Multivariate Regression Research Articles

Correlation between corneal biomechanical and tomographic parameters in cataract patients

AIM: To investigate the relationship between preoperative corneal biomechanical properties and corneal tomographic properties in cataract patients. METHODS: The study consisted of 59 eyes of 30 participants who were diagnosed as cataract in Peking University Third Hospital between September 2019 and November 2019. Stepwise multivariable linear regression analysis was calculated to determine the relationship between corneal biomechanical parameters and tomographic parameters. The patients were classified into three groups of with the rule (WTR) astigmatism, against the rule astigmatism and oblique astigmatism. And the differences in corneal parameters among different groups were compared. RESULTS: There were significant differences in the first applanation time (A1T), the first applanation length (A1L), corneal velocity during the first applanation (Vin), the second applanation time (A2T), highest concavity (HC) radius, displacement amount (DA), DA ratio, stiffness parameter A1 (SPA1) and integrated radius (IR) between oblique astigmatism patients and the other two groups. Total corneal steep meridian (K2) was negatively associated with A1L, A1T and corneal velocity during the second applanation (Vout). Patients with higher anterior corneal curvature had lower HC radius and central corneal thickness (CCT; P=0.001 and 0.006, respectively), while the Ambrosio relational thickness to the horizontal profile (ARTh) was higher than those with lower anterior corneal curvature (P=0.009). CONCLUSION: The study reveals that the elasticity of corneal collagen fibers is greater, but the viscoelasticity of cornea is smaller in patients with oblique astigmatism. There is no significant difference in ARTh between patients with different types of astigmatism, that is, the corneal biomechanical specificity of oblique astigmatism group is probably not caused by corneal thickness. Moreover, we find patients with higher anterior corneal curvature has lower HC radius and CCT but higher ARTh than those with lower anterior corneal curvature.

A descriptive analysis of pediatrician posts on Twitter

ABSTRACT Pediatrician advocates on Twitter successfully organized using the hashtag #tweetiatrician. Data from all 163 users with #tweetiatrician in their bio in April 2022 were analyzed to identify factors associated with message engagement. Posts created between July 17, 2021 and July 17, 2022 were exported and categorized by type and each users’ most engaging 10 tweets for each type were thematically coded. Multivariate regression of followers against account characteristics yielded r2 = 0.52, including tweets shared (β = −0.858 followers/tweet, p < .001), tweet density (tweets/account length) (β = 1269.17 followers/tweet/day, p = .02), and accounts followed (β = −1.44 followers/following, p = .02). Follower count correlated with retweets about health care (β = 280.6 followers per % increase, p = .049) and original tweets on personal topics (β = 341.1 followers per % increase, p = .017). Sentiment analysis revealed an overall neutral tone (score 0.09, SD = 0.85). Pediatricians increased their engagement on Twitter when they posted frequently, used a neutral tone, and shared content relating to topics outside of pediatric advocacy; pediatricians using microblogging for patient advocacy can use these findings to increase engagement with their messages.

Sex-Related Differences in Functional and Neurological Outcomes of Spinal Cord Injury.

Traumatic spinal cord injury (SCI) tends to occur in different demographics and with differing etiology between males and females. Sex-related differences may influence recovery, but there remains a lack of evidence on this subject. Our objective was to quantify the influence of sex on functional and neurological outcomes of SCI. This was a retrospective cohort study of the multicenter, prospectively maintained SCI Model Systems database from 1992 to 2016. Traumatic SCI patients (≥15 years old) enrolled in a participating inpatient rehabilitation center within 30 days of injury with follow-up at 1 year were included. The primary outcome was the Functional Independence Measure (FIM), which quantifies independence in 13 activities of daily living. Secondary outcomes were individual FIM items, American Spinal Injury Association (ASIA) Motor Index Score at 1 year postinjury, and improvement in ASIA Impairment Scale (AIS). The impact of sex on each outcome was evaluated using propensity score-weighted multivariable regression analyses while controlling for covariates such as age, injury severity, and baseline function. The analysis included 3924 patients (20% female). Multivariable linear regression showed that female sex was associated with worse FIM scores at 1 year postinjury (B = -3.1, 95% CI: -4.4 to -1.8). The FIM items with the greatest differences in independence between males and females were bladder management and transfers, which favored males. For ASIA Motor Score, while females had 10-point greater absolute scores at 1 year (P = .03) and 2-point greater improvement (P = .03) compared with males, no effect was present after adjusting for confounding variables in multivariable regression. The rate of ASIA Impairment Scale improvement was higher in females (P = .04), but this was not significant in multivariable regression (odds-ratio: 1.25, 95% CI: 0.96-1.63). Male sex is associated with greater functional independence, despite equal or greater motor recovery in female patients. Female SCI patients may benefit from targeted interventions to improve independence.

When Is the Broken Heart Most Dangerous? Assessing Risk Factors to Predict Inpatient Death in Takotsubo Cardiomyopathy: Analysis of the National Inpatient Sample for 2021.

Takotsubo cardiomyopathy (TC) has a similar clinical presentation to acute coronary syndromes (ACS). As the prevalence and influence on clinical decisions of this condition are being increasingly recognized, prognostic factors have yet to be established. We applied known near-term acute coronary syndrome mortality risk factors to determine their prognostic value in TC. This study aimed to assess the patient characteristics and comorbidities predicting inpatient death from TC. Understanding these risk factors is essential for clinical decision making and improving prognostic assessments. We analyzed the National Inpatient Sample database for 2021. Inclusion criteria were principal diagnosis of TC (International Classification of Diseases, Tenth Revision [ICD-10] code I51.81) and age ≥18 years. Different comorbidities, age, and sex were analyzed, and the primary outcome was inpatient death. Univariate logistic regression was used to test the association of each factor with death, and multivariate logistic regression was then used to test for independent predictive value. A total of 9109 admissions for TC were identified (10.3% men and 89.7% women) with a mean age of 67 years and an inpatient mortality rate of 2.31%. On univariate regression, age (odds ratio [OR], 1.04; P=0.013), heart failure (OR, 3.2; P<0.001), atrial fibrillation (OR, 3.12; P<0.001), and chronic kidney disease (OR, 3.54; P<0.001) were significant predictors of inpatient death. On multivariate regression, only heart failure (OR, 2.8; P=0.007) and chronic kidney disease (OR, 2.34; P=0.032) were independently associated with inpatient death. Preexisting heart failure and a history of chronic kidney disease are poor prognostic factors in patients presenting with TC. Further large-scale studies are required to validate our findings.

Risk Factors for COVID-19-Related Hospitalization and Death in Patients With Cancer: The National Cancer Institute COVID-19 in Cancer Patients Study (NCCAPS).

Retrospective case series have identified having cancer and receiving treatment for cancer as risk factors for inferior COVID-19 outcomes. To determine risk factors for hospitalization and death in patients with cancer with COVID-19 infection. The National Cancer Institute COVID-19 in Cancer Patients Study (NCCAPS) is a prospective longitudinal natural history cohort study examining the impact of COVID-19 on patients with cancer. Adults were eligible within 14 days of an initial positive SARS-CoV-2 test result if they were receiving active treatment for cancer or had prior stem cell/bone marrow transplant or CAR T-cell treatment. The statistical analysis took place between September 2024 and April 2025. The primary objective of the study was to determine patient factors, therapy types, and cancer types associated with COVID-19 severity, defined as hospitalization for or death from COVID-19 within 30 and 90 days after the first positive SARS-CoV-2 test result. Multivariable regressions were performed for COVID-19-specific hospitalization and mortality (proportional hazard and cause-specific hazard models). Of 1572 eligible adult patients (median [range] age, 60 [18-93] years; 840 female [53.4%]), 1066 (67.8%) had a solid tumor, with 683 (64.0%) having metastatic disease; breast (252 [23.6%]) and lung cancer (148 [13.9%]) were most common. At enrollment, 1013 patients (64.4%) were unvaccinated for SARS-CoV-2. COVID-19-related mortality at 90 days was 3.0% and did not increase at subsequent time points. The cumulative incidence of COVID-19-specific death in the first 90 days was highest in patients with lymphoma, intermediate in patients with acute leukemia and lung cancer, and lowest in patients with other solid tumors and other hematologic cancers. In multivariable analysis, receipt of chemotherapy (hazard ratio [HR], 1.97; 95% CI, 1.52-2.54) and baseline history of stroke, atrial fibrillation, or pulmonary embolism (HR, 1.78; 95% CI, 1.33-2.38) were associated with a higher risk of hospitalization. Vaccination prior to SARS-CoV-2 infection was associated with a lower risk of hospitalization (HR, 0.52; 95% CI, 0.38-0.70). Over 2 years of follow-up, there were 1739 cancer treatment disruptions, of which 881 (50.7%) were attributed to COVID-19, with most disruptions occurring within the first 30 days. The results of this prospective cohort study showed that COVID-19 had a significant impact on patients with cancer, including hospitalization, treatment disruptions, and death.

UNC93B1: a novel immune-related prognostic biomarker in breast cancer.

Breast cancer (BRCA) is a prevalent and deadly disease among women. This study investigated the role of UNC93B1, a gene associated with immune function, in BRCA prognosis and immune infiltration. Differentially expressed mRNA (DEmRNA) data related to the prognosis and immunity of BRCA patients were obtained from TCGA, GTE, GEO, and ImmPort databases. The Kruskal-Wallis test was used to identify clinicopathological parameters associated with UNC93B1 expression. Univariate and multivariate COX regression analyses were performed to assess the impact of UNC93B1 expression and clinicopathological parameters on patient survival. We analyzed the target genes' relevant functions and signaling pathways through enrichment analysis. Furthermore, the relationship between UNC93B1 expression and tumor immune infiltration was examined using ssGSEA and Spearman correlation analysis. The findings demonstrated that high expression of UNC93B1 was associated with poorer prognosis in BRCA patients. UNC93B1 was also linked to race, N stage, pathological stage, and overall survival in BRCA patients and emerged as an independent prognostic factor. Functional enrichment analysis indicated significant enrichment of UNC93B1 in oncogenic and immune-related pathways. Moreover, UNC93B1 expression displayed significant associations with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Knockdown of UNC93B1 expression in BRCA cell lines (MDA-MB-231, SK-BR-3) suppresses their proliferation, invasion, and other phenotypes. These results suggest that UNC93B1 may be an immunologically relevant diagnostic and prognostic biomarker for BRCA.

Beyond physical function: the impact of nonmotor symptoms on activities and participation in wheelchair users with multiple sclerosis.

While the impact of physical disabilities on daily activities is well documented, less is known about the influence of nonmotor symptoms on activities and participation. This study aims to fill this gap by examining how nonmotor symptoms affect activities and participation outcomes in wheelchair users with multiple sclerosis (MS). Data from 89 wheelchair users with MS collected through a nationwide survey were analyzed. Participants completed the Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function, PROMIS depression, PROMIS pain interference, Fatigue Severity Scale, and measures of self-efficacy and participation. Hierarchical multivariable linear regression was used to assess the impact of nonmotor symptoms on four self-efficacy and participation outcomes beyond physical function. As expected, physical function was a significant predictor of all outcomes: self-efficacy for managing daily activities (β = 0.59, P < 0.01), control over community participation (β = -1.06, P < 0.01), ability to participate (β = 0.46, P < 0.01), and satisfaction with participation in social roles and activities (β = 0.70, P < 0.01). Beyond physical function, nonmotor symptoms accounted for 6% of the variance in self-efficacy, 21% in control over community participation, 29% in ability to participate in social roles and activities, and 13% in satisfaction with participation in social activities. Among these, pain interference emerged as the most consistent nonmotor symptom, significantly associated with poorer outcomes across all domains (P < 0.05). This study demonstrates that nonmotor symptoms, particularly pain interference, are significantly associated with activities and participation outcomes in wheelchair users with MS.

Online cognitive stimulation intervention (CSI): A novel approach to improve cognitive functions in healthy older adults.

Cognitive interventions demonstrate promising evidence for minimizing cognitive decline in older adults yet are often criticized for their lack of ecological validity. We designed a real-life intervention using mobile-based shopping applications over 22 weeks and examined its effects on cognitive function. We recruited 102 healthy Malaysian older adults (Mage = 66.18, SD = 4.95) who were randomly assigned to three conditions: experimental, active control, and passive control. The first two groups had weekly sessions but not the latter. The experimental group completed tasks designed to assess inhibition and working memory-updating using online shopping applications (trained applications) with varying difficulty levels, whereas active control participants freely interacted with the same applications without any training instructions. All groups completed assessment sessions in the baseline, posttest, and a 1-month follow-up, including noncomputerized versions of Stroop, Digit Span, and the Paced Auditory Serial Addition Test, and an untrained application (Tripadvisor) measuring inhibition and working memory-updating. Data were analyzed using Bayesian analysis of variance and multivariate multiple regression. Results showed that the experimental group performed better in the Paced Auditory Serial Addition Test-3 s compared to the passive control, suggesting training gains in working memory-updating. The experimental group performed better in inhibition and working memory-updating in the untrained application compared to both control groups, indicating a near transfer effect. In summary, our findings provide evidence that cognitive stimulation by tasks using online shopping activities on mobile phones is beneficial for older adults' cognitive function. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Early Vascular Aging Determined by 3-Dimensional Aortic Geometry: Genetic Determinants and Clinical Consequences.

Vascular aging is an important phenotype characterized by structural and geometric remodeling. Some individuals exhibit supernormal vascular aging, associated with improved cardiovascular outcomes; others experience early vascular aging, linked to adverse cardiovascular outcomes. The aorta is the artery that exhibits the most prominent age-related changes; however, the biological mechanisms underlying aortic aging, its genetic architecture, and its relationship with cardiovascular structure, function, and disease states remain poorly understood. We developed sex-specific models to quantify aortic age on the basis of aortic geometric phenotypes derived from 3-dimensional tomographic imaging data in 2 large biobanks: the UK Biobank and the Penn Medicine BioBank. Convolutional neural ne2rk-assisted 3-dimensional segmentation of the aorta was performed in 56 104 magnetic resonance imaging scans in the UK Biobank and 6757 computed tomography scans in the Penn Medicine BioBank. Aortic vascular age index (AVAI) was calculated as the difference between the vascular age predicted from geometric phenotypes and the chronological age, expressed as a percent of chronological age. We assessed associations with cardiovascular structure and function using multivariate linear regression and examined the genetic architecture of AVAI through genome-wide association studies, followed by Mendelian randomization to assess causal associations. We also constructed a polygenic risk score for AVAI. AVAI displayed numerous associations with cardiac structure and function, including increased left ventricular mass (standardized β=0.144 [95% CI, 0.138, 0.149]; P<0.0001), wall thickness (standardized β=0.061 [95% CI, 0.054, 0.068]; P<0.0001), and left atrial volume maximum (standardized β=0.060 [95% CI, 0.050, 0.069]; P<0.0001). AVAI exhibited high genetic heritability (h2=40.24%). We identified 54 independent genetic loci (P<5×10-8) associated with AVAI, which further exhibited gene-level associations with the fibrillin-1 (FBN1) and elastin (ELN1) genes. Mendelian randomization supported causal associations between AVAI and atrial fibrillation, vascular dementia, aortic aneurysm, and aortic dissection. A polygenic risk score for AVAI was associated with an increased prevalence of atrial fibrillation, hypertension, aortic aneurysm, and aortic dissection. Early aortic aging is significantly associated with adverse cardiac remodeling and important cardiovascular disease states. AVAI exhibits a polygenic, highly heritable genetic architecture. Mendelian randomization analyses support a causal association between AVAI and cardiovascular diseases, including atrial fibrillation, vascular dementia, aortic aneurysms, and aortic dissection.

Right Ventricular Function Score by Echocardiography for Predicting Outcomes After Heart Transplantation.

The impaired right ventricular (RV) function may occur after heart transplantation (HT). This study aimed to develop a straightforward RV function score (RVFS) using echocardiography to predict adverse clinical events in a large cohort of subjects after HT. A total of 357 consecutive patients post HT who underwent echocardiography at our single institution were retrospectively included. RV systolic function was evaluated by echocardiography. A multivariate Cox regression analysis was performed to identify the independent predictors of RV function for adverse clinical events. During a median follow-up of 39 months from the date of the echocardiography, a composite of adverse events that included death and major adverse cardiac events occurred in 51 patients. The multivariate Cox analysis revealed that RV fractional area change, tricuspid annular plane systolic excursion, and RV free wall longitudinal strain were independent predictors of outcomes after HT. The RVFS was constructed based on these 3 parameters, assigning a value of 1 when a predictor was below its cutoff value from receiver operating characteristic curves and 0 when above. The RVFS outperformed separate RV function parameters in predicting outcomes (area under the curves: 0.84 versus 0.64-0.78, P<0.05). Moreover, incorporating the RVFS into the base clinical model significantly improved the C-statistic of the prediction model (C-statistic from 0.70 to 0.83, P<0.001). The RVFS, a readily obtainable echo score that combines multiple RV function parameters, exhibits incremental value and significant potential as a robust predictor for adverse outcomes in clinically stable patients after HT.

Transition of BMI Status From Childhood to Adulthood and Cardiovascular-Kidney-Metabolic Syndrome in Midlife: A 36-Year Cohort Study.

We investigated the associations between BMI transitions from childhood to adulthood and cardiovascular-kidney-metabolic (CKM) syndrome and its components in midlife. Using data from the Hanzhong Adolescent Hypertension Study, 1,997 participants aged 6-18 years were followed for 36 years into midlife (mean age 48.12 years). Participants were categorized into four groups based on BMI transitions from childhood to midlife: control, incident, persistent, and resolution. CKM stages ranged from early (stages 0-1), to intermediate (stage 2), to advanced (stages 3-4), defined by cardiovascular disease, chronic kidney disease, and metabolic disorders. Multivariable regression models were used to assess associations between BMI transitions and CKM outcomes. Individuals transitioning from normal childhood BMI to overweight in adulthood had higher risks of intermediate (odds ratio [OR] 5.19 [95% CI 3.15-8.53]) and advanced CKM stages (OR 6.70 [95% CI 3.96-11.33]) compared with those with persistently normal BMI. These risks were attenuated if elevated childhood BMI resolved by adulthood. For specific CKM components, individuals with normal childhood BMI but overweight in adulthood showed higher risks of left ventricular diastolic dysfunction, subclinical kidney damage, albuminuria, and metabolic abnormalities compared with those with persistently normal BMI. These risks were reduced if high childhood BMI normalized by adulthood. Transitioning from normal childhood BMI to overweight in adulthood is associated with increased risks of higher CKM stages in midlife. However, individuals whose high childhood BMI resolved by adulthood exhibit similar risk to those with persistently normal BMI.

Preservation of Distal Mobile Segments Reduces Risk of Rod Breakage in Adult Spinal Deformity Surgery.

Retrospective multicenter observational study. To analyze whether avoiding fusion to the pelvis and preserving distal mobile segments reduces the risk of rod breakage (RB) following adult spinal deformity (ASD) surgery. RB is a major complication in ASD surgery, mostly associated with age, malalignment, and pelvic fixation. However, the impact of different lower instrumented vertebrae (LIV) possibilities as an independent risk factor remains unclear. We included ASD patients (aged 50-75) who underwent fusion of more than six levels, with LIV at or below L4, and a minimum two-year follow-up. Patients were categorized into those who did or did not experienced rod breakage. Univariate and multivariate regression analyses assessed biological, surgical, and radiographic risk factors, with particular focus on LIV as an independent variable. Among 642 patients, 84% were female, mean age 64 years, BMI of 26.3, and ASD Frailty Index (ASD-FI) of 0.44. LIV distribution was L4 (52), L5 (44), S1 (48), and Iliac (498). RB occurred in 17.3% (113 patients). Univariate analysis linked RB to various alignment (preoperative global alignment and pelvic retroversion) and surgical factors (blood loss, osteotomies, levels fused, the use of cages, higher 1-year coronal Cobb angle, and lower implant density). However, multivariate analysis identified two independent risk factors: implant density (OR 0.98; CI 95% 0.97-0.99) and LIV (OR 0.74; CI 95% 0.02-0.312), with LIV being the strongest predictor. Notably, RB appearance was significantly lower in patients with LIV at L4 or L5 (2.1%, 2/96) compared to those with LIV at S1 or Iliac (20.3%, 111/546). Selecting the lowest instrumented vertebra at L4 or L5 in ASD surgery significantly reduces rod breakage risk compared to pelvic fixation, independent of other biological, surgical, and radiographic variables. Preserving distal mobile segments, when feasible, may help prevent rod failure.

Interhospital Variation in Operative Intervention for Firearm-Related Penetrating Traumatic Brain Injury and Associations With Inpatient Mortality.

Firearm-related penetrating traumatic brain injury (pTBI) carries a high mortality risk and grim prognosis. This study aimed to quantify interhospital variation in operative intervention for this patient population and assess whether cranial surgery tendency is associated with inpatient mortality. We conducted a retrospective cohort study using the American College of Surgeons Trauma Quality Improvement Program (TQIP) data set to identify adult patients presenting with firearm-related pTBI. Risk-adjusted hierarchical regression evaluated associations with cranial surgery. Hospitals were stratified into quartiles based on surgical tendency (lowest, quartile 1; highest, quartile 4 [Q4]). Propensity score matching was performed across quartiles, and a multivariable regression model was constructed to investigate associations between hospital quartile and inpatient mortality. Effect modification by pupillary reactivity was tested. Cranial surgery rates for 4895 patients (median age, 31 years) varied widely across 309 hospitals (0%-71%; median, 21%; median odds ratio, 1.33). After matching, treatment at Q4 hospitals was associated with significantly reduced odds of mortality compared with treatment at quartile 1 hospitals (odds ratio, 0.61; 95% CI, 0.47-0.78). Patients presenting with one (interaction P = .03) or both (interaction P = .03) unreactive pupils experienced amplified survival benefits from treatment at Q4 hospitals. Substantial interhospital variation exists in operative intervention for firearm-related pTBI. Hospitals with higher surgical tendency were associated with improved survival, and this effect was amplified for patients presenting with unreactive pupils. These findings suggest a need to standardize operative decision-making for patients with firearm-related pTBI, aligning with ongoing efforts by organizations such as the Brain Trauma Foundation.

Does the Presence of Preoperative Myelomalacia Impact Outcomes Following ACDF?

Retrospective cohort. To compare outcomes after ACDF amongst patients with versus without preoperative myelomalacia. Evidence correlating preoperative myelomalacia with postoperative patient-reported outcome measures (PROMs) after anterior cervical discectomy and fusion (ACDF) is limited. Patients who underwent primary, elective ACDF for myelopathy with 1-year follow-up were included. PROMs were collected at 3/6/12 months, including: Modified Japanese Orthopaedic Association (mJOA), Neck Disability Index (NDI), Visual Analog Scale (VAS) Neck and Arm, and SF-12 Physical (PCS) and Mental (MCS) Component Summary. Preoperative myelomalacia was identified via keyword search and manual chart review. Myelomalacia and non-myelomalacia groups were compared on bivariable and multivariable analyses. A sub-analysis was performed comparing outcomes between single versus multilevel myelomalacia. 518 patients were included (163 with myelomalacia). Groups were similar for MCS and mJOA at all time points. Myelomalacia patients demonstrated lower VAS neck scores at 1 year (2.11±2.32 vs. 2.58±2.40, P=0.034), less common achievement of MCID for 1-year NDI (48.5% vs. 60.3%, P=0.015), and improved 1-year PCS scores (40.2±11.7 vs. 37.8±10.8, P=0.024). Multivariable regression demonstrated that MCID for mJOA and NDI was predicted only by preoperative PROM scores and/or demographic variables. Patients with 2+ levels of myelomalacia had worse preoperative mJOA scores (12.3±3⊡66 vs. 14.3±3⊡25, P=0.008) but more common achievement of MCID at 3 months (78.6% vs. 41.7%, P=0.042) when compared to those with single-level myelomalacia. However, multivariate analyses demonstrated that only higher preoperative mJOA independently decreased 3-month mJOA improvement (estimate: -0.54, P=0.011 for 3mo and estimate: -0.73, P<0.001 for 1y). Myelomalacia was associated with similar mJOA improvement but less NDI improvement, which was attributable to smoking status and less severe baseline disease. Multisegmental myelomalacia correlated with worse baseline mJOA, but only preoperative mJOA impacted mJOA improvement on multivariable analysis. Myelomalacia alone does not appear to negatively impact PROMs after ACDF for myelopathy.

Association between stress hyperglycemia ratio and diabetic retinopathy progression and surgical prognosis: insights from NHANES 2005-2018 and clinical cohort study.

Diabetic retinopathy (DR), a leading cause of vision loss in working-age adults, is strongly influenced by glycemic control. The stress hyperglycemia ratio (SHR), derived from admission glucose and HbA1c, has emerged as a potential predictor of adverse outcomes, yet its link to DR remains unclear. This study aimed to explore the association between SHR and DR using the NHANES database, as well as its impact on recurrent vitreous hemorrhage (RVH) and neovascular glaucoma (NVG) following pars plana vitrectomy (PPV) in patients with proliferative diabetic retinopathy (PDR). First, the association between SHR and DR was evaluated using multivariable logistic regression analysis based on NHANES database (2005-2018), including 4539 eligible diabetic patients, of whom 968 had DR. Second, 250 eyes from 201 PDR patients undergoing PPV were retrospectively analyzed and divided into two groups by median preoperative SHR. Risk factors for complications were identified using multivariable logistic regression, and paired analyses compared SHR levels at complication onset versus initial PPV surgery. In the cross-sectional study based on the NHANES database, multivariate logistic regression revealed a significant positive association between SHR and DR risk after adjusting for all covariates (corrected OR = 1.65, 95% CI: 1.12-2.44; p = 0.014). In the retrospective cohort study, multivariable regression indicated that older age and higher fibrinogen levels were linked to increased postoperative complication risk (p < 0.01). Paired analyses demonstrated significantly higher SHR levels at complication onset compared to initial PPV surgery (p < 0.001). SHR was significantly and positively correlated with the incidence of DR. Furthermore, in individuals with PDR, elevation of SHR was closely associated with the occurrence of postoperative complications, suggesting that SHR may be a valuable marker for postoperative adverse events. These results indicate that SHR provides a new clinical basis for the early warning of DR and risk assessment of postoperative complications. Clinicaltrials.gov NCT05631054 Registered November 30, 2022 https//clinicaltrials.gov/study/NCT05631054.

Programmatic outcomes of adolescents in differentiated service delivery models in South Africa

Background: Adolescents living with HIV face barriers that impede adherence and retention. Differentiated service delivery (DSD) models aim to improve retention and viral suppression (VS), but there is limited programmatic evidence from South Africa on DSD outcomes. Objectives: This study aimed to measure 12 month retention and VS proportions in adolescents enrolled in DSD and clinic-based care, and measure the association between 12 month retention, VS and covariates. Method: A retrospective cohort study was conducted in the Mopani District, Limpopo province, using TIER.Net data. The study included adolescents aged 10–19 years enrolled in DSD between 01 September 2019 and 30 September 2022, and those eligible for DSD with viral load &lt; 50 copies/mL. The study measured 12-month retention and VS proportions. Multivariable logistic regression measured association among 12-month retention, VS and exposure variables. Results: A total of 646 adolescents in DSD and 1282 in clinic-based care were included. Twelve-month retention was 92.7% (599/646) in DSD and 89.0% (1141/1282) in clinic-based care. There was no association between 12-month retention and being enrolled in DSD versus clinic-based care. Twelve-month VS (&lt; 50 copies/mL) was 63.5% (251/395) in DSD, compared to clinic-based care 51.0% (494/969). In multivariable regression, being on DSD was associated with higher VS at &lt; 50 copies/mL (Adjusted Odds Ratio [AOR] 1.6; 95% confidence interval: 1.2–2.1; p &lt; 0.001) than clinic-based care. Conclusion: Differentiated service delivery improved VS in adolescents in a rural setting and should be prioritised to improve outcomes.

Prognostic value of the pre-treatment albumin-to-alkaline phosphatase ratio in patients with lower-grade glioma: a propensity score matching study

Introduction:The albumin-to-alkaline phosphatase ratio (AAPR) has recently emerged as a novel prognostic biomarker in various solid tumors. However, its clinical value in lower-grade glioma (LGG) remains unclear.Methods:We performed propensity score matching (PSM) to balance baseline characteristics between groups. Restricted cubic spline (RCS) analysis was used to evaluate the nonlinear relationship between AAPR and survival outcomes. Survival differences were assessed using Kaplan–Meier analysis, and both univariate and multivariate Cox regression models were applied to identify independent prognostic factors. Finally, a predictive nomogram was developed to estimate 1-, 3-, and 5-year overall survival.Results:RCS analysis revealed a nonlinear relationship between AAPR and OS (p = 0.0349). Patients were stratified by the median AAPR value (0.704), and those in the AAPR-High group (≥0.704) had significantly better OS (log-rank p = 0.0042) and progression-free survival (PFS) (log-rank p = 0.042) than those in the AAPR-Low group. AAPR showed stronger prognostic value in low-risk subgroups. Higher AAPR was significantly associated with better OS in univariate (p = 0.005, HR = 0.541, 95% CI: 0.353–0.829) and multivariate Cox analyses (p = 0.046, HR = 0.630, 95% CI: 0.400–0.993). The AAPR-based nomogram demonstrated good predictive performance for 1-, 3-, and 5-year OS, validated in the PSM cohort.Discussion:Pre-treatment AAPR is a simple, non-invasive, and effective biomarker for predicting prognosis in LGG patients, particularly those at lower clinical risk.

Treatment Persistence in Rheumatoid Arthritis Before and After Etanercept Biosimilar Introduction: A Nationwide Australian Real-World Study.

Australia has one of the highest rates of rheumatoid arthritis (RA) worldwide. Etanercept, a widely used biologic for severe RA, has had a publicly subsidised biosimilar available in Australia since 2017. However, real-world data on how biosimilar availability has affected treatment patterns remain limited. This study aimed to assess treatment persistence-a surrogate measure of long-term treatment effectiveness-with etanercept before and after public subsidy of its biosimilar for RA, utilising a national sample. This retrospective cohort study analysed national healthcare claims data from the Pharmaceutical Benefits Scheme (PBS) via the Australian Bureau of Statistics DataLab. Adults (age ≥18 years) initiating etanercept for severe RA were stratified into two cohorts: historical (before biosimilar PBS listing, comprising only originator users) and contemporary (after biosimilar PBS listing, comprising both biosimilar and originator users). Kaplan-Meier analysis and multivariate Cox regression were employed to assess treatment persistence. Subgroup analysis of older adults and sensitivity analysis limited to biologic-naïve individuals were also performed. A total of 10,234 individuals initiating etanercept for severe RA were included, with 4461 in the historical cohort and 5773 in the contemporary cohort. The median time to treatment discontinuation was 10.0 months (95% confidence interval (CI) 9.7-10.6) in the contemporary cohort and 10.6 months (95% CI 10.0-11.4) in the historical cohort (p = 0.08). At 12 and 24 months, treatment retention rates were similar between cohorts. The adjusted hazard ratio for treatment discontinuation in the contemporary cohort was 1.00 (95% CI 0.96-1.05), indicating no significant differences. Subgroup and sensitivity analyses yielded similar results. This large, population-based study found no significant difference in treatment persistence following the introduction of the etanercept biosimilar in Australia. These findings support the real-world integration of biosimilars into routine care. Further research should include direct comparative analyses of originator and biosimilars to inform long-term treatment strategies, clinician confidence, and sustainable healthcare policy.

Characterization of lactylation modification subtypes and the promoting role of CCL20 in hepatocellular carcinoma progression

BackgroundHepatocellular carcinoma (HCC) is a highly aggressive and deadly malignancy. Early identification of prognostic risk factors is crucial for guiding clinical management and improving patient outcomes. Lactylation modification plays a pivotal role in tumorigenesis, yet the regulatory mechanisms and prognostic significance of lactylation-related genes in HCC remain insufficiently understood.MethodsThis study screened for prognostically significant lactylation modification-related genes based on their expression levels, integrated with DFS, PFS, and OS data. HCC patients were stratified into three distinct lactylation modification subtypes (C1, C2, C3) using the NMF algorithm. Differentially expressed genes across the three subtypes were identified through an intersection analysis. A lactylation modification-related prognostic model was subsequently constructed using LASSO-Cox and multivariate Cox regression analyses. The CIBERSORT algorithm was utilized to analyze immune cell infiltration. Functional validation of the lactylation-related gene CCL20 in HCC was conducted through in vitro experiments using HCC cell lines.ResultsWe identified three distinct lactylation modification patterns, with higher lactylation modification levels correlating with worse prognosis in HCC. A six-gene lactylation modification-based prognostic model (LRPS), including FAM83D, ENO1, PFN2, LCAT, PTGR1, and CCL20, was constructed and validated. Overall survival was markedly reduced in the high LRPS group relative to the low LRPS group. The high LRPS group also showed a significantly higher frequency of TP53 mutations. Correlation analysis of immune cell infiltration revealed a significant association between LRPS and the infiltration abundance of M0 macrophages, Tregs, and neutrophils, suggesting that lactylation modification may influence the tumor immune microenvironment. Overexpression of CCL20 in HCC cells significantly enhanced their proliferative and migratory capacities, indicating a key role for CCL20 in HCC progression.ConclusionThis study established a lactylation modification-based prognostic model that accurately forecasts outcomes in HCC patients. This risk score showed a significant correlation with glucose metabolism and reflected immune cell infiltration patterns. The core model gene, CCL20, promotes HCC cell proliferation and migration, supporting its potential as a valuable prognostic biomarker and a therapeutic target for HCC.

Bioinformatics-based analysis of the relationship between STC1 expression and immune infiltration in gastric cancer

ObjectiveThe study assessed the expression of STC1, and its potential as an immunotherapy target in gastric cancer (GC).MethodsRNAseq data from the TCGA_STAD project and TCGA-GTEx project of UCSC XENA website and microarray data from GEO (GSE66229) were downloaded. Differential STC1 mRNA expression between GC and non-carcinoma tissues was examined. Its relation to clinicopathological characteristics and prognosis was evaluated using univariate and multivariate Cox regression. Tumor infiltrating immune cells (TIICs) in the tumor microenvironment (TME) were assessed by ssGSEA, and T-cell exhaustion by TIMER. Single-cell RNA sequencing (scRNA-seq) analysis was performed to validate the correlation between STC1 expression and T-cell exhaustion markers. Gene Set Enrichment Analysis (GSEA) was also conducted to explore potential functions of STC1 in GC.ResultsSTC1 expression was significantly higher in GC tissues and independently predicted poor overall survival. STC1 expression was related to patient T-stage, location, and overall survival events. Immune infiltration analysis showed significant associations between STC1 and multiple immune cells in TME, with strong links to T-cell exhaustion. scRNA-seq analysis confirmed the co-expression of STC1 with T-cell exhaustion markers in specific cell clusters. GSEA identified several signaling pathways, such as “SIGNALING_BY_INTERLEUKINS” and “JAK_STAT_SIGNALING_PATHWAY,” linked to STC1 expression in GC.ConclusionSTC1 is a promising target for immunotherapy in GC, as its expression is correlated with patient prognosis, immune infiltration, and T-cell exhaustion.