Tag: pubmed

Circ Cardiovasc Qual Outcomes. 2025 Apr 28:e011719. doi: 10.1161/CIRCOUTCOMES.124.011719. Online ahead of print.

ABSTRACT

BACKGROUND: The ability of the American Heart Association Predicting Risk of Cardiovascular Disease Events (PREVENT) calculator to accurately assign 10-year atherosclerotic cardiovascular disease (ASCVD) risk in older individuals, including those aged ≥80 years, is unknown. This study compares PREVENT with the 2013 Pooled Cohort Equation (PCE) calculator for predicting 10-year ASCVD risk in a large cohort of older adults.

METHODS: This was a prospective cohort study of adults without CVD from Australia and the United States aged ≥70 years (≥65 years, if US minorities). They were enrolled from 2010 to 2014 in the ASPREE trial (Aspirin in Reducing Events in the Elderly), a 5-year randomized trial of low-dose aspirin in community-dwelling older adults with posttrial observational follow-up extending to 2022. ASCVD events were adjudicated by expert panels. The discriminative ability of the 2 risk calculators was assessed by Harell C statistic following Cox regression in the 65- to 79-year age group and >80-year age group, separately. For calibration, predicted event numbers were calculated using PREVENT and PCE, scaled for the actual length of follow-up, and compared with the number of observed events in-trial and during extended follow-up.

RESULTS: Among the 15 510 participants aged 65 to 79 years (median age, 73.2 years; 56.1% women), 1084 ASCVD events occurred (median follow-up, 8.3 years); PCE predicted 3102 events while PREVENT predicted 1290 events. For the 2787 participants ≥80 years (median age, 82.6 years; 59.2% women), 355 ASCVD events occurred (median follow-up, 7.4 years); PCE predicted 1067 events while PREVENT predicted 350 events. PREVENT showed superior discriminative performance compared with PCE (PREVENT versus PCE, C statistic, 0.793 versus 0.740; P<0.001 in participants aged 65 -79 years; 0.854 versus 0.799; P<0.001 in those aged ≥80 years).

CONCLUSIONS: The PREVENT risk calculator is superior to the PCE calculator in predicting ASCVD events in older adults from the United States and Australia, including those aged ≥80 years.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583. URL: https://www.isrctn.com; Unique identifier: ISRCTN83772183.

PMID:40289804 | DOI:10.1161/CIRCOUTCOMES.124.011719

Zhonghua Yi Xue Za Zhi. 2025 Apr 29;105(17):1362-1368. doi: 10.3760/cma.j.cn112137-20240829-01991.

ABSTRACT

Objective: To explore the correlation between fat and iron accumulation in the liver and pancreas of obese patients with glycemic metabolic indicators, and to analyze the risk factors for glycemic abnormalities in obese patients. Methods: A prospective study enrolled 160 obese patients who visited Xiangya Third Hospital of Central South University from October 2022 to October 2023. The age [M (Q₁, Q₃)] was 40.8 (29.5, 43.9) years, with 74 males and 86 females. According to the results of the oral glucose tolerance test (OGTT), they were divided into the normal glucose metabolism (NGT) group(n=68), the impaired glucose tolerance (IGR) group(n=37), and the type 2 diabetes mellitus (T2DM) group(n=55). The proton density fat fraction (PDFF) measured by the MRI-based Dixon technique was used to quantitatively assess the fat content in the liver and pancreas, and the R2^* value was used to quantify the iron content in the liver and pancreas. Correlation analysis was used to analyze the correlation between fat and iron deposition in the liver and pancreas of obese patients and glucose metabolism indicators. The multivariate logistic regression model was used to analyze the influencing factors of abnormal glucose metabolism in obese patients. Results: The differences in liver PDFF, liver R2^*, pancreatic PDFF, and pancreatic R2^* among the three groups were all statistically significant (all P<0.05). The pancreatic PDFF in the T2DM group [12.8% (6.9%, 18.5%)] was higher than that in both the NGT group [7.6% (4.7%, 10.3%)] and the IGR group [7.0% (4.1%, 12.0%)] (all P<0.05). The pancreatic R2^* in the T2DM group [33.7 (28.3, 39.0)/s] was higher than that in the NGT group [28.6 (26.3, 33.3)/s] and the IGR group [28.5 (25.9, 32.9)/s] (all P<0.05). Significant differences were also observed among the three groups in terms of the homeostatic model assessment of insulin resistance (HOMA-IR), the homeostatic model assessment of β-cell function (HOMA-β), the insulin sensitivity index (ISI), and blood glucose levels at 0, 0.5, and 2.0 h during the oral glucose tolerance test (OGTT) (all P<0.05). The T2DM group had the lowest HOMA-β, while the NGT group had the highest (all P<0.05). Liver PDFF was positively correlated with HOMA-IR and blood glucose levels at 0, 0.5, and 2.0 h during OGTT (all r>0.25) and negatively correlated with ISI (r=-0.54) (all P<0.05). Pancreatic PDFF was negatively correlated with HOMA-β (r=-0.27) and positively correlated with blood glucose levels at 0, 0.5, and 2.0 h during OGTT (all r>0.24) (all P<0.05). Liver R2^* was positively correlated with HOMA-IR and blood glucose levels at 0, 0.5, and 2.0 h during OGTT (all r>0.24) and negatively correlated with ISI (r=-0.29) (all P<0.05). Pancreatic R2^* was negatively correlated with HOMA-β (r=-0.26) and positively correlated with blood glucose levels at 0, 0.5, and 2.0 h during OGTT (all r>0.21) (all P<0.05). Multivariate logistic regression analysis revealed that liver PDFF≥9.4% (OR=0.044, 95%CI: 1.03-5.76) was a risk factor for abnormal glucose metabolism in obese patients. Conclusions: Fat and iron accumulation in the liver and pancreas of obese patients is closely related to the occurrence of abnormal glucose metabolism. Fat deposition in the liver is a risk factor for abnormal glucose metabolism in obese patients.

PMID:40289778 | DOI:10.3760/cma.j.cn112137-20240829-01991

Zhonghua Yi Xue Za Zhi. 2025 Apr 29;105(17):1355-1361. doi: 10.3760/cma.j.cn112137-20241217-02867.

ABSTRACT

Objective: To compare the differences in perioperative blood loss and the coagulation-fibrinolysis system between patients undergoing robot-assisted or traditional total knee arthroplasty (TKA). Methods: A retrospective cohort study was conducted to analyze the clinical data of 232 patients who underwent TKA at the Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, from March 2021 to September 2023. The cohort included 25 men and 207 women with a mean age of (69.1±7.5) years. The patients were further divided into two groups based on whether robot-assisted surgery was performed: the conventional group (168 patients, including 15 men and 153 women) and the robot-assisted group (64 patients, including 10 men and 54 women). Data on perioperative laboratory tests and postoperative complications were collected. The differences in perioperative blood loss, coagulation index (CI), fibrinolysis index, fibrinogen degradation products (FDP), D-dimer (D-D), and postoperative complications such as ecchymosis and venous thromboembolism (VTE) were compared between the two groups. Results: There was no statistically significant differences in the baseline characteristics between the two groups (all P>0.05). The incidence of bleeding-related complications, specifically ecchymosis, was significantly lower in the robot-assisted group compared to the conventional group [20.3% (13/64) vs 33.9% (57/168), P=0.043]. In terms of blood loss, the robot-assisted group exhibited significantly lower total blood loss and occult blood loss on the first postoperative day compared to the conventional group [total blood loss: (263±167) ml vs (382±173) ml, P<0.001; occult blood loss: (222±163) ml vs (342±173) ml, P<0.001]. Similarly, on the third postoperative day, the robot-assisted group had lower total blood loss and occult blood loss [total blood loss: (504±240) ml vs (680±222) ml, P<0.001; occult blood loss: (468±238) ml vs (640±222) ml, P<0.001]. Regarding coagulation function, the robot-assisted group had a lower CI on thromboelastography postoperatively (0.33±1.34 vs 0.93±1.59, P=0.008) and fewer patients with a hypercoagulable state (CI>3) [0 vs 7.1%(12/168), P=0.028]. In terms of fibrinolysis function, the robot-assisted group had lower levels of FDP and D-D on the first postoperative day [FDP: (6.24±4.49) mg/L vs (9.24±6.47) mg/L, P<0.001; D-D: (3.23±2.96) mg/L vs (4.23±2.97) mg/L, P=0.023]. Conclusion: Compared with manual TKA, robot-assisted TKA not only effectively reduces perioperative blood loss but also offers advantages in controlling postoperative hypercoagulability and hyperfibrinolysis.

PMID:40289777 | DOI:10.3760/cma.j.cn112137-20241217-02867

Med Sci Sports Exerc. 2025 Apr 28. doi: 10.1249/MSS.0000000000003744. Online ahead of print.

ABSTRACT

Purpose: Heart rate (HR) variability thresholds (HRVT) based on detrended fluctuation analysis alpha 1 (DFA a1) generally show reasonable alignment of thresholds estimations based on gas exchange responses under normoxic conditions. This study examined whether acute hypoxia would affect the agreement between HRVTs and the gas exchange equivalents during incremental cycling. Methods: Twelve participants (5 females) completed an incremental ramp test in normobaric hypoxia (FIO2 ≈ 13.5%) and normoxia. Gas exchange and ventilatory responses alongside a high sampling rate electrocardiogram for DFA a1 computation were used to determine thresholds. Comparisons were made between the oxygen consumption (V̇O2) and HR at the gas exchange threshold (GET) and respiratory compensation point (RCP) with the responses at the first and second HRVTs (HRVT1 and HRVT2 respectively). Results: Mean V̇O2 and HR values were not statistically different for GET:HRVT1 (normoxia:1.74±0.41 vs 1.74±0.48 L·min-1,133±18 vs 133±16 bpm; hypoxia:1.47±0.21 vs 1.45±0.37 L·min-1, 135±14 vs 133±15 bpm) and RCP:HRVT2 (normoxia:2.38±0.55 vs 2.37±0.48 L·min-1, 158±13 vs 158±14 bpm, hypoxia:2.07±0.32 vs 1.90±0.43 L·min-1 and 156±13 vs 152±15 bpm) in any condition. All normoxic comparisons passed equivalence testing but only GET:HRVT1 responses passed during hypoxia. Pearsons r correlation coefficients were 0.86 to 0.96 in normoxia and 0.58 to 0.79 in hypoxia. Bland Altman analysis indicated higher degrees of bias and limit of agreements (LOA) during hypoxic testing. Conclusions: Although the V̇O2 and HR at HRVTs retained alignment with GET/RCP in both normoxia and hypoxia, the degrees of correlation, and equivalence were weaker and the bias and LOA were larger in hypoxia. Therefore, whilst using HRVT alone for training boundary guidance in hypoxia is a potential option, further investigation including incorporating complimentary surrogate markers is recommended.

PMID:40289765 | DOI:10.1249/MSS.0000000000003744

Kaohsiung J Med Sci. 2025 Apr 28:e70029. doi: 10.1002/kjm2.70029. Online ahead of print.

ABSTRACT

This study was aimed to elucidate the cytotoxic effects of γδT cells on triple-negative breast cancer (TNBC) cells and assess their antitumor efficacy in a mouse xenograft model. Furthermore, the underlying mechanisms of γδT cell action on TNBC were explored. The study utilized three TNBC cell lines (MDA-MB-231, MDA-MB-468, and BT-549) as target cells, with γδT cells serving as effector cells. Cytotoxicity was assessed in different effector-to-target ratios (E:T) at 5:1, 10:1, and 20:1 subsequent to coculture. To evaluate the antitumor effects of γδT cells in vivo, a xenograft mice model was established by inoculating MDA-MB-231 cells into the mammary fat pad of B-NDG mice. The mice received tail vein injections of γδT cells at different doses. The effects on tumor growth, mouse body weight, and γδT cell accumulation in the spleen were then determined. γδΤ cells at E:T of 10:1 exhibited significant cytotoxicity against all three TNBC cell lines, indicating a statistically significant difference compared to the control group (p < 0.0001). The cytotoxic effect at this ratio was superior to that at 20:1 and 5:1 effector-to-target ratios, as evidenced by statistical significance (p < 0.05). Following 21 days of adoptive transfer via tail vein injection, γδΤ cells at both low and high doses significantly reduced tumor volume and mass compared to the PBS control group (p < 0.001). This reduction was accompanied by an increased accumulation of γδΤ cells in the spleen. In conclusion, γδΤ cells exert significant cytotoxic effects on TNBC cells and effectively inhibit the growth of breast cancer xenografts in mice while also promoting the accumulation of γδΤ cells in the mouse spleen.

PMID:40289760 | DOI:10.1002/kjm2.70029

Arch Pathol Lab Med. 2025 Apr 28. doi: 10.5858/arpa.2024-0448-RA. Online ahead of print.

ABSTRACT

CONTEXT.—: Cervical squamous neoplasia runs the gamut from low-risk intraepithelial processes to aggressive invasive malignancies. A variety of biomarkers can be enlisted to help diagnose, prognosticate, and inform treatment of these lesions. There are ongoing controversies about diagnostic and prognostic biomarker use in squamous intraepithelial lesions, and many pathologists are new to predictive biomarker interpretation in invasive cervical lesions.

OBJECTIVE.—: To provide practical guidance on the appropriate use of diagnostic, prognostic, and predictive biomarkers in cervical squamous intraepithelial lesions and invasive carcinomas.

DATA SOURCES.—: Peer-reviewed literature and the author’s personal experience.

CONCLUSIONS.—: Diagnostic biomarkers such as p16 and human papillomavirus E6/E7 messenger RNA in situ hybridization can have value in the diagnosis of squamous intraepithelial neoplasia, but there are important caveats to their use and interpretation. No prognostic biomarkers have yet demonstrated statistically durable significance for risk stratification of low-grade squamous intraepithelial lesions. Programmed death ligand-1 immunohistochemistry and tumor mutational burden testing are US Food & Drug Administration-approved predictive biomarkers that can be enlisted for the identification of invasive cervical squamous carcinomas that may respond to checkpoint inhibitor-based immunotherapy, whereas human epidermal growth factor receptor 2 (HER2) immunohistochemistry can identify optimal candidates for conjugated anti-HER2 therapies.

PMID:40289713 | DOI:10.5858/arpa.2024-0448-RA

Pharm Stat. 2025 May-Jun;24(3):e70015. doi: 10.1002/pst.70015.

ABSTRACT

The term “minimal clinically important difference” (MCID), though defined as the smallest change in an outcome that is meaningful to the patient, is often used to interpret differences between treatment groups. It is in this context that the limitations of MCID are discussed, which include: the omission of the role of time in its definition for progressive diseases; the unsuitability of adopting MCID derived from open-label studies for randomized, placebo-controlled, blinded studies; the unreliability of MCID in rare disease trials; challenges in interpretation when placebo patients also achieve MCID; the failure to account for how differences in patient populations affect MCID (e.g., inclusion or exclusion of patients on prior treatment); not recognizing the connection between the true treatment effect, MCID and power; lack of consideration of differences in analysis methods (e.g., the extent of missing data and how it is handled); and the limitations of an MCID-based responder analysis. Therefore, the recommendation made is to prospectively define a customized MCID that addresses each deficit. If the deficits cannot be adequately resolved, then the recommendation is that trial results should be interpreted without reference to MCID.

PMID:40289700 | DOI:10.1002/pst.70015

Influenza Other Respir Viruses. 2025 May;19(5):e70097. doi: 10.1111/irv.70097.

ABSTRACT

BACKGROUND: RSV incidence in adults is frequently underestimated due to non-specific symptomatology, limited standard-of-care testing, and lower test sensitivity compared to infants. We conducted a retrospective observational study to estimate RSV-attributable incidence of specific types of cardiorespiratory hospitalizations among adults in Germany between 2015 and 2019.

METHODS: Information on hospitalizations and the number of people at risk of hospitalization (denominator) was gathered from a Statutory Health Insurance database. A quasi-Poisson regression model accounting for periodic and aperiodic time trends and virus activity was fitted to estimate the RSV-attributable incidence rate (IR) of four specific cardiovascular hospitalizations (arrhythmia, ischemic heart diseases, chronic heart failure exacerbations, and cerebrovascular diseases) and four specific respiratory hospitalizations (influenza/pneumonia, bronchitis/bronchiolitis, chronic lower respiratory tract diseases, and upper respiratory tract diseases).

RESULTS: The estimated RSV-attributable IRs of hospitalizations generally increased with age. Among estimated cardiovascular hospitalizations in adults aged ≥ 60 years, arrhythmia and ischemic heart diseases accounted for the highest incidence of RSV-attributable events, followed by chronic heart failure exacerbation, with annual IR ranges of 157-260, 133-214, and 105-169 per 100,000 person-years, respectively. The most frequent RSV-attributable respiratory hospitalizations in adults aged ≥ 60 years were estimated for chronic lower respiratory tract diseases and bronchitis/bronchiolitis, with annual IR ranges of 103-168 and 77-122 per 100,000 person-years, respectively.

CONCLUSIONS: RSV causes a considerable burden of respiratory and cardiovascular hospitalizations in adults in Germany, similar to other respiratory viruses (e.g., influenza and SARS-CoV-2). This highlights the need to implement effective prevention strategies, especially for older adults.

PMID:40289699 | DOI:10.1111/irv.70097

Ann Med. 2025 Dec;57(1):2496798. doi: 10.1080/07853890.2025.2496798. Epub 2025 Apr 28.

ABSTRACT

BACKGROUND: Psychomotor impairments due to alcohol consumption may lead to a series of negative consequences. However, the influence of sex and ALDH2 polymorphism on psychomotor dysfunction has not yet been investigated.

METHODS: One-hundred and three participants, genotyped for ALDH2 rs671, were administered a dose of 1.0 g/kg of white spirits. The blood ethanol concentration (BEC) and acetaldehyde concentration (BAAC) were measured at specific time intervals before and after alcohol consumption. Additionally, auditory simple reaction time (ASRT), visual choice reaction time (VCRT), pursuit tracking task (PTT) and digit-symbol substitution test (DSST) were used to evaluate psychomotor function. Linear mixed-effects model was used to analyze the effects of sex and the ALDH2 genotype on alcohol metabolism and psychomotor function..

RESULTS: Acetaldehyde metabolism depended on both ALDH2 genotype and sex. Women with ALDH2*1/*1 genotype exhibited 2.21 to 18.27 µmol/L higher BAAC levels than men with the same genotype. Conversely, among participants with ALDH2*1/*2 genotype, BAAC levels of women were 0.25 to 31.32 µmol/L lower than men. The impact of ALDH2 genotype on psychomotor function varied across the four tests. VCRT increased significantly in men with ALDH2*1/*2 genotype compared to those with ALDH2*1/*1 at 2-4 h post-consumption. In the PTT test, the percentage of time on target decreased by 3.83% and 3.11% in women relative to men at 1 and 2 h post-consumption, respectively. Notably, ASRT performance was significantly correlated with BAAC levels. No effects of ALDH2 genotype and sex were observed on DSST performance.

CONCLUSIONS: ALDH2 genotype and sex independently or interactively contribute to alcohol-related psychomotor impairment.

PMID:40289679 | DOI:10.1080/07853890.2025.2496798

Addiction. 2025 Apr 28. doi: 10.1111/add.70080. Online ahead of print.

ABSTRACT

AIMS: We measured the effects of public health-oriented cannabis access compared with the illegal market on cannabis use and related mental health outcomes in adult cannabis users.

DESIGN: This was a two-arm, parallel group, open-label, randomized controlled trial. Follow-up outcome measurement took place after 6 months.

SETTING: The study was conducted in Basel-Stadt, Switzerland.

PARTICIPANTS: A total of 378 adult (aged ≥18 years) cannabis users were enrolled and randomized between August 2022 and March 2023, although only 374 users who completed baseline measures could be included.

INTERVENTION AND COMPARATOR: Participants were randomly assigned to the intervention group with public health-oriented recreational cannabis access in pharmacies (regulated cannabis products, safer use information, voluntary counseling, no advertisement; 189/188) or the illegal market control group (continued illicit cannabis sourcing; 189/186).

MEASUREMENTS: The primary outcome was self-reported severity of cannabis misuse after 6 months, as measured by the Cannabis Use Disorders Identification Test – Revised (range 0-32). Secondary outcomes involved depressive, anxiety, and psychotic symptoms, cannabis consumption amount, alcohol, and drug use.

FINDINGS: Ten participants were not followed (2.7%). Primary analysis included those with complete data (182 vs. 182). There was some evidence of a difference in cannabis misuse between the legal cannabis intervention group (mean [M] = 10.1) and the illegal market control group (M = 10.9; β = -0.69, 95% confidence interval [CI] = -1.4 to 0.0, P = 0.052). These results were supported by an intention-to-treat multiple imputation analysis (n = 374). Additional sub-group analysis by whether the participant used other drugs or not suggested that any reduction in cannabis misuse was confined to those in the legal cannabis intervention group who used other drugs (P_Interaction < 0.001). We found no statistically significant changes in any of the secondary outcomes.

CONCLUSIONS: Public health-oriented recreational cannabis access may decrease cannabis use and cannabis-related harms, especially among those using other drugs.

PMID:40289676 | DOI:10.1111/add.70080