Background: Nitroglycerin is suggested to improve flap survival based on promising results; however, there are no data on the effectiveness of treatment initiation time. This study aimed to compare the effect of various nitroglycerin treatment initiation times on partial flap survival. Materials and Methods: The study included 50 Sprague-Dawley rats. Modified McFarlane flaps were elevated on the dorsum of each rat. Group A received placebo treatment. Groups B, C, D, and E received topical nitroglycerin 2% starting 1 day before surgery, on the day of surgery, postoperative d 2, and postoperative d 4, respectively. After 7 days, the flap survival rates were calculated. Afterward, the severity and extent of inflammation and ischemia, and the severity of edema were evaluated histologically. Results: The flap survival rate was highest in group B, followed by groups C, D, E, and A. The difference between groups B and C was not significant, whereas the difference between group B and groups A, D, and E was. In addition, the difference between groups A, D, and E was not significant. Histological analysis showed that inflammation was less severe in groups B and C than in groups A, D, and E. Ischemia was the most severe in groups A and D and was the least severe in group C. Conclusion: Topical nitroglycerin treatment increases flap survival when initiated before or on the day of surgery, but has no benefit when initiated on postsurgery d 2 or 4. Preoperative initiation of nitroglycerin treatment positively affects flap survival.
Contexte: L’utilisation de la nitroglycérine a été proposée pour améliorer la survie d’un lambeau à partir de résultats prometteurs. Il n’y a cependant aucune donnée sur l’efficacité du délai d’instauration du traitement. Cette étude a visé à comparer l’effet de différents moments d’instauration du traitement avec la nitroglycérine sur la survie d’un lambeau partiel. Matériels et méthodes: L’étude a inclus 50 rats Sprague-Dawley. Des lambeaux modifiés de McFarlane ont été surélevés sur le dos de chaque rat. Le groupe A a reçu un placebo, tandis que les groupes B, C, D et E ont reçu de la nitroglycérine topique à 2% en commençant, respectivement, la veille de la chirurgie, le jour de la chirurgie, 2 jours et 4 jours postopératoires. Les taux de survie du volet ont été calculés après 7 jours. Ensuite, la sévérité et l’étendue de l’inflammation et de l’ischémie ainsi que la sévérité de l’œdème ont été évaluées histologiquement. Résultats: Le taux de survie des volets a été le plus élevé dans le groupe B, suivi des groupes C, D, E et A. La différence entre les groupes B et C n’était pas significative, tandis que la différence entre le groupe B et les groupes A, D et E l’était. En outre, la différence entre les groupes A, et E n’était pas significative. L’analyse histologique a montré que l’inflammation était moins sévère dans les groupes B et C que dans les groupes A, D et E. L’ischémie a été la plus importante dans les groupes A et D et la moins importante dans le groupe C. Conclusion: Le traitement topique avec la nitroglycérine augmente la survie d’un lambeau quand il est commencé le jour de la chirurgie ou avant, mais il n’apporte pas d’avantage s’il est instauré au 2e ou au 4e jour postopératoire. L’instauration d’un traitement par la nitroglycérine en préopératoire a un effet positif sur la survie des lambeaux.

BACKGROUND: There are increased indications that physical activity timing, irrespective of intensity, impacts insomnia and circadian clock function. Here, we describe the rationale and design of a randomized cross-over study, called ON TIME, to examine the effects of (changing) physical activity timing on insomnia severity and on multiple exploratory outcomes that are linked to circadian clock function.
METHODS: We will conduct a randomized cross-over trial in 40 healthy older adults (aged 65 to 75 years) with subclinical or clinical insomnia (Insomnia Severity Index (ISI) scores of ≥ 10) from the Dutch municipality of Leiden and surroundings. Participants will undergo 3 intervention periods (14 days each) consecutively: one sedentary period and two periods of increased physical activity (one period with morning activity and one period with evening activity). The intervention periods are separated by a wash-out period of 1 week. In both active intervention arms, participants will follow coached or uncoached outdoor physical exercise sessions comprising endurance, strength, and flexibility exercises for 14 days. The primary outcome is change in insomnia severity as measured by the ISI. Additional exploratory outcomes include multiple components of objective sleep quality measured with tri-axial accelerometry and subjective sleep quality assessed by questionnaires as well as dim light melatonin onset and 24-h rhythms in heart rate, heart rate variability, breathing rate, oxygen saturation, mood, and objective emotional arousal and stress. Additionally, we will collect diary data on eating patterns (timing and composition). Finally, fasting blood samples will be collected at baseline and after each intervention period for measurements of biomarkers of metabolic and physiological functioning and expression of genes involved in regulation of the biological clock.
CONCLUSIONS: We anticipate that this study will make a significant contribution to the limited knowledge on the effect of physical activity timing. Optimizing physical activity timing has the potential to augment the health benefits of increased physical exercise in the aging population.
BACKGROUND: Trial was approved by the Medical Ethics Committee Leiden, The Hague, Delft, The Netherlands (June, 2023). The trial was registered in the CCMO-register https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm under study ID NL82335.058.22 and named (\"Ouderen op tijd in beweging\" or in English \"Older adults exercising on time\"). At time of manuscript submission, the trial was additionally registered at ClinicalTrials.gov under study ID: NL82335.058.22 and is awaiting approval.

UNASSIGNED: Patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) consists of a heterogenic population and improvement in identification of a specific risk profile is needed. In this study we aimed to obtain better insight in the role of different biomarkers for patients undergoing a routine invasive diagnostic strategy within 24 hours after admission.
UNASSIGNED: An Immediate or Early Invasive Strategy in Non-ST-Elevation Acute Coronary Syndrome (OPTIMA-2) study was a randomized controlled prospective open-label multicentre trial, randomizing NSTE-ACS patients. An invasive strategy was either immediate ( < 3 hours) or early (12-24 hours). Peak high-sensitive TroponinT (hsTropT) value was determined within the first 48 hours of admission. N-terminal proB-type natriuretic peptide (NTpro-BNP) and high-sensitivity C-reactive protein (hsCRP) values were determined at admission and at discharge. These biomarkers were then divided into tertiles and related to clinical outcomes up to one year. The relation between these biomarkers and myocardial function recovery established by echocardiography was analyzed as a secondary endpoint.
UNASSIGNED: The OPTIMA-2 study included 249 patients. Overall, there was no significant increase in the risk of developing an adverse cardiovascular event in the first year if biomarker tertiles at admission were compared. However, mean NT-proBNP levels at admission were higher for patients that experienced all-cause death withing the first year (1.93 ± 0.49 vs 1.42 ± 0.58, p = 0.05). Also, peak hs-cTnT (232.0 ± 2846.0 vs 71.5 ± 1152.0, p = 0.06) values at baseline were higher in patients experiencing a myocardial infarction within 1-year. NT-proBNP levels at admission and at discharge correlated with recovery of the left ventricular (LV) function at 30 days (coefficient 0.021 (95% CI = 0.009-0.033) and coefficient 0.016 (95% CI = 0.005-0.027)).
UNASSIGNED: In NSTE-ACS patients treated by an early invasive strategy and administration of modern anticoagulant and antiplatelet therapy, multiple biomarker measurements during admission could not predict the occurrence of recurrent cardiovascular events within the first year of follow-up.

OBJECTIVE: Cerebral arteriovenous malformations (AVMs) are a challenging pathology in pediatric patients, carrying a high risk of morbidity and mortality. Treatment modalities include resection, endovascular embolization and stereotactic radiosurgery (SRS). There is currently no consensus favoring one modality over another. Timing of multimodal therapy with embolization/SRS and resection is not well explored in the literature. Here we present a series of pediatric AVM patients, with special attention paid to the timing of treatment.
METHODS: Electronic medical records of all pediatric patients (<18 years at treatment) with AVMs treated at our institution were retrospectively reviewed after IRB approval. Demographic information, AVM characteristics, treatment variables and outcomes were recorded.
RESULTS: 27 total patients were included. 21 (77.8%) presented with a ruptured AVM. 6 patients (28.6%) had an GCS of 3 to 10, and underwent treatment within 24 hours of presentation. 10 patients (47.6 %) with a GCS of 12 to 15 were treated between 24 to 120 hours. 5 patients (23.8%) were treated 3 weeks to 14 months after AVM rupture. 96% of our cohort, regardless of rupture status, had mRS of 1-2 at most recent follow-up.
CONCLUSIONS: We present our institution\'s experience with pediatric AVM\'s, focusing on the timing of treatment. Based on our experience, early treatment of AVMs seems to be safe and effective regardless of rupture status.

OBJECTIVE: The amplitude, timing, and determinants of improvement with available treatments are uncertain in chronic inflammatory demyelinating polyneuropathy (CIDP). Our primary objective was to quantify categorized outcomes with routine care.
METHODS: We retrospectively studied treatment response within 36 months from initiation in 112 consecutive subjects with CIDP. Response was classified into a proposed new \"CIDP treatment-response category\" (CT-RC), based on achieved endpoints. Determinants of the CT-RC, of timing of maximum improvement, and of treatment discontinuation were ascertained.
RESULTS: The CT-RC demonstrated high concurrent validity with current outcome measures. Thirty-six subjects (32.1%) achieved a \"complete response,\" 37 (33%) a \"good partial response,\" 10 (8.9%) a \"moderate partial response,\" and 15 (13.4%) a \"poor partial response.\" Fourteen subjects (12.5%) were \"nonresponsive.\" The CT-RC was independently predicted only by age. Mean time to maximum improvement was 12.1 months (range = 1-36) and was not associated with any pretreatment covariate. Treatment discontinuation occurred in 24 of 62 (38.2%) partial responders and was only associated with shorter pretreatment disease duration. Nonresponders were older and received a similar number of treatments compared to responders.
CONCLUSIONS: CT-RC classification indicates persistent disability in >60% of treatment responders in CIDP. Timing of maximum improvement is variable, frequently delayed, and unpredictable. Treatment withdrawal without deterioration is achievable in approximately 40% of subjects and may be more likely with prompt treatment. Treatment withdrawal in partial responders and limited escalation in nonresponders suggest implication of physician- and patient-related factors in suboptimal response. More effective treatments/treatment methods and better understanding of other factors influencing response are needed in CIDP.

BACKGROUND: Approximately 20 % of femoral fragility fracture patients take anticoagulants, typically warfarin or Direct Oral AntiCoagulant (DOAC). These can impact timing of surgery affecting patient survival. Due to several possible approaches and numerous factors to consider in the preoperative workup of anticoagulated patients, potential for variations in clinical practice exist. Some hospitals employ dedicated anticoagulation management protocols to address this issue, and to improve time to surgery. This study aimed to determine the proportion of hospitals with such protocols, compare protocol guidance between hospitals, and evaluate the effectiveness of protocols in facilitating prompt surgery.
METHODS: Data was prospectively collected through a collaborative, multicentre approach involving hospitals across the UK. Femoral fragility fracture patients aged ≥60 years and admitted to hospital between 1st May to 31st July 2023 were included. Information from dedicated anticoagulation management protocols were collated on several domains relating to perioperative care including administration of reversal agents and instructions on timing of surgery as well as others. Logistic regression was used to evaluate effects of dedicated protocols on time to surgery.
RESULTS: Dedicated protocols for management of patients taking warfarin and DOACs were present at 41 (52.6 %) and 43 (55.1 %) hospitals respectively. For patients taking warfarin, 39/41 (95.1 %) protocols specified the dose of vitamin k and the most common was 5 milligrams intravenously (n=21). INR threshold values for proceeding to surgery varied between protocols; 1.5 (n=28), 1.8 (n=6), and 2 (n=6). For patients taking DOACs, 35/43 (81.4 %) and 8/43 (18.6 %) protocols advised timing of surgery based on renal function and absolute time from last dose respectively. Analysis of 10,197 patients from 78 hospitals showed fewer patients taking DOACs received surgery within 36 h of admission at hospitals with a dedicated protocol compared to those without (adjusted OR 0.73, 95% CI 0.54-0.99, p=0.040), while there were no differences among patients taking warfarin (adjusted OR 1.64, 95% CI 0.75-3.57, p=0.219).
CONCLUSIONS: Around half of hospitals employed a dedicated anticoagulation management protocol for femoral fragility fracture patients, and substantial variation was observed in guidance between protocols. Dedicated protocols currently being used at hospitals were ineffective at improving the defined targets for time to surgery.

Physical activity is universally acknowledged for its benefits to mental health; however, the specific intensities and timings that best benefit adolescents\' mental health, crucial due to their significant influence on daily schedules, have not been thoroughly investigated. This study addresses the substantive research gap by exploring the varied effects of physical activity intensity (light versus moderate to vigorous) and timing (weekdays versus weekends and holidays) on adolescent mental health. Utilizing a large-scale longitudinal dataset (NT1 = 84,054; NT2 = 44,623) from 158 schools, this research describes the current state of adolescent physical activity and investigates the effects of physical activity on mental health outcomes, including positive (i.e., life satisfaction, positive mental health) and negative indicators (depression, anxiety), over a 6-month period. Participants were adolescents aged 9-19 years (mean age = 12.73 ± 2.43 years, 48.9% female), with the analysis adjusted for potential confounding factors. Results showed that as adolescents grow older, their engagement in moderate-to-vigorous physical activity during both weekdays and weekends/holidays tends to decrease, while light physical activity during weekdays increases. Multilevel regression analysis indicated that moderate-to-vigorous physical activity during weekends/holidays at Time 1 positively correlated with better mental health outcomes at Time 2 (six months later), featuring enhanced positive indicators and reduced negative ones. Moderate-to-vigorous physical activity on weekdays at Time 1 was positively linked to mental health at Time 2. Light physical activity during weekends/holidays at Time 1 positively predicted life satisfaction and positive mental health at Time 2. In contrast, light physical activity on weekdays at Time 1 negatively correlated with life satisfaction at Time 2. The study underscores the importance of promoting moderate-to-vigorous physical activity, particularly on weekends and holidays, to improve mental health outcomes among adolescents.

OBJECTIVE: The aim of this study was to compare the outcomes of early (≤ 90 days) and delayed (> 90 days) cranioplasty following decompressive craniectomy (DC) in patients with traumatic brain injury (TBI).
METHODS: The authors analyzed participants enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and the Neurotraumatology Quality Registry (Net-QuRe) studies who were diagnosed with TBI and underwent DC and subsequent cranioplasty. These prospective, multicenter, observational cohort studies included 5091 patients enrolled from 2014 to 2020. The effect of cranioplasty timing on functional outcome was evaluated with multivariable ordinal regression and with propensity score matching (PSM) in a sensitivity analysis of functional outcome (Glasgow Outcome Scale-Extended [GOSE] score) and quality of life (Quality of Life After Brain Injury [QOLIBRI] instrument) at 12 months following DC.
RESULTS: Among 173 eligible patients, 73 (42%) underwent early cranioplasty and 100 (58%) underwent delayed cranioplasty. In the ordinal logistic regression and PSM, similar 12-month GOSE scores were found between the two groups (adjusted odds ratio [aOR] 0.87, 95% CI 0.61-1.21 and 0.88, 95% CI 0.48-1.65, respectively). In the ordinal logistic regression, early cranioplasty was associated with a higher risk for hydrocephalus than that with delayed cranioplasty (aOR 4.0, 95% CI 1.2-16). Postdischarge seizure rates (early cranioplasty: aOR 1.73, 95% CI 0.7-4.7) and QOLIBRI scores (β -1.9, 95% CI -9.1 to 9.6) were similar between the two groups.
CONCLUSIONS: Functional outcome and quality of life were similar between early and delayed cranioplasty in patients who had undergone DC for TBI. Neurosurgeons may consider performing cranioplasty during the index admission (early) to simplify the patient\'s chain of care and prevent readmission for cranioplasty but should be vigilant for an increased possibility of hydrocephalus. Clinical trial registration nos.: CENTER-TBI, NCT02210221 (clinicaltrials.gov); Net-QuRe, NTR6003 (trialsearch.who.int) and NL5761 (onderzoekmetmensen.nl).

UNASSIGNED: Temporal co-ordination between speech and gestures has been thoroughly studied in natural production. In most cases gesture strokes precede or coincide with the stressed syllable in words that they are semantically associated with.
UNASSIGNED: To understand whether processing of speech and gestures is attuned to such temporal coordination, we investigated the effect of delaying, preposing or eliminating individual gestures on the memory for words in an experimental study in which 83 participants watched video sequences of naturalistic 3D-animated speakers generated based on motion capture data. A target word in the sequence appeared (a) with a gesture presented in its original position synchronized with speech, (b) temporally shifted 500 ms before or (c) after the original position, or (d) with the gesture eliminated. Participants were asked to retell the videos in a free recall task. The strength of recall was operationalized as the inclusion of the target word in the free recall.
UNASSIGNED: Both eliminated and delayed gesture strokes resulted in reduced recall rates compared to synchronized strokes, whereas there was no difference between advanced (preposed) and synchronized strokes. An item-level analysis also showed that the greater the interval between the onsets of delayed strokes and stressed syllables in target words, the greater the negative effect was on recall.
UNASSIGNED: These results indicate that speech-gesture synchrony affects memory for speech, and that temporal patterns that are common in production lead to the best recall. Importantly, the study also showcases a procedure for using motion capture-based 3D-animated speakers to create an experimental paradigm for the study of speech-gesture comprehension.

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