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Nevin Manimala Statistics

Autopsy-Based Pulmonary and Vascular Pathology: Pulmonary Endotheliitis and Multi-Organ Involvement in COVID-19 Associated Deaths

Respiration. 2021 Sep 15:1-11. doi: 10.1159/000518914. Online ahead of print.

ABSTRACT

BACKGROUND: Findings from autopsies have provided evidence on systemic microvascular damage as one of the underlying mechanisms of Coronavirus disease 2019 (CO-VID-19). The aim of this study was to correlate autopsy-based cause of death in SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients with chest imaging and severity grade of pulmonary and systemic morphological vascular pathology.

METHODS: Fifteen SARS-CoV-2 positive autopsies with clinically distinct presentations (age 22-89 years) were retrospectively analyzed with focus on vascular, thromboembolic, and ischemic changes in pulmonary and in extrapulmonary sites. Eight patients died due to COVID-19 associated respiratory failure with diffuse alveolar damage in various stages and/or multi-organ failure, whereas other reasons such as cardiac decompensation, complication of malignant tumors, or septic shock were the cause of death in 7 further patients. The severity of gross and histopathological changes was semi-quantitatively scored as 0 (absent), 1 (mild), and 3 (severe). Severity scores between the 2 groups were correlated with selected clinical parameters, initial chest imaging, autopsy-based cause of death, and compared using Pearson χ2 and Mann-Whitney U tests.

RESULTS: Severe pulmonary endotheliitis (p = 0.031, p = 0.029) and multi-organ involvement (p = 0.026, p = 0.006) correlated significantly with COVID-19 associated death. Pulmonary microthrombi showed limited statistical correlation, while tissue necrosis, gross pulmonary embolism, and bacterial superinfection did not differentiate the 2 study groups. Chest imaging at hospital admission did not differ either.

CONCLUSIONS: Extensive pulmonary endotheliitis and multi-organ involvement are characteristic autopsy features in fatal CO-VID-19 associated deaths. Thromboembolic and ischemic events and bacterial superinfections occur frequently in SARS-CoV-2 infection independently of outcome.

PMID:34525475 | DOI:10.1159/000518914

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Nevin Manimala Statistics

Rapid Risk Stratification of Acute Ischemic Stroke Patients in the Emergency Department: The Incremental Prognostic Role of Left Atrial Reservoir Strain

J Stroke Cerebrovasc Dis. 2021 Sep 12;30(11):106100. doi: 10.1016/j.jstrokecerebrovasdis.2021.106100. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the prognostic value of positive global left atrial strain (LA-GSA+), measured by two-dimensional speckle tracking echocardiography (2D-STE) in a population of acute ischemic stroke (AIS) patients without atrial fibrillation (AF), in the setting of Emergency Department (ED).

METHODS: All consecutive AIS patients with sinus rhythm on ECG and without AF history entered this prospective study. All patients underwent complete blood tests and transthoracic echocardiography implemented with 2D-STE analysis of LA strain parameters within 6-12 h after symptoms onset. At 6-months follow-up, we evaluated the composite endpoint of all-cause mortality plus cardiovascular re-hospitalizations.

RESULTS: A total of 102 AIS patients (76.4 ± 10.8 yrs, 47% males) were prospectively included. LA-GSA+ was markedly reduced in AIS patients (20.8 ± 7.7%), without any statistically significant difference between the stroke subtypes. At 6-months follow-up, 7 deaths and 27 re-hospitalizations occurred. On multivariate Cox regression analysis, variables independently associated with outcome were: LA-GSA+ (per unit) (HR 0.29, 95% CI 0.19-0.39) and C-reactive protein (CRP) (per 0.1 mg/dl) (HR 1.45, 95% CI 1.15-1.75) as continuous variables; statin therapy (HR 0.45, 95%CI 0.28-0.62), and type 2 diabetes (HR 1.65, 95% CI 1.15-2.35) as categorical variables. A LA-GSA+ ≤20.0% predicted the occurrence of the above-mentioned outcome at 6-months follow-up with 94% sensitivity and 81% specificity (AUC=0.84). Interestingly, GSA+ showed a strong inverse correlation with CRP levels (r = -0.86).

CONCLUSIONS: A LA-GSA+ ≤20% reflects a more advanced atrial cardiomyopathy and might provide a rapid and reliable prognostic risk stratification of AIS patients without AF history in the setting of ED.

PMID:34525440 | DOI:10.1016/j.jstrokecerebrovasdis.2021.106100

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Nevin Manimala Statistics

Study of the structure of a multicomponent salt melt using molecular dynamics modeling

J Phys Condens Matter. 2021 Sep 15. doi: 10.1088/1361-648X/ac26fa. Online ahead of print.

ABSTRACT

The composition of the electrolyte is critical in the electrodeposition of high-purity silicon. In this work, molecular dynamics modeling of the preparation of liquid salt melt KF-KCl-KI and a detailed study of its structure based on the method of statistical geometry have been performed. Partial radial distribution functions reflect the size of the ions under consideration and the averaged structure of the generated ionic subsystems. Halogen subsystems have domed angular distributions of nearest geometric neighbors, a wide range of face types of combined polyhedra, and fifth order rotational symmetry. The shape of the distribution of distances to the nearest neighbors of a given type depends on the amount of these ions in the melt. Small-scale thermal fluctuations in the halogen subsystems are predominantly represented by small triangular faces in combined polyhedra. The electrodeposition of silicon was carried out in a homogeneous salt melt, in which each halogen ion had from one to three close contacts with halogen ions of any other type. The simulations performed provide a fundamental understanding of the structure of the electrolyte molten salts used to produce solar silicon.

PMID:34525454 | DOI:10.1088/1361-648X/ac26fa

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Nevin Manimala Statistics

Burden of Renal Cysts Imaging: A Survey of Patients among the Greater Plains Collaborative

Urol Int. 2021 Sep 15:1-7. doi: 10.1159/000517791. Online ahead of print.

ABSTRACT

PURPOSE: Renal cysts are a frequent incidental finding on cross-sectional radiographic imaging. While most cysts are indolent, individuals with such cysts are frequently monitored for interval growth and potential malignant transformation, which is ultimately rare. In this study, we aimed to assess patients’ values and preferences (believes and attitudes) about renal cysts.

METHODS: We deployed a cross-sectional survey to a random sample of patients with a diagnosis of renal cysts who were identified by billing code and self-identification. We collected data about demographics, insurance status, family history and overall health, and characteristics of patients with renal cysts. We performed a binary regression analysis (adjusted for age, gender, family history of cancer and kidney disease, and treatment plan for renal cysts) to determine anxiety predictors in patients with renal cysts.

RESULTS: We included 301 respondents in whom billing code and self-identification corresponded; of these, 138 had renal cysts and 163 did not. In an adjusted regression analysis, there was a suggestion that a clear management plan (OR = 0.49, 95% CI [0.22-1.11]) (p value 0.08) may be associated with less anxiety and a family history of renal disease may be associated with more anxiety (OR = 1.94 [0.76-4.94]) (p value 0.17). Family history of cancer also did not significantly predict anxiety (OR = 0.54 [0.24-1.19]) (p value 0.13). All these results were not statistically significant and had wide confidence intervals of the effect estimates make the results imprecise.

CONCLUSION: Findings of this pilot study suggest a clear management plan for the renal cyst(s) management may be associated with a lower level of anxiety, thereby by emphasizing the importance of good communication, patient engagement and evidence-based guidance. More definitive, adequately powered studies are needed to evaluate this finding further. In addition, further studies exploring differences in imaging practices, patient symptomatology and patient engagement by different provider types would be insightful. Ultimately, tools to improve shared decision-making are needed to provide more patient-centered care.

PMID:34525470 | DOI:10.1159/000517791

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Nevin Manimala Statistics

Identification of concealed structural alerts using QSTR modeling for Pseudokirchneriella subcapitata

Aquat Toxicol. 2021 Sep 8;239:105962. doi: 10.1016/j.aquatox.2021.105962. Online ahead of print.

ABSTRACT

In the present work, QSTR modeling was conducted for microalga Pseudokirchneriella subcapitata using a data set of 271 molecules belonging to different types of chemical classes for the prediction of EC50 for 72 hr based assays. The balanced QSTR model encompasses seven easily interpretable molecular descriptors and possesses statistical robustness with high predictive ability. This Genetic Algorithm Multi-linear regression (GA-MLR) model was subjected to internal validation, Y-randomization test, applicability domain analysis, and external validation as per the recommended OECD guidelines. The newly developed model fulfilled the threshold values for more than 20 recommended validation parameters including R2 = 0.72, Q2LOO = 0.70, etc. The developed QSTR model was successful in identifying the type of hybridization or specific type of atoms of previously reported and newer structural alerts. Thus, the model could be useful for data gap filling and expanding mechanistic interpretation of toxicity for different chemicals.

PMID:34525418 | DOI:10.1016/j.aquatox.2021.105962

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Nevin Manimala Statistics

No association between children’s febrile seizures and S100B protein levels: A meta-analysis

Seizure. 2021 Aug 31;92:158-165. doi: 10.1016/j.seizure.2021.08.015. Online ahead of print.

ABSTRACT

BACKGROUND: In recent years, studies have examined the relationship between febrile seizures in children and S100B protein with contradictory results. We systematically evaluated the relationship between children’s febrile seizures and S100B protein levels.

METHODS: We used Stata 11.0 software to conduct a meta-analysis of the included studies published in The China National Knowledge Infrastructure, VIP, Wanfang, Chinese Biology Medicine Disc, PubMed, Web of Science, Cochrane Library, and EMBASE databases as well as clinical trial registries in China, Europe, and the United States.

RESULTS: Six case-control studies were finally included in the meta-analysis. The results of the meta-analysis showed that the serum S100B protein level of children with febrile seizures was 0.72 higher than the serum S100B protein level of healthy children (Z=6.85, 95% CI 0.52∼0.93, P<0.05). There was no difference in the serum S100B protein level between the children with febrile seizures and children with fever but without seizures (Z=0.70, 95% CI -0.20∼0.41, P>0.05).

CONCLUSION: The level of serum S100B protein in children with febrile seizures was higher than that of healthy children and was statistically significant, whereas the increase in children with higher fever without seizures was not statistically significant. Because there was only a difference in serum S100B protein levels between children with febrile seizures and healthy children but not in febrile children without seizures as the strongest confounding factors for the results, febrile seizures do not elevate the level of S100B protein levels any more than fever.

PMID:34525431 | DOI:10.1016/j.seizure.2021.08.015

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Nevin Manimala Statistics

The exposome in practice: an exploratory panel study of biomarkers of air pollutant exposure in Chinese people aged 60-69 years (China BAPE Study)

Environ Int. 2021 Sep 12;157:106866. doi: 10.1016/j.envint.2021.106866. Online ahead of print.

ABSTRACT

The exposome overhauls conventional environmental health impact research paradigms and provides a novel methodological framework that comprehensively addresses the complex, highly dynamic interplays of exogenous exposures, endogenous exposures, and modifiable factors in humans. Holistic assessments of the adverse health effects and systematic elucidation of the mechanisms underlying environmental exposures are major scientific challenges with widespread societal implications. However, to date, few studies have comprehensively and simultaneously measured airborne pollutant exposures and explored the associated biomarkers in susceptible healthy elderly subjects, potentially resulting in the suboptimal assessment and management of health risks. To demonstrate the exposome paradigm, we describe the rationale and design of a comprehensive biomarker and biomonitoring panel study to systematically explore the association between individual airborne exposure and adverse health outcomes. We used a combination of personal monitoring for airborne pollutants, extensive human biomonitoring, advanced omics analysis, confounding information, and statistical methods. We established an exploratory panel study of Biomarkers of Air Pollutant Exposure in Chinese people aged 60-69 years (China BAPE), which included 76 healthy residents from a representative community in Jinan City, Shandong Province. During the period between September 2018 and January 2019, we conducted prospective longitudinal monitoring with a 3-day assessment every month. This project: (1) leveraged advanced tools for personal airborne exposure monitoring (external exposures); (2) comprehensively characterized biological samples for exogenous and endogenous compounds (e.g., targeted and untargeted monitoring) and multi-omics scale measurements to explore potential biomarkers and putative toxicity pathways; and (3) systematically evaluated the relationships between personal exposure to air pollutants, and novel biomarkers of exposures and effects using exposome-wide association study approaches. These findings will contribute to our understanding of the mechanisms underlying the adverse health impacts of air pollution exposures and identify potential adverse clinical outcomes that can facilitate the development of effective prevention and targeted intervention techniques.

PMID:34525388 | DOI:10.1016/j.envint.2021.106866

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Nevin Manimala Statistics

Analysis of the impact of COVID-19 on collisions, fatalities and injuries using time series forecasting: The case of Greece

Accid Anal Prev. 2021 Sep 4;162:106391. doi: 10.1016/j.aap.2021.106391. Online ahead of print.

ABSTRACT

The current study aims to investigate the impact of the COVID-19 pandemic on road traffic collisions, fatalities, and injuries using time series analyses. To that aim, a database containing road collisions, fatalities, and slight injuries data from Greece were derived from the Hellenic Statistical Authority (HSA) and covered a ten-year timeframe (from January 2010 to August 2020. The chosen time period contained normal operations, as well as the period of the first COVID-19-induced lockdown period in Greece. Three different Seasonal Autoregressive Integrated Moving Average (SARIMA) time series models were implemented in order to compare the observed measurements to forecasted values that were intended to depict assumed conditions; namely, without the appearance of the COVID-19 pandemic. Modelling results revealed that the total number of road collisions, fatalities, and slightly injured were decreased, mainly due to the sharp traffic volume decrease. However, the percentage reduction of the collision variables and traffic volume were found to be disproportionate, which probably indicates that more collisions occurred with regard to the prevailing traffic volume. An additional finding is that fatalities and slightly injured rates were significantly increased during the lockdown period and the subsequent month. Overall, it can be concluded that a worse performance was identified in terms of road safety. Since subsequent waves of COVID-19 cases and other pandemics may reappear in the future, the outcomes of the current study may be exploited for the improvement of road safety from local authorities and policymakers.

PMID:34525414 | DOI:10.1016/j.aap.2021.106391

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Nevin Manimala Statistics

RARG variant predictive of doxorubicin-induced cardiotoxicity identifies a cardioprotective therapy

Cell Stem Cell. 2021 Sep 14:S1934-5909(21)00343-X. doi: 10.1016/j.stem.2021.08.006. Online ahead of print.

ABSTRACT

Doxorubicin is an anthracycline chemotherapy agent effective in treating a wide range of malignancies, but its use is limited by dose-dependent cardiotoxicity. A recent genome-wide association study identified a SNP (rs2229774) in retinoic acid receptor-γ (RARG) as statistically associated with increased risk of anthracycline-induced cardiotoxicity. Here, we show that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from patients with rs2229774 and who suffered doxorubicin-induced cardiotoxicity (DIC) are more sensitive to doxorubicin. We determine that the mechanism of this RARG variant effect is mediated via suppression of topoisomerase 2β (TOP2B) expression and activation of the cardioprotective extracellular regulated kinase (ERK) pathway. We use patient-specific hiPSC-CMs as a drug discovery platform, determining that the RARG agonist CD1530 attenuates DIC, and we confirm this cardioprotective effect in an established in vivo mouse model of DIC. This study provides a rationale for clinical prechemotherapy genetic screening for rs2229774 and a foundation for the clinical use of RARG agonist treatment to protect cancer patients from DIC.

PMID:34525346 | DOI:10.1016/j.stem.2021.08.006

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Nevin Manimala Statistics

A Comparison of Clinical Outcomes Between Two Different Models of Surgical Robots in Roux-en-Y Gastric Bypass

J Laparoendosc Adv Surg Tech A. 2021 Sep;31(9):969-977. doi: 10.1089/lap.2021.0477. Epub 2021 Aug 17.

ABSTRACT

Introduction: For the past 20 years, robotic surgical systems have been used for the Roux-en-Y gastric bypass (RYGB). The da Vinci Surgical System (Intuitive Surgical, Inc.) has been one of the most used robotic platforms. This study aims to retrospectively compare the performance of two models of surgical robots. Materials and Methods: A retrospective comparative study was conducted from a prospective database including all patients who underwent robotic RYGB (RRYGB) from 2011 to 2020. Results: Of a total of 277 patients included, 134 were in the RRYGB using the da Vinci S™ (RRYGB-S™) group and 143 were in the RRYGB using the da Vinci Xi™ (RRYGB-Xi™) group. The mean operative time in the RRYGB-S and RRYGB-Xi groups was 154 ± 28 and 151 ± 32 minutes, respectively (P = .510). The was no statistically significant difference in terms of intraoperative complications between the groups with regard to positive blue test, bleeding, and failure of stapler line. The readmission rate was higher in the RRGB-S group (14.1%) than in the RRYGB-Xi group (3.4%) (P = .004), and it was mainly due to major complications (P = .003) including pouch and gastrojejunostomy anastomotic leaks (P = .001). The nonsurgical complications were statistically significantly higher in the RRYGB-S group (7.4%) than in the RRYGB-Xi group (2.1%) (P < .05), as well as the surgical complications were higher in the RRYGB-S group (7.5%) than in the RRYGB-Xi group (0%) (P < .001). The mean percentage of the total weight loss at 1 and 2 years of follow-up did not show any statistically significant difference (P = .547). Conclusions: The higher complication rate in the S surgical system might be correlated with the initial learning curve and stressed the need for proper robotic surgical training and accurate strategies when introducing emerging technologies into the surgical practice.

PMID:34525316 | DOI:10.1089/lap.2021.0477