Usefulness of quantitative versus qualitative ST-segment depression for risk stratification of non-ST elevation acute coronary syndromes in contemporary clinical practice

This aim of this study was to assess the clinical utility of quantitative ST-segment depression (STD) for refining the risk stratification of non-ST elevation acute coronary syndromes in the prospective, multinational Global Registry of Acute Coronary Events (GRACE). Quantitative measurements of STD on admission electrocardiograms were evaluated independently by a core laboratory, and their predictive value for in-hospital and cumulative 6-month mortality was examined. Although more severe STD is a marker of increased short- and long-term mortality, it is also associated with higher risk clinical features and biomarkers. Thus, after adjustment for these clinically important predictors, quantitative STD does not provide incremental prognostic value beyond simple dichotomous evaluation for the presence of STD. Furthermore, adopting quantitative instead of the prognostically proven qualitative evaluation of STD does not improve risk discrimination afforded by the validated GRACE risk models. In conclusion, the findings do not support the quantification of STD in routine clinical practice beyond simple evaluation for the presence of STD as an integral part of comprehensive risk stratification using the GRACE risk score.     

Patients with functional bowel disorder have disaccharidase deficiency: A single-center study from Russia

BACKGROUNDFunctional bowel disorder (FBD) may be caused by a decrease in disaccharidase activity. Thus, the timely diagnosis of disaccharidase deficiency could lead to a better prognosis in patients with this condition.AIMTo determine the potential value of intestinal disaccharidases glucoamylase, maltase, sucrase, and lactase in understanding the etiology and pathogenesis of FBD.METHODSA total of 82 FBD patients were examined. According to the Rome IV criteria (2016), 23 patients had diarrhea-predominant irritable bowel syndrome (IBS), 33 had functional diarrhea, 10 had constipation-predominant IBS, 4 had functional constipation, and 12 had mixed IBS. The Dahlqvist method was used to measure disaccharidase activity in the brush-border membrane of mature enterocytes of the small intestine, in duodenal biopsies obtained during esophagogastroduodenoscopy.RESULTSLactase deficiency was detected in 86.5% of patients, maltase deficiency in 48.7%, sucrase deficiency in 50%, and glucoamylase deficiency in 84.1%. The activities of all enzymes were reduced in 31.7% of patients, and carbohydrase deficiency was detected in 63.5% of patients. The low activity of enzymes involved in membrane digestion in the small intestine was found in 95.2% of patients.CONCLUSIONIn 78 of the 82 patients with FBD, gastrointestinal symptoms were associated with disaccharidase deficiency.     

Deep learning in forensic gunshot wound interpretation—a proof-of-concept study

International Journal of Legal Medicine - While the applications of deep learning are considered revolutionary within several medical specialties, forensic applications have been scarce despite the...     

Detection of the selective androgen receptor modulator GSK2881078 and metabolites in urine and hair after single oral administration

Hair and urine concentrations of the nonsteroidal selective androgen receptor modulator GSK2881078 were examined following single oral administration to investigate its hair incorporation and estimate the general suitability of hair testing for selected androgen receptor modulators. Hair segments were collected following a single dose of 1.5 mg GSK2881078 by repeated shaving of scalp hair at Week 0 (blank), Week 1 (representing the pre-application period), Week 3 (ideally focusing the time of incorporation), and Weeks 5 and 9 (post-administration period). The intact compound and various (at least 4) hydroxy-metabolites exhibited similar elimination profiles. The peak urinary concentration (approximately 920 pg/ml) was observed after 8 h and is reduced to the detection limit (2 pg/ml) on Day 42 following administration of 760 μg GSK2881078. Correspondingly, hair concentrations of GSK2881078 (intact compound only) following a single oral dose of 1.5 mg GSK2881078 reached a peak concentration of 1.7 pg/mg in the segments collected 3 weeks post administration, representing the time of ingestion. The concentration rapidly declined to trace amounts of 0.7 (Week 5) and 0.2 pg/mg (Week 9), respectively. In conclusion, measurement of the intact compound GSK2881078 is feasible for both urine and hair analysis. However, concentrations in hair after single oral administration are in the low pg/mg range and can only be detected, if the segments cover the administration period.     

Cross-sectional HIV and HCV cascades of care across the regions of Ukraine between 2019 and 2020: findings from the CARE cohort

Introduction

Eastern Europe is facing major HIV and hepatitis C (HCV) epidemics, with many people living with HIV (PLHIV) and HIV/HCV coinfection living in Ukraine. Despite the previous progress towards care quality improvement, the ongoing war in Ukraine is disrupting HIV and HCV care.

Methods

We described an HIV cascade of care (CoC) in PLHIV from two clinical sites and an HCV CoC for anti-HCV-positive PLHIV from six sites in Ukraine, enrolled in the CARE cohort between 1 January 2019 and 1 June 2020. The cross-sectional HIV CoC and HCV CoC are described at study enrolment.

Results

Of 1028 PLHIV, 1014 (98.6%, 95% confidence interval [CI] 97.7–99.3) were on antiretroviral therapy (ART), and 876 (86.4% of those on ART, 95% CI 84.1–88.4) were virologically suppressed. Of 894 participants on ART >6 months, 90.8% (95% CI 88.7–92.6) were virologically suppressed (HIV-RNA <200 copies/ml). Of 2040 anti-HCV-positive PLHIV, 417 (20.4%, 95% CI 18.7–22.3) were ever tested for HCV-RNA prior to enrolment, ranging from 4.9% to 54.4% across sites, and 13.5% were currently HCV-RNA positive. One hundred and eighteen persons (7.3% of ever chronically infected) had received HCV treatment, and 25 persons (1.6% of ever chronically infected) were cured, with variations across sites (0%–7.5%). The site diagnosing 54.4% of people with chronic HCV was the only one providing free RNA testing for all anti-HCV-positive persons, while the intra-country differences in treatment coverage were driven by the number of available direct-acting antiviral (DAA) courses.

Conclusions

Over 98% of PLHIV in care in both CARE sites in Ukraine were receiving ART, and the target of 90% virally suppressed was achieved in persons >6 months on ART. Only one of six HIV/HCV study sites tested over 50% anti-HCV-positive PLHIV for HCV-RNA and treated over 25% of eligible persons. While free HCV-RNA testing and DAA treatment are paramount to achieving HCV elimination targets, they remained a challenge in Ukraine in 2019–2020. The extent of the HIV and HCV care disruption during the war will be further assessed in the CARE cohort and compared with the pre-war findings.