Tag: pubmed

STAR Protoc. 2024 Jan 2;5(1):102806. doi: 10.1016/j.xpro.2023.102806. Online ahead of print.

ABSTRACT

Whole-exome sequencing (WES) is a major approach to uncovering gene-disease associations and pinpointing effector genes. Here, we present a protocol for estimating genetic associations of rare and common variants in large-scale case-control WES studies using MAGICpipeline, an open-access analysis pipeline. We describe steps for assessing gene-based rare-variant association analyses by incorporating multiple variant pathogenic annotations and statistical techniques. We then detail procedures for identifying disease-related modules and hub genes using weighted correlation network analysis, a systems biology approach. For complete details on the use and execution of this protocol, please refer to Su et al. (2023).¹.

PMID:38175747 | DOI:10.1016/j.xpro.2023.102806

Aging (Albany NY). 2024 Jan 3;15. doi: 10.18632/aging.205413. Online ahead of print.

ABSTRACT

Previous studies have indicated a potential connection between plasma levels of Dickkopf-1 (DKK1) and platelet-derived growth factor subunit-B (PDGF-B) with the development of atherosclerosis. However, the causal relationship between DKK1, PDGF-B, and the risk of acute myocardial infarction (AMI) is yet to be established. To address this research gap, we conducted Mendelian randomization (MR) and mediation analyses to investigate the potential mediating role of PDGF-B in the association between DKK1 and AMI risk. Summary statistics for DKK1 (n = 3,301) and PDGF-B (n = 21,758) were obtained from the GWAS meta-analyses conducted by Sun et al. and Folkersen et al., respectively. Data on AMI cases (n = 3,927) and controls (n = 333,272) were retrieved from the UK Biobank study. Our findings revealed that genetic predisposition to DKK1 (odds ratio [OR]: 1.00208; 95% confidence interval [CI]: 1.00056-1.00361; P = 0.0072) and PDGF-B (OR: 1.00358; 95% CI: 1.00136-1.00581; P = 0.0015) was associated with an increased risk of AMI. Additionally, genetic predisposition to DKK1 (OR: 1.38389; 95% CI: 1.07066-1.78875; P = 0.0131) was linked to higher PDGF-B levels. Furthermore, our MR mediation analysis revealed that PDGF-B partially mediated the association between DKK1 and AMI risk, with 55.8% of the effect of genetically predicted DKK1 being mediated through genetically predicted PDGF-B. These findings suggest that genetic predisposition to DKK1 is positively correlated with the risk of AMI, and that PDGF-B partially mediates this association. Therefore, DKK1 and PDGF-B may serve as promising targets for the prevention and treatment of AMI.

PMID:38175715 | DOI:10.18632/aging.205413

J Am Podiatr Med Assoc. 2023 Nov-Dec;113(6):21-179. doi: 10.7547/21-179.

ABSTRACT

BACKGROUND: The aim of this study was to share the clinical results of open calcaneus fractures, which are extremely rare and have become the fearful nightmare of orthopedic surgeons.

METHODS: Between June of 2014 and June of 2020, of 196 patients with the diagnosis of calcaneus fracture, Gustilo-Anderson type IIIB, 17 patients (11 men and six women; mean age, 36.2 ± 4.6 years; range, 22-56 years) under prospective follow-up were retrospectively screened and included in the study. Patients were recorded in terms of classification of fracture, mechanism of injury, comorbidities, surgical progress, complications, and associated orthopedic and nonorthopedic injuries. Functional clinical results and quality of life of the patients were evaluated at the 6-month follow-up with the American Orthopedic Foot and Ankle Society score and the 36-Item Short Form Health Survey questionnaire.

RESULTS: The most common etiologic factor was work-related injuries, with 29.4%. Although triple arthrodesis surgery was performed in three cases because of pseudoarthrosis, amputation was performed in one case because of deep infection. The most common soft-tissue defect was located at the medial aspect of the foot, which was commonly reconstructed with the used of reverse flow island sural flap. The average total American Orthopedic Foot and Ankle Society hindfoot score was 51.6 (range, 48-74) and similarly, physical component, pain, and social parameters on the 36-Item Short Form Health Survey were statistically significant compared to Turkish population normal scores.

CONCLUSIONS: A long and laborious process is required for both the patient and the surgeon in the treatment of open calcaneal fractures. However, it is possible to obtain good results with soft-tissue reconstructions.

PMID:38175701 | DOI:10.7547/21-179

JMIR Form Res. 2024 Jan 4;8:e46515. doi: 10.2196/46515.

ABSTRACT

BACKGROUND: Body dysmorphic disorder (BDD) is defined as excessive concern with mild or nonexistent defects in personal physical appearance, which are not perceived by others. The worldwide prevalence of BDD ranges between 0.5% and 3.2%, with no differences across genders. The mean age of onset of BDD is 16.9 years. BDD is typically associated with young age, psychiatric disorders, and dermatological procedures. Patients with BDD typically display poorer mental health status than patients diagnosed with other mental disorders.

OBJECTIVE: The aim of this study was to estimate the prevalence of BDD in Spain and to identify the variables associated with BDD.

METHODS: We performed a cross-sectional descriptive study by collecting data through an anonymous web-based survey targeting the Spanish population aged 18 years or older. The measures in this study were (1) sociodemographic variables, (2) variables associated with dermatological and psychiatric disorders and cosmetic procedures, (3) scales measuring quality of life (12-item Short Form health survey, version 2) and (4) BDD (BDD Questionnaire). Statistical analysis was performed with SPSS software version 21. P values less than .05 were considered significant.

RESULTS: Of the 2091 participants who took the survey, 322 (15.2%) met the criteria of having BDD. The mean age of the participants with BDD was 23.5 (SD 9.6) years. In terms of BDD prevalence, women accounted for 19.9% (284/1421), men accounted for 5.2% (34/653), and students accounted for 25.2% (263/1043). Approximately 46.6% (150/322) of the participants with BDD reported a history of psychiatric comorbidities, including anxiety disorders, depressive disorders, and eating disorders. BDD was significantly associated with female gender, younger age (18-24 years), students, monthly income of less than €500 (€1=US $1.11), and the presence of dermatological and some psychiatric disorders such as depression, anxiety, and eating disorders (P<.05). The number of body parts of concern in participants with BDD was significantly higher than that in those without BDD (4.6 vs 2.2, respectively; P<.001). Regarding the body parts of concern, body fat was the most common concern for both groups with BDD and without BDD, followed by thighs, face, hips, and skin in the BDD group and thighs, teeth, and hair in the non-BDD group. Participants with BDD showed a significantly poorer self-perception of their mental health, irrespective of the presence of any mental disorder (P<.001).

CONCLUSIONS: Our findings showed that the prevalence of BDD in Spain was higher than expected. Further, BDD is frequently associated with other psychiatric disorders, particularly depressive disorder, anxiety disorder, and eating disorder. Participants with BDD had a poorer perception of quality of life associated with mental but not physical health problems. Finally, the perception of quality of mental health life in participants with BDD was independent of diagnosis of any mental disorder.

PMID:38175692 | DOI:10.2196/46515

Eur J Prev Cardiol. 2024 Jan 4:zwae005. doi: 10.1093/eurjpc/zwae005. Online ahead of print.

ABSTRACT

Coronary artery calcium score (CACS) and polygenic risk score have been used as novel markers to predict cardiovascular (CV) events of asymptomatic individuals compared to traditional scores. No previous studies have directly compared the additive capacity of these two markers relative to conventional scores.

AIM: Evaluate the change in CV risk prediction ability when CACS, genetic risk score (GRS) or both are added to SCORE2.

METHODS: A prospective, observational population-based study involving 1002 asymptomatic subjects (mean age 53.1±6.8years, 73.8%male), free of clinical coronary disease and diabetes, were selected from GENEMACOR-study controls. SCORE2, CACS and GRS were estimated to evaluate CV events’ predictive and discriminative ability through Harrell´s C-statistics. Net Reclassification Improvement (NRI) and Integrated Discrimination Index were used to reclassify the population. Multivariable Cox proportional hazard ratios (HR) analysis assessed the variables independently associated with CV events.

RESULTS: C-statistic demonstrated that the discriminative value for CV events occurrence was 0.608 for SCORE2, increasing to 0.749 (p=0.001) when CACS was added, and improved to 0.802 (p=0.0008) with GRS, showing a better discriminative capacity for CV events. Continuous NRI reclassified >70% of the population. Cox proportional analysis showed that highest categories of SCORE2, CACS and GRS remained in the equation with an HR of 2.9 (p=0.003), 5.0 (p<0.0001) and 3.2 (p=0.003), respectively, when compared with the lowest categories.

CONCLUSION: In our population, CACS added to SCORE2 had better ability than GRS in CV events risk prediction, discrimination and reclassification. However, adding the three scores can become clinically relevant, especially in intermediate-risk persons.

PMID:38175668 | DOI:10.1093/eurjpc/zwae005

JAMA Netw Open. 2024 Jan 2;7(1):e2350242. doi: 10.1001/jamanetworkopen.2023.50242.

ABSTRACT

IMPORTANCE: Short interpregnancy intervals (SIPIs) are associated with increased risk of adverse maternal and neonatal outcomes. Disparities exist across socioeconomic status, but there is little information on SIPIs among women experiencing homelessness.

OBJECTIVE: To investigate (1) differences in rates and characteristics of SIPIs between women experiencing homelessness and domiciled women, (2) whether the association of homelessness with SIPIs differs across races and ethnicities, and (3) whether the association between SIPIs of less than 6 months (very short interpregnancy interval [VSIPIs]) and maternal and neonatal outcomes differs between participant groups.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a Colorado statewide database linking the Colorado All Payer Claims Database, Homeless Management Information System, death records, and infant birth records. Participants included all women who gave birth between January 1, 2016, and December 31, 2021. Data were analyzed from September 1, 2022, to May 10, 2023.

EXPOSURES: Homelessness and race and ethnicity.

MAIN OUTCOMES AND MEASURES: The primary outcome consisted of SIPI, a binary variable indicating whether the interval between delivery and conception of the subsequent pregnancy was shorter than 18 months. The association of VSIPI with maternal and neonatal outcomes was also tested.

RESULTS: A total of 77 494 women (mean [SD] age, 30.7 [5.3] years) were included in the analyses, of whom 636 (0.8%) were women experiencing homelessness. The mean (SD) age was 29.5 (5.4) years for women experiencing homelessness and 30.7 (5.3) years for domiciled women. In terms of race and ethnicity, 39.3% were Hispanic, 7.3% were non-Hispanic Black, and 48.4% were non-Hispanic White. Associations between homelessness and higher odds of SIPI (adjusted odds ratio [AOR], 1.23 [95% CI, 1.04-1.46]) were found. Smaller associations between homelessness and SIPI were found among non-Hispanic Black (AOR, 0.59 [95% CI, 0.37-0.96]) and non-Hispanic White (AOR, 0.57 [95% CI, 0.39-0.84]) women compared with Hispanic women. A greater association of VSIPI with emergency department visits and low birth weight was found among women experiencing homelessness compared with domiciled women, although no significant differences were detected.

CONCLUSIONS AND RELEVANCE: In this cohort study of women who gave birth from 2016 to 2021, an association between homelessness and higher odds of SIPIs was found. These findings highlight the importance of conception management among women experiencing homelessness. Racial and ethnic disparities should be considered when designing interventions.

PMID:38175646 | DOI:10.1001/jamanetworkopen.2023.50242

JAMA Netw Open. 2024 Jan 2;7(1):e2350379. doi: 10.1001/jamanetworkopen.2023.50379.

ABSTRACT

IMPORTANCE: A first step toward understanding whether pediatric medical subspecialists are meeting the needs of the nation’s children is describing rates of use and trends over time.

OBJECTIVES: To quantify rates of outpatient pediatric medical subspecialty use.

DESIGN, SETTING, AND PARTICIPANTS: This repeated cross-sectional study of annual subspecialist use examined 3 complementary data sources: electronic health records from PEDSnet (8 large academic medical centers [January 1, 2010, to December 31, 2021]); administrative data from the Healthcare Integrated Research Database (HIRD) (14 commercial health plans [January 1, 2011, to December 31, 2021]); and administrative data from the Transformed Medicaid Statistical Information System (T-MSIS) (44 state Medicaid programs [January 1, 2016, to December 31, 2019]). Annual denominators included 493 628 to 858 551 patients younger than 21 years with a general pediatric visit in PEDSnet; 5 million beneficiaries younger than 21 years enrolled for at least 6 months in HIRD; and 35 million Medicaid or Children’s Health Insurance Program beneficiaries younger than 19 years enrolled for any amount of time in T-MSIS.

EXPOSURE: Calendar year and type of medical subspecialty.

MAIN OUTCOMES AND MEASURES: Annual number of children with at least 1 completed visit to any pediatric medical subspecialist in an outpatient setting per population. Use rates excluded visits in emergency department or inpatient settings.

RESULTS: Among the study population, the proportion of girls was 51.0% for PEDSnet, 51.1% for HIRD, and 49.3% for T-MSIS; the proportion of boys was 49.0% for PEDSnet, 48.9% for HIRD, and 50.7% for T-MSIS. The proportion of visits among children younger than 5 years was 37.4% for PEDSnet, 20.9% for HIRD, and 26.2% for T-MSIS; most patients were non-Hispanic Black (29.7% for PEDSnet and 26.1% for T-MSIS) or non-Hispanic White (44.9% for PEDSnet and 43.2% for T-MSIS). Annual rates for PEDSnet ranged from 18.0% to 21.3%, which were higher than rates for HIRD (range, 7.9%-10.4%) and T-MSIS (range, 7.6%-8.6%). Subspecialist use increased in the HIRD commercial health plans (annual relative increase of 2.4% [95% CI, 1.6%-3.1%]), but rates were essentially flat in the other data sources (PEDSnet, -0.2% [95% CI, -1.1% to 0.7%]; T-MSIS, -0.7% [95% CI, -6.5% to 5.5%]). The flat PEDSnet growth reflects a balance between annual use increases among those with commercial insurance (1.2% [95% CI, 0.3%-2.1%]) and decreases in use among those with Medicaid (-0.9% [95% CI, -1.6% to -0.2%]).

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that among children, 8.6% of Medicaid beneficiaries, 10.4% of those with commercial insurance, and 21.3% of those whose primary care is received in academic health systems use pediatric medical subspecialty care each year. There was a small increase in rates of subspecialty use among children with commercial but not Medicaid insurance. These data may help launch innovations in the primary-specialty care interface.

PMID:38175643 | DOI:10.1001/jamanetworkopen.2023.50379

JAMA. 2024 Jan 4. doi: 10.1001/jama.2023.27163. Online ahead of print.

NO ABSTRACT

PMID:38175628 | DOI:10.1001/jama.2023.27163

Clin Chem. 2024 Jan 4;70(1):297-306. doi: 10.1093/clinchem/hvad180.

ABSTRACT

BACKGROUND: Cancer of unknown primary (CUP) is defined as a primary metastatic malignancy, in which the primary tumor remains elusive in spite of a comprehensive diagnostic workup. The frequency and prognostic value of circulating tumor cells (CTCs), which are considered to be the source of metastasis, has not yet been systematically evaluated in CUP.

METHODS: A total of 110 patients with a confirmed diagnosis of CUP according to the European Society for Medical Oncology (ESMO) guidelines, who presented to our clinic between July 2021 and May 2023, provided blood samples for CTC quantification using CellSearch methodology. CTC counts were correlated with demographic, clinical, and molecular data generated by comprehensive genomic profiling of tumor tissue.

RESULTS: CTCs were detected in 26% of all patients at initial presentation to our department. The highest CTC frequency was observed among patients with unfavorable CUP (35.5%), while patients with single-site/oligometastatic CUP harbored the lowest CTC frequency (11.4%). No statistically significant association between CTC positivity and the number of affected organs (P = 0.478) or disease burden (P = 0.120) was found. High CTC levels (≥5 CTCs/7.5 mL; 12/95 analyzed patients) predicted for adverse overall survival compared to negative or low CTC counts (6-months overall survival rate 90% vs 32%, log-rank P < 0.001; HR 5.43; 95% CI 2.23-13.2). CTC dynamics were also prognostic for overall survival by landmark analysis (log-rank P < 0.001, HR 10.2, 95% CI 1.95-52.9).

CONCLUSIONS: CTC frequency is a strong, independent predictor of survival in patients with CUP. CTC quantification provides a useful prognostic tool in the management of these patients.

PMID:38175594 | DOI:10.1093/clinchem/hvad180

Ned Tijdschr Geneeskd. 2023 Nov 23;167:D7627.

ABSTRACT

AIM: Determining the added value of preoperative geriatric screening (POGS) in the care path ‘Infrarenal abdominal aortic aneurysm’.

DESIGN: Retrospective observational study in a university hospital.

METHOD: For patients (>60 years) with non-acute aortic pathology, data on preoperative screening (including frailty measures) and treatment was automatically generated from medical records for the period 2018-2021 (42 months). Data has been analysed with descriptive and test statistics. Completeness of the data was checked manually by reading the medical files for the period 2020-2021 (24 months).

RESULTS: A total of 343 cases were included; POGS was performed in 90 patients (26%). In 84.2% of the cases the vascular surgeon adhered to the geriatrician’s advice. In the other cases, the treatment is less (10.5%) or more (5.3%) intrusive than the POGS advice; the patient’s preference seems to be particular decisive here. The geriatric advice is most consistent with the measures from the Clinical Frailty Scale. From the manual data collection, we learned that about 20% of the POGS were missing.

CONCLUSION: Introducing geriatric screening in the care pathway is likely to lead to a more considered choice by healthcare professionals as well as patients. The added value seems embraced by geriatricians and vascular surgeons as the adherence to the geriatric advice is strong. A cardiovascular nurse can use the Clinical Frailty Scale to select the patients that really need a geriatric advice. The advice is to include POGS in the care path ‘Infrarenal abdominal aortic aneurysm’ and possibly also in other care paths.

PMID:38175563