Reliability of brain volume measures of accelerated 3D T1-weighted images with deep learning-based reconstruction.

PURPOSE: The time-intensive nature of acquiring 3D T1-weighted MRI and analyzing brain volumetry limits quantitative evaluation of brain atrophy. We explore the feasibility and reliability of deep learning-based accelerated MRI scans for brain volumetry. METHODS: This retrospective study collected 3D T1-weighted data using 3T from 42 participants for the simulated acceleration dataset and 48 for the validation dataset. The simulated acceleration dataset consists of three sets at different simulated acceleration levels (Simul-Accel) corresponding to level 1 (65% undersampling), 2 (70%), and 3 (75%). These images were then subjected to deep learning-based reconstruction (Simul-Accel-DL). Conventional images (Conv) without acceleration and DL were set as the reference. In the validation dataset, DICOM images were collected from Conv and accelerated scan with DL-based reconstruction (Accel-DL). The image quality of Simul-Accel-DL was evaluated using quantitative error metrics. Volumetric measurements were evaluated using intraclass correlation coefficients (ICCs) and linear regression analysis in both datasets. The volumes were estimated by two software, NeuroQuant and DeepBrain. RESULTS: Simul-Accel-DL across all acceleration levels revealed comparable or better error metrics than Simul-Accel. In the simulated acceleration dataset, ICCs between Conv and Simul-Accel-DL in all ROIs exceeded 0.90 for volumes and 0.77 for normative percentiles at all acceleration levels. In the validation dataset, ICCs for volumes > 0.96, ICCs for normative percentiles > 0.89, and R2 > 0.93 at all ROIs except pallidum demonstrated good agreement in both software. CONCLUSION: DL-based reconstruction achieves clinical feasibility of 3D T1 brain volumetric MRI by up to 75% acceleration relative to full-sampled acquisition.

Microwave-assisted solvothermal synthesis of nanostructured Ga-Doped Li7La3Zr2O12 solid electrolyte with enhanced densification and Li-ion conductivity.

Garnet-type Li7La3Zr2O12 (LLZO) Li-ion solid electrolytes are promising candidates for safe, next-generation solid-state batteries. In this study, we synthesize Ga-doped LLZO (Ga-LLZO) electrolytes using a microwave-assisted solvothermal method followed by low-temperature heat treatment. The nanostructured precursor (<50 nm) produced by the microwave-assisted solvothermal process has a high surface energy, facilitating the reaction for preparing garnet-type Ga-LLZO powders (<800 nm) within a short time (<5 h) at a low calcination temperature (<700 °C). Additionally, the calcined nanostructured Ga-LLZO powder can be sintered to produce a high-density pellet with minimized grain boundaries under moderate sintering conditions (temperature: 1150 °C, duration: 10 h). The optimal doping concentration was determined to be 0.4 mol% Ga, which resulted significantly increased the ionic conductivity (1.04 × 10-3 S cm-1 at 25 °C) and stabilized the cycling performance over 1700 h at 0.4 mA cm-2. This approach demonstrates the potential to synthesize oxide-type solid electrolyte materials with improved properties for solid-state batteries.

Guaijaverin and Epigallocatechin Gallate Complex Modulate Th1 and Th2 Cytokine-Mediated Allergic Responses Through STAT1/T-bet and STAT6/GATA3 Pathways.

We aimed to determine the in vitro and in vivo synergistic antiallergic effect of guaijaverin and epigallocatechin gallate (EGCG) complex (GEC), and the antiallergic rhinitis (AR) properties of guaijaverin-rich Psidium guajava and EGCG-rich Camellia sinensis (ILS-F-2301). GEC showed synergistic inhibition of ß-hexosaminidase by 4.20% and interleukin (IL)-4, -5, and -13 by 4.08%, 0.67%, and 4.71%, respectively, while increasing interferon (IFN)-γ by 12.43%, compared with EGCG only. In addition, 50 µg/mL of ILS-F-2301 inhibited ß-hexosaminidase release, and inhibited IL-4, -5, and -13 by 61.54%, 58.79%, and 59.25%, respectively, while increasing IFN-γ (showing 133.14% activation). Moreover, 50 µg/mL of ILS-F-2301 suppressed p-STAT6 and GATA3, while p-STAT1 and T-bet increased, and 0.039 µg/mL of guaijaverin or 5.275 µg/mL of EGCG modulated T helper (Th)1- and Th2-related proteins. These data suggested that guaijaverin and EGCG in ILS-F-2301 was the main active compound involved in Th1/Th2 modulation. In the AR mouse model, the administration of ILS-F-2301 inhibited ovalbumin (OVA)-specific IgE, histamine in serum; it also inhibited IL-4 and -5 by 28.23% and 47.15%, respectively, while increasing IFN-γ (showing 37.11% activation), compared with OVA/Alu-treated mice. Taken together, our findings suggest that ILS-F-2301 is a functional food for alleviating anti-AR.

Rebound Pain After Arthroscopic Cuff Repair With Interscalene Brachial Plexus Block Anesthesia Is Reduced by Surgeon-Administered Multimodal Shoulder Injections: A Prospective Randomized Controlled Trial.

PURPOSE: To compare the effects of additional multimodal shoulder injections on postoperative rebound pain in patients undergoing arthroscopic rotator cuff repair (ASRCR) under interscalene brachial plexus block (ISBPB) anesthesia. METHODS: A single-blind randomized controlled trial was conducted with 67 patients between April and December 2023. Patients undergoing ASRCR who received ISBPB anesthesia, rather than general anesthesia, with a minimum follow-up period of 48 hours were included. The injection group received 40 mL of 0.75% ropivacaine, 20 mg morphine, 1:200,000 epinephrine, and saline solution, totaling 100 mL. After surgery, the injection was administered to the subacromial space (50 mL) with blind suprascapular nerve block (25 mL) and blind axillary nerve block (25 mL). Control subjects received 100 mL of saline solution. Intravenous patient-controlled analgesia (IV-PCA) was used as adjuvant analgesia for all patients. The primary outcome was evaluated using the visual analog scale (VAS) pain score at 12 hours after surgery, with secondary outcomes of the incidence of rebound pain and VAS pain scores at 0, 2, 4, 8, 24, 36, and 48 hours postoperatively. Fentanyl in the IV-PCA and rescue analgesic amounts, complications, and patient satisfaction were recorded. RESULTS: Sixty-seven patients (32 in the injection group, 35 in the control group) with a mean age of 61.1 ± 9.0 years were included. The primary outcome assessment, VAS pain score at 12 hours, significantly favored the injection group (2.7 ± 0.93 vs 4.1 ± 1.70, P < .001). The incidence of rebound pain was 18.8% and 65.7% in the injection and control groups, respectively (18.8% vs 65.7%, P < .001). The injection group reported better VAS pain scores at 24, 36, and 48 hours and lower fentanyl use over the 48-hour postoperative period (P = .014). The use of rescue analgesics was similar between groups, and no complications were associated with multimodal shoulder injections. Satisfaction levels were similar in both groups. CONCLUSIONS: The present study found that patients who underwent multimodal shoulder injections during ASRCR under ISBPB anesthesia had significantly lower VAS pain scores at 12 hours postoperatively and reduced incidence of rebound pain compared with the control group. Pain levels were consistently lower from 12 to 48 hours postoperatively. Additionally, the injection group had reduced opioid consumption within the first 48 hours postoperatively, with no complications observed. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Clinical validation of artificial intelligence-based preoperative virtual reduction for Neer 3- or 4-part proximal humerus fractures.

BACKGROUND: If reduction images of fractures can be provided in advance with artificial-intelligence (AI)-based technology, it can assist with preoperative surgical planning. Recently, we developed the AI-based preoperative virtual reduction model for orthopedic trauma, which can provide an automatic segmentation and reduction of fractured fragments. The purpose of this study was to validate a quality of reduction model of Neer 3- or 4-part proximal humerus fractures established by AI-based technology. METHODS: To develop the AI-based preoperative virtual reduction model, deep learning performed the segmentation of fracture fragments, and a Monte Carlo simulation completed the virtual reduction to determine the best model. A total of 20 pre/postoperative three-dimensional computed tomography (CT) scans of proximal humerus fracture were prepared. The preoperative CT scans were employed as the input of AI-based automated reduction (AI-R) to deduce the reduction models of fracture fragments, meanwhile, the manual reduction (MR) was conducted using the same CT images. Dice similarity coefficient (DSC) and intersection over union (IoU) between the reduction model from the AI-R/MR and postoperative CT scans were evaluated. Working times were compared between the two groups. Clinical validity agreement (CVA) and reduction quality score (RQS) were investigated for clinical validation outcomes by 20 orthopedic surgeons. RESULTS: The mean DSC and IoU were better when using AI-R that when using MR (0.78 ± 0.13 vs. 0.69 ± 0.16, p < 0.001 and 0.65 ± 0.16 vs. 0.55 ± 0.18, p < 0.001, respectively). The working time of AI-R was, on average, 1.41% of that of MR. The mean CVA of all cases was 81%±14.7% (AI-R, 82.25%±14.27%; MR, 76.75%±14.17%, p = 0.06). The mean RQS was significantly higher when AI-R compared with MR was used (91.47 ± 1.12 vs. 89.30 ± 1.62, p = 0.045). CONCLUSION: The AI-based preoperative virtual reduction model showed good performance in the reduction model in proximal humerus fractures with faster working times. Beyond diagnosis, classification, and outcome prediction, the AI-based technology can change the paradigm of preoperative surgical planning in orthopedic surgery. LEVEL OF EVIDENCE: Level IV.

Predicting stroke volume variation using central venous pressure waveform: a deep learning approach.

Objective. This study evaluated the predictive performance of a deep learning approach to predict stroke volume variation (SVV) from central venous pressure (CVP) waveforms.Approach. Long short-term memory (LSTM) and the feed-forward neural network were sequenced to predict SVV using CVP waveforms obtained from the VitalDB database, an open-source registry. The input for the LSTM consisted of 10 s CVP waveforms sampled at 2 s intervals throughout the anesthesia duration. Inputs of the feed-forward network were the outputs of LSTM and demographic data such as age, sex, weight, and height. The final output of the feed-forward network was the SVV. The performance of SVV predicted by the deep learning model was compared to SVV estimated derived from arterial pulse waveform analysis using a commercialized model, EV1000.Main results. The model hyperparameters consisted of 12 memory cells in the LSTM layer and 32 nodes in the hidden layer of the feed-forward network. A total of 224 cases comprising 1717 978 CVP waveforms and EV1000/SVV data were used to construct and test the deep learning models. The concordance correlation coefficient between estimated SVV from the deep learning model were 0.993 (95% confidence interval, 0.992-0.993) for SVV measured by EV1000.Significance. Using a deep learning approach, CVP waveforms can accurately approximate SVV values close to those estimated using commercial arterial pulse waveform analysis.

Postoperative assessment of the individualized humeral component retroversion in reverse total shoulder arthroplasty-a novel method applying CT scans without an elbow.

BACKGROUND: Humeral component retroversion (HcRV) can be customized to match native humeral retroversion (RV) during reverse total shoulder arthroplasty (RTSA). However, assessing postoperative individualized HcRV using computed tomography (CT) scans without an elbow can be challenging. Therefore, we developed a new method to obtain the HcRV and evaluated its reliability. METHODS: A total of 106 patients underwent RTSA using a single implant, in which the humeral component was implanted based on the preoperative humeral RV (Pre_HRV) using a bilateral CT scan of the elbow. Intraoperatively, a retroversion guide with version hole at 10° intervals was used; Pre_HRV was converted to 5° increments and applied for humeral component implantation. The axis of intertubercular sulcus (ITS) was defined as the line perpendicular to the intertubercular line, and the angle between the axis of ITS and the trans-epicondylar axis was defined as the bicipital groove rotation (BGR). ITS orientation was defined as the angle between the axis of ITS and the central axis of the humeral head. Since the BGR does not change, the postoperative implanted HcRV (Post_HcRV)f is calculated as the BGR minus the value of the postoperative ITS orientation. An agreement analysis was performed between Post_HcRV and both the intraoperatively applied humeral RV (I_HRV) and Pre_HRV, as well as between the pre- and postoperative ITS orientations. The humeral component's insertional errors were also evaluated. RESULTS: All radiologic measurements exhibited excellent inter- and intra-observer reliabilities. The reliabilities between Post_HcRV and both I_HRV and Pre_HRV, as well as between pre- and postoperative ITS orientations, showed excellent agreement (intraclass correlation coefficients: 0.953, 0.952, and 0.873, respectively). The humeral component was inserted within 5° in 86.8% of the planned humeral RV cases. CONCLUSIONS: The HcRV measured using the BGR and ITS orientations achieved good accuracy for restoring the planned humeral RV using a retroversion guide with the forearm axis. Therefore, this new radiological measurement method can aid orthopedic surgeons in confirming Post_HcRV on CT scans without an elbow.

Sesamolin suppresses adipocyte differentiation through Keap1-dependent Nrf2 activation in adipocytes.

Sesamolin, a lignan isolated from sesame oils, has been found to possess neuroprotective, anticancer, and free radical scavenging properties. We hypothesized that sesamolin could stimulate the activity of nuclear factor erythroid-derived 2-like 2 (Nrf2) and inhibit adipocyte differentiation of preadipocytes. The objective of this study was to investigate effects of sesamolin on adipocyte differentiation and its underlying molecular mechanisms. In this study, we determined the effects of treatment with 25 to 100 µM sesamolin on adipogenesis in cell culture systems. Sesamolin inhibited lipid accumulation and suppressed the expression of adipocyte markers during adipocyte differentiation of C3H10T1/2, 3T3-L1, and primary preadipocytes. Mechanism studies revealed that sesamolin increased Nrf2 protein expression without inducing its mRNA, leading to an increase in the expression of Nrf2 target genes such as heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 (Nqo1) in C3H10T1/2 adipocytes and mouse embryonic fibroblasts. These effects were significantly attenuated in Nrf2 knockout (KO) mouse embryonic fibroblasts, indicating that effects of sesamolin were dependent on Nrf2. In H1299 human lung cancer cells with KO of Kelch like-ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, sesamolin failed to further increase Nrf2 protein expression. However, upon reexpressing Keap1 in Keap1 KO cells, the ability of sesamolin to elevate Nrf2 protein expression was restored, highlighting the crucial role of Keap1 in sesamolin-induced Nrf2 activation. Taken together, these findings show that sesamolin can inhibit adipocyte differentiation through Keap1-mediated Nrf2 activation.

The Cancer Clinical Library Database (CCLD) from the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) Project.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea's cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.

C1 Facetectomy and Ventral Fixation of Occipitoatlantoaxial Complex for Concurrent Congenital Atlanto-Occipital Dislocation and Atlantoaxial Instability in a Toy Poodle.

An 8-month-old, 3.4 kg, castrated male Toy Poodle was referred for progressive tetraparesis and respiratory disorder without a history of trauma. Repeated computed tomography (CT) and magnetic resonance imaging (MRI) with different positions of the neck revealed concurrent atlanto-occipital dislocation (AOD) and atlantoaxial instability (AAI) with spinal cord compression. This case was unique due to its congenital nature and the absence of trauma. The surgical treatment involved precise removal of the C1 vertebra's ventral articular facet, which was compressing on the spinal cord, attributed to its fixed and malaligned position within the atlantooccipital joint. Following facetectomy, the stabilization of the occipital bone to the C2 vertebra was achieved by screws, wire, and polymethyl methacrylate. Two days after surgery, the dog recovered ambulation and showed gradual improvement in gait, despite mild residual ataxia. Postoperative CT and radiographs showed successful decompression of the spinal cord. The screw loosening was confirmed at 114 days, which was managed successfully by extracting the affected screws. Through the 21-month monitoring period, the dog showed a normal gait with a wide-based stance of the pelvic limbs when standing and experienced no pain. This case represents the first report of concurrent congenital AOD and AAI treated with a ventral surgical approach, contributing new insights to the understanding and management of such complex cranio-cervical junction disorders in veterinary neurosurgery.

Kidney, ureter, and urinary bladder segmentation based on non-contrast enhanced computed tomography images using modified U-Net.

This study was performed to segment the urinary system as the basis for diagnosing urinary system diseases on non-contrast computed tomography (CT). This study was conducted with images obtained between January 2016 and December 2020. During the study period, non-contrast abdominopelvic CT scans of patients and diagnosed and treated with urinary stones at the emergency departments of two institutions were collected. Region of interest extraction was first performed, and urinary system segmentation was performed using a modified U-Net. Thereafter, fivefold cross-validation was performed to evaluate the robustness of the model performance. In fivefold cross-validation results of the segmentation of the urinary system, the average dice coefficient was 0.8673, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9651, 0.7172, and 0.9196, respectively. In the test dataset, the average dice coefficient of best performing model in fivefold cross validation for whole urinary system was 0.8623, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9613, 0.7225, and 0.9032, respectively. The segmentation of the urinary system using the modified U-Net proposed in this study could be the basis for the detection of kidney, ureter, and urinary bladder lesions, such as stones and tumours, through machine learning.

Association between smoking status and subclinical coronary atherosclerosis in asymptomatic individuals.

Objectives: In this study, we sought to evaluate the association between smoking status and subclinical coronary atherosclerosis, as detected by coronary computed tomography angiography (CCTA), in asymptomatic individuals. Methods: We retrospectively analyzed 9,285 asymptomatic participants (mean age, 53.7±8.0 years; 6,017 [64.8%] male) with no history of coronary artery disease (CAD) who had undergone self-referred CCTA. Of these participants, 4,333 (46.7%) were considered never smokers, 2,885 (31.1%) former smokers, and 2,067 (22.3%) current smokers. We assessed the degree and characteristics of subclinical coronary atherosclerosis using CCTA, with obstructive CAD defined as a diameter stenosis of at least 50%. Results: Compared with never-smokers, former smokers exhibited no significant differences in the probabilities of obstructive CAD, any coronary plaque, calcified plaque, or mixed plaque, as determined using adjusted odds ratios (aORs; p>0.05 for all). However, the risk of non-calcified plaque was significantly higher in former smokers (aOR, 1.34; 95% confidence interval [CI], 1.00 to 1.78; p=0.048). Current smokers had significantly higher rates of obstructive CAD (aOR, 1.46; 95% CI, 1.10 to 1.96; p=0.010), any coronary plaque (aOR, 1.41; 95% CI, 1.20 to 1.65; p<0.001), calcified plaque (aOR, 1.32; 95% CI, 1.13 to 1.55; p=0.001), non-calcified plaque (aOR, 1.72; 95% CI, 1.28 to 2.32; p<0.001), and mixed plaque (aOR, 2.00; 95% CI, 1.39 to 2.86; p<0.001) compared to never smokers. Conclusion: This cross-sectional study revealed a significant association between current smoking and subclinical coronary atherosclerosis, as detected on CCTA. Additionally, former smoking demonstrated an association with non-calcified plaque, indicating elevated cardiovascular risk.

Analgesic Effect of SKI306X on Chronic Postischemic Pain and Spinal Nerve Ligation-Induced Neuropathic Pain in Mice.

Neuropathic pain (NP) results from lesions or diseases affecting the peripheral or central somatosensory system. However, there are currently no drugs that are particularly effective in treating this condition. SKI306X is a blend of purified extracts of three oriental herbs (Clematis mandshurica, Trichosanthes kirilowii, and Prunella vulgaris) commonly used to treat osteoarthritis for their chondroprotective effects. Chronic postischemic pain (CPIP) and spinal nerve ligation (SNL) models were created by binding the upper left ankle of mice with an O-ring for 3 h and ligating the L5 spinal nerve, respectively. Mice with allodynia were injected intraperitoneally with 0.9% normal saline (NS group) or different doses (25, 50, or 100 mg/kg) of SKI306X (SKI groups). We assessed allodynia using von Frey filaments before injection and 30, 60, 90, 120, 180, and 240 min and 24 h after injection to confirm the antiallodynic effect of SKI306X. We also measured glial fibrillary acidic protein (GFAP) levels in the spinal cord and dorsal root ganglia to confirm the change of SKI306X administration. Both models exhibited significant mechanical allodynia. The intraperitoneal injection of SKI306X significantly increased the paw withdrawal threshold in a dose-dependent manner, as the paw withdrawal threshold was significantly increased after SKI306X administration compared with at baseline or after NS administration. GFAP levels in the SKI group decreased significantly (p < 0.05). Intraperitoneal administration of SKI306X dose-dependently attenuated mechanical allodynia and decreased GFAP levels, suggesting that GFAP is involved in the antiallodynic effect of SKI306X in mice with CPIP and SNL-induced NP.

Reduced income, joblessness, and disability among traumatic brain injury survivors: A national cohort study in South Korea.

OBJECTIVE: This study aimed to investigate the effects of traumatic brain injury (TBI) on employment status, household income, and the development of new disabilities among survivors, as well as its correlation with mortality rates over a 2-year period. METHODS: In this nationwide population-based cohort study, we screened all patients admitted to the intensive care unit (ICU) because of TBI between January 1, 2010, and December 31, 2018, in South Korea. Among them, patients who were alive for > 1 year were considered TBI survivors. Changes in unemployment, decreased household income, and newly acquired disabilities were evaluated one year after the date of ICU admission due to TBI. RESULTS: In total, 78,420 TBI survivors were included in this study. Among them, 5.4 %, 22.5 %, and 8.6 % of the TBI survivors experienced unemployment, decreased household income, and newly acquired disabilities within one year after the date of ICU admission, respectively. A longer ICU stay, comorbidities, hospital admission through the emergency room, increased total cost of hospitalization, and mechanical ventilatory support were associated with unemployment, decreased household income, and newly acquired disabilities. Among the three factors, the newly acquired disability was associated with a 27 % increase in 2-year all-cause mortality (hazard ratio: 1.27, 95 % confidence interval: 1.17-1.39; P < 0.001), while unemployment and decreased household income were not significantly associated (P = 0.371 and P = 0.105, respectively). CONCLUSIONS: A significant number of individuals in South Korea who survived TBI faced challenges such as unemployment, reduced household income, and the acquisition of new disabilities within a year of being admitted to the ICU. In addition, the study found that individuals who developed a new disability after TBI had a higher risk of mortality within two years.

Virtual platform to tackle challenges associated with lifelong medical education during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, large in-person conferences were mostly cancelled to avoid further disease contagion. Physicians continued to demand changes in form to enable participation in lifelong medical education programs, and the traditional model of in-person conferences needed to be rethought. As such, a regional branch of the national orthopedic association tried to move in-person conferences onto a virtual platform. This study aimed to investigate the effect of transitioning large in-person conferences to a virtual model during the COVID-19 pandemic, especially examining any differences in the attendance of each type of conference. METHODS: In this retrospective observational study, 776 participants in virtual conferences and 575 participants in in-person conferences were analyzed. Institutions were classified based on their location in a central city and two neighboring cities. Affiliated institutions were divided into resident training hospitals, general hospitals, and private clinics. The change in the number and proportion of participants between the virtual conference year and in-person conference year was calculated. RESULTS: The number of virtual conference participants was significantly greater than that of in-person conference participants (P = 0.01). Although the highest number of participants was from central city for both years, the proportion of participants from the two neighboring cities increased. Although the proportion of participants from resident training hospitals and private clinics decreased, the proportion of participants from general hospitals increased. CONCLUSIONS: We implemented a virtual platform to tackle challenges associated with lifelong medical education during the COVID-19 pandemic. The virtual platforms can be helpful for organizations that must hold regular lifelong medical education programs for members spread across a wide geographic region.

Repeated Infusions of Bone-Marrow-Derived Mesenchymal Stem Cells over 8 Weeks for Steroid-Refractory Chronic Graft-versus-Host Disease: A Prospective, Phase I/II Clinical Study.

Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there are several approved treatments for patients who do not respond to steroids, such as ruxolitinib. Nevertheless, a significant proportion of patients fail second-line treatment, indicating the need for novel approaches. Mesenchymal stem cells (MSCs) have been considered a potential treatment approach for steroid-refractory cGVHD. To evaluate the safety and efficacy of repeated infusions of MSCs, we administered intravenous MSCs every two weeks to ten patients with severe steroid-refractory cGVHD in a prospective phase I clinical trial. Each patient received a total of four doses, with each dose containing 1 × 106 cells/kg body weight from the same donor and same passage. Patients were assessed for their response to treatment using the 2014 National Institutes of Health (NIH) response criteria during each visit. Ten patients with diverse organ involvement were enrolled, collectively undergoing 40 infusions as planned. Remarkably, the MSC infusions were well tolerated without severe adverse events. Eight weeks after the initial MSC infusion, all ten patients showed partial responses characterized by the amelioration of clinical symptoms and enhancement of their quality of life. The overall response rate was 60%, with a complete response rate of 20% and a partial response (PR) rate of 40% at the last follow-up. Overall survival was 80%, with a median follow-up of 381 days. Two patients died due to relapse of their primary disease. Immunological analyses revealed a reduction in inflammatory markers, including Suppression of Tumorigenicity 2 (ST2), C-X-C motif chemokine ligand (CXCL)10, and Secreted phosphoprotein 1(SPP1), following the MSC treatment. Repeated MSC infusions proved to be both feasible and safe, and they may be an effective salvage therapy in patients with steroid-refractory cGVHD. Further large-scale clinical studies with long-term follow-up are needed in the future to determine the role of MSCs in cGVHD.

CBP Expression Contributes to Neuropathic Pain via CREB and MeCP2 Regulation in the Spared Nerve Injury Rat Model.

Background and Objectives: This study aimed to investigate the relationship between neuropathic pain and CREB-binding protein (CBP) and methyl-CpG-binding protein 2 (MeCP2) expression levels in a rat model with spared nerve injury (SNI). Materials and Methods: Rat (male Sprague-Dawley white rats) models with surgical SNI (n = 6) were prepared, and naive rats (n = 5) were used as controls. The expression levels of CBP and MeCP2 in the spinal cord and dorsal root ganglion (DRG) were compared through immunohistochemistry at 7 and 14 days after surgery. The relationship between neuropathic pain and CBP/MeCP2 was also analyzed through intrathecal siRNA administration. Results: SNI induced a significant increase in the number of CBPs in L4 compared with contralateral DRG as well as with naive rats. The number of MeCP2 cells in the dorsal horn on the ipsilateral side decreased significantly compared with the contralateral dorsal horn and the control group. SNI induced a significant decrease in the number of MeCP2 neurons in the L4 ipsilateral DRG compared with the contralateral DRG and naive rats. The intrathecal injection of CBP siRNA significantly inhibited mechanical allodynia induced by SNI compared with non-targeting siRNA treatment. MeCP2 siRNA injection showed no significant effect on mechanical allodynia. Conclusions: The results suggest that CBP and MeCP2 may play an important role in the generation of neuropathic pain following peripheral nerve injury.

Reconstruction of Bilateral Chronic Triceps Brachii Tendon Disruption Using a Suture-Mediated Anatomic Footprint Repair in a Dog.

A 2-year-old, intact female Pomeranian presented with bilateral forelimb lameness, characterized by the olecranon making contact with the ground. The patient experienced two separate incidents of falling, occurring four and three weeks before admission, respectively. Following each episode, non-weight-bearing lameness was initially observed in the left forelimb, followed by the development of crouch gait. Based on the physical examination, radiographic, and ultrasonographic findings, bilateral triceps brachii tendon disruption was diagnosed. Intraoperatively, excessive granulation tissue at the distal end of the tendon was excised. The footprint region of each triceps brachii tendon was decorticated with a high-speed burr until bleeding was observed. The triceps brachii tendon was reattached to completely cover its footprint on the olecranon using the Krackow suture technique. This method involves anchoring the suture through bone tunnels in the ulna. Trans-articular external skeletal fixation was applied to both forelimbs to immobile and stabilize the elbow joints for nine weeks. Subsequently, the dog gradually increased its walking activities while on a leash over a six-week period. At the three-year follow-up, the patient exhibited improved forelimb function and maintained a normal gait without signs of lameness. Suture-mediated anatomic footprint repair proved useful in this single case and may be an effective surgical alternative for the management of chronic triceps brachii tendon disruption in dogs.

Establishment of canine mammary gland tumor cell lines harboring PI3K/Akt activation as a therapeutic target.

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.

Quantification of Infarct Core Volume in Patients with Acute Ischemic Stroke Using Cerebral Metabolic Rate of Oxygen in CT Perfusion.

BACKGROUND AND PURPOSE: The cerebral metabolic rate of oxygen (CMRO2) is considered a robust marker of the infarct core in 15O-tracer-based PET. We aimed to delineate the infarct core in patients with acute ischemic stroke by using commonly used relative CBF (rCBF) < 30% and oxygen metabolism parameter of CMRO2 on CT perfusion in comparison with pretreatment DWI-derived infarct core volume. MATERIALS AND METHODS: Patients with acute ischemic stroke who met the inclusion criteria were recruited. The CMRO2 and CBF maps in CT perfusion were automatically generated by using postprocessing software. The infarct core volume was quantified with relative cerebral metabolic rate of oxygen (rCMRO2) <20% -30% and rCBF <30%. The optimal threshold was defined as those that demonstrated the smallest mean absolute error, lowest mean infarct core volume difference, narrowest 95% limit of agreement, and largest intraclass correlation coefficient (ICC) against the DWI. RESULTS: This study included 76 patients (mean age ± standard deviation, 69.97 ± 12.15 years, 43 men). The optimal thresholds of rCMRO2 <26% resulted in the lowest mean infarct core volume difference, narrowest 95% limit of agreement, and largest ICC among different thresholds. Bland-Altman analysis demonstrated a volumetric bias of 1.96 mL between DWI and rCMRO2 <26%, whereas in cases of DWI and rCBF <30%, the bias was notably larger at 14.10 mL. The highest correlation was observed for rCMRO2 <26% (ICC = 0.936), whereas rCBF <30% showed a slightly lower ICC of 0.934. CONCLUSIONS: CT perfusion-derived CMRO2 is a promising parameter for estimating the infarct core volume in patients with acute ischemic stroke.