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  • Demant posted an update 8 months, 4 weeks ago

    RCCX haplotypes with two copies of the CYP21A2 gene and one copy of the CYP21A1P pseudogene have been widely described in different populations. In most cases, the CYP21A2-like gene downstream of the TNXA gene showed a wild-type sequence or the c.293-13A/C > G variant while the CYP21A2 gene next to TNXB carried the p.(Gln319Ter) variant. Here is the discovery of a novel rare CYP21A2 haplotypes detected in an Italian patient with Non Classical Congenital Adrenal Hyperplasia (NC-CAH). The molecular family study was performed clarifying the previously found phenotype-genotype discrepancy.BACKGROUND The goal of this study was to investigate the potential determinants of 18F-NaF uptake in femoral arteries as a marker of arterial calcification in patients with type 2 diabetes and a history of arterial disease. METHODS AND RESULTS The study consisted of participants of a randomized controlled trial to investigate the effect of vitamin K2 (NCT02839044). In this prespecified analysis, subjects with type 2 diabetes and known arterial disease underwent full body 18F-NaF PET/CT. Target-to-background ratio (TBR) was calculated by dividing the mean SUVmax from both superficial femoral arteries by the SUVmean in the superior vena cava (SVC) and calcium mass was measured on CT. The association between 18F-NaF TBR and cardiovascular risk factors was investigated using uni- and multivariate linear regression corrected for age and sex. In total, 68 patients (mean age 69 ± 8 years; male 52) underwent 18F-NaF PET/CT. Higher CT calcium mass, total cholesterol, and HbA1c were associated with higher 18F-NaF TBR after adjusting. CONCLUSION This study shows that several modifiable cardiovascular risk factors (total cholesterol, triglycerides, HbA1c) are associated with femoral 18F-NaF tracer uptake in patients with type 2 diabetes.BACKGROUND Qualification and interpretation standards are essential for establishing 99mTc-SPECT MPI accuracy vs. alternative modalities. METHODS Rest-stress 99mTc-SPECT phantom scans were acquired on 35 cameras. LV defects were quantified with summed stress (SSS) and difference scores (SDS) at 2 core labs. SDS ≥ 2 in the right coronary artery (RCA) was the qualifying standard. Twenty rest (R)-stress (S) patient images were acquired on qualified cameras and interpreted by core labs. Global scoring differences > 3 between labs or discordant clinical interpretations underwent review. Brensocatib Scoring, interpretation, image quality, and diagnostic parameter agreement were assessed. RESULTS Phantom scans visual scoring confirmed RCA-ischemia on all cameras. Regional SSS, SDS agreement was moderate to very good ICC-r = 0.57, 0.84. Patient scans 90% of global SSS, 85% of SDS differences were ≤ 3. Regional SSS, SDS agreement ICC-r = 0.87, 0.86, and global abnormal (SSS ≥ 4) and ischemic (SDS ≥ 2) interpretation ICC-r = 0.90 were excellent. Clinical interpretation agreement was 100% following review. Image quality agreement was 70%. Automated metrics also agreed ischemic total perfusion deficit ICC-r = 0.75, reversible perfusion defect, transient ischemic dilation, and S-R LV ejection fraction ICC-r ≥ 0.90. CONCLUSION Quantitative scoring and interpretation of scans were highly repeatable with site qualification and clinical interpretation standardization, indicating that dual-core lab interpretation is appropriate to determine 99mTc-SPECT MPI accuracy.BACKGROUND Prolonged empiric antibiotic use, resulting from diagnostic uncertainties, in suspected early onset sepsis (EOS) cases constitutes a significant problem. Unnecessary antibiotic use increases the risk of antibiotic resistance. Furthermore, prolonged antibiotic use increases the risk of mortality and morbidity in neonates. Proactive measures including empiric antibiotic de-escalation are crucial to overcome these problems. METHODS This was a prospective cohort study conducted in the neonatal intensive care units of two public hospitals in Malaysia. Neonates with a gestational age greater than 34 weeks who were started on empiric antibiotics within 72 h of life were screened. The data were then stratified according to de-escalation and non-de-escalation practices, where de-escalation practice was defined as narrowing down or discontinuation of empiric antibiotic within 72 h of treatment. RESULTS A total of 1045 neonates were screened, and 429 were included. The neonates were then divided based on de-escalation (n = 207) and non-de-escalation (n = 222) practices. Neonates under non-de-escalation practices showed significantly longer durations of antibiotic use compared to those under de-escalation practices (p  less then  0.05), with no difference in treatment outcomes. Five factors were found to be associated with de-escalation of antibiotics. They are cesarean section delivery, exposure to antenatal steroids, nil history of maternal pyrexia, absence of meconium-stained amniotic fluid, and normal C-reactive protein ≤ 0.5 mg/dL (p  less then  0.05). CONCLUSIONS Empiric antibiotic de-escalation appears feasible as a routine form of treatment for EOS in late preterm and term neonates.Tislelizumab (®;; Tileilizhu Dankang Zhusheye) is an anti-human programmed death receptor-1 (PD-1) monoclonal IgG4 antibody that is being developed by BeiGene as an immunotherapeutic, anti-neoplastic drug. Tislelizumab has been investigated in haematological cancers and advanced solid tumours, leading to its approval in December 2019 in China for patients with relapsed or refractory classical Hodgkin’s lymphoma after at least second-line chemotherapy. This article summarises the major milestones in the development of tislelizumab for this first approval for classical Hodgkin’s lymphoma, and its potential upcoming approvals in other indications.Cenegermin (Oxervate™), an ophthalmic solution containing 20 µg/mL of recombinant human nerve growth factor (rhNGF), is the first drug to be approved for the treatment of neurotrophic keratitis (NK; also referred to as neurotrophic keratopathy). In the registration trials, the majority of adults with moderate or severe NK experienced complete corneal healing after up to 8 weeks of topical cenegermin therapy. The rate of complete corneal healing was generally higher, and that of disease progression was lower, with cenegermin than with vehicle. Although the drug provided no statistically significant benefit over vehicle in terms of corneal sensitivity or visual acuity after 8 weeks of treatment, few patients with corneal healing experienced disease recurrence over 48 weeks of follow-up. Longer-term data are needed to definitively determine the efficacy of cenegermin with respect to these outcomes; further investigation into cenegermin re-treatment following disease recurrence would also be beneficial. Cenegermin had no detrimental impact on health-related quality of life (in contrast to some surgical treatments) and was generally well tolerated.

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