UBE2N is essential for maintenance of skin homeostasis and suppression of inflammation.

UBE2N, a Lys63-ubiquitin conjugating enzyme, plays critical roles in embryogenesis and immune system development and function. However, its roles in adult epithelial tissue homeostasis and pathogenesis are unclear. We generated conditional mouse models that deleted Ube2n in skin cells in a temporally and spatially controlled manner. We found that Ube2n-knockout (KO) in the adult skin keratinocytes induced a range of inflammatory skin defects characteristic of psoriatic and actinic keratosis. These included inflammation, epidermal and dermal thickening, parakeratosis, and increased immune cell infiltration, as well as signs of edema and blistering. Single cell transcriptomic analyses and RT-qPCR showed that Ube2n KO keratinocytes expressed elevated myeloid cell chemo-attractants such as Cxcl1 and Cxcl2 and decreased the homeostatic T lymphocyte chemo-attractant Ccl27a. Consistently, the infiltrating immune cells were predominantly myeloid-derived cells including neutrophils and M1-like macrophages that expressed high levels of inflammatory cytokines such as Il1ß and Il24. Pharmacological blockade of the IL-1 receptor associated kinases (IRAK1/4) alleviated inflammation, epidermal and dermal thickening, and immune infiltration of the Ube2n mutant skin. Together, these findings highlight a key role of keratinocyte-UBE2N in maintenance of epidermal homeostasis and skin immunity, and identify IRAK1/4 as potential therapeutic target for inflammatory skin disorders.

Effectiveness of a healthy lifestyle program based on a mobile serious game for childhood cancer survivors: A quasi-randomized trial.

PURPOSE: This study aimed to develop and evaluate the effectiveness of a healthy lifestyle program based on a mobile serious game (HLP-MSG) to enhance the lifestyles of childhood cancer survivors (CCSs). METHODS: This program proceeded in two stages: development and evaluation, using a non-synchronized design with a quasi-randomized trial. The participants were CCSs aged 6-13 years whose treatment was terminated at least 12 months prior. Data were collected at baseline, and post-intervention, with a follow-up after four weeks using the Child Healthy Lifestyle Profile (CHLP). The experimental (n = 26) and control groups (n = 25) were compared. Data were analyzed using descriptive statistics, chi-squared tests, t-tests, and repeated-measures ANOVA. RESULTS: The HLP-MSG promoted a healthy lifestyle by solving 26 quests, including seven sub-elements (nutrition, exercise, hygiene, interpersonal relationships, stress management, meaning of life, and health responsibility). This study revealed significant differences in the interaction between measurement time and group assignment in the CHLP (p = .006) and physical activity (p = .013), one of the seven sub-dimensions. CONCLUSIONS: A healthy lifestyle program based on a mobile serious game is a feasible health education modality to enhance the physical, psychological, social, and spiritual health of CCSs. IMPLICATIONS TO PRACTICE: The findings add to scientific evidence on a mobile serious game for health education among CCSs. The HLP-MSG provides an evolutionary educational modality that can be delivered non-face-to-face to promote CCSs' continuous healthy behavior maintenance. Moreover, the HLP-MSG is adolescent-friendly and can be utilized as a healthcare tool for parents and children to cooperate.

Triglyceride-glucose index predicts type 2 diabetes mellitus more effectively than oral glucose tolerance test-derived insulin sensitivity and secretion markers.

AIMS: We explored the role of the triglyceride-glucose (TyG) index as an early and superior predictor of type 2 diabetes mellitus (T2DM) in individuals with normal glucose tolerance (NGT) using a community-based Korean cohort over 18 years. METHODS: We retrospectively examined 6,072 adults with NGT from the Korean Genome and Epidemiology Study. Cox proportional hazard regression models were employed to evaluate the risk of incidence of T2DM and receiver operating characteristic analysis was used to calculate the area under the curve (AUC). RESULTS: At baseline, the TyG index correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) and the composite insulin sensitivity index (ISI) (ß: 0.045, p < 0.001; ß: -0.105, p < 0.001, respectively). Over the 18-year follow-up period, 999 individuals developed T2DM. An increase in the TyG quartile independently predicted the incidence of T2DM [hazard ratio, 2.36 (1.9-2.93) for Q4]. The AUC value of the TyG index was 0.642, the highest value among HOMA-IR and OGTT-derived insulin sensitivity and secretion markers. CONCLUSIONS: The TyG index is associated with HOMA-IR and composite ISI even with NGT. The TyG index demonstrated independent predictability for T2DM incidence in individuals with NGT, better than OGTT-derived insulin sensitivity and secretion markers.

Efficacy of Supplemental Ultrasound-Guided Pericapsular Nerve Group (PENG) Block Combined with Lateral Femoral Cutaneous Nerve Block in Patients Receiving Local Infiltration Analgesia after Hip Fracture Surgery: A Prospective Randomized Controlled Trial.

Background and Objectives: Local infiltration analgesia (LIA) represents a potential approach to reducing pain in patients undergoing total hip arthroplasty (THA). The pericapsular nerve group (PENG) block also provides adequate analgesia for fractures and THA. As most hip surgeries use a lateral incision, affecting the cutaneous supply by branches of the lateral femoral cutaneous nerve (LFCN), the LFCN block can contribute to postoperative analgesia. However, no studies have investigated the effectiveness of supplemental PENG block combined with LFCN block in patients undergoing LIA after hip fracture surgery. Our study aimed to assess the effectiveness of PENG combined with LFCN block following hip fracture surgery in patients who underwent LIA. Materials and Methods: Forty-six patients were randomly assigned to LIA or PENG + LFCN + LIA groups. The primary outcome was the pain score at rest and during movement at 2, 6, 12, 24, and 48 h postoperatively. The total opioid dose for postoperative analgesia was also measured at the same time points. Secondary outcomes included postoperative cognitive function assessment. Results: The median pain scores at rest and during movement were lower in the PENG + LFCN + LIA group throughout the study periods compared to the LIA group, except at 2 h (at rest) and 48 h (during movement) after surgery. The total fentanyl dose was lower in the PENG + LFCN + LIA group at all time points after surgery when compared to the LIA group. Postoperative delirium incidence and the median abbreviated mental test scores were not significantly different between the two groups. Conclusions: The combination of PENG and LFCN blocks may contribute to enhanced recovery for patients undergoing LIA after hip fracture surgery. However, further well-controlled research is necessary to determine the effectiveness of supplemental PENG combined with LFCN block in addressing cognitive deficits in these patients.

UBE2N is essential for maintenance of skin homeostasis and suppression of inflammation.

UBE2N, a Lys63-ubiquitin conjugating enzyme, plays critical roles in embryogenesis and immune system development and function. However, its roles in adult epithelial tissue homeostasis and pathogenesis are unclear. We generated conditional mouse models that deleted Ube2n in skin cells in a temporally and spatially controlled manner. We found that Ube2n-knockout (KO) in the adult skin keratinocytes induced a range of inflammatory skin defects characteristic of psoriatic and actinic keratosis. These included eczematous inflammation, epidermal and dermal thickening, parakeratosis, and increased immune cell infiltration, as well as signs of edema and blistering. Single cell transcriptomic analyses and RT-qPCR showed that Ube2n KO keratinocytes expressed elevated myeloid cell chemo-attractants such as Cxcl1 and Cxcl2 and decreased the homeostatic T lymphocyte chemo-attractant, Ccl27a. Consistently, the infiltrating immune cells of Ube2n-KO skin were predominantly myeloid-derived cells including neutrophils and M1-like macrophages that were highly inflammatory, as indicated by expression of Il1ß and Il24. Pharmacological blockade of the IL-1 receptor associated kinases (IRAK1/4) alleviated eczema, epidermal and dermal thickening, and immune infiltration of the Ube2n mutant skin. Together, these findings highlight a key role of keratinocyte-UBE2N in maintenance of epidermal homeostasis and skin immunity and identify IRAK1/4 as potential therapeutic target for inflammatory skin disorders.

Automated lung tumor segmentation robust to various tumor sizes using a consistency learning-based multi-scale dual-attention network.

BACKGROUND: It is often difficult to automatically segment lung tumors due to the large tumor size variation ranging from less than 1 cm to greater than 7 cm depending on the T-stage. OBJECTIVE: This study aims to accurately segment lung tumors of various sizes using a consistency learning-based multi-scale dual-attention network (CL-MSDA-Net). METHODS: To avoid under- and over-segmentation caused by different ratios of lung tumors and surrounding structures in the input patch according to the size of the lung tumor, a size-invariant patch is generated by normalizing the ratio to the average size of the lung tumors used for the training. Two input patches, a size-invariant patch and size-variant patch are trained on a consistency learning-based network consisting of dual branches that share weights to generate a similar output for each branch with consistency loss. The network of each branch has a multi-scale dual-attention module that learns image features of different scales and uses channel and spatial attention to enhance the scale-attention ability to segment lung tumors of different sizes. RESULTS: In experiments with hospital datasets, CL-MSDA-Net showed an F1-score of 80.49%, recall of 79.06%, and precision of 86.78%. This resulted in 3.91%, 3.38%, and 2.95% higher F1-scores than the results of U-Net, U-Net with a multi-scale module, and U-Net with a multi-scale dual-attention module, respectively. In experiments with the NSCLC-Radiomics datasets, CL-MSDA-Net showed an F1-score of 71.7%, recall of 68.24%, and precision of 79.33%. This resulted in 3.66%, 3.38%, and 3.13% higher F1-scores than the results of U-Net, U-Net with a multi-scale module, and U-Net with a multi-scale dual-attention module, respectively. CONCLUSIONS: CL-MSDA-Net improves the segmentation performance on average for tumors of all sizes with significant improvements especially for small sized tumors.

The Ratio of Estimated Glomerular Filtration Rate Based on Cystatin C and Creatinine Reflecting Cardiovascular Risk in Diabetic Patients.

BACKGROUND: The ratio of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcystatin C/eGFRcreatinine ratio) is related to accumulating atherosclerosis-promoting proteins and increased mortality in several cohorts. METHODS: We assessed whether the eGFRcystatin C/eGFRcreatinine ratio is a predictor of arterial stiffness and sub-clinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, who were followed up during 2008 to 2016. GFR was estimated using an equation based on cystatin C and creatinine. RESULTS: A total of 860 patients were stratified according to their eGFRcystatin C/eGFRcreatinine ratio (i.e., <0.9, 0.9-1.1 [a reference group], and >1.1). Intima-media thickness was comparable among the groups; however, presence of carotid plaque was frequent in the <0.9 group (<0.9 group, 38.3%; 0.9-1.1 group, 21.6% vs. >1.1 group, 17.2%, P<0.001). Brachial-ankle pulse wave velocity (baPWV) was faster in the <0.9 group (<0.9 group, 1,656.3±333.0 cm/sec; 0.9-1.1 group, 1,550.5±294.8 cm/sec vs. >1.1 group, 1,494.0±252.2 cm/sec, P<0.001). On comparing the <0.9 group with the 0.9-1.1 group, the multivariate-adjusted odds ratios of prevalence of high baPWV and carotid plaque were 2.54 (P=0.007) and 1.95 (P=0.042), respectively. Cox regression analysis demonstrated near or over 3-fold higher risks of the prevalence of high baPWV and carotid plaque in the <0.9 group without chronic kidney disease (CKD). CONCLUSION: We concluded that eGFRcystatin C/eGFRcreatinine ratio <0.9 was related to an increased risk of high baPWV and carotid plaque in T2DM patients, especially, those without CKD. Careful monitoring of cardiovascular disease is needed for T2DM patients with low eGFRcystatin C/eGFRcreatinine ratio.

Inter-Slice Resolution Improvement Using Convolutional Neural Network with Orbital Bone Edge-Aware in Facial CT Images.

The 3D modeling of orbital bones in facial CT images is essential to provide a customized implant for reconstructions of orbit and related structures during surgery. However, 3D models of the orbital bone show an aliasing effect and disconnected thin bone in the inter-slice direction because the slice thickness is two to three times larger than the pixel spacing. To improve the inter-slice resolution of facial CT images, we propose a method based on a 2D convolutional neural network (CNN) that uses the spatial information on the sagittal and axial planes and the orbital bone edge-aware (OBE) loss. First, intermediate slices are generated on the sagittal plane. Second, the generated intermediate slices are transformed to an axial image, which is then compared with the original axial image. To generate intermediate slices with an accurate orbital bone structure, the OBE loss considering the orbital bone structure on the sagittal and axial planes is used. To improve the perceptual quality of the generated intermediate slices, the feature map difference loss is additionally used on the axial plane. In the experiment, the proposed method showed the best performance among bilinear and bicubic interpolations, 3D SRGAN, and a 2D CNN-based method. Experimental results confirmed that the proposed method can generate intermediate slices with clear edges of thin bones as well as cortical bones on both the sagittal and the axial plane.

Low relative hand grip strength is associated with a higher risk for diabetes and impaired fasting glucose among the Korean population.

OBJECTIVE: This study investigated the association between relative hand grip strength (HGS) and glycemic status, such as impaired fasting glucose (IFG) and diabetes, using data from the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: We performed a cross-sectional study using the data from the KNHANES of 27,894 individuals from 2014 to 2019. Relative HGS was defined as the absolute HGS divided by body mass index and divided into quartiles in men and women. Odds ratios (OR) for diabetes and IFG were calculated using multivariate logistic regression analysis. All analyses were stratified by sex, and subgroup analysis was age-stratified. RESULTS: The lowest relative HGS quartile had a significant increase in the risk for diabetes (men: OR 2.72, 95% confidence interval [CI] 2.12-3.50; women: OR 3.38, 95% CI 2.70-4.24) and IFG (men: OR 1.35, 95% CI 1.15-1.59; women: OR 1.60, 95% CI 1.40-1.84). The ORs for diabetes and IFG according to the decreasing quartiles of relative HGS gradually increased in both sexes (P for trend <0.001). ORs and 95% CI of the lowest relative HGS quartile for diabetes were higher in the younger age group than that of the older age group (men: 4.47 and 2.80-7.14 for young adults; 2.41 and 1.37-4.25 for older adults; women: 5.91 and 3.06-9.38 for young adults; 1.47 and 0.92-2.33 for older adults). ORs and 95% CI for IFG was similar with the trend of ORs for diabetes (men: 1.80 and 1.43-2.26 for young adults; 1.17 and 0.75-1.84 for older adults; women: 2.20 and 1.77-2.72 for young adults; 1.33 and 0.86-2.07 for older adults). CONCLUSION: Lower relative HGS was associated with a higher risk of not only diabetes but also IFG in both sexes. These trends were stronger in younger adults than in older adults.

Comparison of radiation exposure to physicians between anteroposterior and lateral real-time fluoroscopy when performing lumbar transforaminal epidural steroid injections: A randomized controlled trial.

BACKGROUND: Lumbar transforaminal epidural steroid injections are used widely to alleviate low back radicular pain, but it requires real-time fluoroscopy, which can increase the risk of radiation exposure. Anteroposterior or lateral real-time fluoroscopy can be used during lumbar transforaminal epidural steroid injections, but there have been no comparative studies on the exposure of physicians to radiation from anteroposterior or lateral real-time fluoroscopy. The aim of this study was to compare the cumulative radiation exposure to each body part of the physician according to the method of real-time fluoroscopy when performing lumbar transforaminal epidural steroid injections. METHODS: A single physician performed lumbar transforaminal epidural steroid injections, and 2 groups of patients were formed based on the method used: group A (anteroposterior real-time fluoroscopy) and group L (lateral real-time fluoroscopy). Dosimeters were placed outside the chest, inside the chest, outside the thyroid collar, inside the thyroid collar, outside the groin, inside the groin, outside the lead gloves, and left rim of the glasses. RESULTS: A total of 200 lumbar transforaminal epidural steroid injections were analyzed, and the radiation exposure was measured by cumulative dose equivalents in mSv. The dose equivalents were lower at every level in group A compared with group L except for outside the groin. CONCLUSIONS: The cumulative radiation exposure at all the measurement sites was lower for anteroposterior real-time fluoroscopy compared with lateral real-time fluoroscopy when performing lumbar transforaminal epidural steroid injections, except for outside the groin.

Synergistic Interaction between Hyperuricemia and Abdominal Obesity as a Risk Factor for Metabolic Syndrome Components in Korean Population.

BACKGROUND: The present study investigated the role of synergistic interaction between hyperuricemia and abdominal obesity as a risk factor for the components of metabolic syndrome. METHODS: We performed a cross-sectional study using the data of 16,094 individuals from the seventh Korean National Health and Nutrition Examination Survey (2016 to 2018). The adjusted odds ratios of metabolic syndrome and its components were analyzed by multivariate logistic regression analysis. The presence of synergistic interaction between hyperuricemia and abdominal obesity was evaluated by calculating the additive scales-the relative excess risk due to interaction, attributable proportion due to interaction, and synergy index (SI). RESULTS: There was a synergistic interaction between hyperuricemia and abdominal obesity in hypertriglyceridemia (men: SI, 1.39; 95% confidence interval [CI], 1.01 to 1.98; women: SI, 1.61; 95% CI, 1.02 to 2.69), and low high-density lipoprotein cholesterol (HDL-C) (men: SI, 2.03; 95% CI, 1.41 to 2.91; women: SI, 1.70; 95% CI, 1.05 to 2.95). There was no significant synergistic interaction between hyperuricemia and abdominal obesity for the risk of high blood pressure (men: SI, 1.22; 95% CI, 0.85 to 1.77; women: SI, 1.53; 95% CI, 0.79 to 2.97), and hyperglycemia (men: SI, 1.03; 95% CI, 0.72 to 1.47; women: SI, 1.39; 95% CI, 0.75 to 2.57). CONCLUSION: Hyperuricemia and abdominal obesity synergistically increased the risk of hypertriglyceridemia and low HDL-C in both sexes.

Skin Injury Activates a Rapid TRPV1-Dependent Antiviral Protein Response.

The skin serves as the interface between the body and the environment and plays a fundamental role in innate antimicrobial host immunity. Antiviral proteins (AVPs) are part of the innate host defense system and provide protection against viral pathogens. How breach of the skin barrier influences innate AVP production remains largely unknown. In this study, we characterized the induction and regulation of AVPs after skin injury and identified a key role of TRPV1 in this process. Transcriptional and phenotypic profiling of cutaneous wounds revealed that skin injury induces high levels of AVPs in both mice and humans. Remarkably, pharmacologic and genetic ablation of TRPV1-mediated nociception abrogated the induction of AVPs, including Oas2, Oasl2, and Isg15 after skin injury in mice. Conversely, stimulation of TRPV1 nociceptors was sufficient to induce AVP production involving the CD301b+ cells‒IL-27‒mediated signaling pathway. Using IL-27 receptor‒knockout mice, we show that IL-27 signaling is required in the induction of AVPs after skin injury. Finally, loss of TRPV1 signaling leads to increased viral infectivity of herpes simplex virus. Together, our data indicate that TRPV1 signaling ensures skin antiviral competence on wounding.

Association between serum uric acid and relative hand grip strength in comparison with metabolic syndrome components.

Objectives: To investigate the association between serum uric acid (UA) and relative hand grip strength (HGS) in comparison with metabolic syndrome components. Methods: We analyzed the data of 5247 Korean adults aged ≥ 20 years (2422 men and 2825 women) who participated in the KNHNES VII (2018). Results: Among women, relative HGS was significantly lower in participants with hyperuricemia (1.65 ± 0.04) than in those without (1.95 ± 0.01) and was significantly decreased in the highest quartile (4Q: 1.77 ± 0.02) of serum UA compared with that in the lowest quartile (1Q: 1.98 ± 0.02). Among men, relative HGS was lower in participants with hyperuricemia (3.09 ± 0.04 vs. 3.16 ± 0.02) and decreased in 4Q (3.08 ± 0.03) of serum UA compared with that in 1Q (3.15 ± 0.03); however, these results were not statistically significant. In age- and multivariate-adjusted analyses in men, relative HGS was significantly lower in 4Q compared with that in 1Q in model 1 (adjusted for age), but there were no significant differences in model 2 (adjusted for age, BMI, and waist circumference) and model 3 (adjusted for age, BMI, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, triglycerides, and high-density lipoprotein cholesterol). Meanwhile, in women, relative HGS was significantly decreased in 4Q compared with that in 1Q in all models. Conclusions: A significant inverse correlation was observed between serum UA levels and relative HGS in women, and their significance was maintained even after adjusting for age and metabolic syndrome components.

IL-27 Derived From Macrophages Facilitates IL-15 Production and T Cell Maintenance Following Allergic Hypersensitivity Responses.

Crosstalk between T cells, dendritic cells, and macrophages in temporal leukocyte clusters within barrier tissues provides a new concept for T cell activation in the skin. Activated T cells from these leukocyte clusters play critical roles in the efferent phase of allergic contact hypersensitivity (CHS). However, the cytokines driving maintenance and survival of pathogenic T cells during and following CHS remain mostly unknown. Upon epicutaneous allergen challenge, we here report that macrophages produce IL-27 which then induces IL-15 production from epidermal keratinocytes and dermal myeloid cells within leukocyte clusters. In agreement with the known role of IL-15 as a T cell survival factor and growth cytokine, this signaling axis enhances BCL2 and survival of skin T cells. Genetic depletion or pharmacological blockade of IL-27 in CHS mice leads to abrogated epidermal IL-15 production resulting in a decrease in BCL2 expression in T cells and a decline in dermal CD8+ T cells and T cell cluster numbers. These findings suggest that the IL-27 pathway is an important cytokine for regulating cutaneous T cell immunity.

Prenatal diagnosis of de novo DMD duplication by multiplex ligation-dependent probe amplification (MLPA) after noninvasive prenatal screening (NIPS) at 11 gestational weeks.

OBJECTIVE: Dystrophinopathy is an X-linked recessive muscular dystrophy caused by mutations in the DMD gene. Herein we describe the prenatal detection of DMD gene mutations in a patient with no family history, by multiplex ligation-dependent probe amplification (MLPA) after noninvasive prenatal screening (NIPS). CASE REPORT: A 41-year-old woman underwent NIPS owing to an advanced maternal age. A copy number variation was detected in the maternal X chromosome, and uninformative results were obtained for the fetal sex chromosomes. Following amniocentesis, a duplication was identified in exons 1-29 of the dystrophin gene by MLPA. After interviewing her family members it was confirmed that the patient is a de novo carrier of DMD duplications, and her daughter is a carrier of the same mutation. CONCLUSION: his is the first case report to describe the prenatal diagnosis of duplications in the DMD gene by MLPA following NIPS in a patient with no family history.

Fabrication of Durable Ni-YSZ Hydrogen Electrode for High-Temperature Solid Electrolyzer Cells.

Solid oxide electrolyzer cells with an Ni-Fe-yttria-stabilized zirconia (Ni-Fe-YSZ) hydrogen electrode as the cathode, lanthanum strontium ferrite (LSCF)-gadolinia-doped ceria (GDC) air electrode as the anode, and YSZ as the electrolyte were fabricated, and the oxidation protection effect of sacrificial Fe particles was investigated. X-ray diffraction analysis indicated that Ni was protected from oxidation under a water vapor atmosphere by sacrificial Fe. Scanning electron microscopy observations suggested that the Ni particles accumulated in the Ni-YSZ hydrogen electrode, which might have been associated with the partial oxidation of Ni during cell operation at 700 °C in 50% H2O/15% H2/35% Ar atmosphere. No appreciable microstructural changes were observed for the Ni-Fe-YSZ hydrogen electrode. Furthermore, the presence of the sacrificial Fe particles could be responsible for the superior durability of the cell, compared with that of the cell featuring the conventional Ni-YSZ hydrogen electrode.

Role of tenofovir disoproxil fumarate in prevention of perinatal transmission of hepatitis B virus from mother to child: a systematic review and meta-analysis.

BACKGROUND/AIMS: To prevent the perinatal transmission of hepatitis B virus (HBV) from mother to child, administration of an antiviral agent during pregnancy has been attempted in women who are either hepatitis B e antigen positive or have a high viral load. In this systematic review and meta-analysis with randomized controlled trials, we analyzed the efficacy and safety of tenofovir disoproxil fumarate (TDF) in preventing the perinatal transmission of HBV in pregnant women who have high HBV DNA titers. METHODS: Multiple comprehensive databases (PubMed, EMBASE, and Cochrane databases) were searched for studies evaluating the efficacy of TDF for the prevention of perinatal transmission of HBV. RESULTS: Two studies (one open label study and one double blind study) were included and analyzed. Intention-to-treat analysis (527 pregnancies) showed that the preventive effect of TDF was not significant (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.13 to 2.17; p = 0.38, I2 = 81%). However, the per-protocol analysis showed that TDF significantly reduced perinatal transmission (OR, 0.10; 95% CI, 0.01 to 0.77; p = 0.03, I2 = 0%). There was no significant difference between the TDF group and the control group with respect to maternal and fetal safety outcomes. CONCLUSION: In pregnant women who have high HBV DNA titers, TDF can reduce the perinatal transmission from mother to child without significant adverse events.

Real-world systemic sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Korea.

Background/Aims Regorafenib has been approved as a second-line systemic therapy for hepatocellular carcinoma (HCC) patients after the phase III RESORCE trial. This study analyzed real-world data to assess the clinical effectiveness and safety of regorafenib compared to the RESORCE trial. Methods This multicenter cohort study included HCC patients treated with regorafenib after sorafenib (n = 133). We evaluated the time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety in patients receiving regorafenib along with the predictors of prognosis. Results The median age was 60 years and 81.2% patients were men. Hepatitis B virus infection (68.4%) was the commonest etiology. Most patients were classified as Child-Pugh A (98.5%) and had extrahepatic metastasis (84%) and vascular invasion (45.1%). This study demonstrated similar characteristics apart from more frequent hepatitis B etiology and more vascular or extrahepatic involvement compared with the RESORCE trial. An objective response rate of 12.5% was obtained for response assessment (n = 112); the disease control rate was 34.8%. Thirty-eight patients died during follow-up. With regorafenib, the median OS, PFS, and TTP were 10.0, 2.7, and 2.6 months, respectively. In the exploratory analysis after sorafenib administration, the median OS was 25.8 months. The rate of response and survival were comparable to those in the RESORCE trial. Child-Pugh score > 5, alpha-fetoprotein > 400 ng/ml, and TTP for sorafenib ≥ median were independently associated with OS. Conclusions This real-word regorafenib study showed comparable effectiveness and safety to the RESORCE trial. Regorafenib improves the prognosis of patients with prolonged TTP during previous sorafenib therapy.

Optimization Protocol of Fixation Method for Trophoblast Retrieval from the Cervix (TRIC): A Preliminary Study.

Extravillous trophoblast cells (EVTs) secreted by the uterine cavity may help overcome limitations associated with prenatal testing currently in use. EVTs are isolated using a routine safe liquid-based Pap test (called ThinPrep); however, the ThinPrep solution contains alcohol that hinders the isolation of intact EVTs. We compared the trophoblastic cell isolation efficiency of two different methods of fixation: Thinprep (pre-fixation method) and formalin (post-fixation method). We analyzed EVTs from 20 pregnant women (5-20 weeks of gestation) who underwent invasive prenatal testing. The percentages of placental ß-human chorionic gonadotropin (ß-hCG)-expressing cells were calculated. The presence of XY chromosomes were used to confirm pure trophoblast cells by fluorescence in situ hybridization. The ß-hCG-positive cells obtained from pre- and post-fixation were 66.4 ± 13.3% and 83.2 ± 8.1% (p = 0.003), respectively, and fluorescence-positive cells were 11.1 ± 2.1% and 23.8 ± 4.8%, respectively (p = 0.001). Post-fixation was found to be more efficient in isolating non-trophoblast cells than pre-fixation. For the successful clinical application of trophoblast retrieval and isolation from the cervix in prenatal genetic testing, each step should be optimized for consistent and reliable results.