Time Research Articles

The effect of time from surgery to commencing adjuvant radiotherapy for patients with head and neck squamous cell carcinoma.

Studies reported inferior outcomes when radiotherapy starts >6-8weeks post-surgery for head and neck squamous cell carcinoma (HNSCC) but are limited due to time variable dichotomization. We assessed the relationship between survival and the time between surgery and radiotherapy as a continuous variable, hypothesising there would be no change in patients' survival at 6-8weeks post-surgery. Inclusion criteria: patients with HNSCC who underwent surgery and adjuvant (chemo)radiotherapy, Jan 2014-Dec 2020. A sub-cohort included patients with oral cavity squamous cell carcinoma (OCSCC) treated at the same institution, Jan 2016-Dec 2020. The primary endpoint was overall survival (OS); a multivariable Cox model was fitted. For the OCSCC sub-cohort, the endpoint of interest was progression-free survival (PFS); a multivariable competing risk regression model was fitted. 386 patients with HNSCC were included (main cohort). The median time between surgery and radiotherapy was 44days (IQR: 14days). Plotting time intervals vs log(hazard) did not demonstrate a threshold time where risk of death increases. The time interval between surgery and radiotherapy was not associated with OS (HR 1.00; 95% CI 0.99-1.02; p=0.4). In the sub-cohort of 208 patients with OCSCC, the time interval between surgery and radiotherapy was not associated with increased risk of cancer vs competing events (HR 1.01; 95% CI 0.99-1.03; p=0.5). Increasing time interval between surgery and radiotherapy was not associated with inferior survival outcomes. We suggest patients are considered for radiotherapy >6-8weeks post-surgery and that no threshold is considered for patient selection.

Formulation and Evaluation of Hard Lozenges by Using Garlic Tincture

Background: Lozenges are one of the more well-liked and inventive oral confectionery products in the market. The lozenges also act as solid medications that are flavored, sweetened, and meant to be sucked into the mouth/pharynx or held over that cavity. Garlic contains anti-microbial agents which help to reduce the impact of cough and reduce it. Aims: The goal of the current research is to formulate and investigate herbal lozenges by using garlic tinctures with their antimicrobial action to cure the infection caused by microbes. Methods: Hard lozenges were prepared by Heating and congealing techniques and statistical analysis was done by using one sample chi-square test (IBM SPSS version 20). Results: Hard lozenges were formulated by using garlic tinctures with minimum excipients. According to ICH recommendations, stability experiments were conducted. According to the stability investigations, there were no major changes noticed during the period after the one-month stability test. The antimicrobial activity was studied under different time intervals after 8-72 hours. The inhibition zone value for the test sample was found to be 0.1-0.5 mm and for the standard sample was noticed from 0.5-0.8 mm, respectively. The statistical test outcome revealed, no remarkable difference shown between the prepared and the marketed formulation (p>0.05). Conclusion: From the present work, it was concluded that the prepared lozenges have similar result with minimum ingredients as compared to the marketed formulation (Tulsi-ginger lozenges). Hence, the formulation, testing, and antimicrobial activity for oral use in garlic lozenges were effective.

Abstract TMP76: Inadequate Pre-Procedure Antiplatelet Medication Use May Explain the Higher Risk of Peri-Procedural Stroke and/or Death with Carotid Stent Placement within First 7 Days after Qualifying Ischemic Event

Background and Purpose: In randomized trials, carotid artery stent (CAS) may have higher risk of periprocedural risk compared with carotid endarterectomy (CEA) if performed within the first 7 days after the onset of symptoms. Methods: We analyzed the data from Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). The time interval between the most recent qualifying ischemic event and CAS/CEA procedure was divided in four strata: 1-7 days, 8-14 days, 15-30 days and >30 days. We analyzed the effect of time interval strata between most recent qualifying ischemic event and procedure and procedure type (CEA versus CAS) on peri-procedural stroke and/or death after adjusting for age, gender, symptomatic status and initial severity of stenosis (≥70% versus <70%). Results: The rate of periprocedural stroke and/or death was significantly higher in patients who underwent CAS compared with CEA at 7 days or less after the qualifying event (5.4% versus 0%, p=0.031) but not significantly different in patients who underwent CAS compared with CEA at 8-14 days (3.8%versus 2.0%, p=0.68), at 15-30 days (5.1% versus 1.8%, p=0.26) days and >30 days (CAS 7.8% versus CAE 4.3%, p=0.12), after the most recent qualifying event. In the multivariate analysis, patients who underwent CAS had higher rate of peri-procedural stroke and/or death (odds ratio [OR] 2.36, 95% confidence interval [CI] 1.25- 4.66) but timing of procedure were not associated with higher rate of peri-procedural stroke and/or death after adjustment for potential confounders. The interaction between procedure type and timing of procedure was not significant. The rate of peri-procedural stroke and/or death was significantly higher in CAS patients who received clopidogrel bolus (without 48-hour maintenance dose) among patients treated 7 days or less after the qualifying event compared with those undergoing CEA (6.6% versus 0%, p=0.012) but was not different between CAS patients who received 48 hours of clopidogrel maintenance and those undergoing CEA (0% versus 0%). Conclusions: The higher rate of peri-procedural stroke and/or death seen with CAS (compared with CEA) within the first 7 days may be attributed to factors such as inadequate pre-procedure antiplatelet medication use. The results of CAS and CEA may become comparable within the first 7 days after the qualifying ischemic event with use of newer generation P2Y12 platelet inhibitors that achieve rapid antiplatelet inhibition.

Reduced physiology-induced temporal instability achieved with variable-flip-angle fast low-angle excitation echo-planar technique with multishot echo planar time-resolved imaging.

Echo planar time-resolved imaging (EPTI) is a new imaging approach that addresses the limitations of EPI by providing high-resolution, distortion- and T2/ blurring-free imaging for functional MRI (fMRI). However, as in all multishot sequences, intershot phase variations induced by physiological processes can introduce temporal instabilities to the reconstructed time-series data. This study aims to reduce these instabilities in multishot EPTI. In conventional multishot EPTI, the time intervals between the shots comprising each slice can introduce intershot phase variations. Here, the fast low-angle excitation echo-planar technique (FLEET), in which all shots of each slice are acquired consecutively with minimal time delays, was combined with a variable flip angle (VFA) technique to improve intershot consistency and maximize signal. A recursive Shinnar-Le Roux RF pulse design algorithm was used to generate pulses for different shots to produce consistent slice profiles and signal intensities across shots. Blipped controlled aliasing in parallel imaging simultaneous multislice was also combined with the proposed VFA-FLEET EPTI to improve temporal resolution and increase spatial coverage. The temporal stability of VFA-FLEET EPTI was compared with conventional EPTI at 7 T. The results demonstrated that VFA-FLEET can provide spatial-specific increase of temporal stability. We performed high-resolution task-fMRI experiments at 7 T using VFA-FLEET EPTI, and reliable BOLD responses to a visual stimulus were detected. The intershot phase variations induced by physiological processes in multishot EPTI can manifest as specific spatial patterns of physiological noise enhancement and lead to reduced temporal stability. The VFA-FLEET technique can substantially reduce these physiology-induced instabilities in multishot EPTI acquisitions. The proposed method provides sufficient stability and sensitivity for high-resolution fMRI studies.

The effect of long-term glycemic burden on the incidence of diabetic foot ulcers: A retrospective study

BackgroundThis study aimed to examine the association between mean cumulative glycemic burden (MCGB) and variability cumulative glycemic burden (VCGB) with diabetic foot ulcers (DFUs). MethodsParticipants were followed up at least 4 times with 4 recorded glycosylated hemoglobin (HbA1c) measurements. Glycemic burden during follow-up period was defined as the trapezoidal areas enclosed by the HbA1c measurements taken during two consecutive visits and the responding time interval. MCGB was calculated by dividing sum of total trapezoidal areas by the period of follow-up. VCGB was defined as the standard deviation of the trapezoidal areas divided to the mean of trapezoidal areas. To identify the association between MCGB and VCGB with DFUs, a Cox regression analysis was conducted. ResultsAmong 1876 diabetic patients, 138 (7.4 %) developed foot ulcers. As MCGB increased across quartiles, DFUs incidence also rose significantly (3.2 % to 16.0 %, P < 0.001). Similarly, the prevalence of DFUs increases with increasing quartiles of mean HbA1c level (3.2 % to 16.2 %; P < 0.001). When assessing VCGB, ulcer incidence gradually increased with the quartiles increased (P = 0.040), but HbA1c variability did not follow a similar trend (P = 0.133).Multivariable Cox regression analysis indicates that compared to the first quartile, both MCGB and VCGB in the fourth quartile significantly increase the risk of DFUs (HR = 2.99 and 5.29, respectively). ConclusionsElevated MCGB and VCGB correlate positively with DFUs. In clinical practice, lowering blood glucose levels and reducing glycemic variability are both crucial for reducing the occurrence of diabetic foot ulcers.

Abstract TMP66: Implementing Intracerebral Hemorrhage-Specific Time Interval Metrics in the Emergency Department Reduces Door-to-Goal Blood Pressure Time.

Introduction: The 2022 AHA/ASA Guidelines for Nontraumatic ICH recommend initiating blood pressure (BP) reduction within 2 hours of onset and achieving a target systolic BP of 130-150 mmHg within one hour of initiating a BP medication. This study evaluates the effectiveness of implementing ICH-specific time intervals, modeled after TARGET: STROKE, coupled with provider education to improve the timeliness of BP reduction in ICH patients. Methods: Data were retrospectively collected at a CSC from 01/1/2021 to 12/31/2022 (pre-intervention) and from 1/1/2023 to 5/31/2024 (post-intervention). Emergency Department (ED) code stroke patients with an ICH were included. ED providers were given education on which BP intervals would be measured, and how to improve the timeliness of BP reduction. Baseline demographics, NIHSS, ICH volume, ICH score, 90-day mRS and door-to-BP reduction-related time metrics were collected. The data were analyzed using Kruskal-Wallis and Chi-square tests. Results: 91 code stroke patients presented to the ED with ICH. 32 pre- and 59 post-intervention. There were no differences between mean age, gender, race/ethnicity, NIHSS, ICH score or time from last known well to ED arrival between groups. Both groups had similar median ICH volumes; post- 18.4ml (IQR 5.2-44.7) vs. pre-intervention: 19.7ml (IQR 5.3-44.3) vs. (p=1.0). Door to first BP medication ordered was reduced to 13 (IQR 10.0-21.0) minutes post vs. 19 (IQR 14.5-25.5) minutes pre-intervention (p=0.007). Door to first BP medication administered was reduced to 21.0 (IQR 14.0-34.0) minutes post vs 29.5 (IQR 18.5-47.5) minutes pre-intervention (p=0.03). Time from first BP medication administration to goal SBP in rage of 130-150 improved to 43 minutes (IQR 33-52.3) post vs. 75 minutes (IQR 46.7-80) minutes pre-intervention. Door to first SBP in range of 130-150 mmHg improved to 60 minutes (IQR 46.0-80.0) post vs 98 minutes (IQR 69.5-141.0) pre-intervention p&lt;0.0001. There were no differences in hematoma expansion or 90-day mRS between both groups, possibly due to the small sample size. Conclusion: This is the first study to show that implementing ICH-specific time intervals in the ED, combined with provider education, effectively improve the timeliness of BP management in ICH patients. It highlights the value of ED education on guideline recommended time-targeted treatment of ICH care.

Temporal pavlovian conditioning of a model spiking neural network for discrimination sequences of short time intervals.

The brain's ability to learn and distinguish rapid sequences of events is essential for timing-dependent tasks, such as those in sports and music. However, the mechanisms underlying this ability remain an active area of research. Here, we present a Pavlovian-conditioned spiking neural network model that may help elucidate these mechanisms. Using "three-factor learning rule," we conditioned an initially random spiking neural network to discriminate a specific spatiotemporal stimulus - a sequence of two or three pulses delivered within ms to two or three distinct neuronal subpopulations - from other pulse sequences differing by only a few milliseconds. Through conditioning, a feedforward structure emerges that encodes the target pattern's temporal information into specific topographic arrangements of stimulated subpopulations. In the readout phase, discrimination of different inputs is achieved by evaluating the shape and peak-shift characteristics of the spike density functions (SDFs) of input-triggered population bursts. The network's dynamic range - defined by the duration over which pulse sequences are processed accurately - is limited to around 10 ms, as determined by the duration of the input-triggered population burst. However, by introducing axonal conduction delays, we show that the network can generate "superbursts," producing a more complex and extended SDF lasting up to 30 ms, and potentially much longer. This extension effectively broadens the network's dynamic range for processing temporal sequences. We propose that such conditioning mechanisms may provide insight into the brain's ability to perceive and interpret complex spatiotemporal sensory information encountered in real-world contexts.

Predictive models for post-liver transplant survival using machine learning techniques in three critical time intervals

Predictive models for post-liver transplant survival using machine learning techniques in three critical time intervals

Force Degradation of Intermaxillary Latex Elastics: Comparative In Vitro and In Vivo Study.

This study aimed to compare the force degradation of intermaxillary elastics (IE) in vitro and in vivo while stretching the IE to a precise diameter. IE 3/16″ medium Dentaurum from five different batches of packaging were analyzed. The in vivo study involved 10 volunteers, of which 100 IE were examined. To achieve three times the original diameter of the elastic, the distance between the upper canine and the lower dental arch was measured. Buttons were then placed in the mouth accordingly, and IE and passive aligners were inserted for five sessions of 48 h each. To investigate in vitro, 100 IE were placed in an incubator set at 37°C in a humid environment and stretched three times their diameter. The force of the elastics was measured in both investigations using a force meter at 0, 2, 8, 24, and 48 h. In all patients except one, the three times diameter distance extended from the upper canine to the lower second premolar. The force degradation in vivo at 2, 8, 24, and 48 h was 20.58%, 26.78%, 34.81%, and 38.56% and in vitro was 16.38%, 22.83%, 28.32%, and 30.78%. The amount of stretching of IE varies for each patient when using standard insertion points. The force of IE decreases exponentially, the force degradation in vivo being higher. The clinician must consider the force decrease when advising the patient of the time interval to change the elastics.

Frequency of surveillance CT scan ordering in patients with stage II/III colorectal cancer.

106 Background: Patients with stage II/III colorectal cancer (CRC) undergo surveillance CT scans to detect early asymptomatic oligometastatic spread, which can be treated with curative intent. However, randomized clinical trials show no difference in 5-year mortality in those that undergo low intensity surveillance (annual) compared a higher intensity strategy (every 6 months). In Ontario, the Program in Evidence-Based Care (PEBC), Ontario Health (Cancer Care Ontario) guidelines recommend surveillance CT scan for patients with stage II/III CRC every 12 months. We aimed to determine the frequency at which clinicians in our Ontario-based hospital system ordered surveillance CT scans for patients with stage II/III CRC. Methods: This single centre retrospective cohort study included all patients that underwent surgical resection for CRC from April 1, 2018 – March 31, 2019 at our academic tertiary care centre in Ontario, Canada. We excluded patients that were followed at an outside hospital, had stage IV disease, had disease recurrence, had a concurrent neoplasm, or did not have CRC. The primary outcome was the proportion of surveillance CT scans completed 10+ months after the previous scan. We also described sociodemographic and medical characteristics of included patients. Follow-up was until August 2023. Results: We included 200 patients. The median age was 62 years (IQR: 52-70), 48% (N=96) were female, the rectum was the most commonly involved disease site (43%, N=86), 38% (N=76) had stage III disease, and 54% (N=107) received adjuvant chemotherapy. A total of 1286 scans were ordered during the study period. Of these, 67% (N=860) were ordered as surveillance. Of these, 18% (n=155) were completed 10 months or longer from the previous scan. The median time interval between surveillance scans was 6.6 months (IQR: 5.9-7.9). Approximately 20% (n=137 of 630) of surveillance scans ordered by general surgeons were completed 10 months or longer from the previous scan, whereas only 9% (n=18 of 205) of scans ordered by medical oncologists were completed 10 months or longer from the previous scan. Less than 1% of surveillance scans (n=3) identified new metastatic disease. Conclusions: The minority of surveillance CT scans ordered in patients with stage II/III CRC in our hospital were timed in concordance with Ontario-based guidelines. Future studies should seek to standardize ordering habits such that they align with best practices.

STCNet: Spatio-Temporal Cross Network with subject-aware contrastive learning for hand gesture recognition in surface EMG.

This paper introduces the Spatio-Temporal Cross Network (STCNet), a novel deep learning architecture tailored for robust hand gesture recognition in surface electromyography (sEMG) across multiple subjects. We address the challenges associated with the inter-subject variability and environmental factors such as electrode shift and muscle fatigue, which traditionally undermine the robustness of gesture recognition systems. STCNet integrates a convolutional-recurrent architecture with a spatio-temporal block that extracts features over segmented time intervals, enhancing both spatial and temporal analysis. Additionally, a rolling convolution technique designed to reflect the circular band structure of the sEMG measurement device is incorporated, thus capturing the inherent spatial relationships more effectively. We further propose a subject-aware contrastive learning framework that utilizes both subject and gesture label information to align the representation of vector space. Our comprehensive experimental evaluations demonstrate the superiority of STCNet under aggregated conditions, achieving state-of-the-art performance on benchmark datasets and effectively managing the variability among different subjects. The implemented code can be found at https://github.com/KNU-BrainAI/STCNet.

Alternative dosing regimens of tislelizumab proposed using modeling and simulation.

394 Background: Tislelizumab (TIS; BGB-A317) is approved for the treatment of multiple solid tumors, administered at 200 mg every 3 weeks (Q3W), and has demonstrated a flat exposure–response relationship across a wide range of doses. We evaluated alternative dosing regimens of TIS at 150 mg every 2 weeks (Q2W), 300 mg every 4 weeks (Q4W), and 400 mg every 6 weeks (Q6W) using a model-based approach with the aim of alleviating patient burden by providing longer dosing intervals and/or treatment flexibility compatible with background chemotherapy to meet the needs of patients and healthcare practitioners. Methods: A previously developed population pharmacokinetic (PK) model was used for simulating PK exposure of the alternative regimens, which were selected by exposure-matching to the reference dose of 200 mg Q3W. PK-based criteria (peak concentration [C max ] within 25% and trough concentration [C trough ] within 20% of the reference dose) were also used. Alternative dosing regimen exposures in the first least common time interval and at steady state were compared with the reference. Deviations from PK-based criteria were bridged using appropriate safety and efficacy references and exposure–response analyses using data from four phase 1, 2, and 3 clinical trials of TIS in patients with solid tumors, including gastric cancer and esophageal squamous cell carcinoma. Results: Simulations at steady state shown here demonstrate that the TIS alternative dosing regimens of 150 mg Q2W, 300 mg Q4W, and 400 mg Q6W produce comparable exposures to the 200 mg Q3W reference regimen. Although the simulated C max at 300 mg Q4W and 400 mg Q6W were higher than with the 200 mg Q3W reference dose, these were below the C max of the 5 mg/kg Q3W safety reference (Table). And while the C trough for the 400 mg Q6W dosing regimen was lower than with the 200 mg Q3W reference dose, it was 10.7% higher compared with the 2 mg/kg efficacy reference dose; therefore, it was within the concentration range where a flat exposure–efficacy relationship of TIS has previously been established. Conclusions: TIS alternative dosing regimens of 150 mg Q2W, 300 mg Q4W, and 400 mg Q6W are expected to result in similar safety and efficacy profiles as the 200 mg Q3W reference dosing regimen and may be used interchangeably for indications where 200 mg Q3W is approved. Clinical trial information: NCT04716634 , NCT05014828 , NCT04379635 , NCT02407990 , NCT04068519 , NCT03430843 and NCT03358875 . Steady-state PK exposure metrics for alternative TIS doses vs reference doses. Parameter 150 mg Q2W vs 200 mg Q3W 300 mg Q4Wvs 200 mg Q3W 300 mg Q4Wvs 5 mg/kg Q3W a 400 mg Q6Wvs 200 mg Q3W 400 mg Q6Wvs 5 mg/kg Q3W a 400 mg Q6Wvs 2 mg/kg Q3W b C max −5.8 (Yes) 31.4 (No) −18.7 (Yes) 52.2 (No) −5.8 (Yes) – C average 12.3 (Yes) 12.6 (Yes) – 0.4 (Yes) – – C trough 27.2 (Yes) 0.1 (Yes) – −28.4 (No) – 10.7 (Yes) Data are presented as difference (% = [GM test − GM reference /GM reference ] × 100) vs the 200 mg Q3W reference, a safety reference, or b efficacy reference (meets regulatory criteria, Yes/No). C average , average concentration; GM, geometric mean.

Impact of time to surgery on outcomes in patients with advanced esophageal squamous cell carcinoma following neoadjuvant therapy: An exploratory analysis of phase III trial JCOG1109.

458 Background: JCOG1109, a multicenter three-arm phase III trial, evaluated three neoadjuvant treatment regimens for advanced esophageal squamous cell carcinoma (ESCC), cisplatin and 5-fluorouracil (CF), docetaxel, cisplatin, and 5-fluorouracil (DCF), and cisplatin, 5-fluorouracil, and radiation therapy (CF-RT). The trial demonstrated the superiority of neoadjuvant DCF therapy in improving overall survival (OS). This exploratory analysis investigates the impact of the interval time from completion of neoadjuvant therapy to surgery (time to surgery, TTS) on both short- and long-term outcomes across different neoadjuvant therapy regimens. Methods: This analysis included patients from JCOG1109 who underwent surgery after neoadjuvant therapy. Patients were categorized into four TTS subgroups within each arm, based on quartiles of the overall cohort. Short-term outcomes such as perioperative complications, as well as long-term outcomes including OS and progression-free survival (PFS) were evaluated across these TTS subgroups. Results: Of the 601 patients enrolled in JCOG1109, 546 patients proceeded to surgery following neoadjuvant therapy. The median TTS was 35 days (range: 16-81) for the CF arm, 38 days (range: 17-109) for the DCF arm, and 41 days (range: 14-98) for the CF-RT arm. Baseline characteristics were well-balanced across all TTS subgroups in each treatment arm. Short-term outcomes revealed that operative time and overall proportions of postoperative complications were comparable. However, in the CF-RT arm, a longer TTS was associated with increased blood loss (200 ml, 210 ml, 300 ml, 370 ml; p-value for trend test = 0.010) and tended to increase the risk of anastomotic leakage (6%, 7%, 14%, 18%; p-value for trend test = 0.073). No significant differences in OS or PFS were observed across TTS subgroups in any treatment arm, with hazard ratios indicating no clear trend toward improved or worsened long-term outcomes. Conclusions: The timing of surgery following neoadjuvant therapy does not appear to affect long-term prognosis in patients with advanced ESCC, irrespective of the neoadjuvant therapy regimen. However, for patients undergoing neoadjuvant CF-RT, earlier surgery may be advantageous in reducing the risk of increased surgical complexity and anastomotic leakage.

Can the combination of citicoline and vitamin B12 be beneficial in the healing of corneal nerves after corneal cross-linking?

To evaluate the effect of topical citicoline, vitamin B12 and hyaluronic acid (OMK2 eye drops; Omikron Italia Srl, Italy) on the healing of corneal nerve after corneal cross-linking (CXL) treatment in patients with keratoconus (KC). A total of 44 eyes of 22 patients with KC who underwent CXL were included in this prospective study. After CXL, one eye of these patients received OMK2 eye dropandstandard post-CXL treatment (OMK2 group), while the fellow eye received onlystandard post-CXL treatment (control group). The following parameters were analyzed in the pre- and post-CXL procedure periods (1st, 3rd and 6th months): corneal sensitivity, tear film stability, central corneal thickness (CCT), and the corneal sub-basal nerve plexus (sbNP) parameters (including corneal nerve fiber density [CNFD], corneal nerve branch density [CNBD], corneal nerve fiber length [CNFL], corneal total branch density [CTBD], corneal nerve fiber area [CNFA], corneal nerve fiber width [CNFW]). Following CXL, a comparison of the baseline and month 6 data revealed that CNFA decreased in the control group (p < 0.001) and did not differ in the OMK2 group (p = 0.283). Other corneal sbNP parameters exhibited a decrease when comparing baseline and 6months in each group (all p < 0.05). In addition, CCT in the OMK2 group was not significantly different between baseline and month 6 (p = 0.052). However, a decline in CCT of the control groups was observed during this specified time interval (p = 0.009). Corneal sensitivity or tear film stability parameters did not differ significantly between groups at any time point or over time within each group (all p > 0.05). The use of OMK2 eye drop after CXL may provide more stable CNFA. In addition, it may also provide faster recovery in CCT.

Survival time and success rates of customized prefabricated metal posts: A retrospective study.

The choice of post type is still a controversial issue in dental practice. Furthermore, studies regarding the long-term survival and success of customized prefabricated posts are lacking. The purpose of this retrospective study was to assess the longevity of prefabricated metal posts customized to conform to the root canal. Data obtained from the records of patients who received a customized titanium or stainless-steel post at a private dental practice between July 1998 and March 2022 were analyzed. The prefabricated posts were customized by grinding the threads, reducing their length, and tapering them to fit into the existing canals. The relation between survival time and type of tooth and coronal restoration was searched. The Kaplan-Meier test was used for survival time and Cox regression to evaluate factors associated with survival (α=.05). The data were also analyzed for 5-year time intervals. A total of 1791 posts in 1072 patients were available for the study. The mean overall survival time of the posts was 17.33 years. The mean survival time with regard to the coronal restoration was 15.22 years for direct composite resin restorations, 17.21 years for metal-ceramic crowns, 14.94 years for fixed partial dentures, and 12.63 years for removable partial dentures. The survival time for anterior teeth was 13.16 years and 17.53 years for posterior teeth. The success rate of the posts was 97.5%. This retrospective study of customized prefabricated metal posts resulted in a 17-year post survival time and a success rate of 97.5%.

Tumor-to-tumor metastases: systematic review and meta-analysis of 685 reported cases.

Tumor-to-tumor metastasis is an exceedingly rare phenomenon where secondary deposits of a tumor develops in another one. Our systematic review and meta-analysis aims to uncover and analyze reported cases to enhance our understanding and improve patients' care. A comprehensive search of the literature was conducted to identify 685 cases of tumor-to-tumor metastasis from 543 articles. Key information, including the donor and recipient organs, tumor histology, primary to metastasis time interval, presence of distant metastases and overall survival was extracted and analyzed. The highest incidence of tumor-to-tumor metastasis was observed in breast cancer and lung cancer metastasizing to meningioma (n = 52, 7.6%; n = 49, 6.2%; respectively). There were 131 (19.2%) autopsy cases, 477 (69.6%) cases diagnosed in vivo, and in 77 cases (11.2%), the timing of diagnosis was unavailable. Death of the patient (including autopsy cases) was reported in 256 (37.4%) cases. In 160 (23.35%) patients, the primary of the metastasis (POM) was occult at the time of metastasis, and in 385 (56.2%) cases, the POM was already known. The median period between clinically overt primary cancer diagnosis and tumor-to-tumor metastasis was 2.0years. Donor metastases to other sites were observed in 328 (47.9%) cases. In multivariate Cox regression analysis, the primary-to-metastasis interval (< 3 vs > 3years, HR 2.01, 95% CI 1.18-3.43, p = 0.01) and the presence of donor metastases to other sites (present vs absent; HR 0.37, 95% CI 0.23-0.59, p < 0.001) were significantly associated with survival. In summary, our findings emphasize the necessity for heightened clinical vigilance, early detection, and tailored management to effectively address this unique and challenging clinical scenario.

Assessing Second-Trimester Ferning in Diagnosing Preterm Prelabor Rupture of Membranes.

Preterm prelabor rupture of membranes (PPROM) diagnosis is made through visualization of amniotic fluid (pooling), nitrizine testing, sonographic low amniotic fluid, and microscopic detection of amniotic fluid arborization (ferning). Data exist on the specificity and sensitivity of ferning detection but have not focused on the second trimester. Our objective is to evaluate the presence of ferning in transvaginally collected amniotic fluid in pregnancies with known second-trimester PPROM to determine if there is a difference in ferning based on gestational age and sample drying time. This was a prospective study evaluating amniotic fluid in individuals undergoing termination of pregnancy between 15 and 24 weeks gestation. A control vaginal swab was collected prior to rupture of membranes and a sample vaginal swab was collected at the time of rupture of membranes at a termination procedure. A 10-mL sample of amniotic fluid was collected too and then centrifuged to separate blood. Slides were analyzed at five different drying time intervals after rupture of membranes, on both the vaginal and centrifuged samples, and examined by two blinded investigators to assess for ferning. Maternal demographics, obstetrical history, and termination information were collected. Statistical analysis was performed using descriptive statistics and regression analyses. A total of 99 individuals consented and 93 were included. The mean gestational age at the time of the termination was 19.5 ± 2.5 weeks. There was a significant effect of drying time with the odds of observing ferning increasing with longer drying time, up to 10 minutes (p < 0.001). Gestational age did not impact ferning detection (p = 0.09). Centrifuging increased ferning detection by 15% at 10 minutes compared to the vaginal swab. In cases of known second-trimester PPROM, ferning was detected more often after 10 minutes of sample drying, and centrifuging the amniotic fluid to remove blood. · The detection of ferning in the second trimester was improved with longer drying times.. · The highest detection rate was seen after at least 10 minutes of drying time.. · Gestational age did not impact the rates of ferning.. · Blood contamination impacts the ability to see ferning on microscopic examination..

Morphokinetic characteristics of preimplantation development of human donor embryos

Background: The introduction of time-lapse incubators into assisted reproductive technology practices provides a detailed examination of human pre-implantation embryo development. The continuous time-lapse filming technology is used to determine prognostic markers of embryo viability and implantation potential based on morphokinetic parameters. At present, the main time intervals for morphokinetic events during the pre-implantation phase of human embryo development have been documented primarily in embryos from infertile patients, with limited data available concerning the development of donor embryos. In this regard, it becomes relevant to follow the early development of such embryos and describe the embryonic development timeline using time-lapse technology. Aim: The aim of this study was to determine the time intervals of critical events in the pre-implantation development of human donor embryos. Materials and methods: The material for the study was 18 donor embryos obtained after fertilization of donor oocytes with donor sperm. The embryos were cultured for 140 hours in an EmbryoVisor time-lapse incubator (Westtrade Ltd., Russia). Results: The video image analysis of diploid donor embryo development showed that the disappearance of both pronuclei occurred at 22.2 (21.0–25.4) hours post fertilization, the 2-cell embryo stage was observed at 24.5 (23.4–27.3) hours post fertilization, the 4-cell embryo stage at 35.9 (34.6–38.6) hours post fertilization, and the 8-cell embryo stage at 52.8 (49.0–58.8) hours post fertilization. Morula formation occurred at 86.0 (76.9–95.4) hours post fertilization, and complete blastocyst formation was recorded at 107.0 (99.1–114.3) hours post fertilization. Triploid embryos tended to have a delay in the cleavage stage and a shorter compaction phase, yet generally developed within similar timeframes as diploid embryos. Conclusions: The analysis of video recordings obtained after culturing donor embryos in the time-lapse incubator allows for comparing the morphokinetic parameters of pre-implantation development of the donor embryos, taking into account their ploidy. The checkpoints in the development of pre-implantation embryos from the zygote stage to blastocyst formation are characterized. A tendency is noted for earlier disappearance of pronuclei, a delay at the cleavage stage from four to eight cells, and a shorter compaction stage in the donor embryos with impaired ploidy. Various anomalies in the development of such embryos are also described. Special attention should be paid, perhaps, to embryos that do not fit into the established development intervals, exhibit anomalies such as reverse cleavage, direct division from one to three cells, and excessive fragmentation, or stop developing at one point or another, since this may indicate anomalies in the embryo’s genome such as, for example, aneuploidy. Timely identification of these deviations may lead to the exclusion of embryos with morphokinetic abnormalities from transfer, thereby favoring the selection of normally developing embryos to enhance implantation success and promote ongoing pregnancies. An increase in the sample of donor embryos under study, information on their genetic status and the clinical results of pregnancy after embryo transfer, and further accumulation of data will augment the ability to predict embryo implantation potential without the use of invasive methods.

Critical Time Intervals in Door-to-Balloon Time Linked to One-Year Mortality in ST-Elevation Myocardial Infarction

Background: Timely activation of primary percutaneous coronary intervention (PCI) is crucial for patients with ST-segment elevation myocardial infarction (STEMI). Door-to-balloon (DTB) time, representing the duration from patient arrival to balloon inflation, is critical for prognosis. However, the specific time segment within the DTB that is most associated with long-term mortality remains unclear. In this study we aimed to identify the target time segment within the DTB that is most associated with one-year mortality in STEMI patients. Methods: We conducted a retrospective cohort study at a tertiary teaching hospital. All patients diagnosed with STEMI and activated for primary PCI from the emergency department were identified between January 2013–December 2021. Patient demographics, medical history, triage information, electrocardiogram, troponin-I levels, and coronary angiography reports were obtained. We divided the DTB time into door-to-electrocardiogram (ECG), ECG-to-cardiac catheterization laboratory (cath lab) activation, activation-to-cath lab arrival, and cath lab arrival-to-balloon time. We used Kaplan-Meier survival analysis and multivariable Cox proportional hazards models to determine the independent effects of these time intervals on the risk of one-year mortality. Results: A total of 732 STEMI patients were included. Kaplan-Meier analysis revealed that delayed door-to-ECG time (&amp;gt;10 min) and cath lab arrival-to-balloon time (&amp;gt;30 min) were associated with a higher risk of one-year mortality (log-rank test, P &amp;lt; .001 and P = 0.01, respectively). In the multivariable Cox models, door-to-ECG time was a significant predictor for one-year mortality, whether it was analyzed as a dichotomized (&amp;gt;10 min vs ≤10 min) or a continuous variable. The corresponding adjusted hazard ratios (aHR) were 2.81 (95% confidence interval [CI] 1.42–5.55) for the dichotomized analysis, and 1.03 (95%CI 1.00–1.06) per minute increase, respectively. Cath lab arrival-to-balloon time also showed an independent effect on one-year mortality when analyzed as a continuous variable, with an aHR of 1.02 (95% CI 1.00–1.04) per minute increase. However, ECG-to-cath lab activation and activation-to-cath lab arrival times did not show a significant association with the risk of one-year mortality. Conclusion: Within the door-to-balloon interval, the time from door-to-ECG completion is particularly crucial for one-year survival after STEMI, while cath lab arrival-to-balloon inflation may also be relevant.

Unicompartmental Knee Arthroplasty Patients Recover More Like Total Hip Patients Than Total Knee Patients: A Prospective Longitudinal Study.

The differences in physical activity (PA) recovery between patients who have total hip arthroplasty (THA), unicompartmental (UKA), and total knee arthroplasty (TKA) are lacking. We described the trajectory of recovery based on objective metrics of PA over the first 12 months post-joint arthroplasty (JA). Data from 4,700 patients who underwent a primary unilateral JA surgery between November 2018 and September 2021 from a multi-site prospective study were analyzed. Generalized estimating equations, with an unstructured correlation matrix, were used to evaluate objective PA metrics over time, and the appropriate post-estimation commands were used to compare scores between time intervals. The PA (step count, stair count, gait speed, gait asymmetry) metrics were recorded pre-JA and one, three, six, and 12 months post-JA. Recovery curves were created using longitudinal estimating equations. All groups showed significant improvement in PA metrics over the first 12 months post-JA (all, P < 0.001). The THA and UKA patients were similar at almost all time points in terms of step count, stair count, gait speed, and gait asymmetry, while TKA patients had significantly lower PA scores in nearly all metrics (P < 0.05). The largest margin of meaningful improvement in PA was obtained by three months across all groups, with marginal additional improvement being made up to 12 months post-JA. This study shows early PA improvement post-JA with the greatest recovery being observed in patients post-THA and UKA compared to those post-TKA. Patients can expect the greatest proportion of PA recovery by three months for most PA metrics with less meaningful improvements from six to 12 months post-JA. Clinicians can use this data to educate patients perioperatively, set realistic expectations, and monitor recovery following JA.