Supramolecular chemistry enables vat photopolymerization 3D printing of novel water-soluble tablets

YesVat photopolymerization has garnered interest from pharmaceutical researchers for the fabrication of personalised medicines, especially for drugs that require high precision dosing or are heat labile. However, the 3D printed structures created thus far have been insoluble, limiting printable dosage forms to sustained-release systems or drug-eluting medical devices which do not require dissolution of the printed matrix. Resins that produce water-soluble structures will enable more versatile drug release profiles and expand potential applications. To achieve this, instead of employing cross-linking chemistry to fabricate matrices, supramolecular chemistry may be used to impart dynamic interaction between polymer chains. In this study, water-soluble drug-loaded printlets (3D printed tablets) are fabricated via digital light processing (DLP) 3DP for the first time. Six formulations with varying ratios of an electrolyte acrylate

Comparison of Resting PD/PA with Fractional Flow Reserve Using a Monorail Pressure Catheter

Background: The RXi™ system (ACIST Medical Systems, MN, USA) is a new Fractional Flow Reserve (FFR) technology utilising an ultrathinmonorail microcatheter (Navvus®; ACIST Medical Systems) with an optical pressure sensor located close to the distal catheter tip. FFR measurement using monorail microcatheter is comparable to the conventional pressure wires. However, the predictive value of resting distal coronary artery pressure/aortic pressure (Pd/Pa) on hyperemic FFR value in the real world practice is unknown. Objective: To explore the diagnostic accuracy of resting Pd/Pa in relation to hyperemic FFR using the monorail pressure catheter. Methods: Resting Pd/Pa and FFR were measured using monorail pressure catheter in 67 consecutive patients with intermediate coronary artery lesions (30% to 80% diameter stenoses) between 01-03-2016 to 17-01-2017. Of 121 studied lesions, 29 (23.97%) were excluded because of no hyperemic FFR due to postive resting Pd/Pa (n=17), severe or non-critical stenosis (n=11) and suboptimal acquisition (n=1), leaving 92 lesions for final analysis. Hyperemic FFR was induced with intracoronary adenosine. The selection of coronary wire and the dose of intracoronary nitroglycerine were at the operators’ discretions. Results: Bland-Altman plots showed a moderate degree of scatter between Pd/Pa and FFR value. On average, Pd/Pa exceeded FFR by 0.066 (-0.09 to +0.22). Receiver-operating characteristic curves of the resting Pd/Pa with FFR≤0.80 as the reference variable showed an area under the curve of 0.78 (95% confidence intervals 0.680 to 0.881, pb0.001), with a diagnostic accuracy of 79.3% when the resting Pd/Pa was ≤0.86. Certain cutoff values of Pd/Pa can reliably predict whether hyperemic FFR was positive or negative (FFR cutoff≤0.80). Resting Pd/Pa value of N0.96 had a negative predictive value (NPV) of 100% and sensitivity of 100%; the resting Pd/Pa value of ≤0.82 had a positive predictive value (PPV) of 100% and specificity of 98.3%. These were consistent regardless of coronary vessel, location of lesion or degree of diameter stenosis. Conclusions: Certain range of resting Pd/Pa measured by monorail pressure catheter had excellent NPV and sensitivity or excellent PPV and specificity to predict hyperemic FFR. Clinical outcome studies are required to determine whether the results might obviate the need for hyperemia in selected patients

Thirty-Day Clinical Outcome of Primary Percutaneous Intervention Versus Fibrinolysis Followed by Coronary Angiography in ST-Segment Elevation Myocardial Infarction

Background: Primary percutaneous coronary intervention (PCI)is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI). However, timely PCI cannot be offered to many patients. Objective: The purpose of this study was to compare the 30-day clinical outcome of primary PCI strategy and fibrinolysis followed by coronary angiography strategy in STEMI patients. Methods: This was a prospective, observational, single center study. All patients admitted for STEMI from 1 January 2016 to 30 November 2016 were screened for the study. Patients were divided into 2 reperfusion strategies: primary PCI or fibrinolysis followed by coronary angiography. Primary outcome was composite of all-cause mortality at 30 days. Results: A total of 178 patients were identified: 33 (18.5%) underwent primary PCI and 145 (81.5%) underwent fibrinolysis first. The median door-to-balloon time in the primary PCI group was 161.0 minutes (IQR 84.5). The median time from fibrinolysis-to-arrival at catheterization lab was 1738 minutes (IQR 901). The median total ischaemic time was 369 min (IQR 524) and 210 (IQR 247) for the primary PCI and fibrinolysis first group respectively (p=0.002). Kaplan-Meier survival analysis for 30-day all-cause mortality was 24.2% vs 9.7% respectively in primary PCI and fibrinolysis group p=0.018). Multivariate Linear Regression showed that Killip Class and LVEF were independent predictors of 30-day all-cause mortality. Reperfusion strategy was not associated with 30-day all-cause mortality (p=0.216). Conclusions: The clinical outcome of primary PCI strategy in STEMI is not better than fibrinolysis followed by coronary angiography strategy when timely PCI cannot be performed

Read My Lips: Continuous Signer Independent Weakly Supervised Viseme Recognition

Abstract. This work presents a framework to recognise signer indepen-dent mouthings in continuous sign language, with no manual annotations needed. Mouthings represent lip-movements that correspond to pronun-ciations of words or parts of them during signing. Research on sign lan-guage recognition has focused extensively on the hands as features. But sign language is multi-modal and a full understanding particularly with respect to its lexical variety, language idioms and grammatical structures is not possible without further exploring the remaining information chan-nels. To our knowledge no previous work has explored dedicated viseme recognition in the context of sign language recognition. The approach is trained on over 180.000 unlabelled frames and reaches 47.1 % precision on the frame level. Generalisation across individuals and the influence of context-dependent visemes are analysed

Reversal of cardiac damage in patients with symptomatic severe aortic stenosis following transcatheter aortic valve implantation: An echocardiographic study

Background: Severe aortic stenosis (AS) results in cardiac damages, such as left ventricular hypertrophy, left atrial enlargement, pulmonary pressure elevation and in advanced stage, right ventricular damage. Généreux and colleagues proposed a staging classification based on these extra-valvular damages in 2017, with increasing stage representing more cardiac damage. While regression of these cardiac damages is expected following aortic valve replacement, the reversal of cardiac damage based on this staging system has not been described. Purpose: This study aimed to describe and stage the changes in cardiac structure and function at 6 months and 1 year after transcatheter aortic valve implantation (TAVI) in patients with symptomatic severe AS. Methods: This was a retrospective, single center, longitudinal observational study. Echocardiographic data of patients who underwent TAVI were retrieved and analysed. Results: From May 2018 to Feb 2021, 31 patients underwent TAVI. 5 patients were excluded due to death <6 months post-procedure (n=2) and incomplete echocardiographic data (n=3). The mean age of the remaining 26 patients was 70.9±9.4 years, 57.7% were male, and 34.6% bicuspid aortic valve. After TAVI, transvalvular aortic mean pressure gradient reduced from 45.2±14.5 mmHg to 8.0±5.4 mmHg (p<0.001), and aortic valve area increased from 0.57±0.21 cm2 to 1.75±0.68 cm2 (p<0.001). At baseline, 6-month and 1-year, the left ventricular mass index (LVMi) were 183.4±60.7g/m2, 150.8±55.3 g/m2 and 126.8±42.1 g/m2 (p<0.001) respectively; left-atrial volume index (LAVI) were 60.4±22.8 ml/m2 , 51.7±23.8ml/m2, and 48.1±23.6ml/m2 (p=0.009) respectively; left ventricular ejection fraction (LVEF) were 52.3±25.4%, 64.2±29.3%, and 62.4±12.1% (p=0.005) respectively. Based on the proposed cardiac damage staging for AS, at baseline 38% of patients were stage 1, 65.4% stage 2, 7.7% stage 3 and 23.1% stage 4. At 1 year, 8.3% were stage 0, 29.2% stage 1, 58.3% stage 2, and 4.2% stage 4. 12 patients (46%) showed improvement in cardiac damage staging, and the other 14 (54%) remained in the same stage. Conclusion: In patients with symptomatic severe AS, there were overall significant regression in LVMi and LAVI, and improvement in LVEF at 1 year after TAVI. However, improvement in cardiac damage staging was observed in only 46% of patients

Meta-GWAS identifies the heritability of acute radiation-induced toxicities in head and neck cancer

Background and purpose: We aimed to the genetic components and susceptibility variants associated with acute radiation-induced toxicities (RITs) in patients with head and neck cancer (HNC). Materials and methods: We performed the largest meta-GWAS of seven European cohorts (n = 4,042). Patients were scored weekly during radiotherapy for acute RITs including dysphagia, mucositis, and xerostomia. We analyzed the effect of variants on the average burden (measured as area under curve, AUC) per each RIT, and standardized total average acute toxicity (STATacute) score using a multivariate linear regression. We tested suggestive variants (p < 1.0x10-5) in discovery set (three cohorts; n = 2,640) in a replication set (four cohorts; n = 1,402). We meta-analysed all cohorts to calculate RITs specific SNP-based heritability, and effect of polygenic risk scores (PRSs), and genetic correlations among RITS. Results: From 393 suggestive SNPs identified in discovery set; 37 were nominally significant (preplication < 0.05) in replication set, but none reached genome-wide significance (pcombined < 5 × 10-8). In-silico functional analyses identified “3′-5'-exoribonuclease activity” (FDR = 1.6e-10) for dysphagia, “inositol phosphate-mediated signalling” for mucositis (FDR = 2.20e-09), and “drug catabolic process” for STATacute (FDR = 3.57e-12) as the most enriched pathways by the RIT specific suggestive genes. The SNP-based heritability (±standard error) was 29 ± 0.08 % for dysphagia, 9 ± 0.12 % (mucositis) and 27 ± 0.09 % (STATacute). Positive genetic correlation was rg = 0.65 (p = 0.048) between dysphagia and STATacute. PRSs explained limited variation of dysphagia (3 %), mucositis (2.5 %), and STATacute (0.4 %). Conclusion: In HNC patients, acute RITs are modestly heritable, sharing 10 % genetic susceptibility, when PRS explains < 3 % of their variance. We identified numerus suggestive SNPs, which remain to be replicated in larger studies

The role of extracellular volume fraction in predicting left ventricular reverse remodelling and adverse outcomes in patients with non-ischemic cardiomyopathy and reduced left ventricular ejection fraction

Cardiac magnetic resonance (CMR) permits the quantification of extracellular volume fraction (ECV) which is a surrogate marker of myocardial interstitial fibrosis. ECV has been shown to predict heart failure (HF) events. Conversely, left ventricular reverse remodelling (LVRR) defined as decrease in chamber volumes and improvement in function, has a positive impact on prognosis. In patients with non-ischemic cardiomyopathy (NICM), the role of ECV in LVRR is not established

Electrical characteristics and clinical outcomes during left bundle branch area pacing in patients with narrow QRS and comparison in mechanical synchrony with his bundle pacing, biventricular pacing and right ventricular apical pacing

Conduction system pacing preserves physiological electrical synchrony in comparison to conventional right ventricular apical pacing (RVAP). Left bundle branch area pacing (LBBAP), an alternative modality to His Bundle Pacing (HBP) has been recently reported to have higher implant success rates, stable electrical parameters, and fewer lead-related problems. Limited evidence demonstrated that LBBAP may circumvent the technical and electrophysiological difficulties encountered in His bundl

Prognostic Value of N-terminal B-type Natriuretic Peptide in Patients with Acute Myocardial Infarction: A Multicenter Study

Background: Several models have been developed to help the clinician in risk stratification for Acute Coronary Syndrome (ACS),such as the TIMI and GRACE risk scores. However, there is conflicting evidence for the prognostic value of NT-ProBNP in acute myocardial infarction (AMI). Objective: (1) To explore the association of NT-proBNP with 30-day clinical outcome in AMI patients. (2) To compare the prognostic value of NT-proBNP with TIMI and GRACE risk scores in AMI patients. Methods: We conducted a multicenter, prospective observational study recruiting patients presented with AMI between 29-October-2015 and 14-January-2017, involving 1 cardiology referral centre and 4 non-cardiology hospitals. NT-proBNP level (Alere Triage®, US)was measured within 24 hours fromthe diagnosis of AMI. Patientswere followed-up for 1 month. Results: A total of 186 patients were recruited, 143 from tertiary cardiology centre and 43 from non-cardiology hospitals. Mean age was 54.7±10.0 years, 87.6% male and 64% were STEMI. The NT-proBNP level ranged from 60 to 16700pg/ml, with a median of 714pg/ml. Using the 75th centile as the cutoff, Kaplan-Meier survival analysis for the 30-day cardiac related mortality was significantly higher for patient with NT-proBNP level of ≥1600pg/ml (6.4% vs. 0.7%, p=0.02). Cox-regression analysis showed that NT-proBNP level of ≥1600pg/ml was an independent predictor of 30-day cardiac related mortality, regardless of TIMI risk score, GRACE score, LV ejection fraction and study hospitals (HR 9.274, p=0.054, 95%CI 0.965, 89.161). Readmission for heart failure at 30-day was also higher for patient with NT-proBNP level of ≥1600pg/ml (HR 9.308, p=0.053, 95%CI 0.969, 89.492). NT-proBNP level was not associated with all-cause mortality, risk of readmission for ACS, arrhythmia and stroke (pN0.05). By adding 50 score to GRACE risk score for NT-proBNP level of ≥1600pg/ml, combination of GraceNT-proBNP scores of more than 200 appeared to be a better independent predictor for 30-day cardiac related mortality (HR:28.28, p=0.004, 95%CI 2.94, 272.1). ROC analysis showed that this new score had 75% sensitivity and 91.2% specificity in predicting 30-day cardiac related mortality (AUC 0.791, p=0.046). Conclusions: NT-proBNP is a useful point-of-care risk stratification biomarker in AMI. It can be combined to the current risk score model for better risk stratification in AMI patients

Echocardiographic improvement of left atrial booster pump and reservoir function observed in heart failure with improved ejection fraction and its prognostication

The novel subgroup of Heart Failure with improved ejection fraction(HFimpEF) is focused on improving left ventricle systolic function, but there is sparse data on left atrial(LA) recovery. Recent studies observed reversal remodelling of LA echocardiographic volume indices in HFimpEF. However, there is a lack of data on the echocardiographic description of volumetric LA functions, such as booster pump and reservoir dysfunction, in patients with HFimpEF