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Association of Pathogenic DNA Variants Predisposing to Cardiomyopathy With Cardiovascular Disease Outcomes and All-Cause Mortality

JAMA Cardiol. 2022 May 11. doi: 10.1001/jamacardio.2022.0901. Online ahead of print.

ABSTRACT

IMPORTANCE: Pathogenic variants associated with inherited cardiomyopathy are recognized as important and clinically actionable when identified, leading some clinicians to recommend population-wide genomic screening.

OBJECTIVE: To determine the prevalence and clinical importance of pathogenic variants associated with inherited cardiomyopathy within the context of contemporary clinical care.

DESIGN, SETTING, AND PARTICIPANTS: This was a genetic association study of participants in Atherosclerosis in Risk Communities (ARIC), recruited from 1987 to 1989, with median follow-up of 27 years, and the UK Biobank, recruited from 2006 to 2010, with median follow-up of 10 years. ARIC participants were recruited from 4 sites across the US. UK Biobank participants were recruited from 22 sites across the UK. Participants in the US were of African and European ancestry; those in the UK were of African, East Asian, South Asian, and European ancestry. Statistical analyses were performed between August 1, 2021, and February 9, 2022.

EXPOSURES: Rare genetic variants predisposing to inherited cardiomyopathy.

MAIN OUTCOMES AND MEASURES: Pathogenicity of observed DNA sequence variants in sequenced exomes of 13 genes (ACTC1, FLNC, GLA, LMNA, MYBPC3, MYH7, MYL2, MYL3, PRKAG2, TNNI3, TNNT2, TPM1, and TTN) associated with inherited cardiomyopathies were classified by a blinded clinical geneticist per American College of Medical Genetics recommendations. Incidence of all-cause mortality, heart failure, and atrial fibrillation were determined. Cardiac magnetic resonance imaging, echocardiography, and electrocardiogram measures were assessed in a subset of participants.

RESULTS: A total of 9667 ARIC participants (mean [SD] age, 54.0 [5.7] years; 4232 women [43.8%]; 2658 African [27.5%] and 7009 European [72.5%] ancestry) and 49 744 UK Biobank participants (mean [SD] age, 57.1 [8.0] years; 27 142 women [54.5%]; 1006 African [2.0%], 173 East Asian [0.3%], 939 South Asian [1.9%], and 46 449 European [93.4%] European ancestry) were included in the study. Of those, 59 participants (0.61%) in ARIC and 364 participants (0.73%) in UK Biobank harbored an actionable pathogenic or likely pathogenic variant associated with dilated or hypertrophic cardiomyopathy. Carriers of these variants were not reliably identifiable by imaging. However, the presence of these variants was associated with increased risk of heart failure (hazard ratio [HR], 1.7; 95% CI, 1.1-2.8), atrial fibrillation (HR, 2.9; 95% CI, 1.9-4.5), and all-cause mortality (HR, 1.5; 95% CI, 1.1-2.2) in ARIC. Similar risk patterns were observed in the UK Biobank.

CONCLUSIONS AND RELEVANCE: Results of this genetic association study suggest that approximately 0.7% of study participants harbored a pathogenic variant associated with inherited cardiomyopathy. These variant carriers would be challenging to identify within clinical practice without genetic testing but are at increased risk for cardiovascular disease and all-cause mortality.

PMID:35544052 | DOI:10.1001/jamacardio.2022.0901

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Thank you to The Lancet Microbe clinical and statistical peer reviewers in 2021

Lancet Microbe. 2022 Feb;3(2):e87-e89. doi: 10.1016/S2666-5247(22)00002-7. Epub 2022 Feb 2.

NO ABSTRACT

PMID:35544046 | DOI:10.1016/S2666-5247(22)00002-7

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Influence of Seminal Metals on Assisted Reproduction Outcome

Biol Trace Elem Res. 2022 May 11. doi: 10.1007/s12011-022-03256-w. Online ahead of print.

ABSTRACT

Increased levels of metal ions in human seminal fluid have a significant correlation with male fertility. Few publications explain the effect of metals in semen and their influence on assisted reproductive treatments. Semen parameters and the levels of twenty-two metals were measured in the seminal fluid of 102 men attended in a Reproductive Unit. Metals were determined by optical emission spectrophotometry. A statistical relationship was found between spermiogram and iron, which was lower than expected in pathological spermiograms (p = 0.032); zinc (p = 0.066), calcium (p = 0.047), and magnesium (p = 0.048) mean levels were higher in normozoospermics. More days of sexual abstinence correlates with higher seminal zinc (p = 0.001) and magnesium levels (p = 0.002). Lower vanadium values were found to be associated with higher fertilization rates (p = 0.039). Higher values of lead (p = 0.052) and vanadium (p = 0.032) were obtained in patients who did not reach 100% embryo cleavage rate. Aluminium (p = 0.042) and sodium (p = 0.002) were found in lower amounts associated with better blastocyst rates. The implantation rate shows an inverse association with women’s age and iron and calcium content, compared to magnesium and sodium which presented a significant direct association with this percentage. A significant direct relationship was found between the positive evolution of pregnancy and the values of zinc (p = 0.004), calcium (p = 0.013), potassium (p = 0.002), and magnesium (p = 0.009). The study confirms that zinc, iron, calcium, sodium, aluminium, magnesium, vanadium, and lead have positive-negative effects on reproduction and support the analysis of metals in semen as a new line of study on male fertility with implications for reproductive outcomes.

PMID:35543968 | DOI:10.1007/s12011-022-03256-w

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Factors associated with positive results in English literature of acupuncture for chronic pain

Zhongguo Zhen Jiu. 2022 May 12;42(5):573-8. doi: 10.13703/j.0255-2930.20210311-0008.

ABSTRACT

OBJECTIVE: To analyze the main factors affecting the positive results of acupuncture for chronic pain in English literature of randomized controlled trial (RCT), in order to provide reference for the design of acupuncture clinical research.

METHODS: The RCTs of acupuncture for chronic pain published before March 26, 2020 were searched in PubMed, EMbase and Cochrane Library by computer. A total of 21 factors were analyzed by single-factor analysis, and the factors with statistically significant difference were selected for multivariate Logistic regression analysis.

RESULTS: A total of 69 RCTs were included, including 47 RCTs (68.12%) with positive results and 22 RCTs (31.88%) with non-positive results. The multivariate Logistic regression analysis was performed with the three screened factors (publication year, treatment frequency and intervention form) selected by single-factor analysis, and the results showed that the positive results were related to the frequency of acupuncture treatment. The positive rate of RCT with frequency≥2 times a week was 3.24 times of that with frequency<2 times a week (OR=3.24, 95%CI =[1.07,9.83], P<0.05).

CONCLUSION: Acupuncture frequency may be the main factor affecting the positive results of RCT in English literature of acupuncture for chronic pain. More researches are needed in the future to explore the influence of acupuncture frequency on the curative effect.

PMID:35543952 | DOI:10.13703/j.0255-2930.20210311-0008

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Vaccinating across the aisle: using co-partisan source cues to encourage COVID-19 vaccine uptake in the ideological right

J Behav Med. 2022 May 11. doi: 10.1007/s10865-022-00323-4. Online ahead of print.

ABSTRACT

Overcoming the COVID-19 pandemic in the United States will require most Americans to vaccinate against the disease. However, considerable research suggests that a significant proportion of Americans intend to forego vaccination, putting pandemic recovery at risk. Republicans are one of the largest groups of COVID-19 vaccine hesitant individuals. Therefore, identifying strategies to reduce vaccine hesitancy within this group is vital to ending the pandemic. In this study, we investigate the effectiveness of messages from co-partisan sources in reducing vaccine hesitancy. In a large (N = 3000) and demographically representative survey, we find that exposing “Middle-of-the-Road” partisans to pro-vaccine messages from co-partisan source cues reduces vaccine hesitancy. However, for those who identify as “Strong” or “Weak” partisans, we find no statistically significant differences in vaccination intentions when exposed to pro-vaccine messages from co-partisan sources. We conclude by discussing how our findings are helpful for vaccine communication efforts.

PMID:35543897 | DOI:10.1007/s10865-022-00323-4

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Implementation and first experiences with a multimodal mentorship curriculum for medicine-paediatrics residents

Ann Med. 2022 Dec;54(1):1313-1319. doi: 10.1080/07853890.2022.2070661.

ABSTRACT

INTRODUCTION: Mentorship increases trainee productivity, promotes career satisfaction and reduces burnout. Beginning in 2016, our Medicine-Paediatrics residency program developed and implemented a longitudinal mentorship curriculum among trainees. We report initial experiences with that program and discuss potential future directions.

CURRICULUM STRUCTURE AND METHOD OF IMPLEMENTATION: We implemented and adapted a peer mentorship model and expanded it to include guest lectures and workshops centred around 13 core topics. Our expanded model included five longitudinal components: (1) peer mentorship; (2) virtual check-ins with residency leadership; (3) focussed didactics and workshops; (4) small-group dinners highlighting different career paths; and (5) dedicated faculty who pair residents with mentors based on common interests. We compared annual survey results on resident satisfaction with program mentorship, using chi-square and fisher’s exact tests to assess statistically significant differences pre- (2012-2016) and post-intervention (2016-2020).

RESULTS: We analysed 112 responses with annual response rate varying between 41.2% and 100%. Overall satisfaction with mentorship improved from 57.6% to 73.4% (p = .53), satisfaction with emotional support improved from 63.1% to 71.6% (p = .21), and satisfaction with career-specific mentorship improved from 48.5% to 59.5% (p = .70). Residents reported consistently high satisfaction with peer mentorship (77.8%-100%). The percent of residents reporting they had identified a career mentor increased from 60.0% in 2017 to 88.9% in 2019, which was sustained at 90.0% in 2020.

CONCLUSION: We report our experience in implementing and adapting a mentorship curriculum for resident physicians in a single training program, including transitioning to a primarily online-based platform at the outset of the SARS-CoV-2 pandemic. Our results showed a trend towards improvement in resident satisfaction with overall and career-specific mentorship, as well as improved emotional support. Future work is needed using more objective outcome markers among a larger and more diverse group of residents. KEY MESSAGESAmong resident physicians in a single training program, a mix of mentor-mentee dyads, group-based peer mentoring and a structured curriculum has shown promise in improving resident-reported satisfaction with programmatic mentorshipWhile we attempted to adapt the mentorship curriculum to an online platform with the development of the SARS-CoV-2 pandemic, reported satisfaction in overall mentorship and emotional support decreased in comparison to the prior year, an important focus for future work.

PMID:35543194 | DOI:10.1080/07853890.2022.2070661

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Effects of exposure to air pollution on acute cardiovascular and respiratory admissions to the hospital and early mortality at emergency department

Adv Clin Exp Med. 2022 May 11. doi: 10.17219/acem/149400. Online ahead of print.

ABSTRACT

BACKGROUND: Particulate matter (PM) and NO2 induce pathophysiological changes which contribute to an increased incidence of acute cardiovascular (CV) and respiratory (Rp) events.

OBJECTIVES: To analyze the relationship between air quality and the frequency of admissions to the emergency department (ED) due to the CV diseases and Rp causes.

MATERIAL AND METHODS: The study analyzed the reasons for admissions to the ED during the cold periods from January 2017 to January 2020. These data were combined with the average daily concentrations of NO2, PM2.5 and PM10, and the individual air quality indexes (IAQIs) for these pollutants.

RESULTS: Our analyses have shown that 3468 (11.4%) and 1053 (3.46%) of all 30,419 analyzed patients were admitted to the ED for CV and Rp reasons, respectively. Cardiovascular patients were significantly more often admitted to the ED when the IAQI for NO2 was worse than very good, and the IAQI for PM2.5 or PM10 was worse than good. In such periods, diagnoses such as ischemic heart disease (IHD) or syncope were statistically more common and the risk of admission of a patient with a diagnosis such as IHD, heart failure (HF), syncope, stroke, or transient ischemic attack (TIA) was increased. Registered deaths occurred significantly more often among patients admitted on days with moderate or worse than moderate air quality determined in relation to PM10 in comparison to days with very good or good air quality (0.35% and 0.23%, respectively, p = 0.04).

CONCLUSIONS: Air quality significantly affects the admissions to the ED for CV and Rp reasons and has an impact on mortality.

PMID:35543202 | DOI:10.17219/acem/149400

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The Impact of Chronic Illness on the Patient Experience: Results From a Cross-Sectional Comparative Study in a Comprehensive Tertiary Hospital in China

Inquiry. 2022 Jan-Dec;59:469580221090382. doi: 10.1177/00469580221090382.

ABSTRACT

OBJECTIVE: Improving the satisfaction and medical experience of patients is a basic goal of the comprehensive reform of public hospitals in China. This study aimed to investigate the patient experience and its influencing factors, and to compare medical experiences between patients with and without chronic disease, with a view to providing suggestions for improving the quality of public hospitals in China.

METHODS: A cross-sectional comparative study involving 102 patients discharged from Taizhou Hospital of Zhejiang Province, a tertiary public hospital in China, was conducted. The patients were invited to participate in a survey comprising the Picker Patient Experience Questionnaire (PPE-15), and an overall satisfaction evaluation (on a scale of 1-10). The patients were divided into two groups according to whether or not they had a chronic disease, and the medical experience and overall satisfaction of the groups were compared. Descriptive statistics (frequency, median, mean), chi-square analysis, and Mann-Whitney U tests were used to analyze the data.

RESULTS: No statistical significance was found in overall satisfaction between patients with and without chronic diseases, but there were differences in the patient experience score. Chronic illness had negative impacts on the experience of care coordination for patients and respect for patient preferences. Of the seven dimensions of the PPE-15, the scores for emotional support and respect for patient preferences were the lowest in both groups, and the item “want to be more involved in decisions made about care and treatment” scored the lowest among all items.

CONCLUSIONS: Hospital managers and staff members should pay more attention to the emotional support and preferences of patients. For patients with chronic diseases, the standardization of medical care and patient participation in the medical process should be strengthened. Hospitals should also subdivide patient groups, ascertain the demands and expectations of patients, and carry out targeted evaluation and intervention measures.

PMID:35543187 | DOI:10.1177/00469580221090382

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Regional Analysis of Liver Surface Nodularity in a Single Axial MR Image for Staging Liver Fibrosis

J Magn Reson Imaging. 2022 May 11. doi: 10.1002/jmri.28208. Online ahead of print.

ABSTRACT

BACKGROUND: The assessment of liver surface nodularity (LSN) for staging hepatic fibrosis is restricted in clinical practice because it requires customized software and time-consuming procedures. A simplified method to estimate LSN score may be useful in the clinic.

PURPOSE: To evaluate the regional analysis of LSN and processing time in a single axial liver MR image for staging liver fibrosis.

STUDY TYPE: Retrospective.

POPULATION: A total of 210 subjects, a multicenter study.

FIELD STRENGTH/SEQUENCE: A 3 T/noncontrast gradient echo T1WI.

ASSESSMENT: Subjects were divided into five fibrosis groups (F0 = 29; F1 = 20; F2 = 32; F3 = 50; F4 = 79) based on the METAVIR fibrosis scoring system. The mean LSN (on three slices) and regional LSN (on one slice) measurements, and the processing times, are compared. The regional LSN scores in five regions-of-interests (ROI1-5 ) were analyzed in a single axial MRI at the level of the hilum by two independent observers.

STATISTICAL TESTS: Regional variations in LSN scores were compared using ANOVA with Tukey test. Agreement between the mean and regional LSN measurements was evaluated using Pearson correlation coefficients (r) and Bland-Altman plots. The diagnostic performance of mean and regional LSN scores according to fibrosis stage was evaluated with the AUROC. A P value < 0.05 was considered statistically significant.

RESULTS: Total processing time for a regional LSN measurement (3.6 min) was 75.5% less than that for mean LSN measurement (14.7 min). Mean LSN scores and all five regional LSN scores showed significant differences between fibrosis groups. Among regional LSN scores, ROI5 showed the highest AUROC (0.871 at cut-off 1.12) for discriminating F0-2 vs. F3-4 and the best correlation with mean LSN score (r = 0.800, -0.07 limit of agreement).

CONCLUSION: Quantitative regional LSN measurement in a single axial MR image reduces processing time. Regional ROI5 LSN score might be useful for clinical decision-making and for distinguishing the difference between early fibrosis (F0-2 ) and advanced fibrosis (F3-4 ) in the liver.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

PMID:35543163 | DOI:10.1002/jmri.28208

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Reduced tumor growth in EP2 knockout mice is related to signaling pathways favoring an increased local anti‑tumor immunity in the tumor stroma

Oncol Rep. 2022 Jun;47(6):118. doi: 10.3892/or.2022.8329. Epub 2022 May 11.

ABSTRACT

Inflammatory signaling through prostaglandin E2 receptor subtype 2 (EP2) is associated with malignant tumor growth in both experimental models and cancer patients. Thus, the absence of EP2 receptors in host tissues appears to reduce tumor growth and systemic inflammation by inducing major alterations in gene expression levels across tumor tissue compartments. However, it is not yet well‑established how signaling pathways in tumor tissue relate to simultaneous signaling alterations in the surrounding tumor‑stroma, at conditions of reduced disease progression due to decreased host inflammation. In the present study, wild‑type tumor cells, producing high levels of prostaglandin E2 (MCG 101 cells, EP2+/+), were inoculated into EP2 knockout (EP2‑/‑) and EP2 wild‑type (EP2+/+) mice. Solid tumors were dissected into tumor‑ and tumor‑stroma tissue compartments for RNA expression microarray screening, followed by metabolic pathway analyses. Immunohistochemistry was used to confirm adequate dissections of tissue compartments, and to assess cell proliferation (Ki‑67), prostaglandin enzymes (cyclooxygenase 2) and immunity biomarkers (CD4 and CD8) at the protein level. Microarray analyses revealed statistically significant alterations in gene expression in the tumor‑stroma compartment, while significantly less pathway alterations occurred in the tumor tissue compartment. The host knockout of EP2 receptors led to a significant downregulation of cell cycle regulatory factors in the tumor‑stroma compartment, while interferon γ‑related pathways, chemokine signaling pathways and anti‑tumor chemokines [chemokine (C‑X‑C motif) ligand 9 and 10] were upregulated in the tumor compartment. Thus, such gene alterations were likely related to reduced tumor growth in EP2‑deficient hosts. On the whole, pathway analyses of both tumor‑ and tumor‑stroma compartments suggested that absence of host EP2 receptor signaling reduces ‘remodeling’ of tumor microenvironments and increase local immunity, probably by decreased productions of stimulating growth factors, perhaps similar to well‑recognized physiological observations in wound healing.

PMID:35543149 | DOI:10.3892/or.2022.8329