Consistent efficacy of hepatic artery infusion chemotherapy irrespective of PD­L1 positivity in unresectable hepatocellular carcinoma.

Atezolizumab/bevacizumab is the first line of treatment for unresectable hepatocellular carcinoma (HCC), combining immune checkpoint inhibitor and anti-VEGF monoclonal antibodies. Hepatic arterial infusion chemotherapy (HAIC) is administered when the above-described combination fails to confer sufficient clinical benefit. The present study aimed to explore the association between tumor programmed cell death-ligand 1 (PD-L1) positivity and HAIC response. A total of 40 patients with HCC who had undergone HAIC with available biopsy samples obtained between January 2020 and May 2023 were retrospectively enrolled. Tumor response, progression-free survival (PFS), disease control rate (DCR) and overall survival (OS) were evaluated. PD-L1 expression in tumor samples was assessed using a combined positivity score. The response rates of HAIC-treated patients with advanced HCC after failure of atezolizumab/bevacizumab combination therapy were recorded. OS (P=0.9717) and PFS (P=0.4194) did not differ between patients with and without PD-L1 positivity. The objective response rate (P=0.7830) and DCR (P=0.7020) also did not differ based on PD-L1 status. In conclusion, the current findings highlight the consistent efficacy of HAIC, regardless of PD-L1 positivity.

Compact Solid Electrolyte Interface Realization Employing Surface-Modified Fillers for Long-Lasting, High-Performance All-Solid-State Li-Metal Batteries.

The implementation of polymer-based Li-metal batteries is hindered by their low coulombic efficiency and poor cycling stability attributed to continuous electrolyte decomposition. Enhancement of the solid electrolyte interface (SEI) stability is key to mitigating electrolyte decomposition. This study proposes surface-functionalized silica mesoball fillers to fabricate a composite polymer electrolyte (MSBM-CPE). As a result of surface modification, the polyethylene oxide matrix benefits from the uniform distribution of the filler, which provides a large surface area and Lewis acid sites. Molecular dynamics simulations reveal that the dissociation energy of lithium bis(trifluoromethanesulfonyl)imide in the filler is fourfold higher (-1.95 eV) than that of the filler-free electrolyte. Consequently, the MSMB-CPE diffusivity is 30 times higher than its filler-free counterpart. The MSMB-CPE of ionic conductivity of 1.16 × 10-2 S cm-1 @60 °C and a venerable Li-ion transference number of 0.81. The excellent compatibility of MSMB-CPE with the Li anode is demonstrated by its stable symmetric cell performance under high current density (200 µA cm-2 @60 °C) for over 5000 h. Approximately 85.60% retention capacity of the [Li/MSMB-CPE/LiFePO4] full cell after 700 cycles. Furthermore, compositional analysis reveals that the SEI layer in MSMB-CPE is smooth with fewer by-products at the electrolyte/Li interface.

Effect of Biliary Drainage on the Prognosis of Patients with Hepatocellular Carcinoma and Bile Duct Invasion.

Background/Aims: Bile duct invasion (BDI) is rarely observed in patients with advanced hepatocellular carcinoma (HCC), leading to hyperbilirubinemia. However, the efficacy of pretreatment biliary drainage for HCC patients with BDI and obstructive jaundice is currently unclear. Thus, the aim of this study was to assess the effect of biliary drainage on the prognosis of these patients. Methods: We retrospectively enrolled a total of 200 HCC patients with BDI from multicenter cohorts. Patients without obstructive jaundice (n=99) and those who did not undergo HCC treatment (n=37) were excluded from further analysis. Finally, 64 patients with obstructive jaundice (43 subjected to drainage and 21 not subjected to drainage) were included. Propensity score matching was then conducted. Results: The biliary drainage group showed longer overall survival (median 10.13 months vs 4.43 months, p=0.004) and progression-free survival durations (median 7.00 months vs 1.97 months, p<0.001) than the non-drainage group. Multivariate analysis showed that biliary drainage was a significantly favorable prognostic factor for overall survival (hazard ratio, 0.42; p=0.006) and progression-free survival (hazard ratio, 0.30; p<0.001). Furthermore, in the evaluation of first response after HCC treatment, biliary drainage was beneficial (p=0.005). Remarkably, the durations of overall survival (p=0.032) and progression-free survival (p=0.004) were similar after propensity score matching. Conclusions: Biliary drainage is an independent favorable prognostic factor for HCC patients with BDI and obstructive jaundice. Therefore, biliary drainage should be contemplated in the treatment of advanced HCC with BDI to improve survival outcomes.

Chuna Manual Therapy or Electroacupuncture with Pregabalin for Chemotherapy-Induced Peripheral Neuropathy: A Randomized Controlled Pilot Study.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common side effects of chemotherapy, and effective treatments for CIPN are still lacking. For this reason, there is a growing interest in complementary and alternative medicine as a potential source of nonsurgical treatments for CIPN symptoms alongside pregabalin. One such option being explored is Chuna manual therapy (CMT), a traditional Korean manual therapy. Methods: This study compares the effectiveness and safety of using only pregabalin (PG) as a conventional method of treating breast and colorectal cancer patients with CIPN symptoms with a combination of both PG and electroacupuncture (EA) or CMT, while also assessing the feasibility of future large-scale clinical studies. Due to the COVID-19 pandemic, only 74 CIPN patients were recruited to this study. Twenty-five were assigned to the PG group, 26 to the PG + EA group, and 22 to the PG + CMT group for a five-week treatment and a four-week follow-up study. Results: For the primary outcome, we evaluated the mean differences in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) compared to the baseline at week 5 (visit 4). Although we found that the PG + CMT group showed the biggest difference (-16.64 [95% CI: -25.16, -8.11]) compared to the PG group (-8.60 [95% CI: -14.93, -2.27]) and the PG + EA group (-6.73 [95% CI: -12.34, -1.13]), this finding lacked statistical significance (p = 0.2075). In terms of safety, two patients in the PG + CMT group reported side effects: one bruise and one headache. Conclusions: The low attrition and high adherence rates of all the groups, and the similar rates of side effects among them, support the feasibility of larger-scale follow-up studies.

The utility of intraoperative ultrasonography for spinal cord surgery.

OBJECTIVES: Intraoperative ultrasonography (IOUS) offers the advantage of providing real-time imaging features, yet it is not generally used. This study aims to discuss the benefits of utilizing IOUS in spinal cord surgery and review related literature. MATERIALS AND METHODS: Patients who underwent spinal cord surgery utilizing IOUS at a single institution were retrospectively collected and analyzed to evaluate the benefits derived from the use of IOUS. RESULTS: A total of 43 consecutive patients were analyzed. Schwannoma was the most common tumor (35%), followed by cavernous angioma (23%) and ependymoma (16%). IOUS confirmed tumor extent and location before dura opening in 42 patients (97.7%). It was particularly helpful for myelotomy in deep-seated intramedullary lesions to minimize neural injury in 13 patients (31.0% of 42 patients). IOUS also detected residual or hidden lesions in 3 patients (7.0%) and verified the absence of hematoma post-tumor removal in 23 patients (53.5%). In 3 patients (7.0%), confirming no intradural lesions after removing extradural tumors avoided additional dural incisions. IOUS identified surrounding blood vessels and detected dural defects in one patient (2.3%) respectively. CONCLUSIONS: The IOUS can be a valuable tool for spinal cord surgery in identifying the exact location of the pathologic lesions, confirming the completeness of surgery, and minimizing the risk of neural and vascular injury in a real-time fashion.

Genomic Biomarkers to Predict Response to Atezolizumab Plus Bevacizumab Immunotherapy in Hepatocellular Carcinoma: Insights from the IMbrave150 Trial.

Introduction: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge. Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full model. We further validated ISS10 in an independent HCC cohort treated with nivolumab plus ipilimumab. Results: The study identified a significant association between the ISS and treatment response. Among patients classified as high responders, those treated with the atezolizumab plus bevacizumab combination exhibited improved overall and progression-free survival as well as better objective response rate compared to those treated with sorafenib. We also observed a significant correlation between ISS10 and response to nivolumab plus ipilimumab treatment. Analysis of immune cell subpopulations revealed distinct characteristics associated with ISS subtypes. In particular, the ISS10 high subtype displayed a more favorable immune environment with higher proportions of anti-tumor macrophages and activated T-cells, potentially explaining its better response. Conclusions: Our study suggests that ISS and ISS10 are promising predictive biomarkers for enhanced therapeutic outcomes in HCC patients undergoing combination immunotherapy. These markers are crucial for refining patient stratification and personalized treatment approaches to advance the effectiveness of standard-of-care regimens.

Effect of endocrine-disrupting chemicals on the expression of a calcium ion channel receptor (ryanodine receptor) in the mud crab (Macrophthalmus japonicus).

Endocrine-disrupting chemicals (EDCs) are toxic pollutants generated by artificial activities. Moreover, their hormone-like structure induces disturbances, such as mimicking or blocking metabolic activity. Previous studies on EDCs have focused on the adverse effect of the endocrine system in vertebrates, with limited investigations conducted on ion channels in invertebrates. Thus, in this study, we investigated the potential adverse effects of exposure to bisphenol-A (BPA) and di-(2-ethylhexyl) phthalate (DEHP) at the molecular level on the ryanodine receptor (RyR), a calcium ion channel receptor in Macrophthalmus japonicus. In the phylogenetic analysis, the RyR amino acid sequences in M. japonicus clustered with those in the Crustacean and formed separated branches for RyR in insects and mammals. When exposed to 1 µg L-1 BPA, a significant increase in RyR mRNA expression was observed in the gills on day 1, although a similar level to the control group was observed from day 4 to day 7. However, the RyR expression due to DEHP exposure decreased on days 1 and 4, although it increased on day 7 following exposure to 10 µg L-1. The RyR expression pattern in the hepatopancreas increased for up to 4 days, depending on the BPA concentration. However, there was a tendency for the expression to decrease gradually after the statistical significance increased during the early stage of DEHP exposure (D1). Hence, the transcriptional alterations in the M. japonicus RyR gene observed in the study suggest that exposure toxicities to EDCs, such as BPA and DEHP, have the potential to disrupt calcium ion channel signaling in the gills and hepatopancreas of M. japonicus crabs.

Quantification method of ctDNA using cell-free DNA methylation profile for noninvasive screening and monitoring of colon cancer.

BACKGROUND: Colon cancer ranks as the second most lethal form of cancer globally. In recent years, there has been active investigation into using the methylation profile of circulating tumor DNA (ctDNA), derived from blood, as a promising indicator for diagnosing and monitoring colon cancer. RESULTS: We propose a liquid biopsy-based epigenetic method developed by utilizing 49 patients and 260 healthy controls methylation profile data to screen and monitor colon cancer. Our method initially identified 901 colon cancer-specific hypermethylated (CaSH) regions in the tissues of the 49 cancer patients. We then used these CaSH regions to accurately quantify the amount of circulating tumor DNA (ctDNA) in the blood samples of these same patients, utilizing cell-free DNA methylation profiles. Notably, the methylation profiles of ctDNA in the blood exhibited high sensitivity (82%) and specificity (93%) in distinguishing patients with colon cancer from the control group, with an area under the curve of 0.903. Furthermore, we confirm that our method for ctDNA quantification is effective for monitoring cancer patients and can serve as a valuable tool for postoperative prognosis. CONCLUSIONS: This study demonstrated a successful application of the quantification of ctDNA among cfDNA using the original cancer tissue-derived CaSH region for screening and monitoring colon cancer.

Biological and prognostic significance of NDRG2 downregulation in oral squamous cell carcinoma.

OBJECTIVE: Downregulation of N-myc downstream-regulated gene 2 (NDRG2), a tumor suppressor gene, has been associated with poor clinical outcomes in various cancers. However, the prognostic significance of NDRG2 in oral squamous cell carcinoma (OSCC) remains unknown. This study aimed to evaluate the prognostic value of NDRG2 downregulation in OSCC and to elucidate the mechanism by which NDRG2 is downregulated and the biological role of NDRG2 in tumor progression. METHODS: Immunohistochemical and in silico analyses of NDRG2 expression were performed, and the correlation between NDRG2 expression and clinicopathological data was analyzed. The effect of NDRG2 knockdown on the biological behavior of OSCC cells was investigated and the effect of 5-aza-2'-deoxycytidine (5-aza-dC) on NDRG2 expression was determined. RESULTS: NDRG2 expression was significantly downregulated and DNA hypermethylation of NDRG2 was frequently found in head and neck SCC, including OSCC. Low NDRG2 expression was significantly correlated with adverse clinicopathological features and worse survival in OSCC. NDRG2 knockdown could enhance the oncogenic properties of OSCC cells. NDRG2 mRNA levels in OSCC cells could be restored by 5-aza-dC. CONCLUSION: Downregulation of NDRG2 promotes tumor progression and predicts poor prognosis in OSCC. Therefore, restoration of NDRG2 expression may be a potential therapeutic strategy in OSCC.

Zingiber officinale promotes autophagy and apoptosis in human oral cancer through the C/EBP homologous protein.

The rhizome of Zingiber officinale (Z. officinale), commonly known as ginger, has been characterized as a potential drug candidate due to its antitumor effects. However, the chemotherapeutic effect of ginger on human oral cancer remains poorly understood. In this study, we examined the effects of an ethanol extract of Z. officinale rhizomes (ZOE) on oral cancer and identified the components responsible for its pharmacological activity. ZOE exerts its inhibitory activity in oral cancer by inducing both autophagy and apoptosis simultaneously. Mechanistically, ZOE-induced autophagy and apoptosis in oral cancer are attributed to the reactive oxygen species (ROS)-mediated endoplasmic reticulum stress response. Additionally, we identified two active components of ZOE, 1-dehydro-6-gingerdione and 8-shogaol, which were sufficient to stimulate autophagy initiation and apoptosis induction by enhancing CHOP expression. These results suggest that ZOE and its two active components induce ROS generation, upregulate CHOP, initiate autophagy and apoptosis, and hold promising therapeutics against human oral cancer.

Spreading and Capillary Imbibition of Viscous Oil Lens into an Open-Cell Porous Structure.

Oil pollution in the ocean is becoming more and more of a serious issue, which increases interest in both ways for combating its cause and methods for observing and monitoring how oil spreads. A promising approach based on an optical method with empirical relations for selected viscous oil-water systems is presented. Based on a modified melamine sponge (MMS), the microscopic spreading and oil capillary penetration phenomenon of the porous structure were investigated. The objective of this study is 2-fold: (i) to present a more thorough experimental description of the spreading of viscous oil lens on the water surface and capillary action of oil lens into MMS porous structure; and (ii) to provide a theoretical description that helps to explain some of the observed behavior. With knowledge of δ∞2=-2SρW/gρO(ρW-ρO), we can determine the spreading coefficient S. It needs to be pointed out that the oil lens floating on the water surface does satisfy Neumann's rule as the spreading coefficient of the air-oil-water system is negative (- 9.8 mN/m), indicating the ability to form a stable oil lens with thickness δO = 3.04 mm and radius RL = 38.64 mm after 60 min of spreading test. Furthermore, to better understand the capillary phenomena from a mechanical approach, an oil lens in contact with the surface of the MMS porous structure, by in-depth visualization, is properly defined as the balance of forces acting. Finally, as an illustration of this method, we utilized this approach to obtain the equilibrium height of the capillary rise and take it into account in terms of effective material thickness.

Ir(triNHC)-Catalyzed Upcycling of Waste PET for Lactic Acid Production with Sustainable Isolation via Bipolar Membrane Electrodialysis.

For the upcycling of waste polyethylene terephthalate (PET), encompassing both colored and fabric PET materials, we investigated the Ir(triNHC)-catalyzed dehydrogenative coupling of PET and methanol, leading to the production of sodium lactate with good yields. We proposed a sustainable method for isolating lactic acid from the catalytic reaction mixture of sodium lactate and regenerating the base using bipolar membrane electrodialysis (BMED). This isolation method demonstrated high effectiveness, achieving isolation of lactic acid while maintaining economic feasibility at $ 0.10 per kg of lactic acid, and enabling sustainable NaOH regeneration with complete resource circulation. We assessed the recyclability of the catalyst and elucidated the mechanism involving base-mediated depolymerization and catalyst-promoted dehydrogenation, highlighting the importance of triNHC ligands in enhancing catalytic activity.

Correction: Sung et al. Linear Tumor Regression of Rectal Cancer in Daily MRI during Preoperative Chemoradiotherapy: An Insight of Tumor Regression Velocity for Personalized Cancer Therapy. Cancers 2022, 14, 3749.

In the original publication [...].

Effect of direct-acting antivirals on disease burden of hepatitis C virus infection in South Korea in 2007-2021: a nationwide, multicentre, retrospective cohort study.

Background: It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data. Methods: This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality. Findings: Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001). Interpretation: Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests. Funding: The Korea Disease Control and Prevention Agency.

Automated Scoring of Alzheimer's Disease Atrophy Scale with Subtype Classification Using Deep Learning-Based T1-Weighted Magnetic Resonance Image Segmentation.

Background: Application of visual scoring scales for regional atrophy in Alzheimer's disease (AD) in clinical settings is limited by their high time cost and low intra/inter-rater agreement. Objective: To provide automated atrophy scoring using objective volume driven from deep-learning segmentation methods for AD subtype classification using magnetic resonance imaging (MRI). Methods: We enrolled 3,959 participants (1,732 cognitively normal [CN], 1594 with mild cognitive impairment [MCI], and 633 with AD). The occupancy indices for each regional volume were calculated by dividing each volume by the size of the lateral and inferior ventricular volumes. MR images from 355 participants (119 CN, 119 MCI, and 117 AD) from three different centers were used for validation. Two neuroradiologists performed visual assessments of the medial temporal, posterior, and global cortical atrophy scores in the frontal lobe using T1-weighted MR images. Images were also analyzed using the deep learning-based segmentation software, Neurophet AQUA. Cutoff values for the three scores were determined using the data distribution according to age. The scoring results were compared for consistency and reliability. Results: Four volumetric-driven scoring results showed a high correlation with the visual scoring results for AD, MCI, and CN. The overall agreement with human raters was weak-to-moderate for atrophy scoring in CN participants, and good-to-almost perfect in AD and MCI participants. AD subtyping by automated scores also showed usefulness as a research tool. Conclusions: Determining AD subtypes using automated atrophy scoring for late-MCI and AD could be useful in clinical settings or multicenter studies with large datasets.

Damage-free dry transfer method using stress engineering for high-performance flexible two- and three-dimensional electronics.

Advanced transfer printing technologies have enabled the fabrication of high-performance flexible and stretchable devices, revolutionizing many research fields including soft electronics, optoelectronics, bioelectronics and energy devices. Despite previous innovations, challenges remain, such as safety concerns due to toxic chemicals, the expensive equipment, film damage during the transfer process and difficulty in high-temperature processing. Thus a new transfer printing process is needed for the commercialization of high-performance soft electronic devices. Here we propose a damage-free dry transfer printing strategy based on stress control of the deposited thin films. First, stress-controlled metal bilayer films are deposited using direct current magnetron sputtering. Subsequently, mechanical bending is applied to facilitate the release of the metal bilayer by increasing the overall stress. Experimental and simulation studies elucidate the stress evolution mechanisms during the processes. By using this method, we successfully transfer metal thin films and high-temperature-treated oxide thin films onto flexible or stretchable substrates, enabling the fabrication of two-dimensional flexible electronic devices and three-dimensional multifunctional devices.

Antitumor activity of afatinib in EGFR T790M-negative human oral cancer therapeutically targets mTOR/Mcl-1 signaling axis.

PURPOSE: This study investigates the role and effectiveness of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in oral cancer, focusing on the clinical relevance of EGFR and myeloid cell leukemia-1 (Mcl-1) in head and neck cancers (HNCs). It aims to explore the molecular mechanism of afatinib, a TKI, in treating human oral cancer. METHODS: We conducted an in silico analysis using databases like The Cancer Genome Atlas, Gene Expression Omnibus, and Clinical Proteomic Tumor Analysis Consortium, along with immunohistochemistry staining, to study EGFR and Mcl-1 expression in HNCs. For investigating afatinib's anticancer properties, we performed various in vitro and in vivo analyses, including trypan blue exclusion assay, Western blotting, 4'-6-diamidino-2-phenylindole staining, flow cytometry, quantitative real-time PCR, Mitochondrial membrane potential assay, overexpression vector construction, transient transfection, and a tumor xenograft model. RESULTS: Higher expression levels of EGFR and Mcl-1 were observed in HNC patient tissues compared to normal tissues, with their co-expression significantly linked to poor prognosis. There was a strong correlation between EGFR and Mcl-1 expressions in oral cancer patients. Afatinib treatment induced apoptosis and suppressed Mcl-1 in oral cancer cell lines without the EGFR T790M mutation. The mechanism of afatinib-induced apoptosis involved the EGFR/mTOR/Mcl-1 axis, as shown by the effects of mTOR activator MHY1485 and inhibitor rapamycin. Afatinib also increased Bim expression, mitochondrial membrane permeabilization, and cytochrome c release. It significantly lowered tumor volume without affecting body, liver, and kidney weights. CONCLUSION: Afatinib, targeting the EGFR/mTOR/Mcl-1 axis, shows promise as a therapeutic strategy for oral cancer, especially in patients with high EGFR and Mcl-1 expressions.

Pure varus posteromedial rotatory instability of the elbow: Radiographic findings, treatment, and outcomes.

INTRODUCTION: Although varus posteromedial rotatory instability (VPMRI) is a subtle elbow injury that involves anteromedial coronoid facet (AMCF) fracture and ligamentous injuries, treatment options and outcomes of VPMRI remains controversial. The aim of this study was to investigate radiographic findings, treatments, and outcomes of a large series of VPMRI. METHODS: We retrospectively reviewed 91 pure VPMRI cases with AMCF fracture (O'Driscoll classification anteromedial type) which were treated at 6 hospitals. Clinical and radiographic outcomes were investigated with a mean follow-up period of 46.8 months using the Mayo elbow performance score (MEPS), and the Quick Disabilities of the Arm, Shoulder and Hand (Quick-DASH) score, and serial plain radiographs. RESULTS: In AMCF fracture, there were 4 cases of subtype 1, 67 cases of subtype 2, and 20 cases of subtype 3. On MRI, complete tears of lateral collateral ligament and medial collateral ligament were observed in 83.1 % (59/71 cases) and 33.8 % (24/71 cases). Operative treatment was performed in 68 cases (74.7 %) including both side fixation in 40 cases (58.8 %), medial side fixation only in 17 cases (25.0 %), and lateral side fixation only in 11 cases (16.2 %). Nonoperative treatment was performed in 23 cases (25.3 %). The mean final MEPS and Quick-DASH scores were 93.7 and 7.9. The overall complication and reoperation rates were 22.0 % and 15.4 %. No significant differences regarding final clinical scores and range of motions were observed between the operative group and the nonoperative group, but significant differences were observed regarding number (p = 0.019) and displacement (p = 0.002) of coronoid fragment, and complication rate (p < 0.001) between the two groups. CONCLUSION: Depending on the pattern of coronoid fragment and the degree of ligamentous injuries, operative treatment of unstable VPMRI using various fixation techniques including coronoid fixation and ligament repair yielded satisfactory final clinical outcomes. However, surgeons should be aware of the high complication and reoperation rates after operative treatment. Stable VPMRI with AMCF fracture involving minimal displacement or small number of fragments can be treated nonoperatively.

Reducing Peptidoglycan Crosslinking by Chemical Modulator Reverts ß-lactam Resistance in Methicillin-Resistant Staphylococcus aureus.

Small molecule can be utilized to restore the effectiveness of existing major classes of antibiotics against antibiotic-resistant bacteria. In this study, it is demonstrated that celastrol, a natural compound, can modify the bacterial cell wall and subsequently render bacteria more suceptible to ß-lactam antibiotics. It is shown that celastrol leads to incomplete cell wall crosslinking by modulating levels of c-di-AMP, a secondary messenger, in methicillin-resistant Staphylococcus aureus (MRSA). This mechanism enables celastrol to act as a potentiator, effectively rendering MRSA susceptible to a range of penicillins and cephalosporins. Restoration of in vivo susceptibility of MRSA to methicillin is also demonstrated using a sepsis animal model by co-administering methicillin along with celastrol at a much lower amount than that of methicillin. The results suggest a novel approach for developing potentiators for major classes of antibiotics by exploring molecules that re-program metabolic pathways to reverse ß-lactam-resistant strains to susceptible strains.

Biomechanical analysis using finite element analysis of orbital floor fractures reproduced in a realistic experimental environment with an anatomical model.

Introduction: In this study, we attempted to demonstrate the actual process of orbital floor fracture visually and computationally in anatomically reconstructed structures and to investigate them using finite element analysis. Methods: A finite element model of the skull and cervical vertebrae was reconstructed from computed tomography data, and an eyeball surrounded by extraocular adipose was modeled in the orbital cavity. Three-dimensional volume mesh was generated using 173,894 of the 4-node hexahedral solid elements. Results: For the cases where the impactor hit the infraorbital foramen, buckling occurred at the orbital bone as a result of the compressive force, and the von Mises stress exceeded 150 MPa. The range of stress components included inferior orbital rim and orbital floor. For the cases where the impactor hit the eyeball first, the orbital bone experienced less stress and the range of stress components limited in orbital floor. The critical speeds for blowout fracture were 4 m/s and 6 m/s for buckling and hydraulic mechanism. Conclusion: Each mechanism has its own fracture inducing energy and its transmission process, type of force causing the fracture, and fracture pattern. It is possible to determine the mechanism of the fracture based on whether an orbital rim fracture is present.