A case of nearly complete response in hepatocellular carcinoma with disseminated lung metastasis by combination therapy of nivolumab and ipilimumab after treatment failure of atezolizumab plus bevacizumab

Recently, the efficacy of immuno-oncologic agents for advanced hepatocellular carcinoma (HCC) has been proven in several trials. In particular, atezolizumab with bevacizumab (AteBeva), as a first-line therapy for advanced HCC, has shown tremendous advances in the IMBrave150 study. However, second or third-line therapy after treatment failure with AteBeva has not been firmly established. Moreover, clinicians have continued their attempts at multidisciplinary treatment that includes other systemic therapy and radiotherapy (RT). Here, we report a case that showed a near complete response (CR) of lung metastasis to nivolumab with ipilimumab therapy after achieving a near CR of intrahepatic tumor using sorafenib and RT in a patient with advanced HCC who had experienced treatment failure of AteBeva

Comprehensive Proteome Profiling of Platelet Identified a Protein Profile Predictive of Responses to An Antiplatelet Agent Sarpogrelate

Sarpogrelate is an antiplatelet agent widely used to treat arterial occlusive diseases. Evaluation of platelet aggregation is essential to monitor therapeutic effects of sarpogrelate. Currently, no molecular signatures are available to evaluate platelet aggregation. Here, we performed comprehensive proteome profiling of platelets collected from 18 subjects before and after sarpogrelate administration using LC-MS/MS analysis coupled with extensive fractionation. Of 5423 proteins detected, we identified 499 proteins affected by sarpogrelate and found that they strongly represented cellular processes related to platelet activation and aggregation, including cell activation, coagulation, and vesicle-mediated transports. Based on the network model of the proteins involved in these processes, we selected three proteins (cut-like homeobox 1; coagulation factor XIII, B polypeptide; and peptidylprolyl isomerase D) that reflect the platelet aggregation-related processes after confirming their alterations by sarpogrelate in independent samples using Western blotting. Our proteomic approach provided a protein profile predictive of therapeutic effects of sarpogrelate. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.1

Rapid Hepatobiliary Excretion of Micelle-Encapsulated/Radiolabeled Upconverting Nanoparticles as an Integrated Form

In the field of nanomedicine, long term accumulation of nanoparticles (NPs) in the mononuclear phagocyte system (MPS) such as liver is the major hurdle in clinical translation. On the other hand, NPs could be excreted via hepatobiliary excretion pathway without overt tissue toxicity. Therefore, it is critical to develop NPs that show favorable excretion property. Herein, we demonstrated that micelle encapsulated Cu-64-labeled upconverting nanoparticles (micelle encapsulated Cu-64-NOTA-UCNPs) showed substantial hepatobiliary excretion by in vivo positron emission tomography (PET) and also upconversion luminescence imaging (ULI). Ex vivo biodistribution study reinforced the imaging results by showing clearance of 84% of initial hepatic uptake in 72 hours. Hepatobiliary excretion of the UCNPs was also verified by transmission electron microscopy (TEM) examination. Micelle encapsulated Cu-64-NOTA-UCNPs could be an optimal bimodal imaging agent owing to quantifiability of Cu-64, ability of in vivo/ex vivo ULI and good hepatobiliary excretion property.

Intelligent smartphone-based multimode imaging otoscope for the mobile diagnosis of otitis media

Otitis media (OM) is one of the most common ear diseases in children and a common reason for outpatient visits to medical doctors in primary care practices. Adhesive OM (AdOM) is recognized as a sequela of OM with effusion (OME) and often requires surgical intervention. OME and AdOM exhibit similar symptoms, and it is difficult to distinguish between them using a conventional otoscope in a primary care unit. The accuracy of the diagnosis is highly dependent on the experience of the examiner. The development of an advanced otoscope with less variation in diagnostic accuracy by the examiner is crucial for a more accurate diagnosis. Thus, we developed an intelligent smartphone-based multimode imaging otoscope for better diagnosis of OM, even in mobile environments. The system offers spectral and autofluorescence imaging of the tympanic membrane using a smartphone attached to the developed multimode imaging module. Moreover, it is capable of intelligent analysis for distinguishing between normal, OME, and AdOM ears using a machine learning algorithm. Using the developed system, we examined the ears of 69 patients to assess their performance for distinguishing between normal, OME, and AdOM ears. In the classification of ear diseases, the multimode system based on machine learning analysis performed better in terms of accuracy and F1 scores than single RGB image analysis, RGB/fluorescence image analysis, and the analysis of spectral image cubes only, respectively. These results demonstrate that the intelligent multimode diagnostic capability of an otoscope would be beneficial for better diagnosis and management of OM. © 2021 OSA - The Optical Society. All rights reserved.1

Late Simultaneous Presentation of Left Ventricular Pseudoaneurysm and Tricuspid Regurgitation after Blunt Chest Trauma

A 32-yr-old man developed progressive exertional dyspnea 4 yr after blunt chest trauma due to an automobile accident. Two-dimensional echocardiography and computed-tomographic coronary angiography demonstrated a large pseudoaneurysm of the left ventricle and severe tricuspid regurgitation. The patient underwent successful surgical exclusion of the pseudoaneurysm by endoaneurysmal patch closure and repair of the tricuspid valve regurgitation. To the best of our knowledge, this is the first case of these 2 different pathologies presenting late simultaneously after blunt chest trauma and successful surgical repairs in the published literature

KMT-2016-BLG-1107: A New Hollywood-Planet Close/Wide Degeneracy

We show that microlensing event KMT-2016-BLG-1107 displays a new type of degeneracy between wide-binary and close-binary Hollywood events in which a giant-star source envelops the planetary caustic. The planetary anomaly takes the form of a smooth, two-day "bump" far out on the falling wing of the light curve, which can be interpreted either as the source completely enveloping a minor-image caustic due to a close companion with mass ratio $q=0.036$, or partially enveloping a major-image caustic due to a wide companion with $q=0.004$. The best estimates of the companion masses are both in the planetary regime ($3.3^{+3.5}_{-1.8}\,M_{\rm jup}$ and $0.090^{+0.096}_{-0.037}\,M_{\rm jup}$) but differ by an even larger factor than the mass ratios due to different inferred host masses. We show that the two solutions can be distinguished by high-resolution imaging at first light on next-generation ("30m") telescopes. We provide analytic guidance to understand the conditions under which this new type of degeneracy can appear.Comment: 23 pages, 7 figures, accepted for publication in A

KMT-2018-BLG-1990Lb: A Nearby Jovian Planet From A Low-Cadence Microlensing Field

We report the discovery and characterization of KMT-2018-BLG-1990Lb, a Jovian planet $(m_p=0.57_{-0.25}^{+0.79}\,M_J)$ orbiting a late M dwarf $(M=0.14_{-0.06}^{+0.20}\,M_\odot)$, at a distance (D_L=1.23_{-0.43}^{+1.06}\,\kpc), and projected at $2.6\pm 0.6$ times the snow line distance, i.e., a_{\rm snow}\equiv 2.7\,\au (M/M_\odot), This is the second Jovian planet discovered by KMTNet in its low cadence ($0.4\,{\rm hr}^{-1}$) fields, demonstrating that this population will be well characterized based on survey-only microlensing data.Comment: 24 pages, 7 figures, 4 table

KMT-2018-BLG-1292: A Super-Jovian Microlens Planet in the Galactic Plane

We report the discovery of KMT-2018-BLG-1292Lb, a super-Jovian $M_{\rm planet} = 4.5\pm 1.3\,M_J$ planet orbiting an F or G dwarf $M_{\rm host} = 1.5\pm 0.4\,M_\odot$, which lies physically within {\cal O}(10\,\pc) of the Galactic plane. The source star is a heavily extincted $A_I\sim 5.2$ luminous giant that has the lowest Galactic latitude, $b=-0.28^\circ$, of any planetary microlensing event. The relatively blue blended light is almost certainly either the host or its binary companion, with the first explanation being substantially more likely. This blend dominates the light at $I$ band and completely dominates at $R$ and $V$ bands. Hence, the lens system can be probed by follow-up observations immediately, i.e., long before the lens system and the source separate due to their relative proper motion. The system is well characterized despite the low cadence $\Gamma=0.15$--$0.20\,{\rm hr^{-1}}$ of observations and short viewing windows near the end of the bulge season. This suggests that optical microlensing planet searches can be extended to the Galactic plane at relatively modest cost.Comment: 35 pages, 3 Tables, 8 figure