Deep Learning Prediction of Ovarian Malignancy at US Compared with O-RADS and Expert Assessment.

Background Deep learning (DL) algorithms could improve the classification of ovarian tumors assessed with multimodal US. Purpose To develop DL algorithms for the automated classification of benign versus malignant ovarian tumors assessed with US and to compare algorithm performance to Ovarian-Adnexal Reporting and Data System (O-RADS) and subjective expert assessment for malignancy. Materials and Methods This retrospective study included consecutive women with ovarian tumors undergoing gray scale and color Doppler US from January 2019 to November 2019. Histopathologic analysis was the reference standard. The data set was divided into training (70%), validation (10%), and test (20%) sets. Algorithms modified from residual network (ResNet) with two fusion strategies (feature fusion [hereafter, DLfeature] or decision fusion [hereafter, DLdecision]) were developed. DL prediction of malignancy was compared with O-RADS risk categorization and expert assessment by area under the receiver operating characteristic curve (AUC) analysis in the test set. Results A total of 422 women (mean age, 46.4 years ± 14.8 [SD]) with 304 benign and 118 malignant tumors were included; there were 337 women in the training and validation data set and 85 women in the test data set. DLfeature had an AUC of 0.93 (95% CI: 0.85, 0.97) for classifying malignant from benign ovarian tumors, comparable with O-RADS (AUC, 0.92; 95% CI: 0.85, 0.97; P = .88) and expert assessment (AUC, 0.97; 95% CI: 0.91, 0.99; P = .07), and similar to DLdecision (AUC, 0.90; 95% CI: 0.82, 0.96; P = .29). DLdecision, DLfeature, O-RADS, and expert assessment achieved sensitivities of 92%, 92%, 92%, and 96%, respectively, and specificities of 80%, 85%, 89%, and 87%, respectively, for malignancy. Conclusion Deep learning algorithms developed by using multimodal US images may distinguish malignant from benign ovarian tumors with diagnostic performance comparable to expert subjective and Ovarian-Adnexal Reporting and Data System assessment. © RSNA, 2022 Online supplemental material is available for this article.

Pt-Au/MOx-CeO2 (M = Mn, Fe, Ti) Catalysts for the Co-Oxidation of CO and H2 at Room Temperature.

A series of nanostructured Pt-Au/MOx-CeO2 (M = Mn, Fe, Ti) catalysts were prepared and their catalytic performance for the co-oxidation of carbon monoxide (CO) and hydrogen (H2) were evaluated at room temperature. The results showed that MOx promoted the CO oxidation of Pt-Au/CeO2, but only the TiO2 could enhance co-oxidation of CO and H2 over Pt-Au/CeO2. Related characterizations were conducted to clarify the promoting effect of MOx. Temperature-programmed reduction of hydrogen (H2-TPR) and X-ray photoelectron spectroscopy (XPS) results suggested that MOx could improve the charge transfer from Au sites to CeO2, resulting in a high concentration of Ce3+ and cationic Au species which benefits for the CO oxidation. In-situ diffuse reflectance infrared Fourier transform spectroscopy (In-situ DRIFTS) results indicated that TiO2 could facilitate the oxidation of H2 over the Pt-Au/TiO2-CeO2 catalyst.

PTEN gene polymorphisms and susceptibility to oral squamous cell carcinoma in a Chinese Han population.

The tumor suppressor gene phosphatase and tensin homologue (PTEN) plays a significant role in regulating cell growth, proliferation, and apoptosis. However, there are no data regarding the role of PTEN polymorphisms in the development of oral squamous cell carcinoma (OSCC). A hospital-based case-control study was conducted to investigate the potential association between PTEN polymorphisms and the risk of OSCC in a Chinese Han population. The study population comprised 201 patients with OSCC and 199 healthy controls. Seventeen single-nucleotide polymorphisms (SNPs) of PTEN were investigated and genotyped using Sequenom Mass ARRAY and iPLEX-MALDI-TOF technology. The observed genotype frequencies of these polymorphisms were in agreement with Hardy-Weinberg equilibrium in the control group (P > 0.05 for all). The heterozygous CT genotype was not associated with significantly increased risk for OSCC (OR = 0.89, 95 % CI = (0.55-1.42), P = 0.83), the TT genotype was not associated with increased risk for OSCC (OR = 1.01, 95 % CI = (0.58-1.74), P = 0.74) compared to the PTEN SNP rs1234224 homozygous CC genotype. Meanwhile, CT/TT variants were not associated with increased risk for OSCC compared with the CC genotype (OR = 0.93, 95 % CI = 0.60-1.44, P = 0.73). The T allele was not associated with significantly increased risk compared to the C allele (OR = 0.99, 95 % CI = 0.72-1.58, P = 0.69). Similar associations with the risk of OSCC were observed for the other genotypes of PTEN gene polymorphisms. There were no significant differences in the distribution of the genotype and allele frequencies of polymorphisms of the PTEN gene between the OSCC patients and controls in a Chinese Han population. Further studies are needed to clarify the specific roles of PTEN polymorphisms in the etiology of OSCC.

Gelsolin rs1078305 and rs10818524 polymorphisms were associated with risk of oral squamous cell carcinoma in a Chinese Han population.

BACKGROUND: Gelsolin (GSN) is one of the most abundant actin-binding proteins, and is involved in cancer development and progression. PATIENTS AND METHODS: A hospital-based case-control study including 201 patients with OSCC and 199 healthy controls was conducted. Seventeen single-nucleotide polymorphisms (SNPs) of GSN were investigated by Sequenom Mass ARRAY and iPLEX-MALDI-TOF technology. RESULTS: Through comparison of the 17 SNPs on GSN gene between the two groups, SNP rs1078305 and rs10818524 were verified to be significantly associated with an increased risk of OSCC. For GSN rs1078305, the TT genotype was associated with increased risk for OSCC (OR = 1.92, 95% CI = 1.11-3.32, p = 0.028). CT/TT variants were also associated with increased risk for OSCC compared to the CC genotype (OR = 1.83, 95% CI = 1.25-3.84, p = 0.032). CONCLUSION: The rs1078305 and rs10818524 SNPs of GSN were associated with increased risk for OSCC development in a Chinese Han population.

Estimation of Viscoelastic Properties of Cells Using Acoustic Tweezing Cytometry.

OBJECTIVES: Recently developed acoustic tweezing cytometry uses ultrasound-responsive targeted microbubbles for biomechanical stimulation of live cells at the subcellular level. The purpose of this research was to estimate the viscoelastic characteristics of cells from the displacements of cell-bound microbubbles in response to ultrasound pulses on acoustic tweezing cytometry. METHODS: Microbubbles were bound to NIH/3T3 fibroblasts and ATDC5 cells through an integrin-cytoskeleton linkage. The evolution of microbubble behaviors under irradiation by ultrasound pulses was captured by a high-speed camera and tracked by a customized algorithm. The total damping constant, stiffness, and rigidity of the cells were estimated by fitting the measured temporal displacement profiles to a Kelvin-Voigt-based model. RESULTS: The mean maximum displacement of the microbubbles attached to NIH/3T3 fibroblasts was much greater than that for ATDC5 cells. The mean fitted damping constant and stiffness ± SD for ATDC5 cells were 28.16 ± 7.08 mg/s and 0.5041 ± 0.1381 mN/m, respectively, and the values for NIH/3T3 fibroblasts were 13.12 ± 4.23 mg/s and 0.2591 ± 0.0715 mN/m. The rigidity for ATDC5 cells was 331.46 ± 106.50 MPa, whereas that for NIH/3T3 fibroblasts was 117.92 ± 34.83 MPa. CONCLUSIONS: The Arg-Gly-Asp-integrin-cytoskeleton system of NIH/3T3 fibroblasts appears to be softer than that of ATDC5 cells. The rigidity of ATDC5 cells was significantly greater than that of NIH/3T3 fibroblasts at the 95% confidence level. This strategy provides a novel way to determine the viscoelastic properties of the live cells.

Catalytic Oxidation of NO over MnOx-CeO2 and MnOx-TiO2 Catalysts.

A series of MnOx-CeO2 and MnOx-TiO2 catalysts were prepared by a homogeneous precipitation method and their catalytic activities for the NO oxidation in the absence or presence of SO2 were evaluated. Results show that the optimal molar ratio of Mn/Ce and Mn/Ti are 0.7 and 0.5, respectively. The MnOx-CeO2 catalyst exhibits higher catalytic activity and better resistance to SO2 poisoning than the MnOx-TiO2 catalyst. On the basis of Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), and scanning transmission electron microscope with mapping (STEM-mapping) analyses, it is seen that the MnOx-CeO2 catalyst possesses higher BET surface area and better dispersion of MnOx over the catalyst than MnOx-TiO2 catalyst. X-ray photoelectron spectroscopy (XPS) measurements reveal that MnOx-CeO2 catalyst provides the abundance of Mn3+ and more surface adsorbed oxygen, and SO2 might be preferentially adsorbed to the surface of CeO2 to form sulfate species, which provides a protection of MnOx active sites from being poisoned. In contrast, MnOx active sites over the MnOx-TiO2 catalyst are easily and quickly sulfated, leading to rapid deactivation of the catalyst for NO oxidation. Furthermore, temperature programmed desorption with NO and O2 (NO + O2-TPD) and in situ diffuse reflectance infrared transform spectroscopy (in situ DRIFTS) characterizations results show that the MnOx-CeO2 catalyst displays much stronger ability to adsorb NOx than the MnOx-TiO2 catalyst, especially after SO2 poisoning.

Use of Extended Lateral Upper Arm Free Flap for Tongue Reconstruction After Radical Glossectomy for Tongue Cancer.

BACKGROUND: This study evaluated the safety and effectiveness of the extended lateral arm free flap (ELAFF) for repair of partial tongue defects after radical resection of tongue cancer. METHODS: The study included nine consecutive patients who underwent repair of a partial tongue defect with an ELAFF after radical resection of tongue cancer from November 2010 to December 2013. Lesions were at the tip or margin of the tongue. Details of the reconstructive surgery, donor-site and recipient-site morbidity, and functional and esthetic outcomes were evaluated during a minimum of 12 months follow-up. Patient-reported Visual Analog Scale (VAS) scores on a scale of 0 (minimum satisfaction) to 10 (maximum satisfaction) were used to evaluate esthetic outcomes. RESULTS: All patients were followed up for 12 months (median 24 months). The overall survival rate was 88 % (8/9). The donor site was closed primarily in all patients. The most frequent donor-site morbidity was a broad scar. Poor functional outcomes were associated with postoperative adjuvant radiotherapy. The shape and function of the reconstructed tongue were satisfactory. VAS scores (mean ± SD) for patient satisfaction with recipient-site and donor-site esthetics were 6.92 ± 1.70 and 7.33 ± 2.01, respectively. CONCLUSION: The ELAFF is a safe and effective option for repair of partial tongue defects after radical resection of tongue cancer. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Asymmetric Synthesis of 1,3-Oxazolidine Derivatives with Multi-Component Reaction and Research of Kinetic Resolution.

An efficient multi-component reaction to synthesize multi-substituted 1,3-oxazolidine compounds of high optical purity was described. All the products were well-characterized and the absolute configuration of one chiral center was determined. The plausible mechanism was proposed and a kinetic resolution of epoxides process was confirmed.

Application of near-infrared fluorescence imaging in lingual lymph node screening and drainage pattern observation for tongue cancer.

Objective: Lingual lymph node (LLN) metastasis is regarded as an indicator of unfavorable prognosis and a crucial sign of the high degree of primary tumor aggressiveness. However, detecting LLN metastasis is an important but frequently overlooked aspect of diagnosis and surgical treatment planning. The study aims to identify LLNs by intraoperative near-infrared (NIR) fluorescence imaging with indocyanine green absorbed into human serum albumin (ICG: HSA) and describe the presence of lymphatic drainage channels from the floor of the mouth in patients with tongue carcinoma. Materials and Methods: 21 patients diagnosed with cT1-T4 squamous cell carcinoma (SCC) of the tongue margin and scheduled to undergo tumor resection and unilateral neck dissection were enrolled. After exposing the neck, the patients were injected with 0.3 ml of ICG: HSA (500 µM) in three quadrants around the tumor, excluding the mucous membrane of the basal region cavity. Employing a near-infrared fluorescence imaging system, the fluorescence of levels I, II, III, and IV was measured during neck dissection. Results: LLNs were detected in four patients and were identified as metastatic LLNs in all 21 patients. The near-infrared fluorescence imaging system showed the existence of lymphatic drainage channels in the floor of the mouth. In patients receiving peritumoral injection of ICG: HSA, the mean fluorescence intensity (MFI)of metastatic lymph nodes (LNs) (178.4 ± 64.39, mean ± SD) was higher than that in non-metastatic LNs (132.0 ± 76.5, mean ± SD) (p < 0.05). Conclusion: NIR fluorescence imaging with ICG: HSA could be used for intraoperative identification of LLNs and assist in the determination of metastatic lymph nodes for tongue carcinoma patients. Additionally, this finding demonstrates the feasibility of near-infrared fluorescence imaging in defining lymphatic drainage channels in the head and neck.

The Clinical Relevance and Tumor Promoting Function of C19orf10 in Kidney Renal Clear Cell Carcinoma.

Kidney renal clear cell carcinoma (KIRC) is the most common primary renal neoplasms. Currently, there are few molecular indicators and therapeutic targets that can be used in diagnostic and prognostic assessment. In this study, we identified the C19orf10 expression in KIRC specimens and explored the diagnostic and prognostic value of C19orf10 in KIRC using TCGA and CPTAC database. Loss-of- and gain-of- function of C19orf10 was performed to investigate the roles of C19orf10 on KIRC cell viability, proliferation, migration and invasion via CCK-8, Edu incorporation and Transwell assays respectively. C19orf10 was overexpressed in KIRC tissues and the elevated C19orf10 expression was closely associated with clinicopathological characteristics of KIRC including histological grade, TNM stage, metastatic status. Silencing C19orf10 significantly suppressed the viability, proliferation, migration and invasion ability, while overexpression of C19orf10 promoted the progression and malignant phenotype in KIRC cells. Furthermore, C19orf10 exerted its carcinogenic function by regulating ZO-1 and PTEN/Akt signaling pathway. Moreover, the Kaplan-Meier survival analysis, Cox regression analysis and receiver operating curve analysis showed that patients with C19orf10 overexpression have poor survival time. C19orf10 could discriminate KIRC patients with high-risk from low-risk. Taken together, C19orf10 contributes to KIRC development via ZO-1 and PTEN/Akt signaling pathway and C19orf10 could serve as a potential diagnostic and prognostic candidate and therapeutic target of KIRC.

Injectable pre-cultured tissue modules catalyze the formation of extensive functional microvasculature in vivo.

Revascularization of ischemic tissues is a major barrier to restoring tissue function in many pathologies. Delivery of pro-angiogenic factors has shown some benefit, but it is difficult to recapitulate the complex set of factors required to form stable vasculature. Cell-based therapies and pre-vascularized tissues have shown promise, but the former require time for vascular assembly in situ while the latter require invasive surgery to implant vascularized scaffolds. Here, we developed cell-laden fibrin microbeads that can be pre-cultured to form primitive vascular networks within the modular structures. These microbeads can be delivered in a minimally invasive manner and form functional microvasculature in vivo. Microbeads containing endothelial cells and stromal fibroblasts were pre-cultured for 3 days in vitro and then injected within a fibrin matrix into subcutaneous pockets on the dorsal flanks of SCID mice. Vessels deployed from these pre-cultured microbeads formed functional connections to host vasculature within 3 days and exhibited extensive, mature vessel coverage after 7 days in vivo. Cellular microbeads showed vascularization potential comparable to bulk cellular hydrogels in this pilot study. Furthermore, our findings highlight some potentially advantageous characteristics of pre-cultured microbeads, such as volume preservation and vascular network distribution, which may be beneficial for treating ischemic diseases.

High Frequency Spectral Ultrasound Imaging to Detect Metastasis in Implanted Biomaterial Scaffolds.

For most cancers, metastasis is the point at which disease is no longer curable. Earlier detection of metastasis, when it is undetectable by current clinical methods, may enable better outcomes. We have developed a biomaterial implant that recruits metastatic cancer cells in mouse models of breast cancer. Here, we investigate spectral ultrasound imaging (SUSI) as a non-invasive strategy for detecting metastasis to the implanted biomaterial scaffolds. Our results show that SUSI, which detects parameters related to tissue composition and structure, identified changes at an early time point when tumor cells were recruited to scaffolds in orthotopic breast cancer mouse models. These changes were not associated with acellular components in the scaffolds but were reflected in the cellular composition in the scaffold microenvironment, including an increase in CD31 + CD45-endothelial cell number in tumor bearing mice. In addition, we built a classification model based on changes in SUSI parameters from scaffold measurements to stratify tumor free and tumor bearing status. Combination of a linear discriminant analysis and bagged decision trees model resulted in an area under the curve of 0.92 for receiver operating characteristics analysis. With the potential for early non-invasive detection, SUSI could facilitate clinical translation of the scaffolds for monitoring metastatic disease.

4-(4-Bromo-phen-yl)-2,6-diphenyl-pyridine.

In the title compound, C(23)H(16)BrN, the three benzene rings show a disrotatory counter-rotating arrangement around the central pyridine ring and are twisted with respect to the pyridine ring with dihedral angles of 19.56 (13), 27.54 (13) and 30.51 (13)°.

(µ-Pyridine-2-carbaldehyde azine)bis-[bis-(triphenyl-phosphine-κP)copper(I)] bis-(tetra-fluorido-borate) dichloro-methane disolvate.

In the centrosymmetric title complex, [Cu(2)(C(12)H(10)N(4))(C(18)H(15)P)(4)](BF(4))(2)·2CH(2)Cl(2), the Cu(I) atom adopts a distorted tetra-hedral geometry, defined by two P atoms from two triphenyl-phosphine ligands and two N atoms from a pyridine-2-carbaldehyde azine ligand. The two Cu atoms are bridged by the centrosymmetric pyridine-2-carbaldehyde azine ligand. The F atoms of the tetra-fluorido-borate anion are disordered over two sites [occupancy factors = 0.68 (5) and 0.32 (5)]. The dichloro-methane solvent mol-ecule is disordered over four sites, with occupancy factors of 0.513 (4), 0.173 (5), 0.141 (5) and 0.173 (5).

Injectable osteogenic microtissues containing mesenchymal stromal cells conformally fill and repair critical-size defects.

Repair of complex fractures with bone loss requires a potent, space-filling intervention to promote regeneration of bone. We present a biomaterials-based strategy combining mesenchymal stromal cells (MSC) with a chitosan-collagen matrix to form modular microtissues designed for delivery through a needle to conformally fill cavital defects. Implantation of microtissues into a calvarial defect in the mouse showed that osteogenically pre-differentiated MSC resulted in complete bridging of the cavity, while undifferentiated MSC produced mineralized tissue only in apposition to native bone. Decreasing the implant volume reduced bone regeneration, while increasing the MSC concentration also attenuated bone formation, suggesting that the cell-matrix ratio is important in achieving a robust response. Conformal filling of the defect with microtissues in a carrier gel resulted in complete healing. Taken together, these results show that modular microtissues can be used to augment the differentiated function of MSC and provide an extracellular environment that potentiates bone repair.

Acoustic tweezing cytometry for mechanical phenotyping of macrophages and mechanopharmaceutical cytotripsy.

Macrophages are immune cells responsible for tissue debridement and fighting infection. Clofazimine, an FDA-approved antibiotic, accumulates and precipitates as rod-shaped, crystal-like drug inclusions within macrophage lysosomes. Drug treatment as well as pathophysiological states could induce changes in macrophage mechanical property which in turn impact their phenotype and function. Here we report the use of acoustic tweezing cytometry as a new approach for in situ mechanical phenotyping of macrophages and for targeted macrophage cytotripsy. Acoustic tweezing cytometry applies ultrasound pulses to exert controlled forces to individual cells via integrin-bound microbubbles, enabling a creep test for measuring cellular mechanical property or inducing irreversible changes to the cells. Our results revealed that macrophages with crystal-like drug inclusions became significantly softer with higher cell compliance, and behaved more elastic with faster creep and recovery time constants. On the contrary, phagocytosis of solid polyethylene microbeads or treatment with soluble clofazimine rendered macrophages stiffer. Most notably, application of ultrasound pulses of longer duration and higher amplitude in ATC actuated the integrin-bound microbubbles to mobilize the crystal-like drug inclusions inside macrophages, turning the rod-shaped drug inclusions into intracellular microblender that effectively destructed the cells. This phenomenon of acoustic mechanopharmaceutical cytotripsy may be exploited for ultrasound activated, macrophage-directed drug release and delivery.

Multimode ultrasound viscoelastography for three-dimensional interrogation of microscale mechanical properties in heterogeneous biomaterials.

Both static and time-dependent mechanical factors can have a profound impact on cell and tissue function, but it is challenging to measure the mechanical properties of soft materials at the scale which cells sense. Multimode ultrasound viscoelastography (MUVE) uses focused ultrasound pulses to both generate and image deformations within soft hydrogels non-invasively, at sub-millimeter resolution, and in 3D. The deformation and strain over time data are used to extract quantitative parameters that describe both the elastic and viscoelastic properties of the material. MUVE was used in creep mode to characterize the viscoelastic properties of 3D agarose, collagen, and fibrin hydrogels. Quantitative comparisons were made by extracting characteristic viscoelastic parameters using Burger's lumped parameter constitutive model. Spatial resolution of the MUVE technique was found to be approximately 200 µm, while detection sensitivity, defined as the capability to differentiate between materials based on mechanical property differences, was approximately 0.2 kPa using agarose hydrogels. MUVE was superior to nanoindentation and shear rheometry in generating consistent microscale measurements of viscoelastic behavior in soft materials. These results demonstrate that MUVE is a rapid, quantitative, and accurate method to measure the viscoelastic mechanical properties of soft 3D hydrogels at the microscale, and is a promising technique to study the development of native and engineered tissues over time.

Acoustic Tweezing Cytometry Induces Rapid Initiation of Human Embryonic Stem Cell Differentiation.

Mechanical forces play critical roles in influencing human embryonic stem cell (hESC) fate. However, it remains largely uncharacterized how local mechanical forces influence hESC behavior in vitro. Here, we used an ultrasound (US) technique, acoustic tweezing cytometry (ATC), to apply targeted cyclic subcellular forces to hESCs via integrin-bound microbubbles (MBs). We found that ATC-mediated cyclic forces applied for 30 min to hESCs near the edge of a colony induced immediate global responses throughout the colony, suggesting the importance of cell-cell connection in the mechanoresponsiveness of hESCs to ATC-applied forces. ATC application generated increased contractile force, enhanced calcium activity, as well as decreased expression of pluripotency transcription factors Oct4 and Nanog, leading to rapid initiation of hESC differentiation and characteristic epithelial-mesenchymal transition (EMT) events that depend on focal adhesion kinase (FAK) activation and cytoskeleton (CSK) tension. These results reveal a unique, rapid mechanoresponsiveness and community behavior of hESCs to integrin-targeted cyclic forces.

High-frequency spectral ultrasound imaging (SUSI) visualizes early post-traumatic heterotopic ossification (HO) in a mouse model.

PURPOSE: Early treatment of heterotopic ossification (HO) is currently limited by delayed diagnosis due to limited visualization at early time points. In this study, we validate the use of spectral ultrasound imaging (SUSI) in an animal model to detect HO as early as one week after burn tenotomy. METHODS: Concurrent SUSI, micro CT, and histology at 1, 2, 4, and 9weeks post-injury were used to follow the progression of HO after an Achilles tenotomy and 30% total body surface area burn (n=3-5 limbs per time point). To compare the use of SUSI in different types of injury models, mice (n=5 per group) underwent either burn/tenotomy or skin incision injury and were imaged using a 55MHz probe on VisualSonics VEVO 770 system at one week post injury to evaluate the ability of SUSI to distinguish between edema and HO. Average acoustic concentration (AAC) and average scatterer diameter (ASD) were calculated for each ultrasound image frame. Micro CT was used to calculate the total volume of HO. Histology was used to confirm bone formation. RESULTS: Using SUSI, HO was visualized as early as 1week after injury. HO was visualized earliest by 4weeks after injury by micro CT. The average acoustic concentration of HO was 33% more than that of the control limb (n=5). Spectroscopic foci of HO present at 1week that persisted throughout all time points correlated with the HO present at 9weeks on micro CT imaging. CONCLUSION: SUSI visualizes HO as early as one week after injury in an animal model. SUSI represents a new imaging modality with promise for early diagnosis of HO.

A rare case report of acyclovir-induced immune thrombocytopenia with tongue hematomas as the first sign, and a literature review.

BACKGROUND: Acyclovir has been widely used to treat infections caused by herpes simplex virus (HSV) and varicella zoster virus (VZV). The common adverse effects of this drug include nausea, diarrhea, headache, dizziness and mental changes. The immune thrombocytopenia induced by acyclovir is rare. CASE PRESENTATION: A 67-year-old Chinese male who was given acyclovir 5 mg kg-1 8 hourly intravenously for treatment of VZV infection developed severe thrombocytopenia with fist sign in oral cavity within 10 days of starting using acyclovir. The patient's condition was improved by stopping using acyclovir and further supportive treatment. The acyclovir-dependent platelet antibody test showed positive results, which implicated acyclovir as the causative agent. The final definitive diagnosis of acyclovir-induced immune thrombocytopenia was established basing on the time correlation between the start of using acyclovir and the onset of symptoms of thrombocytopenia, combining with excluding of other common causes of thrombocytopenia. CONCLUSION: There have been few reports of acyclovir-induced immune thrombocytopenia. This is the first case report and literature review of acyclovir-induced immune thrombocytopenia, with tongue hematoma as the first sign. Dentists should never overlook this rare adverse effect of acyclovir, as a rapid and appropriate treatment may prevent further severe life-threatening complications.