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Methods | 150 patients, ASA physical status I–II, aged ≥ 60 years, no limitation in gender, BMI 18–25 kg/cm | PMC10069053 |
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Results | There was no significant difference in VAS score and PCA compression times ( | PMC10069053 |
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Conclusions | depression, postoperative pain, anxiety | Esketamine can reduce short-term postoperative anxiety and depression, relieve postoperative pain and stress response, shorten bed rest time after total hip replacement, and accelerate postoperative recovery. | PMC10069053 |
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Keywords | PMC10069053 |
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Introduction | fractures, Femoral neck fractures | Femoral neck fractures account for roughly 54% of hip fractures [ | PMC10069053 |
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Materials and methods | PMC10069053 |
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Clinical data | depression, femoral neck fracture, THA | Since there is no accurate result of esketamine in reducing the depression rate after THA in patients with femoral neck fracture, the main measure was defined as the depression rate 7 days after surgery, assuming that the difference between the two groups was up to 20%. According to a unilateral test conducted using the PASS15.0 software, test level The hospital’s ethics committee granted approval for this study (Ethics No.: 2022188), and patients signed informed consent forms. Patients with ASA I or II grade, age ≧ 60 years old, no restriction on gender, BMI 18–25 kg/cm | PMC10069053 |
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Methods | pain | All patients were fasting and drinking water before operation. After entering the operating room, ECG, SBP, DBP, SPO2 and BIS were monitored. Conventional open venous access was used for intravenous infusion of compound sodium chloride injection, low flow nasal oxygen inhalation (2L/min), radial artery puncture and catheterization under ultrasound guidance, and ART was invasive monitored.The same induction regimen was utilized for all patient groups: midazolam 0.03 mg/kg, sufentanil 0.4 ug/kg, etomidate 0.3 mg/kg, and rocuronium 0.6 mg/kg were administered intravenously. After 3 min of pressure mask oxygenation to exclude nitrogen, the laryngeal mask was applied. Once the laryngeal mask was in a good position (The two groups performed an ultrasond-guided lateral fascia ilicaca block utilizing the suprainguinal facial iliaca (iliaca) technique, 0.33% ropivacaine + 0.66% lidocaine 30 ml. At the same time, PCIA was connected for analgesia. Combined with the references and preliminary experimental results, Esketamine (Jiangsu Hengrui Pharmaceutical Co., LTD., specification: 2 ml/50 mg, batch number: 210922BL), dissolved in normal saline and prepared to 100 ml, was given to group A at a dose of 2.5 mg/kg, with a background dose of 2 ml/h, a PCA dose of 3 ml, and a locking period of 15 min. Sufentanil (Yichang Renfu Pharmaceutical Co., LTD., specification: 1 ml/50ug, batch number: 21A03271) was dissolved in normal saline at a rate of 2.5ug/kg and then combined to a final volume of 100 ml in group B. The PCIA parameters matched those in group A.After the procedure, the patient was transferred to the Postanesthesia Care Unit (PACU), where the laryngeal mask was removed once the patient's spontaneous breathing and level of consciousness had returned to normal. After 30 min of observation, the patient was sent back to the ward when the vital signs stabilized and the Steward score reached > 4. PCA compression is advised to ease pain if the pain score is > 4 after returning to the ward. | PMC10069053 |
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Observational indices | dizziness, nausea, postoperative adverse reactions, HAD | CHRONIC ILLNESS | Patients' demographic information was gathered, including age, gender, BMI, level of education, occupation, chronic illness, preoperative HAD and preoperative Harris scores, length of surgery, and length of hospital stay. The first time out of bed, the ambulation distance, and the number of PCA presses within 48 h after operation were also noted. The resting VAS score at 2, 4, 12, 24 and 48 h after the operation and the active VAS score at 12, 24 and 48 h after the operation were also noted. The incidence of postoperative adverse reactions such as drowsiness, dizziness, nausea and vomiting, multilingual were recorded. In the morning of the surgery day ( | PMC10069053 |
Statistical analysis | SPSS26.0 software was adopted for data analysis, measurement data are represented as | PMC10069053 |
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Results | PMC10069053 |
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General data | There was no significant difference in baseline characteristics between the two groups (Comparison of general data between the two groups | PMC10069053 |
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Postoperative VAS score | There was no significant difference in VAS scores between the two groups at rest and in active state after operation (Comparison of postoperative VAS scores between the two groups (points, M(IQR)) | PMC10069053 |
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Patient recovery, length of hospital time and PCA compression times | The time of first getting out of bed, the distance of activity and the length of hospital stay in group A were better than those in group B, and the differences were statistically significant (The first time to get out of bed, the distance of activity and the length of hospital stay were compared between the two groups, | PMC10069053 |
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Comparison of adverse responses between the two groups | dizziness, postoperative adverse reactions, nausea, vomiting | Compared with group A, the incidences of nausea, vomiting and dizziness in group B were significantly higher (Comparison of postoperative adverse reactions between the two groups [ | PMC10069053 |
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Patient stress index | There was no significant difference in the levels of IL-6 and CRP between the two groups in the morning of the operation day (Comparison of IL-6 and CRP between the two groups. | PMC10069053 |
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Comparison of patients’ HAD scores | depression, HAD, anxiety | Compared with group B, the scores of anxiety and depression in group A were significantly reduced at 3 days and 1 week after operation, and the differences were statistically significant (HAD scores were compared between the two groups. | PMC10069053 |
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Harris score | The Harris score of group A at 3 days, 1 week and 1 month after operation was significantly higher than that of group B, and the difference was statistically significant (Harris score was compared between the two groups at 3 days, 1 week and 1 month after operation ( | PMC10069053 |
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Discussion | femoral neck fractures, anxiety, nausea and vomiting, pain, dizziness, depression, trauma | ADVERSE EFFECTS, SCHWARTZ | The most common form of depression in older patients with femoral neck fractures is anxiety [The results of this study showed that there was no significant difference in VAS score between the two groups within 48 h after operation, but in terms of adverse effects, esketamine group in the incidence of nausea and vomiting and dizziness than sufentanil group. In a meta-analysis on postoperative deopioid analgesia published by Wang et al. [At the same time, surgery, as a kind of trauma treatment, is also a major source of stress after surgery, in which inflammatory factors will also change significantly under the stress of surgery, while IL-6 and CRP, often as stress indicators of pain, have also been proved to play an important role in the diagnosis and treatment of depression, which is considered to induce immune response in the human body under stress [When total hip replacement patients were followed up for almost 3 years, Schwartz et al. [ | PMC10069053 |
Conclusions | depression, anxiety, pain | Esketamine has good clinical application value because it can more effectively relieve pain in elderly patients who have had total hip arthroplasty, reduce perioperative stress response, improve perioperative anxiety and depression symptoms, shorten bed rest time, and encourage postoperative rehabilitation. | PMC10069053 |
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Author contributions | MM | MM was responsible for the design, implementation and manuscript writing. DC was responsible for literature search and follow-up. CX is responsible for data processing and literature search. XW is in charge of manuscript editing. All authors have contributed to the manuscript and all authors have approved the submission. | PMC10069053 |
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Funding | This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. | PMC10069053 |
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Declarations | PMC10069053 |
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Competing interests | The authors declare no competing interests. | PMC10069053 |
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References | PMC10069053 |
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Background | orthodontic | Whether slim the face or not after removed third molars is the concern of some orthodontic treatment candidates. The aim of this article is to explore the volume changes of facial soft and hard tissues after third molars extraction, as well as develop a reproducible clinical protocol to precisely assess facial soft tissue volume change. | PMC10362706 |
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Methods | A non-randomized, non-blind, self-controlled pilot study was conducted. 24 adults aged 18–30 had ipsilateral third molars extracted. The body weight change was controlled within 2 kg. Structured light scans were taken under a standardized procedure pre-extraction (T0), three (T1), and six (T2) months post-extraction; CBCTs were taken at T0 and T2. The projection method was proposed to measure the soft tissue volume (STV) and the soft tissue volume change (STVC) by the Geomagic software. The hard tissue volume change (HTVC) was measured in the Dragonfly software. | PMC10362706 |
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Results | The final sample size is 23, including 5 males (age 26.6 ± 2.5 years) and 18 females (age 27.3 ± 2.5 years). The HTVC was − 2.33 ± 0.46ml on the extraction side. On the extraction side, the STV decreased by 1.396 (95% CI: 0.323–2.470) ml (P < 0.05) at T1, and increased by 1.753 (95% CI: -0.01-3.507) ml (P = 0.05) at T2. T2 and T0 had no difference (P > 0.05). The inter and intra-raters ICC of the projection method was 0.959 and 0.974. There was no correlation between the STVC and HTVC (P > 0.05). | PMC10362706 |
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Conclusions | After ipsilateral wisdom teeth extraction, the volume of hard tissue on the extraction side reduces, and the volume of facial soft tissue does not change evidently. However, further research with large sample size is still needed. The STV measurement has excellent repeatability. It can be extended to other interested areas, including forehead, nose, paranasal, upper lip, lower lip and chin, which is meaningful in the field of orthodontics and orthopedics. | PMC10362706 |
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Trial registration | ChiCTR, ChiCTR1800018305 (11/09/2018), | PMC10362706 |
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Keywords | PMC10362706 |
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Background | tooth, atrophies | SLS, ATROPHIES | The wisdom teeth extraction influences maxillofacial hard tissue dimensions and may affect facial soft tissue dimensions. Previous research proved that the alveolar bone is tooth-dependent tissue and atrophies due to the loss of the tooth [Presume “face slim” happens, the soft tissue change is relatively small which needs to be measured by precise detection methods. Therefore, it is vital to record the 3D facial soft tissue morphology pre and post extraction under the same condition and conduct proper measurement procedure in the software.Structured light scanning (SLS) is one of the 3D facial recording methods, producing the shape, color, and texture of human faces in OBJ format. The nominal accuracy of the FaceScan SLS system (Isravision, Darmstadt, Germany) is 0.2 mm. A standardized procedure was developed by the author in a previous study [In most studies, 3D facial morphology assessments are still in the form of length and angle [Distance map is another commonly used method in the studies of 3D facial morphology, which is often used to evaluate anthropometric facial features [Facial volume measurement has been widely used in orthognathic surgery [The common method to measure soft tissue volume change is constructing a closed entity between two surfaces and testing the entity volume [With the development of Cone-beam computed tomography (CBCT) image analysis techniques, 3D indicators are more and more commonly used to evaluate the bone tissues [The purpose of this study was to explore the volume changes of facial hard and soft tissues after third molars extraction, as well as develop a reproducible clinical protocol to precisely assess facial soft tissue volume change. The article hypothesized the extraction of ipsilateral wisdom teeth do not influence the facial hard and soft tissue volume, and there is no correlation between the facial soft tissue volume change (STVC) and the facial hard tissue volume change (HTVC). | PMC10362706 |
Methods | PMC10362706 |
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Study design/sample | inflammation, periodontitis, pericoronitis, tooth | INFLAMMATION, PERIODONTITIS, PERICORONITIS, IMPACTION | A non-randomized, non-blind, self-controlled clinical study was conducted.Sample size calculation: According to the method by W. Viechtbauer et al. [Inclusion criteria:
18–30 years old, with a balanced face; Voluntary to pull out ipsilateral wisdom teeth simultaneously. There is no limit of the impaction classification.Exclusion criteria:
Pregnant or preparing to conceive during the study;Tumors and other severe systemic diseases;Acute inflammation of oral-maxillofacial region;Moderate to severe periodontitis around third molars;The bone resorption around the third molar is larger than the crown volume of the wisdom tooth due to pericoronitis or periapical inflammation;Congenital maxillofacial deformity;Distinctive facial asymmetry or severe skeletal Class II and III malocclusion;Received facial plastic treatment before the trial, or receiving orthodontic, orthognathic, and facial plastic therapy during the trial;The body weight fluctuates widely and is uncontrollable in the future. | PMC10362706 |
Clinical intervention and follow-up | SLS | The ipsilateral third molars were extracted by the same experienced surgeon at one follow-up visit. SLS and the bodyweight were taken at T0, T1, and T2. CBCT was taken at T0 and T2. Patients were required to control weight change within ± 2 kg. | PMC10362706 |
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The data collection | PMC10362706 |
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SLS acquisition | SLS | The parameters of the FaceScan SLS system (Isravision, Darmstadt, Germany) are: scanning speed of 0.8 s, scanning accuracy of 0.2 mm, scanning range from 270 degrees to 320 degrees, 5 million CCD pixels. A standardized procedure [ | PMC10362706 |
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CBCT acquisition | teeth bite | CBCT images were taken with i-CAT (Imaging Sciences International, Hatfield, PA, USA) at 120kVp, 18.45mAs, 20-second acquisition time, and 16 × 13 cm field of view. The effective radiation dose was 69–87µSv. Each patient was instructed to hold still, maintain her or his head upright and fixed by a headrest, with the teeth bite together in a standing position. The CBCTs were exported in Digital Imaging Communication in Medicine (DICOM) format for analysis. | PMC10362706 |
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The data evaluation | PMC10362706 |
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SLS analysis | SD | The facial scans were processed in Geomagic 2014 (2014, Germany) software by the following steps:
Alignment and registration:The scan of T0 was set to be a fixed module, while the scans of T1 and T2 were floating modules. T1 and T2 scans were registered to T0 according to the upper third of the face [
The registration of T1 with T0 according to the upper third of the face
Buccal region division.The bilateral buccal regions were divided by the “draw” operation connecting Posterotragion (pt’) to Alare (al’), Exocanthion (ex’) to Cheilion (ch’), Cheilion (ch’) to Chin footpoint (cf’), and multiple points along the lower border of the mandible. The landmark definitions are listed in Table
The abbreviation and definition of landmarks used in the studyThe upper corner maker (’) refers to Capulometric landmarks (on soft tissue) apart from Craniometric landmarks (on skull)
The mid-sagittal plane establishment.The mid-sagittal plane only established on T0 scan by the orthogonal lasers, Fig.
The establishment of the mid-sagittal plane according to the orthogonal lasers projected on T0 scan When capture the scan, the horizontal laser will be reflected by the two mirrors behind the subject’s head bilaterally [
Buccal boundary projection.The projection method measures the volume from the buccal area projecting perpendicular to the mid-sagittal plane. To avoid the error of boundary determination between different time point, the buccal boundary was projected from scan T0 to T1 and T2 in the direction perpendicular to the mid-sagittal plane either. Using the right side as an example, the specific process refers to Fig.
Buccal boundary projection from scan T0 to T1 and T2 in the direction perpendicular to the mid-sagittal plane
Buccal region deviation analysis.By the “Deviation/ 3D Compare” function, mean (µ), standard deviation (SD), and root mean square (RMS) of the buccal area were calculated. The definition of SD and RMS are as follows.
Buccal soft tissue volume change (STVC) measurement.Soft tissue volume (STV) is the volume from the buccal region perpendicular to the mid-sagittal plane, Fig.
The measurement of buccal STV; On the left side from top to bottom are the right buccal models of T0, T1, and T2; Plane 2 is the mid-sagittal plane, and buccal STV is the volume of the buccal patch model projecting to the mid-sagittal plane
The reliability of the projection method.Ten samples were randomly selected by drawing lots for the reliability test. Two well-trained investigators measured the STVC by the projection method independently. One investigator repeated the measurements after a two-week interval. | PMC10362706 |
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CBCT analysis | The CBCTs were imported into Dragonfly software (version 4.3, Objects Research Systems, Montreal, QC, Canada) in DICOM format for analysis.
Alignment based on voxel information.CBCT of T0 was set as a “fixed module”. CBCT of T2 was aligned to the T0 through manual rotation and translation until the teeth and bone contour were overlapped exactly. Although the maximum occlusal position was asked during CBCT acquirement, occlusion position variation of the same patient occurs occasionally. Therefore, the upper and lower jaws were aligned separately.
Region segmentation.Through the threshold segmentation method, cortical bone and dental tissues were selected and saved as regions of interest (ROIs) of T0 and T2, Fig.
CBCT region segmentation, Boolean subtraction, and HTVC region division. The green region is the result of region segmentation. The orange region is the HTVC region of the maxilla, which the volume is calculated by pixel counting
Boolean subtraction and volume change region selection.With the Boolean subtraction of ROIs (T2-T0), the three-dimensional voxel model of the changing area of the hard tissues can be obtained. As the maxilla and mandible were aligned separately, two cubes were drawn in the space which selected the volume change regions, containing the wisdom teeth of the maxilla or mandible as well as the alveolar bone around the wisdom teeth, Fig.
Voxels counting and HTVC measurement.By counting the number of voxels, the volume of the selection region can be calculated directly (the orange region in Fig. | PMC10362706 |
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Statistical methods | Data were analyzed using SPSS software (version 23.0; SPSS, IBM; Chicago). As for the reliability of the projection method, the intraclass correlation coefficient (ICC) for absolute agreement, single measure, based on 2-way random effects, was calculated. The Shapiro-Wilk test was used to assess the data distribution. Two-way repeated measure ANOVA was used to analyze the influence of the interaction of treatment and time on buccal STV. Paired t-test was used to verify the difference of STVC between extraction and non-extraction side during each period. One-way repeated measure ANOVA was used to analyze the difference of STV at different time points.For the hard tissue, the descriptive statistics of the HTVC were calculated. Pearson correlation coefficient was used to verify the correlation between the HTVC and the STVC to answer whether the volume decrease of the maxillofacial hard tissue would cause soft tissue change. | PMC10362706 |
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Results | A total of 24 volunteers were recruited, and one (male, age 30) was excluded due to unqualified data. Specifically, there was obvious deformation in the post-extraction facial scan, which may be due to the mandible position deviation or the defect of structural light scanning. A total of 23 volunteers were included, including 5 males (age 26.6 ± 2.5 years) and 18 females (age 27.3 ± 2.5 years). The T1 follow-up time was 3.86 ± 0.89 months (17 patients completed); the T2 follow-up time was 8.08 ± 1.71 months (21 patients completed). The characteristics of the third molars included are listed in Table
The characteristics of the third molars*The number is counted by corresponding tooth surface (buccal, lingual/palatal, distal, mesial) which was involved in the cortical bone removal during extractionAs for the reliability of the projection method, the inter-observer ICC is 0.959, 95%CI 0.925–0.978, P < 0.01;and intra-observer ICC is 0.974, 95%CI 0.935–0.988, P < 0.01.Descriptive statistics of RMS on the extraction side and non-extraction side are displayed in Table
Descriptive statistics of RMS on extraction side and non-extraction side (/mm)Two-way repeated measure ANOVA was used to assess the influence of extraction over time on STV. The interaction of treatment * time had no significant effect on STV, f (2,30) = 3.300, P = 0.051.One-way repeated measure ANOVA was used to analyze the STV over time. For the extraction side (n = 16): there was significant difference in STV between T0, T1 and T2, f (2,30) = 4.906, P < 0.05. Pairwise comparison indicated that, from T0 to T1, the STV decreased by 1.396 (95% CI: 0.323–2.470) ml (P < 0.05), and from T1 to T2 the STV increased by 1.753 (95% CI: − 0.01–3.507) ml (P = 0.05). There was no significant difference of STV between T2 and T0 (P > 0.05). For the non-extraction side (n = 16), there was no significant difference in STV between T0, T1 and T2, f (2,30) = 1.555, P > 0.05.Paired t-test was adopted to compare extraction and non-extraction side for mean distance (µ), standard deviation (SD), root mean square error (RMS), and STVC of the buccal region in each period (T1-T0, T2-T0, T2-T1). According to the Shapiro-Wilk test, besides the RMS of T2-T0 (P = 0.007) and T2-T1 (P = 0.006) did not follow the normal distribution, the other groups conformed to the normal distribution (P > 0.05). Wilcoxon signed-rank test was adopted for data of abnormal distribution. The results are listed in Table The HTVC on the extraction side was − 2.33 ± 0.46 ml of T2-T0. The Pearson correlation coefficient of the HTVC and STVC was − 0.397 (P > 0.05), proving no apparent correlation between the HTVC and the STVC.
Paired-t test of µ, SD, RMS, STVC of the extraction side and non-extraction side in three time period*The mean and standard deviation of the difference of the extracted side and the non-extracted side**P < 0.05, so the data did not follow the normal distribution***The data were analyzed by Wilcoxon signed rank test. The results showed that there was no significant difference in RMS of two sides (P > 0.05) | PMC10362706 |
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Discussion | SLS, IMPACTION | The pilot study is exploratory in methodological feasibility of facial soft tissue volume measurement and rationality of experimental design for the preparation of further research. A non-randomized, non-blind, and self-controlled clinical trial was conducted to measure the 3D soft and hard tissue changes of the human face after ipsilateral wisdom teeth removal.It was found that the HTV on the extraction side decreased by 2.33 ± 0.46ml at T2. There was no obvious correlation between the HTVC and the STVC. The pilot study has not distinguished third molars impaction types. Due to the classification of the impacted wisdom teeth may influence the quantity of bone removal, the variation may influence the HTV decrease.The paired t-test showed no significant difference in the shape (µ, SD, RMS) or volume (STVC) between the extraction side and the non-extraction side. Interestingly, extraction of wisdom teeth may result in a decrease of STV on the extraction side in a short time (the STV decreased by 1.396ml (P < 0.05) between T0 toT1), which return to the T0 level (P > 0.05)) in a long time (the STV increased by 1.753ml (P = 0.05) between T1 and T2). There is no such change on the non-extraction side. However, statistical significance does not imply clinical significance. The reproducibility of FaceScan SLS system applied to real person in buccal region is 0.4195 mm with 95%CI (0.3960, 0.4429) mm, P < 0.05 [The great thickness of buccal soft tissue and the prominent bone support around the buccal area may be the essential reasons why the deep-seated HTVC does not reveal on the surface. A study investigated the tissue response of defined amounts of filler material injected into facial fat compartments using the surface-volume coefficient (the surface volume change observed divides the actual injection volume) as outcome variables [From the perspective of methodology: The projection method is appropriate for small facial soft tissue volume change measurement and is reproducible. It can be applied to other facial regions, such as the nose, paranasal area, upper lip, lower lip, and chin (the coronal plane can be used as the reference plane). It provides a new, feasible and detailed method for orthodontics, orthognathic surgery, plastic surgery, and other disciplines concerned with facial morphological changes.The main disadvantage of the SLS is that the reliability is significantly influenced by the facial soft tissue variability in vivo. One case of the unqualified facial scan was excluded in this study, which may be due to mandibular position variation or SLS quality defects. This suggests that even with the standardized procedure [The limitations of this study are the sample size was small and the third molars were not classified by impact types or bone removal quantity. Although the standardized procedure [ | PMC10362706 |
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Acknowledgements | The author would like to thank the National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, PR China, for software support. | PMC10362706 |
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Authors’ contributions | SLS | WXW designed and operated the study, and write the manuscript. YHH processed the CBCT data. WEB extracted teeth and collected clinical data. CXY processed part of the SLS data and duplicated the STV measurement. ZYJ contributed to the software utilization. JJH designed the study and revised the manuscript. All authors read and approved the final manuscript. | PMC10362706 |
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Funding | This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. | PMC10362706 |
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Data Availability | All data generated or analysed during this study are included in this published article. | PMC10362706 |
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Declarations | PMC10362706 |
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Competing interests | The authors declare that they have no competing interests. | PMC10362706 |
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Ethics approval and consent to participate | This study was approved by the ethics committee of Peking University School of Stomatology, Beijing, China (number PKUSSIRB-201838117). Informed consent has been obtained from all volunteers in written. All methods in this study were carried out in accordance with relevant guidelines and regulations. | PMC10362706 |
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Consent for publication | Informed consent for publication of images has been obtained from the volunteer. | PMC10362706 |
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List of abbreviations | soft tissue volumehard tissue volumesoft tissue volume changehard tissue volume changeStructured light scanningCone-beam computed tomographyRoot mean squareRegions of interestIntraclass correlation coefficientIterative closest point | PMC10362706 |
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References | PMC10362706 |
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ABSTRACT | PMC10375926 |
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Background | muscle soreness, fatigue | Olive fruit is rich in bioactive pentacyclic triterpenoids, primarily maslinic acid (MA). Previous studies have demonstrated that MA exhibits anti-inflammatory and anti-oxidative effects; however, it is unclear whether MA intake during training inhibits perceptual fatigue and muscle soreness in athletes. This study analyzed the effects of MA supplementation during athletic training on perceptual fatigue and muscle soreness. | PMC10375926 |
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Methods | muscle soreness, perceptual fatigue | This randomized, double-blind, cross-over, and placebo-controlled trial involved 12 young, healthy male water polo athletes. After daily training for seven days, they ingested either olive fruit extract, containing 60 mg/day MA, or a placebo. We measured perceptual fatigue and muscle soreness during the intervention using a visual analog scale and inflammatory and oxidative stress-related proteins. | PMC10375926 |
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Results | Perceptual fatigue, muscle soreness | Perceptual fatigue and muscle soreness and the area under the curve during the training period were significantly lower (main effect of MA; | PMC10375926 |
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Conclusion | inflammation, muscle soreness, perceptual fatigue | INFLAMMATION, OXIDATIVE STRESS | These findings suggest that MA intake not only reduces perceptual fatigue and muscle soreness but also decreases inflammation and oxidative stress in the blood and skeletal muscle. | PMC10375926 |
GRAPHICAL ABSTRACT | PMC10375926 |
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KEYWORDS | PMC10375926 |
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Introduction | fatigue | INFLAMMATION, GLYCOGEN DEPLETION | Chronic fatigue can impact physical and mental athletic performance. A tired athlete may have less energy to exert themselves during practice or a game. Exercise-induced fatigue, which is attributable to many factors, including the accumulation of reactive oxygen species, inflammation, and muscle glycogen depletion, affects athletic performance [Olives are an essential oilseed crop that has been consumed since ancient times. Recent studies have indicated that maslinic acid (MA) with pentacyclic triterpene structures from olive extracts have various health benefits [Water polo is a goal-based ball game played in the water, and it consists of such a robust offense and defense that it is considered “underwater fighting” because of its intensity. Water polo is characterized by complex activities, such as swimming with various strengths, and treading water [Most athletic performance studies focus on conditioning, such as peaking and tapering [ | PMC10375926 |
Materials and methods | PMC10375926 |
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Participants | This randomized, placebo-controlled, double-blind trial was conducted with 12 Japanese first-division national-level male university water polo athletes. The characteristics of the participants are shown in Grouping condition and characteristics of participants.Training schedule from Day 1 to Day 7 during intervention. | PMC10375926 |
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Training schedule | The participants maintained a fixed training regimen ( | PMC10375926 |
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Anthropometric measurements | Anthropometric measurements were performed bare feet in light clothes. Body mass was measured to the nearest 0.1 kg using a digital scale (InBody 770; InBody Japan, Tokyo, Japan). Height was measured to the nearest 0.1 cm using a wall-mounted stadiometer (Digital Height Meter AD-6227 by A&D, Tokyo, Japan). Body mass index (BMI) values were calculated by dividing the weight (kg) by the height (cm) square. Total body fat was estimated using bioelectrical impedance analysis (InBody 770). | PMC10375926 |
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Performance trial (eggbeater kick ability) | Participants conducted the performance trial measurements in a 50-m indoor pool with a maximum depth of 3.8 m. A blood sample was taken from the fingertip and blood lactate levels were measured with Lactate Pro2 (Arkray. Kyoto. Japan) before and after the performance trial. Participants performed a 20-second eggbeater kick while holding a 10-kg weight (with no arm sculls) and keeping their manubrium (superior part of the sternum) above the water surface. Afterward, the participants stood on the underwater sidewalk (staging point on the pool wall) and rested for 20 seconds with the weight on the poolside. This interval exercise (20-second eggbeater kick + 20-second rest) was performed as one set until exhaustion. During the test, subjects were instructed to maintain as high a body position as possible; when participants could no longer maintain the reference line (upper sternal border at the water surface), they were considered exhausted, and the test was stopped. | PMC10375926 |
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Perceptual assessments of fatigue and muscle soreness | muscle soreness, fatigue | The perceptual assessment of fatigue and muscle soreness in the whole or parts of body were surveyed using the visual analog scale (VAS) [ | PMC10375926 |
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Serum tumor necrosis factor α (TNF-α) levels and other biochemical markers | TNF-α | BLOOD | Blood samples were collected from each participant in the morning after fasting for 12 h overnight. Each blood sample was placed in a serum separator tube and centrifuged at 2,000 rpm for 15 minutes at 4°C. The serum was stored at −80°C until further analysis. Serum TNF-α levels were measured by ELISA using the Human TNF-α Assay kit (#KHC3011, Invitrogen – Thermo Fisher scientific, Tokyo, Japan), according to the manufacturer's protocol. Serum levels creatine kinase (CK), hs-CRP, and creatinine were determined using standard enzymatic techniques. These analyses were outsourced to Tsukuba i-Laboratory LLP (Tsukuba, Japan). | PMC10375926 |
Thiobarbituric acid reactive substance (TBARS) assay | Serum TBARS were measured as described previously [ | PMC10375926 |
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Cell culture | WEST | Murine C2C12 skeletal muscle cells (passage numbers 10–12) were seeded into 12-well plates and maintained in Dulbecco’s modified Eagle’s medium (DMEM) (11966025, Gibco) containing 10% (vol/vol) fetal bovine serum (FBS; F9665, Sigma-Aldrich, St. Louis, MO), 1% (vol/vol) penicillin-streptomycin (15070–063, Gibco), 5 mM glucose (G7021, Sigma−Aldrich), 1 mM sodium pyruvate, and 1 mM GlutaMAX (35050–038, Gibco) under standard conditions (5% CO2, 100% humidity, 37℃). When the cells reached 90% confluence, the medium was switched to a differentiation medium consisting of DMEM supplemented with 2% calf serum (Bio West) and 1% nonessential amino acids (Invitrogen). This timing was designed Day 0. The differentiation medium was changed every 24 h. On Day 5 of differentiation, myotubes were changed to an amino acid and serum-free medium (D9800–13, US Biological, Salem, MA) (pH 7.3). The cells were incubated for 1 h without serum and amino acids prior to treatment. Myotubes were subsequently treated with a medium containing 10% human serum with placebo or MA before or after intervention for 24 h. The serum dose was determined from reflating previous studies, which ranged from 5% to 20% [ | PMC10375926 |
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Western blot analysis | LYSIS | Total protein from the C2C12 cells was extracted with a lysis buffer containing 50 mM HEPES (pH: 7.6), 150 mM NaCl, 10 mM EDTA, 10 mM Na | PMC10375926 |
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Primary antibodies | TNF-α | The following primary antibodies were used for western blot analysis: TNF-α (1:500, 52B83; sc -52,746, Santa Cruz), total-nuclear factor-kappa B (NF-κB) (1:1000, #8242; Cell signaling Technology, Danvers, MA, USA), phospho-NF-κB (1:1000, #3033; Cell signaling Technology, Danvers, MA, USA), cyclooxygenase 2 (COX2) (1:1000, #4842S; Cell signaling Technology, Danvers, MA, USA), superoxide dismutase 2 (SOD2) (1:1000, 13141S; Cell signaling Technology, Danvers, MA, USA), heme oxygenase 1 (Hmox1) (1:1000, 70081S; Cell signaling Technology, Danvers, MA, USA), glutathione peroxidase (GPX) (1:1000, B-6; sc -133,160, Santa Cruz), Catalase (1:3000, H-9; sc271803, Santa Cruz), and α-tubulin (1:3000, #2144; Cell signaling Technology, Danvers, MA, USA). | PMC10375926 |
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Statistical analyses | Data are expressed as means ± standard deviation (SD) or individual values ( | PMC10375926 |
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Results | PMC10375926 |
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P | To determine whether MA affects treading water performance, we measured the maximum number of sets of high-intensity interval exercises with an eggbeater kick for water polo athletes. The exhaustion set count for the performance trial was lower than before the intervention but was not affected by MA intake (data are not shown). Lactate concentration levels were elevated after the performance trial, but no effect of MA was observed (data are not shown).MA intake did not affect performance tests. | PMC10375926 |
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Perceptual fatigue and muscle soreness | fatigue, muscle soreness, lower back muscle soreness, femur muscle soreness, muscle fatigue, chest muscle soreness, perceptual fatigue | We measured perceptual fatigue and muscle soreness as the primary outcomes. Regarding fatigue, whole-body fatigue and muscle fatigue were lower in the MA condition compared with those in the placebo condition (MA intake attenuates perceptual fatigue and muscle soreness during the one-week intervention. (a) whole body fatigue, (b) whole body muscle fatigue, (c) eye strain, (d) whole-body muscle soreness,(e) shoulder muscle soreness, (f) chest muscle soreness, (g) lower back muscle soreness and (h) femur muscle soreness. All data are expressed as the means and individual values ( | PMC10375926 |
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Inflammatory and damage markers in blood | inflammation, TNF-α | INFLAMMATION | To elucidate the mechanism of the anti-inflammatory effects of MA, we measured inflammatory (TNF-α and high sensitive C-reactive protein) and damage (CK and creatinine) biomarkers in the blood. For TNF-α, an interaction was observed between the placebo and the MA condition after intervention and the rate of change in TNF-α before to after intervention was lower in the MA condition compared with that in the placebo condition (MA intake inhibits the accumulation of inflammation in the blood during a one-week intervention. Levels of (A) TNF-α, (B) hs-CRP, (C) creatin and (D) creatinine concentration. All data are expressed as the means and individual values ( | PMC10375926 |
Oxidative stress (TBARS) in blood | OXIDATIVE STRESS | To determine the effect of MA on oxidative stress, we measured TBARS in the serum. TBARS is a representative oxidative stress marker and is a protein that is primarily produced when fat is oxidized. Between the placebo and MA conditions after the intervention, an interaction was observed (interaction: MA intake inhibits oxidative stress accumulation in blood during a one-week intervention. All data are expressed as means and individual values ( | PMC10375926 |
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Inflammatory and antioxidant related proteins in vitro | Finally, we performed an Inflammatory related proteins are decreased within myotubes treated with serum from MA-conditioned participants after intervention. (a) western blot band images, protein expression levels of (b) TNF-α, (c) NF-κB, and (d) COX2. All data are expressed as means and individual values (Antioxidant factor-related proteins are also decreased within myotubes treated with serum from MA-conditioned participants after intervention. (a) western blot band images, protein expression levels of (b) SOD2, (c) Hmox1, (d) GPX, and (e) catalase. All data are expressed as means and individual values ( | PMC10375926 |
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Discussion | INFLAMMATION, OXIDATIVE STRESS | The findings of this study show that seven consecutive days of MA supplementation effectively reduced perceptual fatigue, soreness, inflammation, and oxidative stress markers in the blood in highly trained water polo athletes. In an | PMC10375926 |
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MA and exercise performance | muscle soreness, muscle damage, fatigue | INFLAMMATION, OXIDATIVE STRESS | This is the first study to report the effects of MA supplementation on inflammation, oxidative stress, and swimming (treading water) performance in team sport athletes. Contrary to our (and previous studies) hypothesis, the MA ingestion did not affect performance, but suppressed perceptual fatigue and muscle soreness. These results may be linked to the magnitude of inflammation, oxidative stress and muscle damage induced by training in this study being substantially lower than in previous studies [ | PMC10375926 |
Perceptual evaluation | arthralgia pain | HAND ARTHRITIS | We observed the main effect of MA in all indexes of the evaluation by VAS, which is the main outcome of this study. Our previous study reported that MA attenuates arthralgia pain in the elderly and arthritis in inflammatory mouse models [ | PMC10375926 |
Evaluation of inflammatory and oxidative stress in blood | INFLAMMATION, OXIDATIVE STRESS | We quantified some factors associated with inflammation, damage, and oxidative stress in the blood plasma to determine the effects of MA intake. Reduced inflammation, damage, and oxidative stress after intervention indicate the maintenance of muscular function. It likely mitigates soreness, possibly explaining the preservation and recovery of strength observed in previous studies in which MA was consumed [ | PMC10375926 |
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Effects of MA-ingested serum on cultured cells | inflammation | INFLAMMATION, OXIDATIVE STRESS | As a new insight, we investigated whether the addition of serum before and after the intervention from the participants to cultured cells would affect the protein expression on inflammation or antioxidant. This experiment enables us to examine in more detail the effects of MA and metabolites resulting from MA intake. Although our study here did not allow us to examine the effects of biopsy on protein expression in skeletal muscle, we were able to use the previously reported in vitro model of Allen et al. to understand the mechanisms that inhibit inflammation and oxidative stress accumulation in MA from blood and in vitro data [ | PMC10375926 |
Limitations | inflammation | INFLAMMATION | One limitation of this study was the short duration of MA ingestion. Our study was conducted for a short period of one week to ascertain the impact of MA on inflammation and injury. In addition, because this study was conducted with active athletes, it was limited to one week because of the constraints of accommodating their schedules. Therefore, future studies will need to extend the duration of the study to examine the effects of MA in more detail. Additionally, since we did not measure training load during intervention, it is possible that differences in training load may have affected the degree of damage/inflammation. Furthermore, the positional qualities of water polo players may have affected the training load, therefore future studies should include individual differences in protocols. Another limitation is that the participants of the experiment were rare top water polo athletes in Japan. By targeting athletes with well-defined athlete and competition characteristics, such as power and endurance athletes, rather than complex water polo athletes, it may be possible to confirm the detailed effects of MA on metabolic characteristics and to inform nutritional strategies according to energy mechanisms. Future research should consider the degree of competition, gender differences, and the competition itself in order to generalize the outcomes of this study and make them more applicable to the field. | PMC10375926 |
Conclusion | inflammation, muscle soreness, fatigue | INFLAMMATION, OXIDATIVE STRESS | In this study, we determined the effect of MA on fatigue and muscle soreness in a randomized, double-blind, cross-over, and placebo-controlled trial. Our results suggest that MA intake for one-week significantly attenuated fatigue and muscle soreness by reducing inflammation and damage. Furthermore, we found novel MA benefits, such as the inhibition of oxidative stress in skeletal muscle cells by adding of serum from MA-treated athletes using an | PMC10375926 |
Abbreviations | Tumor necrosis | TUMOR NECROSIS | ANOVA: analysis of variance, AUC: area under the curve, BMI: Body mass index, CK: Creatine kinase, COX2: Cyclooxygenase 2, DMEM: Dulbecco’s modified Eagle’s medium, GPX: Glutathione peroxidase, Hmox1: Heme oxygenase 1, hs-CRP: High-sensitivity C-reactive protein, MA: maslinic acid, mTOR: Mechanistic target of rapamycin, NF-κB: Nuclear factor-kappa B, SD: Standard deviation, SOD2: Superoxide dismutase 2, TBARS: Thiobarbituric acid reactive substance, TNF-α, Tumor necrosis factor α, VAS: Visual analog scale. | PMC10375926 |
Acknowledgments | Ota | The authors would also like to thank Kohei Takeda (Meiji University), Yuya Ota, Hideto Hanakita, Shota Kumamoto, Koichiro Tanahashi, and Jiyeon Park (University of Tsukuba) for help with the measurements. | PMC10375926 |
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Disclosure statement | This study was funded by NIPPN CORPORATION. Yuki Yamauchi and Keito Suzuki are employees of NIPPN CORPORATION. The other authors have no personal or financial conflicts of interest. | PMC10375926 |
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Author contributions | Significant manuscript writer: TS. Concept and design: T.S., E.K., K.M., Y.Y., K.S., and T.T. Data acquisition: T.S., E.K., K.M., Y.Y., and K.S. Data analysis and interpreted: T.S. and YY. Prepared figure: T.S. Drafted manuscript: T.S. Edited and revised manuscript: T.S., H.T., S.M and T.T. All authors read and approved the final manuscript. | PMC10375926 |
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Data availability statement | The sharing of data in an open-access repository was not included in our participants consent. Thus, in accordance with standard ethical practice, data may only be available on request from the corresponding author. | PMC10375926 |
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Ethics approval | This study conformed to the Declaration of Helsinki principles and was approved by the University of Tsukuba Research Ethics Committee approved this study (Tai29–75). This study was registered in the UMIN Clinical Trial Registry under the ID UMIN 000030479. Written informed consent was obtained from all participants before testing. | PMC10375926 |
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Consent for publication | The Journal of the International Society of Sports Nutrition submission standards and the article’s content have the approval of all authors. | PMC10375926 |
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References | PMC10375926 |
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Background | bleeding, non-critically ill | BLEEDING | Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. | PMC10594805 |
Methods | bleeding | DISEASE, BLEEDING | A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45–60 kg, 80 mg for 61–100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4–0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). | PMC10594805 |
Results | bleeding | BLEEDING, EVENT | Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC ( | PMC10594805 |
Conclusions | non-critically ill | Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. | PMC10594805 |
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Trial registration | The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020. | PMC10594805 |
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