Bleeding risk prediction after acute myocardial infarction-integrating cancer data: the updated PRECISE-DAPT cancer score.

BACKGROUND AND AIMS: This study assessed the impact of incorporating cancer as a predictor on performance of the PRECISE-DAPT score. METHODS: A nationally linked cohort of ST-elevation myocardial infarction patients between 1 January 2005 and 31 March 2019 was derived from the UK Myocardial Ischaemia National Audit Project and the UK Hospital Episode Statistics Admitted Patient Care registries. The primary outcome was major bleeding at 1 year. A new modified score was generated by adding cancer as a binary variable to the PRECISE-DAPT score using a Cox regression model and compared its performance to the original PRECISE-DAPT score. RESULTS: A total of 216 709 ST-elevation myocardial infarction patients were included, of which 4569 had cancer. The original score showed moderate accuracy (C-statistic .60), and the modified score showed modestly higher discrimination (C-statistics .64; hazard ratio 1.03, 95% confidence interval 1.03-1.04) even in patients without cancer (C-statistics .63; hazard ratio 1.03, 95% confidence interval 1.03-1.04). The net reclassification index was .07. The bleeding rates of the modified score risk categories (high, moderate, low, and very low bleeding risk) were 6.3%, 3.8%, 2.9%, and 2.2%, respectively. According to the original score, 65.5% of cancer patients were classified as high bleeding risk (HBR) and 21.6% were low or very low bleeding risk. According to the modified score, 94.0% of cancer patients were HBR, 6.0% were moderate bleeding risk, and no cancer patient was classified as low or very low bleeding risk. CONCLUSIONS: Adding cancer to the PRECISE-DAPT score identifies the majority of patients with cancer as HBR and can improve its discrimination ability without undermining its performance in patients without cancer.

Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials.

AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients. METHODS AND RESULTS: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation. CONCLUSION: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen. STUDY REGISTRATION: PROSPERO registration number CRD42021284004.

Complex reconstruction of the clavicle with a prefabricated medial femur condyle chimeric flap including a superficial circumflex iliac artery perforator flap: A case report.

The medial femur condyle (MFC) cortico-periosteal flap is a popular flap for bone reconstruction. The use of a chimeric version of this flap with a skin island has been described, but anatomical arterial variation can occur that prevent its harvest. Furthermore, the donor area of the skin paddle has been debated as poor because of the scarring in a visible area and because of the difficulty in obtaining pliable thin skin. We present a fabricated chimeric MFC cortico-periosteal flap joined with a superficial inferior epigastric perforator (SCIP) flap to reconstruct and augment a sclerotic and insufficient small clavicula with the skin paddle acting as a monitor and as a substitute for the overlying skin. A 52-year-old female patient had a history of multiple refractures of the right hypoplastic clavicle with a diameter of 7 mm, resulting in a sclerotic bone with a fibrotic scar. The reconstruction was done in one surgical session using a cortico-periosteal flap from the left medial condyle and a thin SCIP flap from the left groin. The area of the clavicle to be reconstructed was 3 cm, and the direct overlying skin (approximately 6 × 3 cm) was severely scarred and painful. The MFC flap was 5 × 4 cm, while the SCIP flap was 7 × 3.5 cm. The SCIP flap artery was anastomosed on the table end-to-side to the descending genicular (DG) artery of the MFC, and the vein was anastomosed end-to-end to a comitans vein of the DG artery. The flap fully survived after an initial congestion. At 12 months, we observed a satisfactory reconstruction of the clavicle with an enhanced diameter of 12 mm. The patient recovered full function of the shoulder with no pain. Using a fabricated chimeric flap composed of a medial femoral condyle and a superficial circumflex artery perforator flap may be an additional option for tailored reconstruction of complex osteo-cutaneous defect of clavicle.

External validation of bleeding risk models for the prediction of long-term bleeding risk in patients with established cardiovascular disease.

OBJECTIVE: The long-term predictive performance of existing bleeding risk models in patients with various manifestations of cardiovascular disease (CVD) is not well known. This study aims to assess and compare the performance of relevant existing bleeding risk models in estimating the long-term risk of major bleeding in a cohort of patients with established CVD. METHODS: Seven existing bleeding risk models (PRECISE-DAPT, DAPT, Ducrocq et al, de Vries et al, S2TOP-BLEED, Intracranial B2LEED3S and HAS-BLED) were identified and externally validated in 7,249 patients with established CVD included in the Utrecht Cardiovascular Cohort-second manifestations of arterial disease study. Predictive performance was assessed in terms of discrimination and calibration, both at 10 years and the original prediction horizon of the models. Major bleeding was defined as Bleeding Academic Research Consortium type 3 or 5. RESULTS: After a median follow-up of 8.4 years (interquartile range 4.5-12.5), a total of 233 (3.2%) major bleeding events occurred. C-statistics for discrimination at 10 years ranged from 0.53 (95%CI 0.49-0.57) to 0.64 (95%CI 0.60-0.68). Calibration plots after recalibration to 10 years showed best agreement between predicted and observed bleeding risk for De Vries et al, S2TOP-BLEED, DAPT and PRECISE-DAPT. CONCLUSIONS: The performance of existing bleeding risk models to predict long-term bleeding in patients with CVD varied. Discrimination and calibration were best for the models of de Vries et al, S2TOP-BLEED, DAPT and PRECISE-DAPT. Of these, recalibrated models requiring the least predictors may be preferred for use to personalize prevention with antithrombotic therapy.

Rationale and design of the PARTHENOPE trial: A two-by-two factorial comparison of polymer-free vs biodegradable-polymer drug-eluting stents and personalized vs standard duration of dual antiplatelet therapy in all-comers undergoing PCI.

BACKGROUND: Over the past few decades, percutaneous coronary intervention (PCI) has undergone significant advancements as a result of the combination of device-based and drug-based therapies. These iterations have led to the development of polymer-free drug-eluting stents. However, there is a scarcity of data regarding their clinical performance. Furthermore, while various risk scores have been proposed to determine the optimal duration of dual antiplatelet therapy (DAPT), none of them have undergone prospective validation within the context of randomized trials. DESIGN: The PARTHENOPE trial is a phase IV, prospective, randomized, multicenter, investigator-initiated, assessor-blind study being conducted at 14 centers in Italy (NCT04135989). It includes 2,107 all-comers patients with minimal exclusion criteria, randomly assigned in a 2-by-2 design to receive either the Cre8 amphilimus-eluting stent or the SYNERGY everolimus-eluting stent, along with either a personalized or standard duration of DAPT. Personalized DAPT duration is determined by the DAPT score, which accounts for both bleeding and ischemic risks. Patients with a DAPT score <2 (indicating higher bleeding than ischemic risk) receive DAPT for 3 or 6 months for chronic or acute coronary syndrome, respectively, while patients with a DAPT score ≥2 (indicating higher ischemic than bleeding risk) receive DAPT for 24 months. Patients in the standard DAPT group receive DAPT for 12 months. The trial aims to establish the noninferiority between stents with respect to a device-oriented composite end point of cardiovascular death, target-vessel myocardial infarction, or clinically-driven target-lesion revascularization at 12 months after PCI. Additionally, the trial aims to demonstrate the superiority of personalized DAPT compared to a standard approach with respect to a net clinical composite of all-cause death, any myocardial infarction, stroke, urgent target-vessel revascularization, or type 2 to 5 bleeding according to the Bleeding Academic Research Consortium criteria at 24-months after PCI. SUMMARY: The PARTHENOPE trial is the largest randomized trial investigating the efficacy and safety of a polymer-free DES with a reservoir technology for drug-release and the first trial evaluating a personalized duration of DAPT based on the DAPT score. The study results will provide novel insights into the optimizing the use of drug-eluting stents and DAPT in patients undergoing PCI.

Economic impact of a more extensive use of FENO testing on the Italian population with asthma.

BACKGROUND: Asthma is a common chronic inflammatory airway affecting over 260 million people worldwide, and characterized, in the large majority of cases, by the so-called "type 2 inflammation". Fractional exhaled nitric oxide (FENO) testing is noninvasive point-of-care tool to assess type 2 inflammation and therefore improve asthma management. It has been suggested to determine eligibility for a specific biologic therapy and predict likelihood to respond. The aim of this study was to estimate the overall economic impact of an extensive use of FENO testing on the Italian population with asthma, including extra costs of testing and savings generated by more appropriate prescriptions, increased adherence and lower frequency of exacerbations. METHODS: A cost of illness analysis was firstly performed to estimate the yearly economic burden from the National Healthcare Service (NHS) perspective in Italy of the management of asthmatic patients with standard of care (SOC) according to the application of GINA (Global Initiative for Asthma) guidelines; then, we evaluated the changes in the economic burden in patient management by introducing FENO testing into clinical practice. The cost items considered were: visits/exams, exacerbations, drugs, management of adverse events caused by short-term oral corticosteroids use. Efficacy of FeNO test and SOC is based on literature evidence. Costs refer to published data or Diagnosis Related Group/outpatient tariffs. RESULTS: Considering one asthma visit every 6 months, the total yearly cost for the management of patients with asthma in Italy is 1,599,217,876€ (409.07€ per patient), while for FENO testing strategy this figure is 1,395,029,747€ (356.84€ per patient). An increased utilization rate of FENO testing from 50 to 100% of patients may lead to savings for the NHS from about 102 to 204 million € compared to SOC. CONCLUSIONS: Our study showed that FeNO testing strategy may improve the management of asthmatic patients leading to significant savings for the NHS.

Site-specific concordance of targeted and systematic biopsy cores at the index lesion on multiparametric magnetic resonance: can we spare the double-tap?

PURPOSE: To define the impact of systematic biopsy (SB) cores directed in the same area of index lesion in patients undergoing targeted biopsy (TB) and SB for prostate cancer (PCa) suspicion. METHODS: We retrospectively analyzed data of biopsy-naïve patients with one single suspicious lesion at mpMRI who underwent TB plus SB at our institution between January 2015 and September 2021. A convenient sample of 336 patients was available for our analyses. The primary outcome was to evaluate the impact of overlapping SB cores directed to the index lesion at mpMRI. The secondary outcome was to evaluate the SB cores concordance in terms of highest Gleason Score Detection with TB cores. RESULTS: 56% of patients were found to have site-specific concordance. SB cores determined disease upgrade in 22.1% patients. Thirty-one (16.4%) site-concordant patients experienced upgrade through overlapping SB cores, while 149 (79.3%) had no benefit by SB cores, and 8 (4.3%) patients had the worst ISUP at TB cores. 50% of the patients with negative-TB were upgraded to insignificant PCa, and 17.5% was upgraded from negative to unfavorable-intermediate- or high-risk PCa. Overall, 14 (19.4%) patients were also upgraded from ISUP 1 on TB to csPCa, with 28.5% of these harboring high-risk PCa. In csPCas at TB, 9 (12.5%) patients were upgraded from intermediate- to high-risk disease by SB. CONCLUSIONS: TB alone consents to identify worst ISUP PCa in vast majority of patients scheduled for biopsy. A non-negligible number of patients are upgraded via-SB cores, including also index lesion overlapping cores. Omitting these cores might lead to a suboptimal patient management.

Interaction of Substrates with γ-Secretase at the Level of Individual Transmembrane Helices-A Methodological Approach.

Intramembrane proteases, such as γ secretase, typically recruit multiple substrates from an excess of single-span membrane proteins. It is currently unclear to which extent substrate recognition depends on specific interactions of their transmembrane domains (TMDs) with TMDs of a protease. Here, we investigated a large number of potential pairwise interactions between TMDs of γ secretase and a diverse set of its substrates using two different configurations of BLaTM, a genetic reporter system. Our results reveal significant interactions between TMD2 of presenilin, the enzymatic subunit of γ secretase, and the TMD of the amyloid precursor protein, as well as of several other substrates. Presenilin TMD2 is a prime candidate for substrate recruitment, as has been shown from previous studies. In addition, the amyloid precursor protein TMD enters interactions with presenilin TMD 4 as well as with the TMD of nicastrin. Interestingly, the Gly-rich interfaces between the amyloid precursor protein TMD and presenilin TMDs 2 and 4 are highly similar to its homodimerization interface. In terms of methodology, the economics of the newly developed library-based method could prove to be a useful feature in related future work for identifying heterotypic TMD-TMD interactions within other biological contexts.

Off-Target Effects of P2Y12 Receptor Inhibitors: Focus on Early Myocardial Fibrosis Modulation.

Several studies have demonstrated that, beyond their antithrombotic effects, P2Y12 receptor inhibitors may provide additional off-target effects through different mechanisms. These effects range from the preservation of endothelial barrier function to the modulation of inflammation or stabilization of atherosclerotic plaques, with an impact on different cell types, including endothelial and immune cells. Many P2Y12 inhibitors have been developed, from ticlopidine, the first thienopyridine, to the more potent non-thienopyridine derivatives such as ticagrelor which may promote cardioprotective effects following myocardial infarction (MI) by inhibiting adenosine reuptake through sodium-independent equilibrative nucleoside transporter 1 (ENT1). Adenosine may affect different molecular pathways involved in cardiac fibrosis, such as the Wnt (wingless-type)/beta (ß)-catenin signaling. An early pro-fibrotic response of the epicardium and activation of cardiac fibroblasts with the involvement of Wnt1 (wingless-type family member 1)/ß-catenin, are critically required for preserving cardiac function after acute ischemic cardiac injury. This review discusses molecular signaling pathways involved in cardiac fibrosis post MI, focusing on the Wnt/ß-catenin pathway, and the off-target effect of P2Y12 receptor inhibition. A potential role of ticagrelor was speculated in the early modulation of cardiac fibrosis, thanks to its off-target effect.

New-Onset Atrial Fibrillation and Early Mortality Rate in COVID-19 Patients: Association with IL-6 Serum Levels and Respiratory Distress.

Background and objectives: COVID-19 is associated with an aberrant inflammatory response that may trigger new-onset cardiac arrhythmias. The aim of this study was to assess the mortality risk in hospitalized COVID-19 patients according to IL-6 serum levels and new-onset atrial fibrillation (AF) according to PaO2/FiO2 stratification. Materials and Methods: 175 COVID-19 patients (25 new-onset AF, 22 other types of AF and 128 no-AF) were included in this single-center, retrospective study; clinical and demographic data, vital signs, electrocardiograms and laboratory results were collected and analyzed. The primary outcome of the study was to evaluate the mortality rate in new-onset AF patients according to IL-6 serum levels and PaO2/FiO2 stratification. Results: The incidence of new-onset AF in the study population was 14.2%. Compared to the no-AF group, new-onset AF patients were older with a positive history of chronic kidney disease and heart failure, had higher IL-6, creatinine and urea serum levels whereas their platelet count was reduced. After PaO2/FiO2 stratification, 5-days mortality rate was higher in new-onset AF patients compared to patients with other types of AF and no-AF patients, and mortality risk increases 5.3 fold compared to no-AF (p = 0.0014) and 4.8 fold compared to other forms of AF (p = 0.03). Conclusions: New-onset AF is common in COVID-19 patients and is associated with increased IL-6 serum levels and early mortality. Further studies are needed to support the use of IL-6 as an early molecular target for COVID-19 patients to reduce their high rate of mortality.

Antithrombotic strategies in patients needing oral anticoagulation undergoing percutaneous coronary intervention: A network meta-analysis.

BACKGROUND: The optimal antithrombotic regimen in patients with a concomitant indication for oral anticoagulation (OAT) presenting with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) remains unclear. OBJECTIVES: To perform a network meta-analysis of all randomized controlled trials (RCTs) evaluating different antithrombotic regimens among patients with ACS or undergoing PCI requiring OAT. METHODS: Network meta-analysis was performed in a frequentist framework. Antithrombotic regimens were categorized by OAC type (vitamin K antagonist-based [VKA]; non-VKA OAT [NOAC]) and antiplatelet agents (P2Y inhibitor only: dual therapy [DAT]; P2Y plus aspirin: triple therapy [TAT]). Safety outcomes were Thrombolysis in Myocardial Infarction (TIMI) major bleeding and intracranial hemorrhage (ICH). Efficacy outcomes were cardiovascular death, myocardial infarction, stroke and stent-thrombosis (ST). RESULTS: Five RCTs were included, encompassing 10,797 patients (atrial fibrillation 69-100%, ACS 28-62%, PCI 77-100%). Both VKA and NOAC-based DAT regimens reduced the occurrence of TIMI major bleeding compared to VKA TAT (VKA DAT: RR 0.62, 95% CI 0.39-0.98; NOAC DAT: RR 0.52, 95% CI 0.39-0.70). Nevertheless, only NOAC DAT significantly reduced the occurrence of ICH compared to VKA TAT (RR 0.33, 95% CI 0.17-0.64). Ischemic outcomes were similar among the four treatment regimens. However, numerical, potentially clinically important, higher ST occurrence was observed for NOAC DAT as compared to both VKA TAT (1.50, 95% confidence interval [CI] 0.96-2.33) and NOAC TAT (1.86, 95% CI 0.93-3.73). CONCLUSION: DAT regimens present the highest safety profile among antithrombotic strategies, with a NOAC-specific impact on ICH reduction. NOAC DAT might entail clinically important higher ST occurrence, warranting a case-by-case comprehensive evaluation that integrates patient- and procedure-related residual ischemic risk with the patient-specific bleeding risk.

Accuracy of the PARIS score and PCI complexity to predict ischemic events in patients treated with very thin stents in unprotected left main or coronary bifurcations.

BACKGROUND: The PARIS risk score (PARIS-rs) and percutaneous coronary intervention complexity (PCI-c) predict clinical and procedural residual ischemic risk following PCI. Their accuracy in patients undergoing unprotected left main (ULM) or bifurcation PCI has not been assessed. METHODS: The predictive performances of the PARIS-rs (categorized as low, intermediate, and high) and PCI-c (according to guideline-endorsed criteria) were evaluated in 3,002 patients undergoing ULM/bifurcation PCI with very thin strut stents. RESULTS: After 16 (12-22) months, increasing PARIS-rs (8.8% vs. 14.1% vs. 27.4%, p < .001) and PCI-c (15.2% vs. 11%, p = .025) were associated with higher rates of major adverse cardiac events ([MACE], a composite of death, myocardial infarction [MI], and target vessel revascularization), driven by MI/death for PARIS-rs and target lesion revascularization/stent thrombosis for PCI-c (area under the curves for MACE: PARIS-rs 0.60 vs. PCI-c 0.52, p-for-difference < .001). PCI-c accuracy for MACE was higher in low-clinical-risk patients; while PARIS-rs was more accurate in low-procedural-risk patients. ≥12-month dual antiplatelet therapy (DAPT) was associated with a lower MACE rate in high PARIS-rs patients, (adjusted-hazard ratio 0.42 [95% CI: 0.22-0.83], p = .012), with no benefit in low to intermediate PARIS-rs patients. No incremental benefit with longer DAPT was observed in complex PCI. CONCLUSIONS: In the setting of ULM/bifurcation PCI, the residual ischemic risk is better predicted by a clinical risk estimator than by PCI complexity, which rather appears to reflect stent/procedure-related events. Careful procedural risk estimation is warranted in patients at low clinical risk, where PCI complexity may substantially contribute to the overall residual ischemic risk.

A rare case of giant calcified thoracic disc herniation, OPLL and OLF: how I do it.

BACKGROUND: Thoracic myelopathy can have different aetiologies. Based on the location and on the nature of spinal cord compression, different surgical approaches may be indicated. METHOD: We present a rare case of thoracic myelopathy caused by the coexistence of a giant disc herniation, OPLL and OLF, and we describe the surgical approach, with a focus on technical nuances and strategies to avoid complications. CONCLUSION: Careful presurgical planning and microsurgery are fundamental in achieving a satisfactory spinal cord decompression. IONM, endoscopy-assisted microsurgery and intraoperative navigation can enhance the safety of surgery and the extent of safe surgical decompression.

A 4-item PRECISE-DAPT score for dual antiplatelet therapy duration decision-making.

The originally-proposed PRECISE-DAPT score is a 5-item risk score supporting decision-making for dual antiplatelet therapy1 duration after PCI. It is unknown if a simplified version of the score based on 4 factors (age, hemoglobin, creatinine clearance, prior bleeding), and lacking white-blood cell count, retains potential to guide DAPT duration. The 4-item PRECISE-DAPT was used to categorize 10,081 patients who were randomized to short (3-6 months) or long (12-24 months) DAPT regimen according to high (HBR defined by PRECISE-DAPT ≥25 points) or non-high bleeding risk (PRECISE-DAPT<25) status. Long treatment duration was associated with higher bleeding rates in HBR (ARD +2.22% [95% CI +0.53 to +3.90]) but not in non-HBR patients (ARD +0.25% [-0.14 to +0.64]; pint = 0.026), and associated with lower ischemic risks in non-HBR (ARD -1.44% [95% CI -2.56 to -0.31]), but not in HBR patients (ARD +1.16% [-1.91 to +4.22]; pint = 0.11). Only non-HBR patients experienced lower net clinical adverse events (NACE) with longer DAPT (pint = 0.043). A 4-item simplified version of the PRECISE-DAPT score retains the potential to categorize patients who benefit from prolonged DAPT without concomitant bleeding liability from those who do not.

Assessment of serum cytokines predicts clinical and endoscopic outcomes to vedolizumab in ulcerative colitis patients.

AIMS: Vedolizumab (VDZ) prevents migration of activated leucocytes into inflamed mucosa. This study aimed to assess the patterns of serum cytokines in ulcerative colitis (UC) patients at baseline and during VDZ treatment, and to investigate their association with mucosal healing and clinical remission. METHODS: We enrolled consecutive UC patients eligible for treatment with VDZ. A panel of serum cytokines were measured by fluorescence assay at weeks 0, 6 and 22. Colonoscopy was performed at baseline and week 54, to evaluate mucosal healing. The time trends of serum cytokines were analysed by log-linear mixed effect models, and their prognostic accuracy was evaluated by logistic regression. RESULTS: Out of 27 patients included in the analysis, at week 54 mucosal healing was achieved in 12 (44%) and clinical remission in 17 (63%). Mucosal healing was associated with higher interleukin (IL)-8 values at baseline and with significant decrease in IL-6 and IL-8 levels over the first 6 weeks. A significant reduction of IL-6 and IL-8 levels over the first 6 weeks of treatment was associated also with clinical remission. Logistic models including, among the predictors, IL-6 and IL-8 at baseline and their changes over the first 6 weeks of treatment had 83% sensitivity and 87% specificity to predict mucosal healing, and 82% sensitivity and 90% specificity to predict clinical remission. CONCLUSION: In UC patients, the serum patterns of IL-6 and IL-8 at baseline and over the first 6 weeks of treatment with VDZ could be useful to predict therapeutic outcome.

Corticosteroid Treatment at Diagnosis: An Analysis of Relapses, Disease Extension, and Colectomy Rate in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis is a chronic relapsing disease usually treated with mesalamine. The need of steroid therapy at diagnosis is generally considered as a poor prognostic factor. AIMS: The aim of our study was to assess whether patients treated with corticosteroids at diagnosis have more clinical relapses, disease progression, or an increased risk of colectomy during a 5-year follow-up. METHODS: We retrospectively evaluated patients who had received diagnosis of ulcerative colitis with a 5-year follow-up. Relapse was defined as a worsening of symptoms requiring an increase in medical treatment. Progression of disease was defined as a proximal extension of mucosal involvement, comparing the colonoscopy performed 5 years after diagnosis with the first one. The need of corticosteroid treatment at diagnosis was correlated to number of relapses, disease progression, and colectomy rate. RESULTS: We included 230 patients, 116 of them (50%) treated with steroids at diagnosis. Multivariate analysis demonstrated that there is a strong correlation between corticosteroid use and number of relapses (p < 0.01), as well as with disease progression (p < 0.05). Seventeen patients (7.4%) underwent colectomy, but the correlation with steroids was not statistically significant. CONCLUSIONS: These data provide evidence that the need of corticosteroids at diagnosis is associated with a worse clinical outcome.

Standardized classification and framework for reporting, interpreting, and analysing medication non-adherence in cardiovascular clinical trials: a consensus report from the Non-adherence Academic Research Consortium (NARC).

Non-adherence has been well recognized for years to be a common issue that significantly impacts clinical outcomes and health care costs. Medication adherence is remarkably low even in the controlled environment of clinical trials where it has potentially complex major implications. Collection of non-adherence data diverge markedly among cardiovascular randomized trials and, even where collected, is rarely incorporated in the statistical analysis to test the consistency of the primary endpoint(s). The imprecision introduced by the inconsistent assessment of non-adherence in clinical trials might confound the estimate of the calculated efficacy of the study drug. Hence, clinical trials may not accurately answer the scientific question posed by regulators, who seek an accurate estimate of the true efficacy and safety of treatment, or the question posed by payers, who want a reliable estimate of the effectiveness of treatment in the marketplace after approval. The Non-adherence Academic Research Consortium is a collaboration among leading academic research organizations, representatives from the U.S. Food and Drug Administration and physician-scientists from the USA and Europe. One in-person meeting was held in Madrid, Spain, culminating in a document describing consensus recommendations for reporting, collecting, and analysing adherence endpoints across clinical trials. The adoption of these recommendations will afford robustness and consistency in the comparative safety and effectiveness evaluation of investigational drugs from early development to post-marketing approval studies. These principles may be useful for regulatory assessment, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.

Fully automated radiological analysis of spinal disorders and deformities: a deep learning approach.

PURPOSE: We present an automated method for extracting anatomical parameters from biplanar radiographs of the spine, which is able to deal with a wide scenario of conditions, including sagittal and coronal deformities, degenerative phenomena as well as images acquired with different fields of view. METHODS: The location of 78 landmarks (end plate centers, hip joint centers, and margins of the S1 end plate) was extracted from three-dimensional reconstructions of 493 spines of patients suffering from various disorders, including adolescent idiopathic scoliosis, adult deformities, and spinal stenosis. A fully convolutional neural network featuring an additional differentiable spatial to numerical (DSNT) layer was trained to predict the location of each landmark. The values of some parameters (T4-T12 kyphosis, L1-L5 lordosis, Cobb angle of scoliosis, pelvic incidence, sacral slope, and pelvic tilt) were then calculated based on the landmarks' locations. A quantitative comparison between the predicted parameters and the ground truth was performed on a set of 50 patients. RESULTS: The spine shape predicted by the models was perceptually convincing in all cases. All predicted parameters were strongly correlated with the ground truth. However, the standard errors of the estimated parameters ranged from 2.7° (for the pelvic tilt) to 11.5° (for the L1-L5 lordosis). CONCLUSIONS: The proposed method is able to automatically determine the spine shape in biplanar radiographs and calculate anatomical and posture parameters in a wide scenario of clinical conditions with a very good visual performance, despite limitations highlighted by the statistical analysis of the results. These slides can be retrieved under Electronic Supplementary Material.