Category: Statistics

Neurology. 2025 Nov 25;105(10):e214321. doi: 10.1212/WNL.0000000000214321. Epub 2025 Oct 29.

ABSTRACT

BACKGROUND AND OBJECTIVES: X-linked adrenoleukodystrophy (ALD) is the most common leukodystrophy with an incidence of 1:15,000 births. Newborn screening has enabled widespread use of serial brain MRI scans for early detection and treatment of cerebral ALD (cALD). Differentiating early cALD lesions from incidental findings remains challenging. We sought to characterize incidental MRI findings during cALD surveillance and describe features that may help distinguish them from early cALD lesions.

METHODS: MRI reports from boys with ALD followed at the Lucile Packard Children’s Hospital and Weill Cornell Medicine from 2012 to 2023 were reviewed. Inclusion criteria were boys with ALD who had at least 1 presymptomatic MRI before the age of 12 and no neurologic symptoms. We analyzed narrative content of available MRI reports, manually verified definite cALD lesions, and classified all other findings as incidental.

RESULTS: Our study included 69 boys with ALD (median age of 6.9 years, interquartile range 4.0-9.5),, with a total of 390 MRI reports reviewed. Participants had either pathogenic ABCD1 variants (45%, n = 31), likely pathogenic variants (9%, n = 6), variants of uncertain significance (39%, n = 27), or a positive family history with confirmatory biochemical testing (7%, n = 5). During surveillance, 11% (n = 8) developed cALD lesions with classical cALD neuroimaging features. Incidental findings were common (74%, n = 51). The most frequent incidental findings included punctate T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities in the frontal lobe (29%, n = 20), abnormal T2/FLAIR signal in the periatrial or periventricular white matter (19%, n = 13), prominent perivascular spaces (17%, n = 12), T2/FLAIR hyperintensities in non-frontal lobe regions (14%, n = 10), delayed myelination (14%, n = 10), and stable curvilinear T2/FLAIR hyperintensity in the splenium or genu (13%, n = 9), with the latter requiring follow-up imaging to distinguish from cALD. Only 23% (n = 16) had neither cALD nor incidental findings reported across all time points. Incidental findings were neither statistically associated with genotype classification nor predictive of cALD.

DISCUSSION: Incidental findings were commonly reported during cALD surveillance, possibly reflecting radiologists’ intent to differentiate them from cALD. Incidental findings were distinguishable from true cALD lesions based on anatomic location, stability over time, and persistent absence of contrast enhancement. Our findings provide a practical framework for differentiating incidental findings from cALD lesions during surveillance.

PMID:41160796 | DOI:10.1212/WNL.0000000000214321

Neurology. 2025 Nov 25;105(10):e214310. doi: 10.1212/WNL.0000000000214310. Epub 2025 Oct 29.

ABSTRACT

BACKGROUND AND OBJECTIVES: Prospective cohort studies have demonstrated elevated risks of incident dementia in patients with essential tremor (ET). The explanation for this enhanced risk of dementia in ET is unknown. We aimed to elucidate the underlying neuropathologic features of ET-dementia.

METHODS: In a 10-year, prospective cohort study of cognition in ET, we followed participants with detailed neuropsychological testing (assessing 5 primary domains) and assigned cognitive diagnoses (normal cognition, mild cognitive impairment [MCI], or dementia) by expert consensus; brains were collected at death. Participants resided in 43 US states. The detailed neuropathologic assessment included a Braak neurofibrillary tangle stage, Braak Lewy pathology stage, Thal β-amyloid score, and neuritic plaque score. The overall level of Alzheimer disease neuropathologic changes (ADNCs) was reported using the “ABC” scale. Other tauopathies and comorbid cerebrovascular pathologies were diagnosed. During statistical comparisons, we stratified each of the above neuropathologic features into 2 categories: high vs low. We examined how neuropathologic findings mapped onto cognitive diagnoses.

RESULTS: The 381 participants yielded 86 brains (mean age at death 90.1 years, 55.8% female). Participants with ET-dementia (n = 40) had higher odds of having severe AD-type pathologies than ET-NC (n = 30): advanced Braak AD stage odds ratio (OR) = 22.8, Thal score OR = 8.0, Consortium to Establish a Registry for Alzheimer Disease score OR = 5.7, and ADNC score OR = 21.1; cerebral amyloid angiopathy scores were also higher (OR = 4.3) (all p ≤ 0.01). Participants with ET-MCI (n = 16) demonstrated intermediate neuropathology, with greater odds of higher Braak AD stages than those with ET-NC (OR = 8.0, p = 0.009). Other neuropathologies were similar across cognitive groups.

DISCUSSION: Our neuropathologic description of ET-dementia shows that, in this sample of 40 participants with ET-dementia, Alzheimer pathology is the prime driver of marked cognitive impairment in ET. Further studies are needed to refine our understanding of the nature of tau aggregation in ET and the extent to which this is similar to or diverges from that seen in AD. One implication of the current finding, which is a more direct link between ET and AD, is that this opens the door to blood-based biomarker testing in individuals with ET who are experiencing cognitive difficulties.

PMID:41160795 | DOI:10.1212/WNL.0000000000214310

Neurology. 2025 Nov 25;105(10):e214344. doi: 10.1212/WNL.0000000000214344. Epub 2025 Oct 29.

ABSTRACT

BACKGROUND AND OBJECTIVES: Higher mortality, relative to the general population, is associated with epilepsy and with particular types of traumatic brain injury (TBI). It is thus presumed that posttraumatic epilepsy (PTE), which indicates epilepsy after TBI, would have higher mortality relative to nontraumatic epilepsy (NTE). However, previous studies have not established a difference in mortality between PTE and NTE.

METHODS: We analyzed administrative data in the Veterans Health Administration to identify US military veterans diagnosed with epilepsy from 2005 to 2022 using previously validated criteria. PTE was defined as TBI documented in the 5 years before the epilepsy index date. TBIs were classified as skull/facial fracture, diffuse cerebral, focal cerebral, extracerebral, or concussion, based on International Classification of Diseases codes. Adjusted Kaplan-Meier survival curves and multivariable Cox proportional hazards models were fitted to compare mortality between PTE and NTE.

RESULTS: Among 210,182 veterans with epilepsy, 28,832 had PTE (mean onset age 52.6 years, 7.4% female) and 181,350 had NTE (mean onset age 60.9 years, 8.5% female). Mortality rate in PTE was higher compared with NTE and varied with the underlying TBI, being the highest with underlying diffuse cerebral injury (hazard ratio [HR] 1.17, 95% CI 1.07-1.28, p < 0.001), focal cerebral injury (HR 1.16, 95% CI 1.07-1.26, p < 0.001), or skull/facial fracture (HR 1.18, 95% CI 1.09-1.28, p < 0.001). However, underlying concussion had a mortality rate lower than all NTE combined (HR 0.91, 95% CI 0.86-0.95, p < 0.001). The relative mortality rate also varied with age at PTE onset, being the highest among young-onset PTE with extracerebral injury (HR 2.02, 95% CI 1.47-2.78, p < 0.001).

DISCUSSION: This study demonstrates that PTE leads to higher mortality compared with other forms of epilepsy, being up to 2 times higher in selected subgroups. The mechanism of underlying TBI influenced mortality rate. PTE after diffuse cerebral TBI, focal cerebral TBI, or skull/facial fractures led to higher mortality relative to NTE. Relative to NTE, young-onset PTE had the greatest rate of mortality. These results show that the age of PTE onset and the TBI precipitating PTE influence mortality and are relevant to consider in clinical practice. Future work should explore the reasons underlying higher mortality in PTE and refine TBI classification using additional data sources.

PMID:41160793 | DOI:10.1212/WNL.0000000000214344

JCO Glob Oncol. 2025 Oct;11:e2500311. doi: 10.1200/GO-25-00311. Epub 2025 Oct 29.

ABSTRACT

PURPOSE: Breast cancer (BC) is the most prevalent malignancy among women worldwide, with disparities in health care access and educational outreach, especially in low-resource settings. This study evaluates the impact of a structured 3-hour educational program for patients with newly diagnosed BC and their caregivers at the Breast Cancer Comprehensive Center, National Cancer Institute, Cairo University.

METHODS: A quasi-experimental pretest/post-test study was conducted between June and September 2024. Participants included 149 patients and 178 caregivers. The educational program covered BC risk factors, symptoms, diagnostic methods, treatment options, nutritional counseling, and psychological support using audiovisual and interactive techniques in the Colloquial Egyptian dialect. Pre- and postintervention knowledge assessments were conducted using validated questionnaires. Statistical analysis included paired t-tests and Wilcoxon signed-rank tests.

RESULTS: The educational program significantly improved knowledge scores across multiple domains (all P < .001). Symptom awareness improved from 5.8 (±1.8) to 7.5 (±0.82), misconception correction from 2.4 (±1.2) to 5.5 (±1.3), nutrition knowledge from 0.6 (±0.8) to 1.8 (±0.4), and self-examination awareness from 0.6 (±0.7) to 1.6 (±0.5). Caregivers’ knowledge scores increased from 6.2 (±2.2) to 9.1 (±1.6). In addition, 82.7% of participants had never performed breast self-examinations before the program, and 78.7% of patients were diagnosed coincidentally.

CONCLUSION: The educational program significantly improved BC knowledge among patients and caregivers. These findings highlight the need for structured education to promote earlier diagnosis and informed treatment decisions in low-resource settings.

PMID:41160783 | DOI:10.1200/GO-25-00311

JCO Glob Oncol. 2025 Oct;11:e2500390. doi: 10.1200/GO-25-00390. Epub 2025 Oct 29.

ABSTRACT

PURPOSE: Colonoscopy is a proven screening method for reducing mortality from colorectal cancer (CRC), the most frequently diagnosed cancer in Ukraine. To enhance colonoscopy quality, international societies have defined key performance measures (PMs). We aimed to evaluate adherence to these PMs among Ukrainian endoscopists and explore factors affecting screening colonoscopy quality.

METHODS: We conducted a cross-sectional study using a web-based survey among members of Ukraine’s endoscopy society EndoAcademy (Kyiv, Ukraine) (October-November 2023). The questionnaire assessed colonoscopy practices and adherence to globally recognized PMs, categorized as six calculated (requiring ongoing numerical data tracking) and six noncalculated (performed/not performed practices).

RESULTS: Of 540 invited endoscopists, 122 (22.6%) responded. The median number of adhered to quality PMs was 6 (IQR, 5-8), with noncalculated being reported more frequently: medians 4 (IQR, 4-5) versus 2 (IQR, 1-3), P < .01. Among noncalculated PMs, most common were postpolypectomy surveillance recommendations (98.4%, n = 120) and retrieval of removed polyps (96.7%, n = 118). For calculated PMs, cecal intubation (61.5%, n = 75) and adenoma detection (59.8%, n = 73) rates were most frequently reported. In multivariable analysis, adherence to each additional quality PM increased the odds of optimal polyp treatment (odds ratio [OR], 1.32 [95% CI, 1.03 to 1.70]), with photo/video recording (OR, 7.57 [95% CI, 1.66 to 34.49]) and adequate procedure time allocation (OR, 3.86 [95% CI, 1.18 to 12.61]) showing the strongest associations.

CONCLUSION: To our knowledge, this first national study of colonoscopy PMs in Ukraine highlights key documentation gaps and variation in polyp management. As the country implements a population-based CRC screening program, structured quality assurance, audit-and-feedback systems, and education grounded in international PMs will be critical to improving outcomes.

PMID:41160779 | DOI:10.1200/GO-25-00390

J Orthop Surg (Hong Kong). 2025 Sep-Dec;33(3):10225536251392628. doi: 10.1177/10225536251392628. Epub 2025 Oct 29.

ABSTRACT

ObjectiveThe feasibility of placing longer, larger diameter double-threaded screws into the pedicle for good fixation in osteoporotic patients with lumbar spondylolisthesis was investigated via robot-assisted optimal access planning.MethodA total of 80 patients with degenerative lumbar spondylolisthesis needed posterior incision decompression and bone grafting combined with pedicle screw fixation due to spondylolisthesis. The patients were equally and randomly assigned to a robot-assisted group and a bone cement-strengthened group. The operative time, intraoperative blood loss, and intraoperative radiation dose were recorded. X-ray and CT scans were routinely reviewed after the surgery. The ratio of screw diameter to pedicle width (SD/PW) was calculated. The pedicle position was graded. The Bub score assessed proximal facet joint invasion. Visual analogue pain scale (VAS) was recorded before surgery and 3 days after surgery. The Oswestry Disability Index (ODI) and health Survey Summary Form (SF-36 to assess patients’ quality of life) were performed before surgery and 6 months after surgery. The rate of screw loosening, removal, complications and revision were evaluated by X-ray and CT 12 months after operation.ResultsVAS score on day 3 after surgery was significantly better in the robot-assisted group than in the bone cement-strengthened group. (p = 0.027). The operative time and intraoperative radiation dose of the robot-assisted group were lower than those of the bone cement-strengthened group (p < 0.001). The ratios of screw length, screw diameter, and SD/PW in both groups were significantly better in the robot-assisted group than in the bone cement-strengthened group (p < 0.001). The incidence of screw small joint invasion was 10.2% in the robot-assisted group and 19.1% in the bone cement-strengthened group, with a statistically significant difference between the two (p = 0.020). The Oswestry Disability Index (ODI) and Health Survey Summary Form (SF-36) at 6 months after surgery were significantly improved in both groups.ConclusionPatients with osteoporotic lumbar spondylolisthesis who use robot assistance to implant longer, thicker-diameter double-threaded screws achieved a similar fixation effect as those of bone cement-reinforced screws. Meanwhile, the operation time was shorter, the radiation damage was less, and the difficulty of later revision surgery was reduced. Thus, the proposed surgical protocol can be applied as a new option for patients with osteoporotic lumbar spondylolisthesis.

PMID:41160758 | DOI:10.1177/10225536251392628

Dis Colon Rectum. 2025 Oct 29. doi: 10.1097/DCR.0000000000004002. Online ahead of print.

ABSTRACT

BACKGROUND: Although defunctioning stoma creation is routine during intersphincteric resection for low rectal cancer, it carries significant complication risks and necessitates reoperation for closure. Defunctioning stoma omission in intersphincteric resection could avoid these complications; however, its feasibility remains unproven.

OBJECTIVE: This study aims to compare Grade C anastomotic leakage and secondly evaluate postoperative complications and economic impact of stoma-free vs. defunctioning stoma-intersphincteric resection procedures.

DESIGN: A prospective non-randomized cohort design.

SETTING: This study was conducted at a single tertiary referral center.

PATIENTS: Patients diagnosed with low rectal cancer, scheduled for intersphincteric resection from 2023 to 2025, were recruited, with those who received neoadjuvant radiotherapy excluded. The cohort was stratified by stoma free vs defunctioning stoma, which was dependent on patient decision.

MAIN OUTCOME MEASURES: Grade C anastomotic leakage.

RESULTS: A total of 101 patients were enrolled in this study, with 79 and 22 patients in the stoma-free and defunctioning stoma cohorts, respectively. Baseline demographic characteristics, tumor profiles, and preoperative comorbidities showed no statistically significant intergroup differences. Intraoperative parameters, including lymph node yield [13.00 (IQR 10.00-17.00) vs. 14.50 (IQR 10.75-17.00), p = 0.59] and intraoperative blood loss [20.00 (IQR 20.00-50.00) vs. 30.00 (IQR 20.00-50.00) mL, p = 0.10], were similar. Within 30 days, safety outcomes were comparable: Grade C anastomotic leakage (1.3% vs. 4.5%, p = 0.39) and overall complications (Clavien-Dindo I-IV, p = 0.46). Notably, the stoma-free group had shorter hospital stays (5 days [IQR 4-6] vs. 6 days [IQR 5-9], p = 0.004) and lower hospitalization costs (CNY 29,598 [IQR 26,803-33,863] vs CNY 49,734 [IQR 36,731-65,018], p < 0.001).

LIMITATIONS: This study was conducted at a single tertiary referral center with a limited patient population.

CONCLUSIONS: Under standardized perioperative protocols, stoma-free intersphincteric resection surgery exhibits comparable Grade C leak rates to defunctioning stoma procedures, along with lower medical costs in patients with low rectal cancer without neoadjuvant radiotherapy. See Video Abstract.

PMID:41160071 | DOI:10.1097/DCR.0000000000004002

J Phys Chem B. 2025 Oct 29. doi: 10.1021/acs.jpcb.5c04908. Online ahead of print.

ABSTRACT

The accuracy of the MM/PBSA binding free energy calculation depends on both the employed force field and the statistical quality of sampling. However, the impact of sampling sufficiency has often been underestimated in previous studies. Here, we systematically analyze multiple protein-ligand systems using conventional and enhanced molecular dynamics simulations of different lengths. Our results show that short simulations may sometimes give the illusion of convergence while failing to capture slow conformational transitions that affect the computed free energies. Longer or enhanced simulations can reveal these hidden motions but do not always improve agreement with experiments, indicating that force-field limitations may dominate once statistical convergence is achieved. From a theoretical perspective, sufficient sampling is the fundamental requirement for converging thermodynamic quantities such as ΔΔG, independent of the simulation length. Practically, the degree of sampling sufficiency depends on system-specific dynamics and research goals. This work highlights the importance of recognizing sampling sufficiency as a statistical prerequisite rather than equating it with long simulations and calls for more adaptive strategies to balance efficiency and reliability in MM/PBSA analyses.

PMID:41160056 | DOI:10.1021/acs.jpcb.5c04908

Acta Anaesthesiol Scand. 2026 Jan;70(1):e70137. doi: 10.1111/aas.70137.

ABSTRACT

BACKGROUND: The ratio of arterial oxygen partial pressure to fraction of inspired oxygen (PaO₂/FiO₂, hereafter P/F ratio) is a key component of the Sequential Organ Failure Assessment (SOFA) score. It reflects the severity of hypoxaemic respiratory failure. The ongoing revision of the SOFA score requires data-driven cutoffs for P/F ratio as well as rational criteria for respiratory support. In this study, we aimed to determine the optimal P/F ratio cutoffs for determining respiratory failure categories in the revised SOFA score and examined whether advanced respiratory support should be a prerequisite for the most severe categories.

METHODS: We used the database of the intensive care unit of Kuopio University Hospital, Finland, for cutoff derivation and the eICU database, a multicenter U.S. intensive care registry, for external validation. We identified cutoffs most discriminative for hospital mortality using the log-rank statistic test with the Contal and O’Quigley method. In external validation, these cutoffs were compared with those in the current respiratory SOFA score.

RESULTS: Optimal cutoffs were identified as follows: P/F ratio > 40 kPa (normal), 30-40 kPa (mild impairment), 20-30 kPa (moderate impairment), 10-20 kPa (severe impairment), and ≤ 10 kPa (critical impairment). These cutoffs resulted in clear separation of the severity categories (chi-square for log-rank statistic 356.9). They outperformed the current respiratory SOFA score cutoffs in the validation cohort (AUROC 0.615, 95% CI 0.607-0.622 vs. AUROC 0.610, 95% CI 0.603-0.618, p < 0.001). Advanced respiratory support was associated with higher mortality, but its inclusion as a prerequisite improved discrimination only in the moderately impaired respiratory function category, not in the severely or critically impaired categories.

CONCLUSION: P/F ratio cutoffs using 10 kPa (75 mmHg) intervals were identified to be optimal for distinguishing stages of respiratory failure severity. The impact of respiratory support on P/F ratio-mortality associations suggests the need to calibrate any P/F ratio-based score by support level, but optimal calibration methods require further study.

EDITORIAL COMMENT: In this study, the cut-off values for the partial pressure of arterial oxygen to the fraction of inspired oxygen (P/F ratio) were investigated in a large Finnish intensive care database and validated externally with the US intensive care registry. The aim was to support a revision of the cut-off values for the P/F ratio in the Sequential Organ Failure Assessment (SOFA) score. The results showed that incremental changes in the P/F ratio of 10 kPa are better than 13 kPa and emphasize the need for critical assessment of the current SOFA score.

PMID:41160043 | DOI:10.1111/aas.70137

JAMA Dermatol. 2025 Oct 29. doi: 10.1001/jamadermatol.2025.4161. Online ahead of print.

ABSTRACT

IMPORTANCE: Dermatomyositis (DM) is associated with increased rates of hospitalization and mortality. However, characteristics present at the time of admission that are associated with in-hospital mortality remain poorly defined in the US.

OBJECTIVE: To evaluate whether features of DM present at admission, including active rash and muscle disease, interstitial lung disease (ILD), elevated neutrophil to lymphocyte ratio (NLR), myositis-specific autoantibody status, and baseline treatment regimens, are associated with in-hospital mortality among patients admitted with DM.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included adults with pre-existing DM (confirmed by documentation by a dermatologist or rheumatologist) who were admitted for any cause at a single tertiary referral center from January 2013 to May 2024. Data were analyzed from August 2024 to August 2025.

EXPOSURES: Clinical, serologic, and laboratory features of DM at the time of admission as well as baseline treatment prior to hospitalization.

MAIN OUTCOMES AND MEASURES: The primary outcome was in-hospital mortality. Statistical analyses included descriptive statistics and multivariable logistic regression with the Firth correction, adjusting for demographics and DM subtype. Bonferroni correction was applied to control for multiple comparisons.

RESULTS: Among 153 patients with DM (113 females [73.9%]; mean [SD] age, 56.5 [14.3] years), 16 (10.5%) died during hospitalization. Deceased patients were more likely than survivors to have active rash (13 of 16 [81.3%] vs 47 of 137 [34.3%]), ILD (14 of 16 [87.5%] vs 57 of 137 [41.6%]), and elevated NLR (mean [SD], 12.5 [7.43] vs 4.90 [3.82]). Myositis prevalence did not differ significantly between deceased patients and survivors. In multivariable analysis, active rash (odds ratio [OR], 12.13; 95% CI, 3.18-46.28; P = .003), ILD (OR, 6.43; 95% CI, 1.78-23.13; P = .04), and NLR (OR per 1-unit increase, 1.29 [95% CI, 1.16-1.44]; P < .001) were independently associated with mortality. No association with baseline intravenous immunoglobulin use was observed among patients who died after Bonferroni correction.

CONCLUSIONS AND RELEVANCE: In this study, active rash, ILD, and elevated NLR were independently associated with in-hospital mortality in patients with DM, regardless of disease subtype or myositis-specific autoantibody status. Recognizing these high-risk features may guide inpatient management and support future risk stratification strategies.

PMID:41160039 | DOI:10.1001/jamadermatol.2025.4161