Tag: pubmed

J Heart Lung Transplant. 2023 Jun 26:S1053-2498(23)01920-4. doi: 10.1016/j.healun.2023.06.013. Online ahead of print.

ABSTRACT

BACKGROUND: Reasons for women’s increased probability to experience adverse events (AEs) after left ventricular assist device (LVAD) implantation compared with men’s remain uncertain. We explored the role of psychosocial risk in the experience of AEs in women and men.

METHODS: INTERMACS patients receiving a primary continuous-flow LVAD between 7/2006 and 12/2017, median follow-up 13.6 months, were included (n=20123, 21.3% women). Time-to-event was calculated with cumulative incidence functions for 10 types of AEs separately (e.g., infection, device malfunction), each time accounting for the competing outcomes death, heart transplant and device explant due to recovery. Event-specific Cox proportional hazard models were run with a binary psychosocial risk variable (including: substance abuse, psychiatric diagnoses, limited social support, limited cognition, repeated noncompliance), controlled for covariates.

RESULTS: Psychosocial risk was more prevalent in men than in women (21.4% vs. 17.5%, p <.001). Seven out of ten AEs were more likely in women than in men (e.g., infection 44.5% vs. 39.2%, p <.001). The association of psychosocial risk with each AE was either stronger in women than in men (e.g., device malfunction HR_adj 1.29, 95% CI [1.06-1.56] vs. HR_adj 1.10, 95% CI [0.97-1.25]; rehospitalization HR_adj 1.15, 95% CI [1.02-1.29] vs. HR_adj 1.03, 95% CI [0.97-1.10]) or similar between sexes.

CONCLUSIONS: Independent of clinical parameters, the presence of psychosocial risk is associated with increases in AEs. This suggests that early modification of psychosocial risk factors may have the potential to lower the risk for AEs in this patient population.

PMID:37380090 | DOI:10.1016/j.healun.2023.06.013

Am J Prev Med. 2023 Jun 26:S0749-3797(23)00277-5. doi: 10.1016/j.amepre.2023.06.014. Online ahead of print.

ABSTRACT

INTRODUCTION: This study examines the association between prior incarceration and health insurance status and whether living in a state adopting the Affordable Care Act (ACA) Medicaid expansion moderates this relationship.

METHODS: Data are from the National Longitudinal Study of Adolescent to Adult Health (Wave I [1993-1994]; Wave IV [2008] and Wave V [2016-2018]; n = 8,965). Multiple logistic regression with multiplicative interaction terms were performed to assess the relationship between previous incarceration and ACA Medicaid expansion on (a) being insured and (b) being on public health insurance. Analyses were performed in 2023.

RESULTS: Findings demonstrate a positive and statistically significant interaction in the association between previous incarceration and living in a state with ACA Medicaid expansion on having public health insurance (OR = 2.402; 95% CI = 1.257, 4.588).

CONCLUSIONS: The ACA Medicaid expansion was associated with a greater likelihood of public health insurance coverage for formerly incarcerated persons in the United States. These findings suggest that Medicaid expansion could be critical in improving health insurance coverage among formerly incarcerated individuals who are a population that is more likely to be uninsured.

PMID:37380089 | DOI:10.1016/j.amepre.2023.06.014

J Biol Chem. 2023 Jun 26:104973. doi: 10.1016/j.jbc.2023.104973. Online ahead of print.

ABSTRACT

Prostate cancer (PCa) is initially regulated by the androgen receptor (AR), a ligand-activated, transcription factor (hormone-sensitive PCa (HSPC)), but eventually become androgen-refractory or castration-resistant (CRPC) because of mechanisms that bypass the AR, including ErbB3, a member of the epidermal growth factor receptor (EGFR) family. ErbB3 is synthesized in the cytoplasm and transported to the plasma membrane for ligand binding and dimerization, where it regulates downstream signaling, but nuclear forms are reported. Here, we demonstrate in prostatectomy samples that ErbB3 nuclear localization is observed in malignant, but not benign prostate. and that cytoplasmic (but not nuclear) ErbB3 correlated positively with AR expression but negatively with AR transcriptional activity. In support of the latter, androgen depletion upregulated cytoplasmic, but not nuclear ErbB3, while in vivo studies showed that castration suppressed ErbB3 nuclear localization in HSPC, but not CRPC tumors. In vitro treatment with the ErbB3 ligand heregulin-1β (HRG) induced ErbB3 nuclear localization, which was androgen-regulated in HSPC but not in CRPC. In turn, HRG upregulated AR transcriptional activity in CRPC but not in HSPC cells. Positive correlation between ErbB3 and AR expression was demonstrated in AR-null PC-3 cells where stable transfection of AR restored HRG-induced ErbB3 nuclear transport, while AR knockdown in LNCaP reduced cytoplasmic ErbB3. Mutations of ErbB3’s kinase domain did not affect its localization but was responsible for cell viability in CRPC cells. Taken together, we conclude that AR expression regulated ErbB3 expression, its transcriptional activity suppressed ErbB3 nuclear translocation, and HRG binding to ErbB3 promoted it.

PMID:37380074 | DOI:10.1016/j.jbc.2023.104973

J Cardiol. 2023 Jun 26:S0914-5087(23)00157-0. doi: 10.1016/j.jjcc.2023.06.012. Online ahead of print.

ABSTRACT

BACKGROUND: Iron deficiency in patients with heart failure (HF) is underdiagnosed and undertreated. The role of intravenous (IV) iron is well-established to improve quality of life measures. Emerging evidence also supports its role in preventing cardiovascular events in patients with HF.

METHODOLOGY: We conducted a literature search of multiple electronic databases. Randomized controlled trials that compared IV iron to usual care among patients with HF and reported cardiovascular (CV) outcomes were included. Primary outcome was the composite of first heart failure hospitalization (HFH) or CV death. Secondary outcomes included HFH (first or recurrent), CV death, all-cause mortality, hospitalization for any cause, gastrointestinal (GI) side effects, or any infection. We performed trial sequential and cumulative meta-analyses to evaluate the effect of IV iron on the primary endpoint, and on HFH.

RESULTS: Nine trials enrolling 3337 patients were included. Adding IV iron to usual care significantly reduced the risk of first HFH or CV death [risk ratio (RR) 0.84; 95 % confidence interval (CI) 0.75-0.93; I² = 0 %; number needed to treat (NNT) 18], which was primarily driven by a reduction in the risk of HFH of 25 %. IV iron also reduced the risk of the composite of hospitalization for any cause or death (RR 0.92; 95 % CI 0.85-0.99; I² = 0 %; NNT 19). There was no significant difference in the risk of CV death, all-cause mortality, adverse GI events, or any infection among patients receiving IV iron compared to usual care. The observed benefits of IV iron were directionally consistent across trials and crossed both the statistical and trial sequential boundaries of benefit.

CONCLUSION: In patients with HF and iron deficiency, the addition of IV iron to usual care reduces the risk of HFH without affecting the risk of CV or all-cause mortality.

PMID:37380069 | DOI:10.1016/j.jjcc.2023.06.012

Am J Perinatol. 2023 Jun 28. doi: 10.1055/a-2115-0147. Online ahead of print.

ABSTRACT

BACKGROUND: To determine whether objectively measured Sleep-Disordered Breathing (SDB) during pregnancy is associated with an increased risk of adverse neonatal outcomes in a cohort of nulliparous individuals.

METHODS: Secondary analysis of the nuMom2b- sleep disordered breathing substudy was performed. Individuals underwent in-home sleep studies for SDB assessment in early- (6-15 weeks’ gestation) and mid-pregnancy (22-31 weeks’ gestation). SDB was defined as an apnea-hypopnea index ≥5 events/hour at either time point. Primary outcome was a composite outcome of respiratory distress syndrome, transient tachypnea of the newborn, or receipt of respiratory support, treated hyperbilirubinemia or hypoglycemia, large-for-gestational age (LGA), seizures treated with medications or confirmed by electroencephalography, confirmed sepsis, or neonatal death. Individuals were categorized into 1) early pregnancy SDB (6-15 weeks’ gestation), 2) new onset mid-pregnancy SDB (22-31 weeks’ gestation), and 3) no SDB. Log-binomial regression was used to calculate adjusted risk ratios (RR) and 95% confidence intervals (CI) representing the association. Adjustments were made for maternal age, chronic hypertension, pregestational diabetes, progesterone use and Body Mass Index (BMI), new onset mid-pregnancy SDB to establish if a relationship was still present.

RESULTS: Among 2,106 participants, 3% percent (n=75) had early pregnancy SDB and 5.7% (n=119) developed new onset mid-pregnancy SDB. The incidence of the primary outcome was higher in offspring of individuals with early- (29.3%) and new onset mid- pregnancy SDB (30.3%) compared to individuals with no SDB (17.8%). After adjustment for maternal age, chronic hypertension, pregestational diabetes, progesterone use and BMI, new onset mid-pregnancy SDB conferred increased risk (RR=1.42, 95% CI: 1.05, 1.92), where there was no longer statistically significant association between early pregnancy SDB and the primary outcome.

CONCLUSION: New Onset, Mid- pregnancy SDB is independently associated with neonatal morbidity.

PMID:37380034 | DOI:10.1055/a-2115-0147

J Shoulder Elbow Surg. 2023 Jun 26:S1058-2746(23)00485-8. doi: 10.1016/j.jse.2023.05.025. Online ahead of print.

ABSTRACT

BACKGROUND: Phenotypic differences and functional limitations in children with congenital radial and ulnar longitudinal deficiencies (RLD/ULD) are well understood for the forearm and hand. However, anatomical features of shoulder elements in these pathologies have only been scarcely reported. Moreover, shoulder function has not been assessed in this patient population. Therefore, we aimed to define radiologic features and shoulder function of these patients at a large tertiary referral center.

METHODS: We prospectively enrolled all patients with RLD and ULD (minimum age: 7 years) for this study. Eighteen patients (12 RLD, 6 ULD) with a mean age of 17.9 years (range, 8.5-32.5) were evaluated using clinical examination (shoulder motion and stability), patient-reported outcome measures (Visual Analogue Scale [VAS], Pediatric/Adolescent Shoulder Survey [PASS], Pediatric Outcomes Data Collection Instrument [PODCI]), and radiologic grading of shoulder dysplasia (including length and width discrepancy of the humerus, glenoid dysplasia in the anteroposterior and axial view [Waters classification], and scapular and acromioclavicular dysplasia assessment). Descriptive statistics and Spearman correlation analyses were performed.

RESULTS: Despite five (28%) cases having anterioposterior shoulder instability and five (28%) cases with decreased motion, outcome scores indicated an overall excellent function of the shoulder girdle, with mean VAS of 0.3 (range, 0-5), mean PASS of 97 (range, 75-100), and mean PODCI Global Functioning Scale of 93 (range, 76-100). The humerus was, on average, 15 mm shorter (range, 0-75), and metaphyseal and diaphyseal diameters both reached 94% of the contralateral side. Glenoid dysplasia was detected in nine (50%) cases, with increased retroversion evident in 10 (56%) cases. However, scapular (n=2) and acromioclavicular (n=1) dysplasia were rare. Based on radiographic findings, a radiologic classification system for dysplasia types IA, IB, and II was developed.

CONCLUSIONS: Adolescent and adult patients with longitudinal deficiencies exhibit various mild-to-severe radiologic abnormalities around the shoulder girdle. Nevertheless, these findings did not seem to negatively affect shoulder function as the overall outcome scores were excellent.

PMID:37379966 | DOI:10.1016/j.jse.2023.05.025

Virology. 2023 Jun 15;585:186-195. doi: 10.1016/j.virol.2023.06.006. Online ahead of print.

ABSTRACT

Infection with Senecavirus A (SVA) causes differential phenotypes in cells. In this study, cells were inoculated with SVA for culture. At 12 and 72 h post infection, cells were independently harvested for high-throughput RNA sequencing, and further methylated RNA immunoprecipitation sequencing. The resultant data were comprehensively analyzed for mapping N⁶-methyladenosine (m⁶A)-modified profiles of SVA-infected cells. More importantly, m⁶A-modified regions were identified in the SVA genome. A dataset of m⁶A-modified mRNAs was generated for screening out differentially m⁶A-modified mRNAs, further subjected to a series of in-depth analyses. This study not only showed statistical differentiation of m⁶A-modified sites between two SVA-infected groups, but also demonstrated that SVA genome, as a positive-sense, single-stranded mRNA, itself could be modified through the m⁶A pattern. Out of the six samples of SVA mRNAs, only three were identified to be m⁶A-modified, implying that the epigenetic effect might not be a crucial driving force for SVA evolution.

PMID:37379620 | DOI:10.1016/j.virol.2023.06.006

Eur J Prev Cardiol. 2023 Jun 28:zwad214. doi: 10.1093/eurjpc/zwad214. Online ahead of print.

ABSTRACT

AIMS: To assess the sex- and age- specific trends in acute myocardial infarction (AMI) mortality in the modern European Union (EU-27) member states between years 2012 and 2020.

METHODS AND RESULTS: Data on cause-specific deaths and population numbers by sex for each country of the EU-27 were retrieved through publicly available European Statistical Office (EUROSTAT) dataset for the years 2012 to 2020. AMI-related deaths were ascertained when codes for AMI (ICD-10 codes I21.0-I22.0) were listed as the underlying cause of death in the medical death certificate. Deaths occurring before the age of 65 years were defined as premature deaths. To calculate annual trends, we assessed the average (AAPC) annual percent change with relative 95% confidence intervals (CIs) using Joinpoint regression. During the study period, 1,793,314 deaths (1,048,044 males and 745,270 females) occurred in the EU-27 due to of AMI. The proportion of AMI-related deaths per 1,000 total deaths decline from 5.0% to 3.5% both in the entire population (p for trend <0.001) and in males or females, separately. Joinpoint regression analysis revealed a continuous linear decrease in age-adjusted AMI-related mortality from 2012 to 2020 among EU-27 members [AAPC: -4.6% (95% CI: -5.1 to -4.0), p < 0.001]. The age-adjusted mortality rate showed a plateau in some Eastern European countries and was more pronounced in EU-27 females and in subjects aged ≥ 65 years old.

CONCLUSIONS: Over the last decade, the age-adjusted AMI-related mortality has been continuously declining in most of the in EU-27 Member States. However, some disparities still exist between western and eastern European countries.

PMID:37379577 | DOI:10.1093/eurjpc/zwad214

Biochemistry. 2023 Jun 28. doi: 10.1021/acs.biochem.3c00279. Online ahead of print.

ABSTRACT

The disordered and basic C-terminal 14 residues of human troponin T (TnT) are essential for full inhibition of actomyosin ATPase activity at low Ca²⁺ levels and for limiting activation at saturating Ca²⁺. In previous studies, stepwise truncation of the C-terminal region of TnT increased activity in proportion to the number of positive charges eliminated. To define key basic residues more closely, we generated phosphomimetic-like mutants of TnT. Phosphomimetic mutants were chosen because of reports that phosphorylation of TnT, including sites within the C terminal region, depressed activity, contrary to our expectations. Four constructs were made where one or more Ser and Thr residues were replaced with Asp residues. The S275D and T277D mutants, near the IT helix and adjacent to basic residues, produced the greatest activation of ATPase rates in solution; the effects of the S275D mutant were recapitulated in muscle fiber preparations with enhanced myofilament Ca²⁺ sensitivity. Actin filaments containing S275D TnT were also shown to be incapable of populating the inactive state at low Ca²⁺ levels. Actin filaments containing both S275D/T284D were not statistically different from those containing only S275D in both solution and cardiac muscle preparation studies. Finally, actin filaments containing T284D TnT, closer to the C-terminus and not adjacent to a basic residue, had the smallest effect on activity. Thus, the effects of negative charge placement in the C-terminal region of TnT were greatest near the IT helix and adjacent to a basic residue.

PMID:37379571 | DOI:10.1021/acs.biochem.3c00279

Medicina (B Aires). 2023;83(3):420-427.

ABSTRACT

INTRODUCTION: The effectiveness of physical rehabilitation therapies on patients who required prolonged mechanical ventilation and were discharged from the Intensive Care Unit (ICU) with post-COVID-19 neuromuscular weakness is known in the acute period. The objective of this study was to characterize the functional recovery in people hospitalized with post-ICU neuromuscular weakness due to COVID-19 admitted to rehab.

METHODS: Retrospective study which included 42 patients with post-COVID-19 neuromuscular weakness, who were admitted to two tertiary care rehabilitation centers, from April 2020 to April 2022.

RESULTS: We found statistically significant differences between the functional evaluations of admission and discharge. The Functional Independence Measure improved from 49 [41-57] a 107 [94-119] (p < 0.001). The Berg scale from 4 [1-6] a 47 [36-54] (p < 0.001), the 6-minute test from 0 [0-0] a 254 [167-400] (p < 0.001), and the 10-meter test from 0 [0-0] a 0.83 [0.4-1.2] (p < 0.001). There were no statistically significant differences between the admission and discharge total score of the functional assessments with age and respiratory complexity.

DISCUSSION: Treatment for functional recovery in a tertiary and long-term center is beneficial for people with severe post-ICU neuromuscular weakness due to COVID-19, even though 43% did not reach the previous level of mobility. Age and respiratory complexity are variables that did not impact the final recovery.

PMID:37379539