Facial vascular visualization enhancement based on optical detection technology.

OBJECTIVE: This study aims to develop a facial vascular enhancement imaging system and analyze vascular distribution in the facial region to assess its potential in preventing unintended intravascular injections during cosmetic facial filling procedures. METHODS: A facial vascular enhancement imaging system based on optical detection technology was designed, and volunteers were recruited. The system was utilized to detect and analyze vascular distribution in various anatomical regions of the faces. The vascular visualization-enhanced images generated by the system were compared with visible light images to validate the vascular visualization capability of the system. Additionally, the reliability of vascular visualization was assessed by comparing the observed vascular patterns in the vascular visualization-enhanced images with those in near-infrared light images. RESULTS: Thirty volunteers were recruited. The vascular visualization-enhanced images produced by the system demonstrated a significant capacity to identify vascular morphology and yielded a higher vessel count compared to visible light images, particularly in the frontal, orbital, perioral, mental, temporal, cheek, and parotid masseter regions (p < 0.05). The temporal region exhibited the highest vascular density, followed by the cheek region and then the frontal region. Reliability analysis of vascular visualization enhancement indicated that the system's imaging of facial vasculature not only demonstrated reliability but also enhanced physicians' visual perception. CONCLUSION: Blood vessel distribution varies across facial regions. The facial vascular enhancement imaging system facilitates real-time and clear visualization of facial vasculature, offering immediate visual feedback to surgeons. This innovation holds promise for enhancing the safety and effectiveness of facial filling procedures.

Cecal Metastasis of Clear Cell Renal Cell Carcinoma After Previous Nephrectomy.

Metastasis of renal cell carcinoma (RCC) to the gastrointestinal (GI) tract is exceedingly rare. We present a case of a man in his 40s with a history of RCC that had metastasized to his abdominal wall and brain who then presented with abdominal pain and melena. On presentation, imaging showed new bone metastases and a colonic mass in the ascending colon. The biopsy of the mass from colonoscopy demonstrated RCC primary. Although rare, this case report highlights the importance of a thorough evaluation of patients with a history of RCC and considers GI tract involvement in those presenting with GI bleeding.

Mesoporous bioactive glass scaffolds for the delivery of bone marrow stem cell-derived osteoinductive extracellular vesicles lncRNA promote senescent bone defect repair by targeting the miR-1843a-5p/Mob3a/YAP axis.

Bone repair in elderly patients poses a huge challenge due to the age-related progressive decline in regenerative abilities attributed to the senescence of bone marrow stem cells (BMSCs). Bioactive scaffolds have been applied in bone regeneration due to their various biological functions. In this study, we aimed to fabricate functionalized bioactive scaffolds through loading osteoinductive extracellular vesicles (OI-EVs) based on mesoporous bioactive glass (MBG) scaffolds (1010 particles/scaffold) and to investigate its effects on osteogenesis and senescence of BMSCs. The results suggested that OI-EVs upregulate the proliferative and osteogenic capacities of senescent BMSCs. More importantly, The results showed that loading OI-EVs into MBG scaffolds achieved better bone regeneration. Furthermore, OI-EVs and BMSCs RNAs bioinformatics analysis indicated that OI-EVs play roles through transporting pivotal lncRNA acting as a "sponge" to compete with Mob3a for miR-1843a-5p to promote YAP dephosphorylation and nuclear translocation, ultimately resulting in elevated proliferation and osteogenic differentiation and reduced senescence-related phenotypes. Collectively, these results suggested that the OI-EVs lncRNA ceRNA regulatory networks might be the key point for senescent osteogenesis. More importantly, the study indicated the feasibility of loading OI-EVs into scaffolds and provided novel insights into biomaterial design for facilitating bone regeneration in the treatment of senescent bone defects. STATEMENT OF SIGNIFICANCE: Constructing OI-EVs/MBG delivering system and verification of its bone regeneration enhancement in senescent defect repair. Aging bone repair poses a huge challenge due to the age-related progressive degenerative decline in regenerative abilities attributed to the senescence of BMSCs. OI-EVs/MBG delivering system were expected as promising treatment for senescent bone repair, which could provide an effective strategy for bone regeneration in elderly patients. Clarification of potential OI-EVs lncRNA ceRNA regulatory mechanism in senescent bone regeneration OI-EVs play important roles through transferring lncRNA-ENSRNOG00000056625 sponging miR-1843a-5p that targeted Mob3a to activate YAP translocation into nucleus, ultimately alleviate senescence, promote proliferation and osteogenic differentiation in O-BMSCs, which provides theoretical basis for EVs-mediated therapy in future clinical works.

Impact of Liver Transplantation on Adipose Tissue Compartments and Its Association With Metabolic Sequela.

BACKGROUND: Loss of skeletal muscle can be accompanied by an increase in adipose tissue leading to sarcopenic obesity. There are limited data on how liver transplantation (LT) might impact adipose tissue compartments, particularly among patients with metabolically active disease, such as nonalcoholic steatohepatitis (NASH) and subsequent metabolic sequela. METHODS: Skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured using cross-sectional imaging performed in 190 patients pre-LT, 6 mo post-LT and 12 mo post-LT. Changes in adipose tissue and their impact on metabolic diseases were determined in patients transplanted for NASH versus non-NASH. RESULTS: Skeletal muscle, VAT, and SAT were similar in patients with NASH and non-NASH pre-LT despite a higher burden of metabolic diseases in patients with NASH. Following LT, no significant differences between skeletal muscle and SAT were observed in the entire cohort and among patients with NASH (versus non-NASH). LT recipients with the highest muscle mass pre-LT were at the greatest risk for muscle loss post-LT. A time-dependent increase in VAT was noted post-LT, which was more robust among patients with a history of NASH cirrhosis. In adjusted multivariate analysis, NASH versus non-NASH was a strong predictor of post-LT increase in VAT (ß-coefficient 3.00, P = 0.04). Pre-LT VAT was an independent predictor of post-LT serum triglycerides (ß-coefficient 5.49 ± 2.78, P = 0.05) and low-density lipoprotein cholesterol (ß-coefficient 1.80 ± 0.75, P = 0.02). A trend between pre-LT VAT and diabetes was noted but did not reach statistical significance. CONCLUSIONS: VAT but not SAT increases rapidly after LT, especially among patients transplanted for NASH cirrhosis and predicts future metabolic burden.

ScRNA-seq links dental fibroblasts heterogeneity with mechanoresponsiveness.

BACKGROUND AND OBJECTIVE: Periodontal ligament (PDL) and dental pulp (DP) share a common origin but have distinct biological and mechanical functions. To what extent the mechanoresponsive property of PDL can be attributed to its unique transcriptional profiles of cellular heterogeneity is unclear. This study aims to decipher cellular heterogeneity and distinct mechanoresponsive characteristics of odontogenic soft tissues and their underlying molecular mechanisms. MATERIALS AND METHODS: A single-cell comparison of digested human periodontal ligament (PDL) and dental pulp (DP) was performed using scRNA-seq. An in vitro loading model was constructed to measure mechanoresponsive ability. Dual-luciferase assay, overexpression, and shRNA knockdown were used to investigate the molecular mechanism. RESULTS: Our results demonstrate striking fibroblast heterogeneity across and within human PDL and DP. We demonstrated that a tissue-specific subset of fibroblasts existed in PDL exhibiting high expression of mechanoresponsive extracellular matrix (ECM) genes, which was verified by an in vitro loading model. ScRNA-seq analysis indicated a particularly enriched regulator in PDL-specific fibroblast subtype, Jun Dimerization Protein 2 (JDP2). Overexpression and knockdown of JDP2 extensively regulated the downstream mechanoresponsive ECM genes in human PDL cells. The force loading model demonstrated that JDP2 responded to tension and that knockdown of JDP2 effectively inhibited the mechanical force-induced ECM remodeling. CONCLUSIONS: Our study constructed the PDL and DP ScRNA-seq atlas to demonstrate PDL and DP fibroblast cellular heterogeneity and identify a PDL-specific mechanoresponsive fibroblast subtype and its underlying mechanism.

Bidirectional prediction of facial and bony shapes for orthognathic surgical planning.

This paper proposes a deep learning framework to encode subject-specific transformations between facial and bony shapes for orthognathic surgical planning. Our framework involves a bidirectional point-to-point convolutional network (P2P-Conv) to predict the transformations between facial and bony shapes. P2P-Conv is an extension of the state-of-the-art P2P-Net and leverages dynamic point-wise convolution (i.e., PointConv) to capture local-to-global spatial information. Data augmentation is carried out in the training of P2P-Conv with multiple point subsets from the facial and bony shapes. During inference, network outputs generated for multiple point subsets are combined into a dense transformation. Finally, non-rigid registration using the coherent point drift (CPD) algorithm is applied to generate surface meshes based on the predicted point sets. Experimental results on real-subject data demonstrate that our method substantially improves the prediction of facial and bony shapes over state-of-the-art methods.

Reciprocating Rasp for Use in Mandibular Anterior Subapical Osteotomy.

The article describes a reciprocating rasp used in the mandibular anterior subapical osteotomy. Over the past 2 years, reciprocating rasp osteotomy was introduced in the Oral and Craniomaxillofacial Surgery Department of Shanghai Ninth People's Hospital. No complication such as bleeding, wound infection, or tissue necrosis has been encountered. The use of reciprocating rasp avoids iatrogenic damage to adjacent structures and reduces the time spent operating mandibular anterior subapical osteotomy. Therefore, it is recommended for mandibular anterior subapical osteotomy.

Mandibular stability and condylar changes following orthognathic surgery in mandibular hypoplasia patients associated with preoperative condylar resorption.

OBJECTIVES: To evaluate postoperative mandibular stability and condylar changes in patients with mandibular hypoplasia and preoperative condylar resorption (CR) undergoing orthognathic surgery. MATERIALS AND METHODS: Fifty-four patients were included in this retrospective study. Computed tomography (CT) scans were acquired preoperatively (T0), 2-7 days immediate postoperatively (T1), and at least 1 year postoperatively (T2). Three-dimensional (3D) cephalometric analysis and measurements of condylar angle, volume, and position (joint spaces) were performed. A 2-mm mandibular relapse was deemed clinically acceptable. We also analyzed the correlations between relapse and postoperative CR and susceptible factors using a multivariate logistic regression model. RESULTS: The results showed one year after the surgery, the average mandibular relapse was 1.0 mm (p < 0.05), and the average reduction of condylar volume was 152.4 mm3 (12.7%). Condyle-fossa relationships were improved immediately after the surgery, with a tendency of returning to their original state in the follow-up (p < 0.05). Anteroposterior advancement at point B (B-CP advancement) at T1 and superior joint space (SJS) at T0 were significantly correlated with mandibular relapse, and postoperative CR was mainly associated with vertical increasement at point B (B-AP increasement) at T1. The optimal cut-off values were as follows: 1.6 mm for SJS, 4.2 mm for B-CP advancement, and 1.8 mm for B-AP increasement. Concomitant advancement Genioplasty showed no significant correlation with relapse and postoperative CR. CONCLUSIONS: While patients with mandibular hypoplasia and preoperative CR were vulnerable to further condylar resorption after mandibular advancement, the treatment outcomes were generally clinically acceptable. Postoperative relapse was associated with a larger than 4.2 mm of mandibular advancement measured at B-CP and a larger than 1.6 mm of superior joint space measured at SJS, and postoperative CR was associated with a larger than 1.8 mm of mandibular vertical increasement measured at B-AP. CLINICAL RELEVANCE: The findings of this study suggested that the mandibular advancement might be limited to 5 mm for patients with preoperative CR. A concomitant advancement genioplasty might also be considered to achieve a better facial profile in these patients.

Two-dimensional nanovermiculite and polycaprolactone electrospun fibers composite scaffolds promoting diabetic wound healing.

BACKGROUND: Promoting diabetic wound healing is still a challenge, and angiogenesis is believed to be essential for diabetic wound healing. Vermiculite is a natural clay material that is very easy to obtain and exhibits excellent properties of releasing bioactive ions, buffering pH, adsorption, and heat insulation. However, there are still many unsolved difficulties in obtaining two-dimensional vermiculite and using it in the biomedical field in a suitable form. RESULTS: In this study, we present a versatile organic-inorganic composite scaffold, which was constructed by embedding two-dimensional vermiculite nanosheets in polycaprolactone electrospun fibers, for enhancing angiogenesis through activation of the HIF-1α signaling pathway and promoting diabetic wound healing both in vitro and in vivo. CONCLUSIONS: Together, the rational-designed polycaprolactone electrospun fibers-based composite scaffolds integrated with two-dimensional vermiculite nanosheets could significantly improve neo-vascularization, re-epithelialization, and collagen formation in the diabetic wound bed, thus promoting diabetic wound healing. This study provides a new strategy for constructing bioactive materials for highly efficient diabetic wound healing.

Collaborative Control Method and Experimental Research on Robot-Assisted Craniomaxillofacial Osteotomy Based on the Force Feedback and Optical Navigation.

OBJECTIVE: Surgical robot has advantages in high accuracy and stability. But during the robot-assisted bone surgery, the lack of force information from surgical area and incapability of intervention from surgeons become the obstacle. The aim of the study is to introduce a collaborative control method based on the force feedback and optical navigation, which may optimally combine the excellent performance of surgical robot with clinical experiences of surgeons. MATERIALS AND METHODS: The CMF ROBOT system was integrated with the force feedback system to ensure the collaborative control. Force-velocity control algorithm based on force feedback was designed for this control method. In the preliminary experimental test, under the collaborative control mode based on force feedback and optical navigation, the craniomaxillofacial surgical robot entered the osteotomy line area according to the preoperative surgical plan, namely, right maxillary Le Fort I osteotomy, left maxillary Le Fort I osteotomy, and genioplasty. RESULTS: The force sensor was able to collect and record the resistance data of the cutting process of the robot-assisted craniomaxillofacial osteotomy assisted in real time. The statistical results showed that the repeatability of collaborative control mode was acceptable in bilateral maxillary Le Fort I osteotomies (right, P =0.124>0.05 and left, P =0.183>0.05) and unfavorable in genioplasty ( P =0.048<0.05). CONCLUSION: The feasibility of robot-assisted craniomaxillofacial osteotomy under the collaborative control method based on the force feedback and optical navigation was proved in some extent. The outcome of this research may improve the flexibility and safety of surgical robot to meet the demand of craniomaxillofacial osteotomy.

Reducing relapse and accelerating osteogenesis in rapid maxillary expansion using an injectable mesoporous bioactive glass/fibrin glue composite hydrogel.

Rapid maxillary expansion (RME), as a common treatment for craniomaxillofacial deformity, faces the challenge of high relapse rates and unsatisfactory therapeutic effects. In this study, a standardized Sprague-Dawley (SD) rat RME model was first established with a modified expander as well as retainer design and optimized anterior maxillary expanding force of 100 g which exerted the most synchronized mobility of mid-palatal suture and incisors. Via the standardized model, the high relapse rate was proven to be attributed to insufficient osteogenesis in expanded suture, requiring long-term retainer wearing in clinical situations. To reduce the relapse rate, mesoporous bioactive glass/fibrin glue (MBG/FG) composite hydrogels were developed for an in situ minimal invasive injection that enhance osteogenesis in the expanded palate. The component of 1 wt% MBG was adopted for enhanced mechanical strength, matched degradation rate and ion dissolution, excellent in vitro biocompatibility and osteoinductivity. Effects of 1%MBG/FG composite hydrogel on osteogenesis in expanded mid-palatal sutures with/without retention were evaluated in the standardized model. The results demonstrated that injection of 1%MBG/FG composite hydrogel significantly promoted bone formation within the expanded mid-palatal suture, inhibited osteoclastogenesis and benefited the balance of bone remodeling towards osteogenesis. Combination of retainer and injectable biomaterial was demonstrated as a promising treatment to reduce relapse rate and enhance osteogenesis after RME. The model establishment and the composite hydrogel development in this article might provide new insight to other craniomaxillofacial deformity treatment and design of bone-repairing biomaterials with higher regenerative efficiency.

Precise Intraoral Condylectomy With the Guide of Three-Dimensional Printed Template in a Mandibular Condylar Hyperplasia Patient.

PURPOSE: This study aimed to introduce an innovative method for mandibular condylectomy. A customized three-dimensional (3D) printed template is used to perform precise condylectomy in an intraoral approach. METHODS: Condylectomy combined with orthognathic surgery was used for the treatment of facial asymmetry secondary to unilateral condylar hyperplasia. The customized 3D printed osteotomy guide was placed with an intraoral approach under endoscopy, in order to perform a precise condylectomy. RESULT: With the customized 3D printed template, the condylectomy was performed more precisely, and the conventional extraoral incision was avoided. The osteotomy line was accurately transferred from the virtual surgical plan to the real surgery, which assured the precise resection. CONCLUSIONS: The intraoral approach combined with a 3D printed template provides a novel solution to perform the condylectomy precisely.

Glomerular filtration rate early after liver transplantation independently predicts atherosclerotic events.

Cardiovascular disease (CVD) is an important cause of mortality among liver transplantation (LT) recipients; however, the data on CVD risk stratification following LT are limited. Thus, the primary aim of this study was to evaluate the association between decline in renal function early after LT and atherosclerotic events. This retrospective study included all patients receiving LT between 2007 and 2019. Early renal function was quantified as estimated glomerular filtration rate (GFR) 6 months after LT. The primary endpoint for the study was a composite atherosclerotic cardiovascular event of three-point major adverse cardiovascular events (MACEs), which includes nonfatal myocardial infarction (MI), nonfatal stroke, or death from CVD. A total of 553 LT recipients met entry criteria. After a median follow-up of 74 months (interquartile range 46-111), 94 (17%) LT recipients died and CVD-associated death occurred in 20 patients. MACE-3 occurred in 66 (12%) patients, with nonfatal MI being the most common event (n = 30). A strong inverse relationship between early GFR and MACE-3 was noted in unadjusted analysis with hazard ratio (HR) 0.96 (95% confidence interval [CI] 0.95-0.98; p = 0.0001) and remained significant even after accounting for age, sex, coronary artery disease, diabetes mellitus, hypertension, calcineurin inhibitor use, and Framingham Risk Score (FRS; HR 0.96, 95% CI 0.95-0.97; p = 0.0001 per unit increase in GFR). Furthermore, an independent interaction between GFR, FRS, and likelihood of developing an MACE-3 was noted. GFR 6 months following LT is a strong predictor of developing atherosclerotic events. This relationship is independent of traditional CVD risk stratification models (e.g. FRS) and thus has the potential to be incorporated into CVD risk assessment after LT but requires further validation.

Differential fuel utilization in liver transplant recipients and its relationship with non-alcoholic fatty liver disease.

Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT). METHODS: Patients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation). RESULTS: The two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p < .001), indicative of impaired FA utilization. In subgroup analysis of the NASH cohort, body mass index but not liver fat content (MRI-PDFF) was an independent predictor of fasting RQ. In NASH, fasting RQ inversely correlated with fat-free muscle volume and directly with visceral adipose tissue. CONCLUSION: Reduced metabolic flexibility in patients transplanted for NASH cirrhosis may precede the development of non-alcoholic fatty liver disease after LT.

Designing Porous Ion Emitters for Thermal Ionization Mass Spectrometry: Evaluating Metal-Organic Frameworks.

This work describes the first exploration of metal-organic frameworks (MOFs) as "next-generation" ion emitters for thermal ionization mass spectrometry (TIMS). MOFs were identified as promising candidates for this application given the synthetic control over their desired structural properties. This tunability results in well-ordered, high-surface-area, high-porosity frameworks with targeted sorption affinities. Here, we explored an aluminum-based, bipyridine-containing MOF (MOF-253) with and without incorporating a high work function metal, rhenium (Re). After analysis of an Nd-bearing MOF, we hypothesized that the well-dispersed, sponge-like interconnected network of the degraded structure would enhance Nd ionization more than traditional TIMS loading techniques (i.e., phosphoric acid). Compared to filaments loaded with phosphoric acid that require an additional benzene carburization step, the Nd ionization efficiencies (atoms detected relative to atoms loaded) for heated filaments loaded with MOF-253 were similar (∼1%). Electron microscopy after TIMS analysis demonstrated that the MOF was retained on the filament. While these results are preliminary, they demonstrate that MOFs have potential to enhance ionization and exceed the performance of traditional loading techniques by forming nanoporous ion emitters. Thus, further experimentation is likely to exceed this performance through more specific selection of the base MOF structure and modifications to porosity and composition. This work represents a novel application of MOFs and a next step in the pursuit of advanced thermal ionization with potential to expand across the periodic table.

Effect of Swell1 on regulating chondrocyte hypertrophy during the condylar osteochondral development process in mice.

Chondrocyte hypertrophy is a significant factor in cartilage development, yet the molecular mechanism for cell volume expand during the process is remains unclear. In the present study, the relationship between Swell1, a cell volume regulated anion channel, and chondrocyte hypertrophy was explored. The results reveal that the spatiotemporal expression of Swell1 was similar with the development process of hypertrophic chondrocytes in condyles. Through Col10a1 mediated knock out of Swell1 in hypertrophy chondrocytes, we found that there are less obvious boundary between different condylar cartilage layers in which increased hypertrophic chondrocytes were scattered in all three cartilage layers. The cortical bone mass and bone mineral density in the subchondral bone significantly increased. Additionally, knock out of Swell1 could increase the expression of OCN in the femur condyle. Based on the aforementioned findings, a conclusion could be drawn that Swell1 is a significant factor in chondrocyte hypertrophy during the condylar osteochondral development process, and there was some difference between the mandibular and femur condyles, which will provide some new clues for understanding the development of cartilage and related diseases.

Modified Gap Arthroplasty for Temporomandibular Joint Ankylosis Following Radiotherapy for Rhabdomyosarcoma: Report of an Unusual Case and Brief Literature Review.

Radiotherapy at the temporomandibular joint (TMJ) area often results in trismus, however, post radiation ankylosis is extremely rare and has not been previously reported in literature. Radiation is known to impact the vasculature of bony structures leading to bone necrosis with certain risk factors including surgical intervention, even teeth extraction, that could lead to osteoradionecrosis. Accordingly, gap arthroplasty for such case seemed rather challenging. In this report, we introduce for the first time, a rare case of temporomandibular joint ankylosis post radiotherapy for management of rhabdomyosarcoma in a 12 years-old boy. A modified gap arthroplasty technique combined simultaneously with pterygo-masseteric muscle flap was applied to lower the risk of osteoradionecrosis due surgical trauma at irradiated area. Computed tomographic scan on the head indicated that the TMJ architecture was completely replaced by bone, with fusion of the condyle, sigmoid notch, and coronoid process to the zygomatic arch and glenoid fossa. The patient's problem was totally solved with no osteoradionecrosis or relapse of ankylosis observed at follow up visits. Herein, the modified gap arthroplasty combined with pterygo-masseteric muscle flap could be recommended to be applied on other cases of ankylosis especially after receiving radiotherapy.

A Self-Supervised Deep Framework for Reference Bony Shape Estimation in Orthognathic Surgical Planning.

Virtual orthognathic surgical planning involves simulating surgical corrections of jaw deformities on 3D facial bony shape models. Due to the lack of necessary guidance, the planning procedure is highly experience-dependent and the planning results are often suboptimal. A reference facial bony shape model representing normal anatomies can provide an objective guidance to improve planning accuracy. Therefore, we propose a self-supervised deep framework to automatically estimate reference facial bony shape models. Our framework is an end-to-end trainable network, consisting of a simulator and a corrector. In the training stage, the simulator maps jaw deformities of a patient bone to a normal bone to generate a simulated deformed bone. The corrector then restores the simulated deformed bone back to normal. In the inference stage, the trained corrector is applied to generate a patient-specific normal-looking reference bone from a real deformed bone. The proposed framework was evaluated using a clinical dataset and compared with a state-of-the-art method that is based on a supervised point-cloud network. Experimental results show that the estimated shape models given by our approach are clinically acceptable and significantly more accurate than that of the competing method.

Severe Vitamin B12 Deficiency Mimicking Microangiopathic Hemolytic Anemia.

Most individuals with vitamin B12 deficiency present with anemia, fatigue, and neurologic disturbances such as paresthesia and loss of sensory function if chronic. However, in severe states, it may manifest as hemolytic anemia, thrombocytopenia, schistocytosis, elevated lactate dehydrogenase, and low reticulocyte production. This phenomenon is known as pseudo-thrombotic microangiopathy (TMA), and is most commonly due to pernicious anemia. The overlap in clinical presentation with primary TMA creates a challenge in the diagnosis and management of pseudo-TMA. Primary TMA, particularly thrombotic thrombocytopenic purpura, is emergently managed with plasma exchange and may require admission to an intensive care unit due to high risk of mortality. In contrast, pseudo-TMA does not respond to plasma exchange and instead is treated with vitamin B12 supplementation. Patients with this atypical presentation of B12 deficiency may receive unnecessary, costly, and potentially harmful therapy. We present the case of a patient with pseudo-TMA in the setting of pernicious anemia.

N2-Polarized Neutrophils Guide Bone Mesenchymal Stem Cell Recruitment and Initiate Bone Regeneration: A Missing Piece of the Bone Regeneration Puzzle.

The role of neutrophils in bone regeneration remains elusive. In this study, it is shown that intramuscular implantation of interleukin-8 (IL-8) (commonly recognized as a chemotactic cytokine for neutrophils) at different levels lead to outcomes resembling those of fracture hematoma at various stages. Ectopic endochondral ossification is induced by certain levels of IL-8, during which neutrophils are recruited to the implanted site and are N2-polarized, which then secrete stromal cell-derived factor-1α (SDF-1α) for bone mesenchymal stem cell (BMSC) chemotaxis via the SDF-1/CXCR4 (C-X-C motif chemokine receptor 4) axis and its downstream phosphatidylinositol 3'-kinase (PI3K)/Akt pathway and ß-catenin-mediated migration. Neutrophils are pivotal for recruiting and orchestrating innate and adaptive immunocytes, as well as BMSCs at the initial stage of bone healing and regeneration. The results in this study delineate the mechanism of neutrophil-initiated bone regeneration and interaction between neutrophils and BMSCs, and innate and adaptive immunities. This work lays the foundation for research in the fields of bone regenerative therapy and biomaterial development, and might inspire further research into novel therapeutic options.