Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Time poor : rushing decreases the accuracy and reliability of blood pressure measurement technique in pregnancy

Background: In pregnancy, absolute blood pressure (BP) limits define preeclampsia. Therefore, BP in pregnancy should be measured accurately and in accordance with accepted guidelines. Accuracy of BP readings determined by rate of cuff deflation was analyzed. This study also investigated the compliance of clinical staff at Royal Prince Alfred Hospital, Australia, to guidelines for BP measurement. Methods: The study was an observational trial of 98 normotensive antenatal or recently postnatal patients. Two BP readings were taken, each with fast (>5 mm Hg/sec) and slow (2 mm Hg/sec) descent of mercury and compared by Bland-Altman analysis. Also, BP techniques used by junior doctors, specialist obstetricians, and midwives were compared using a 9-point scale. Findings: Australian national guidelines recommend slow descent of mercury. Fast descent underestimated the systolic BP by 9 mm Hg (95% confidence interval [CI], -23 to +5 mm Hg) (p < 0.001). Fast descent measured the iastolic BP within 2 mm Hg (95% CI, -10 to +14 mm Hg) (not different, p = 0.151). Accuracy of fast cuff deflation was 28% for systolic BP and 50% for diastolic BP for <5 mm Hg, and respectively, 64% and 68% for <10 mm Hg, 84% and 80% for <15 mm Hg and 91% and 87% for <20 mm Hg. Compliance with guidelines was greatest for specialists and midwives (p = 0.001) and their most commonly missed feature (76% to100%) was slow cuff deflation. Interpretation: Rapid cuff deflation underestimates the systolic BP compared to accepted guidelines (2 mm Hg/sec). Medical and midwifery staff may not follow accepted guidelines for BP measurement, particularly with regard to rate of cuff deflation. Potential misdiagnosis and under-treatment of patients with hypertension may compromise pregnancy outcomes

Perceptions of post-caesarean section pain and blood pressure in normotensive women

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A transcriptomic based deconvolution framework for assessing differentiation stages and drug responses of AML

The diagnostic spectrum for AML patients is increasingly based on genetic abnormalities due to their prognostic and predictive value. However, information on the AML blast phenotype regarding their maturational arrest has started to regain importance due to its predictive power for drug responses. Here, we deconvolute 1350 bulk RNA-seq samples from five independent AML cohorts on a single-cell healthy BM reference and demonstrate that the morphological differentiation stages (FAB) could be faithfully reconstituted using estimated cell compositions (ECCs). Moreover, we show that the ECCs reliably predict ex-vivo drug resistances as demonstrated for Venetoclax, a BCL-2 inhibitor, resistance specifically in AML with CD14+ monocyte phenotype. We validate these predictions using LUMC proteomics data by showing that BCL-2 protein abundance is split into two distinct clusters for NPM1-mutated AML at the extremes of CD14+ monocyte percentages, which could be crucial for the Venetoclax dosing patients. Our results suggest that Venetoclax resistance predictions can also be extended to AML without recurrent genetic abnormalities and possibly to MDS-related and secondary AML. Lastly, we show that CD14+ monocytic dominated Ven/Aza treated patients have significantly lower overall survival. Collectively, we propose a framework for allowing a joint mutation and maturation stage modeling that could be used as a blueprint for testing sensitivity for new agents across the various subtypes of AML.Pattern Recognition and Bioinformatic

Ground steel target plates in combination with direct transfer of clinical Candida isolates improves frequencies of species-level identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry

Ground steel target plates in combination with direct transfer of clinical Candida isolates improves frequencies of species-level identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry in comparison with polished steel target plates

SARS-CoV-2 Spike-specific IFN-γ T-cell Response After COVID-19 Vaccination in Patients With Chronic Kidney Disease, on Dialysis, or Living With a Kidney Transplant.

Background: Studies have shown that coronavirus disease 2019 (COVID-19) vaccination is associated with a lower humoral response in vulnerable kidney patients. Here, we investigated the T-cell response following COVID-19 vaccination in kidney patients compared with controls. Methods: Patients with chronic kidney disease (CKD) stage G4/5 [estimated glomerular filtration rate <30 mL/min/1.73 m2], on dialysis, or living with a kidney transplant and controls received 2 doses of the mRNA-1273 COVID-19 vaccine. Peripheral blood mononuclear cells were isolated at baseline and 28 d after the second vaccination. In 398 participants (50% of entire cohort; controls n = 95, CKD G4/5 n = 81, dialysis n = 78, kidney transplant recipients [KTRs] n = 144)' SARS-CoV-2-specific T cells were measured using an IFN-γ enzyme-linked immune absorbent spot assay. Results: A significantly lower SARS-CoV-2-specific T-cell response was observed after vaccination of patients on dialysis (54.5%) and KTRs (42.6%) in contrast to CDK G4/5 (70%) compared with controls (76%). The use of calcineurin inhibitors was associated with a low T-cell response in KTRs. In a subset of 20 KTRs, we observed waning of the cellular response 6 mo after the second vaccination, which was boosted to some extent after a third vaccination, although T-cell levels remained low. Conclusion: Our data suggest that vaccination is less effective in these patient groups, with humoral nonresponders also failing to mount an adequate cellular response, even after the third vaccination. Given the important role of T cells in protection against disease and cross-reactivity to SARS-CoV-2 variants, alternative vaccination strategies are urgently needed in these high-risk patient groups