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PubMed2002

How does early ultrasound scan estimation of gestational age lead to higher rates of preterm birth?

OBJECTIVE: Early ultrasound scanning estimation of gestational age is known to increase the reported preterm delivery rate (<37 completed weeks) compared with estimation by date of the last normal menstrual period, but it is unclear how this systematic difference arises. STUDY DESIGN: This study was a hospital-based study of 44,623 women who delivered a live-born or stillborn infant between January 1, 1978, and March 31, 1996, and who had both last normal menstrual period-based and early (usually at 16-18 weeks) ultrasound scan-based gestational age estimates. Cross-classification of the 2 estimates by completed weeks was used to examine the direction and magnitude of the differences between them and to compare the resulting classifications of preterm birth. RESULTS: The early ultrasound scan-based gestational age distribution was shifted uniformly to the left (ie, lower gestational age) relative to the last normal menstrual period gestational age distribution; the early ultrasound scan-based preterm delivery rate was 9.1%, which was 19.5% (n = 659 births) higher than the 7.6% rate by last normal menstrual period (P <.0001). The last normal menstrual period estimate exceeded the early ultrasound scan estimate far more often than the reverse, up to and including early ultrasound scan estimates of 40 weeks. No concentration of 4-week discrepancies was observed in either direction, as would be expected with random or systematic errors in recall of the last normal menstrual period. The absolute number of births at 37 to 39 weeks of gestation (by last normal menstrual period) that were reclassified as preterm (n = 1206 births) was much higher than the number of preterm births at 34 to 36 weeks of gestation that were reclassified as term (n = 581 births). The net increase of 625 preterm births (from 581 to 1206 births) that resulted from reclassification of births at 37 to 39 last normal menstrual period weeks accounted for 95% of the total 659-birth increase in early ultrasound scan-based preterm births at all last normal menstrual period gestational ages. CONCLUSION: Early ultrasound scanning reduces the gestational age estimate across the entire gestational age range; early ultrasound scan-based reclassification of gestational age results in a substantial increase in the prevalence of preterm births. Small downward reclassifications exceed upward reclassifications of similar magnitude, which is consistent with previous reports that delayed (>14 days) ovulation is more frequent than early (<14 days) ovulation.

Adult↗

PubMed2005

Prostate cancer and the Will Rogers phenomenon.

BACKGROUND: Information on tumor stage and grade are used to assess cancer prognosis and to produce standardized comparisons of end results over time. Changes in the interpretation of classification schemes can alter the apparent distribution of cancer stage or grade in the absence of a true biologic change. Since the introduction of prostate-specific antigen testing, the reported incidence of low-grade prostate cancer has declined. To determine whether this decline is in part a result of Gleason score reclassification during the same time period, we documented the potential impact of reclassification between 1992 and 2002 on clinical outcomes. METHODS: A population-based cohort of 1858 men who were < or = 75 years of age at diagnosis of prostate cancer in 1990-1992 was assembled retrospectively from the Connecticut Tumor Registry. Histology slides of the diagnostic prostate tissue were retrieved and reread in 2002-2004 by an experienced pathologist blinded to the original Gleason score readings. Prostate cancer mortality rates for the cohort calculated using the original Gleason score readings were compared with those calculated using the contemporary Gleason score readings. Statistical tests were two sided. RESULTS: The contemporary Gleason score readings were statistically significantly higher than the original readings (mean score increased from 5.95 to 6.8; difference = 0.85, 95% confidence interval = 0.79 to 0.91; P < .001). Consequently, the Gleason score-standardized contemporary prostate cancer mortality rate (1.50 deaths per 100 person-years) appeared to be 28% lower than standardized historical rates (2.08 deaths per 100 person-years), even though the overall outcome was unchanged. This apparent improvement in mortality held for all Gleason score categories. CONCLUSIONS: In this population, a decline in the reported incidence of low-grade prostate cancers appears to be the result of Gleason score reclassification over the past decade. This reclassification resulted in apparent improvement in clinical outcomes. This finding reflects a statistical artifact known as the Will Rogers phenomenon.

Aged↗

PubMed2025

Ten years of exome sequencing and reanalysis among racial, ethnic, and ancestral groups: The importance of equitable reanalysis access.

PURPOSE: Race, ethnicity, and ancestry (REA) affect the diagnostic utility of genetic testing. In addition to barriers to accessing genetics services, some non-European REA groups experience decreased diagnostic results and increased uncertain results. Exome sequencing (ES) is a unique genetic test because data can be reanalyzed with new information and variants may be reclassified after the original result. METHODS: We performed a retrospective review of 10,416 clinical ES cases originally analyzed by Ambry Genetics between 2011 and 2021 with reanalysis events through 2023. The relationship between assigned REA group, ES result, reanalysis and reclassification rates, and reanalysis initiators were analyzed with logistic regression. RESULTS: Reanalyses increased the total diagnostic yield from 21.4% to 25.5%. There were no significant differences in reclassification rate among REA groups. However, the African American and Black group (P = 2.8E-07), the Hispanic and Latino group (P = .0022), and the Asian group (P = .033) were significantly less likely to receive provider-initiated reanalysis compared with the White group. CONCLUSION: Although reclassification rates were not found to be associated with REA group, not all REA groups had the same access to ES reanalysis. Laboratory-initiated proactive reanalysis can help reduce disparities in ES diagnostic utility by reducing barriers to accessing reanalysis.

Female↗

PubMed1992

Time trends in accuracy of classification of testicular tumours, with clinical and epidemiological implications.

Initial classifications of 1009 testicular tumours were reviewed as part of a population based survey of all testicular neoplasms in Victoria, Australia, between 1950 and 1978. All reviews were made by one of two pathologists at the Peter MacCallum Cancer Institute, using the system of the British Testicular Tumour Panel. Accuracy of diagnosis varied markedly over the time period and with pathological category. Seven cases were initially designated malignancies but were determined to be non-malignant conditions upon review. In each decade, review reduced the proportion of seminomas and increased the proportion of non-seminoma germ cell tumours (NSGCT) and non germ cell tumours. Reclassification resulted in changed age specific incidences of seminoma and NSGCT, most noticeably in 1950-59. Trends in age standardised incidence of seminoma and NSGCT were not affected by reclassification although the values were. The trend in age standardised incidence of non germ cell tumours was affected by reclassification. The implications of the changes in classification for epidemiological studies and clinical management are discussed.

Age Factors↗

PubMed2002

Nonsymptomatic generalized epilepsy in children younger than six years: excellent prognosis, but classification should be reconsidered after follow-up: the Dutch Study of Epilepsy in Childhood.

PURPOSE: To assess the prognosis and the accuracy of the epilepsy classification in young children with nonsymptomatic generalized epilepsy. METHODS: Of the cohort of the Dutch Study of Epilepsy in Childhood (n = 466), all children younger than 6 years with a diagnosis of idiopathic (IGE) or cryptogenic (CGE) generalized epilepsy either at intake (n = 108) and/or after 2 years of follow-up (n = 102) were included. The number of reclassifications after 2 years was determined, and the reasons for reclassification were analyzed. All children receiving a diagnosis of IGE or CGE at 2 years were followed up for 5 years to study their outcome in terms of terminal remission (TR). Data on their level of intellectual functioning were collected at the start of this analysis. RESULTS: The epilepsy syndrome was reclassified in 17 children. In 14 of them, the seizure type also was reclassified, and in three, the course of the epilepsy determined the new epilepsy type. Two other children had a reclassification of their seizure types without a change of the epilepsy type. Many children were categorized as having IGE not otherwise specified. In all probability, this is a heterogeneous group, containing patients with various epilepsy syndromes, with generalized tonic-clonic seizures as a common hallmark. Of the 102 children with IGE or CGE at 2 years of follow-up, 75% had a TR of >6 months after 2 years, and 85% a TR of >or=1 year after 5 years. CONCLUSIONS: In a fair proportion of children with nonsymptomatic generalized epilepsy in this age group, it is not possible to classify firmly the epilepsy and/or the seizures immediately after the intake. Instead, they are reclassified during the course of the disease. This and the apparent heterogeneity of the category IGE not otherwise specified point to inherent drawbacks of the current International League Against Epilepsy (ILAE) classification of epilepsy and epileptic syndromes. The prognosis of IGE at this young age is generally excellent.

Age Factors↗

PubMed2006

Are the American College of Cardiology/Emergency Cardiac Care (ACC/ECC) guidelines useful in triaging patients to telemetry units?

PURPOSE: To determine if the ACC/ECC guidelines (1991) properly stratify patients according to risk of arrhythmia, defined as a single event on cardiac monitoring, and benefit, defined as a subsequent management change from a recorded telemetry event. SUBJECTS AND METHODS: In 2003, a prospective study of 217 consecutive patients admitted to a 24-bed telemetry unit was conducted for 25 days at a major academic hospital. Patients were categorized per ACC/ECC guidelines as appropriate (class I & II) or inappropriate (class III) based on a non-cardiologist admission diagnosis. A cardiologist-led group then reclassified patients at the time of admission using a brief interview. Continuous telemetry-recorded arrhythmias and resultant management changes were reviewed and recorded daily. Subgroup analysis of patients admitted with a chief complaint of chest pain was also performed. In 2004, after this trial was performed, the American Heart Association released a scientific statement updating practice standards for ECG monitor; however, this paper is based upon the original 1991 ACC/ECC guidelines. RESULTS: Reclassification significantly decreased the percentage of all class I & II patients from 91% to 71% (P<0.001) and the percentage of class I & II patients with chest pain from 100% to 58% (P<0.001) without increasing the percentage of arrhythmias occurring in class III patients. Class II patients had a statistically significant higher percentage of arrhythmias than class I and III patients before and after reclassification (P<0.001 and P<0.001, respectively). Management changes occurring as a direct result of telemetry events were higher in class II than class I or III patients before and after reclassification (P = 0.01 and P = 0.03). Life-threatening arrhythmias (sustained ventricular tachycardia or ventricular fibrillation) occurred in 1% of the 216 patients enrolled in this study. CONCLUSIONS: (1) Cardiology input using ACC/ECC guidelines and a brief interview at admission safely reduced total admissions primarily by identifying low risk chest pain admissions inappropriate for inpatient telemetry monitoring. (2) Life threatening arrhythmias occurring in patients admitted to telemetry are rare.

Arrhythmias, Cardiac↗

PubMed2004

SARS outbreak, Taiwan, 2003.

We studied the severe acute respiratory syndrome (SARS) outbreak in Taiwan, using the daily case-reporting data from May 5 to June 4 to learn how it had spread so rapidly. Our results indicate that most SARS-infected persons had symptoms and were admitted before their infections were reclassified as probable cases. This finding could indicate efficient admission, slow reclassification process, or both. The high percentage of nosocomial infections in Taiwan suggests that infection from hospitalized patients with suspected, but not yet classified, cases is a major factor in the spread of disease. Delays in reclassification also contributed to the problem. Because accurate diagnostic testing for SARS is currently lacking, intervention measures aimed at more efficient diagnosis, isolation of suspected SARS patients, and reclassification procedures could greatly reduce the number of infections in future outbreaks.

Cross Infection↗

PubMed1974

Classification systems used in medical libraries.

The present study identifies the classification systems used in 941 libraries. It explores the reasons behind the choice of the National Library of Medicine Classification by 589 libraries. Reclassification procedures were investigated through a questionnaire sent to twenty-five libraries that have changed to NLM since 1959. Statistics and replies are given on: the classification systems employed prior to reclassification; the use of broad or specific Library of Congress class numbers in the LC schedules outside the scope of the NLM schedules; the number of catalogers in each library doing the reclassification; the use of cut-off dates for retrospective materials; the adoption of MeSH headings; user preference; and cost differences. Chief reasons for the change to NLM proved to be local circumstances, currency, arrangement of subclasses by NLM, its dovetailing with the LC Classification, and reliance upon nationally centralized cataloging services.

Book Classification↗

PubMed1979

[Iliac crest biopsy findings in malignant non-Hodgkin lymphoma].

Issuing from the clinico-prognostic importance of the classification after Kiel of the malignant non-Hodgkin-lymphomas the results of the attempt of a reclassification of positive bioptic findings of the iliac crest judged according to the former German nomenclature are described and discussed after the Kiel classification. In the total material of 725 biopsies 76 positive findings of the marrow were stated in malignant non-Hodgkin-lymphomas, which at 67.1% consist of such with a lower and at 32.9% of such with a high degree of malignity, in which case a strong decrease of the formerly diagnosed CLL is to be seen after reclassification, whereas the immunocytomas render the by far largest proportion. The former malignant reticuloses disappear per definitionem after reclassification and, as it was expected, are broadly distributed. In 112 biopsies which were performed on account of the suspicion of an affection of the marrow in malignant non-Hodgkin-lymphomas the 76 positive findings correspond to a frequency of 67.9%, which, however, must critically be judged, since the case in question are very selected numbers of patients.

Biopsy↗

PubMed2025

Contributions of Common, Rare, and Somatic Genetic Variants to Incidence of Atrial Fibrillation.

IMPORTANCE: Atrial fibrillation (AF) has a complex genetic architecture involving common, rare, and somatic variants. The association between these components requires further investigation. OBJECTIVE: To examine the individual and combined contributions of polygenic, monogenic, and somatic genetic variants to AF incidence, and develop an integrated genomic model (IGM-AF) for improved risk prediction. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used whole-genome sequence data from participants of the UK Biobank, with follow-up for AF events through hospital records, death registries, and self-report. The UK Biobank recruited participants aged 40 to 69 years in the UK between 2006 and 2010. Study data were analyzed from August 2022 to November 2024. EXPOSURES: IGM-AF comprising an AF polygenic risk score (PRS), a composite rare variant gene set (AFgeneset), and somatic variants associated with clonal hematopoiesis of indeterminate potential (CHIP). Clinical AF risk was estimated using the Cohorts for Heart and Aging Research in Genomic Epidemiology AF (CHARGE-AF) score. MAIN OUTCOMES AND MEASURES: The primary outcome was hazard ratios (HRs) for 5-year incident AF attributable to PRS, AFgeneset, CHIP, and their interactions. The predictive performance of IGM-AF and its components was quantified using HRs, C statistics, and reclassification indices. RESULTS: A total of 416 085 individuals (mean [SD] age, 56.6 [8.0] years; 224 642 female [54.0%]) with 30 797 AF cases were included. The PRS (HR per 1 SD, 1.65; 95% CI, 1.63-1.67; P < 1 × 10-8), AFgeneset (HR, 1.63; 95% CI, 1.52-1.75; P = 1.46 × 10-42), and CHIP (HR, 1.26; 95% CI, 1.15-1.38; P = 1.41 × 10-6) were associated with incident AF. The 5-year cumulative incidence of AF was at least 2-fold among individuals having all 3 genetic drivers (common, rare, and somatic drivers) compared with those with only 1 driver. Integration of IGM-AF with a clinical risk model (CHARGE-AF) showed higher predictive performance (C statistic, 0.80; 95% CI, 0.80-0.80) compared with IGM-AF and CHARGE-AF alone. The classification of the at-risk population for AF was improved when IGM-AF was added to CHARGE-AF (net reclassification index, 0.08; 95% CI, 0.07-0.09). CONCLUSIONS AND RELEVANCE: Results of this cohort study demonstrated the complementary value of common, rare, and somatic variants in shaping genomic AF risk. Leveraging comprehensive genetic information may enhance screening and preventive interventions for AF.

Humans↗

PubMed1991

Nuclear texture parameters as discriminant factors in cell cycle and drug sensitivity studies.

The authors have recently shown that cell cycle characteristics of in situ cell populations can be determined using the SAMBA 200 cell image processor by computing 15 densitometric and texture parameters on each Feulgen-stained nucleus and multiparametric analysis of data. The present paper displays the importance of chromatin pattern assessment and detection of conformational changes in DNA structure, based on nine nuclear texture parameters measured from the grey level cooccurrence and the run-length section matrices. Reference files were constructed by merging respective reference files (G0/G1, S, G2 and M) of MDA AG and MCF-7, two mammary epithelial cell lines presenting different morphological aspects and hormone responses, these files were found to be valid in the reclassification of any mammary epithelial cell in culture with a diploid or near diploid pattern. Moreover, the authors demonstrate that chromatin texture changes, following direct interaction of chemotherapeutic drugs with DNA, may be assessed owing to nuclear texture parameters. Consecutive to daunomycin addition (0.5 microgram/ml) and concomitant to the appearance of nuclear morphological alterations in MDA AG sensitive cells as viewed by microscopic observation, discriminant factorial analysis showed progressively increasing erroneous reclassification from 15 to 72 h of treatment. These experimental results were exploited with a kinetic mathematical model to quantify the daunomycin blocking effect: 20% in S phase and 80% in G2 phase. Interestingly, no textural change was observed on MDA A1 anthracycline resistant cells, indicating that these texture parameters may permit distinction of drug sensitive cells. This methodology 1) can be applied to test in vitro resistance-reversal molecules, 2) may be extended to other therapeutic agents giving rise to conformational changes in DNA structure, and 3) can be applied to cytopunctions or imprints of tumor biopsies with diploid-like DNA content to follow evolution of drug sensitivity or resistance during course of therapy.

Antibiotics, Antineoplastic↗

PubMed2002

Taxonomy--General comments and update on taxonomy of Clostridia and Anaerobic cocci.

Since such things as sites of normal carriage, type and severity of infections produced, and antimicrobial susceptibility patterns may vary according to the particular species involved, accurate taxonomy for differentiation of species is important. For example, reclassification of the 'Bacteroides gracilis group' revealed that Sutterella wadsworthensis is actually responsible for the antimicrobial resistance seen in that group. With clostridia and anaerobic cocci, as with other taxa, there have been a number of recent changes in classification of existing taxa as well as description of novel taxa. It is important that both clinicians and microbiologists adapt quickly to new classification schemes and new taxa as soon as they are validated. For example, Peptostreptococcus is now restricted to the species P. anaerobius and five new genera have been created. There has also been significant reclassification of clostridia and new species of clostridia have also been described.

Journal Article↗

PubMed1985

Detection of cystic fibrosis heterozygotes using a modified loading with bromide.

A three day loading with sodium bromide was performed in 19 healthy controls, 16 definite cystic fibrosis heterozygotes, and 14 homozygote patients with cystic fibrosis. After three days sodium, potassium, chloride, and bromide were determined in serum and sweat. Using a multivariate discriminant analysis two nonelementary functions with the features sodium index, bromide index, potassium index, and chloride in sweat allowed us to identify the three groups. The reclassification of the probands, however, was correct in only 69.3%. A second analysis with the groups of controls and heterozygotes only resulted in a unidimensional nonelementary function with the features potassium index, bromide/sodium in sweat, and sodium index. The reclassification of the probands was correct in 91.4%. The discriminant values were 8.28 +/- 0.96 in the controls and 11.67 +/- 1.03 in the heterozygotes with an overlap of twice the standard deviations between 9.61 and 10.20.

Administration, Oral↗

PubMed1996

Taxonomic relationships of Thiobacillus halophilus, T. aquaesulis, and other species of Thiobacillus, as determined using 16S rDNA sequencing.

Total base sequences of the 16S rRNA genes of Thiobacillus halophilus and Thiobacillus aquaesulis show that these bacteria fall into the gamma- and beta-subdivisions, respectively of the Proteobacteria. The closest relative of T. halophilus is Thiobacillus hydrothermalis (with 98.7% similarity), and the closest relative of T. aquaesulis is Thiobacillus thioparus (93.2% similarity). Physiological properties and mol% G+C content of their DNA serve to confirm that these four organisms are all distinct species. It is reiterated that the species currently assigned to the genus Thiobacillus are clearly so diverse that they need reclassification into several genera. The type species, T. thioparus, is unequivocally placed in the beta-subdivision of the Proteobacteria, thus requiring that the use of the genus name Thiobacillus be restricted to the chemolithoautotrophic species falling into that group. T. aquaesulis and T. thioparus may thus be regarded as true species of Thiobacillus. The relatively large number of obligately chemolithoautotrophic Thiobacillus species falling in the gamma-subdivision of the Proteobacteria need further study in order to assess the case for reclassification into one or more new or different genera.

Bacteriological Techniques↗

PubMed2025

Extracting and calibrating evidence of variant pathogenicity from population biobank data.

Genomic medicine requires a robust evidence base of variant phenotypic impacts, which remains incomplete even in extensively studied genes with monogenic disease associations. Here, we evaluated the broad potential of using population cohort data to identify evidence that can be used in variant assessment. Across 41 genes related to 18 clinically actionable monogenic phenotypes, we calculated variant-level odds ratios of disease enrichment using data from 469,803 UK Biobank participants. We found significant differences in odds ratio values between ClinVar-labeled pathogenic and benign variants in 11 phenotypes, spanning both common and rare disorders. To facilitate clinical translation, we calibrated the strength of evidence provided by variant-level odds ratios to align with American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) interpretation guidelines (PS4 criterion) and found that odds ratios may reach "moderate," "strong," or "very strong" evidence, varying by phenotype and gene. Overall, we found that 2.6% (N = 12,350) of participants harbor a rare variant of uncertain significance (VUS) with at least moderate evidence of pathogenicity-an indication of potentially unrecognized disease risk. Finally, by incorporating computational and functional data alongside population-based odds ratios, we identified variants that met the criteria for clinical reclassification. Notably, using this approach, we identified that 12.4% of rare VUSs in LDLR seen in participants meet diagnostic criteria to be classified as likely pathogenic, demonstrating its potential to scale the reclassification of VUSs.

Humans↗

PubMed2006

Why are eligible thrombolysis candidates left untreated?

BACKGROUND: Despite proven efficacy, thrombolytics are used in a minority of eligible candidates. Because some of the exclusion criteria are vague, relying on documented contraindications could disguise biases in usage. This study sought to identify barriers to tissue-type plasminogen activator (tPA) treatment among eligible patients with acute ischemic stroke. METHODS: The study prospectively identified all patients with an initial diagnosis of ischemic stroke arriving within 2.5 hours of symptom onset at 11 hospitals participating in the Centers for Disease Control and Prevention-sponsored California Acute Stroke Prototype Registry during two 3-month periods in 2002 and 2003. Potential risk factors for nontreatment with thrombolytics among patients categorized as eligible were examined, based on directly documented contraindications. Analyses were repeated after reclassification of eligibility based on record review. RESULTS: Of 625 patients with ischemic stroke, 126 (20%) arrived at the emergency department within 2.5 hours of symptom onset. Based on direct documentation, 72 (11.5% of all patients; 57% of in-time arrivals) were eligible for thrombolysis; 32 (44% of eligible patients) who received tPA within the 3-hour time window and 40 who did not receive thrombolytic medications despite having no documented contraindication to treatment. Factors predictive of nontreatment were older age (p=0.0005), later arrival (p=0.004), and admittance to a non-academic hospital (p=0.03). After record review, slightly fewer patients (n=61) were deemed eligible, with a tPA treatment rate of 52% among those eligible. Older age (p=0.002) and later arrival (p=0.002) continued to be predictive of nontreatment with thrombolytics after reclassification. CONCLUSIONS: Even when more-comprehensive eligibility standards are applied, older age and later hospital arrival are associated with nontreatment with thrombolytics.

Acute Disease↗

PubMed2025

Cardiac Troponins and Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

BACKGROUND: The extent to which high-sensitivity cardiac troponin can predict cardiovascular disease (CVD) is uncertain. OBJECTIVES: We aimed to quantify the potential advantage of adding information on cardiac troponins to conventional risk factors in the prevention of CVD. METHODS: We meta-analyzed individual-participant data from 15 cohorts, comprising 62,150 participants without prior CVD. We calculated HRs, measures of risk discrimination, and reclassification after adding cardiac troponin T (cTnT) or I (cTnI) to conventional risk factors. The primary outcome was first-onset CVD (ie, coronary heart disease or stroke). We then modeled the implications of initiating statin therapy using incidence rates from 2.1 million individuals from the United Kingdom. RESULTS: Among participants with cTnT or cTnI measurements, 8,133 and 3,749 incident CVD events occurred during a median follow-up of 11.8 and 9.8 years, respectively. HRs for CVD per 1-SD higher concentration were 1.31 (95% CI: 1.25-1.37) for cTnT and 1.26 (95% CI: 1.19-1.33) for cTnI. Addition of cTnT or cTnI to conventional risk factors was associated with C-index increases of 0.015 (95% CI: 0.012-0.018) and 0.012 (95% CI: 0.009-0.015) and continuous net reclassification improvements of 6% and 5% in cases and 22% and 17% in noncases. One additional CVD event would be prevented for every 408 and 473 individuals screened based on statin therapy in those whose CVD risk is reclassified from intermediate to high risk after cTnT or cTnI measurement, respectively. CONCLUSIONS: Measurement of cardiac troponin results in a modest improvement in the prediction of first-onset CVD that may translate into population health benefits if used at scale.

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 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 = 5.12; 95% CI: 2.57-12.24; p < 0.001). RCS analysis revealed a significant nonlinear association between SIRI and mortality (p-nonlinearity < 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 = 0.045) and significantly improved risk reclassification (cNRI = 0.4778, p < 0.001; IDI = 0.0240, p = 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↗