Far cortical locking constructs for fixation of distal femur fractures in an Asian population: A prospective observational study.

BACKGROUND: The stiffness of locked plates suppresses healing process, prompting the introduction of far cortical locking to address this issue. This study aimed to demonstrate the clinical efficacy of far cortical locking constructs in treating distal femoral fractures in an Asian population. METHODS: This multicenter prospective observational study was conducted at four university hospitals between February 2018 and February 2021. Demographic data, the presence of metaphyseal comminution, and surgical fixation details were recorded. Clinical outcomes, including single-leg standing, EQ-5D, and EQ-VAS scores, and radiologic outcomes, including the RUST score of each cortex, were evaluated and compared according to the presence of metaphyseal comminution. RESULTS: There were 37 patients (14 men and 23 women) with a mean age of 67.3 ± 11.8 years. Twenty-two patients had metaphyseal comminution (59%), and 15 presented simple fractures in metaphyseal areas. Four patients (13%) could stand on one leg >10s at 6 weeks, and 24 patients (92%) at 1 year. EQ-5D increased from 0.022 ± 0.388 to 0.692 ± 0.347, and the mean EQ-VAS 51.1 ± 13.1 to 74.1 ± 24.1 between discharge (n = 37) and post-operative 1 year (n = 33), respectively. RUST score presented increment for time, from 6.2 ± 1.8 at 6 week to 11.6 ± 1.1 at 1 year. Radiological healing demonstrated rapid increase from week 6 (16/28, 43%) to month 3 (27/31, 87%), with no obvious increase was observed in 6 months (23/26, 89%) or 12 months (25/28, 89%). Simple metaphyseal fractures presented significantly higher RUST scores at 6 weeks and 3 months, but there was no difference in RUST scores at 6 months or 1 year according to metaphyseal comminution. CONCLUSIONS: Plate constructs with far cortical locking screws provided safe and effective fixation for distal femoral fractures, with consistent radiological and clinical results, regardless of metaphyseal comminution.

Application of multiple-finding segmentation utilizing Mask R-CNN-based deep learning in a rat model of drug-induced liver injury.

Drug-induced liver injury (DILI) presents significant diagnostic challenges, and recently artificial intelligence-based deep learning technology has been used to predict various hepatic findings. In this study, we trained a set of Mask R-CNN-based deep algorithms to learn and quantify typical toxicant induced-histopathological lesions, portal area, and connective tissue in Sprague Dawley rats. We compared a set of single-finding models (SFMs) and a combined multiple-finding model (MFM) for their ability to simultaneously detect, classify, and quantify multiple hepatic findings on rat liver slide images. All of the SFMs yielded mean average precision (mAP) values above 85%, suggesting that the models had been successfully established. The MFM showed better performance than the SFMs, with a total mAP value of 92.46%. We compared the model predictions for slide images with ground-truth annotations generated by an accredited pathologist. For the MFM, the overall and individual finding predictions were highly correlated with the annotated areas, with R-squared values of 0.852, 0.952, 0.999, 0.990, and 0.958 being obtained for portal area, infiltration, necrosis, vacuolation, and connective tissue (including fibrosis), respectively. Our results indicate that the proposed MFM could be a useful tool for detecting and predicting multiple hepatic findings in basic non-clinical study settings.

Two weeks dose range-finding and four weeks repeated dose oral toxicity study of a novel reversible monoamine oxidase B inhibitor KDS2010 in cynomolgus monkeys.

A novel reversible monoamine oxidase B inhibitor, KDS2010, has been developed as a therapeutic candidate for neurodegenerative diseases. This study investigated its potential toxicity in non-human primates before human clinical trials. Daily KDS2010 doses (25, 50, or 100 mg/kg) were orally administered to cynomolgus monkeys (1 animal/sex/group, 4 males and 4 females) for 2 weeks to determine the dose range. One male was moribund, and one female was found dead in the 100 mg/kg/day group. One male was also found dead in the 50 mg/kg/day group. The death was considered an adverse effect in both sexes since distal tubules/collecting duct dilation and hypertrophy in the epithelium of the papillary duct were observed in their kidneys. Based on dose range finding results, KDS2010 (10, 20, or 40 mg/kg/day) was administered orally for 4 weeks, and animals were given 2 weeks for recovery. No significant changes were observed during daily clinical observations and macro-and microscopic examinations, including body weight, food consumption, hematology, clinical chemistry, and organ weight. And, the kidney was seen as the primary target organ of KDS2010 in the 2 weeks study, but no adverse effect was observed in the 4 weeks study. Therefore, 40 mg/kg/day is considered the no-observed-adverse-effect level in both sexes of cynomolgus monkeys. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00182-4.

Clinical outcome of rim-plate-augmented separate vertical wiring with supplementary fixation for the treatment of patellar fracture associated comminuted inferior pole.

Despite the variety of treatment methods, comminuted inferior pole fractures of the patella remain difficult and technically demanding to achieve stable internal fixation. The purpose of this study is to evaluate the clinical outcomes of rim plate-augmented separate vertical wiring with supplementary fixation in the management of comminuted inferior pole fractures, AO/OTA 34-A1, C2, and C3, which has the secondary horizontal fracture line on lower articular boundary. From our study, bony union was achieved in all patients at an average of 3.1 ± 1.4 months after surgery. There was no patient with loss of reduction, fixation failure, or infection during follow-up. The average final range of motion was 131.6° ± 7.2°. Lysholm knee scores gradually increased over 3, 6, 9, and 12 months postoperatively by 58.7, 74.0, 82.9, and 89.4, respectively. Isokinetic peak torque deficit of the knee extensor muscles in 3, 6, 9, and 12 months postoperatively was 59.9%, 49.7%, 35.7%, and 28.1%, respectively. The rim plate-augmented separate vertical wiring with supplementary fixation for the treatment of patellar fracture associated comminuted inferior pole is effective and can be safely applied AO/OTA 34-C2 or C3 with favorable outcomes.

A comparative study on the implementation of deep learning algorithms for detection of hepatic necrosis in toxicity studies.

Deep learning has recently become one of the most popular methods of image analysis. In non-clinical studies, several tissue slides are generated to investigate the toxicity of a test compound. These are converted into digital image data using a slide scanner, which is then studied by researchers to investigate abnormalities, and the deep learning method has been started to adopt in this study. However, comparative studies evaluating different deep learning algorithms for analyzing abnormal lesions are scarce. In this study, we applied three algorithms, SSD, Mask R-CNN, and DeepLabV3+, to detect hepatic necrosis in slide images and determine the best deep learning algorithm for analyzing abnormal lesions. We trained each algorithm on 5750 images and 5835 annotations of hepatic necrosis including validation and test, augmented with 500 image tiles of 448 × 448 pixels. Precision, recall, and accuracy were calculated for each algorithm based on the prediction results of 60 test images of 2688 × 2688 pixels. The two segmentation algorithms, DeepLabV3+ and Mask R-CNN, showed over 90% of accuracy (0.94 and 0.92, respectively), whereas SSD, an object detection algorithm, showed lower accuracy. The trained DeepLabV3+ outperformed all others in recall while also successfully separating hepatic necrosis from other features in the test images. It is important to localize and separate the abnormal lesion of interest from other features to investigate it on a slide level. Therefore, we suggest that segmentation algorithms are more appropriate than object detection algorithms for use in the pathological analysis of images in non-clinical studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00173-5.

The Clinical Efficacy of Contouring Periarticular Plates on a 3D Printed Bone Model.

We report our experience of preoperative plate contouring for periarticular fractures using three-dimensional printing (3DP) technology and describe its benefits. We enrolled 34 patients, including 11 with humerus midshaft fractures, 12 with tibia plateau fractures, 2 with pilon fractures, and 9 with acetabulum fractures. The entire process of plate contouring over the 3DP model was videotaped and retrospectively analyzed. The total time and number of trials for the intraoperative positioning of precontoured plates and any further intraoperative contouring events were prospectively recorded. The mismatch between the planned and postoperative plate positions was evaluated. The average plate contouring time was 9.2 min for humerus shaft, 13.8 min for tibia plateau fractures, 8.8 min for pilon fractures, and 11.6 min for acetabular fractures. Most precontoured plates (88%, 30/34) could sit on the planned position without mismatch. In addition, only one patient with humerus shaft fracture required additional intraoperative contouring. Preoperative patient specific periarticular plate contouring using a 3DP model is a simple and efficient method that may alleviate the surgical challenges involved in plate contouring and positioning.

Segmentation algorithm can be used for detecting hepatic fibrosis in SD rat.

BACKGROUND: Liver fibrosis is an early stage of liver cirrhosis. As a reversible lesion before cirrhosis, liver failure, and liver cancer, it has been a target for drug discovery. Many antifibrotic candidates have shown promising results in experimental animal models; however, due to adverse clinical reactions, most antifibrotic agents are still preclinical. Therefore, rodent models have been used to examine the histopathological differences between the control and treatment groups to evaluate the efficacy of anti-fibrotic agents in non-clinical research. In addition, with improvements in digital image analysis incorporating artificial intelligence (AI), a few researchers have developed an automated quantification of fibrosis. However, the performance of multiple deep learning algorithms for the optimal quantification of hepatic fibrosis has not been evaluated. Here, we investigated three different localization algorithms, mask R-CNN, DeepLabV3+, and SSD, to detect hepatic fibrosis. RESULTS: 5750 images with 7503 annotations were trained using the three algorithms, and the model performance was evaluated in large-scale images and compared to the training images. The results showed that the precision values were comparable among the algorithms. However, there was a gap in the recall, leading to a difference in model accuracy. The mask R-CNN outperformed the recall value (0.93) and showed the closest prediction results to the annotation for detecting hepatic fibrosis among the algorithms. DeepLabV3+ also showed good performance; however, it had limitations in the misprediction of hepatic fibrosis as inflammatory cells and connective tissue. The trained SSD showed the lowest performance and was limited in predicting hepatic fibrosis compared to the other algorithms because of its low recall value (0.75). CONCLUSIONS: We suggest it would be a more useful tool to apply segmentation algorithms in implementing AI algorithms to predict hepatic fibrosis in non-clinical studies.

Preparing pathological data to develop an artificial intelligence model in the nonclinical study.

Artificial intelligence (AI)-based analysis has recently been adopted in the examination of histological slides via the digitization of glass slides using a digital scanner. In this study, we examined the effect of varying the staining color tone and magnification level of a dataset on the result of AI model prediction in hematoxylin and eosin stained whole slide images (WSIs). The WSIs of liver tissues with fibrosis were used as an example, and three different datasets (N20, B20, and B10) were prepared with different color tones and magnifications. Using these datasets, we built five models trained Mask R-CNN algorithm by a single or mixed dataset of N20, B20, and B10. We evaluated their model performance using the test dataset of three datasets. It was found that the models that were trained with mixed datasets (models B20/N20 and B10/B20), which consist of different color tones or magnifications, performed better than the single dataset trained models. Consequently, superior performance of the mixed models was obtained from the actual prediction results of the test images. We suggest that training the algorithm with various staining color tones and multi-scaled image datasets would be more optimized for consistent remarkable performance in predicting pathological lesions of interest.

Application of convolutional neural network for analyzing hepatic fibrosis in mice.

Recently, with the development of computer vision using artificial intelligence (AI), clinical research on diagnosis and prediction using medical image data has increased. In this study, we applied AI methods to analyze hepatic fibrosis in mice to determine whether an AI algorithm can be used to analyze lesions. Whole slide image (WSI) Sirius Red staining was used to examine hepatic fibrosis. The Xception network, an AI algorithm, was used to train normal and fibrotic lesion identification. We compared the results from two analyses, that is, pathologists' grades and researchers' annotations, to observe whether the automated algorithm can support toxicological pathologists efficiently as a new apparatus. The accuracies of the trained model computed from the training and validation datasets were greater than 99%, and that obtained by testing the model was 100%. In the comparison between analyses, all analyses showed significant differences in the results for each group. Furthermore, both normalized fibrosis grades inferred from the trained model annotated the fibrosis area, and the grades assigned by the pathologists showed significant correlations. Notably, the deep learning algorithm derived the highest correlation with the pathologists' average grade. Owing to the correlation outcomes, we conclude that the trained model might produce results comparable to those of the pathologists' grading of the Sirius Red-stained WSI fibrosis. This study illustrates that the deep learning algorithm can potentially be used for analyzing fibrotic lesions in combination with Sirius Red-stained WSIs as a second opinion tool in non-clinical research.

Iatrogenic radial nerve palsy in the surgical treatment of humerus shaft fracture -anterolateral versus posterior approach: A systematic review and meta-analysis.

BACKGROUND: Although many studies have investigated iatrogenic radial nerve palsy (RNP) in humerus shaft fracture, there is inconsistent evidence on which approach leads to iatrogenic RNP. Moreover, no meta-analysis has directly compared the anterolateral and posterior approaches regarding iatrogenic RNP. METHODS: In this systematic review and meta-analysis, the MEDLINE, Embase, and Cochrane Library databases were searched systematically for studies published before March 30, 2021. We included studies that (1) assessed the RNP in the surgical treatment of humerus shaft fracture and (2) directly compared the anterolateral and posterior approaches regarding the RNP. We performed synthetic analyses of the incidence of iatrogenic RNP and the recovery rate of iatrogenic RNP in humerus shaft fracture between the anterolateral and posterior approaches. RESULTS: Our study enrolled nine studies, representing 1303 patients who underwent surgery for humerus shaft fracture. After exclusion of traumatic RNP, iatrogenic RNP was reported in 35 out of 678 patients in the anterolateral approach and in 69 out of 497 patients in the posterior approach. Pooled analysis revealed that the incidence of iatrogenic RNP was significantly higher in the posterior approach than in the anterolateral approach (OR = 2.72; 95% confidence interval (CI), 1.70-4.35; P < 0.0001, I2 = 0%), but there was no significant difference in the recovery rates of iatrogenic RNP between the two approaches (OR = 1.55; 95% CI, 0.26-9.18; P = 0.63, I2 = 0%). CONCLUSION: In this meta-analysis, the posterior approach showed a higher incidence of iatrogenic RNP than the anterolateral approach in the surgical treatment of humerus shaft fracture. With limited studies, it is difficult to anticipate if any particular approach favors the recovery of iatrogenic RNP.

Radiographic rotational profiles of the proximal and distal humerus: analysis of 46 computed tomography scans with 3-dimensional simulation.

BACKGROUND: To date, no study has investigated the radiographic rotational profiles (RRPs) of the proximal and distal humerus. However, malrotation after minimally invasive surgery for humeral fracture has been an unsolved problem. Therefore, we aimed to investigate the RRPs of the proximal and distal humerus that linearly correlate with rotational status and show significant differences as the rotational status changes. METHODS: Forty-six computed tomography scans of the humerus were 3-dimensionally reconstructed, and 5 rotational statuses (20° and 10° of internal rotation; neutral; and 10° and 20° of external rotation) were simulated. Seven candidate RRPs of the proximal humerus and 4 candidates of the distal humerus were measured for each rotational status. The overall differences and trends in the RRPs as the rotational status changed were evaluated, and multiple comparisons were performed between the RRPs for each of the 5 rotational statuses. Moreover, the correlations between the RRPs and rotational status with adjustment of retroversion were analyzed. Finally, interobserver and intraobserver reliabilities were evaluated. RESULTS: The following proximal and distal RRPs were linearly correlated with rotational status, differed significantly between the rotational statuses, and showed a relatively low prediction error and excellent interobserver and intraobserver reliabilities: the distance from the tip of the lesser tuberosity to the lateral margin of the proximal humerus (PL1) and the medial margin of the head (PL2), as well as the PL1 to PL2 ratio (PRL), in the proximal humerus; and the distance from the medial margin of the olecranon process to the medial epicondyle (DOP), the widest width of the overlapped olecranon fossa (DOF), and the distance from the lateral margin of the capitellum to the lateral epicondyle (DC) in the distal humerus. CONCLUSION: Our findings suggest that PL1, PL2, and PRL in the proximal humerus and DOP, DOF, and DC in the distal humerus are potentially useful and reproducible RRPs for restoring the intrinsic rotational alignment in humeral fractures.

Outcome of multi-staged induced membrane technique based on post-debridement cultures for the management of critical-sized bone defect following fracture-related infection.

The authors' institution utilizes multi-staged induced membrane technique protocol based on post-debridement culture in treating patients with critical-sized bone defect in lower extremity due to infected nonunion or post-traumatic osteomyelitis. This study aimed to evaluate the success rate of this limb reconstruction method and which risk factors are associated with recurrence of infection. 140 patients were treated with multi-staged induced membrane technique from 2013 to 2018 and followed up more than 24 months after bone grafting. The primary success rate of limb reconstruction was 75% with a mean follow-up of 45.3 months. The mean Lower Extremity Functional Scale in success group improved from 12.1 ± 8.5 to 56.6 ± 9.9 after the treatment. There were 35 cases of recurrence of infection at a mean of 18.5 months after bone grafting. Independent risk factors for recurrence of infection were infected free flap, surprise positive culture, deviation from our surgical protocol, and elevated ESR before final bone graft procedure. In conclusion, this study showed that multi-staged induced membrane technique protocol based on post-debridement culture resulted in 75% success rate and revealed a number of risk factors for recurrence of infection.

The difference in the corridor of the antegrade posterior column screw according to the presence of pelvic dysmorphism.

INTRODUCTION: Antegrade posterior column screw (aPCS) fixation via the anterior approach has been widely used for separated the posterior columns in acetabular fracture treatment. Although the relationship between pelvic dysmorphism and sacroiliac screws has been widely studied, no studies have reported on the clinical impact of pelvic dysmorphism on acetabular fractures. This study aimed to reveal the difference in the insertion angle and entry point of aPCS between the dysmorphic and normal pelvises. METHODS: Patients diagnosed with unilateral acetabular fractures and who underwent pelvic computed tomography scans between 2013 and 2019 in two institutes were enrolled in this study. Patients were divided into the dysmorphic and control groups according to the sacral dysmorphic score, which predicts the presence of pelvic dysmorphism, and each group enrolled 130 patients. The semitransparent 3D hemipelvis model was reconstructed using a 3D reconstruction program. The sagittal and coronal angles of a virtual cylinder that fill the safe corridor of the column screw the most were measured. The surface area of the safe corridor and distance of the optimal entry point from the anterior border of the sacroiliac joint were analyzed. The measurements were compared between the dysmorphic and control groups. RESULTS: The average sacral dysmorphic score in the normal and dysmorphic pelvis groups was 56.1 and 81.0, respectively. There were no significant differences in demographic data, including age, sex, height, weight, and body mass index, between the dysmorphic and control groups. There was a significant difference in the average sagittal insertion angle of PCs, which was 38.3° in the control group and 27.2° in the dysmorphic group (P < 0.001). The coronal insertion angles were not significantly different. The dysmorphic group presented longer straight distances (25.9 vs 24.8 mm, P = 0.026) and had a smaller aPCS surface area (685 vs 757 mm2, P < 0.001) than the control group. CONCLUSION: The present study describes a difference in the corridor of aPCS between the dysmorphic and normal pelvis. Insertion of aPCS in the dysmorphic pelvis requires a more acute angular trajectory in the sagittal plane than that in the normal pelvis.

Artificial Intelligence-Assisted Image Analysis of Acetaminophen-Induced Acute Hepatic Injury in Sprague-Dawley Rats.

Although drug-induced liver injury (DILI) is a major target of the pharmaceutical industry, we currently lack an efficient model for evaluating liver toxicity in the early stage of its development. Recent progress in artificial intelligence-based deep learning technology promises to improve the accuracy and robustness of current toxicity prediction models. Mask region-based CNN (Mask R-CNN) is a detection-based segmentation model that has been used for developing algorithms. In the present study, we applied a Mask R-CNN algorithm to detect and predict acute hepatic injury lesions induced by acetaminophen (APAP) in Sprague-Dawley rats. To accomplish this, we trained, validated, and tested the model for various hepatic lesions, including necrosis, inflammation, infiltration, and portal triad. We confirmed the model performance at the whole-slide image (WSI) level. The training, validating, and testing processes, which were performed using tile images, yielded an overall model accuracy of 96.44%. For confirmation, we compared the model's predictions for 25 WSIs at 20× magnification with annotated lesion areas determined by an accredited toxicologic pathologist. In individual WSIs, the expert-annotated lesion areas of necrosis, inflammation, and infiltration tended to be comparable with the values predicted by the algorithm. The overall predictions showed a high correlation with the annotated area. The R square values were 0.9953, 0.9610, and 0.9445 for necrosis, inflammation plus infiltration, and portal triad, respectively. The present study shows that the Mask R-CNN algorithm is a useful tool for detecting and predicting hepatic lesions in non-clinical studies. This new algorithm might be widely useful for predicting liver lesions in non-clinical and clinical settings.

Stress fracture after implant removal from the tibia reconstructed by the induced membrane technique: A case report.

Background: The induced membrane technique promotes vascularization and corticalization of the grafted bone and has become one of the mainstays in treatment of segmental bone defects. However, there are clinical concerns regarding the quality of bony consolidation using the induced membrane technique including a thin cortex formation and cortical notching after consolidation. We present the case of a tibial stress fracture in the bone reconstructed by the induced membrane technique after implant removal. Case: A 49-year-old male presented post-traumatic osteomyelitis of the right tibia and was treated with staged segmental bone resection leading to an 11 cm defect which was reconstructed using the induced membrane technique. The patient requested implant removal at 33 months after bony consolidation. Four months after implant removal, he developed acute, atraumatic leg pain due to a tibial stress fracture caused by small notching in the reconstructed tibial segment. His stress fracture treated with intramedullary nailing and later healed uneventfully. Conclusion: Caution is warranted prior to implant removal from bone reconstructed by the induced membrane technique as cortical notching may result in stress fractures.

Treatment of Critical-Sized Bone Defects Involving the Ankle Joints: Staged Tibiotalocalcaneal Arthrodesis With Induced Membrane Technique and Intramedullary Nail.

OBJECTIVES: To report the outcomes of staged tibiotalocalcaneal (TTC) arthrodesis for critical-sized bone defects involving the ankle joints. DESIGN: Retrospective review of case series. SETTING: Two academic Level 1 trauma centers. PATIENTS/PARTICIPANTS: The study included 20 patients with critical-sized (≥2 cm) segmental bone defects around the ankle joints. INTERVENTION: Staged TTC arthrodesis was performed with induced membrane technique and retrograde intramedullary nail. MAIN OUTCOME MEASUREMENTS: We investigated the radiological evaluation, including modified radiographic union scale for tibia fractures score, time to union, and leg length discrepancy, and functional outcomes using foot and ankle outcome score and American Orthopaedic Foot and Ankle Society ankle-hindfoot score. RESULTS: The average bone defect was 6.4 cm (range: 2.4-12.3). Two of the 20 (10%) patients developed recurrence of infection. Fifteen patients (75%) achieved primary healing. Three patients (15%) were treated with repeated bone grafting and additional plating. The average time to union and leg length discrepancy were 10 months (range: 5-21) and 9 mm (range: 0-31), respectively. The mean foot and ankle outcome score and American Orthopaedic Foot and Ankle Society ankle-hindfoot score were 63 (range: 52-71) and 74 (range: 64-81), respectively. CONCLUSIONS: Staged TTC arthrodesis with induced membrane technique and intramedullary nail can be an effective treatment method for critical-sized bone defects involving the ankle joints. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Effect of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) with Hydroxyapatite Carrier in Induced Membrane Technique: A Retrospective Propensity Score-Matched Study.

OBJECTIVES: To determine the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) with hydroxyapatite (HA) carrier augmentation in managing critical-sized bone defect (CSBD) with induced membrane technique (IMT). DESIGN: Retrospective comparative study. SETTING: Academic level I trauma center. PATIENTS/PARTICIPANTS: The study included 14 patients who underwent rhBMP-2 with HA carrier (rhBMP-2/HA) augmentation in IMT for managing CSBD (BMP group). Moreover, 14 patients who underwent IMT without rhBMP-2 augmentation were matched by propensity score analysis (non-BMP group). INTERVENTION: IMT with or without rhBMP-2/HA augmentation. MAIN OUTCOME MEASUREMENT: Changes in quality and quantity measurements of grafted bone to regenerated bone using serial computed tomography. RESULTS: In the BMP and non-BMP groups, the changes in densities from grafted bone to regenerated bone were +379.63 Hounsfield unit and +248.55 Hounsfield unit (P = 0.034), changes in dense bone percentage were +37.52% and +23.31% (P = 0.027), corticalization rates under the plate were 79.70% and 39.30% (P = 0.007), changes in volume were -20.77% and -23.35% (P = 0.812), union rates were 85.71% and 78.57% (P = 0.622), numbers of patients requiring additional procedures were 4 and 3 (P = 0.663), and time to union were 316.3 and 585.45 days (P = 0.040), respectively. CONCLUSIONS: RhBMP-2/HA augmentation increases the density of regenerated bone, enhances corticalization under the plate, and shortens the time to union while managing CSBD with IMT. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Outcomes of embedded rafting k-wire technique for intermediate articular fragment fixation in comminuted olecranon fractures.

BACKGROUND: Severely comminuted olecranon fractures are challenging injuries. Commonly used tension band wiring exerts excessive compressive forces causing olecranon shortening and joint incongruity. This study aimed to introduce the embedded rafting k-wire technique with the bridging technique for intermediate articular fragment fixation in comminuted olecranon fractures and evaluate its clinical and radiological outcomes. MATERIALS AND METHODS: A total of 34 patients with comminuted olecranon fractures were treated with rafting k-wire fixation combined with a locking plate. Time to union, the number of rafting k-wires in the intermediate articular fragment, quality of joint reduction, and secondary reduction loss were analyzed. Elbow range of motion, Mayo Elbow Performance Score (MEPS), and complications were evaluated at the final follow-up. RESULTS: Fracture union was obtained in all patients. The mean number of intermediate articular fragments was 2.4 ± 0.7, and the average number of rafting k-wires was 3.0 ± 1.2. There were mild and moderate degree early posttraumatic osteoarthritis in 6 cases (17.6%) at the mean 20.8 months of follow-up. At the final follow-up, the mean range of elbow motion was 4.6° of flexion contracture and 133.5° of further flexion. The average MEPS was 97.1 (range, 75-100). Two patients had heterotrophic ossification without functional impairment. CONCLUSION: The embedded rafting k-wire technique with bridging plates in comminuted olecranon fractures exhibited satisfactory outcomes. This method might serve as an alternative when considering the ability to restore articular congruency and stability in severely comminuted olecranon fragments. LEVEL OF EVIDENCE: Level IV, therapeutic.

Adverse postnatal developmental effects in offspring from humidifier disinfectant biocide inhaled pregnant rats.

Inhalation exposure to polyhexamethylene guanidine phosphate (PHMG-P), one of the primary biocides used in humidifier disinfectants, caused a fatal pulmonary disease in Korea. Pregnant women were also exposed to PHMG-P, and subsequent studies showed that PHMG-P inhalation during pregnancy adversely affects their health and embryo-fetal development. However, the postnatal developmental effects after birth on prenatally PHMG-P-exposed offspring have not yet been investigated. Therefore, in this study, we aimed to examine the postnatal development of prenatally PHMG-P-exposed offspring. Pregnant rats (22 or 24 females per group) were exposed to PHMG-P during pregnancy in a whole-body inhalation chamber at the target concentrations of 0, 0.14, 1.60, and 3.20 mg/m3. After parturition, the prenatally exposed offspring were transferred to non-exposed surrogate mothers to minimize the secondary effects of severe maternal toxicities. Postnatal development of offspring was then examined with a modified extended one-generation reproductive toxicity study design. At 3.20 mg/m3 PHMG-P, increased perinatal death rates and decreased viability index (postnatal survival of offspring between birth and postnatal day 4) were observed. In addition, F1 offspring had lower body weight at birth that persisted throughout the study. PHMG-P-exposed pregnant rats also had severe systemic toxicities and increased gestation period. At 1.60 mg/m3 PHMG-P, a decreased viability index was also observed with systemic toxicities of PHMG-P-exposed pregnant rats. These results indicate that prenatal PHMG-P exposure adversely affects the offspring's future health and could be used for human risk assessment.

Implementation and Practice of Deep Learning-Based Instance Segmentation Algorithm for Quantification of Hepatic Fibrosis at Whole Slide Level in Sprague-Dawley Rats.

Exponential development in artificial intelligence or deep learning technology has resulted in more trials to systematically determine the pathological diagnoses using whole slide images (WSIs) in clinical and nonclinical studies. In this study, we applied Mask Regions with Convolution Neural Network (Mask R-CNN), a deep learning model that uses instance segmentation, to detect hepatic fibrosis induced by N-nitrosodimethylamine (NDMA) in Sprague-Dawley rats. From 51 WSIs, we collected 2011 cropped images with hepatic fibrosis annotations. Training and detection of hepatic fibrosis via artificial intelligence methods was performed using Tensorflow 2.1.0, powered by an NVIDIA 2080 Ti GPU. From the test process using tile images, 95% of model accuracy was verified. In addition, we validated the model to determine whether the predictions by the trained model can reflect the scoring system by the pathologists at the WSI level. The validation was conducted by comparing the model predictions in 18 WSIs at 20× and 10× magnifications with ground truth annotations and board-certified pathologists. Predictions at 20× showed a high correlation with ground truth (R2 = 0.9660) and a good correlation with the average fibrosis rank by pathologists (R2 = 0.8887). Therefore, the Mask R-CNN algorithm is a useful tool for detecting and quantifying pathological findings in nonclinical studies.