Bionic nanotheranostic for multimodal imaging-guided NIR-II-photothermal cancer therapy.

In photothermal therapy (PTT), the photothermal conversion of the second near-infrared (NIR-II) window allows deeper penetration and higher laser irradiance and is considered a promising therapeutic strategy for deep tissues. Since cancer remains a leading cause of deaths worldwide, despite the numerous treatment options, we aimed to develop an improved bionic nanotheranostic for combined imaging and photothermal cancer therapy. We combined a gold nanobipyramid (Au NBP) as a photothermal agent and MnO2 as a magnetic resonance enhancer to produce core/shell structures (Au@MnO2; AM) and modified their surfaces with homologous cancer cell plasma membranes (PM) to enable tumour targeting. The performance of the resulting Au@MnO2@PM (AMP) nanotheranostic was evaluated in vitro and in vivo. AMP exhibits photothermal properties under NIR-II laser irradiation and has multimodal in vitro imaging functions. AMP enables the computed tomography (CT), photothermal imaging (PTI), and magnetic resonance imaging (MRI) of tumours. In particular, AMP exhibited a remarkable PTT effect on cancer cells in vitro and inhibited tumour cell growth under 1064 nm laser irradiation in vivo, with no significant systemic toxicity. This study achieved tumour therapy guided by multimodal imaging, thereby demonstrating a novel strategy for the use of bionic gold nanoparticles for tumour PTT under NIR-II laser irradiation.

Polydopamine-Modified 2D Iron (II) Immobilized MnPS3 Nanosheets for Multimodal Imaging-Guided Cancer Synergistic Photothermal-Chemodynamic Therapy.

Manganese phosphosulphide (MnPS3 ), a newly emerged and promising member of the 2D metal phosphorus trichalcogenides (MPX3 ) family, has aroused abundant interest due to its unique physicochemical properties and applications in energy storage and conversion. However, its potential in the field of biomedicine, particularly as a nanotherapeutic platform for cancer therapy, has remained largely unexplored. Herein, a 2D "all-in-one" theranostic nanoplatform based on MnPS3 is designed and applied for imaging-guided synergistic photothermal-chemodynamic therapy. (Iron) Fe (II) ions are immobilized on the surface of MnPS3 nanosheets to facilitate effective chemodynamic therapy (CDT). Upon surface modification with polydopamine (PDA) and polyethylene glycol (PEG), the obtained Fe-MnPS3 /PDA-PEG nanosheets exhibit exceptional photothermal conversion efficiency (η = 40.7%) and proficient pH/NIR-responsive Fenton catalytic activity, enabling efficient photothermal therapy (PTT) and CDT. Importantly, such nanoplatform can also serve as an efficient theranostic agent for multimodal imaging, facilitating real-time monitoring and guidance of the therapeutic process. After fulfilling the therapeutic functions, the Fe-MnPS3 /PDA-PEG nanosheets can be efficiently excreted from the body, alleviating the concerns of long-term retention and potential toxicity. This work presents an effective, precise, and safe 2D "all-in-one" theranostic nanoplatform based on MnPS3 for high-efficiency tumor-specific theranostics.

US/CT fusion imaging and virtual navigation to guide lumbar intradiscal oxygen-ozone therapy: a pilot study.

PURPOSE: To test the feasibility of US/CT fusion imaging to guide lumbar intradiscal O2/O3 therapy to treat discogenic degenerative low back pain due to lumbar disc herniation (LDH). METHODS: We retrospectively included consecutive patients affected by low back pain and/or sciatica due to LDH resistant to conservative therapies, who underwent to lumbar intradiscal O2/O3 injection under CT/US fusion imaging guidance (Fusion Group) and standard CT guidance (Control Group). For each procedure, we collected procedure operative time, room utilization time, number of CT passes, complications, and O2/O3 intradiscal diffusion adequacy. Technical success was defined as the ability to complete the procedure as initially planned to reach the disc. Technical efficacy was based on O2/O3 intradiscal diffusion adequacy, as demonstrated by the last CT scan. RESULTS: Six patients (4 males; mean age: 68 ± 15 years) were included in the Fusion group, six (4 males; mean age: 66 ± 12 years) in Control group. No complications were observed in both groups. In Fusion group we found significantly lower room utilization time (30 ± 6 min vs. 46 ± 10 min, p = 0.008), procedure operative time (14 ± 3 min vs. 24 ± 6 min, p = 0.008), and number of CT passes (2 [2,2] vs. 3 [3,3], p = 0.006) than in Control Group, respectively. Technical success and efficacy were 100% in both Groups. CONCLUSION: CT/US fusion imaging seems to be a feasible and safe guidance for intradiscal O2/O3 injections, allowing decrease of procedure time and number of CT passes.

Study of compatibility between a 3T MR system and detector modules for a second-generation RF-penetrable TOF-PET insert for simultaneous PET/MRI.

BACKGROUND: Simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) has shown promise in acquiring complementary multiparametric information of disease. However, designing these hybrid imaging systems is challenging due to the propensity for mutual interference between the PET and MRI subsystems. Currently, there are integrated PET/MRI systems for clinical applications. For neurologic imaging, a brain-dedicated PET insert provides superior spatial resolution and sensitivity compared to body PET scanners. PURPOSE: Our first-generation prototype brain PET insert ("PETcoil") demonstrated RF-penetrability and MR-compatibility. In the second-generation PETcoil system, all analog silicon photomultiplier (SiPM) signal digitization is moved inside the detectors, which results in substantially better PET detector performance, but presents a greater technical challenge for achieving MR-compatibility. In this paper, we report results from MR-compatibility studies of two fully assembled second-generation PET insert detector modules. METHODS: We studied the effect of the presence of the two second-generation TOF-PET insert detectors on parameters that affect MR image quality and evaluated TOF-PET detector performance under different MRI pulse sequence conditions. RESULTS: With the presence of operating PET detectors, no RF noise peaks were induced in the MR images, but the relative average noise level was increased by 15%, which led to a 3.1 to 4.2-dB degradation in MR image signal-to-noise ratio (SNR). The relative homogeneity of MR images degraded by less than 1.5% with the two operating TOF-PET detectors present. The reported results also indicated that ghosting artifacts (percent signal ghosting (PSG) ⩽ 1%) and MR susceptibility artifacts (0.044 ppm) were insignificant. The PET detector data showed a relative change of less than 5% in detector module performance between running outside and within the MR bore under different MRI pulse sequences except for energy resolution in EPI sequence (13% relative difference). CONCLUSIONS: The PET detector operation did not cause any significant artifacts in MR images and the performance and time-of-flight (TOF) capability of the former were preserved under different tested MR conditions.

A Spiky Silver-Iron Oxide Nanoparticle for Highly Efficient Targeted Photothermal Therapy and Multimodal Imaging of Thrombosis.

Thrombosis and its complications are responsible for 30% of annual deaths. Limitations of methods for diagnosing and treating thrombosis highlight the need for improvements. Agents that provide simultaneous diagnostic and therapeutic activities (theranostics) are paramount for an accurate diagnosis and rapid treatment. In this study, silver-iron oxide nanoparticles (AgIONPs) are developed for highly efficient targeted photothermal therapy and imaging of thrombosis. Small iron oxide nanoparticles are employed as seeding agents for the generation of a new class of spiky silver nanoparticles with strong absorbance in the near-infrared range. The AgIONPs are biofunctionalized with binding ligands for targeting thrombi. Photoacoustic and fluorescence imaging demonstrate the highly specific binding of AgIONPs to the thrombus when functionalized with a single chain antibody targeting activated platelets. Photothermal thrombolysis in vivo shows an increase in the temperature of thrombi and a full restoration of blood flow for targeted group but not in the non-targeted group. Thrombolysis from targeted groups is significantly improved (p < 0.0001) in comparison to the standard thrombolytic used in the clinic. Assays show no apparent side effects of AgIONPs. Altogether, this work suggests that AgIONPs are potential theranostic agents for thrombosis.

Hybrid FeWO4-Hyaluronic Acid Nanoparticles as a Targeted Nanotheranostic Agent for Multimodal Imaging-Guided Tumor Photothermal Therapy.

Background: Development of versatile nanoplatform still remains a great challenge due to multistep synthesis and complicated compositions. Therefore, it is significant to develop a facile method to synthesize a nanocomposite to achieve multimodal imaging and even imaging-guided cancer therapeutics. Methods and Results: In our study, hyaluronic acid-functionalized iron (II) tungstate nanoparticles (HA-FeWO4 NPs) were successfully synthesized as a versatile nanoplatform by a facile one-pot hydrothermal procedure. The formed multifunctional HA-FeWO4 NPs were investigated via a series of characterization techniques, which demonstrated good biocompatibility, excellent dispersion, low cytotoxicity, active tumor-targeting ability and high photothermal efficiency. Furthermore, tumor was clearly visualized by HA-FeWO4 NPs with multimodal imaging of infrared thermal imaging, magnetic resonance imaging, computed tomography imaging in 4T1 tumor bearing mice. More importantly, HA-FeWO4 could achieve multimodal imaging-guided photothermal therapy of 4T1 tumors. Conclusion: The constructed HA-FeWO4 NPs have great potential as ideal nanotheranostic agents for multimodal imaging and even imaging-guided cancer theranostics in biological systems.

Two-Stage Targeted Bismuthene-Based Composite Nanosystem for Multimodal Imaging Guided Enhanced Hyperthermia and Inhibition of Tumor Recurrence.

A key challenge for nanomedicines in clinical application is to reduce the dose while achieving excellent efficacy, which has attracted extensive attention in dose toxicity and potential risks. It is thus necessary to reasonably design nanomedicine with high-efficiency targeting and accumulation. Here, we designed and synthesized a tetragonal bismuthene-based "all-in-one" composite nanosystem (TPP-Bi@PDA@CP) with two-stage targeting, multimodal imaging, photothermal therapy, and immune enhancement functions. Through the elaborate design of its structure, the composite nanosystem possesses multiple properties including (i) two-stage targeting function of hepatoma cells and mitochondria [the aggregation at the tumor site is 2.63-fold higher than that of traditional enhanced permeability and retention (EPR) effect]; (ii) computed tomography (CT) contrast-enhancement efficiency as high as ∼51.8 HU mL mg-1 (3.16-fold that of the clinically available iopromide); (iii) ultrahigh photothermal conversion efficiency (52.3%, 808 nm), promising photothermal therapy (PTT), and high-contrast infrared thermal (IRT)/photoacoustic (PA) imaging of tumor; (iv) benefitting from the two-stage targeting function and excellent photothermal conversion ability, the dose used in this strategy is one of the lowest doses in hyperthermia (the inhibition rate of tumor cells was 50% at a dose of 15 µg mL-1 and 75% at a dose of 25 µg mL-1); (v) the compound polysaccharide (CP) shell with hepatoma cell targeting and immune enhancement functions effectively inhibited the recurrence of tumor. Therefore, our work reduces the dose toxicity and potential risk of nanomedicines and highlights the great potential as an all-in-one theranostic nanoplatform for two-stage targeting, integrated diagnostic imaging, photothermal therapy, and inhibition of tumor recurrence.

Photothermal Effect and Multi-Modality Imaging of Up-Conversion Nanomaterial Doped with Gold Nanoparticles.

Two key concerns exist in contemporary cancer chemotherapy in clinics: limited therapeutic efficiency and substantial side effects in patients. In recent years, researchers have been investigating revolutionary cancer treatment techniques and photo-thermal therapy (PTT) has been proposed by many scholars. A drug for photothermal cancer treatment was synthesized using the hydrothermal method, which has a high light-to-heat conversion efficiency. It may also be utilized as a clear multi-modality bioimaging platform for photoacoustic imaging (PAI), computed tomography (CT), and magnetic resonance imaging (MRI). When compared to single-modality imaging, multi-modality imaging delivers far more thorough and precise details for cancer diagnosis. Furthermore, gold-doped upconverting nanoparticles (UCNPs) have an exceptionally high target recognition for tumor cells. The gold-doped UCNPs, in particular, are non-toxic to normal tissues, endowing the as-prepared medications with outstanding therapeutic efficacy but exceptionally low side effects. These findings may encourage the creation of fresh effective imaging-guided approaches to meet the goal of photothermal cancer therapy.

The Additive Value of 3D Total Body Imaging for Sequential Monitoring of Skin Lesions: A Case Series.

BACKGROUND: Timely diagnosis is the cornerstone of melanoma morbidity and mortality reduction. 2D total body photography and dermoscopy are routinely used to assist with early detection of skin malignancies. Polarized 3D total body photography is a novel technique that enables fast image acquisition of almost the entire skin surface. We aimed to determine the added value of 3D total body photography alongside dermoscopy for monitoring cutaneous lesions. METHODS: Lesion images from high-risk individuals were assessed for long-term substantial changes via dermoscopy and 3D total body photography. Three case studies are presented demonstrating how 3D total body photography may enhance lesion analysis alongside traditional dermoscopy. RESULTS: 3D total body photography can assist clinicians by presenting cutaneous lesions in their skin ecosystem, thereby providing additional clinical context and enabling a more holistic assessment to aid dermoscopy interpretation. For lesion cases where previous dermoscopy is unavailable, corresponding 3D images can substitute for baseline dermoscopy. Additionally, 3D total body photography is not susceptible to artificial stretch artefacts. CONCLUSION: 3D total body photography is valuable alongside dermoscopy for monitoring cutaneous lesions. Furthermore, it is capable of surveilling almost the entire skin surface, including areas not traditionally monitored by sequential imaging.

Smart-Polypeptide-Coated Mesoporous Fe3O4 Nanoparticles: Non-Interventional Target-Embolization/Thermal Ablation and Multimodal Imaging Combination Theranostics for Solid Tumors.

Tumor theranostics hold great potential for personalized medicine in the future, and transcatheter arterial embolization (TAE) is an important clinical treatment for unresectable or hypervascular tumors. In order to break the limitation, simplify the procedure of TAE, and achieve ideal combinatorial theranostic capability, here, a kind of triblock-polypeptide-coated perfluoropentane-loaded mesoporous Fe3O4 nanocomposites (PFP-m-Fe3O4@PGTTCs) were prepared for non-interventional target-embolization, magnetic hyperthermia, and multimodal imaging combination theranostics of solid tumors. The results of systematic animal experiments by H22-tumor-bearing mice and VX2-tumor-bearing rabbits in vivo indicated that PFP-m-Fe3O4@PGTTC-6.3 has specific tumor accumulation and embolization effects. The tumors' growth has been inhibited and the tumors disappeared 4 weeks and ≤15 days post-injection with embolization and magnetic hyperthermia combination therapy, respectively. The results also showed an excellent effect of magnetic resonance/ultrasound/SPECT multimodal imaging. This pH-responsive non-interventional embolization combinatorial theranostics system provides a novel embolization and multifunctional theranostic candidate for solid tumors.

Biodegradable and Excretable 2D W1.33 C i-MXene with Vacancy Ordering for Theory-Oriented Cancer Nanotheranostics in Near-Infrared Biowindow.

MXenes, a new class of two-dimensional (2D) nanomaterials, have shown enormous potential for biological applications. Notably, the development of 2D MXenes in nanomedicine is still in its infancy. Herein, a distinct W1.33 C i-MXene with multiple theranostic functionalities, fast biodegradation, and satisfactory biocompatibility is explored. By designing a parent bulk laminate in-plane ordered (W2/3 Y1/3 )2 AlC ceramic and optionally etching aluminum (Al) and yttrium (Y) elements, 2D W1.33 C i-MXene nanosheets with ordered divacancies are efficiently fabricated. Especially, theoretical simulations reveal that W1.33 C i-MXene possesses a strong predominance of near-infrared (NIR) absorbance. The constructed ultrathin W1.33 C nanosheets feature excellent photothermal-conversion effectiveness (32.5% at NIR I and 49.3% at NIR II) with desirable biocompatibility and fast degradation in normal tissue rather than in tumor tissue. Importantly, the multimodal-imaging properties and photothermal-ablation performance of W1.33 C-BSA nanosheets are systematically revealed and demonstrated both in vitro and in vivo. The underlying mechanism and regulation factors for the W1.33 C-BSA nanosheets-induced hyperthermia ablation are also revealed by transcriptome and proteome sequencing. This work offers a paradigm that i-MXenes achieve the tailoring biomedical applications through composition and structure design on the atomic scale.

Dendritic calcium signals in rhesus macaque motor cortex drive an optical brain-computer interface.

Calcium imaging is a powerful tool for recording from large populations of neurons in vivo. Imaging in rhesus macaque motor cortex can enable the discovery of fundamental principles of motor cortical function and can inform the design of next generation brain-computer interfaces (BCIs). Surface two-photon imaging, however, cannot presently access somatic calcium signals of neurons from all layers of macaque motor cortex due to photon scattering. Here, we demonstrate an implant and imaging system capable of chronic, motion-stabilized two-photon imaging of neuronal calcium signals from macaques engaged in a motor task. By imaging apical dendrites, we achieved optical access to large populations of deep and superficial cortical neurons across dorsal premotor (PMd) and gyral primary motor (M1) cortices. Dendritic signals from individual neurons displayed tuning for different directions of arm movement. Combining several technical advances, we developed an optical BCI (oBCI) driven by these dendritic signalswhich successfully decoded movement direction online. By fusing two-photon functional imaging with CLARITY volumetric imaging, we verified that many imaged dendrites which contributed to oBCI decoding originated from layer 5 output neurons, including a putative Betz cell. This approach establishes new opportunities for studying motor control and designing BCIs via two photon imaging.

PET Molecular Imaging: A Holistic Review of Current Practice and Emerging Perspectives for Diagnosis, Therapeutic Evaluation and Prognosis in Clinical Oncology.

PET/CT molecular imaging has been imposed in clinical oncological practice over the past 20 years, driven by its two well-grounded foundations: quantification and radiolabeled molecular probe vectorization. From basic visual interpretation to more sophisticated full kinetic modeling, PET technology provides a unique opportunity to characterize various biological processes with different levels of analysis. In clinical practice, many efforts have been made during the last two decades to standardize image analyses at the international level, but advanced metrics are still under use in practice. In parallel, the integration of PET imaging with radionuclide therapy, also known as radiolabeled theranostics, has paved the way towards highly sensitive radionuclide-based precision medicine, with major breakthroughs emerging in neuroendocrine tumors and prostate cancer. PET imaging of tumor immunity and beyond is also emerging, emphasizing the unique capabilities of PET molecular imaging to constantly adapt to emerging oncological challenges. However, these new horizons face the growing complexity of multidimensional data. In the era of precision medicine, statistical and computer sciences are currently revolutionizing image-based decision making, paving the way for more holistic cancer molecular imaging analyses at the whole-body level.

Deep Learning Improves Speed and Accuracy of Prostate Gland Segmentations on Magnetic Resonance Imaging for Targeted Biopsy.

PURPOSE: Targeted biopsy improves prostate cancer diagnosis. Accurate prostate segmentation on magnetic resonance imaging (MRI) is critical for accurate biopsy. Manual gland segmentation is tedious and time-consuming. We sought to develop a deep learning model to rapidly and accurately segment the prostate on MRI and to implement it as part of routine magnetic resonance-ultrasound fusion biopsy in the clinic. MATERIALS AND METHODS: A total of 905 subjects underwent multiparametric MRI at 29 institutions, followed by magnetic resonance-ultrasound fusion biopsy at 1 institution. A urologic oncology expert segmented the prostate on axial T2-weighted MRI scans. We trained a deep learning model, ProGNet, on 805 cases. We retrospectively tested ProGNet on 100 independent internal and 56 external cases. We prospectively implemented ProGNet as part of the fusion biopsy procedure for 11 patients. We compared ProGNet performance to 2 deep learning networks (U-Net and holistically-nested edge detector) and radiology technicians. The Dice similarity coefficient (DSC) was used to measure overlap with expert segmentations. DSCs were compared using paired t-tests. RESULTS: ProGNet (DSC=0.92) outperformed U-Net (DSC=0.85, p <0.0001), holistically-nested edge detector (DSC=0.80, p <0.0001), and radiology technicians (DSC=0.89, p <0.0001) in the retrospective internal test set. In the prospective cohort, ProGNet (DSC=0.93) outperformed radiology technicians (DSC=0.90, p <0.0001). ProGNet took just 35 seconds per case (vs 10 minutes for radiology technicians) to yield a clinically utilizable segmentation file. CONCLUSIONS: This is the first study to employ a deep learning model for prostate gland segmentation for targeted biopsy in routine urological clinical practice, while reporting results and releasing the code online. Prospective and retrospective evaluations revealed increased speed and accuracy.

BiVO4/Fe3O4@polydopamine superparticles for tumor multimodal imaging and synergistic therapy.

BACKGROUND: Despite tremendous progress has been achieved in tumor theranostic over the past decade, accurate identification and complete eradication of tumor cells remain a great challenge owing to the limitation of single imaging modality and therapeutic strategy. RESULTS: Herein, we successfully design and construct BiVO4/Fe3O4@polydopamine (PDA) superparticles (SPs) for computed tomography (CT)/photoacoustic (PA)/magnetic resonance (MR) multimodal imaging and radiotherapy (RT)/photothermal therapy (PTT) synergistic therapy toward oral epithelial carcinoma. On the one hand, BiVO4 NPs endow BiVO4/Fe3O4@PDA SPs with impressive X-ray absorption capability due to the high X-ray attenuation coefficient of Bi, which is beneficial for their utilization as radiosensitizers for CT imaging and RT. On the other hand, Fe3O4 NPs impart BiVO4/Fe3O4@PDA SPs with the superparamagnetic property as a T2-weighted contrast agent for MR imaging. Importantly, the aggregation of Fe3O4 NPs in SPs and the presence of PDA shell greatly improve the photothermal conversion capability of SPs, making BiVO4/Fe3O4@PDA SPs as an ideal photothermal transducer for PA imaging and PTT. By integrating advantages of various imaging modalities (CT/PA/MR) and therapeutic strategies (RT/PTT), our BiVO4/Fe3O4@PDA SPs exhibit the sensitive multimodal imaging feature and superior synergistic therapeutic efficacy on tumors. CONCLUSIONS: Since there are many kinds of building blocks with unique properties appropriating for self-assembly, our work may largely enrich the library of nanomateirals for tumor diagnosis and treatment.

The value of multimodal imaging with 123I-FP-CIT SPECT in differential diagnosis of dementia with Lewy bodies and Alzheimer's disease dementia.

Reduced nigrostriatal uptake on N-(3-fluoropropyl)-2ß-carbomethoxy-3ß-(4-[123I]iodophenyl) nortropane (123I-FP-CIT) SPECT reflects dopamine dysfunction, while other imaging markers could be complementary when used together. We assessed how well 123I-FP-CIT SPECT differentiates dementia with Lewy bodies (DLBs) from Alzheimer's disease dementia (ADem) and whether multimodal imaging provides additional value. 123I-FP-CIT SPECT, magnetic resonance imaging, [18F]2-fluoro-deoxy-D-glucose-positron emission tomography (PET), and 11C-Pittsburgh compound B (PiB)-PET were assessed in 35 participants with DLBs and 14 participants with ADem (autopsy confirmation in 9 DLBs and 4 ADem). Nigrostriatal dopamine transporter uptake was evaluated with 123I-FP-CIT SPECT using DaTQUANT software. Hippocampal volume was calculated with magnetic resonance imaging, cingulate island sign ratio with FDG-PET, and global cortical PiB retention with PiB-PET. The DaTQUANT z-scores of the putamen showed the highest c-statistic of 0.916 in differentiating DLBs from ADem among the analyzed imaging biomarkers. Adding another imaging modality to 123I-FP-CIT SPECT had c-statistics ranging from 0.968 to 0.975, and 123I-FP-CIT SPECT in combination with 2 other imaging modalities presented c-statistics ranging from 0.987 to 0.996. These findings suggest that multimodal imaging with 123I-FP-CIT SPECT aids in differentiating DLBs and ADem and in detecting comorbid Lewy-related and Alzheimer's disease pathology in patients with DLBs and ADem.

Acute syphilitic posterior placoid chorioretinopathy presenting as atypical multiple evanescent white dot syndrome.

BACKGROUND: This paper reports the case of a young man who presented with syphilis masquerading as multiple evanescent white dots syndrome (MEWDS), which turned out to be an acute syphilitic posterior placoid chorioretinopathy (ASPPC) during follow-up. CASE PRESENTATION: A 59-year-old healthy male consulted for a three days' history of visual impairment in both eyes. On multimodal imaging, he was diagnosed as MEWDS. Fundus fluorescein angiography (FFA) showed early peripheral bilateral granular hyperfluorescence that correlated with the yellow-white dots found on fundus exam. Indocyanine green angiography (ICGA) depicted hypofluorescent dots on late phase. Spectral-domain optical coherence tomography (SD-OCT) revealed numerous inner retinal highly reflective deposits in the outer nuclear layer and disruption of the ellipsoid zone. After initial improvement, he presented again for a sudden visual loss at 3 weeks. FFA, ICGA and SD-OCT demonstrated the same but more numerous and outer lesions suggesting an ASPPC. A full inflammatory work-up revealed highly positive titers of rapid plasma regain (RPR) and fluorescent treponemal antibody absorption (FTA-Abs), suggesting a syphilis infection. The ophthalmological manifestations dramatically improved after the patient was admitted for high-dose intravenous penicillin G 24 million per day for 2 weeks. CONCLUSION: This is the first case that reports an ocular syphilitic infection masquerading as MEWDS at presentation and that turns to be an ASPPC. Syphilis serology should be routinely done in every case of atypical MEWDS especially when unusually presented in a young healthy man, with bilateral involvement and a bad clinical evolution.

Gold-based Inorganic Nanohybrids for Nanomedicine Applications.

Noble metal Au nanoparticles have attracted extensive interests in the past decades, due to their size and morphology dependent localized surface plasmon resonances. Their unique optical property, high chemical stability, good biocompatibility, and easy functionalization make them promising candidates for a variety of biomedical applications, including bioimaging, biosensing, and cancer therapy. With the intention of enhancing their optical response in the near infrared window and endowing them with additional magnetic properties, Au nanoparticles have been integrated with other functional nanomaterials that possess complementary attributes, such as copper chalcogenides and magnetic metal oxides. The as constructed hybrid nanostructures are expected to exhibit unconventional properties compared to their separate building units, due to nanoscale interactions between materials with different physicochemical properties, thus broadening the application scope and enhancing the overall performance of the hybrid nanostructures. In this review, we summarize some recent progresses in the design and synthesis of noble metal Au-based hybrid inorganic nanostructures for nanomedicine applications, and the potential and challenges for their clinical translations.

Biodegradable hollow mesoporous organosilica nanotheranostics (HMON) for multi-mode imaging and mild photo-therapeutic-induced mitochondrial damage on gastric cancer.

BACKGROUND: CuS-modified hollow mesoporous organosilica nanoparticles (HMON@CuS) have been preferred as non-invasive treatment for cancer, as near infrared (NIR)-induced photo-thermal effect (PTT) and/or photo-dynamic effect (PDT) could increase cancer cells' apoptosis. However, the certain role of HMON@CuS-produced-PTT&PDT inducing gastric cancer (GC) cells' mitochondrial damage, remained unclear. Moreover, theranostic efficiency of HMON@CuS might be well improved by applying multi-modal imaging, which could offer an optimal therapeutic region and time window. Herein, new nanotheranostics agents were reported by Gd doped HMON decorated by CuS nanocrystals (called HMON@CuS/Gd). RESULTS: HMON@CuS/Gd exhibited appropriate size distribution, good biocompatibility, L-Glutathione (GSH) responsive degradable properties, high photo-thermal conversion efficiency (82.4%) and a simultaneous reactive oxygen species (ROS) generation effect. Meanwhile, HMON@CuS/Gd could efficiently enter GC cells, induce combined mild PTT (43-45 °C) and PDT under mild NIR power density (0.8 W/cm2). Surprisingly, it was found that PTT might not be the only factor of cell apoptosis, as ROS induced by PDT also seemed playing an essential role. The NIR-induced ROS could attack mitochondrial transmembrane potentials (MTPs), then promote mitochondrial reactive oxygen species (mitoROS) production. Meanwhile, mitochondrial damage dramatically changed the expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax). Since that, mitochondrial permeability transition pore (mPTP) was opened, followed by inducing more cytochrome c (Cyto C) releasing from mitochondria into cytosol, and finally activated caspase-9/caspase-3-depended cell apoptosis pathway. Our in vivo data also showed that HMON@CuS/Gd exhibited good fluorescence (FL) imaging (wrapping fluorescent agent), enhanced T1 imaging under magnetic resonance imaging (MRI) and infrared thermal (IRT) imaging capacities. Guided by FL/MRI/IRT trimodal imaging, HMON@CuS/Gd could selectively cause mild photo-therapy at cancer region, efficiently inhibit the growth of GC cells without evident systemic toxicity in vivo. CONCLUSION: HMON@CuS/Gd could serve as a promising multifunctional nanotheranostic platform and as a cancer photo-therapy agent through inducing mitochondrial dysfunction on GC.

Pain in Men Undergoing Transperineal Free-Hand Multiparametric Magnetic Resonance Imaging Fusion Targeted Biopsies under Local Anesthesia: Outcomes and Predictors from a Multicenter Study of 1,008 Patients.

PURPOSE: Several transperineal biopsy series have proven feasibility under local anesthesia. However, there is a lack of large analyses detailing pain outcomes and factors influencing pain. MATERIALS AND METHODS: From 2016 to 2019 we performed a multicenter prospective study in men undergoing multiparametric magnetic resonance imaging-transperineal fusion biopsies (target+systematic cores) under local anesthesia. Primary outcomes were 1) pain scores (assessed through a 0 to 10-point numeric rating scale) and 2) identification of factors associated with severe pain. The secondary outcome was to evaluate pain influence on clinically significant prostate cancer target cores detection. RESULTS: We included 1,008 men undergoing transperineal fusion biopsies under local anesthesia. Mean±SD numeric rating scale pain scores were 3.9±2.1 at local anesthesia administration and 3.1±2.3 when performing biopsies. Pain was not associated with lower clinically significant prostate cancer detection on targeted cores (p=0.23 and p=0.47 depending on clinically significant prostate cancer definition). On multivariate analysis age (OR 0.96, 95% CI 0.94-0.99) and severe anxiety (OR 2.99, 95% CI 1.83-4.89) were a protective and risk factor, respectively, for severe biopsy pain. Procedural time was also associated with an increased risk of experiencing severe biopsy pain (OR 1.04, 95% CI 1.00-1.08). If aiming to test the possible effects of anxiety preventive measures on pain, an anxiety cutoff greater than 6 on a numeric rating scale would decrease to 13% the number of patients being treated while identifying 56% of those experiencing severe pain. CONCLUSIONS: Transperineal fusion biopsies under local anesthesia result in moderate pain. Pain does not influence clinically significant prostate cancer target detection. Patient anxiety predicts pain. A numeric rating scale based anxiety assessment may be used to identify those at higher risk for experiencing severe pain in men undergoing transperineal fusion biopsies.