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PubMed1996

Phylogeny of ticks (Ixodida) inferred from nuclear ribosomal DNA.

Phylogenetic relationships of 9 species of ticks were inferred from nucleotide sequences of the D1 domain of large subunit ribosomal DNA (rDNA), the V4 region of small subunit rDNA and sequences immediately adjacent to these regions. Six of the 7 subfamilies in the Argasidae and Ixodidae were represented: Ornithodorinae and Argasinae from the Argasidae (soft ticks); and Ixodinae, Amblyomminae, Haemaphysalinae and Rhipicephalinae from the Ixodidae (hard ticks). A mite, Phytoseiulus persimilis, from the Mesostigmata, the putative sister group of the Ixodida, was used for out-group reference. Our sequence alignment, which contained the D1, V4 and adjacent sequences, comprised 503 sites; 209 of these varied among the species studied and 77 were phylogenetically informative, i.e. at least 2 different nucleotides were represented at least twice. This alignment was subjected to maximum parsimony, genetic distance and maximum likelihood analyses. We found strong support in bootstrap resampling experiments for the following relationships: (i) monophyly of the 7 species of Ixodidae (98-100% support); (ii) monophyly of the 2 species of Amblyomma (93-99%); (iii) monophyly of the 6 species of Metastriata (96-99%); (iv) a sister-group relationship between Ixodes pilosus and the 6 species of Metastriata (98-100%); and (v) a sister-group relationship between Ornithodoros capensis (Ornithodorinae) and the 7 species of Ixodidae (94-99% support). The last result may be preliminary evidence that the Argasidae family (soft ticks) is paraphyletic since the 2 argasid species did not form a monophyletic group. The paraphyletic status of the Argasidae has been previously suggested by Black & Piesman (1994; Proceedings of the National Academy of Sciences U.S.A. 91: 10034). Our study indicates that the D1, V4 and adjacent sequences may be used to answer long-standing questions about the phylogeny of the Ixodida.

Animals↗
PubMed2006

Reduced 6-month resource use and costs associated with cilostazol in patients after successful coronary stent implantation: results from the Cilostazol for RESTenosis (CREST) trial.

BACKGROUND: The CREST trial demonstrated that after successful coronary stent implantation, the 6-month rate of target vessel revascularization (TVR) was similar (15.4% vs 16%, P = .90) for the 2 treatment groups, but restenosis rate was lower (22.0% vs 34.5%, P = .002) in cilostazol-treated patients. We sought to evaluate resource use, cost, and cost-effectiveness of cilostazol in CREST. METHODS: A total of 705 patients were randomized to cilostazol 100 mg twice daily (n = 354) versus placebo (n = 351) for 6 months. Resources included rehospitalizations, medications, and outpatient services. Costs were determined from the Medicare fee schedule. Cilostazol was priced at 1.64 dollars a day. Base-case cost and cost-effectiveness analysis was performed for the entire population using TVR as a measure of effectiveness. Sensitivity analysis was conducted among 526 patients because restenosis data were available only for this patient population. A bootstrap resample approach (5000 samples) was used to obtain confidence intervals for cost differences. RESULTS: For the entire population, costs of rehospitalizations, concomitant medications, outpatient tests, and physician or emergency department visits were lower during follow-up for cilostazol-treated patients. Overall, total 6-month follow-up costs remained 447 dollars lower for cilostazol (4178 dollars vs 4625 dollars), although this difference did not reach significance (95% CI -1458 dollars to 515 dollars). Cilostazol is likely a cost-saving strategy (similar rate of TVR and lower costs). Sensitivity analysis showed that cilostazol is likely a dominant strategy (lower restenosis rate and costs, 85% dominant, 88.9% <1000 dollars per restenosis averted). CONCLUSIONS: Treatment with cilostazol is likely a cost-saving or dominant strategy in patients with successful coronary bare metal stent implantation. Cilostazol may offer a low-cost alternative to restenosis prevention in patients who do not receive drug-eluting stents.

Adult↗
PubMed2004

Use of a scoring model combining clinical, exercise test, and echocardiographic data to predict mortality in patients with known or suspected coronary artery disease.

The aim of this study was to derive and validate a model for predicting mortality by combining clinical, exercise testing, and echocardiographic data in patients with known or suspected coronary artery disease. We studied 5,679 patients (aged 62 +/- 12 years; 3,231 men) who were followed for a mean of 3 years after treadmill exercise echocardiography. Patients were randomly divided into 2 groups of equal size. (1) The modeling group underwent multivariate analysis to define independent predictors of mortality. Three hundred bootstrap resamplings were performed to determine parameter coefficients. Patients were divided into 5 risk categories according to their composite score and survival rate in each category was estimated by the Kaplan-Meier method. (2) The validation group comprised patients for whom the risk model was applied. Patients were divided into 5 risk categories based on data obtained from the modeling group. During follow-up, 315 patients died (151 in the modeling group). Independent predictors of mortality were exercise wall motion score index (chi-square 22.4, p <0.0001), workload (chi-square 17.1, p <0.0001), male gender (chi-square 15.4, p <0.0001), and age (chi-square 5.5, RR 1.02, 95% confidence interval 1 to 1.04; p = 0.02). Application of the composite score in the validation group resulted in an effective stratification of patients for mortality and cardiac events. This study provides a model for assessing risk of death by combining clinical, exercise testing, and echocardiographic data using a single composite score.

Coronary Artery Disease↗
PubMed2026

Protamine gene expression is associated with sperm motility in rams: An integrative experimental and gene network analysis.

Protamine 1 (PRM1) and protamine 2 (PRM2) are essential regulators of sperm chromatin condensation and genome integrity, and their dysregulation has been associated with impaired male fertility. However, their role in rams remains insufficiently characterized. This study investigated the relationship between protamine gene expression and semen quality in rams and explored their potential upstream regulatory mechanisms using gene regulatory network (GRN) analysis. Fifteen ejaculates from five rams were analyzed. Based on total sperm motility using computer-assisted sperm analysis (CASA), ejaculates were classified into a high-motility group (n&#x202f;=&#x202f;8) and a low-motility group (n&#x202f;=&#x202f;7). PRM1 and PRM2 expression levels were quantified by RT-qPCR. Following normality confirmation (p&#x202f;>&#x202f;0.05), parametric tests were applied using the ejaculate as the biological experimental unit. Samples with reduced motility showed significantly lower expression of both protamines (p&#x202f;<&#x202f;0.01). Moreover, progressive sperm motility was strongly correlated with both PRM1 (r&#x202f;=&#x202f;0.71, p&#x202f;=&#x202f;0.019) and PRM2 (r&#x202f;=&#x202f;0.69, p&#x202f;=&#x202f;0.03) transcript levels. Cross-species GRN inference using scGeneRAI and a reference human spermatogenesis dataset identified several hypothesis-generating candidate transcription factors, including HMGB4, HMGB1, H2AFZ, NKX6-1, and SMC3, consistently supported across multiple bootstrap resampling runs. These findings demonstrate a strong association between protamine expression and sperm motility in rams. While the identified candidate regulators provide a valuable framework for future species-specific validation, they also highlight promising candidate molecular biomarkers of male fertility in livestock.

Gene regulatory networks↗
PubMed2007

Tumour volume and high grade tumour volume are the best predictors of pathologic stage and biochemical recurrence after radical prostatectomy.

INTRODUCTION: Our goal was to examine to what extent tumour volume (TV) and percentage of high grade tumour volume (%HGTV) affect the rate of positive surgical margins and the rate of biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: TV and %HGTV were routinely planimetrically quantified in a cohort of 780 consecutive patients. Mean follow-up was 46.7 months. Multivariable regression models addressed two separate endpoints: positive surgical margins and biochemical recurrence. The increase in model predictive accuracy related to the addition of TV and %HGTV to radical prostatectomy stage and grade was assessed, after 200 bootstrap resamples to reduce overfit bias. RESULTS: In multivariable logistic regression models addressing positive surgical margins rate, predictive accuracy increased by 1.9% (p<0.001) when TV was added to other covariates. No further increment was noted when %HGTV was added (p=0.3). In multivariable Cox regression models addressing biochemical recurrence, accuracy increased by 0.6% (p=0.002) when TV was added and an additional increase of 0.7% was recorded when %HGTV (p<0.001) was added. CONCLUSION: Tumour bulk reflected by TV affects local cancer control rate, which is reflected in the rate of positive surgical margins. Conversely, high grade cancer determines the rate of biochemical recurrence. These two variables represent the most powerful predictors of cancer control in men treated for localised prostate cancer. Moreover, they increase the ability of established predictors to predict the outcomes of interest. In consequence, they warrant consideration in future predictive and prognostic tools.

Adult↗
PubMed2004

A model for the internal evaluation of the quality of care after lung resection in the elderly.

OBJECTIVES: The objective of this study was to develop a logistic model for internal audit in a population of elderly patients submitted to lung resection. METHODS: Three hundred twenty-six patients older than 70 years of age and submitted to lung resection for lung carcinoma were retrospectively analyzed. Univariate and logistic regression analyses yielded a model for the prediction of postoperative complications that was validated by bootstrap resampling analysis. The model was then used to assess the performance of our unit during two successive periods of activity ('early', 1993-1999; 'late', 2000-2003). RESULTS: Significant independent predictors of postoperative complications were a low ppoFEV1 (P < 0.0001) the presence of concomitant cardiac disease (P = 0.01) and extended resection (P = 0.03). The observed morbidity rate in the late period was higher than that in the early period (48.3 vs. 33.8%; P = 0.008). The predicted morbidity rate was also higher in the late period, compared to that in the early period (44 vs. 39%; P = 0.003). Moreover, no differences were noted between predicted and observed morbidity rates in each of the two periods (early, P = 0.4 late, P = 0.5). CONCLUSIONS: We showed that applying a model of risk-adjustment in elderly patients submitted to lung resection was useful for the internal evaluation of the quality of care and prevented misleading information derived by the comparison of the crude rates of the observed morbidity.

Aged↗
PubMed2006

A nomogram for staging of exclusive nonobturator lymph node metastases in men with localized prostate cancer.

OBJECTIVES: Some patients with localized prostate cancer are at risk of nonobturator lymph node invasion (NOLNI) and may require an extended pelvic lymph node dissection (ePLND). We explored the rate of exclusive NOLNI and developed a nomogram to predict it. MATERIAL AND METHODS: We mapped all ePLND specimens according to their anatomic location (obturator, external iliac, internal iliac lymph nodes) and assessed the location-specific rate of LNI in 565 patients. A multivariate logistic regression-based nomogram predicting NOLNI was then internally validated with 200 bootstrap resamples. RESULTS: Overall, 11.1% (63 of 565) had LNI and 21 (3.7%) had exclusive NOLNI. The nomogram predicting exclusive NOLNI was 80.2% accurate. The nomogram's negative predictive value was 99%, when it predicted 0-10% probability of NOLNI. This approach could allow the omission of an ePLND in 350 of 565 (61.9%) patients and still correctly stage 85.8% of NOLNI cases. CONCLUSIONS: Our nomogram-based approach offers the possibility of identifying men who are at virtually zero risk of exclusive NOLNI. In these men, an ePLND may be safely avoided.

Adult↗
PubMed2006

Precystectomy nomogram for prediction of advanced bladder cancer stage.

OBJECTIVE: To evaluate precystectomy prediction of pT and pN stages at cystectomy. METHODS: Multivariate logistic regression analyses modelled variables of 726 evaluable patients treated with radical cystectomy and bilateral pelvic lymphadenectomy. The first set of models predicted pT(3-4) stage at cystectomy, and the second set predicted pN(1-3) stages at cystectomy. Transurethral resection (TUR) predictors consisted of 2002 T stage, 1973 WHO tumour grade, presence of carcinoma in situ, age, gender, and delivery of neo-adjuvant chemotherapy. The area under the ROC curve quantified nomogram accuracy. Two hundred bootstrap resamples were used to reduce overfit bias. RESULTS: At TUR, 11% of patients were staged as pT(3-4) versus 42% at cystectomy. Lymph node metastases were found in 24% of patients at cystectomy (pN(1-3)). The multivariate pT(3-4) nomogram was 75.7% accurate versus 71.4% for TUR T stage. The multivariate pN(1-3) nomogram was 63.1% accurate versus 61.0% for TUR T stage. CONCLUSION: Multivariate nomograms are not perfect, but they do predict more accurately than TUR T stage alone.

Adult↗
PubMed2006

Development and external validation of an extended 10-core biopsy nomogram.

OBJECTIVES: To test the accuracy of a previously externally validated sextant biopsy nomogram in referred men exposed to > or =10 or more biopsy cores. Moreover, we explored the hypothesis that a more accurate predictive tool could be developed. METHODS: Previous nomogram predictors (age, digital rectal examination, prostate-specific antigen, and percent free PSA) were used to assess the accuracy of our previous nomogram in a cohort consisting of 2900 men referred for prostatic evaluation. Moreover, these variables were complemented with sampling density (SD) (i.e., ratio of gland volume and the number of planned biopsy cores) within multivariable logistic regression models (LRM) predicting presence of prostate cancer (pCA) on the initial 10 or more core biopsy. The LRMs were used to develop and internally validate (200 bootstrap resamples) a new nomogram in 1162 men from Hamburg, Germany. The LRMs' external validity was tested in three separate cohorts (Hamburg, n=582; Milan, n=961; Seattle, n=195). RESULTS: The contemporary external validation of the previously validated sextant nomogram demonstrated 70% accuracy. Internal validation of the new nomogram demonstrated 77% accuracy, and external cohorts demonstrated 73-76% accuracy. CONCLUSIONS: In the era of extended biopsy schemes, previously developed predictive models are less accurate in predicting the probability of pCA on initial biopsy. We developed a new tool that allows obtaining more accurate predictions. Moreover, before biopsy, it also allows defining the ideal ratio between gland volume and the number of planned biopsy cores that would yield the ideal biopsy rate.

Adult↗
PubMed2006

Prediction of pathological stage is inaccurate in men with PSA values above 20 ng/mL.

INTRODUCTION: We hypothesized that either very low (0-2.5 ng/mL) or very high (>20 ng/mL) PSA values may limit the accuracy of pathological stage predictions. To test this hypothesis, we examined 5193 consecutive patients subjected to radical prostatectomy (RP) for localized prostate cancer (PCa). MATERIAL AND METHODS: Patients were divided into three cohorts according to their pre-treatment PSA value: </=2.5 (n=331), 2.51-20 (n=4545) and >20 ng/mL (n=317). Subsequently in each cohort, the ability of PSA, clinical stage and biopsy Gleason sum was tested in multivariable logistic regression models predicting three separate endpoints: extracapsular extension (ECE), seminal vesicle invasion (SVI) and lymph node invasion (LNI). Predictive accuracy represented the performance benchmark. All models were adjusted for year of surgery and subjected to 200 bootstrap resamples to reduce overfit bias. RESULTS: For PSA </=2.5 ng/mL, predictive accuracy was 76.7%, 72.3% and 82.8% for respectively ECE, SVI and LNI. For PSA 2.51-20 ng/mL, the predictive accuracy for the same endpoints was 67.8%, 77.4% and 81.6%. Finally, for PSA >20 ng/mL, predictive accuracy was 63.6%, 63.7% and 70.6%. CONCLUSIONS: The ability to predict pathological stage in patients with PSA values in excess of 20 ng/mL significantly decreased, compared to patients with lower PSA values. Therefore, accurate staging of these patients may require alternative markers or staging schemes.

Adult↗
PubMed2006

Modeling radiation pneumonitis risk with clinical, dosimetric, and spatial parameters.

PURPOSE: To determine the clinical, dosimetric, and spatial parameters that correlate with radiation pneumonitis. METHODS AND MATERIALS: Patients treated with high-dose radiation for non-small-cell lung cancer with three-dimensional treatment planning were reviewed for clinical information and radiation pneumonitis (RP) events. Three-dimensional treatment plans for 219 eligible patients were recovered. Treatment plan information, including parameters defining tumor position and dose-volume parameters, was extracted from non-heterogeneity-corrected dose distributions. Correlation to RP events was assessed by Spearman's rank correlation coefficient (R). Mathematical models were generated that correlate with RP. RESULTS: Of 219 patients, 52 required treatment for RP (median interval, 142 days). Tumor location was the most highly correlated parameter on univariate analysis (R = 0.24). Multiple dose-volume parameters were correlated with RP. Models most frequently selected by bootstrap resampling included tumor position, maximum dose, and D35 (minimum dose to the 35% volume receiving the highest doses) (R = 0.28). The most frequently selected two- or three-parameter models outperformed commonly used metrics, including V20 (fractional volume of normal lung receiving >20 Gy) and mean lung dose (R = 0.18). CONCLUSIONS: Inferior tumor position was highly correlated with pneumonitis events within our population. Models that account for inferior tumor position and dosimetric information, including both high- and low-dose regions (D(35), International Commission on Radiation Units and Measurements maximum dose), risk-stratify patients more accurately than any single dosimetric or clinical parameter.

Adult↗
PubMed2006

Recurrent events counted in evaluations of predictive accuracy.

OBJECTIVES: To describe an alternate approach for the calculation of sensitivity and specificity when analyzing the accuracy of screening tools, which can be used when standard calculations may be inappropriate. Sensitivity(ER) (ER denoting event rate) is the number of events correctly predicted, divided by the total number of events. Specificity(ER) is the amount of time that study participants are predicted to be event negative, divided by the total amount of participant observed time. Variance estimates for these statistics are constructed by bootstrap resampling, taking into account event dependence. METHODS: Standard and alternate approaches for calculating sensitivity and specificity were applied to hospital falls risk screening tool data. In this application, the outcome of interest was a recurrent event, there were multiple applications of the screening tool, delays in screening tool completion, and patients' follow-up durations were unequal. RESULTS: Application of sensitivity(ER) and specificity(ER) to this data not only provided a clearer description of the screening tool's overall accuracy, but also allowed examination of accuracy over time, accuracy in predicting specific event numbers, and evaluation of the added value that screening tool reapplications may have. CONCLUSION: Sensitivity(ER) and specificity(ER) provide a valuable approach to screening tool evaluation in the clinical setting.

Accidental Falls↗
PubMed2006

Metric variation and sexual dimorphism in the dentition of Ouranopithecus macedoniensis.

The fossil sample attributed to the late Miocene hominoid taxon Ouranopithecus macedoniensis is characterized by a high degree of dental metric variation. As a result, some researchers support a multiple-species taxonomy for this sample. Other researchers do not think that the sample variation is too great to be accommodated within one species. This study examines variation and sexual dimorphism in mandibular canine and postcanine dental metrics of an Ouranopithecus sample. Bootstrapping (resampling with replacement) of extant hominoid dental metric data is performed to test the hypothesis that the coefficients of variation (CV) and the indices of sexual dimorphism (ISD) of the fossil sample are not significantly different from those of modern great apes. Variation and sexual dimorphism in Ouranopithecus M(1) dimensions were statistically different from those of all extant ape samples; however, most of the dental metrics of Ouranopithecus were neither more variable nor more sexually dimorphic than those of Gorilla and Pongo. Similarly high levels of mandibular molar variation are known to characterize other fossil hominoid species. The Ouranopithecus specimens are morphologically homogeneous and it is probable that all but one specimen included in this study are from a single population. It is unlikely that the sample includes specimens of two sympatric large-bodied hominoid species. For these reasons, a single-species hypothesis is not rejected for the Ouranopithecus macedoniensis material. Correlations between mandibular first molar tooth size dimorphism and body size dimorphism indicate that O. macedoniensis and other extinct hominoids were more sexually size dimorphic than any living great apes, which suggests that social behaviors and life history profiles of these species may have been different from those of living species.

Animals↗
PubMed2006

Size and shape variation in Australopithecus afarensis proximal femora.

The degree of size and shape variation in the A. afarensis fossil sample has been interpreted in a variety of ways. Size variation has been described as exceeding that of extant hominoids, similar to that of strongly sexually dimorphic hominoids, and best matched to modern humans. The degree of shape variation has been characterized both as great and negligible. Recent fieldwork has increased the proximal femoral sample, providing new data with which to examine variation. The proximal femur of A. afarensis is analyzed in a comparative framework in order to gauge the magnitude of size and shape variation in this element. Seven of the best-preserved A. afarensis proximal femora contribute to the analysis (A.L. 128-1, A.L. 152-2, A.L. 211-1, A.L. 288-1ap, A.L. 333-3, A.L. 333-123, A.L. 827-1). Comparative samples from Pan, Pongo, Gorilla, and Homo provide context for interpreting variation among the fossils. The coefficient of variation (CV) of linear measurements is used to estimate size variation. Bootstrap resampling of CVs from extant hominoids provides distributions for comparison to A. afarensis CVs. Ratios of linear measurements provide scale-free shape variables that are used in pairwise comparisons. The Euclidean distance between pairs of A. afarensis are compared to the Euclidean distances between extant hominoid pairs. As found in some earlier analyses, size variation in A. afarensis is accommodated best in gorillas and orangutans. The magnitude of difference in shape between A. afarensis pairs is exceeded by most taxa, indicating that shape variation is not extreme. These general findings are contradicted by a few instances of excessive size and shape variation. These are uncharacteristic results and could point to temporal bias, although other alternatives are explored. The signal from the proximal femur is that size variation in A. afarensis is like that of the strongly sexually dimorphic apes, and shape variation is well within the range of most hominoids irrespective of their degree of size dimorphism.

Animals↗
PubMed2026

Systemic biomarkers of treatment response to methotrexate in people with painful knee osteoarthritis: A biological substudy of the PROMOTE randomised controlled clinical trial.

OBJECTIVE: Stratification of therapeutic responses may help identify efficacious therapies for osteoarthritis (OA). In the PROMOTE randomised trial, participants with elevated baseline high-sensitivity C-reactive protein (hs-CRP) showed greater pain reduction after methotrexate treatment. We set out to interrogate a broader panel of serum/plasma inflammatory response markers relevant to methotrexate actions as potential biomarkers of therapeutic effect. Our objectives were to: (i) characterize changes in these systemic markers during methotrexate treatment; determine whether (ii) baseline levels or (iii) changes in any marker during treatment were associated with treatment response; and (iv) compare these findings with the more established clinical inflammatory marker, hs-CRP. DESIGN: Plasma/serum samples from participants in PROMOTE's biological substudy were analysed for 35 inflammatory markers at baseline (pre-treatment) and at 6-months (post-treatment), by MesoScale V-plex multiplex assay. Those with paired biological and clinical data at both baseline and 6-months were included in the substudy analysis set. Relationships between markers and overall data structure were assessed by Pearson correlation and Principal Component analysis. Associations between markers (baseline levels or change over time) and change in average knee pain severity in past week (numerical rating scale, NRS) were evaluated by univariable linear regression, adjusting for baseline age, sex, and body mass index. Least Absolute Shrinkage and Selection Operator (LASSO) regression with bootstrap resampling enabled marker selection. Benjamini-Hochberg correction adjusted for multiple testing (Padj). RESULTS: 87 participants with paired blood marker and clinical data were eligible for substudy analysis. 18/35 markers were quantifiable and analysed. Systemic IL-8 and TNF-&#x3b1; levels decreased (Padj=0.015, 0.048 respectively) while IL-15 increased (Padj=0.033) with methotrexate treatment over 6-months. Analysing within this active treatment randomised arm, higher baseline IFN-&#x3b3; was associated with greater reduction in NRS pain change (0.66 [0.01, 1.31], P=0.047), as was decreasing TNF-&#x3b1; over 6-months (2.25 [0.00, 4.5], P=0.049). LASSO identified higher IFN-&#x3b3;, lower plasma IL-15 and IL-16, and younger age as the most important baseline predictors of pain improvement. hs-CRP was highly selected by LASSO for treatment response in both arms. In a secondary univariate treatment arm-by-biomarker interaction analysis, of the 19 markers, only hs-CRP showed consistent effects in adjusted models (at baseline, coeffic. 2.34 [0.53, 4.15], P=0.001; change over 6-months, (0.36 [0.06, 0.66], P=0.018). CONCLUSIONS: Blood measurement of IFN-&#x3b3;, TNF-&#x3b1;, IL-15 and IL-16 as well as hs-CRP could act as potential markers to stratify the treatment response by average knee pain to methotrexate in knee osteoarthritis.

Humans↗
PubMed2026

Association of time-averaged systemic immune-inflammation indices with in-hospital mortality after intracerebral hemorrhage: a retrospective study.

BACKGROUND: Systemic inflammation plays a central role in secondary brain injury following intracerebral hemorrhage (ICH). Although inflammatory indices such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) are linked to poor outcomes, their associations with mortality are commonly assumed to be linear, potentially overlooking nonlinear patterns where mortality risk rises steeply at higher levels. METHODS: We conducted a retrospective study using the MIMIC-IV database, including 440 patients with non-traumatic ICH who were alive and remained in the ICU for at least 72&#xa0;h after admission. Mean NLR, SII, and SIRI were calculated from measurements obtained during this period. Multivariable logistic regression and restricted cubic spline (RCS) analyses were applied to assess their independent and nonlinear associations with in-hospital mortality. Model discrimination and calibration were internally validated using 1,000 bootstrap resamples. RESULTS: The in-hospital mortality rate was 26.1%. After multivariable adjustment, NLR and SIRI remained independently associated with mortality. Patients in the highest SIRI quartile had the highest risk of death (aOR&#xa0;=&#xa0;5.12; 95% CI: 2.57-12.24; p&#xa0;<&#xa0;0.001). RCS analysis revealed a significant nonlinear association between SIRI and mortality (p-nonlinearity&#xa0;<&#xa0;0.05), showing a steep risk increase at higher SIRI levels. Adding SIRI to the base model provided a modest improvement in discrimination (AUC 0.762 to 0.785, p&#xa0;=&#xa0;0.045) and significantly improved risk reclassification (cNRI&#xa0;=&#xa0;0.4778, p&#xa0;<&#xa0;0.001; IDI&#xa0;=&#xa0;0.0240, p&#xa0;=&#xa0;0.0151). CONCLUSIONS: Among patients with ICH who met the 72-hour eligibility criterion, higher 72-hour average SIRI was independently associated with in-hospital mortality. As a time-averaged measure, SIRI should be interpreted as a dynamic marker integrating the initial inflammatory state and the early clinical course rather than as a purely baseline prognostic factor. Although adding SIRI to the base model modestly improved discrimination and risk reclassification, it should be considered a candidate prognostic marker requiring external validation before clinical application.

Humans↗
PubMed2026

Factors associated with additional intervention requirement following ESWL in pediatric patients with urolithiasis.

OBJECTIVE: To identify predictors of additional intervention following extracorporeal shock wave lithotripsy (ESWL) in pediatric patients and to develop a clinically applicable predictive model. MATERIALS AND METHODS: This retrospective cohort study included 647 pediatric patients who underwent ESWL between 2015 and 2025. Demographic, clinical, and radiological variables were analyzed. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of additional intervention. Model performance was evaluated using receiver operating characteristic curve analysis. RESULTS: Additional intervention was required in 65 patients (10.0%). On multivariable analysis, stone size 10-20 mm (OR: 3.04, p = 0.003), moderate (OR: 2.16, p = 0.049) and severe hydronephrosis (OR: 6.05, p < 0.001), and multiple stones (OR: 3.52, p = 0.030) were identified as independent risk factors. Increasing age (OR: 0.84, p = 0.026), history of urolithiasis (OR: 0.41, p = 0.006), and lower calyx location (OR: 0.14, p = 0.034) were associated with a reduced risk. The model demonstrated good discriminative performance (AUC: 0.794), with a sensitivity of 72% and specificity of 75%. Internal validation using bootstrap resampling demonstrated stable model performance, yielding a corrected AUC of 0.732. CONCLUSION: Stone burden, hydronephrosis severity, and stone multiplicity are key determinants of additional intervention after ESWL in pediatric patients. The proposed model shows good predictive performance and may support individualized risk stratification and clinical decision-making.

Humans↗