Association between blood carboxyhemoglobin level and bronchopulmonary dysplasia in extremely low birthweight infants

Carboxyhemoglobin (CO-Hb) can be endogenously formed in the presence of oxidative stress and may be elevated in inflammatory lung disease. There is lack of evidence of its relationship with the development of bronchopulmonary dysplasia (BPD) in extremely low birthweight (ELBW) infants. The objective of the study is to evaluate the relationship between blood CO-Hb levels in the first 14 days of life (DOL) in ELBW infants and the development of BPD at 36 weeks postmenstrual age (PMA). This is a retrospective cohort study of 58 ELBW infants born at LAC-USC Medical Center between June 2015 and and June 2019 who survived to 36 weeks PMA. CO-Hb values were collected daily from DOL 1 to DOL 14. BPD definition using the recent 2019 NICHD criteria was used. Multivariate logistic regression was performed to determine the association between blood CO-Hb levels and BPD. Receiver operator curve was used to evaluate the ability of the median fraction of inspired oxygen (FiO2) level used at DOL 11–14 in discriminating absent to mild BPD versus moderate to severe BPD. 58 ELBW infants were included in the study. 24 (41%) were diagnosed with moderate to severe BPD, while 34 (59%) were diagnosed with no to mild BPD. Severity of BPD was fairly discriminated by FiO2 at DOL 11–14, but not with CO-Hb levels at any point within the first 14 DOL. The role and mechanism of CO-Hb production in this population need to be further studied.

RADT-22. RE-IRRADIATION FOR RECURRENT GLIOBLASTOMAS (GBM)

AIMS In this report, we describe our experience in dealing with recurrent GBMs in terms of efficacy and toxicity of second RT course (re-RT) with 3DCTR or VMAT protocols. We carefully reviewed our patient’s outcomes and additionally performed a comprehensive and updated meta-analysis of recent recurrent re-RT GBMs literature to compare our results with the ongoing findings of the t studies. METHODS We retrospectively collected data between 2017 and 2020 at our Institution. Also, we used the random-effects model to pool outcomes across studies about re-RT GBMs from the recent literature (prospective studies from 2010 to 2020, ≥ 30 patients, re-RT with 3DCTR or IMRT-VMAT) to have a more homogenous cohort in terms of treatment modalities, thus reducing the selection bias. RESULTS Re-irradiation was performed at a median interval time of 13.5 (range 4 - 192 months) months from the first RT. The median re-RT dose was 18 Gy (range 12–36 Gy), and the median fraction size was 3,45 Gy (range 1,8–6 Gy). The total median equivalent dose (EQD2) was 84 Gy (range 65.7 – 110 Gy). Our cohort median PFS is 12.5 months (range 4 – 192 months), while the median OS was 26 months (range 6 – 213 months). Our results show that OS-6 and OS-12, from time of re-irradiation, to be 69.2% and 30.7% respectively and the PFS-6 and PFS-12 to be 76.9% and 23.0%, respectively. None of our patients experienced acute toxicity. In our literature research, we found 22 eligible studies, including 1065 patients. The results of the pooled outcomes were: OS-12 rate 35% (95% CI: 30–40%), PFS-12 rate 16% (95% CI 13–19%), and Grade 3 + AE rate < 5% (95% CI 0–10%). CONCLUSIONS Our data confirm re-RT is safe and feasible treatment with a limited toxicity for salvage treatment in recurrent GBMs.

Thrombus Histology of Basilar Artery Occlusions

Background For patients with acute vessel occlusions of the anterior circulation histopathology of retrieved cerebral thrombi has been reported to be associated to stroke etiology. Due to the relatively small incidence of posterior circulation stroke, exclusive histopathologic analyses are missing for this subgroup. The aim of the study was to investigate thrombus histology for patients with basilar artery occlusions and uncover differences to anterior circulation clots with respect to underlying etiology. Methods A total of 59 basilar thrombi were collected during intracranial mechanical recanalization and quantitatively analyzed in terms of their relative fractions of the main constituents, e.g. fibrin/platelets (F/P), red (RBC) and white blood cells (WBC). Data were compared to histopathological analyses of 122 thrombi of the anterior circulation with respect to underlying pathogenesis. Results The composition of basilar thrombi differed significantly to thrombi of the anterior circulation with an overall higher RBC amount (median fraction in % (interquartile range):0.48 (0.37–0.69) vs. 0.37 (0.28–0.50), p < 0.001) and lower F/P count (0.45 (0.21–0.58) vs. 0.57 (0.44–0.66), p < 0.001). Basilar thrombi composition did not differ between the different etiological stroke subgroups. Conclusion The results depict a differing thrombus composition of basilar thrombi in comparison to anterior circulation clots with an overall higher amount of RBC. This may reflect different pathophysiologic processes between anterior and posterior circulation thrombogenesis, e.g. a larger proportion of appositional thrombus growth in the posterior circulation.

Topologic Analysis of Plasma Mitochondrial DNA Reveals the Coexistence of Both Linear and Circular Molecules

BACKGROUND Cellular mitochondrial DNA (mtDNA) is organized as circular, covalently closed and double-stranded DNA. Studies have demonstrated the presence of short mtDNA fragments in plasma. It is not known whether circular mtDNA might concurrently exist with linear mtDNA in plasma. METHODS We elucidated the topology of plasma mtDNA using restriction enzyme BfaI cleavage signatures on mtDNA fragment ends to differentiate linear and circular mtDNA. mtDNA fragments with both ends carrying BfaI cleavage signatures were defined as circular-derived mtDNA, whereas those with no cleavage signature or with 1 cleavage signature were defined as linear-derived mtDNA. An independent assay using exonuclease V to remove linear DNA followed by restriction enzyme MspI digestion was used for confirming the conclusions based on BfaI cleavage analysis. We analyzed the presence of BfaI cleavage signatures on plasma DNA ends in nonhematopoietically and hematopoietically derived DNA molecules by sequencing plasma DNA of patients with liver transplantation and bone marrow transplantation. RESULTS Both linear and circular mtDNA coexisted in plasma. In patients with liver transplantation, donor-derived (i.e., liver) mtDNA molecules were mainly linear (median fraction, 91%; range, 75%–97%), whereas recipient-derived (i.e., hematopoietic) mtDNA molecules were mainly circular (median fraction, 88%; range, 77%–93%). The proportion of linear mtDNA was well correlated with liver DNA contribution in the plasma DNA pool (r = 0.83; P value = 0.0008). Consistent data were obtained from a bone marrow transplantation recipient in whom the donor-derived (i.e., hematopoietic) mtDNA molecules were predominantly circular. CONCLUSIONS Linear and circular mtDNA molecules coexist in plasma and may have different tissue origins.

A fully automatic method yielding initial models from high-resolution electron cryo-microscopy maps

A fully automated procedure for optimization and interpretation of reconstructions from cryo-EM is developed and applied to 476 datasets with resolution of 4.5 Å or better, including reconstructions of 47 ribosomes and 32 other protein-RNA complexes. The median fraction of residues in the deposited structures reproduced automatically was 71% for reconstructions determined at resolutions of 3 Å or better and 47% for those at lower resolution.

Estimating the contribution of ion–ion recombination to sub-2 nm cluster concentrations from atmospheric measurements

The significance of ion–ion recombination for atmospheric new particle formation is not well quantified. Here we present and evaluate a method for determining the size distribution of recombination products from the size distributions of neutral and charged clusters. We applied this method to the data measured in Hyytiälä, Finland, to estimate the contribution of ion–ion recombination to the concentrations of atmospheric clusters in the size range of 0.9–2.1 nm. We observed that the concentration of recombination products was highest in the size classes between 1.5 and 1.9 nm. The median concentrations of recombination products were between 1 and 79 cm−3 in different size classes, which resulted in a small proportion of all neutral clusters, varying between 0.05% and 15%. When examining the whole size range between 0.9 and 2.1 nm, the median fraction of recombination products of all neutral clusters was only 1.5%. Overall, the applied method was concluded to be reasonable, and the results are consistent with the earlier estimates on the contribution of recombination products to atmospheric cluster population in Hyytiälä. Still, in order to determine the size distribution of recombination products more accurately in the future, more precise measurements of the size distribution of sub-2 nm clusters would be needed.

Analysis of atmospheric neutral and charged molecular clusters in boreal forest using pulse-height CPC

We measured the size distribution of atmospheric neutral and charged clusters and particles down to mobility diameter around 1.5 nm by applying pulse-height CPC technique at SMEAR II station in Hyytiälä, southern Finland during spring 2007 and May 2008. The concentration of molecular clusters smaller than 3 nm seems to be highly variable in boreal forest environment, the concentration varied typically between 500–50 000 cm−3. By comparing to concentrations measured with ion spectrometers, we conclude that ion clusters and neutral clusters produced by ion-ion recombination are usually not sufficient to explain all of the observed clusters; the median fraction of recombination products from all neutral clusters was 4.9%. Before and during most new particle formation events the cluster formation rate rose only slightly, or remained close to stable. Nocturnal formation of clusters was also frequently observed.

Analysis of atmospheric neutral and charged molecular clusters in boreal forest using pulse-height CPC

We measured the size distribution of atmospheric neutral and charged clusters and particles down to mobility diameter around 1.5 nm by applying pulse-height CPC technique at SMEAR II station in Hyytiälä, southern Finland during spring 2007 and May 2008. The concentration of molecular clusters smaller than 3 nm seems to be highly variable in boreal forest environment. The concentration varied typically between 500–50 000 cm−3, the medians being 8060 cm−3 in year 2007 and 3380 cm−3 in 2008. By comparing to concentrations measured with ion spectrometers, we conclude that ion clusters and neutral clusters produced by ion-ion recombination are usually not sufficient to explain all of the observed clusters; the median fraction of recombination products from all neutral clusters was 4.9%. Before and during most new particle formation events the cluster formation rate rose only slightly, or remained close to stable. Nocturnal formation of clusters was also frequently observed.