"A Feeling of Safeness and Freedom": The Promotion of Mental Health Recovery Through Co-Production in an Italian Community Organization.

In mental health promotion, recovery is a process that leads to personal strengthening, control over crucial life decisions, and participation in communities through relevant professional, educational, or family social roles. Co-production, a key aspect of the recovery-oriented approach, emphasizes collaboration and active participation of people with mental health first-hand experience, family members, and citizens. Even though studies on co-production are limited and fragmented, there is evidence that co-production leads to positive outcomes, including improved well-being, empowerment, social connectedness, inclusion, and personal competencies. This study aimed to contribute to the limited literature on co-production in mental health by evaluating the co-production process in a non-profit mental health organization and its impact on empowerment processes and personal recovery outcomes. The research team adopted a collaborative approach and conducted qualitative research, including 13 individual semi-structured interviews and four focus groups. Results showed how the different dimensions of empowerment are promoted in and by the organization: (a) co-production processes supported empowered outcomes on an individual level, such as self-awareness; (b) the organization was perceived to promote empowering processes, such as a sense of safeness and protection; (c) co-production was a mean to build and maintain a network with mental health services that acknowledges the dignity and value of each subjectivity and promotes participation and recovery. Peer support workers were seen as facilitators of mental illness management, and the organization as a place for sharing mental health experiences and fostering individual recovery journeys.

REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial.

BACKGROUND: Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others. As regorafenib inhibits these signaling pathways, it was hypothesized that it could be more active as upfront therapy in advanced KP-wtGIST. METHODS: Adult patients with advanced KP-wtGIST after central confirmation by NGS, naïve of systemic treatment for advanced disease, were included in this international phase II trial. Eligible patients received regorafenib 160 mg per day for 21 days every 28 days. The primary endpoint was disease control rate (DCR), according to RECIST 1.1 at 12 weeks by central radiological assessment. RESULTS: From May 2016 to October 2020, 30 patients were identified as KP-wtGIST by Sanger sequencing and 16 were confirmed by central molecular screening with NGS. Finally, 15 were enrolled and received regorafenib. The study was prematurely closed due to the low accrual worsened by COVID outbreak. The DCR at 12 weeks was 86.7% by central assessment. A subset of 60% experienced some tumor shrinkage, with partial responses and stabilization observed in 13% and 87% respectively, by central assessment. SDH-deficient GIST showed better clinical outcome than other KP-wtGIST. CONCLUSIONS: Regorafenib activity in KP-wtGIST compares favorably with other tyrosine kinase inhibitors, especially in the SDH-deficient GIST subset and it should be taken into consideration as upfront therapy of advanced KP-wtGIST. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02638766.

Gender differences in percutaneous coronary intervention for chronic total occlusions from the ERCTO study.

BACKGROUND: Gender-specific data addressing percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) in female patients are scarce and based on small sample size studies. AIMS: We aimed to analyze gender-differences regarding in-hospital clinical outcomes after CTO-PCI. METHODS: Data from 35,449 patients enrolled in the prospective European Registry of CTOs were analyzed. The primary outcome was the comparison of procedural success rate in the two cohorts (women vs. men), defined as a final residual stenosis less than 20%, with Thrombolysis In Myocardial Infarction grade flow = 3. In-hospital major adverse cardiac and cerebrovascular events (MACCEs) and procedural complications were deemed secondary outcomes. RESULTS: Women represented 15.2% of the entire study population. They were older and more likely to have hypertension, diabetes, and renal failure, with an overall lower J-CTO score. Women showed a higher procedural success rate (adjusted OR [aOR] = 1.115, confidence interval [CI]: 1.011-1.230, p = 0.030). Apart from previous myocardial infarction and surgical revascularization, no other significant gender differences were found among predictors of procedural success. Antegrade approach with true-to-true lumen techniques was more commonly used than retrograde approach in females. No gender differences were found regarding in-hospital MACCEs (0.9% vs. 0.9%, p = 0.766), although a higher rate of procedural complications was observed in women, such as coronary perforation (3.7% vs. 2.9%, p < 0.001) and vascular complications (1.0% vs. 0.6%, p < 0.001). CONCLUSIONS: Women are understudied in contemporary CTO-PCI practice. Female sex is associated with higher procedural success after CTO-PCI, yet no sex differences were found in terms of in-hospital MACCEs. Female sex was associated with a higher rate of procedural complications.

Solid Lipid Nanoparticles Administering Antioxidant Grape Seed-Derived Polyphenol Compounds: A Potential Application in Aquaculture.

The supply of nutrients, such as antioxidant agents, to fish cells still represents a challenge in aquaculture. In this context, we investigated solid lipid nanoparticles (SLN) composed of a combination of Gelucire® 50/13 and Precirol® ATO5 to administer a grape seed extract (GSE) mixture containing several antioxidant compounds. The combination of the two lipids for the SLN formation resulted in colloids exhibiting mean particle sizes in the range 139-283 nm and zeta potential values in the range +25.6-43.4 mV. Raman spectra and X-ray diffraction evidenced structural differences between the free GSE and GSE-loaded SLN, leading to the conclusion that GSE alters the structure of the lipid nanocarriers. From a biological viewpoint, cell lines from gilthead seabream and European sea bass were exposed to different concentrations of GSE-SLN for 24 h. In general, at appropriate concentrations, GSE-SLN increased the viability of the fish cells. Furthermore, regarding the gene expression in those cells, the expression of antioxidant genes was upregulated, whereas the expression of hsp70 and other genes related to the cytoskeleton was downregulated. Hence, an SLN formulation containing Gelucire® 50/13/Precirol® ATO5 and GSE may represent a compelling platform for improving the viability and antioxidant properties of fish cells.

Isolation and characterization of urine microvesicles from prostate cancer patients: different approaches, different visions.

BACKGROUND: Because of their specific and biologically relevant cargo, urine extracellular vesicles (EVs) constitute a valuable source of potential non-invasive biomarkers that could support the clinical decision-making to improve the management of prostate cancer (PCa) patients. Different EV isolation methods differ in terms of complexity and yield, conditioning, as consequence, the analytical result. METHODS: The aim of this study was to compare three different isolation methods for urine EVs: ultracentrifugation (UC), size exclusion chromatography (SEC), and a commercial kit (Exolute® Urine Kit). Urine samples were collected from 6 PCa patients and 4 healthy donors. After filtered through 0.22 µm filters, urine was divided in 3 equal volumes to perform EVs isolation with each of the three approaches. Isolated EVs were characterized by spectrophotometric protein quantification, nanoparticle tracking analysis, transmission electron microscopy, AlphaScreen Technology, and whole miRNA Transcriptome. RESULTS: Our results showed that UC and SEC provided better results in terms of EVs yield and purity than Exolute®, non-significant differences were observed in terms of EV-size. Interestingly, luminescent AlphaScreen assay demonstrated a significant enrichment of CD9 and CD63 positive microvesicles in SEC and UC methods compared with Exolute®. This heterogeneity was also demonstrated in terms of miRNA content indicating that the best correlation was observed between UC and SEC. CONCLUSIONS: Our study highlights the importance of standardizing the urine EV isolation methods to guaranty the analytical reproducibility necessary for their implementation in a clinical setting.

Pazopanib for treatment of typical solitary fibrous tumours: a multicentre, single-arm, phase 2 trial.

BACKGROUND: Solitary fibrous tumour is an ultra-rare sarcoma, which encompasses different clinicopathological subgroups. The dedifferentiated subgroup shows an aggressive course with resistance to pazopanib, whereas in the malignant subgroup, pazopanib shows higher activity than in previous studies with chemotherapy. We designed a trial to test pazopanib activity in two different cohorts of solitary fibrous tumour: the malignant-dedifferentiated cohort, which was previously published, and the typical cohort, which is presented here. METHODS: In this single-arm, phase 2 trial, adult patients (aged ≥18 years) diagnosed with confirmed metastatic or unresectable typical solitary fibrous tumour of any location, who had progressed in the previous 6 months (by Choi criteria or Response Evaluation Criteria in Solid Tumors [RECIST]) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were enrolled at 11 tertiary hospitals in Italy, France, and Spain. Patients received pazopanib 800 mg once daily, taken orally, until progression, unacceptable toxicity, withdrawal of consent, non-compliance, or a delay in pazopanib administration of longer than 3 weeks. The primary endpoint was proportion of patients achieving an overall response measured by Choi criteria in patients who received at least 1 month of treatment with at least one radiological assessment. All patients who received at least one dose of the study drug were included in the safety analyses. This study is registered in ClinicalTrials.gov, NCT02066285, and with the European Clinical Trials Database, EudraCT 2013-005456-15. FINDINGS: From June 26, 2014, to Dec 13, 2018, of 40 patients who were assessed, 34 patients were enrolled and 31 patients were included in the response analysis. Median follow-up was 18 months (IQR 14-34), and 18 (58%) of 31 patients had a partial response, 12 (39%) had stable disease, and one (3%) showed progressive disease according to Choi criteria and central review. The proportion of overall response based on Choi criteria was 58% (95% CI 34-69). There were no deaths caused by toxicity, and the most frequent adverse events were diarrhoea (18 [53%] of 34 patients), fatigue (17 [50%]), and hypertension (17 [50%]). INTERPRETATION: To our knowledge, this is the first prospective trial of pazopanib for advanced typical solitary fibrous tumour. The manageable toxicity and activity shown by pazopanib in this cohort suggest that this drug could be considered as first-line treatment for advanced typical solitary fibrous tumour. FUNDING: Spanish Group for Research on Sarcomas (GEIS), Italian Sarcoma Group (ISG), French Sarcoma Group (FSG), GlaxoSmithKline, and Novartis.

Magnesium-Based Resorbable Scaffold Versus Permanent Metallic Sirolimus-Eluting Stent in Patients With ST-Segment Elevation Myocardial Infarction: The MAGSTEMI Randomized Clinical Trial.

BACKGROUND: The use of poly-l-lactide acid-based bioresorbable scaffolds is limited in daily clinical practice because of safety concerns and lack of physiological benefit. Magnesium-based bioresorbable scaffold (MgBRS) presents a short resorption period (<1 year) and have the potential of being thromboresistant and exhibiting early restoration of vasomotor function. To date, however, no randomized clinical trial has investigated the performance of MgBRS. Therefore, this study aimed to compare the in-stent/scaffold vasomotion between MgBRS and permanent metallic sirolimus-eluting stent (SES) at 12-month follow-up in ST-segment-elevation myocardial infarction patients. METHODS: This investigator-driven, multicenter, randomized, single-blind, controlled trial randomized ST-segment-elevation myocardial infarction patients 1:1 to SES or MgBRS at 11 academic centers. The primary end point was the rate of increase (≥3%) after nitroglycerin in mean lumen diameter of the in-stent/scaffold segment at 12 months with superiority of MgBRS over SES in the as-treated population. The main secondary end points included angiographic parameters of restenosis, device-oriented composite end point, their individual components, and device thrombosis rate. Besides, endothelial-dependent vasomotor response to acetylcholine (ie, endothelial function) was also assessed in a subgroup of patients (n=69). RESULTS: Between June 2017 and June 2018, 150 ST-segment-elevation myocardial infarction patients were randomized (MgBRS, n=74; SES, n=76). At 1 year, the primary end point was significantly higher in the MgBRS arm (56.5% versus 33.8%; P=0.010). Conversely, late lumen loss was significantly lower in the SES group (in-segment: 0.39±0.49mm versus 0.02±0.27mm, P<0.001; in-device: 0.61±0.55mm versus 0.06±0.21mm; P<0.001). The device-oriented composite end point was higher in the MgBRS arm driven by an increase in ischemia-driven target lesion revascularization rate (12[16.2%] versus 4[5.2%], P=0.030). Definite thrombosis rate was similar between groups (1[1.4%] in the MgBRS arm versus 2[2.6%] in the SES group; P=1.0). Endothelial function assessment at device segment evidenced a more pronounced vasoconstrictive response to maximal dose of acetylcholine in the MgBRS arm (-8.3±3.5% versus -2.4±1.3% in the SES group, P=0.003). CONCLUSIONS: When compared to SES, MgBRS demonstrated a higher capacity of vasomotor response to pharmacological agents (either endothelium-independent or endothelium-dependent) at 1 year. However, MgBRS was associated with a lower angiographic efficacy, a higher rate of target lesion revascularization, without thrombotic safety concerns. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03234348.

Safety and efficacy of a sirolimus-eluting coronary stent with ultra-thin strut for treatment of atherosclerotic lesions (TALENT): a prospective multicentre randomised controlled trial.

BACKGROUND: Supraflex is a sirolimus-eluting stent with a biodegradable polymer coating and ultra-thin struts. We aimed to compare Supraflex with the standard of care, Xience, an everolimus-eluting stent with a durable polymer coating, regarding clinical outcomes with a randomised trial in an all-comer population. METHODS: We did a prospective, randomised, single-blind, multicentre study (TALENT) across 23 centres in Europe (the Netherlands, Poland, the UK, Spain, Bulgaria, Hungary, and Italy). Eligible participants were aged 18 years or older, had one or more coronary artery stenosis of 50% or greater in a native coronary artery, saphenous venous graft, or arterial bypass conduit, and had a reference vessel diameter of 2·25-4·50 mm. Patients underwent percutaneous coronary intervention in an all-comer manner. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting stent with a biodegradable polymer coating and ultra-thin struts (Supraflex) or an everolimus-eluting stent with a durable polymer coating (Xience). Randomisation was done by local investigators by use of a web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint-cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation-between groups at 12 months after the procedure, assessed in an intention-to-treat population. On assumption of 1-year composite endpoint prevalence of 8·3%, a margin of 4·0% was defined for non-inferiority of the Supraflex group compared with the Xience group. This trial is registered with ClinicalTrials.gov, number NCT02870140. FINDINGS: Between Oct 21, 2016, and July 3, 2017, 1435 patients with 1046 lesions were randomly assigned to Supraflex, of whom 720 received the index procedure, and 715 patients with 1030 lesions were assigned to Xience, all receiving the index procedure. At 12 months, the primary endpoint had occurred in 35 patients (4·9 %) in the Supraflex group and in 37 patients (5·3%) in the Xience group (absolute difference -0·3% [one-sided 95% upper confidence bound 1·6%], pnon-inferiority<0·0001). Definite or probable stent thrombosis prevalence, a safety indicator, was low in both groups and did not differ between them. INTERPRETATION: The Supraflex stent was non-inferior to the Xience stent for a device-oriented composite clinical endpoint at 12 months in an all-comer population. Supraflex seems a safe and effective alternative drug-eluting stent to other stents in clinical practice. FUNDING: European Cardiovascular Research Institute.

A Tetra-Panel of Serum Circulating miRNAs for the Diagnosis of the Four Most Prevalent Tumor Types.

The purpose of this study is to clinically validate a series of circulating miRNAs that distinguish between the 4 most prevalent tumor types (lung cancer (LC); breast cancer (BC); colorectal cancer (CRC); and prostate cancer (PCa)) and healthy donors (HDs). A total of 18 miRNAs and 3 housekeeping miRNA genes were evaluated by qRT-PCR on RNA extracted from serum of cancer patients, 44 LC, 45 BC, 27 CRC, and 40 PCa, and on 45 HDs. The cancer detection performance of the miRNA expression levels was evaluated by studying the area under the curve (AUC) of receiver operating characteristic (ROC) curves at univariate and multivariate levels. miR-21 was significantly overexpressed in all cancer types compared with HDs, with accuracy of 67.5% (p = 0.001) for all 4 tumor types and of 80.8% (p < 0.0001) when PCa cases were removed from the analysis. For each tumor type, a panel of miRNAs was defined that provided cancer-detection accuracies of 91%, 94%, 89%, and 77%, respectively. In conclusion, we have described a series of circulating miRNAs that define different tumor types with a very high diagnostic performance. These panels of miRNAs would constitute the basis of different approaches of cancer-detection systems for which clinical utility should be validated in prospective cohorts.

Long-term impact of diabetes in patients with ST-segment elevation myocardial infarction: Insights from the EXAMINATION randomized trial.

BACKGROUND: Long-term outcomes of diabetic patients suffering from ST-segment elevation myocardial infarction (STEMI) and treated with second-generation drug-eluting stent have been scarcely evaluated. The aim of this posthoc subanalysis of the EXAMINATION trial was to compare 5-year outcomes according to the presence of diabetes mellitus. METHODS: From a total of 1,497 patients included in the trial, 258 were diabetics (n = 137, received everolimus-eluting stent (EES) and n = 121 bare-metal stent (BMS); whereas 1,239 were nondiabetics (n = 613 treated with EES and n = 626 with BMS). Patient-oriented combined endpoint (POCE) defined as all-cause death, any MI or any revascularization, and other clinical parameters were collected up to 5-years. All results were adjusted for various potential confounders. RESULTS: At 5-years, patients with diabetes showed similar rates of POCE between diabetics treated with EES and those treated with BMS (32.8% vs. 32.2%; p = 0.88). However, rates of TLR were significantly lower in the EES group (4.4% vs. 9.9%; HR 0.52 (0.29-0.94); P = 0.03). In non-diabetics, the use of EES was associated with a significant improvement in all-clinical parameters except for MI rate: POCE: [10.0% vs. 12.6%; HR 0.78(0.62-0.98); P = 0.038], all cause death: [7.0% vs. 12.1%; HR 0.62(0.42-0.90); P = 0.014], and [TLR: 4.2 vs. 6.7; HR 0.60 (0.37-0.98); P = 0.04]. Overall, diabetics showed higher rate of POCE at 5-years (32.6% vs. 21.5% in nondiabetics HR1.45[1.03-2.04];p = 0.03) driven by increased rates of MI and the need for revascularization that occurred in coronary segments remote from target lesions [2.7% vs. 1.1%; HR: 2.27 (1.12-5.23); P = 0.02 and 14% vs. 6.2%; HR: 2.11 (1.38-3.22); P = 0.001, respectively]. CONCLUSIONS: Diabetics had worse clinical outcomes than nondiabetics after STEMI mainly due to atherosclerosis progression. At 5-years, the treatment with EES did not reduce the rate of POCE in diabetics but reduced the need for revascularization compared with BMS.

MAGnesium-based bioresorbable scaffold and vasomotor function in patients with acute ST segment elevation myocardial infarction: The MAGSTEMI trial: Rationale and design.

AIM: Use of a Bioresorbable Scaffolds (BRS) either in clinical practice or in the setting of an acute myocardial infarction (MI) is controversial. Despite an overall high rate of thrombosis, vascular healing response following BRS implantation tend to superiority as compared to metallic drug-eluting stent in ST-segment elevation myocardial infarction (STEMI) patients. We sought to compare the in-stent/scaffold vasomotion between metallic BRS and sirolimus eluting stent (SES) at 12-month angiographic follow-up in the setting of patients with STEMI treated by primary PCI. STUDY DESIGN: This is an investigator-driven, prospective, multicenter, randomized, single blind, two-arm, controlled trial (ClinicalTrials.gov number: NCT03234348). This trial will randomize ~148 patients 1:1 to SES or BRS. Primary end-point is the in-stent/scaffold change in mean lumen diameter after nitroglycerin administration at 12-month angiographic follow-up. Besides, patient-oriented combined endpoint of all-cause death, any MI, and any revascularization, together with scaffold/stent thrombosis rate and device-oriented endpoint of cardiac death, target vessel (TV)-MI and TVR at 1 year will be also evaluated. Clinical follow-up will be scheduled yearly up to 5 years. CONCLUSION: This trial will shed light on the vascular vasomotion following BRS implantation in the complex scenario of STEMI.

Chemokine Expression Is Involved in the Vascular Neogenesis of Ewing Sarcoma: A Preliminary Analysis of the Early Stages of Angiogenesis in a Xenograft Model.

BACKGROUND: Ewing sarcoma (EWS) is the second most common bone cancer in pediatric patients. Angiogenesis is a major factor for tumor growth and metastasis. Our aim was to carry out a histological, immunohistochemical, and molecular characterization of the neovascularization established between xenotransplanted tumors and the host during the initial phases of growth in nude mice in three angiogenesis experiments (ES2, ES3, and ES4). METHODS: The original human EWS were implanted subcutaneously on the backs of three nude mice. Tumor pieces 3 mm-4 mm in size from early passages of Nu432, Nu495, and Nu471 were also implanted subcutaneously on the backs of three sets (ES2, ES3, and ES4) of athymic Balb-c nude mice (n = 14 each). The animals were sacrificed at 24, 48, and 96 hours and at 7, 14, 21, and 28 days after implantation to perform histological, immunohistochemical, and molecular studies (neovascularization experiments). RESULTS: We observed histological, ultrastructural, and immunohistochemical changes in the xenografted tumor at different times after implantation. Chemokine ligand expression peaked twice, once during the first 48 hours and again in the second week. We observed that tumor cells in contact with murine peritumoral stroma presented higher expression of chemokine ligands as well as more tumor cells around the capillary vessels. Mouse serum vascular endothelial growth factor levels peaked twice, once in the first hours and then in the second week after tumor implantation. CONCLUSION: Chemokines and other angiogenic factors may be relevant in the angiogenic mechanism during tumor growth. This model provides information on the early stages of the angiogenic process and could be a useful tool in researching anti-angiogenic drugs for new therapeutic strategies in EWS.

Implementation of massive sequencing in the genetic diagnosis of hereditary cancer syndromes: diagnostic performance in the Hereditary Cancer Programme of the Valencia Community (FamCan-NGS).

BACKGROUND: Approximately 5 to 10% of all cancers are caused by inherited germline mutations, many of which are associated with different Hereditary Cancer Syndromes (HCS). In the context of the Program of Hereditary Cancer of the Valencia Community, individuals belonging to specific HCS and their families receive genetic counselling and genetic testing according to internationally established guidelines. The current diagnostic approach is based on sequencing a few high-risk genes related to each HCS; however, this method is time-consuming, expensive and does not achieve a confirmatory genetic diagnosis in many cases. This study aims to test the level of improvement offered by a Next Generation Sequencing (NGS) gene-panel compared to the standard approach in a diagnostic reference laboratory setting. METHODS: A multi-gene NGS panel was used to test a total of 91 probands, previously classified as non-informative by analysing the high-risk genes defined in our guidelines. RESULTS: Nineteen deleterious mutations were detected in 16% of patients, some mutations were found in already-tested high-risk genes (BRCA1, BRCA2, MSH2) and others in non-prevalent genes (RAD51D, PALB2, ATM, TP53, MUTYH, BRIP1). CONCLUSIONS: Overall, our findings reclassify several index cases into different HCS, and change the mutational status of 14 cases from non-informative to gene mutation carriers. In conclusion, we highlight the necessity of incorporating validated multi-gene NGS panels into the HCSs diagnostic routine to increase the performance of genetic diagnosis.

Parathyroid autotransplantation in thyroid surgery.

BACKGROUND: Careful parathyroid gland dissection and in situ preservation was the time-honored approach to prevent parathyroid failure after total thyroidectomy. The relative success of parathyroid autotransplantation of hyperplastic parathyroid tissue in patients with renal or hereditary hyperparathyroidism did popularize the use of normal parathyroid tissue autografts during thyroidectomy to prevent permanent hypoparathyroidism. Proof of autograft function in this setting, however, is controversial. PURPOSE: This narrative review aims at reviewing critically the current status of parathyroid autotransplantation during total thyroidectomy. It is also meant to analyze from the historical, methodological, and clinical points of view the claimed benefit of normal parathyroid gland autotransplantation. A focus is placed on the prevention of permanent hypoparathyroidism by parathyroid autotransplantation. CONCLUSIONS: Liberal parathyroid autotransplantation was proposed in the mid 1970s but evidence of function is scarce. Proofs are accumulating that parathyroid autografts not only increase the rate of postoperative hypocalcemia, but may be also contribute to permanent hypoparathyroidism.

Clinical outcomes in patients with ST-segment elevation myocardial infarction treated with everolimus-eluting stents versus bare-metal stents (EXAMINATION): 5-year results of a randomised trial.

BACKGROUND: Data for the safety and efficacy of new-generation drug-eluting stents at long-term follow-up, and specifically in patients with ST-segment elevation myocardial infarction, are scarce. In the EXAMINATION trial, we compared everolimus-eluting stents (EES) with bare-metal stents (BMS) in an all-comer population with ST-segment elevation myocardial infarction. In this study, we assessed the 5-year outcomes of the population in the EXAMINATION trial. METHODS: In the multicentre EXAMINATION trial, done in Italy, Spain, and the Netherlands, patients with ST-segment elevation myocardial infarction were randomly assigned in a 1:1 ratio to receive EES or BMS. The random allocation schedule was computer-generated and central randomisation (by telephone) was used to allocate patients in blocks of four or six, stratified by centre. Patients were masked to treatment assignment. At 5 years, we assessed the combined patient-oriented outcome of all-cause death, any myocardial infarction, or any revascularisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00828087. FINDINGS: 1498 patients were randomly assigned to receive either EES (n=751) or BMS (n=747). At 5 years, complete clinical follow-up data were obtained for 731 patients treated with EES and 727 treated with BMS (97% of both groups). The patient-oriented endpoint occurred in 159 (21%) patients in the EES group versus 192 (26%) in the BMS group (hazard ratio 0·80, 95% CI 0·65-0·98; p=0·033). This difference was mainly driven by a reduced rate of all-cause mortality (65 [9%] vs 88 [12%]; 0·72, 0·52-0·10; p=0·047). INTERPRETATION: Our findings should be taken as a point of reference for the assessment of new bioresorbable polymer-based metallic stents or bioresorbable scaffolds in patients with ST-segment elevation myocardial infarction. FUNDING: Spanish Heart Foundation.

Long-term outcomes of rotational atherectomy for the percutaneous treatment of chronic total occlusions.

OBJECTIVES: To study the long-term outcomes of rotational atherectomy (RA) for chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: There is little evidence on the incidence, procedural results and long-term outcomes of RA for CTO PCI. METHODS: This registry included data from consecutive patients undergoing CTO PCI at four specialized centers. Major adverse cardiac events (MACE: cardiac death, target-vessel myocardial infarction and ischemia-driven target-vessel revascularization) on follow-up were the primary endpoint. RESULTS: A total of 1003 patients were included. Of these, 35 (3.5%) required RA. As compared with Conventional PCI, RA patients were older (68.9 ± 9.5 vs. 64.6 ± 10.7 years, P = 0.02), had higher prevalence of diabetes (58% vs. 37%, P = 0.01) and of a J-CTO score ≥2 (80% vs. 58%, P = 0.009), driven by severe calcification. Antegrade wire escalation was used more frequently in RA (74% vs. 53%, P = 0.08). RA was performed for balloon failure-to-cross in 51% and failure-to-expand in 49%. One burr was utilized in 86%. The 1.25-mm burr was the largest burr used in 43%. Slow flow/no-reflow was observed in 17%. No other serious RA-related complications were observed. Procedural success was 77% vs. 89% (P = 0.04) in RA vs. Conventional PCI. After a mean follow-up of 658 ± 412 days, MACE rates were similar between groups (15% vs. 13%, P = 0.70). CONCLUSIONS: The use of RA in CTO PCI was safe, despite a worse patient risk profile and higher procedural complexity, as compared with conventional techniques. Although procedural success was lower in the RA group, there were no differences in long-term clinical outcomes between groups. © 2016 Wiley Periodicals, Inc.

Quality of care assessment and improvement in aortic stenosis - rationale and design of a multicentre registry (IMPULSE).

BACKGROUND: Severe aortic stenosis (AS) is a common, serious valve disease in which no effective medical therapy is available and, if not treated by intervention, has a 5-year survival of only 40-60%. Despite the availability of guidelines supporting the effective use of surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) to treat the majority of these patients, adherence to these guidelines in clinical practice is still unsatisfactory. Several recent studies have emphasised the necessity for improved communication between multidisciplinary teams, with the aim to ensure that severe AS patients receive appropriate treatment. METHODS/DESIGN: IMPULSE is a prospective, multicentre, European registry designed to gather data over 12 months on the treatment decisions made by referring physicians for patients newly diagnosed with severe AS. Each patient has a follow-up of 3 months. The study will consist of two observational phases to assess the appropriateness and rate of referral based on current guidelines prior to and after an interventional phase aiming to determine whether a simple quality of care intervention improves patient management. DISCUSSION: Data will be analysed firstly, to determine the appropriateness of treatment decisions for the management of severe AS in current European clinical practice, and secondly, to evaluate the effectiveness of facilitated data relay from a designated echocardiography department nurse to the referring physician early after diagnosis in improving quality of care. Additionally, variables will be identified that are associated with inappropriate decision-making. Collectively, the aim will be to design a clinical pathway that will improve the timely management of patients with newly diagnosed severe AS.

Failure of fragmented parathyroid gland autotransplantation to prevent permanent hypoparathyroidism after total thyroidectomy.

PURPOSE: Parathyroid autotransplantation during total thyroidectomy leads to higher rates of postoperative hypocalcaemia. It has been argued, however, that it prevents permanent hypoparathyroidism. The impact of autografted normal parathyroid gland fragments on long-term parathyroid status has not been assessed properly. To clarify this, the short- and long-term parathyroid function was assessed in patients with three glands remaining in situ after total thyroidectomy, in whom the fourth gland was either autotransplanted (Tx) or accidentally resected (AR). METHODS: Consecutive patients (n = 669) undergoing first-time total thyroidectomy were prospectively studied recording the number of parathyroid glands remaining in situ: PGRIS =4-(glands autografted + glands in the specimen). The study was focused on the subgroup of 186 patients with three parathyroid glands remaining in situ as a result of either accidental resection (AR, n = 76) or autotransplantation into the sternocleidomastoid muscle (Tx, n = 110). Prevalence of postoperative hypocalcaemia, protracted, and permanent hypoparathyroidism were compared between the two groups. Demographic, disease-related, laboratory, and surgical variables were recorded. All patients were followed for at least 1 year. RESULTS: Both groups were comparable in terms of disease and extent of surgery. Mean postoperative serum calcium was the same (AR: 1.97 ± 0.2 vs Tx: 1.97 ± 0.22 mmol/L). Rates of protracted (AR: 24% vs Tx: 25.5%) and permanent hypoparathyroidism (AR: 5.3% vs Tx: 7.3%) were similar in both groups. CONCLUSIONS: The prevalence of parathyroid failure syndromes after total thyroidectomy was similar whether a parathyroid gland was inadvertently excised or autotransplanted. Autotransplantation did not influence the permanent hypoparathyroidism rate.

Niosomes as Drug Nanovectors: Multiscale pH-Dependent Structural Response.

The use of nanocarriers, which respond to different stimuli controlling their physicochemical properties and biological responsivness, shows a growing interest in pharmaceutical science. The stimuli are activated by targeting tissues and biological compartments, e.g., pH modification, temperature, redox condition, enzymatic activity, or can be physically applied, e.g., a magnetic field and ultrasound. pH modification represents the easiest method of passive targeting, which is actually used to accumulate nanocarriers in cells and tissues. The aim of this paper was to physicochemically characterize pH-sensitive niosomes using different experimental conditions and demonstrate the effect of surfactant composition on the supramolecular structure of niosomes. In this attempt, niosomes, made from commercial (Tween21) and synthetic surfactants (Tween20 derivatives), were physicochemically characterized by using different techniques, e.g., transmission electron microscopy, Raman spectroscopy, and small-angle X-ray scattering. The changes of niosome structure at different pHs depend on surfactants, which can affect the supramolecular structure of colloidal nanocarriers and their potential use both in vitro and in vivo. At pH 7.4, the shape and structure of niosomes have been maintained; however, niosomes show some differences in terms of bilayer thicknesses, water penetration, membrane coupling, and cholesterol dispersion. The acid pH (5.5) can increase the bilayer fluidity, and affect the cholesterol depletion. In fact, Tween21 niosomes form large vesicles with lower curvature radius at acid pH; while Tween20-derivative niosomes increase the intrachain mobility within a more interchain correlated membrane. These results demonstrate that the use of multiple physicochemical procedures provides more information about supramolecular structures of niosomes and improves the opportunity to deeply investigate the effect of stimuli responsiveness on the niosome structure.

Compliance with recommendations on surgery for primary hyperparathyroidism-from guidelines to real practice: results from an Iberian survey.

PURPOSE: Knowledge about compliance with recommendations derived from the positional statement of the European Society of Endocrine Surgeons on modern techniques in primary hyperparathyroidism surgery and the Third International Workshop on management of asymptomatic primary hyperparathyroidism is scarce. Our purpose was to check it on a bi-national basis and determine whether management differences may have impact on surgical outcomes. METHODS: An online survey including questions about indications, preoperative workup, surgical approach, intraoperative adjuncts, and outcomes was sent to institutions affiliated to the endocrine surgery divisions of the National Surgical Societies from Spain and Portugal. A descriptive evaluation of the responses was performed. Finally, we assessed the correlation between the different types of management with the achievement of optimal results, defined as a cure rate equal or greater than the median of all interviewed institutions. RESULTS: Fifty-seven hospitals (41 Spanish, 16 Portuguese) answered the survey. First-ordered imaging tests were neck ultrasound and sestamibi scan. Facing negative or non-concordant results, 44 % of surgeons ordered additional tests before first-time surgery, and 84 % before reoperations. When indicated, selective parathyroidectomy was an acceptable option for 95 % of institutions as first-time surgery and for 51 % in reoperations. Intraoperative parathormone measurements were used by 92 % of departments. The surgical outcomes were good in most institutions (median cure rate 97 %) and were influenced mostly by the presence of an endocrine surgery unit in the surgical department (p = 0.038). CONCLUSIONS: Practice of Iberian endocrine surgeons is consistent with current recommendations on surgery for primary hyperparathyroidism, with variability in some areas.