates at long-term (93.9% vs. 91.6%, p= 0.018). DT implants showed a higher rate of implant breakage (0.6%, p= 0.011) and a lower rate of aseptic loosening (p= 0.005). There were no differences in terms of revisions for dislocation. No metallosis occurred. There were more revisions in DT implants in males <65 years, with a 28-mm head size or smaller.Conclusions: Modularity did not result in lower survival rates in dysplastic patients and may even reduce the rate of aseptic loosening in comparison to ST stems. The rate of implant breakage is not negligible. Younger males are not good candidates for titanium DT stems.

Temporal (or time-evolving) networks are commonly used to model complex systems and the evolution of their components throughout time. Although these networks can be analyzed by different means, visual analytics stands out as an effective way for a pre-analysis before doing quantitative/statistical analyses to identify patterns, anomalies, and other behaviors in the data, thus leading to new insights and better decision-making. However, the large number of nodes, edges, and/or timestamps in many real-world networks may lead to polluted layouts that make the analysis inefficient or even infeasible. In this paper, we propose LargeNetVis, a web-based visual analytics system designed to assist in analyzing small and large temporal networks. It successfully achieves this goal by leveraging three taxonomies focused on network communities to guide the visual exploration process. The system is composed of four interactive visual components: the first (Taxonomy Matrix) presents a summary of the network characteristics, the second (Global View) gives an overview of the network evolution, the third (a node-link diagram) enables community- and node-level structural analysis, and the fourth (a Temporal Activity Map – TAM) shows the community- and node-level activity under a temporal perspective. We demonstrate the usefulness and effectiveness of LargeNetVis through two usage scenarios and a user study with 14 participants.

In a hostile groin, it may be difficult to perform antegrade endovascular procedures at the lower extremities using the ipsilateral common femoral artery as vascular access; therefore, the use of the ipsilateral superficial femoral artery (SFA) could be a useful alternative. In this study, we evaluated the feasibility and safety of ultrasound-guided SFA puncture versus traditional SFA cutdown to achieve arterial access.

abstract:In a proleptically queer mode, Avery Cardinal Dulles's Models of the Church argued that the church—a mystery—must bear multiple simultaneously true, dynamic, indispensable, yet inadequate labels. If so, one theological test of our ethics is their ability to sustain ecclesiological multiplicity. The anti-trans* policies of some US dioceses and of the Congregation for Catholic Education (CCE) document "'Male and Female He Created Them'" embrace Dulles's institution model to the point of exclusive authoritarian institutionalism, while other CCE documents, embracing open-ended, loving dialogue across difference, favor his communion and community of disciples models without discarding the other dimensions of church. Dulles's belief in the dynamism and temporality of ecclesiological models is permission to replace the institution model, which is vulnerable to abuse, with a kenotic model drawn from queer theology that installs apophasis and self-criticism as indispensable elements of ecclesiology. Ethics of sexuality and gender must pass this ecclesiological test.

Androgen receptor (AR) inhibitor therapy is a developing treatment for AR-positive breast cancer (BC) with ongoing clinical trials. AR splice variant-7 (AR-V7) is a truncated variant of AR that leads to AR inhibitor therapy resistance in prostate cancer; recent studies have identified AR-V7 in BC and theorized that AR-V7 can have a similar impact. This study assessed the prevalence and clinicopathologic features associated with AR-V7 in a large BC cohort. BC samples were evaluated by MSK-Fusion targeted RNAseq for AR-V7 detection and MSK-IMPACT targeted DNAseq, including triple-negative tumors with no driver alteration and estrogen receptor-positive/ESR1wildtype tumors progressing on therapy. Among 196 primary and metastatic/recurrent cases (196 RNAseq, 194DNAseq), 9.7% (19/196) were AR-V7 positive and 90.3% (177/196) AR-V7 negative. All AR-V7 positive BC were AR-positive by immunohistochemistry (19/19). The prevalence of AR-V7 by receptor subtype (N= 189) was: 18% (12/67) in ER-/PgR-/HER2-negative BC, 3.7% (4/109) in ER-positive/HER2-negative BC, and 15.4% (2/13) in HER2-positive BC; AR-V7 was detected in one ER-positive/HER2-unknown BC. Apocrine morphology was observed in 42.1% (8/19) of AR-V7 positive BC and 3.4% (6/177) AR-V7 negative BC (P< 0.00001). Notably, AR-V7 was detected in 2 primary BC and 7 metastatic/recurrent BC patients with no prior endocrine therapy. We conclude that positive AR IHC and apocrine morphology are pathologic features that may indicate testing for AR-V7 is warranted in both primary and metastatic BC in the appropriate clinical context. The study findings further encourage the assessment of AR-V7 as a predictive biomarker for AR antagonist benefit in ongoing clinical BC trials.

ObjectivesHorizon scanning methodologies are employed in healthcare to identify and prioritise innovations at the early stages of development processes. To date, horizon scanning has been predominantly applied to early awareness systems of health technologies to facilitate healthcare planning. Still, horizon scanning methodologies may also be relevant for identifying novel healthcare delivery models and interventions. This study aimed to examine perceptions of determinants for adopting horizon scanning in the context of the development of integrated care models.MethodsQualitative semistructured interviews were conducted between March and May 2021. The interviewees (n=10) were participants in innovation projects in the South-Eastern Norway Regional Health Authority. Data were analysed thematically with the aid of a predefined framework adapted from behavioural change theory.ResultsDeterminants of adopting horizon scanning were reported at the individual, organisational and wider institutional levels. Seven domains were perceived to enable or hinder stakeholders’ potential use of horizon scanning: knowledge of structured reviews, skills to perform horizon scanning, beliefs about consequences (validity and reliability of information, outcomes of filtering and priority setting, stakeholder involvement), beliefs about capabilities (technical skills, knowledge of roles and professional identities, organisational regulations), emotions (positivity, engagement, change fatigue), organisational resources (professional library, time, management support), context (complexity of ‘integrated care’, professional hierarchies, legal and political regulations).ConclusionsThis study provides novel insights into potential determinants for adopting horizon scanning to identify, assess and prioritise innovative integrated care models. The findings may assist organisations considering using horizon scanning and inform strategies to mitigate barriers and promote facilitators.

Phenylselenenylzinc chloride (PhSeZnCl) is an air-stable selenolate, easily synthesizable through oxidative insertion of elemental zinc into the Se-halogen bond of the commercially available phenylselenyl chloride. PhSeZnCl was shown to possess a marked GPx-like activity both in NMR and in vitro tests, and to effectively react with cellular thiols, and was supposed for a potential use in the chemotherapy of drug-resistant cancers. However, activity of PhSeZnCl in hepatic cells has never been tested before now. In this in vitro approach, we evaluated the cytotoxic, genotoxic, and apoptotic activities, as well as the effects on cell cycle of PhSeZnCl in two preclinical hepatic models, namely HepG2 and HepaRG cells. Results showed that cell viability of HepG2 and HepaRG cells decreased in a dose-dependent manner, with a more marked effect in HepG2 tumour cells. Moreover, treatment with 50 µg/mL PhSeZnCl caused an increase of primary DNA damage (4 h) and a statistically significant increase of HepG2 cells arrested in G2/M phase. In addition, it altered mitochondrial membrane potential and induced chromosomal DNA fragmentation (24 h). In HepaRG cells, PhSeZnCl was able to determine a cell cycle-independent induction of apoptosis. Particularly, 50 µg/mL induced mitochondrial membrane depolarization after 24 h and apoptosis after 4 h treatment. Futhermore, all PhSeZnCl concentrations tested determined a significant increase of apoptotic cells after 24 h. Apoptosis was also highlighted by the detection of active Caspase-3 by Western Blot analysis after 24 h exposure. In conclusion, this first toxicological assessment provides new insights into the biological activity of PhSeZnCl in preclinical hepatic models that will be useful in future safety assessment investigation of this compound as a potential pharmaceutical.

BackgroundThe idea that individuals are responsible for their health has been the focus of debate in the theoretical literature and in its concrete application to healthcare policy in many countries. Controversies persist regarding the form, substance and fairness of allocating health responsibility to the individual, particularly in universal, need-based healthcare systems.ObjectiveTo examine how personal health responsibility has been framed and rationalised in Norwegian key policy documents on priority setting.MethodsDocuments issued or published by the Ministry of Health and Care Services between 1987 and 2018 were thematically analysed (n=14). We developed a predefined conceptual framework that guided the analysis. The framework included: (1) the subject and object of responsibility, (2) the level of conceptual abstraction, (3) temporality, (4) normative justificatory arguments and (5) objections to the application of personal health responsibility.ResultsAs an additional criterion, personal health responsibility has been interpreted as relevant if: (A) the patient’s harmful behaviour is repeated after receiving treatment (retrospectively), and if (B) the success of the treatment is conditional on the patient’s behavioural change (prospectively). When discussed as a retrospective criterion, considerations of reciprocal fairness have been dominant. When discussed as a prospective criterion, the expected benefit of treatment justified its relevance.ConclusionPersonal health responsibility appears to challenge core values of equality, inclusion and solidarity in the Norwegian context and has been repeatedly rejected as a necessary criterion for priority setting. However, the responsibility criterion seems to have some relevance in particular priority setting decisions.

Childhood obesity is an increasing health problem. Prior empirical research suggests that, although discussing lifestyle behaviours with parents could help prevent childhood obesity and its health-related consequences, physicians are reluctant to address parental responsibility in the clinical setting. Therefore, this paper questions whether parents might be (or might be held) responsible for their children’s obesity, and if so, whether parental responsibility ought to be addressed in the physician–patient/parent encounter. We illustrate how different ideal-typical models of the physician–patient/parent interaction emphasise different understandings of patient autonomy and parental responsibility and argue that these models advocate different responses to an appeal for discussing parents’ role in childhood obesity. We suggest that responsibility should be attributed to parents because of their parental roles in providing for their children’s welfare. We also argue that whether, and how, this responsibility gives rise to a requirement to act depends on the parents’ capacities. A deliberative-oriented physician–patient/parent interaction best captures the current ideals of antipaternalism, patient autonomy, and shared and evidence-informed decision-making, and might facilitate parental role development. We conclude that, while not discussing parental responsibility for childhood obesity in the clinical setting can be warranted in particular cases, this cannot be justified as a general rule.

AbstractBackgroundConflicting results have been described in the scientific literature regarding the relationship between electrocardiographic parameters and complications in patients with Takotsubo syndrome (TTS). Aim of the present study was to investigate whether there is an association between markers of ventricular repolarization and major adverse cardiovascular events (MACE) during hospitalisation.MethodsA retrospective chart review was conducted on a sample of patients with diagnosis of TTS, based on the fulfilment of the revised Mayo Clinic criteria. MACE included acute heart failure, cardiogenic shock, sustained ventricular tachycardia, ventricular fibrillation, and death. The following parameters, assessed on the admission electrocardiogram, were analysed: ST-segment elevation, ST-segment depression, T wave inversion, presence of Q waves, QT interval, QT interval corrected for heart rate, QT-dispersion, Tpeak–Tend (Tpe) interval, Tpe dispersion, Tpe/QT ratio, and QTpeak/QT ratio.ResultsPatients with MACE, compared to patients without MACE, showed more commonly anterior ST-segment elevation and had significantly higher values of Tpe/QT ratio. Low ejection fraction and Tpe/QT ratio > 0.27 identified a sub-population of patients more likely to have MACE during hospitalisation.ConclusionsTpe/QT ratio represents a useful electrocardiographic parameter in the acute phase of TTS.

Introduction: Articular surface replacement (ASR) XL implants exhibit higher-than-expected revision rates, blood ion concentrations and soft tissue lesions, making revisions troublesome and potentially unsatisfying. Appropriate techniques and outcomes in ASR XL revisions are rarely documented. The aims of this study were the assessments of pre-revision data, post-revision clinical and radiographic outcomes and ion levels in isolated acetabular ASR XL revisions performed using highly porous titanium cups and Delta ceramic articulations.Methods: 18 isolated acetabular ASR XL revisions in 16 patients were performed using Ti-Por cups (Adler Ortho, Milan, Italy) and Delta bearings (CeramTec, Plochingen, Germany). Pre-revision demographic, clinical, radiological and implant-related features were assessed. Clinical and radiographic parameters (cup positioning, osseointegration) after revisions were evaluated at a minimum follow-up of 5 years. Ion concentrations in blood and urine were collected in pre-revision setting and 1 year after revision.Results: 4 complications occurred in 3 different revisions (16.7%), 1 dislocation, 2 infections, 1 psoas impingement. No re-revision was performed at 5 years (1 scheduled arthroscopy). Good clinical outcomes were achieved (HHS score: 88.3 ± 9.2). All the cups showed reassuring signs of osseointegration (>3 parameters). Blood ion concentrations significantly decreased: patients with Co blood ion concentration over the threshold (7 μg/l) decreased from 76.5% to 0%. No pre-revision or intraoperative data influenced the revision outcomes.Conclusions: Highly porous titanium cups and Delta ceramic articulations provided reliable mid-term clinical and radiographic outcomes in isolated acetabular ASR XL revisions. Ion concentrations significantly decreased. Multicentre prospective controlled studies are required to confirm these preliminary outcomes.

The retroperitoneal approach (RP) is a well-established procedure for juxtarenal and infrarenal (IR) abdominal aortic aneurysm (AAA) repair when an endovascular option is not available. The aim of this study is to compare the effect of suprarenal (SR) and IR aortic clamping on postoperative renal function following an Enhanced Recovery Protocol (ERP). Since there are no defined guidelines within aortic surgery, we focused our attention on the role of fluid and vasopressor administration in the development of postoperative acute kidney injury (AKI).

Introduction: Aim of this study was to describe the clinical outcomes of 16 patients with iliopsoas (IP) impingement after primary total hip arthroplasty (THA), treated with an arthroscopic tendon release.Methods: 16 patients (11 females/5 males), with a mean age of 57.8 ± 11.1 years (age at THA: 54.4 ± 11 years) and a diagnosis of IP impingement after primary THA, were treated with the Wettstein tenotomy. Preoperatively, every patient underwent a diagnostic ultrasonography guided peritendinous injection and a computed tomography (CT) scan. Every patient was clinically evaluated using WOMAC score. Subjective pain relief and active hip flexion strength were measured.Results: No complications related to arthroscopy were detected. Every cup was prominent with a mean axial overhang of 13 ± 4.8 mm (range 5–20 mm). At a mean follow-up of 27 ± 20.1 months (range 6–48 months), the WOMAC score was 83.7 ± 10.1 points. 13 patients out of 16 (81.3%) had a complete pain relief. 14 patients out of 16 (88%) regained full active hip flexion strength at the final follow-up. 1 patient was scheduled for cup revision after 6 months, due to persistent symptomatology. No demographic data or CT measurements about cup position statistically influenced the outcome.Conclusions: When preceded by an appropriate diagnosis, arthroscopic tenotomy proved safe and effective for IP impingement, regardless the magnitude of cup protrusion.

ABSTRACTRhoA and RhoC contribute to the regulation of glutamine metabolism, which is a crucial determinant of cell growth in some types of cancer. Here we investigated the participation of RhoA and RhoC in the response of prostate cancer cells to glutamine deprivation. We found that RhoA and RhoC activities were up- or downregulated by glutamine reduction in PC3 and LNCaP cell lines, which was concomitant to a reduction in cell number and proliferation. Stable overexpression of wild type RhoA or RhoC did not alter the sensitivity to glutamine deprivation. However, PC3 cells expressing dominant negative RhoAN19or RhoCN19mutants were more resistant to glutamine deprivation. Our results indicate that RhoA and RhoC activities could affect cancer treatments targeting the glutamine pathway.

Androgen receptor (AR) inhibitor therapy is a developing treatment for AR-positive breast cancer (BC) with ongoing clinical trials. AR splice variant-7 (AR-V7) is a truncated variant of AR that leads to AR inhibitor therapy resistance in prostate cancer; recent studies have identified AR-V7 in BC and theorized that AR-V7 can have a similar impact. This study assessed the prevalence and clinicopathologic features associated with AR-V7 in a large BC cohort. BC samples were evaluated by MSK-Fusion targeted RNAseq for AR-V7 detection and MSK-IMPACT targeted DNAseq, including triple-negative tumors with no driver alteration and estrogen receptor-positive/ESR1wildtype tumors progressing on therapy. Among 196 primary and metastatic/recurrent cases (196 RNAseq, 194DNAseq), 9.7% (19/196) were AR-V7 positive and 90.3% (177/196) AR-V7 negative. All AR-V7 positive BC were AR-positive by immunohistochemistry (19/19). The prevalence of AR-V7 by receptor subtype (N= 189) was: 18% (12/67) in ER-/PgR-/HER2-negative BC, 3.7% (4/109) in ER-positive/HER2-negative BC, and 15.4% (2/13) in HER2-positive BC; AR-V7 was detected in one ER-positive/HER2-unknown BC. Apocrine morphology was observed in 42.1% (8/19) of AR-V7 positive BC and 3.4% (6/177) AR-V7 negative BC (P< 0.00001). Notably, AR-V7 was detected in 2 primary BC and 7 metastatic/recurrent BC patients with no prior endocrine therapy. We conclude that positive AR IHC and apocrine morphology are pathologic features that may indicate testing for AR-V7 is warranted in both primary and metastatic BC in the appropriate clinical context. The study findings further encourage the assessment of AR-V7 as a predictive biomarker for AR antagonist benefit in ongoing clinical BC trials.

The Ventana PD-L1 SP142 immunohistochemistry (IHC) assay is the FDA-approved companion diagnostic assay for atezolizumab therapy selection for patients with PD-L1-positive locally advanced or metastatic triple-negative breast carcinoma (TNBC). We aimed to elucidate clinical, pathologic, and molecular features associated with PD-L1 expression in TNBCs. Clinical, pathologic, and next-generation sequencing (NGS)-based molecular data for TNBCs tested with PD-L1 (SP142) IHC at our institution between 11/2018 and 12/2019 were retrieved and reviewed. PD-L1 positivity was defined as ≥1% IC staining. Patients with metastatic TNBC treated at first line with atezolizumab regimens were evaluated for treatment response and for time to treatment failure (TTF). Among 156 TNBCs, PD-L1 was positive in 47.4% of cases. Primary TNBCs were significantly more frequently PD-L1 positive, compared with recurrent/metastatic samples (p= 0.002). PD-L1-positive TNBCs had increased stromal IC, compared with PD-L1-negative samples (p< 0.001). The repertoire of somatic genetic alterations of PD-L1-positive and PD-L1-negative TNBCs was similar. Matched primary and recurrent/metastatic TNBC samples were available for eight patients, in whom four had discordant results. Thirty patients with metastatic TNBC were treated with atezolizumab regimens, with treatment failure occurring in 16 patients and a median TTF of 5.1 months in this early evaluation. The findings of this study show stromal ICs in primary TNBCs are more likely to show PD-L1 positivity than in recurrent or metastatic samples. This information should guide selection of samples suitable for testing. Further studies are needed to identify other features associated with PD-L1-positive breast carcinomas and clinical benefit of treatment.

The question of when and how to drain a malignant biliary obstruction (MBO), both intrinsic or extrinsic, remains a controversial point among endoscopists. An important factor that influences the decision to drain an MBO or not is if the patient is a surgical candidate or not and, in the former case, if the patients must undergo neoadiuvant chemotherapy or not. Other questions arising during biliary drainage in MBO patients is which type of stent should be chosen, plastic or metal, and if endoscopic biliary sphincterotomy must be performed or not when a stent is placed. The present review attempts to answer these questions and summarizes the optimal approach toward patients with MBO based on the available evidence.

Nanotechnology plays a key role in the development of innovative scaffolds for bone tissue engineering (BTE) allowing the incorporation of nanomaterials able to improve cell proliferation and differentiation. In this study, Mg-HA-Coll type I scaffolds (Mg-HA-based scaffolds) were nanofunctionalized with gold nanorods (Au NRs), palladium nanoparticles (Pd NPs) and maghemite nanoparticles (MAG NPs). Nanofunctionalized Mg-HA-based scaffolds (NF-HA-Ss) were tested for their ability to promote both the proliferation and the differentiation of adipose-derived mesenchymal stem cells (hADSCs). Results clearly highlight that MAG nanofunctionalization substantially improves cell proliferation up to 70% compared with the control (Mg-HA-based scaffold), whereas both Au NRs and Pd NPs nanofunctionalization induce a cell growth inhibition of 94% and 89%, respectively. Similar evidences were found for the osteoinductive properties showing relevant calcium deposits (25% higher than the control) for MAG nanofunctionalization, while a decreasing of cell differentiation (20% lower than the control) for both Au NRs and Pd NPs derivatization. These results are in agreement with previous studies that found cytotoxic effects for both Pd NPs and Au NRs. The excellent improvement of both osteoconductivity and osteoinductivity of the MAG NF-HA-S could be attributed to the high intrinsic magnetic field of superparamagnetic MAG NPs. These findings may pave the way for the development of innovative nanostructured scaffolds for BTE.

Background and aims: Post-GI surgical wall defects are frequent and life-threatening complications, with limited literature regarding current treatment. This case series aims to assess the safety, feasibility, and outcomes of endoluminal therapy with the overstitch endoscopic suturing system (Apollo Endosurgery Inc, Austin). Materials and methods: All patients who underwent endoscopic suturing for post-surgical wall defect management at IRCCS-ISMETT Palermo from October 2017 until January 2019 were retrospectively enrolled. Stratification therapy was applied according to the clinical scenario, time from surgery to endoscopic intervention, and structural condition of the wall defect layers (tissue status and suture feasibility). The therapeutic endoscopic strategy was divided into three groups (A: pure endoscopic direct suture; B: combined therapy with endoscopic direct suture + FC-SEMS placement + anchoring; C: FC-SEMS placement + anchoring). Success was considered the resolution of symptoms and the presence of a regular intestinal transit after a period of 4–6 weeks. Results: Twenty (20) patients (male/female 7/13; mean age 54 ± 13.43 years) were included in the study (group A: 9 patients, group B: 7 patients, group C: 4 patients). The types of operative procedures were bariatric (9/20), post-tracheostomy (3/20), post-operative GI surgery (8/20). The post-surgical defects were predominantly intermediate and chronic (24–72 h: 1/20; 3–30 days: 13/20; > 30 days: 6/20). The overall clinical success was 80% (17/20 patients), with a success of 94% (16/17 patients) when excluding the three cases of tracheo-esophageal fistula. No evidence of migration was detected. The only complication was short stenosis of the distal esophagus, present in 4 patients (19%) and successfully treated with a novel lumen-apposing metal stent. Conclusions: In our experience, considering the absence of clear guidelines, the endoluminal approach with the overstich endoscopic suturing system is a valid alternative to conventional therapy, offering mini-invasiveness, and presenting promising opportunities in terms of technical feasibility and clinical efficacy.

Background Autoimmune pancreatitis (AIP) is a rare, and relatively new, form of chronic pancreatitis. The management of AIP can vary considerably among different centres in daily clinical practice.Objectives The aim of this study is to present a picture of epidemiological, clinical characteristics, outcomes, and the real-life practice in terms of management in several academic and non-academic centres in Italy.Methods Data on the clinical presentation, diagnostic work-up, treatments, frequency of relapses, and long-term outcomes were retrospectively collected in a cohort of AIP patients diagnosed at 14 centres in Italy.Results One hundred and six patients were classified as type 1 AIP, 48 as type 2 AIP, and 19 as not otherwise specified. Epidemiological, clinical, radiological, and serological characteristics, and relapses were similar to those previously reported for different types of AIP. Endoscopic cytohistology was available in 46.2% of cases, and diagnostic for AIP in only 35.2%. Steroid trial to aid diagnosis was administered in 43.3% cases, and effective in 93.3%. Steroid therapy was used in 70.5% of cases, and effective in 92.6% of patients. Maintenance therapy with low dose of steroid (MST) was prescribed in 25.4% of cases at a mean dose of 5 (±1.4) mg/die, and median time of MST was 60 days. Immunosuppressive drugs were rarely used (10.9%), and rituximab in 1.7%. Faecal elastase-1 was evaluated in only 31.2% of patients, and was pathological in 59.2%.Conclusions In this cohort of AIP patients, diagnosis and classification for subtype was frequently possible, confirming the different characteristics of AIP1 and AIP2 previously reported. Nevertheless, we observed a low use of histology and steroid trial for a diagnosis of AIP. Steroid treatment was the most used therapy in our cohort. Immunosuppressants and rituximab were rarely used. The evaluation of exocrine pancreatic insufficiency is underemployed considering its high prevalence.

The 2017 European LeukemiaNet 2017 acute myeloid leukemia (AML) risk stratification (ELN2017) is widely used for risk-stratifying patients with AML. However, its applicability in low- and middle-income countries is limited because of a lack of full cytogenetic and molecular information at diagnosis. Here, we propose an alternative for risk stratification (the Adapted Genetic Risk [AGR]), which permits cytogenetic or molecular missing data while retaining prognostic power. We first analyzed 167 intensively treated patients with nonacute promyelocytic leukemia AML enrolled in São Paulo, Brazil (Faculdade de Medicina da Universidade de São Paulo), as our training data set, using ELN2017 as the standard for comparison with our AGR. Next, we combined our AGR with clinical prognostic parameters found in a Cox proportional hazards model to create a novel scoring system (survival AML score, SAMLS) that stratifies patients with newly diagnosed AML. Finally, we have used 2 independent test cohorts, Faculdade de Medicina de Ribeirão Preto (FMRP; Brazil, n = 145) and Oxford University Hospitals (OUH; United Kingdom, n = 157) for validating our findings. AGR was statistically significant for overall survival (OS) in both test cohorts (FMRP, P = .037; OUH, P = .012) and disease-free survival in FMRP (P = .04). The clinical prognostic features in SAMLS were age (>45 years), white blood cell count (<1.5 or >30.0 × 103/μL), and low albumin levels (<3.8 g/dL), which were associated with worse OS in all 3 cohorts. SAMLS showed a significant difference in OS in the training cohort (P < .001) and test cohorts (FMRP, P = .0018; OUH, P < .001). Therefore, SAMLS, which incorporates the novel AGR evaluation with clinical parameters, is an accurate tool for AML risk assessment.

Simultaneous measurements of light hydrocarbon species based on near-infrared (near-IR) supercontinuum laser absorption spectroscopy (SCLAS) are demonstrated. SCLAS is a broadband absorption diagnostic technique that provides significant advantages over existing absorption diagnostic techniques. Coupled with a fast spectrum analysis strategy, accurate measurements of multiple hydrocarbon concentrations can be made concurrently. Methane (CH4), acetylene (C2H2), ethylene (C2H4), and their mixtures were probed near ambient temperature and pressure conditions. Light hydrocarbons are found in many fuel and energy applications, and a sensor that can accurately and simultaneously probe multiple species’ concentrations and temperature would greatly enhance measurement versatility. Absorption spectra of the three hydrocarbon species were measured between 1.5 and 1.7 μm in this study. These spectra can be very convoluted, where broad absorption features interfere with neighboring features, be it from the same or different species. Species concentrations and temperatures were resolved using a spectrum analysis strategy based on linear regression. Experimental results showed good agreement with test conditions even in the presence of significant spectral overlap.

Purpose: To examine the effect of a long-term nutritional supplementation on age-related macular degeneration progression.Methods: In this prospective, double-blind, placebo-controlled study, 80 patients with intermediate age-related macular degeneration were randomized (2:1) to receive 1 tablet/day of a nutritional supplement containing a mixture of carotenoids, vitamins and omega-3 fatty acids or placebo. Age-related macular degeneration progression assessed by digital fundus photography (primary outcome) and best-corrected visual acuity were evaluated. Differences between arms were tested using chi-square test or Fisher’s exact test.Results: Seventy-four patients completed the follow-up at 24 months (48 in the treated arm and 26 in the placebo arm). An age-related macular degeneration progression was observed in the 2.1% of patients of the treated arm and in the 15.4% of patients in the placebo arm (p = 0.05, Fisher’s exact test). Best-corrected visual acuity data alone were not statistically significant among groups.Conclusion: A clinically meaningful stabilization of intermediate age-related macular degeneration over a period of 2 years may be obtained by treating patients with a mixture of carotenoids, vitamins and omega-3 fatty acids.

ObjectivesPrescription of proton pump inhibitors (PPIs) may be a source of potentially clinically relevant drug–drug interactions (DDIs) and related complications for elderly patients with complex polytherapy at discharge from hospital. The aim of the study was to identify, through the analysis of hospital discharge records, the co-administrations (PPIs + one or more drugs potentially generating DDIs) hypothetically leading to severe consequences according to the literature and online databases. Subsequently, alternatives to PPIs were evaluated for the treatment of gastric acidity and ulcers.MethodsThe medical records of 1288 patients, discharged from a geriatric ward at the Città della Salute e della Scienza Hospital in Turin from January 2012 to December 2013, were collected in an Excel database for analysis of DDIs using the literature and online sources such as Micromedex.Results Six hundred and sixty-three of the 1288 clinical folders had a PPI prescription. A list of 18 drugs considered potentially hazardous and able to trigger a DDI when co-administrated with PPIs was drafted; the frequencies of the co-prescriptions of each PPI with one of the listed drugs were esomeprazole 65.38%, lansoprazole 52.87%, omeprazole 48.19% and pantoprazole 37.11%. An analysis of these co-prescriptions, according to Micromedex classification, gave a percentage of major interactions of 11.01% over 663 clinical folders including a PPI.ConclusionsThis study provides a collection of potentially hazardous drug associations and helpful suggestions to improve the quality of prescriptions for elderly patients and strengthens the case for synergic work between doctors and pharmacists in the wards.

Osteoarthritis (OA) is one of the most common disabling pathologies, characterized by joint pain and reduced function, significantly worsening the quality of life. Even if important progresses have been made in OA research, little is yet known about the precise cellular and molecular mechanisms underlying OA. Understanding dysregulated signaling networks and their crosstalk in OA may offer a strong opportunity for the development of combined targeted therapies. Hence, this review highlights the recent findings on the main pathways involved in OA development, including Wnt, Notch, Hedgehog, MAPK, AMPK, and JAK/STAT, providing insights on current targeted therapies in OA patients’ management.

To describe patient-reported outcomes (PROs) after initiation of treatment with canagliflozin (CANA) for type 2 diabetes mellitus (T2DM) in a real-world Canadian setting.