Category: Statistics

Mol Cancer Ther. 2025 Jan 24. doi: 10.1158/1535-7163.MCT-23-0614. Online ahead of print.

ABSTRACT

TIGIT and PVRIG are immune checkpoints co-expressed on activated T and NK cells, contributing to tumor immune evasion. Simultaneous blockade of these pathways may enhance therapeutic efficacy, positioning them as promising dual targets for cancer immunotherapy. This study aimed to develop a bispecific antibody (BsAb) to co-target TIGIT and PVRIG. Expression of TIGIT and PVRIG was assessed on tumor-infiltrating lymphocytes (TILs) from patients with various cancers, including non-small cell lung cancer (n=63) and colorectal cancer (n=26). The BsAb was engineered by fusing anti-PVRIG nanobodies to the N terminus of anti-TIGIT antibodies. Functional characterization of the BsAb was performed in vitro and in vivo, including assessments of T and NK cell activation and cytotoxicity. Pharmacokinetics and safety profiles were evaluated in cynomolgus monkeys. Statistical analyses were conducted using the Student’s t-test. The results showed that the BsAb effectively blocked TIGIT and PVRIG from binding their respective ligands, CD155 and CD112, leading to significant increases in T cell activation (2.8-fold, p<0.05) and NK cell cytotoxicity (1.8-fold, p<0.05). In vivo, the BsAb demonstrated potent anti-tumor activity, both as a monotherapy and in combination with anti-PD-1 or anti-PD-L1, in humanized PBMC and transgenic mouse models. Pharmacokinetic studies in cynomolgus monkeys revealed a favorable profile, with no dose-limiting toxicities observed after four repeated doses of 200 mg/kg. These findings provide compelling preclinical evidence for the therapeutic potential of targeting the TIGIT-PVRIG axis with a bispecific antibody. This approach shows promise for enhancing anti-tumor immunity and warrants further investigation in clinical trials.

PMID:39851063 | DOI:10.1158/1535-7163.MCT-23-0614

Circ Genom Precis Med. 2025 Jan 24:e004631. doi: 10.1161/CIRCGEN.124.004631. Online ahead of print.

ABSTRACT

BACKGROUND: Lp(a; Lipoprotein[a]) is a predictor of atherosclerotic cardiovascular disease (ASCVD); however, there are few algorithms incorporating Lp(a), especially from real-world settings. We developed an electronic health record (EHR)-based risk prediction algorithm including Lp(a).

METHODS: Utilizing a large EHR database, we categorized Lp(a) cut points at 25, 50, and 75 mg/dL and constructed 10-year ASCVD risk prediction models incorporating Lp(a), with external validation in a pooled cohort of 4 US prospective studies. Net reclassification improvement was determined among borderline-intermediate risk patients.

RESULTS: We included 5902 patients aged ≥18 years (mean age 48.7±16.7 years, 51.2% women, and 7.7% Black). Our EHR model included Lp(a), age, sex, Black race/ethnicity, systolic blood pressure, total and high-density lipoprotein cholesterol, diabetes, smoking, and hypertension medication. Over a mean follow-up of 6.8 years, ASCVD event rates (per 1000 people-years) ranged from 8.7 to 16.7 across Lp(a) groups. A 25 mg/dL increment in Lp(a) was associated with an adjusted hazard ratio of 1.23 (95% CI, 1.10-1.37) for composite ASCVD. Those with Lp(a) ≥75 mg/dL had an 88% higher risk of ASCVD (hazard ratio, 1.88 [95% CI, 1.30-2.70]) and more than double the risk of incident stroke (hazard ratio, 2.55 [95% CI, 1.54-4.23]). C-statistics for our EHR and EHR+Lp(a) models in our EHR training data set were 0.7475 and 0.7556, respectively, with external validation in our pooled cohort (n=21 864) of 0.7350 and 0.7368, respectively. Among those at borderline/intermediate risk, the net reclassification improvement was 21.3%.

CONCLUSIONS: We show the feasibility of developing an improved ASCVD risk prediction model incorporating Lp(a) based on a real-world adult clinic population. The inclusion of Lp(a) in ASCVD prediction models can reclassify risk in patients who may benefit from more intensified ASCVD prevention efforts.

PMID:39851061 | DOI:10.1161/CIRCGEN.124.004631

Arch Ital Urol Androl. 2025 Jan 23:12658. doi: 10.4081/aiua.2025.12658. Online ahead of print.

ABSTRACT

OBJECTIVES: This research aimed to compare the prostate cancer (PCa) features, survival rate, and functional outcomes after open suprapubic Radical Prostatectomy (RP) between younger men (≤ 55 years) and older men (> 55 years).

METHODS: In this retrospective cohort study, we studied 134 patients with clinically localized PCa who underwent RP at our centers between 2011 and 2019, with 26 (19.40%) patients aged ≤ 55. Pathological parameters, survival rate (at 5 and 10 years), and functional outcomes such as erectile function and continence rate (at two years from RP) were evaluated retrospectively, and the two groups were compared. The Chi-square test, Kaplan-Meier, and Cox proportional hazards method were used for statistical analysis.

RESULTS: Men aged ≤ 55 had greater rates of organ-confined tumors, lower D’Amico risk grouping, and pathologic Gleason grade than their older counterparts (all p<0.05). The median follow-up was 81 months. The overall survival rate at five and ten years in younger men vs older counterparts was 96.15% vs. 93.47% and 92.15% v. 82.13% but was not statistically significant (p=0.1539). Five-year biochemical recurrence-free and metastasis-free survival rates in younger men vs older counterparts were 96.2% vs 81.5% and 75.7% vs 51.5%. Men > 55 years were associated with worse BCR-free and metastasis-free survival in univariate analysis and worsening BCR in multivariate analysis. The continence rate was significantly improved in men aged ≤ 55 years compared to older counterparts (OR: 5.08; 95% CI: 1.61-22.61; p=0.013). However, erectile function was not statistically significant between groups [for moderate ED: (OR:1.08; 95% CI: 0.43-2.79, p=0.865), for severe ED (OR: 1.60; 95% CI: 0.35-11.50, p=0.579=)].

CONCLUSIONS: Our study showed that survival rates were similar in younger men (≤ 55 years) and their older counterparts. However, older patients who underwent RP had more advanced disease, worse BCR-free survival, and worse continence rate. For localized prostate cancer patients under 55 years of age, radical prostatectomy is an excellent treatment option with excellent long-term survival results. Given the relatively small number of patients younger than 55, a large cohort study with long-term postprocedural follow-up is needed to validate this observation.

PMID:39851058 | DOI:10.4081/aiua.2025.12658

Circ Cardiovasc Interv. 2025 Jan 24:e014528. doi: 10.1161/CIRCINTERVENTIONS.124.014528. Online ahead of print.

ABSTRACT

BACKGROUND: Intravascular imaging (IVI) is widely recognized to improve outcomes after percutaneous coronary intervention (PCI). However, IVI is underutilized and is not yet established as a performance measure for quality PCI.

METHODS: We examined temporal trends of IVI use for all PCIs performed at Veterans Affairs hospitals in the United States from 2010 to 2022 using retrospective observational cohorts. IVI was defined as intravascular ultrasound or optical coherence tomography. A contemporary subset of PCIs from 2020 to 2022 was used to examine clinical characteristics associated with IVI use and test the reliability of IVI as a pass/fail performance measure. We then used a generalized linear mixed model to estimate the proportion of IVI use variability attributable to the hospital, physician, and patient level. Cox proportional hazard models were used to assess the association of IVI with clinical outcomes at 1 year.

RESULTS: IVI use increased from 12.3% in 2010 to 43.1% in 2022 in 136 071 PCIs included in the study. Among 22 918 PCIs in the contemporary cohort, IVI was more frequent with nonemergent presentations, chronic total occlusions, and left main lesions but usage variability was primarily attributable to hospital (54%) and physician (33%) levels. As a pass/fail performance measure, reliability was high (>0.96) at hospital and physician levels. However, IVI use was not associated with statistically significant differences in mortality or major adverse cardiovascular events in this cohort.

CONCLUSIONS: IVI use for PCI is increasing rapidly at Veterans Affairs hospitals in the United States but with marked variation at the hospital and physician levels. IVI meets established criteria for an effective performance measure and should be measured and reported by local and national organizations to encourage further uptake. Ongoing training and quality improvement may be required to maximize the benefit of IVI as it is more widely utilized.

PMID:39851056 | DOI:10.1161/CIRCINTERVENTIONS.124.014528

Arch Ital Urol Androl. 2025 Jan 23:13268. doi: 10.4081/aiua.2025.13268. Online ahead of print.

ABSTRACT

INTRODUCTION: Excision and primary anastomosis (EPA) urethroplasty is the standard treatment for traumatic urethral strictures, but managing them remains challenging for urologists. Identifying factors leading to EPA urethroplasty failure benefits both patients and surgeons. This study aims to analyze risk factors for urethral stricture recurrence after one-year follow-up of EPA urethroplasty.

MATERIALS AND METHODS: Data on male patients undergoing EPA urethroplasty at the Urology Department of Saiful Anwar General Hospital from January 2013 until December 2023 were prospectively recorded. Successful urethroplasty, defined as the absence of additional treatment necessity, was assessed until 12 months follow-up. Demographic data, time to surgery, stricture etiology, comorbidities, prior urethral interventions, and operation steps were recorded. Univariate and multivariate Cox regression analyses were performed using IBM SPSS Statistics version 21.

RESULT: Total 95 patients were observed, and 89 patients were included, averaging 41.2 ± 15.59 years old. EPA urethroplasty succeeded in 91% of cases over a median follow-up of 16.3 months. Pelvic fracture urethral injury (PFUI) was the predominant etiology in 74% of cases, with an average stricture length of 25.4 ± 16.3 mm. The average time to surgery was performed on average 6.67 ± 4.07 months after diagnosis. In univariate analysis, body mass index (BMI), time to surgery, and stricture length were associated with urethral stricture recurrence. However, only time to surgery showed a significant association in multivariate analysis.

CONCLUSIONS: Obesity, the length of the stricture, and delayed surgical intervention are associated with an increased risk of urethral stricture recurrence in patients following EPA. EPA urethroplasty demonstrates a high success rate in managing traumatic urethral strictures.

PMID:39851052 | DOI:10.4081/aiua.2025.13268

J Atten Disord. 2025 Jan 24:10870547251313879. doi: 10.1177/10870547251313879. Online ahead of print.

ABSTRACT

OBJECTIVE: This study investigated the psychometric properties of the Arabic version of the Adult Self-Report Scale-5 (the ASRS-5-AR) within a large sample of adults residing in Saudi Arabia.

METHODS: This cross-sectional study applied the ASRS-5-AR to a random sample of 4,299 Saudi and non-Saudi adults, aged 19 to 66 years (31.16 ± 9.26 years), living in the regions of Riyadh, Makkah, and the Eastern Province in Saudi Arabia. Collected data were analyzed using IBM SPSS Statistics 26, JASP 0.18.3.0 software, and MedCalc 22.030 statistical software.

RESULTS: The ASRS-5-AR demonstrated strong internal consistency, with all six items showing significant positive correlation with the total score (.675-.735). Results of confirmatory factor analysis revealed a goodness-of-fit coefficient of 0.983 for the one-factor model and McDonald’s omega, Cronbach’s α, and Spearman-Brown coefficients of 0.786, 0.788, and 0.724, respectively. In addition, the findings revealed statistically significant differences in self-reported ADHD symptoms based on age (F = 18.68; p < .001), level of education (F = 2.61; p < .05), and marital status (F = 22.30; p < .001). However, there were no significant differences in self-reported ADHD symptoms between males and females (t = 0.625; p > .05) or Saudi and non-Saudi participants (t = 0.409; p > .05) or based on region of residence (t = 2.19; p > .05).

CONCLUSIONS: This study provides valuable insights into the psychometric properties of the ASRS-5-AR within a large sample of adults in Saudi Arabia. The findings demonstrate acceptable reliability of the ASRS-5-AR within this population. While these findings suggest the ASRS-5-AR may be a useful tool for initial assessment, further research is crucial. Future studies should focus on establishing accurate cutoff scores by comparing a general population sample with a clinically diagnosed sample of adults with ADHD in Saudi Arabia. This will allow for a more accurate evaluation of the scale’s utility in identifying individuals who may require further clinical assessment.

PMID:39851051 | DOI:10.1177/10870547251313879

Circ Genom Precis Med. 2025 Jan 24:e004681. doi: 10.1161/CIRCGEN.124.004681. Online ahead of print.

ABSTRACT

BACKGROUND: Earlier identification of high coronary artery disease (CAD) risk individuals may enable more effective prevention strategies. However, existing 10-year risk frameworks are ineffective at earlier identification. We sought to understand how the variable importance of genomic and clinical factors across life stages may significantly improve lifelong CAD event prediction.

METHODS: A longitudinal study was performed using data from 2 cohort studies: the FOS (Framingham Offspring Study) with 3588 participants aged 19 to 57 years and the UKB (UK Biobank) with 327 837 participants aged 40 years to 70 years. A total of 134 765 and 3 831 734 person-time years were observed in FOS and UKB, respectively. Hazard ratios for CAD were calculated for polygenic risk score (PRS) and clinical risk factors at each age of enrollment. The relative importance of PRS and pooled cohort equations in predicting CAD events was also evaluated by age groups.

RESULTS: The importance of CAD PRS diminished over the life course, with a hazard ratio of 3.58 (95% CI, 1.39-9.19) at the age of 19 years in FOS and a hazard ratio of 1.51 (95% CI, 1.48-1.54) by the age of 70 years in UKB. Clinical risk factors exhibited similar age-dependent trends. PRS significantly outperformed pooled cohort equations in identifying subsequent CAD events in the 40- to 45-year age group, with 3.2-fold more appropriately identified events. Overall, adding PRS improved the area under the receiving operating curve of the pooled cohort equations by an average of +5.1% (95% CI, 4.9%-5.2%) across all age groups; among individuals <55 years, PRS augmented the area under the curve-ROC of the pooled cohort equations by 6.5% (95% CI, 5.5%-7.5%; P<0.001).

CONCLUSIONS: Genomic and clinical risk factors for CAD display time-varying importance across the lifespan. The study underscores the added value of CAD PRS, particularly among individuals younger than 55 years, for enhancing early risk prediction and prevention strategies. All results are available at https://surbut.github.io/dynamicHRpaper/index.html.

PMID:39851049 | DOI:10.1161/CIRCGEN.124.004681

Eur J Psychotraumatol. 2025 Dec;16(1):2451480. doi: 10.1080/20008066.2025.2451480. Epub 2025 Jan 24.

ABSTRACT

Background: Individuals impacted by adverse childhood experiences (ACEs) are at greater risk of developing obesity, however, few studies have prospectively measured ACEs and obesity during childhood. Associations with the adoption of obesogenic behaviours during childhood, which directly contribute to obesity are also understudied.Objective: To examine associations between individual and cumulative ACEs, obesity, and obesogenic behaviours during childhood.Methods: Data came from Growing Up in New Zealand. The study sample was restricted to those who provided obesity data at age 8 and one child per mother, resulting in an analytic sample of 4895 children. A newly developed ACEs index consisted of nine individual ACEs and cumulative ACEs scores (0, 1, 2, 3, 4+ ACEs), two obesity measures (BMI and waist circumference/height ratio), and eight obesogenic behaviours including unhealthy dietary behaviours, inadequate sleep duration, excessive screen time, and physical inactivity were included in the analyses.Results: ACEs were prevalent among this cohort of NZ children. By age eight, 87.1% of children experienced at least one ACE and 16% experienced at least 4 ACEs. Six individuals assessed ACEs showed significant associations with childhood obesity (AORs ranging from 1.22 to 1.44). A significant dose-response effect was observed where the experience of a higher number of ACEs was associated with greater risk for obesity (AORs increased from 1.78 for one ACE to 2.84 for 4+ ACEs). Further, a significant dose-response relationship was found between experiencing two or more ACEs and higher odds of adopting obesogenic behaviours (AORs ranging from 1.29 for physical inactivity to 3.16 for no regular breakfast consumption).Conclusions: ACEs exposure contributes to population-level burden of childhood obesity. Our findings highlight the importance of a holistic understanding of the determinants of obesity, reinforcing calls for ACEs prevention and necessitating incorporation of ACEs-informed services into obesity reduction initiatives.

PMID:39851037 | DOI:10.1080/20008066.2025.2451480

Acta Orthop Belg. 2024 Sep;90(3):549-558. doi: 10.52628/90.3.12669.

ABSTRACT

This meta-analysis focuses on the controversial efficacy and safety of microfragmented adipose tissue (MFAT) as compared with platelet-rich plasma (PRP) in the clinical treatment of knee osteoarthritis (KOA). We have attempted to provide an evidence-based medicine protocol for the conservative treatment of KOA. Researchers collected and compared randomized controlled trials (RCTs) that used microfragmented adipose tissue and platelet-rich plasma to treat knee osteoarthritis. We searched CNKI, Wanfang Database, CMJD, PubMed, Sinomed, Cochrane Library, and Embase for studies published up to May 31, 2023. Two investigators independently screened literature, extracted data, and assessed bias risk using the Cochrane bias risk tool. The researchers then performed a meta-analysis using Revman 5.4 statistics software provided by the Cochrane Library. A total of 4 randomized controlled trials involving 266 patients (326 knees) were included. There were 161 knees in the MFAT group and 165 knees in the PRP group. Meta-analysis showed a statistically significant difference in VAS scores between the MFAT group and the PRP group at 12 months after treatment [MD=0.99, 95% CI (0.31, 1.67), P=0.004]. This result showed that VAS scores were lower in the PRP group than in the MFAT group, and that PRP injection reduced pain more effectively than MFAT injection. At 6 months after treatment, Tegner activity scale scores in the MFAT group were higher than that in the PRP group [MD=0.65, 95% CI (0.11, 1.19), P=0.02], and the difference was statistically significant. There were no significant differences in the remaining indicators between the two groups. Based on this meta-analysis, PRP appears to be more effective than MFAT in treating KOA in terms of long-term pain relief. However, MFAT was superior to PRP in improving short-term activity function. Overall, there was no significant difference between MFAT and PRP in the treatment of KOA. In addition, MFAT does not increase the risk of adverse events compared to PRP. However, at present, there are few clinical studies on MFAT and PRP, which need to be verified by more rigorously designed clinical trials.

PMID:39851028 | DOI:10.52628/90.3.12669

Acta Orthop Belg. 2024 Sep;90(3):535-542. doi: 10.52628/90.3.12274.

ABSTRACT

Avascular necrosis (AVN) is a known complication during the management of developmental dysplasia of the hip (DDH). It has the potential to alter the growth of the head or acetabulum and prevent the best outcomes. While past literature has evaluated the risks of AVN and strategies to avoid it, studies on the impact of AVN on the outcomes are scarce. In this systematic review, we aim to study the extent of the effects of AVN on the outcomes, in the management of DDH. In this systematic review series for 1990 to 2021 were pooled. The clinical and radiological outcomes of the AVN and non-AVN groups were compared. The effects of other modifying factors were also evaluated. A total of 170 AVN and 585 non-AVN hips from 21 papers were compared. The analysis did not show any statistically significant difference between the AVN and non-AVN groups in terms of clinical or radiological parameters. Interestingly patients who had the index surgery at a younger age had a higher risk of further surgery, with acetabular osteotomy being the most common secondary procedure. The negative impact of AVN may not be as severe as previously thought. Thus, the fear of AVN should not take precedence over the primary goal of DDH management i.e. obtaining a stable concentric mobile hip.

PMID:39851026 | DOI:10.52628/90.3.12274