Experimental study on soil improvement by electrochemical injection of calcium chloride solutions with time interval.

An improved electroosmotic method is proposed in this paper to enhance the non-uniform effect and efficiency of electroosmotic process. Such method is electroosmotic flow with injection of calcium chloride through the anode, followed by injection through the central tube (a tube at the midpoint between the anode and the cathode) with a suitable time interval between injections. Experimental results indicate that using this method can significantly improve the non-uniform reduction in water content throughout the soil, mitigate the formation of cracks in the anode section, and therefore considerably inhibit the increase in the electric resistance. After treatment, the drained water could be raised to 3.59 times more than that of pure electroosmotic flow, and 1.3 times that of simultaneous injection through both the anode and the central tube with considerably slight increase in power consumption. Moreover, the area of cementation was also expanded, approximately twice larger than that of pure electroosmotic flow and one and a half that of simultaneous injection. It is also worth noting that the proposed method performs better with the same power consumption. The results demonstrate that electroosmotic flow with a suitable time interval between injections could improve the efficiency of electroosmotic process and expand the treatment region in soils, hence can be a promising and economic technique for soil improvement in practical engineering.

Repetition of thyroid fine-needle aspiration cytology after an initial nondiagnostic result: Is there an optimal timing?

INTRODUCTION: It is suggested to wait at least 3 months to repeat a fine needle aspiration cytology (FNAC) to avoid possible inflammatory cytological changes induced by a previous procedure. This study evaluated the influence of the interval between 2 FNACs in a cohort with a previous non-diagnostic (ND) FNAC. We analysed the occurrence of ND or atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) results in the second FNAC, based on the intervals between procedures. PATIENTS AND METHODS: Retrospective study (2017-2020) including thyroid nodules with a ND result, subjected to another FNAC. Demographic, clinical and echographic data, interval between FNACs and their results were collected. We considered the intervals: ≤/>3 months and ≤/>6 months. Second FNAC results were classified as ND, AUS/FLUS or diagnostic (including the other Bethesda categories). RESULTS: Included 190 nodules (190 patients - 82.1% women, mean age 60±13.7 years) with a first ND FNAC. The second FNAC results were: ND in 63 cases, AUS/FLUS in 9 and diagnostic in 118 cases. There were no statistical differences in FNAC results performed≤3 months (13 ND, 2 AUS/FLUS, 19 diagnostic) vs >3 months (50 ND, 7 AUS/FLUS, 99 diagnostic; p=0.71). Similarly, there were no statistical differences considering a longer time interval: ≤6 months (32 ND, 3 AUS/FLUS, 59 diagnostic) vs >6 months (31 ND, 6 AUS/FLUS, 59 diagnostic; p=0.61). CONCLUSIONS: Time interval between FNACs was not relevant to the final cytological result. Early FNAC repetition did not increase the cases of ND or AUS/FLUS.

Associations between the time interval from myomectomy to subsequent pregnancy and the obstetric outcomes: A population-based cohort study.

OBJECTIVE: To investigate the associations between time interval from myomectomy to pregnancy (TIMP) and subsequent pregnancy and obstetric complications, and to explore whether these associations vary according to maternal age at birth. METHODS: A retrospective population-based cohort study was conducted from 2008 to 2017. Data were extracted from the National Health Insurance Research Database and the Taiwan Maternal and Child Health Database, comprising 2024 379 births from 1 391 856 pregnancies. Eligible cases were identified using diagnostic and procedure codes; 4006 first singleton births in 4006 women after their first laparotomic myomectomy were identified. We estimated the risks of pregnancy and obstetric outcomes according to TIMP (<6, 6-11, and ≥12 months). Subgroup analysis was performed by further dividing according to maternal age at birth (18-34 vs ≥35 years old). RESULTS: We observed higher risks of gestational hypertensive disorders (adjusted odds ratio [aOR] 1.97, 95% confidence interval [CI] 1.22-3.18, P = 0.005) and neonatal death (aOR 4.59, 95% CI 1.49-14.18, P = 0.008) for TIMP of <6 months versus TIMP of 6-11 months. Likewise, a TIMP ≥12 months was associated with increased risks of gestational hypertensive disorders (aOR 1.72, 95% CI 1.14-2.58, P = 0.010), and neonatal death (aOR 3.27, 95% CI 1.16-9.24, P = 0.025) versus a TIMP of 6-11 months. In subgroup analysis, women over 35 years old still had higher risks of gestational hypertensive disorders when TIMP was <6 months (aOR 2.26, 95% CI 1.17-4.37, P = 0.015) or ≥12 months (aOR 2.04, 95% CI 1.17-3.54, P = 0.012), and a higher risk of neonatal death when TIMP was <6 months (aOR 4.05, 95% CI 1.06-15.53, P = 0.041); whereas women aged 18-34 years old did not. CONCLUSIONS: This study suggests that a TIMP between 6 and 11 months is associated with lower risks of gestational hypertensive disorders and neonatal death compared with a TIMP <6 months or ≥12 months, especially for women over 35 years old.

Impact of time to start of tranexamic acid treatment on rebleed risk and outcome in aneurysmal subarachnoid hemorrhage.

INTRODUCTION: The ULTRA-trial investigated effectiveness of ultra-early administration of tranexamic acid (TXA) in subarachnoid hemorrhage (SAH) and showed that TXA reduces the risk of rebleeding without concurrent improvement in clinical outcome. Previous trials in bleeding conditions, distinct from SAH, have shown that time to start of antifibrinolytic treatment influences outcome. This post-hoc analysis of the ULTRA-trial investigates whether the interval between hemorrhage and start of TXA impacts the effect of TXA on rebleeding and functional outcome following aneurysmal SAH. PATIENTS AND METHODS: A post-hoc comparative analysis was conducted between aneurysmal SAH patients of the ULTRA-trial, receiving TXA and usual care to those receiving usual care only. We assessed confounders, hazard ratio (HR) of rebleeding and odds ratio (OR) of good outcome (modified Rankin Scale 0-3) at 6 months, and investigated the impact of time between hemorrhage and start of TXA on the treatment effect, stratified into time categories (0-3, 3-6 and >6 h). RESULTS: Sixty-four of 394 patients (16.2%) in the TXA group experienced a rebleeding, compared to 83 of 413 patients (19.9%) with usual care only (HR 0.86, 95% confidence interval (CI): 0.62-1.19). Time to start of TXA modifies the effect of TXA on rebleeding rate (p < 0.001), with a clinically non-relevant reduction observed only when TXA was initiated after 6 h (absolute rate reduction 1.4%). Tranexamic acid treatment showed no effect on good outcome (OR 0.96, 95% CI: 0.72-1.27) with no evidence of effect modification on the time to start of TXA (p = 0.53). DISCUSSION AND CONCLUSIONS: This study suggests that the effect of TXA on rebleeding is modified by time to treatment, providing a protective, albeit clinically non-relevant, effect only when started after 6 h. No difference in functional outcome was seen. Routine TXA treatment in the aneurysmal SAH population, even within a specified time frame, is not recommended to improve functional outcome.

Effect of the time interval between denudation and ICSI on fresh embryo transfer reproductive outcomes: a retrospective study.

Purpose: This study aims to determine if the incubation after oocyte denudation before Intra-cytoplasmic sperm injection (ICSI) affects the clinical pregnancy rate. Methods: This was a retrospective, consecutive data analysis of 1370 patients who underwent ICSI cycles at the Department of Reproductive Medicine of West China Second University of Sichuan University (Chengdu, Sichuan) between January 2020 and July 2022. The primary outcome was the clinical pregnancy rate. The second outcome included fertilization rate, biochemical pregnancy rate, and miscarriage rates. Results: A total of 1370 continuous fresh transferred ICSI cycles were analyzed. Multivariate linear regression and logistic regression analysis of factors related to clinical pregnancy rates revealed that clinical pregnancy rates were significantly associated with denudation (DEN)-ICSI time interval. Long DEN-ICSI intervals are associated with a higher clinical pregnancy rate during fresh embryo transfer. Conclusion: The DEN-ICSI time interval is an independent factor for clinical outcomes in fresh ICSI transfer cycles.

Factors affecting the time interval of endoscopic ultrasound-guided endoscopic necrosectomy of walled-off pancreatic necrosis: A retrospective single-center study in China.

BACKGROUND AND AIM: Endoscopic ultrasound (EUS)-guided endoscopic necrosectomy is an effective and minimally invasive treatment for walled-off pancreatic necrosis (WON). This study investigated the factors affecting the time interval of EUS-guided WON necrosectomy. METHODS: Patients who received EUS-guided necrosectomy in the Endoscopy Center of the First Affiliated Hospital of Chongqing Medical University in the past 5 years were retrospectively analyzed. Data including general information, etiology, blood biochemical indexes, physical signs, CT severity grade, location, size, solid necrotic ratio, type and number of stents, and immediate necrosectomy were collected to explore the relationships between these factors and the interval of endoscopic necrosectomy. RESULTS: A total of 51 WON patients were included. No significant correlation has been noted between the endoscopic debridement interval and the following indexes, including the patients' general information, the etiology of pancreatitis, blood biochemical indexes (leukocyte count, neutrophil percentage, C-reactive protein), preoperative fever, and WON's location and size, type and number of stents, and whether immediate necrosectomy. However, there were significant differences between the debridement interval and the modified CT Severity Index (MCTSI) (p < 0.001), the solid necrotic ratio of WON (p < 0.001) before the intervention, postoperative fever (p = 0.038), C-reactive protein increasing (p = 0.012) and fever before reintervention (p = 0.024). CONCLUSIONS: The EUS-measured solid necrotic ratio, the MCTSI, postoperative fever, C-reactive protein increase, and fever before reintervention in patients affect the time interval of EUS-guided endoscopic necrosectomy in WON patients. These five indicators may be promisingly effective in predicting and managing endoscopic necrosectomy intervals.

Effect of time interval between surgery and the initiation of adjuvant therapy on the oncologic outcomes of early-stage endometrial cancer.

OBJECTIVE: To identify the impact of time interval between surgery and initial adjuvant radiotherapy on oncologic outcomes in early-stage endometrial cancer. METHODS: This retrospective cohort study included patients with stage I/II endometrial cancer who underwent surgical staging and adjuvant therapy at Songklanagarind Hospital from January 1, 2007, to December 31, 2017. Patients were categorized into two groups: TI <6 weeks and TI ≥6 weeks. The effects of TI and clinicopathological factors on recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox proportional-hazards regression. RESULTS: In total, 177 patients were enrolled, with 52% receiving adjuvant radiotherapy at <6 weeks (overall median TI 5.7 weeks). The recurrence and death rates were 13% and 10.2%, respectively. The median follow-up time was 46.6 months. The overall 3-year RFS and OS rates were 88.2% and 85.2%, respectively. The TI significantly affected the 3-year RFS (94.4% vs 81.2%; P = 0.008) and 3-year OS (95.5% vs 83.2%; P = 0.012) in patients with TI <6 and ≥6 weeks, respectively. In multivariate analysis, the depth of myometrial invasion (MI), presence of lymphovascular space invasion, and TI were independent prognostic factors for both RFS and OS. Delaying the TI (≥6 weeks) was significantly associated with a worse RFS (hazard ratio [HR] 3.70; 95% confidence interval [CI]: 1.34-10.22; P = 0.012) and an inferior OS (HR 3.80; 95% CI: 1.23-11.69; P = 0.02). CONCLUSION: A delay in the TI between surgery and the initiation of adjuvant radiotherapy of ≥6 weeks negatively affected the oncologic outcomes in early-stage endometrial cancer.

An intelligent quantification system for fetal heart rhythm assessment: A multicenter prospective study.

BACKGROUND: The motion relationship and time intervals of the pulsed-wave Doppler (PWD) spectrum are essential for diagnosing fetal arrhythmia. However, few technologies currently are available to automatically calculate fetal cardiac time intervals (CTIs). OBJECTIVE: The purpose of this study was to develop a fetal heart rhythm intelligent quantification system (HR-IQS) for the automatic extraction of CTIs and establish the normal reference range for fetal CTIs. METHODS: A total of 6498 PWD spectrums of 2630 fetuses over the junction between the left ventricular inflow and outflow tracts were recorded across 14 centers. E, A, and V waves were manually labeled by 3 experienced fetal cardiologists, with 17 CTIs extracted. Five-fold cross-validation was performed for training and testing of the deep learning model. Agreement between the manual and HR-IQS-based values was evaluated using the intraclass correlation coefficient and Spearman's rank correlation coefficient. The Jarque-Bera test was applied to evaluate the normality of CTIs' distributions, and the normal reference range of 17 CTIs was established with quantile regression. Arrhythmia subset was compared with the non-arrhythmia subset using the Mann-Whitney U test. RESULTS: Significant positive correlation (P <.001) and moderate-to-excellent consistency (P <.001) between the manual and HR-IQS automated measurements of CTIs was found. The distribution of CTIs was non-normal (P <.001). The normal range (2.5th to 97.5th percentiles) was successfully established for the 17 CTIs. CONCLUSIONS: Using our HR-IQS is feasible for the automated calculation of CTIs in practice and thus could provide a promising tool for the assessment of fetal rhythm and function.

What is the maximal timeframe between sperm acquisition to sperm cryopreservation, in different "culture" conditions?

OBJECTIVE: Most of the literature about postmortem sperm retrieval (PMSR) deals with the controversies surrounding ethical and legal aspects, while the optimal time interval between the death and viable sperm acquisition is indefinite. In an attempt to aid fertility specialists, while counseling whether to pursue and adopt PMSR, we aim to explore the maximal time frame from ejaculated sperm acquisition to sperm cryopreservation in different "culture" conditions, observations that might be extrapolated to PMSR requests. PATIENTS AND METHODS: Five healthy men with normal semen analysis were enrolled. The sperm specimen from each man was diluted to 6.5 mL. After extracting 0.5 mL for cryopreservation, the remaining 6 mL were divided into three tubes: one was maintained in room temperature (23-25 °C), the second in an incubator (37 °C), and the third in a refrigerator (4 °C). Thereafter, every day, a 0.5 mL of each sample was extracted, examined, and cryopreserved. A week later, all the cryopreserved samples were thawed and tested for sperm motility and viability. RESULTS: While at room temperature, frozen/thawed sperm were still motile (6.5%) and viable (9.9%) up to 96 h; those maintained in the refrigerator, following freezing/thawing were immotile already at 48 h in culture, but still viable (6.0%) up to 72 h in culture. Those maintained in the incubator demonstrated the worse results with negligible motility (1.5%) and viability (3.7%) following freezing/thawing, already after 48 h in culture. CONCLUSIONS: The timeframe cut-off between ejaculated sperm acquisition and cryopreservation should be 72 h, unless sperm was maintained at room temperature, where it might be longer. It would be prudent to check for sperm vitality prior to freezing in cases where only immotile sperms are present.

Administration of Antenatal Corticosteroids: Optimal Timing.

The effectiveness of antenatal corticosteroids (ACS) in significantly reducing respiratory distress syndrome (RDS) depends crucially on the timing. It is successful if delivery takes place between 24 hours and seven days following administration; after this period, the side effects seem to predominate. In addition, an increased rate of mental impairment and behavioral disorders are observed in children born full-term after ACS administration. The optimal timing of ACS administration depends crucially on the given indication; to date, it has been achieved in only 25-40% of cases. ACS administration is always indicated in PPROM, in severe early pre-eclampsia, in fetal IUGR with zero or reverse flow in the umbilical artery, in placenta previa with bleeding, and in patients experiencing premature labor with a cervical length < 15 mm. The risk of women with asymptomatic cervical insufficiency giving birth within seven days is very low. In this case, ACS should not be administered even if the patient's cervical length is less than 15 mm, provided that the cervix is closed and there are no other risk factors for a premature birth. The development of further diagnostic methods with improved power to predict premature birth is urgently needed in order to optimize the timing of ACS administration in this patient population. Caution when administering ACS is also indicated in women experiencing premature labor who have a cervical length ≥ 15 mm. Further studies using amniocentesis are needed in order to identify the patient population with microbial invasion of the amniotic cavity/intra-amniotic infection (MIAC/IAI), and to define threshold values at which delivery is indicated. ACS administration is not performed as an emergency measure, usually not even before transfer to a perinatal center. Therefore, whenever possible, the indication for ACS administration should be determined by a clinician who is highly experienced in perinatology.

Feasibility of Noninvasive Assessment of Cardiac Output during Exercise in Healthy Adults by a Novel Elaboration on Systolic Time Intervals.

BACKGROUND: Although assessment of cardiovascular hemodynamics during exercise can provide clinical insights, it is challenging to acquire it in clinical settings. OBJECTIVES: Accordingly, this preliminary study was to determine whether a novel elaboration on systolic time interval measures (eSTICO) method of quantifying cardiac output and stroke volume was comparable to those obtained using a validated soluble gas (open circuit CO measure [OpCircCO]) method or calculation based on oxygen consumption (oxygen consumption-based CO [VO2CO]) during exercise. METHODS: For the present study, 14 healthy subjects (male: n = 12, female: n = 2) performed incremental exercise on a recumbent cycle ergometer. At rest and during exercise, cardiac output (CO) was obtained via the eSTICO method, while the OpenCircCO and VO2CO measures were obtained at the last minute of each workload. RESULTS: At peak, there was no difference between eSTICO and OpCircCO (12.39 ± 3.06 vs. 13.96 ± 2.47 L/min, p > 0.05), while there was a slight difference between eSTICO and VO2CO (12.39 ± 3.06 vs. 14.28 ± 2.55 L/min, p < 0.05). When we performed correlation analysis with all subjects and all measures of CO at all WL, between eSTICO and OpenCircCO, there was a good relationship (r = 0.707, p < 0.001) with a Bland and Altman agreement analysis demonstrating a -1.6 difference (95% LoA: -6.3-3.5). Between eSTICO and VO2CO, we observed an r = 0.865 (p < 0.001) and a Bland and Altman agreement analysis with a -1.2 difference (95% LoA: -4.8-2.4). CONCLUSION: A novel exploitation of cardiac hemodynamics using systolic timing intervals may allow a relatively good assessment of CO during exercise in healthy adults.

National Improvement of Waiting Times: First Results From the Dutch Head and Neck Audit.

OBJECTIVE: Timely treatment initiation in head and neck cancer (HNC) care is of great importance regarding survival, oncological, functional, and psychological outcomes. Therefore, waiting times are assessed in the Dutch Head and Neck Audit (DHNA). This audit aims to assess and improve the quality of care through feedback and benchmarking. For this study, we examined how waiting times evolved since the start of the DHNA. STUDY DESIGN: Prospective cohort study. SETTING: National multicentre study. METHODS: The DHNA was established in 2014 and reached national coverage of all patients treated for primary HNC in 2019. DHNA data on curative patients from 2015 to 2021 was extracted on national (benchmark) and hospital level. We determined 3 measures for waiting time: (1) the care pathway interval (CPI, first visit to start treatment), (2) the time to treatment interval (TTI, biopsy to start treatment), and (3) CPI-/TTI-indicators (percentage of patients starting treatment ≤30 days). The Dutch national quality norm for the CPI-indicator is 80%. RESULTS: The benchmark median CPI and TTI improved between 2015 and 2021 from 37 to 26 days and 37 to 33 days, respectively. Correspondingly, the CPI- and TTI-indicators, respectively, increased from 39% to 64% and 35% to 40% in 2015 to 2021. Outcomes for all hospitals improved and dispersion between hospitals declined. Four hospitals exceeded the 80% quality norm in 2021. CONCLUSION: Waiting times improved gradually over time, with 4 hospitals exceeding the quality standard in 2021. On the hospital-level, process improvement plans have been initiated. Systematic registration, auditing, and feedback of data support the improvement of quality of care.

Comparison of the Efficacy and Safety of Sublingual Versus Oral Misoprostol for the Induction of Labor: A Randomized Open-Label Study.

Introduction Misoprostol (prostaglandin E1 analog) is being used for the induction of labor by vaginal, oral, and sublingual routes. Oral misoprostol is the preferred route for induction of labor, but the use of sublingual misoprostol appears promising due to a faster onset of action. This study was done to compare the efficacy and safety of oral and sublingual misoprostol for induction of labor in term pregnancy. Materials and methods One hundred and sixty patients were randomly allocated to one of the two groups to receive 50 micrograms of oral and sublingual misoprostol four hourly for a maximum of six doses. Primigravida at 37-42 weeks of gestation with singleton pregnancy, cephalic presentation, Bishop score (<5), and reassuring fetal heart rate were included in the study. Misoprostol dose was withheld if the active phase of labor was reached or if the cervix was favorable for amniotomy (Bishop score greater than or equal to eight). The change in the Bishop score with misoprostol was studied along with adverse effects and neonatal outcomes. Results The mean number of 50 mcg misoprostol doses required was significantly less in the sublingual group (2.94±0.97 versus 2.13±0.92; p<0.0001). The rate of change of the mean Bishop score was faster in the sublingual group. After four hours of the first dose, the mean Bishop score changed to 3.52±2.14 versus 4.68±2.34 (p=0.001), and, similarly, after eight hours, it was 10.48±2.59 versus 11.39±2.06, and this difference was statistically significant (p=0.015). The mean induction delivery interval was significantly lower in the sublingual group. The need for labor augmentation, mode of delivery, and adverse effects were similar in both groups. The incidence of meconium-stained liquor and NICU admission was also similar in both groups. Conclusion Sublingmisoprostolstol has a short induction delivery interval and comparable side effects when compared to omisoprostolstol. Sublingmisoprostolstol is recommended for induction of labor at term.

"Low-risk groups" deserve more attention than "high-risk groups" in imported COVID-19 cases.

Objective: To estimate the optimal quarantine period for inbound travelers and identify key risk factors to provide scientific reference for emerging infectious diseases. Methods: A parametric survival analysis model was used to calculate the time interval between entry and first positive nucleic acid test of imported cases in Guangzhou, to identify the influencing factors. And the COVID-19 epidemic risk prediction model based on multiple risk factors among inbound travelers was constructed. Results: The approximate 95th percentile of the time interval was 14 days. Multivariate analysis found that the mean time interval for inbound travelers in entry/exit high-risk occupations was 29% shorter (OR 0.29, 95% CI 0.18-0.46, p < 0.0001) than that of low-risk occupations, those from Africa were 37% shorter (OR 0.37, 95% CI 0.17-0.78, p = 0.01) than those from Asia, those who were fully vaccinated were 1.88 times higher (OR 1.88, 95% CI 1.13-3.12, p = 0.01) than that of those who were unvaccinated, and those in other VOC periods were lower than in the Delta period. Decision tree analysis showed that a combined entry/exit low-risk occupation group with Delta period could create a high indigenous epidemic risk by 0.24. Conclusion: Different strata of imported cases can result in varying degrees of risk of indigenous outbreaks. "low-risk groups" with entry/exit low-risk occupations, fully vaccinated, or from Asia deserve more attention than "high-risk groups."

The Impact of the COVID-19 Outbreak on Emergency Medical Service: An Analysis of Patient Transportations and Time Intervals.

BACKGROUND: This study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) outbreak on the Emergency Medical Service (EMS) system in South Korea. The study focused on the differences in EMS time intervals following the COVID-19 outbreak, particularly for patients with fever. METHODS: A retrospective analysis of EMS patient transportation data from 2017 to 2022 was conducted using the national EMS database. RESULTS: Starting from the year 2020, coinciding with the COVID-19 outbreak, all EMS time intervals experienced an increase. For the years 2017 to 2022, the mean response time interval values were 8.6, 8.6, 8.6, 10.2, 12.8, and 11.4 minutes, and the mean scene time interval values were 7.1, 7.2, 7.4, 9.0, 9.8, and 10.9 minutes. The mean transport time interval (TTI) values were 12.1, 12.3, 12.4, 14.2, 16.9, and 16.2 minutes, and the mean turnaround time interval values were 27.6, 27.9, 28.7, 35.2, 42.0, and 43.1 minutes. Fever (≥ 37.5°C) patients experienced more pronounced prolongations in EMS time intervals compared to non-fever patients and had a higher probability of being non-transported. The mean differences in TTI between fever and non-fever patients were 0.8, 0.8, 0.8, 4.3, 4.8, and 3.2 minutes, respectively, from 2017 to 2022. Furthermore, the odds ratios for fever patients being transported to the emergency department were 2.7, 2.9, 2.8, 1.1, 0.8, and 0.7, respectively, from 2017 to 2022. CONCLUSION: The study findings highlight the significant impact of the COVID-19 outbreak on the EMS system and emphasize the importance of ongoing monitoring to evaluate the burden on the EMS system.

Impact of follow ups, time interval and study duration in diffusion & myelin MRI clinical study in MS.

It is currently unknown how quantitative diffusion and myelin MRI designs affect the results of a longitudinal study. We used two independent datasets containing 6 monthly MRI measurements from 20 healthy controls and 20 relapsing-remitting multiple sclerosis (RR-MS) patients. Six designs were tested, including 3 MRI acquisitions, either over 6 months or over a shorter study duration, with balanced (same interval) or unbalanced (different interval) time intervals between MRI acquisitions. First, we show that in RR-MS patients, the brain changes over time obtained with 3 MRI acquisitions were similar to those observed with 5 MRI acquisitions and that designs with an unbalanced time interval showed the highest similarity, regardless of study duration. No significant brain changes were found in the healthy controls over the same periods. Second, the study duration affects the sample size in the RR-MS dataset; a longer study requires more subjects and vice versa. Third, the number of follow-up acquisitions and study duration affect the sensitivity and specificity of the associations with clinical parameters, and these depend on the white matter bundle and MRI measure considered. Together, this suggests that the optimal design depends on the assumption of the dynamics of change in the target population and the accuracy required to capture these dynamics. Thus, this work provides a better understanding of key factors to consider in a longitudinal study and provides clues for better strategies in clinical trial design.

The timing of durvalumab administration affects the risk of pneumonitis in patients with locally advanced non-small cell lung cancer: a systematic review and meta-analysis.

PURPOSE: The PACIFIC study has demonstrated that the administration of durvalumab following concurrent chemoradiotherapy can significantly improve both overall survival and progression-free survival rates in patients with locally advanced unresectable non-small cell lung cancer. While the latest NCCN guidelines recommend this combination regimen, they do not specify the optimal timing for administering durvalumab after completing radiotherapy. The PACIFIC study suggested initiating durvalumab within 42 days of completing radiotherapy, but early administration of the drug may increase the incidence of pneumonitis. Therefore, we conducted this study to investigate whether the time interval between completion of radiotherapy and initiation of durvalumab treatment is associated with the risk of pneumonitis (Grade ≥ 3), which is the primary endpoint, as well as progression-free survival, which is the secondary endpoint. METHODS: A comprehensive search of clinical trials in PubMed and EMBASE was conducted up to March 2023 to identify clinical trials involving locally advanced unresectable non-small cell lung cancer patients who were treated with durvalumab following chemoradiotherapy. Meta-analysis was performed on single-arm studies to estimate the incidence of pneumonitis (Grade ≥ 3) and progression-free survival in all studies, as well as in studies that administered durvalumab within 42 days after completion of radiotherapy. RESULTS: This meta-analysis consisted of nine studies with a total of 2560 patients. The analysis showed that the incidence of pneumonitis (Grade ≥ 3) was 5.36% [95%CI (0.03, 0.08), I2 = 18.41%, p = 0.29], while the 1-year progression-free survival rate was 57.91% [95%CI (0.53, 0.63), I2 = 10.57%, p = 0.35]. Furthermore, when the duration between completion of radiotherapy and initiation of durvalumab treatment was shorter than 42 days, the incidence of pneumonitis (Grade ≥ 3) was 4.12% [95%CI (0.02, 0.06), I2 = 0.00%, p = 0.56], with a 1-year progression-free survival rate of 61.03% [95%CI (0.51, 0.71), I2 = 59.06%, p = 0.09]. CONCLUSION: Overall, based on the available evidence, it appears that there is no significant increase in pneumonitis or decrease in progression-free survival (PFS) when the time interval is less than 42 days and a shorter interval between treatment sessions does not necessarily have a detrimental effect on the rate of pneumonitis. We recommend that clinicians carefully evaluate the specific circumstances of each patient to determine the optimal timing for initiating immunotherapy.

The Impact of Time Interval on Prognosis in Patients with Non-Small Cell Lung Cancer Brain Metastases After Metastases Surgery.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a prominent malignancy often linked to the development of brain metastases (BM), which commonly appear at diverse time intervals (TI) following the lung cancer diagnosis. This study endeavors to determine the prognostic significance of the time interval in patients with NSCLC who undergo BM surgery. Through this investigation, we aim to improve our understanding of the factors impacting the prognosis of BM cases originating from NSCLC. METHODS: We analyzed data from 74 patients (2011-2021) who underwent BM surgery at our institution. The relationship between various clinical, radiological, and histopathological factors, as well as TI and overall survival (OS), was examined. RESULTS: The median TI from initial NSCLC diagnosis to BM surgery was 19 months (range: 9-36 months). Notably, a shorter TI of less than 23 months was found to be independently associated with postoperative survival (adjusted odds ratio [aOR] 2.87, 95% confidence interval [CI] 1.03-8.02, P = 0.045). Additionally, a shorter TI was independently correlated with the absence of adjuvant chemotherapy for NSCLC (aOR 0.25, 95% CI 0.07-0.83, P = 0.023) and lack of targeted therapy (aOR 0.02, 95% CI 0.00-0.16, P < 0.001). Late-onset BM (TI ≥ 36 months) was observed in 15 cases (20.3%), in this subgroup, patients aged 60 years or older at the time of lung cancer diagnosis exhibited a significant independent correlation with late-onset BM (aOR 7.24, 95% CI 1.59-32.95, P = 0.011). NSCLC patients who underwent adjuvant chemotherapy displayed a notable correlation with late-onset BM (aOR 6.46, 95% CI 1.52-27.43, P = 0.011), while those who received targeted therapy also exhibited an independent association (aOR 2.27, 95% CI 1.70-3.03, P < 0.001). CONCLUSIONS: Multiple factors contribute to the variability in the onset interval of BM subsequent to NSCLC diagnosis. The occurrence of BM within TI < 23 months following the initial diagnosis of NSCLC was demonstrated as an independent factor associated with an unfavorable prognosis following BM surgery. Furthermore, patients with NSCLC who did not receive adjuvant chemotherapy and lacked targeted therapy were shown to have an elevated likelihood of developing BM after a long progression-free survival.

Radiomic Assessment of Radiation-Induced Alterations of Skeletal Muscle Composition in Head and Neck Squamous Cell Carcinoma within the Currently Clinically Defined Optimal Time Window for Salvage Surgery-A Pilot Study.

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) frequently require primary radiochemotherapy (RCT). Despite intensity modulation, the desired radiation-induced effects observed in HNSCC may also be observed as side effects in healthy tissue, e.g., the sternocleidomastoid muscle (SCM). These side effects (e.g., tissue fibrosis) depend on the interval between the completion of RCT and restaging CT. For salvage surgery, the optimal time window for surgery is currently clinically postulated at between 6 and 12 weeks after completion of RCT. Thus, no extensive tissue fibrosis is to be expected. This interval is based on clinical studies exploring surgical complications. Studies directly exploring radiation-induced changes of the SCM in HNSCC patients are sparse. The present study quantified tissue alterations in the SCM and paravertebral musculature (PVM) after RCT, applying radiomics to determine the optimal time window for salvage surgery. Three radiomic key parameters, (1) volume, (2) mean positivity of pixels (MPP), and (3) uniformity, were extracted with mint LesionTM in the staging CTs and restaging CTs of 98 HNSCC patients. Of these, 25 were female, the mean age was 62 (±9.6) years, and 80.9% were UICC Stage IV. The mean restaging interval was 55 (±28; range 29-229) days. Only the mean volume significantly decreased after RCT, from 9.0 to 8.4 and 96.5 to 91.9 mL for the SCM and PVM, respectively (both p = 0.007, both Cohen's d = 0.28). In addition, the mean body mass index (BMI) decreased from 23.9 (±4.2) to 21.0 (±3.6) kg/m² (p < 0.001; Cohen's d = 0.9). The mean BMI decreased significantly and was correlated with the volume decrease for the SCM (r = 0.27; p = 0.007) and PVM (r = 0.41; p < 0.001). If t-test p-values were adjusted for the BMI decrease, no significant change in volumes for the SCM and PVM was observed (both p > 0.05). The present data support the clinically postulated optimal interval for salvage surgery of 6 to 12 weeks.

Optimal Time Interval between Neoadjuvant Platinum-Based Chemotherapy and Interval Debulking Surgery in High-Grade Serous Ovarian Cancer.

BACKGROUND: There is limited data on the optimal time interval between the last dose of neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) in high-grade serous ovarian carcinoma (HGSC). METHODS: We retrospectively identified patients with stage IIIC/IV HGSC who received NACT followed by IDS during a 15-year period (January 2003-December 2018) in our Institution. RESULTS: Overall, 115 patients with stage IIIC/IV HGSC were included. The median age of diagnosis was 62.7 years (IQR: 14.0). A total of 76.5% (88/115) of patients were diagnosed with IIIC HGSC and 23.5% (27/115) with IV HGSC. Median PFS was 15.7 months (95% CI: 13.0-18.5), and median OS was 44.7 months (95% CI: 38.8-50.5). Patients were categorized in groups according to the time interval from NACT to IDS: <4 weeks (group A); 4-5 weeks (group B); 5-6 weeks (group C); >6 weeks (group D). Patients with a time interval IDS to NACT ≥4 weeks had significantly shorter PFS (p = 0.004) and OS (p = 0.002). Median PFS was 26.6 months (95% CI: 24-29.2) for patients undergoing IDS <4 weeks after NACT vs. 14.4 months (95% CI: 12.6-16.2) for those undergoing IDS later (p = 0.004). Accordingly, median OS was 66.3 months (95% CI: 39.1-93.4) vs. 39.4 months (95% CI: 31.8-47.0) in the <4 week vs. >4 week time interval NACT to IDS groups (p = 0.002). On multivariate analysis, the short time interval (<4 weeks) from NACT to IDS was an independent factor of PFS (p = 0.004) and OS (p = 0.003). CONCLUSION: We have demonstrated that performing IDS within four weeks after NACT may be associated with better survival outcomes. Multidisciplinary coordination among ovarian cancer patients is required to avoid any unnecessary delays.