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Predictive plasma biomarkers of long-term increase in hepatic steatosis index after HCV eradication in HIV/HCV-coinfected patients

Biomed Pharmacother. 2023 May 20;164:114913. doi: 10.1016/j.biopha.2023.114913. Online ahead of print.

ABSTRACT

Hepatic steatosis is a common condition found in the liver of hepatitis C virus (HCV)-infected patients, contributing to more severe forms of liver disease. In addition, the human immunodeficiency virus (HIV) may accelerate this process. Alternatively, several immune checkpoint proteins have been reported to be upregulated and correlated with disease progression during HCV and HIV infections. In steatosis, a detrimental immune system activation has been established; however, the role of the immune checkpoints has not been addressed so far. Thus, this study aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before antiviral therapy) with hepatic steatosis index (HSI) increase at the end of follow-up (∼ five years after sustained virologic response (SVR)). We performed a multicenter retrospective study in 62 patients coinfected with HIV/HCV who started antiviral therapy. Immune checkpoint proteins were analyzed at baseline using a Luminex 200TM analyzer. The statistical association analysis was carried out using Generalized Linear Models (GLM) and Partial Least Squares Discriminant Analysis (PLS-DA). Fifty-three percent of the patients showed HSI increase from baseline to the end of follow-up. Higher immune checkpoint protein levels of BTLA, CD137(4-1BB), CD80, GITR, LAG-3, and PD-L1 before HCV therapy were associated with a long-term increase in HSI after successful HCV therapy, suggesting a potential predictive role for early detection of progression towards steatosis in HIV/HCV-coinfected patients.

PMID:37216704 | DOI:10.1016/j.biopha.2023.114913

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The effect of reclined seatback angles on the motion of booster-seated children during lateral-oblique low-acceleration impacts

Accid Anal Prev. 2023 May 20;188:107117. doi: 10.1016/j.aap.2023.107117. Online ahead of print.

ABSTRACT

Belt-positioning boosters (BPB) may prevent submarining in novel seating configurations such as seats with reclined seatbacks. However, several knowledge gaps in the motion of reclined child occupants remain as previous reclined child studies only examined responses of a child anthropomorphic test device (ATD) and the PIPER finite element (FE) model in frontal impacts. The aim of this study is to investigate the effect of reclined seatback angles and two types of BPBs on the motion of child volunteer occupants in low-acceleration far-side lateral-oblique impacts. Six healthy children (3 males, 3 females, 6-8 years, seated height: 66±3.2 cm, weight: 25.2±3.2 kg) were seated on two types of low-back BPB (standard and lightweight) on a vehicle seat and restrained by a 3-point simulated-integrated seatbelt on a low-acceleration sled. The sled exposed the participants to a low-speed lateral-oblique (80° from frontal) pulse (2 g). Three seatback recline angles (25°, 45°, 60° from vertical) with two BPB (standard and lightweight) were tested. A 10-camera 3D-motion-capture system (Natural Point Inc.) was used to capture peak lateral head and trunk displacements and forward knee-head distance. Three seat-belt load cells (Denton ATD Inc) captured peak seatbelt loads. Electromyography (EMG, Delsys Inc) recorded muscle activation. Repeated Measure 2-way ANOVAs were performed to evaluate the effect of seatback recline angle and BPB on kinematics. Tukey’s post-hoc test for pairwise comparisons was used. P-level was set to 0.05. Peak lateral head and trunk displacement decreased with the increasing seatback recline angle (p < 0.005, p < 0.001, respectively). Lateral peak head displacement was greater in the 25° compared to the 60° condition (p < 0.002) and in the 45° condition compared to the 60° condition (p < 0.04). Lateral peak trunk displacement was greater in the 25° condition than the 45° condition (p < 0.009) and the 60° condition (p < 0.001), and in the 45° condition than the 60° condition (p < 0.03). Overall peak lateral head and trunk displacements and knee-head forward distance were slightly greater in the standard than the lightweight BPB (p < 0.04), however these differences between BPBs were small (∼10 mm). Shoulder belt peak load decreased as the reclined seatback angle increased (p < 0.03): the shoulder belt peak load was statistically greater in the 25° condition than the 60° condition (p < 0.02). Muscle activation from the neck, upper trunk, and lower legs showed great activation. Neck muscles activation increased with the increase in seatback recline angle. Thighs, upper arms, and abdominal muscles showed small activation and no effect of conditions. Child volunteers showed decreased displacement suggesting that reclined seatbacks placed the booster-seated children in a more favorable position within the shoulder belt in a low-acceleration lateral-oblique impact, compared to nominal seatback angles. BPB type seemed to minimally influence the children’s motion: the small differences found may have been due to the slight difference in heights between the two BPBs. Future research with more severe pulses is needed to better understand reclined children’s motion in far-side lateral-oblique impacts.

PMID:37216696 | DOI:10.1016/j.aap.2023.107117

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Validation of a symptom scale for COVID-19 patients in ambulatory care

Rev Med Inst Mex Seguro Soc. 2023 May 2;61(3):348-355.

ABSTRACT

BACKGROUND: A symptom scale can be useful for the standardization of clinical evaluations and follow-up of COVID-19 patients in ambultaroy care. Scale development should be accompanied by an assessment of its reliablility and validity.

OBJECTIVE: To develop and measure the psychometric characteristics of a COVID-19 symptom scale to be answered by either healthcare personnel or adult patients in ambulatory care.

MATERIAL AND METHODS: The scale was developed by an expert panel using the Delphi method. We evaluated inter-rater reliability, where we defined a good correlation if Spearman’s Rho was ≥ 0.8; test-retest, where we defined a good correlation if Spearman’s Rho was ≥ 0.7; factor analysis using principal component methodology; and discriminant validity using Mann-Whitney’s U test. A p < 0.05 was considered statistically significant.

RESULTS: We obtained an 8 symptom scale, each symptom is scored from 0-4, with a total minimum score of 0 and a maximum of 32 points. Inter-rater reliability was 0.995 (n = 31), test-retest showed correlation of 0.88 (n = 22), factor analysis detected 4 factors (n = 40) and discriminant capacity of healthy versus sick adults was significant (p < 0.0001, n = 60).

CONCLUSIONS: We obtained a reliable and valid Spanish (from Mexico) symptom scale for COVID-19 ambulatory care, answerable by patients and health care staff.

PMID:37216678

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Vitamin K1 and progression of cardiovascular calcifications in hemodialysis patients: the VitaVasK randomized controlled trial

Clin Kidney J. 2022 Aug 24;15(12):2300-2311. doi: 10.1093/ckj/sfac184. eCollection 2022 Dec.

ABSTRACT

BACKGROUND: Cardiovascular calcifications are prevented by matrix Gla protein (MGP), a vitamin K-dependent protein. Haemodialysis patients exhibit marked vitamin K deficiency. The randomized, prospective, open-label, multicentre VitaVasK trial analysed whether vitamin K1 supplementation reduces progression of coronary artery calcifications (CACs) and thoracic aortic calcifications (TACs).

METHODS: Patients with pre-existing CACs were randomized to continue on standard care or to additionally receive 5 mg of vitamin K1 orally thrice weekly. Hierarchically ordered primary endpoints were progression of TAC and CAC in computed tomography scans at 18 months. Linear mixed effects models with repeated measures at baseline and 12 and 18 months assessed treatment effects after adjusting for study site.

RESULTS: Of 60 randomized patients, 20 dropped out for reasons unrelated to vitamin K1, resulting in 23 control and 17 vitamin K1 patients. The trial was stopped early due to slow recruitment. At 18 months, the average TAC progression was 56% lower in the vitamin K1 compared with the control group (p = .039). CAC significantly progressed within the control group, but not within the vitamin K1 group. Average progression at 18 months was 68% lower in the vitamin K1 compared to the control group (P = .072). Vitamin K1 reduced plasma levels of pro-calcific uncarboxylated MGP by 69% at 18 months. No treatment-related adverse events were noted.

CONCLUSION: Vitamin K1 intervention is a potent, safe and cost-effective approach to correct vitamin K deficiency and to potentially reduce cardiovascular calcification in this high-risk population.

PMID:37216675 | PMC:PMC9664584 | DOI:10.1093/ckj/sfac184

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Association of neutrophil, lymphocyte, platelet ratio with acute kidney injury in sepsis

Rev Med Inst Mex Seguro Soc. 2023 May 2;61(3):342-347.

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is frequent in sepsis (25 to 51%), with high mortality (40 to 80%) and long-term complications. Despite its importance we do not have accessible markers in intensive care. In other entities (post-surgical and COVID-19) the neutrophil/lymphocyte and platelet (N/LP) ratio has been associated with acute kidney injury; however, this relationship has not been studied in a pathology with a severe inflammatory response such as sepsis.

OBJECTIVE: To demonstrate the association between N/LP with AKI secondary to sepsis in intensive care.

MATERIAL AND METHODS: Ambispective cohort study in patients over 18 years who were admitted to intensive care with a diagnosis of sepsis. The N/LP ratio was calculated from admission up to the seventh day and up to the diagnosis of AKI and outcome. Statistical analysis was performed with chi squared test, Cramer’s V and multivariate logistic regression.

RESULTS: Out of the 239 patients studied, the incidence of AKI developed in 70%. 80.9% of patients with N/LP ratio > 3 had AKI (p < 0.0001, Cramer’s V 0.458, OR 3.05, 95% CI 1.602-5.8) and increased renal replacement therapy (21.1 vs. 11.1%, p = 0.043).

CONCLUSION: N/LP ratio > 3 has a moderate association with AKI secondary to sepsis in the intensive care unit.

PMID:37216673

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Prenatal Exposure to Perfluoroalkyl Substances and Cognitive and Neurobehavioral Development in Children at 6 Years of Age

Environ Sci Technol. 2023 May 22. doi: 10.1021/acs.est.2c06535. Online ahead of print.

ABSTRACT

Epidemiological evidence regarding the effects of prenatal exposure to perfluoroalkyl substances (PFASs) on neurodevelopment in children is inconclusive. In 449 mother-child pairs from the Shanghai-Minhang Birth Cohort Study, we measured the concentrations of 11 PFASs in maternal plasma samples obtained at 12-16 weeks of gestation. We assessed children’s neurodevelopment at 6 years of age by the fourth edition of the Chinese Wechsler Intelligence Scale for Children and Child Behavior Checklist for ages 6-18. We evaluated the association between prenatal exposure to PFASs and children’s neurodevelopment and the effect modification of maternal dietary factors during pregnancy and the child’s sex. We found that prenatal exposure to multiple PFASs was associated with increased scores for attention problems, and the individual effect of perfluorooctanoic acid (PFOA) was statistically significant. However, no statistically significant association between PFASs and cognitive development was observed. Additionally, we found the effect modification of maternal nut intake and child’s sex. In conclusion, this study suggests that prenatal exposure to PFASs was associated with more attention problems, and maternal nut intake during pregnancy may alter the potential effect of PFASs. However, these findings were exploratory because of multiple testing and the relatively small sample size.

PMID:37216669 | DOI:10.1021/acs.est.2c06535

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Impact of hyperglycemia on the prognosis of patients hospitalized for severe pneumonia in COVID-19

Rev Med Inst Mex Seguro Soc. 2023 May 2;61(3):335-341.

ABSTRACT

BACKGROUND: Adequate glycemic control improves the prognosis of patients hospitalized for pneumonia associated with severe COVID-19.

OBJECTIVE: To evaluate the impact of hyperglycemia (HG) on the prognosis of patients hospitalized for severe pneumonia associated with COVID-19 in unvaccinated patients.

MATERIAL AND METHODS: Prospective cohort study. We included patients hospitalized from August 2020 to February 2021, with severe COVID-19 pneumonia, not vaccinated against SARS-CoV-2. Data was collected from admission to discharge. We used descriptive and analytical statistics according to the data distribution. ROC curves were used to determine the cut-off points with the highest predictive performance for HG and mortality, with the IBM SPSS program, version 25.

RESULTS: We included 103 patients, 32% women, 68% men, age 57 ± 13 years; 58% were admitted with HG (191, IQR 152-300 mg/dL) and 42% with normoglycemia (NG < 126 mg/dL). Mortality was higher in HG at admission 34 (56.7%) than in NG 13 (30.2%) (p = 0.008). HG was associated with diabetes mellitus 2 and neutrophilia (p < 0.05). The risk of death increases 1.558 times (95% CI 1.118-2.172) if HG is at admission and 1.43 times (95% CI 1.14-1.79) during hospitalization. Maintaining NG throughout the hospitalization contributed independently to survival (RR = 0.083 [95% CI 0.012-0.571], p = 0.011).

CONCLUSION: HG significantly impacts prognosis by increasing mortality more than 50% during hospitalization for COVID-19.

PMID:37216668

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Temporal Trends in the Use of Computed Tomographic Pulmonary Angiography for Suspected Pulmonary Embolism in the Emergency Department : A Retrospective Analysis

Ann Intern Med. 2023 May 23. doi: 10.7326/M22-3116. Online ahead of print.

ABSTRACT

BACKGROUND: Recently, validated clinical decision rules have been developed that avoid unnecessary use of computed tomographic pulmonary angiography (CTPA) in patients with suspected pulmonary embolism (PE) in the emergency department (ED).

OBJECTIVE: To measure any resulting change in CTPA use for suspected PE.

DESIGN: Retrospective analysis.

SETTING: 26 European EDs in 6 countries.

PATIENTS: Patients with CTPA performed for suspected PE in the ED during the first 7 days of each odd month between January 2015 and December 2019.

MEASUREMENTS: The primary end points were the CTPAs done for suspected PE in the ED and the number of PEs diagnosed in the ED each year adjusted to an annual census of 100 000 ED visits. Temporal trends were estimated using generalized linear mixed regression models.

RESULTS: 8970 CTPAs were included (median age, 63 years; 56% female). Statistically significant temporal trends for more frequent use of CTPA (836 per 100 000 ED visits in 2015 vs. 1112 in 2019; P < 0.001), more diagnosed PEs (138 per 100 000 in 2015 vs. 164 in 2019; P = 0.028), a higher proportion of low-risk PEs (annual percent change [APC], 13.8% [95% CI, 2.6% to 30.1%]) with more ambulatory management (APC, 19.3% [CI, 4.1% to 45.1%]), and a lower proportion of intensive care unit admissions (APC, -8.9% [CI, -17.1% to -0.3%]) were observed.

LIMITATION: Data were limited to 7 days every 2 months.

CONCLUSION: Despite the recent validation of clinical decision rules to limit the use of CTPA, an increase in the CTPA rate along with more diagnosed PEs and especially low-risk PEs were instead observed.

PRIMARY FUNDING SOURCE: None specific for this study.

PMID:37216659 | DOI:10.7326/M22-3116

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Knowledge and experience of Primary Education teachers regarding childhood asthma: mixed study

Rev Esc Enferm USP. 2023 May 22;57:e20220329. doi: 10.1590/1980-220X-REEUSP-2022-0329en. eCollection 2023.

ABSTRACT

OBJECTIVE: To analyze the knowledge of Primary Education teachers regarding asthma and learn about their experiences with the exacerbation of symptoms at school.

METHOD: Sequential explanatory mixed study. In the quantitative stage, the Newcastle Asthma Knowledge Questionnaire and the characterization instrument were applied. Data analyzed by descriptive and inferential statistics. The production of qualitative data occurred from written statements analyzed using the deductive content analysis method.

RESULTS: Two hundred and seven teachers, mostly women (92%) and working in public schools (82%). As for knowledge, 132 (63.8%) had unsatisfactory performance. The questions with the lowest rates of correct answers were about medications used regularly and during the attacks. Teachers with higher scores had less time in the occupation (p = 0.017) and had been diagnosed with asthma (p = 0.006). In the qualitative stage, 35 teachers participated and the statements corroborated the quantitative findings, especially in relation to the knowledge gap and feeling of greater safety among asthmatic teachers.

CONCLUSION: Teachers showed insufficient knowledge and reported fear and unpreparedness in the face of the situation.

PMID:37216653 | DOI:10.1590/1980-220X-REEUSP-2022-0329en

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Longitudinal changes in Alzheimer’s-related plasma biomarkers and brain amyloid

Alzheimers Dement. 2023 May 22. doi: 10.1002/alz.13157. Online ahead of print.

ABSTRACT

INTRODUCTION: Understanding longitudinal plasma biomarker trajectories relative to brain amyloid changes can help devise Alzheimer’s progression assessment strategies.

METHODS: We examined the temporal order of changes in plasma amyloid-β ratio ( A β 42 / A β 40 ${{rm A}beta }_{42}/{{rm A}beta }_{40}$ ), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau ratios ( p-tau181 / A β 42 $text{p-tau181}/mathrm{A}{beta}_{42}$ , p-tau231 / A β 42 $text{p-tau231}/mathrm{A}{beta}_{42}$ ) relative to 11 C-Pittsburgh compound B (PiB) positron emission tomography (PET) cortical amyloid burden (PiB-/+). Participants (n = 199) were cognitively normal at index visit with a median 6.1-year follow-up.

RESULTS: PiB groups exhibited different rates of longitudinal change in A β 42 / A β 40 ( β = 5.41 × 10 4 , SE = 1.95 × 10 4 , p = 0.0073 ) ${{rm A}beta }_{42}/{{rm A}beta }_{40} ( {beta = 5.41 times {{10}}^{ – 4},{rm{ SE }} = 1.95 times {{10}}^{ – 4}, p = 0.0073} )$ . Change in brain amyloid correlated with change in GFAP (r = 0.5, 95% CI = [0.26, 0.68]). The greatest relative decline in A β 42 / A β 40 ${{rm A}beta }_{42}/{{rm A}beta }_{40}$ (-1%/year) preceded brain amyloid positivity by 41 years (95% CI = [32, 53]).

DISCUSSION: Plasma A β 42 / A β 40 ${{rm A}beta }_{42}/{{rm A}beta }_{40}$ may begin declining decades prior to brain amyloid accumulation, whereas p-tau ratios, GFAP, and NfL increase closer in time. HIGHLIGHTS Plasma A β 42 / A β 40 ${{rm A}beta }_{42}/{{rm A}beta }_{40}$ declines over time among PiB- but does not change among PiB+. Phosphorylated-tau to Aβ42 ratios increase over time among PiB+ but do not change among PiB-. Rate of change in brain amyloid is correlated with change in GFAP and neurofilament light chain. The greatest decline in A β 42 / A β 40 ${{rm A}beta }_{42}/{{rm A}beta }_{40}$ may precede brain amyloid positivity by decades.

PMID:37216632 | DOI:10.1002/alz.13157