BACKGROUND:Some patients who test trace positive on Xpert MTB/RIF Ultra ("Ultra"), a highly sensitive molecular diagnostic platform, may not have tuberculosis (TB) disease. A better understanding of the prevalence of TB, associated clinical characteristics, and utility of additional diagnostic tests among people with trace sputum (PWTS) could aid clinical decision-making. METHODS:We enrolled adults and adolescents with trace-positive sputum on initial TB diagnostic evaluation in Uganda and South Africa. Participants were extensively evaluated at enrollment; those with uncertain TB status were followed off treatment, with interval reevaluations by TB clinicians, for up to 3 months. We assessed TB prevalence and associated patient characteristics and diagnostic results. RESULTS:Among 311 PWTS, TB was identified by sputum culture at enrollment in 20% of participants (61/311, 95% CI 15%-24%). Within 3 months, 48% (145/301, 95% CI 43%-54%) had been judged to warrant TB treatment, and among those followed until microbiologic outcomes, 30% (68/227, 95% CI 24%-36%) had positive culture and 41% (99/240, 95% CI 35%-47%) had positive culture or Ultra. Two participants died. Having TB symptoms, advanced human immunodeficiency virus (HIV), and no recent TB history were associated with microbiologically confirmed TB disease, as were an abnormal chest X-ray (in those without recent TB) or elevated C-reactive protein (CRP). CONCLUSIONS:Roughly half of PWTS were recommended TB therapy. This prevalence supports treating most PWTS when multimodal testing and repeated clinical evaluations are infeasible. However, given low observed mortality, some people with low-risk characteristics and negative results on other widely available diagnostic tests could safely defer treatment with clinical follow-up.
BACKGROUND:In recent years, key TB indicators have improved in the Siberian and Far Eastern federal districts (FDs) of Russia, but these regions still face the challenge of reducing the numbers of patients with drug-resistant-TB and TB/HIV co-infection. TB care and support interventions recommended by the WHO have been implemented, such as home-based and outpatient treatment, use of digital technologies and provision of psychosocial support. METHODS:The study used a short survey to assess the influence of these interventions on patient adherence to treatment during the period 2018-2022 in the Siberian and Far Eastern FDs. The survey was sent to the heads of TB clinics in the 21 regions. RESULTS:Of the 21 regions invited to take part in the study, 20 returned answers; 14 of these completed the survey fully, and the other six only partially (as some of the data requested are not routinely collected in those regions). The results show that TB care and support interventions, especially psychosocial interventions, are associated with a reduction of number of patients lost to follow-up and the number of TB cases. CONCLUSION:Care and support interventions have only been implemented for a relatively short period, and their use needs to be continued, along with the creation of a data repository to enable monitoring and further studies to meet targets on TB control.
To assess the possibility of integrating extracellular double-stranded DNA fragments into the recipient genome of hematopoietic stem cells, a complex substrate was constructed consisting of the entire M13F-AluI-M13R fragment and its two restrictive derivatives, appearing after hydrolysis with restriction endonucleases EcoRI and HindIII: M13FAluI-EcoRI and M13R-AluI-HindIII. The substrate contained a pBlueScript+ plasmid polylinker sequence, absent in the human genome, which framed the human AluI fragment cloned at the EcoRV site. Human bone marrow cells were treated with the DNA of the constructed complex substrate; taking into account the repair time of pangenomic single-strand breaks, preparations of metaphase plates were obtained. FISH revealed specific fluorescent signals. Simultaneously, DNA isolated from colonies obtained from bone marrow cells treated with a complex substrate was sequenced. Two rounds of sequencing were carried out: whole-genome and selective after targeted hybridization on metal beads. The results obtained indicate that homologous exchange between extrachromosomal and chromosomal DNA is possible. Integration into the genome via the single-strand annealing mechanism, involving microhomologies, is also possible. Intermediates were discovered that suggest the existence of an unusual integration into the genome at the nick of one end of the fragment and the other end of the fragment hanging freely into the interchromosomal space. A direct assessment of the possibility of integrating TAMRA-labeled fragments of fragmented human DNA and E. coli DNA into the genome of recipient cells was carried out using a human bone marrow cell model. The results obtained indicate that specific signals of homologous DNA are distributed throughout the chromosome body (human bone marrow cell model). Signals from nonhomologous E. coli DNA are predominantly concentrated in the centromeric regions of chromosomes. The ratio of the number of obtained reads with integration elements and FISH signals suggested the existence of a strong interaction between extracellular fragments and chromosomal DNA. Experiments have been conducted showing that linear plasmid DNA, after internalization into hematopoietic stem cells, forms a monomer ring. Internalized into the intracellular space, extracellular plasmid DNA is isolated together with chromosomal DNA after stringent purification and fractionation procedures. This fact suggests the existence of a strong ring associate of plasmid DNA and chromosome DNA formed without the participation of a protein framework in the form of a looped chromosomal strand.
BACKGROUND:Ulnar artery access may provide an alternative access route for chronic total occlusion percutaneous coronary intervention (CTO PCI), but data is limited. AIMS:To assess the utilization, patient characteristics, and in-hospital outcomes of ulnar artery access compared with radial access and non-ulnar access in patients undergoing CTO PCI. METHODS:We analyzed patients who underwent CTO PCI between 2012 and 2024 at 51 centers within the PROGRESS-CTO Registry. Patients were stratified by access: (1) no radial/ulnar, (2) radial without ulnar, and (3) ulnar. The primary endpoint was in-hospital major adverse cardiovascular events (MACE). Secondary endpoints included technical success. Multivariable logistic regression was used to identify independent predictors of outcomes. RESULTS:Among 18,826 patients, 8844 (47.0%) had no radial/ulnar access, 9835 (52.2%) radial without ulnar, and 147 (0.8%) ulnar. Ulnar patients were younger (62.5 ± 10.4 vs. 64.0 ± 10.4 radial and ulnar, 65.1 ± 10.5 no radial/ulnar, p < 0.001) and had higher prevalence of prior PCI (73.6% vs. 59.3% and 64.0%, p < 0.001) and peripheral arterial disease (23.9% vs. 12.1% and 15.1%, p < 0.001). Lesion complexity was lower with ulnar access (J-CTO 2.19 ± 1.27 vs. 2.32 ± 1.27 radial and 2.47 ± 1.21 no radial/ulnar, p < 0.001). In-hospital outcomes were similar: MACE (2.7% ulnar vs. 1.8% radial vs. 2.0% no radial/ulnar, p = 0.315), technical success (83.7% vs. 87.3% vs. 87.2%, p = 0.425), and access complications (0.7% vs. 0.7% vs. 1.2%, p = 0.001). Logistic regression showed no independent association between ulnar access and MACE, technical success, or access-site complications. CONCLUSION:In the largest series to date, ulnar access was used in 0.8% of CTO PCI with similar outcomes to radial and femoral access. Given its use in lower complexity cases, these findings are hypothesis-generating and warrant prospective evaluation.
