A multidimensional singular stochastic control problem on a finite time horizon

A singular stochastic control problem in n dimensions with timedependent coefficients on a finite time horizon is considered. We show that the value function for this problem is a generalized solution of the corresponding HJB equation with locally bounded second derivatives with respect to the space variables and the first derivative with respect to time. Moreover, we prove that an optimal control exists and is unique

A common variant in the hepatobiliary phospholipid transporter ABCB4 modulates liver injury in PBC but not in PSC : prospective analysis in 867 patients

Background: The ATP-binding cassette subfamily B member 4 (ABCB4) gene encodes the hepatic phospholipid transporter. Variants in the ABCB4 gene are associated with various cholestatic phenotypes, some of which progress to liver fbrosis and cirrhosis. The aim of our study was to investigate the role of the cholestasis-associated variant ABCB4 c.711A>T (p.I237I, rs2109505) in patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Results: Two cohorts of Polish patients took part in this study. The Szczecin cohort comprised 196 patients with PBC (174 females, 38% with cirrhosis) and 135 patients with PSC (39 females, 39% with cirrhosis). The Warsaw cohort consisted of 260 patients with PBC (241 females, 44% with cirrhosis) and 276 patients with PSC (97 females, 33% with cirrhosis). Two control cohorts—150 healthy blood donors and 318 patients without liver disease, were recruited in Szczecin and in Warsaw, respectively. The ABCB4 c.711A>T polymorphism was genotyped using TaqMan assay. In both PBC cohorts, carriers of the risk variant presented more frequently with cirrhosis (Szczecin: OR=1.841, P=0.025; Warsaw: OR=1.528, P=0.039). The risk allele was associated with increased serum AST, GGT and ALP (all P<0.05) at inclusion. During the follow-up, patients in both cohorts signifcantly improved their laboratory results, independently of their ABCB4 c.711A>T genotype (P>0.05). During 8±4 years follow-up, a total of 22 patients in the Szczecin PBC group developed cirrhosis, and this risk was higher among carriers of the risk variant (OR=5.65, P=0.04). In contrast to PBC, we did not detect any association of ABCB4 c.711A>T with a liver phenotype in PSC cohorts. Conclusions: The frequent pro-cholestatic variant ABCB4 c.711A>T modulates liver injury in PBC, but not in PSC. In particular, carriers of the major allele are at increased risk of progressive liver scarring

Molecular perturbations in cholangiocarcinoma: is it time for precision medicine?

The complexity of cholangiocarcinoma (CCA) cellularity and the molecular perturbation mechanisms that underlie the diversity of growth patterns of this malignancy remain a clinical concern. Tumours of the biliary system display significant intrinsic chemoresistance, caused by significant stromal involvement and genome–wide tumour heterogeneity, hampering disease remission and palliation as well as promoting the metastatic behaviour. It is crucial to advance our present understanding of the risk and molecular pathogenesis of CCA. This will facilitate the delineation of patient subsets based on molecular perturbations and adjust for precision therapies

Selective mutism - Prevalence and key characteristics: A population study

We report the first-ever prevalence study of selective mutism in Poland. Preschool and primary school teachers were surveyed at four locations; parents were followed up if selective mutism was suspected. Our point prevalence rate of selective mutism (per thousand children) was 5.7 for 3-6 years-old preschoolers (95% confidence interval: 3.7-8.8); 2.0 (1.1-3.9) for 1st-3rd graders; and 2.1 (0.9-5.1) for 4th-6th graders. The accuracy of that estimate may be compromised by low response rate. 56% were girls. Less than 20% had been formally diagnosed with the condition, which suggests lack of adequate recognition and support.Przedstawiamy wyniki pierwszych polskich badań nad rozpowszechnieniem mutyzmu wybiórczego. Badania przeprowadzonow czterech lokalizacjach metodą kwestionariuszową, ankiety wypełnili nauczyciele wychowania przedszkolnego oraz szkół podstawowych; w przypadku wstępnych podejrzeń mutyzmu wybiórczego także rodzice. Częstotliwość występowania aktywnego („niepokonanego”) mutyzmu wybiórczego (na tysiąc dzieci) wyniosła 5.7 wśród 3-6 letnich przedszkolaków (95% przedział ufności: 3.7-8.8); 2.0 (1.1-3.9) w klasach 1-3; oraz 2.1 (0.9-5.1) w klasach 4-6. Precyzja tej estymacji jest ograniczona niskim odsetkiem odpowiedzi. 56% grupy dzieci z mutyzmem stanowiły dziewczynki. Mniej niż 20% dzieci z mutyzmem miało formalną diagnozę tego zaburzenia, co sugeruje brak świadomości tego problemu oraz adekwatnego wsparcia

Superior early diagnostic performance of a sensitive cardiac troponin assay as compared to a standard troponin test in the diagnosis of acute myocardial infarction

Background: New generation cardiac troponin assays have sufficient precision to detect and quantify plasma troponin concentrations below the lower threshold of detection of the currently employed troponin tests. However, diagnostic performance of the newer generation assays in daily clinical practice is not well established. Aim: To evaluate the diagnostic performance of a sensitive assay as compared to a standard assay in a single reading at admission in the diagnosis of acute myocardial infarction (AMI) in patients presenting to the Emergency Department with chest pain. Methods: The study comprised 187 consecutive patients admitted to the Institute of Cardiology in Warsaw in June and July 2010 with chest pain in whom the attending physician ordered troponin assay to rule AMI in or out. In all of these patients, in addition to the standard Dimension Flex Troponin I (Siemens Healthcare Diagnostics, Inc.) the sensitive Architect Stat Troponin I (Abbott Diagnostics) test was assayed. The triage of patients as well as all diagnostic and treatment decisions were left to the discretion of the attending physician who was blinded to the sensitive troponin test readings. The final diagnosis was adjudicated by a team of two cardiologists on the basis of all the available medical records except for sensitive troponin test results. Results: Mean age of the study cohort (n = 187) was 64.3 &#177; 13.9 years and 119 (63.6%) were males. The final diagnosis of AMI was adjudicated in 84 (44.9%) patients (mean age 67.5 &#177; 12.9 years; 119 [63.6%] males). Receiver operating characteristic (ROC) analysis showed greater area under the curve (AUC) for the sensitive cardiac troponin assay compared to the standard assay (AUC = 0.916, 95% CI = 0.866&#8211;0.951 vs AUC = 0.863, 95% CI = 0.806&#8211;0.909, respectively; p = 0.02) in a single reading at admission. Sensitive assay was characterised by higher sensitivity (87%), specificity (88%), positive (86%) and negative (89%) predictive values in the detection of AMI compared to the standard troponin test (82%, 81%, 78%, and 85% respectively). Conclusions: The newer generation sensitive cardiac troponin assay presented superior diagnostic accuracy in the diagnosis of AMI compared to the standard troponin test in a single reading at admission with improved sensitivity and specificity. The sensitive troponin assay has the potential to improve early detection and/or exclusion of AMI.Background: New generation cardiac troponin assays have sufficient precision to detect and quantify plasma troponin concentrations below the lower threshold of detection of the currently employed troponin tests. However, diagnostic performance of the newer generation assays in daily clinical practice is not well established. Aim: To evaluate the diagnostic performance of a sensitive assay as compared to a standard assay in a single reading at admission in the diagnosis of acute myocardial infarction (AMI) in patients presenting to the Emergency Department with chest pain. Methods: The study comprised 187 consecutive patients admitted to the Institute of Cardiology in Warsaw in June and July 2010 with chest pain in whom the attending physician ordered troponin assay to rule AMI in or out. In all of these patients, in addition to the standard Dimension Flex Troponin I (Siemens Healthcare Diagnostics, Inc.) the sensitive Architect Stat Troponin I (Abbott Diagnostics) test was assayed. The triage of patients as well as all diagnostic and treatment decisions were left to the discretion of the attending physician who was blinded to the sensitive troponin test readings. The final diagnosis was adjudicated by a team of two cardiologists on the basis of all the available medical records except for sensitive troponin test results. Results: Mean age of the study cohort (n = 187) was 64.3 +- 13.9 years and 119 (63.6%) were males. The final diagnosis of AMI was adjudicated in 84 (44.9%) patients (mean age 67.5 +- 12.9 years; 119 [63.6%] males). Receiver operating characteristic (ROC) analysis showed greater area under the curve (AUC) for the sensitive cardiac troponin assay compared to the standard assay (AUC = 0.916, 95% CI = 0.866&#8211;0.951 vs AUC = 0.863, 95% CI = 0.806&#8211;0.909, respectively; p = 0.02) in a single reading at admission. Sensitive assay was characterised by higher sensitivity (87%), specificity (88%), positive (86%) and negative (89%) predictive values in the detection of AMI compared to the standard troponin test (82%, 81%, 78%, and 85% respectively). Conclusions: The newer generation sensitive cardiac troponin assay presented superior diagnostic accuracy in the diagnosis of AMI compared to the standard troponin test in a single reading at admission with improved sensitivity and specificity. The sensitive troponin assay has the potential to improve early detection and/or exclusion of AMI

Benefits of the selective invasive strategy guided by CTA and CT-FFR in patients with coronary artery disease

Background: Coronary computed tomography angiography (CTA) has high diagnostic accuracy in ruling out significant stenosis of coronary arteries. The additional use of CTA- derived FFR further enhances diagnostic utility of coronary CTA. Some of the patients interrogated non-invasively have diseased coronary arteries and undergo further diagnostic testing, including invasive coronary angiography (ICA). Patients with one vessel disease may benefit from invasive interrogation limited to the diseased vessel only. Aims: In 100 patients, we analysed the impact of a “diseased-vessel-only”, selective invasive diagnostic approach in patients undergoing ICA following coronary CTA (and CT-FFR) as compared to the traditional, “full ICA” approach. Our aim was to compare contrast volume and radiation dose used during ICA in both scenarios, seeking potential benefit for the patient in reducing those values by “diseased-vessel-only” approach. Results: Sensitivity, specificity, positive predictive value and negative predictive value of CTA in prediction of subsequent revascularization were 96%, 75%, 51% and 99%, respectively, and for CT-FFR 90%, 90%, 69% and 97%, respectively. Using CTA as a method to guide ICA would reduce contrast volume and estimated radiation dose (ED), by 35% and 42.0% respectively (P &lt;0.0001 for both). Taking into consideration CT-FFR results, contrast volume would be reduced by 57% and ED by 69% (P &lt;0.0001 for both). Conclusion: These real-world data support the concept that vessels with &lt;50% diameter stenosis in QCT and hemodynamically insignificant in CTA-derived FFR may be skipped during ICA. Such approach would result in substantial reductions in contrast media volume used, as well as patient’s exposure to radiation during during ICA, while not leading to missed diagnoses

High-density lipoprotein cholesterol, triglycerides, and characteristics of coronary atherosclerosis in patients with significant coronary artery disease newly diagnosed by computed tomography coronary angiography

Background: The Current European Society of Cardiology guidelines indicate specific target low-density lipoprotein cholesterol (LDL-C) levels for different cardiovascular risk categories in terms of prevention. However, the target for high-density lipoprotein cholesterol (HDL-C) and triglycerides has not been established.Aim: The study aims to investigate the associations between HDL-C, triglycerides, and coronary plaque characteristics.Methods: This was a prospective single-center study with enrolled consecutive patients with newly diagnosed significant (≥1 stenosis ≥50%) CAD on computed tomography coronary angiography (CTCA). Patients had lipids and CTCA analysis, including high-risk plaque (HRP) features: low-attenuation plaque (LAP), napkin-ring sign (NRS), positive remodeling (PR), and spotty calcium (SC), type of the plaque (calcified, noncalcified, mixed), and their composition (calcified, fibrous, fibro-fatty, necrotic core).Results: The study included 300 patients (191 men, 66 [8] years). Sixty-six percent of them had lipid-lowering therapy. HRP was found in 208 patients. There was no association between LDL-C, plaque composition, and HRP presence. There was a negative correlation between HDL-C, fibro-fatty and necrotic core plaque components (P = 0.0002, P = 0.0009). There was a positive correlation between triglycerides and necrotic core (P = 0.038). There were differences in HDL-C and triglycerides in patients with and without NRS (47 vs. 53 mg/dl, P = 0.0002 and 128 vs. 109 mg/dl, P = 0.02). In logistic regression, HDL-C (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.93–0.98; P &lt;0.001), triglycerides (OR, 1.00; 95% CI, 1.00–1.01; P = 0.02), and male sex (OR, 3.04; 95% CI, 1.41–6.52; P = 0.004) were NRS predictors. In multivariable regression, only HDL-C (OR, 0.96; 95% CI, 0.93–0.99; P = 0.02) was an independent predictor of NRS.Conclusion: Lower HDL-C and higher triglycerides were associated with NRS presence and more necrotic core plaque components in coronary plaques in patients with newly diagnosed CAD

Identification of noncalcified coronary plaque characteristics using machine learning radiomic analysis of non-contrast high-resolution computed tomography

Background: Novel imaging and analysis techniques may offer the ability to detect noncalcified or high-risk coronary plaques on a non-contrast computer tomography (CT) scan, advancing cardiovascular diagnostics.Aims: We aimed to explore whether machine learning (ML) radiomic analysis of low-dose high-resolution non-contrast electrocardiographically (ECG) gated cardiac CT scan allows for the identification of noncalcified coronary plaque characteristics.Methods: We prospectively enrolled 125 patients with noncalcified plaques and adverse plaque characteristics (APC) and 25 controls without visible atherosclerosis on coronary CT angiography (CCTA). All patients underwent non-contrast CT exam before CCTA. Four hundred and nineteen radiomic features were calculated to identify the presence of any coronary artery disease (CAD), obstructive CAD (stenosis &gt;50%), plaque with ≥2 APC, degree of calcification, and specific APCs. ML models were trained on a training set (917 segmentations) and tested (validation) on a separate set (292 segmentations).Results: Among the radiomic features, 88.3% were associated with a plaque, 0.9% with obstructive CAD, and 76.4% with the presence of at least two APCs. Overall, 80.2%, 88.5%, and 36.5%, of features were associated with calcified, partially calcified, and noncalcified plaques, respectively. Regarding APCs, 61.1%, 61.8%, 84.2%, and 61.3% of features were associated with low attenuation (LAP), napkin-ring sign (NRS), spotty calcification (SC), and positive remodeling (PR), respectively. ML models outperformed conventional methods for the presence of plaque obstructive stenosis, and the presence of 2 APCs, as well as for noncalcified plaques and partially calcified plaques, but not for calcified plaques. ML models also significantly outperformed identification of LAP and PR, but neither NRS nor SC.Conclusion: Radiomic analysis of non-contrast cardiac CT exams may allow for the identification of specific noncalcified coronary plaque characteristics displaying the potential for future clinical applications

Prebiotic potential of spent brewery grain – In vitro study

Spent brewery grain (SBG) is a by-product of the brewery industry. The study aimed to investigate the prebiotic potential of SBG. The chemical composition and fermentation capacity of SBG were checked. The gut microbiota response to SBG was assessed in two in vitro models (batch fermentation and dynamic system). Substances with prebiotic properties, including arabinoxylans (16.7 g/100 g) and polyphenols (49.1 mg/100 g), were identified in SBG. Suitable growth and fermentation by probiotic bacteria were observed. The modulatory effect of gut microbiota depends on the in vitro system used. In batch fermentation, there was no stimulation of Bifidobacterium or lactic acid bacteria (LAB), but short-chain fatty acid (SCFA) and branched short-chain fatty acids (BCFA) synthesis increased. In dynamic, SBG exhibited a moderate bifidogenic effect, promoting Akkermansia and LAB growth while reducing Bacteroides and Escherichia-Shigella. SCFA stabilisation and reduction of BCFA content were noted. Moderate prebiotic effects were observed

MARC1 p.A165T variant is associated with decreased markers of liver injury and enhanced antioxidant capacity in autoimmune hepatitis

The clinical picture of autoimmune hepatitis (AIH) varies markedly between patients, potentially due to genetic modifiers. The aim of this study was to evaluate genetic variants previously associated with fatty liver as potential modulators of the AIH phenotype. The study cohort comprised 313 non-transplanted adults with AIH. In all patients, the MARC1 (rs2642438), HSD17B13 (rs72613567), PNPLA3 (rs738409), TM6SF2 (rs58542926), and MBOAT7 (rs641738) variants were genotyped using TaqMan assays. Mitochondrial damage markers in serum were analyzed in relation to the MARC1 variant. Carriers of the protective MARC1 allele had lower ALT and AST (both P < 0.05). In patients treated for AIH for ≥ 6 months, MARC1 correlated with reduced AST, ALP, GGT (all P ≤ 0.01), and lower APRI (P = 0.02). Patients carrying the protective MARC1 genotype had higher total antioxidant activity (P < 0.01) and catalase levels (P = 0.02) in serum. The PNPLA3 risk variant was associated with higher MELD (P = 0.02) in treated patients, whereas MBOAT7 increased the odds for liver cancer (OR = 3.71). None of the variants modulated the risk of death or transplantation. In conclusion, the MARC1 polymorphism has protective effects in AIH. Genotyping of MARC1, PNPLA3, and MBOAT7 polymorphisms might help to stratify patients with AIH