OBJECTIVE: A better understanding of the factors influencing D-dimer levels in code stroke patients is needed to guide further investigations of concomitant thrombotic conditions. This study aimed to investigate the impact of time from symptom onset and other factors on D-dimer levels in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA).
METHODS: Data on consecutive AIS and TIA patients treated at our tertiary-care stroke center between January 2015 and December 2020 were retrospectively assessed. Patients with available D-dimer levels were evaluated for eligibility. Multivariable non-linear regression analyses were performed.
RESULTS: In total, 2467 AIS patients and 708 TIA patients were included. The median D-dimer levels differed between the AIS and TIA groups (746 µg/L [interquartile range 381-1468] versus 442 µg/L [interquartile range 244-800], p<0.001). In AIS patients, an early increase in D-dimer levels was demonstrated within the first 6 h (standardized beta coefficient [β] 0.728; 95% confidence interval [CI] 0.324-1.121). This was followed by an immediate decrease (β -13.022; 95% CI -20.401 to -5.643) and then by a second, late increase after 35 h (β 11.750; 95% CI 4.71-18.791). No time-dependent fluctuation in D-dimer levels was observed in TIA patients.
CONCLUSIONS: The time from symptom onset may affect D-dimer levels in patients with AIS but not those with TIA. Further studies confirming these findings and validating time-specific variations are needed to enable D-dimer levels to be used efficiently as an acute stroke and thrombotic risk biomarker.

UNASSIGNED: To assess the delayed presentation of Retinal Detachment (RD), its association from travel distance to the referral hospital (TDH), the period from symptom onset to consultation (SO-C), Proliferative vitreoretinopathy (PVR) severity, and 6 months follow-up attendance (6mo-FA).
UNASSIGNED: A retrospective review based on medical records. Age, sex, initial best-corrected visual acuity (BCVA), TDH, SO-C, PVR type, and 6mo-FA were recorded. Multivariable ordered logistic regression was used to analyze the association between TDH and SO-C, and SO-C and PVR severity. Multivariable logistic regression was used to analyze 6mo-FA according to TDH. Multiple linear regression was used to assess the association between initial BCVA and TDH. Age and sex were included in all multivariable adjustments.
UNASSIGNED: A total of 387 patients had RD with 59.2% predominantly males and the mean age±SD was 46.3±13.9 years. The initial BCVA of less than 3/60 was 81.1%. The averages of SO-C and TDH were 183.5±456 days and 160.9±364 km, respectively. The TDH of more than 120 km distance was significantly associated with longer SO-C (adjusted OR 1.78; CI 95% 1.09-2.92). PVR was noted in 17.6% of patients. The SO-C of 31-60 days was significantly associated with PVR severity (adjusted OR 4.28; CI 95% 1.47-12.51). The TDH of more than 120 km distance was significantly associated with 6mo-FA (adjusted OR 0.46; CI 95% 0.27-0.93).
UNASSIGNED: Long TDH was significantly associated with a longer period from symptom onset to consultation and 6mo-FA. Hence, accessible eye care is essential to refer RD cases in a timely fashion.

OBJECTIVE: We aimed to develop and validate a radiomics nomogram based on dual-energy computed tomography (DECT) images and clinical features to classify the time since stroke (TSS), which could facilitate stroke decision-making.
METHODS: This retrospective three-center study consecutively included 488 stroke patients who underwent DECT between August 2016 and August 2022. The eligible patients were divided into training, test, and validation cohorts according to the center. The patients were classified into two groups based on an estimated TSS threshold of ≤ 4.5 h. Virtual images optimized the visibility of early ischemic lesions with more CT attenuation. A total of 535 radiomics features were extracted from polyenergetic, iodine concentration, virtual monoenergetic, and non-contrast images reconstructed using DECT. Demographic factors were assessed to build a clinical model. A radiomics nomogram was a tool that the Rad score and clinical factors to classify the TSS using multivariate logistic regression analysis. Predictive performance was evaluated using receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA) was used to compare the clinical utility and benefits of different models.
RESULTS: Twelve features were used to build the radiomics model. The nomogram incorporating both clinical and radiomics features showed favorable predictive value for TSS. In the validation cohort, the nomogram showed a higher AUC than the radiomics-only and clinical-only models (AUC: 0.936 vs 0.905 vs 0.824). DCA demonstrated the clinical utility of the radiomics nomogram model.
CONCLUSIONS: The DECT-based radiomics nomogram provides a promising approach to predicting the TSS of patients.
CONCLUSIONS: The findings support the potential clinical use of DECT-based radiomics nomograms for predicting the TSS.
CONCLUSIONS: Accurately determining the TSS onset is crucial in deciding a treatment approach. The radiomics-clinical nomogram showed the best performance for predicting the TSS. Using the developed model to identify patients at different times since stroke can facilitate individualized management.

OBJECTIVE: To compare the effect of early meniscal surgery versus exercise and education with the option of later surgery on pain, function, and quality of life in young patients with a meniscal tear, taking symptom onset into account. DESIGN: Randomized controlled trial. METHODS: In a randomized controlled trial (the \"Danish RCT on Exercise versus Arthroscopic Meniscal surgery for young adults\" [DREAM] trial), 121 patients aged 18-40 years with a magnetic resonance imaging-verified meniscal tear were randomized to surgery or 12 weeks of supervised exercise and patient education. For this exploratory study, the analyses were stratified by symptom onset (traumatic/nontraumatic). The main outcome was the difference in change after 12 months in the mean score of 4 Knee injury and Osteoarthritis Outcome Score subscales (KOOS4) covering pain, symptoms, function in sport and recreation, and quality of life. RESULTS: Forty-two patients (69%) in the exercise therapy group and 47 (78%) in the surgery group were categorized as having a traumatic tear. We observed no difference in change in the KOOS4 after 12 months between the 2 treatment groups for either traumatic tears (18.8 versus 16.0 in the surgery versus exercise therapy groups; adjusted mean difference, 4.8 [95% confidence interval, -1.7 to 11.2]) or nontraumatic tears (20.6 versus 17.3 in the surgery versus exercise therapy groups; adjusted mean difference, 7.0 [95% confidence interval, -3.7 to 17.7]). CONCLUSION: In patients with traumatic and nontraumatic meniscus tears, early meniscal surgery did not appear superior to exercise and education in improving pain, function, and quality of life after 12 months. Further research is needed to confirm the clinical applicability of these findings. J Orthop Sports Phys Ther 2024;54(5):1-10. Epub 22 February 2024. doi:10.2519/jospt.2024.12245.

UNASSIGNED: To explore whether dual-energy computed tomography (DECT) angiography can provide reliable quantitative information on net water uptake (NWU) of ischemic brain to identify stroke patients within 4.5 h.
UNASSIGNED: We retrospectively reviewed 142 patients with stroke occurrence and who underwent DECT angiography between August 2016 and May 2022. DECT angiography manual drawn the ischemic area by referring to the normal area of the contralateral hemisphere and follow-up images. The NWU in the ischemic area was determined using virtual non-contrast and monoenergetic (VNC &VM) images acquired from DECT angiography. The NWU values in the ischemic area were compared between stroke patients within and beyond 4.5 h. The diagnostic performance of the NWU values derived from the VNC and VM images was assessed through receiver operating characteristic curve analysis. Additionally, Furthermore, we examined the correlation between the NWU values and the stroke onset time.
UNASSIGNED: Seventy-eight (54.93 %) stroke patients underwent DECT angiography and within 4.5 h. These patients with lower median National Institute of Health stroke scale (NIHSS) scores on admission than those beyond 4.5 h (p < 0.05). Furthermore, the group within 4.5 h had lower NWU values than did the group beyond 4.5 h on all VNC and VM images (p < 0.001). The analysis revealed that the NWU values determined using the VM (60 keV) images had the highest predictive efficiency (AUC, 0.95; sensitivity, 100 %; and specificity, 89.06 %) and showed the strongest positive correlation with stroke onset time (r-value = 0.58, p < 0.001).
UNASSIGNED: Our findings showed that DECT angiography-based quantification of NWU helps identify the stroke patients within 4.5 h with high predictive efficiency. Thus, NWU values determined using VM (60 keV) images could serve as a significant biomarker for stroke onset time.

BACKGROUND: Current guidelines emphasize the diagnostic value of non-cardiac or possibly cardiac chest pain. The goal of this analysis was to determine whether German chest pain units (CPUs) adequately address conditions with \"atypical\" chest pain in existing diagnostic structures.
METHODS: A total of 11,734 patients from the German CPU registry were included. The analyses included mode of admission, critical time intervals, diagnostic steps, and differential diagnoses.
RESULTS: Patients with unspecified chest pain were younger, more often female, were less likely to have classic cardiovascular risk factors and tended to present more often as self-referrals. Patients with acute coronary syndrome (ACS) mostly had prehospital medical contact. Overall, there was no difference between these two groups regarding the time from the onset of first symptoms to arrival at the CPU. In the CPU, the usual basic diagnostic measures were performed irrespective of ACS as the primary working diagnosis. In the non-ACS group, further ischemia-specific diagnostics were rarely performed. Extra-cardiac differential diagnoses were not specified.
CONCLUSIONS: The establishment of broader awareness programs and opening CPUs for low-threshold evaluation of self-referring patients should be discussed. Regarding the rigid focus on the clarification of cardiac causes of chest pain, a stronger interdisciplinary approach should be promoted.
UNASSIGNED: HINTERGRUND: Aktuelle Leitlinien betonen die diagnostische Wertigkeit auch des nichtkardialen oder möglicherweise nichtkardialen Thoraxschmerzes. In der aktuellen Arbeit wird untersucht, ob die deutschen Chest Pain Units (CPU) Erkrankungen mit „atypischen“ Brustschmerzen innerhalb der bestehender Diagnosestrukturen bereits angemessen behandeln.
METHODS: Eingeschlossen wurden 11.734 Patienten aus dem deutschen CPU-Register. Die Analysen umfassten Aufnahmeart, kritische Zeitintervalle, diagnostische Schritte und Differenzialdiagnosen.
UNASSIGNED: Patienten mit nicht näher bezeichneten Brustschmerzen waren jünger, häufiger weiblich, wiesen seltener klassische kardiovaskuläre Risikofaktoren auf und stellten sich tendenziell häufiger als Selbsteinweiser vor. Patienten mit akutem Koronarsyndrom (ACS) hatten meist bereits präklinischen Kontakt zum Gesundheitssystem. Insgesamt gab es keinen Unterschied hinsichtlich des Auftretens der ersten Symptome bis zum Eintreffen in der CPU. Innerhalb der CPU wurden bei allen Patienten und unabhängig von der initialen Arbeitsdiagnose ACS die üblichen Basisdiagnostikmaßnahmen durchgeführt. In der Nicht-ACS-Gruppe wurde selten weitere Ischämiediagnostik durchgeführt. Extrakardiale Differenzialdiagnosen wurden nicht weiter differenziert.
UNASSIGNED: Die Einrichtung umfassenderer Awarenessprogramme und die niederschwellige Selbstvorstellungsmöglichkeit in die CPU sollten intensiver diskutiert werden. Angesichts der häufig starren Fokussierung auf die Abklärung ischämischer/kardialer Ursachen des akuten Thoraxschmerzes sollte ein stärkerer interdisziplinärer Ansatz gefördert werden.

BACKGROUND: The serial interval is the period of time between symptom onset in the primary case and symptom onset in the secondary case. Understanding the serial interval is important for determining transmission dynamics of infectious diseases like COVID-19, including the reproduction number and secondary attack rates, which could influence control measures. Early meta-analyses of COVID-19 reported serial intervals of 5.2 days (95% CI: 4.9-5.5) for the original wild-type variant and 5.2 days (95% CI: 4.87-5.47) for Alpha variant. The serial interval has been shown to decrease over the course of an epidemic for other respiratory diseases, which may be due to accumulating viral mutations and implementation of more effective nonpharmaceutical interventions. We therefore aggregated the literature to estimate serial intervals for Delta and Omicron variants.
METHODS: This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A systematic literature search was conducted of PubMed, Scopus, Cochrane Library, ScienceDirect, and preprint server medRxiv for articles published from April 4, 2021, through May 23, 2023. Search terms were: (\"serial interval\" or \"generation time\"), (\"Omicron\" or \"Delta\"), and (\"SARS-CoV-2\" or \"COVID-19\"). Meta-analyses were done for Delta and Omicron variants using a restricted maximum-likelihood estimator model with a random effect for each study. Pooled average estimates and 95% confidence intervals (95% CI) are reported.
RESULTS: There were 46,648 primary/secondary case pairs included for the meta-analysis of Delta and 18,324 for Omicron. Mean serial interval for included studies ranged from 2.3-5.8 days for Delta and 2.1-4.8 days for Omicron. The pooled mean serial interval for Delta was 3.9 days (95% CI: 3.4-4.3) (20 studies) and Omicron was 3.2 days (95% CI: 2.9-3.5) (20 studies). Mean estimated serial interval for BA.1 was 3.3 days (95% CI: 2.8-3.7) (11 studies), BA.2 was 2.9 days (95% CI: 2.7-3.1) (six studies), and BA.5 was 2.3 days (95% CI: 1.6-3.1) (three studies).
CONCLUSIONS: Serial interval estimates for Delta and Omicron were shorter than ancestral SARS-CoV-2 variants. More recent Omicron subvariants had even shorter serial intervals suggesting serial intervals may be shortening over time. This suggests more rapid transmission from one generation of cases to the next, consistent with the observed faster growth dynamic of these variants compared to their ancestors. Additional changes to the serial interval may occur as SARS-CoV-2 continues to circulate and evolve. Changes to population immunity (due to infection and/or vaccination) may further modify it.

To assess the demographic and geographic variations in access time - defined as years between the date of symptom onset and initial date of neurological care - in pediatric patients presenting with staring spells.
We conducted a secondary analysis of a retrospective chart review study from 2011 to 2021. A total of 1,353 staring spell patients, aged 0 to 17.9 years, were analyzed for age, sex, race/ethnicity, insurance, county, average county annual per capita personal income, and access time.
Patients aged 0-2.9 years had the shortest median access time of 0.3 years, compared to 1.2 years in patients aged 3-12.9 years and 1.0 year in patients aged 13-17.9 years. Statistically significant differences were seen based on race/ethnicity and insurance with White patients having shorter access time of 0.5 years compared to Black patients with 1.0 year and self-pay patients having the shortest access time of 0.4 years compared to patients with private insurance (0.7 years). Warren County had the largest annual per capita personal income of $65,855 and access time of 0.5 years compared to Preble county with the least annual per capita personal income of $45,016 and access time of 1.1 years.
Demographic parameters of age, race/ethnicity, insurance, and annual county per capita personal income appeared to be associated with access time to initial neurological care in patients with staring spells. These associations need to be investigated further to ensure timely access to neurological care and to ensure equity in health care.

There are several differences between younger and older adults with acute coronary syndrome (ACS). However, few studies have evaluated these differences. We analysed the pre-hospital time interval [symptom onset to first medical contact (FMC)], clinical characteristics, angiographic findings, and in-hospital mortality in patients aged ≤50 (group A) and 51-65 (group B) years hospitalised for ACS. We retrospectively collected data from 2010 consecutive patients hospitalised with ACS between 1 October 2018 and 31 October 2021 from a single-centre ACS registry. Groups A and B included 182 and 498 patients, respectively. ST-segment elevation myocardial infarction (STEMI) was more common in group A than group B (62.6 and 45.6%, respectively; P < 0.001). The median time from symptom onset to FMC in STEMI patients did not significantly differ between groups A and B [74 (40-198) and 96 (40-249) min, respectively; P = 0.369]. There was no difference in the rate of sub-acute STEMI (symptom onset to FMC > 24 h) between groups A and B (10.4% and 9.0%, respectively; P = 0.579). Among patients with non-ST elevation acute coronary syndrome (NSTE-ACS), 41.8 and 50.2% of those in groups A and B, respectively, presented to the hospital within 24 h of symptom onset (P = 0.219). The prevalence of previous myocardial infarction was 19.2% in group A and 19.5% in group B (P = 1.00). Hypertension, diabetes, and peripheral arterial disease were more common in group B than group A. Active smoking was more common in group A than group B (67 and 54.2%, respectively; P = 0.021). Single-vessel disease was present in 52.2 and 37.1% of participants in groups A and B, respectively (P = 0.002). Proximal left anterior descending artery was more commonly the culprit lesion in group A compared with group B, irrespective of the ACS type (STEMI, 37.7 and 24.2%, respectively; P = 0.009; NSTE-ACS, 29.4 and 21%, respectively; P = 0.140). The hospital mortality rate for STEMI patients was 1.8 and 4.4% in groups A and B, respectively (P = 0.210), while for NSTE-ACS patients it was 2.9 and 2.6% in groups A and B, respectively (P = 0.873). No significant differences in pre-hospital delay were found between young (≤50 years) and middle-aged (51-65 years) patients with ACS. Although clinical characteristics and angiographic findings differ between young and middle-aged patients with ACS, the in-hospital mortality rate did not differ between the groups and was low for both of them.

A complex interaction between genetic and external factors determines the development of amyotrophic lateral sclerosis (ALS). Epidemiological studies on large patient cohorts have suggested that ALS is a multi-step disease, as symptom onset occurs only after exposure to a sequence of risk factors. Although the exact nature of these determinants remains to be clarified, it seems clear that: (i) genetic mutations may be responsible for one or more of these steps; (ii) other risk factors are probably linked to environment and/or to lifestyle, and (iii) compensatory plastic changes taking place during the ALS etiopathogenesis probably affect the timing of onset and progression of disease. Current knowledge on ALS mechanisms and therapeutic targets, derives mainly from studies involving superoxide dismutase 1 (SOD1) transgenic mice; therefore, it would be fundamental to verify whether a multi-step disease concept can also be applied to these animal models. With this aim, a meta-analysis study has been performed using a collection of primary studies (n = 137), selected according to the following criteria: (1) the studies should employ SOD1 transgenic mice; (2) the studies should entail the presence of a disease-modifying experimental manipulation; (3) the studies should make use of Kaplan-Meier plots showing the distribution of symptom onset and lifespan. Then, using a subset of this study collection (n = 94), the effects of treatments on key molecular mechanisms, as well as on the onset and progression of disease have been analysed in a large population of mice. The results are consistent with a multi-step etiopathogenesis of disease in ALS mice (including two to six steps, depending on the particular SOD1 mutation), closely resembling that observed in patient cohorts, and revealed an interesting relationship between molecular mechanisms and disease manifestation. Thus, SOD1 mouse models may be considered of high predictive value to understand the determinants of disease onset and progression, as well as to identify targets for therapeutic interventions.