Nevin Manimala

J Am Heart Assoc. 2021 Sep 28:e021748. doi: 10.1161/JAHA.120.021748. Online ahead of print.

ABSTRACT

Background The treatment of aortic stenosis is evolving rapidly. Pace of change in the care of patients undergoing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) differs. We sought to determine differences in temporal changes in 30-day mortality, 30-day readmission, and length of stay after TAVR and SAVR. Methods and Results We conducted a retrospective cohort study of patients treated in the United States between 2012 and 2019 using data from the Medicare Data Set Analytic File 100% Fee for Service database. We included consecutive patients enrolled in Medicare Parts A and B and aged ≥65 years who had SAVR or transfemoral TAVR. We defined 3 study cohorts, including all SAVR, isolated SAVR (without concomitant procedures), and elective isolated SAVR and TAVR. The primary end point was 30-day mortality; secondary end points were 30-day readmission and length of stay. Statistical models controlled for patient demographics, frailty measured by the Hospital Frailty Risk Score, and comorbidities measured by the Elixhauser Comorbidity Index (ECI). Cox proportional hazard models were developed with TAVR versus SAVR as the main covariates with a 2-way interaction term with index year. We repeated these analyses restricted to full aortic valve replacement hospitals offering both SAVR and TAVR. The main study cohort included 245 269 patients with SAVR and 188 580 patients with TAVR, with mean±SD ages 74.3±6.0 years and 80.7±6.9 years, respectively, and 36.5% and 46.2% female patients, respectively. Patients with TAVR had higher ECI scores (6.4±3.6 versus 4.4±3) and were more frail (55.4% versus 33.5%). Total aortic valve replacement volumes increased 61% during the 7-year span; TAVR volumes surpassed SAVR in 2017. The magnitude of mortality benefit associated with TAVR increased until 2016 in the main cohort (2012: hazard ratio [HR], 0.76 [95% CI, 0.67-0.86]; 2016: HR, 0.39 [95% CI, 0.36-0.43]); although TAVR continued to have lower mortality rates from 2017 to 2019, the magnitude of benefit over SAVR was attenuated. A similar pattern was seen with readmission, with a lower risk of readmission from 2012 to 2016 for patients with TAVR (2012: HR, 0.68 [95% CI, 0.63-0.73]; 2016: HR, 0.43 [95% CI, 0.41-0.45]) followed by a lesser difference from 2017 to 2019. Year over year, TAVR was associated with increasingly shorter lengths of stay compared with SAVR (2012: HR, 1.91 [95% CI, 1.84-1.98]; 2019: HR, 5.34 [95% CI, 5.22-5.45]). These results were consistent in full aortic valve replacement hospitals. Conclusions The rate of improvement in TAVR outpaced SAVR until 2016, with the recent presence of U-shaped phenomena suggesting a narrowing gap between outcomes. Future longitudinal research is needed to determine the long-term implications of lowering risk profiles across treatment options to guide case selection and clinical care.

PMID:34581191 | DOI:10.1161/JAHA.120.021748

J Agric Food Chem. 2021 Sep 28. doi: 10.1021/acs.jafc.1c05599. Online ahead of print.

ABSTRACT

The angiotensin-converting enzyme (ACE) inhibitory peptide QIGLF derived from egg white was shown to have significant in vivo antihypertensive effects in our previous study, but the intervention mechanisms at the metabolic level are still unclear. The UPLC-QTOF/MS-based untargeted metabolomics approach was used to clarify the potential antihypertensive mechanisms of QIGLF in the serum of spontaneously hypertensive rats (SHRs). Multivariate statistical analysis showed a clear difference in the metabolite profiles between the QIGLF and model groups. The results suggested that eight potential biomarkers were identified, that is, adrenic acid, ursodeoxycholic acid, glycocholic acid, taurocholic acid, tryptophan, acetylindoxyl, tyrosine, and 2-phenylethanol, which were mainly involved in aromatic amino acid biosynthesis and metabolism, biosynthesis of bile acid, and biosynthesis of unsaturated fatty acids. QIGLF might exert antihypertensive effects by improving endothelial dysfunction. This study provides a theoretical basis for future research and application of ACE inhibitory peptides in the prevention and improvement of hypertension.

PMID:34581184 | DOI:10.1021/acs.jafc.1c05599

Tuberk Toraks. 2021 Sep;69(3):297-306. doi: 10.5578/tt.20219701.

ABSTRACT

INTRODUCTION: Acute pulmonary thromboembolism (PTE) is a common cause of cardiovascular mortality. Right ventricular (RV) dysfunction is the most important cause of mortality. Computed Tomography Pulmonary Angiography (CTPA) can detect right ventricular enlargement which is an indicator of RV dysfunction at the time of diagnosis. This study aimed to determine the parameters indicating RV dysfunction in CTPA and correlation of early mortality findings.

MATERIALS AND METHODS: In this retrospective study, electronic files of patients diagnosed PTE with CTPA between January 2012 and December 2017 were evaluated. Measurements of heart chambers, IVC reflux, and IVS morphology were calculated. In-hospital mortality of the patients after acute PTE diagnosis was evaluated.

RESULT: There were 206 eligible patients. Among the evaluated radiological parameters, right atrium (RA) size (p= 0.002), PA size (p= 0.003), Ao size (p= 0.006), and the presence of IVC reflux (p= 0.001) were associated with mortality. No significant relationship was found between RV/LV ≥1 and mortality (p= 0.908). All patients with PTE-related mortality had RV/LV ratio ≥1 in CTPA and had IVC reflux. Patients with an RV/LV ratio of ≥1 had statistically significantly higher troponin levels (p= 0.004) and IVC reflux (p= 0.025) compared to patients with an RV/LV ratio of <1.

CONCLUSIONS: In conclusion, RV/LV ratio should be evaluated together with cardiac biomarkers to define mortality risk.

PMID:34581150 | DOI:10.5578/tt.20219701

Huan Jing Ke Xue. 2021 Oct 8;42(10):4925-4932. doi: 10.13227/j.hjkx.202101043.

ABSTRACT

Antibiotics and heavy metals are both important environmental pollutants and selective stressors for antibiotic resistance. However, the impact of their environmental concentrations on antibiotic resistance levels is still unclear. In this paper, research published before 2019 reporting the abundance of antibiotic resistance genes(ARGs), antibiotics concentrations, or heavy metal concentrations were extracted from the Web of Science database, and then statistical regression was used to investigate their correlative association. The results show that antibiotic selection pressure has a statistically significant effect on the increase in the abundance of ARGs in environmental media such as surface water, sediment, and soil, even at very low antibiotic concentrations(P<0.05). Different classes of antibiotics show different potential to select and enrich ARGs. Heavy metals and the interaction between antibiotics and heavy metals also have significant effects on ARG transmission(P<0.05). Multivariate statistical regression models can better explain the variance of ARG abundance, with R² values for the water phase and solid phase environmental samples of 0.482 and 0.707 respectively, which are much higher than those achieved using univariate regression models. However, additional environmental factors not included may also affect ARG abundance. The results of this work provide a basis for the evaluation and control of environmental antibiotic resistance.

PMID:34581136 | DOI:10.13227/j.hjkx.202101043

Huan Jing Ke Xue. 2021 Oct 8;42(10):4897-4907. doi: 10.13227/j.hjkx.202012118.

ABSTRACT

This study used 21 rock samples and 193 sets of paddy soil and rice grain samples collected form Baiwang Town, an area of clastic sedimentary rocks in Guangxi, China, to evaluate the potential for selenium-rich agriculture. We analyzed the concentrations of selenium and heavy metals in the soil and rice samples, and discuss the influencing factors by means of statistics and correlation analysis. The results showed that the selenium-rich rate of paddy soil and rice grain in Baiwang Town were 67.4% and 64.8%, respectively, but the content of cadmium in the selenium-rich soil samples was generally higher than the baseline value for China and the background value for Guangxi. In comparison to the screening value of soil pollution risk for agricultural land(GB 15618-2018), the over-standard rate of cadmium was 46.1%, while the over-standard rates of other heavy metals were negligible. The comparison shows that the selenium-rich rate of rice was 61.1% in the southern area of Baiwang Town with a negligible heavy metal content, and the advantages of green selenium-rich rice planting were clear. The correlation analysis showed that secondary enrichment was the main form of selenium enrichment in the study area. The soil pH and texture of the root-zone soil also affected the selenium content of the soil. The selenium content of rice seeds was mainly affected by the selenium content, active selenium content, pH, and aluminum oxide content of the root-zone soil. The risk assessment showed that the level of dietary exposure to cadmium is generally within safe limits, but it is still necessary to strengthen the monitoring of cadmium in rice and control cadmium pollution to reduce the levels of dietary exposure, especially in the central region of Baiwang Town.

PMID:34581133 | DOI:10.13227/j.hjkx.202012118

Proc Natl Acad Sci U S A. 2021 Oct 5;118(40):e2105841118. doi: 10.1073/pnas.2105841118.

ABSTRACT

We present a comprehensive statistical framework to analyze data from genome-wide association studies of polygenic traits, producing interpretable findings while controlling the false discovery rate. In contrast with standard approaches, our method can leverage sophisticated multivariate algorithms but makes no parametric assumptions about the unknown relation between genotypes and phenotype. Instead, we recognize that genotypes can be considered as a random sample from an appropriate model, encapsulating our knowledge of genetic inheritance and human populations. This allows the generation of imperfect copies (knockoffs) of these variables that serve as ideal negative controls, correcting for linkage disequilibrium and accounting for unknown population structure, which may be due to diverse ancestries or familial relatedness. The validity and effectiveness of our method are demonstrated by extensive simulations and by applications to the UK Biobank data. These analyses confirm our method is powerful relative to state-of-the-art alternatives, while comparisons with other studies validate most of our discoveries. Finally, fast software is made available for researchers to analyze Biobank-scale datasets.

PMID:34580220 | DOI:10.1073/pnas.2105841118

Proc Natl Acad Sci U S A. 2021 Oct 5;118(40):e2100117118. doi: 10.1073/pnas.2100117118.

ABSTRACT

How early human foragers impacted insular forests is a topic with implications across multiple disciplines, including resource management. Paradoxically, terminal Pleistocene and Early Holocene impacts of foraging communities have been characterized as both extreme-as in debates over human-driven faunal extinctions-and minimal compared to later landscape transformations by farmers and herders. We investigated how rainforest hunter-gatherers managed resources in montane New Guinea and present some of the earliest documentation of Late Pleistocene through mid-Holocene exploitation of cassowaries (Aves: Casuariidae). Worldwide, most insular ratites were extirpated by the Late Holocene, following human arrivals, including elephant birds of Madagascar (Aepyornithidae) and moa of Aotearoa/New Zealand (Dinornithiformes)-icons of anthropogenic island devastation. Cassowaries are exceptional, however, with populations persisting in New Guinea and Australia. Little is known of past human exploitation and what factors contributed to their survival. We present a method for inferring past human interaction with mega-avifauna via analysis of microstructural features of archaeological eggshell. We then contextualize cassowary hunting and egg harvesting by montane foragers and discuss the implications of human exploitation. Our data suggest cassowary egg harvesting may have been more common than the harvesting of adults. Furthermore, our analysis of cassowary eggshell microstructural variation reveals a distinct pattern of harvesting eggs in late ontogenetic stages. Harvesting eggs in later stages of embryonic growth may reflect human dietary preferences and foraging seasonality, but the observed pattern also supports the possibility that-as early as the Late Pleistocene-people were collecting eggs in order to hatch and rear cassowary chicks.

PMID:34580213 | DOI:10.1073/pnas.2100117118

Neurol Neuroimmunol Neuroinflamm. 2021 Sep 27;8(6):e1061. doi: 10.1212/NXI.0000000000001061. Print 2021 Nov.

ABSTRACT

BACKGROUND AND OBJECTIVES: To determine in a mouse model whether neonatal Fc receptor (FcRn) blockade prevents the placental transfer of class G immunoglobulin (IgG) derived from patients with anti-NMDA receptor (NMDAR) encephalitis and their pathogenic effects on the fetuses and offspring.

METHODS: Pregnant C57BL/6J mice were administered via tail vein FcRn antibody (FcRn-ab) or saline solution 6 hours before administration of patients’ or controls’ IgG on days 14, 15, and 16 of gestation. Three experimental groups were established: mice receiving controls’ IgG, patients’ IgG, or patients’ IgG along with pretreatment with FcRn-ab. Immunohistochemical staining, confocal microscopy, hippocampal long-term potentiation, and standardized developmental and behavioral tasks were used to assess the efficacy of treatment with FcRn-ab.

RESULTS: In pregnant mice that received patients’ IgG, treatment with FcRn-ab prevented the IgG from reaching the fetal brain, abrogating the decrease of NMDAR clusters and the reduction of cortical plate thickness that were observed in fetuses from untreated pregnant mice. Moreover, among the offspring of mothers that received patients’ IgG, those whose mothers were treated with FcRn-ab did not develop the alterations that occurred in offspring of untreated mothers, including impairment in hippocampal plasticity, delay in innate reflexes, and visuospatial memory deficits.

DISCUSSION: FcRn blockade prevents placental transfer of IgG from patients with anti-NMDAR encephalitis and abrogates the synaptic and neurodevelopmental alterations caused by patients’ antibodies. This model has potential therapeutic implications for other antibody-mediated diseases of the CNS during pregnancy.

PMID:34580181 | DOI:10.1212/NXI.0000000000001061

Respir Care. 2021 Sep 27:respcare.09244. doi: 10.4187/respcare.09244. Online ahead of print.

ABSTRACT

Background: Ribavirin is an antiviral drug that for many years has been administered to the lungs by aerosolization. Despite advancements in oral delivery routes, there has been a renewed interested in delivering ribavirin via the pulmonary system in select and the severely ill. The vibrating mesh nebulizer (VMN) was previously demonstrated to be an effective alternative to the small particle aerosol generator (SPAG) in particle size, chemical makeup, and concentrations of the ribavirin pre and post nebulization. However, the antiviral activity of ribavirin has never been examined. We sought to study ribavirin’s activity pre and post nebulization via VMN. Methods: We grew and infected human epithelial type 2 cells (HEp2) and primary airway epithelial cells with respiratory syncytial virus (RSV). We then compared the antiviral effect of non-nebulized (control) and aerosolized ribavirin to untreated controls. We used traditional plaque assay and real-time polymerase chain reaction to determine the quantity of virus. Results: Both non-nebulized (control) and nebulized ribavirin reduced the size of RSV plaques compared to untreated controls. Additionally, the non-nebulized and nebulized ribavirin equally inhibited RSV replication. There were no statistically significant differences between the non-nebulized and nebulized ribavirin across all time points. Conclusions: The VMN nebulizer does not affect the antiviral properties of nebulized ribavirin when compared to non-nebulized drug. Our findings add supporting evidence for the use of the VMN in the administration of inhaled ribavirin.

PMID:34580175 | DOI:10.4187/respcare.09244

J Investig Med. 2021 Sep 27:jim-2021-001948. doi: 10.1136/jim-2021-001948. Online ahead of print.

ABSTRACT

Early studies have reported various electrolyte abnormalities at admission in patients with severe COVID-19. 104 out of 193 patients admitted to our institution presented with hypermagnesemia at presentation. It is believed this may be important in the evaluation of severe SARS-CoV-2 infections. This study evaluated the outcomes of hypermagnesemia in patients with COVID-19. A retrospective chart review of patients admitted to the hospital with confirmed SARS-CoV-2 infection was conducted. A review of the medical literature regarding hypermagnesemia, magnesium levels in critical care illness and electrolyte abnormalities in patients with COVID-19 was performed. Differences in demographic and clinical characteristics of patients with hypermagnesemia and normomagnesemia were evaluated using descriptive statistics. Other known variables of disease severity were analyzed. 104 patients (54%) were identified with hypermagnesemia (≥2.5 mg/dL). 48 of those patients were admitted to the intensive care unit (46%, p<0.001). 34 patients required ventilator support (32%, p<0.0001). With age-adjusted logistic regression analysis hypermagnesemia was associated with mortality (p=0.007). This study demonstrates that hypermagnesemia is a significant marker of disease severity and adverse outcome in SARS-CoV-2 infections. We recommend serum magnesium be added to the panel of tests routinely ordered in evaluation of severe SARS-CoV-2 infections.

PMID:34580159 | DOI:10.1136/jim-2021-001948