Bilateral Implant-based Breast Reconstruction with Unilateral Radiotherapy: A Matched Cohort Study Comparing Nipple-sparing Mastectomy and Skin-sparing Mastectomy.

Background: Nipple-sparing mastectomy (NSM) preserves the natural nipple-areola complex and entire native breast skin, with the goal of better cosmetic outcomes in breast reconstruction. In bilateral TE/implant-based reconstruction requiring unilateral postmastectomy radiotherapy (PMRT), progressive radiation-induced fibrosis can lead to increasing nipple asymmetry with cosmetic dissatisfaction. Thus, PMRT may ultimately negate the intended positive cosmetic value of NSM compared with skin-sparing mastectomy (SSM). This study compares (1) surgical complications, (2) patient satisfaction, and (3) aesthetic outcomes between NSM versus SSM in bilateral implant-based reconstruction with unilateral PMRT. Methods: This retrospective matched cohort study included consecutive NSM patients with bilateral TE/implant breast reconstruction + unilateral PMRT matched 1:2 to SSM group. Patients completed PMRT and TE exchange to implants. Demographics, oncologic stage, comorbidities, and complications were collected. Patient satisfaction was evaluated by BREAST-Q. Aesthetic outcomes were assessed by blinded reviewers with a five-point Likert scale. Results: Among 58 patients who underwent bilateral TE/implant reconstruction with unilateral PMRT, 17 NSM patients were matched to 41 SSM patients by age, body mass index, and comorbidities. No significant differences existed in overall surgical complications and individual BREAST-Q questionnaire scores between cohorts. However, aesthetic outcomes scores were higher in SSM compared with NSM. Conclusions: Although NSM is generally associated with superior cosmetic outcomes compared with SSM, it has far less impact in bilateral implant-based breast reconstruction with unilateral PMRT due to the negative postradiotherapy effect on nipple symmetry.

High Shear Stress Reduces ERG Causing Endothelial-Mesenchymal Transition and Pulmonary Arterial Hypertension.

Pathological high shear stress (HSS, 100 dyn/cm 2 ) is generated in distal pulmonary arteries (PA) (100-500 µm) in congenital heart defects and in progressive PA hypertension (PAH) with inward remodeling and luminal narrowing. Human PA endothelial cells (PAEC) were subjected to HSS versus physiologic laminar shear stress (LSS, 15 dyn/cm 2 ). Endothelial-mesenchymal transition (EndMT), a feature of PAH not previously attributed to HSS, was observed. H3K27ac peaks containing motifs for an ETS-family transcription factor (ERG) were reduced, as was ERG-Krüppel-like factors (KLF)2/4 interaction and ERG expression. Reducing ERG by siRNA in PAEC during LSS caused EndMT; transfection of ERG in PAEC under HSS prevented EndMT. An aorto-caval shunt was preformed in mice to induce HSS and progressive PAH. Elevated PA pressure, EndMT and vascular remodeling were reduced by an adeno-associated vector that selectively replenished ERG in PAEC. Agents maintaining ERG in PAEC should overcome the adverse effect of HSS on progressive PAH.

In Vitro Assessment of Anti-Adipogenic and Anti-Inflammatory Properties of Black Cumin (Nigella sativa L.) Seeds Extract on 3T3-L1 Adipocytes and Raw264.7 Macrophages.

Background and Objectives: This study evaluated the in vitro anti-adipogenic and anti-inflammatory properties of black cumin (Nigella sativa L.) seed extract (BCS extract) as a potential candidate for developing herbal formulations targeting metabolic disorders. Materials and Methods: We evaluated the BCS extract by assessing its 2,2-diphenyl-1-picrohydrazyl (DPPH) radical scavenging activity, levels of prostaglandin E2 (PGE2) and nitric oxide (NO), and mRNA expression levels of key pro-inflammatory mediators. We also quantified the phosphorylation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinases (MAPK) signaling molecules. To assess anti-adipogenic effects, we used differentiated 3T3-L1 cells and BCS extract in doses from 10 to 100 µg/mL. We also determined mRNA levels of key adipogenic genes, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/BEPα), adipocyte protein 2 (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), and sterol-regulated element-binding protein 1c (SREBP-1c) using real-time quantitative polymerase chain reaction (qPCR). Results: This study showed a concentration-dependent DPPH radical scavenging activity and no toxicity at concentrations up to 30 µg/mL in Raw264.7 cells. BCS extract showed an IC50 of 328.77 ± 20.52 µg/mL. Notably, pre-treatment with BCS extract (30 µg/mL) significantly enhanced cell viability in lipopolysaccharide (LPS)-treated Raw264.7 cells. BCS extract treatment effectively inhibited LPS-induced production of PGE2 and NO, as well as the expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), interleukin (IL)-1ß and IL-6, possibly by limiting the phosphorylation of p38, p65, inhibitory κBα (I-κBα), and c-Jun N-terminal kinase (JNK). It also significantly attenuated lipid accumulation and key adipogenic genes in 3T3-L1 cells. Conclusions: This study highlights the in vitro anti-adipogenic and anti-inflammatory potential of BCS extract, underscoring its potential as a promising candidate for managing metabolic disorders.

Anti-Osteoarthritic Effects of Antarctic Krill Oil in Primary Chondrocytes and a Surgical Rat Model of Knee Osteoarthritis.

Osteoarthritis (OA) is characterized by progressive cartilage destruction and synovitis; however, there are no approved disease-modifying OA drugs. Krill oil (KO) has been reported to possess anti-inflammatory properties and alleviate joint pain in knee OA, indicating its potential to target the inflammatory mechanism of OA. Therefore, the anti-OA effects of KO were investigated in primary chondrocytes and a surgical rat model of knee OA. The oral administration of KO at 200 and 100 mg/kg for 8 weeks improved joint swelling and mobility in the animal model and led to increased bone mineral density and compressive strength in the cartilage. The oral KO doses upregulated chondrogenic genes (type 2 collagen, aggrecan, and Sox9), with inhibition of inflammation markers (5-lipoxygenase and prostaglandin E2) and extracellular matrix (ECM)-degrading enzymes (MMP-2 and MMP-9) in the cartilage and synovium. Consistently, KO treatments increased the viability of chondrocytes exposed to interleukin 1α, accompanied by the upregulation of the chondrogenic genes and the inhibition of the ECM-degrading enzymes. Furthermore, KO demonstrated inhibitory effects on lipopolysaccharide-induced chondrocyte inflammation. Histopathological and immunohistochemical analyses revealed that KO improved joint destruction and synovial inflammation, probably due to the anti-inflammatory, anti-apoptotic, and chondrogenic effects. These findings suggest the therapeutic potential of KO for knee OA.

Krill oil inhibited adipogenic differentiation by inducing the nuclear Nrf2 expression and the AMPK activity.

The current study investigated the antiadipogenic mechanism of krill oil from the 3T3-L1 adipocytes. The krill oil adhered to the criteria as a food standard by showing 50.8% of the total phospholipid, 5.27% myristic acid, and 1.63% linoleic acid. The lipid accumulation that was measured in the 3T3-L1 cells using oil red O staining was reduced up to 54% by the krill oil. The krill oil treatment reduced the adipogenic transcription factors by downregulating the sterol regulatory element binding protein 1 (SREBP1) and acetyl-CoA carboxylase (ACC), phospho-ACC, and AMP-activated protein kinase (AMPK) phosphorylation. The current study confirmed that the krill oil inhibited adipogenesis by downregulating SREBP1 and ACC via the upregulation of the AMPK and nuclear factors E2-related factor 2 (Nrf2) signaling pathway in the 3T3-L1 adipocytes. These findings suggest that krill oil is a good source of phospholipid and phosphatidylcholine, which could be a potential natural antiobesity ingredient by inhibiting adipogenesis.

Characterization of chemoresistant human non-small cell lung cancer cells by metabolic and lipidomic profiling.

INTRODUCTION: Lung cancer is one of the most malignant cancers and the leading cause of cancer-related deaths worldwide, while acquired chemoresistance would represent a major problem in the treatment of non-small cell lung cancer (NSCLC) because of the reduced treatment effect and increased rates of recurrence. METHODS: To establish the chemoresistant NSCLC cells, doxorubicin was treated to A549 cells over 3 months at gradually increasing concentrations from 0.03 to 0.5 µM. Real-time PCR and Western blotting were employed for investigating mRNA and protein expression of the glutathione peroxidase (GPX) protein family and multidrug resistance protein 1 (MRP1) in A549 and A549/CR cells. We also employed gas chromatography mass-spectrometry and nano electrospray ionization mass-spectrometry coupled with multivariate statistical analysis to characterize the unique metabolic and lipidomic profiles of chemoresistant NSCLC cells in order to identify potential therapeutic targets. RESULTS: Reactive oxygen species levels were decreased, and mRNA and protein levels of GPX2 and multidrug resistance protein 1 (MRP1) were increased in A549/CR. We identified 87 metabolites and intact lipid species in A549 and A549/CR. Among these metabolites, lactic acid, glutamic acid, glycine, proline, aspartic acid, succinic acid, and ceramide, alongside the PC to PE ratio, and arachidonic acid-containing phospholipids were suggested as characteristic features of chemoresistant NSCLC cells (A549/CR). CONCLUSIONS: This study reveals characteristic feature differences between drug-resistance NSCLC cells and their parental cells. We suggest potential therapeutic targets in chemoresistant NSCLC. Our results provide new insight into metabolic and lipidomic alterations in chemoresistant NSCLC. This could be used as fundamental information to develop therapeutic strategies for the treatment of chemoresistant NSCLC patients.

Development of Thiol-Ene Reaction-Based HA Hydrogel with Sustained Release of EGF for Enhanced Skin Wound Healing.

This study develops a novel drug delivery system using a hyaluronic acid (HA) hydrogel for controlled release of epidermal growth factor (EGF) to enhance skin wound healing. Conventional hydrogel-based methods suffer from a burst release and limited drug delivery times. To address this, we employ bioconjugation to introduce an acrylate group to EGF, enabling chemical bonding to the HA hydrogel matrix through thiol-ene cross-linking. This approach results in sustained-release delivery of EGF based on the degradation rate of the HA matrix, overcoming diffusion-based limitations. We confirm the introduction of the acrylate group using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. We evaluated the hydrogel morphology and rheological properties following binding of acrylate-conjugated EGF to the HA matrix. Assessment of the EGF release profile demonstrates delayed release compared to unconjugated EGF. We evaluate the impact on cells through cell proliferation and scratch assays, indicating the system's efficacy. In a rat wound healing model, the sustained release of EGF from the hydrogel system promotes appropriate tissue healing and restores it to a normal state. These findings suggest that this practical drug delivery system, involving the modification of growth factors or drugs to chemically bind healing factors to hydrogels, can achieve long-lasting effects.

Krill Oil's Protective Benefits against Ultraviolet B-Induced Skin Photoaging in Hairless Mice and In Vitro Experiments.

Krill oil (KO) shows promise as a natural marine-derived ingredient for improving skin health. This study investigated its antioxidant, anti-inflammatory, anti-wrinkle, and moisturizing effects on skin cells and UVB-induced skin photoaging in hairless mice. In vitro assays on HDF, HaCaT, and B16/F10 cells, as well as in vivo experiments on 60 hairless mice were conducted. A cell viability assay, diphenyl-1-picryhydrazyl (DPPH) radical scavenging activity test, elastase inhibition assay, procollagen content test, MMP-1 inhibition test, and hyaluronan production assay were used to experiment on in vitro cell models. Mice received oral KO administration (100, 200, or 400 mg/kg) once a day for 15 weeks and UVB radiation three times a week. L-Ascorbic acid (L-AA) was orally administered at 100 mg/kg once daily for 15 weeks, starting from the initial ultraviolet B (UVB) exposures. L-AA administration followed each UVB session (0.18 J/cm2) after one hour. In vitro, KO significantly countered UVB-induced oxidative stress, reduced wrinkles, and prevented skin water loss by enhancing collagen and hyaluronic synthesis. In vivo, all KO dosages showed dose-dependent inhibition of oxidative stress-induced inflammatory photoaging-related skin changes. Skin mRNA expressions for hyaluronan synthesis and collagen synthesis genes also increased dose-dependently after KO treatment. Histopathological analysis confirmed that krill oil (KO) ameliorated the damage caused by UVB-irradiated skin tissues. The results imply that KO could potentially act as a positive measure in diminishing UVB-triggered skin photoaging and address various skin issues like wrinkles and moisturization when taken as a dietary supplement.

Hyaluronic acid hydrogel for controlled release of heterobifunctional photocleavable linker-modified epidermal growth factor in wound healing.

Peptide and protein drugs, such as epidermal growth factor (EGF), face challenges related to stability and bioavailability. Recently, hydrogels have emerged as promising carriers for these drugs. This study focuses on a light-responsive hydrogel-based drug delivery system for the controlled release of EGF in wound healing. A photocleavable (PC) linker was designed to bind EGF to the hydrogel matrix, enabling UV light-triggered release of EGF. Hydrogels have evolved from drug reservoirs to controlled release systems, and the o-nitrobenzyl-based PC linkers offer selective cleavage under UV irradiation. We used a thiol-ene crosslinked hyaluronic acid (HA) hydrogel matrix modified with the PC-linked EGF. The release of EGF from the HA hydrogel under UV irradiation was evaluated, along with in vitro and in vivo experiments to assess the controlled effect of EGF on wound healing. Our results indicate that the successful development of a light-responsive hydrogel-based system for precise temporal release of EGF enhances the therapeutic potential in wound healing. This study highlights the importance of incorporating stimulus-responsive functionalities into hydrogel-based drug delivery systems to optimize protein drugs in clinical applications.

Efficacy Confirmation Test of Black Cumin (Nigella sativa L.) Seeds Extract Using a High-Fat Diet Mouse Model.

To deal with the adverse effects associated with the use of currently available treatments for metabolic disorders, such as type 2 diabetes, there is a need to find an alternative drug compound. In the present study, we investigated the therapeutic potential of black cumin (Nigella sativa L.) seeds extract (BCS extract) for type 2 diabetes using a 45% Kcal-fed obese mouse model. The BCS extract at different doses (400-100 mg/kg) showed a dose-dependent improvement tendency in high-fat diet (HFD)-induced obesity, non-alcoholic fatty liver disease (NAFLD), hyperlipidemia, and diabetic nephropathy compared to the metformin (250 mg/kg). In particular, BCS extract at a dose of 200 mg/kg significantly inhibited the HFD-induced metabolic conditions. The oral administration of BCS extract (200 mg/kg) significantly inhibited the oxidative stress through lipid peroxidation, normalized the activity of sugar metabolism-related enzymes and the expression of genes involved in fat metabolism, and inhibited insulin resistance through glucose and fat metabolism by regulating the 5'-AMP-activated protein kinase (AMPK) expression. Furthermore, BCS extract (200 mg/kg) showed renal damage improvement effects compared to the metformin (250 mg/kg). The results clearly show that BCS aqueous extract at an appropriate concentration could help in the treatment of metabolic disorders, and BCS aqueous extract can be used as a functional food for various diabetic complications, such as obesity, diabetes, and NAFLD.

Increased risk of cataract surgery in patients with allergic disease: a population based cohort study.

We investigated the association between cataract and allergic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma using 2,631,015 subjects' data from the 2009 National Health Insurance Service-Health Screening Cohort in Korea. Each allergic disease was defined as three or more occasions of diagnosis within 1 year with dedicated ICD-10 codes. The primary endpoint was newly received cataract surgery during the follow-up period. In total, 447,883 subjects had at least one allergic disease. During the mean follow-up of 7.8 ± 1.7 years, newly developed cataract surgery was observed in 301,693 subjects (allergic group, n = 69,321; non-allergic group, n = 232,372). After adjusting for demographic characteristics (age, sex), systemic and ocular comorbidities, socioeconomic status, and lifestyle factors (smoking, drinking, regular exercise), the allergic group had a higher hazard ratio (HR) for cataract development compared with the non-allergic group. We further performed a subgroup analysis for patients regarding sex and age. In the subgroup analysis of subjects with AD, men aged < 50 years had a higher HR compared to women of the same age group. In conclusion, subjects with allergic diseases had a higher risk of cataract surgery than their counterparts, and the combination of AD and AR resulted in the highest risk. Particularly, the association was more evident in male than female patients with AD aged < 50 years.

Treatment of dural tear with nerve root herniation after unilateral biportal endoscopic decompression using an epidural blood patch: a case report.

We present a case of a dural tear associated with nerve root herniation following unilateral biportal endoscopic decompression (UBED) that was successfully treated using a computed tomography-guided epidural blood patch. A 60-year-old man underwent UBED for radicular pain because of spinal stenosis at L4-5. A left partial hemilaminectomy and flavectomy were performed; however, the left dorsolateral side dura mater was torn during the procedure. TachoComb® was applied at the dural tear site, and the pain was relieved following UBED. However, 3 weeks post-UBED, the patient reported severe pain with an electric shock-like sensation in the left buttock and posterior thigh region with no other neurologic symptoms. The pain was aggravated by standing and spinal motion. Follow-up lumbar spinal magnetic resonance imaging was performed. Axial images indicated protrusion of the left S2 nerve root through the left dorsolateral side of the dura mater. The patient was further diagnosed with nerve root herniation following a dura mater tear. A computed tomography-guided epidural blood patch was performed, with successful therapeutic results. The outcome of this study indicates that a small dural tear that occurs during minimally invasive spinal surgery can be efficiently treated using an epidural blood patch prior to open surgery.

Preventive and Therapeutic Effects of Krill Oil on Obesity and Obesity-Induced Metabolic Syndromes in High-Fat Diet-Fed Mice.

Obesity increases the risks of metabolic syndromes including nonalcoholic fatty liver disease (NAFLD), diabetic dyslipidemia, and chronic kidney disease. Dietary krill oil (KO) has shown antioxidant and anti-inflammatory properties, thereby being a therapeutic potential for obesity-induced metabolic syndromes. Thus, the effects of KO on lipid metabolic alteration were examined in a high-fat diet (HFD)-fed mice model. The HFD model (n = 10 per group) received an oral gavage with distilled water as a control, metformin at 250 mg/kg, and KO at 400, 200, and 100 mg/kg for 12 weeks. The HFD-induced weight gain and fat deposition were significantly reduced in the KO treatments compared with the control. Blood levels were lower in parameters for NAFLD (e.g., alanine aminotransferase, and triglyceride), type 2 diabetes (e.g., glucose and insulin), and renal dysfunction (e.g., blood urea nitrogen and creatinine) by the KO treatments. The KO inhibited lipid synthesis through the modification of gene expressions in the liver and adipose tissues and adipokine-mediated pathways. Furthermore, KO showed hepatic antioxidant activities and glucose lowering effects. Histopathological analyses revealed that the KO ameliorated the hepatic steatosis, pancreatic endocrine/exocrine alteration, adipose tissue hypertrophy, and renal steatosis. These analyses suggest that KO may be promising for inhibiting obesity and metabolic syndromes.

MEK1/2 inhibition rescues neurodegeneration by TFEB-mediated activation of autophagic lysosomal function in a model of Alzheimer's Disease.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder, which is characterized by cognitive deficit due to synaptic loss and neuronal death. Extracellular amyloid ß plaques are one of the pathological hallmarks of AD. The autophagic lysosomal pathway is the essential mechanism to maintain cellular homeostasis by driving clearance of protein aggregates and is dysfunctional in AD. Here, we showed that inhibiting MEK/ERK signaling using a clinically available MEK1/2 inhibitor, trametinib (GSK1120212, SNR1611), induces the protection of neurons through autophagic lysosomal activation mediated by transcription factor EB (TFEB) in a model of AD. Orally administered trametinib recovered impaired neural structures, cognitive functions, and hippocampal long-term potentiation (LTP) in 5XFAD mice. Trametinib also reduced Aß deposition via induction of autophagic lysosomal activation. RNA-sequencing analysis revealed upregulation of autophagic lysosomal genes by trametinib administration. In addition, trametinib inhibited TFEB phosphorylation at Ser142 and promoted its nuclear translocation, which in turn induced autophagic lysosomal related genes, indicating that trametinib activates the autophagic lysosomal process through TFEB activation. From these observations, we concluded that MEK inhibition provides neuronal protection from the Aß burden by increasing autophagic lysosomal activity. Thus, MEK inhibition may be an effective therapeutic strategy for AD.

Neuropathic pain due to compression of cervical medial branch by cervical Juxtafacet cyst: A case report.

In the current report, we describe an interesting case of cervical juxtafacet that developed outside the intervertebral foramen, compressing the cervical medial branch and causing neuropathic pain in the posterior inferior neck pain. A 61-year-old woman visited a local pain clinic due to neuropathic pain with a tingling and burning nature (numeric rating scale [NRS]: 5 out of 10) on the left posterior inferior neck area for 4 months. Paresthesia was observed in the left posterior inferior neck area. On cervical radiography, segmental instability was observed at the C3-4 and C4-5 levels. Moreover, on the magnetic resonance imaging (MRI) of the cervical spine, a cyst (size: 1.3 cm × 0.7 cm × 1 cm) was outside the intervertebral foramen, contacting the left C4-5 facet joint and left C5 articular pillar. We thought that the compression of the left C5 medial branch by the cyst could cause the patient's pain. We conducted computed tomography (CT)-guided percutaneous needle aspiration of a cervical juxtafacet cyst. An 18-gauge needle was advanced under the guidance of CT into the largest portion of the cyst through a posterolateral oblique approach. Gelatinous mucoid fluid (approximately 0.5 cc) was aspirated. Immediately after the aspiration, 80% of the patient's pain was disappeared, and dysesthesia was completely disappeared. At the 1-, 3-, and 6-month follow-ups, the patient reported slight pain (NRS: 1) on the left posterior inferior neck. Cervical juxtafacet cysts can develop outside of the intervertebral foramen and spinal canal. Percutaneous needle aspiration can be a useful therapeutic tool for the treatment of such cysts.

A pilot study on the effect of formulation and individual muscle mass on vitamin C absorption in randomized clinical study.

The current study investigated that the vitamin C absorption in plasma depends on the individual muscle mass and the formulation including drinks (Vita 500), capsules, and tablets by using a randomized and double-blind clinical study. The volunteers were divided into two groups that depended on their muscle mass, including those whose muscle mass was greater than 40% ( ≥ $ \ge $ 40%) and less than 40% muscle mass (<40%). Levels of vitamin C in blood plasma was analyzed by high-performance liquid chromatography by ultraviolet detection (HPLC-UV). The existing HPLC method was modified according to lab conditions but maintained a constantly low pH sample reduction procedure. The analytical method validated stability, linearity, recovery, reliability, and accuracy. The vitamin C absorption was the highest at 120 min after ingesting Vita 500 (21.47 ± 15.99 µmol/L). It was higher in the group that has more than 40% muscle mass compared to other formulations, such as tablets and capsules. The results from the current study indicate that vitamin C formulations differently affect the vitamin C absorption, and its effect depends on the muscle mass. As the results, liquid type vitamin C formulations could enhance vitamin C absorption, which resulted in an improvement of vitamin C absorption according to muscle mass. PRACTICAL APPLICATION: The results of this study may recommend using vitamin C supplementation as liquid type. It may also provide evidence that people with higher muscle mass can absorb vitamin C more efficiently.

Level of interleukin-18 binding protein is significantly different in patients with anaphylaxis than urticaria.

BACKGROUND: Acute urticaria is a common cutaneous disease encountered in children, while anaphylaxis can show cutaneous symptoms as well as systemic symptoms. One study found that urticaria tends to precede anaphylaxis, but studies on the different role of eosinophils and related cytokines in anaphylaxis and urticaria are lacking. OBJECTIVE: The aim of this study was to compare the clinical features, total eosinophil count, serum levels of interleukin (IL)-18, IL-18 binding protein (BP), IL-1 receptor-like (RL) 1, and IL-33 and compare with tryptase to examine if any differences could be found between patients who experienced anaphylaxis and urticaria. METHODS: We included 63 patients with urticaria and 52 patients with anaphylaxis. We measured total eosinophil count and the serum levels of total IgE, tryptase, IL-18, IL-18BP, IL-1RL1, and IL-33, and we compared the differences between the groups. Lastly, receiver operating characteristic curves were constructed to determine which factors accurately diagnosed anaphylaxis. RESULTS: No significant differences were observed in the clinical characteristics or sensitization between urticaria group and anaphylaxis group. Laboratory findings showed that total eosinophil count and IL-18BP were significantly lower in the anaphylaxis group, compared with the urticaria group. IL-18BP showed significant correlation with tryptase. The receiver operating characteristic curve for IL-18BP for diagnosing anaphylaxis had an area under the curve of 0.530. CONCLUSIONS: IL-18BP level was significantly different in patients with anaphylaxis compared to those with urticaria. Serum IL-18BP level may be used to differentiate between the patients with urticaria or anaphylaxis.

One-year changes in the pediatric emergency department caused by prolonged coronavirus disease 2019 pandemic.

BACKGROUND: With the coronavirus disease 2019 (COVID-19) pandemic lasting for more than a year, it is imperative to identify the associated changes in the use of emergency medical care for efficient operation of the pediatric emergency department (PED). This study was conducted to determine the long-term impact of the COVID-19 pandemic on patterns of PED visits. METHODS: This is a retrospective observational study of visits to the PED of six hospitals, between January 1, 2017, and December 31, 2020. We compared changes in the characteristics of patients before and during the COVID-19 pandemic. RESULTS: A total of 245 022 visits were included in this analysis. After the first case of COVID-19 was reported in Korea, we observed a significant decrease (54.2%) in PED visits compared with the annual average number of visits in the previous 3 years. Since then, the weekly number of PED visits decreased by 11.9 person/week (95% CI: -15.3--8.4, P < 0.001), which included an increase of 0.21% (95% CI: 0.15%-0.26%, P < 0.001) per week in high acuity patients. From 2017 to 2020, the proportion of infectious respiratory diseases by year was 25.9%, 27.0%, 28.6%, and 16.3%, respectively, demonstrating a significant decrease in 2020 (P < 0.001). CONCLUSIONS: During the COVID-19 pandemic, the number of patient visits to PEDs continues to decline, especially among those with infectious diseases. However, the disease severity of patients has gradually increased. There has been a change in the characteristics of visits to PEDs after COVID-19 which will require an appropriate response from a long-term perspective.

In vivo biocompatibility evaluation of in situ-forming polyethylene glycol-collagen hydrogels in corneal defects.

The available treatment options include corneal transplantation for significant corneal defects and opacity. However, shortage of donor corneas and safety issues in performing corneal transplantation are the main limitations. Accordingly, we adopted the injectable in situ-forming hydrogels of collagen type I crosslinked via multifunctional polyethylene glycol (PEG)-N-hydroxysuccinimide (NHS) for treatment and evaluated in vivo biocompatibility. The New Zealand White rabbits (N = 20) were randomly grouped into the keratectomy-only and keratectomy with PEG-collagen hydrogel-treated groups. Samples were processed for immunohistochemical evaluation. In both clinical and histologic observations, epithelial cells were able to migrate and form multilayers over the PEG-collagen hydrogels at the site of the corneal stromal defect. There was no evidence of inflammatory or immunological reactions or increased IOP for PEG-collagen hydrogel-treated corneas during the four weeks of observation. Immunohistochemistry revealed the presence of α-smooth muscle actin (α-SMA) in the superior corneal stroma of the keratectomy-only group (indicative of fibrotic healing), whereas low stromal α-SMA expression was detected in the keratectomy with PEG-collagen hydrogel-treated group. Taken together, we suggest that PEG-collagen may be used as a safe and effective alternative in treating corneal defect in clinical setting.

Prepectoral versus subpectoral implant-based breast reconstruction after skin-sparing mastectomy or nipple-sparing mastectomy (OPBC-02/ PREPEC): a pragmatic, multicentre, randomised, superiority trial.

INTRODUCTION: The emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin-sparing or nipple-sparing mastectomy (SSM/ NSM) for breast cancer treatment or prevention. During the same operation, a so-called immediate breast reconstruction is performed. The breast can be reconstructed by positioning of a breast implant above (prepectoral) or below (subpectoral) the pectoralis major muscle or by using the patients' own tissue (autologous reconstruction). The optimal positioning of the implant prepectoral or subpectoral is currently not clear. Subpectoral implant-based breast reconstruction (IBBR) is still standard care in many countries, but prepectoral IBBR is increasingly performed. This heterogeneity in breast reconstruction practice is calling for randomised clinical trials (RCTs) to guide treatment decisions. METHODS AND ANALYSIS: International, pragmatic, multicentre, randomised, superiority trial. The primary objective of this trial is to test whether prepectoral IBBR provides better QoL with respect to long-term (24 months) physical well-being (chest) compared with subpectoral IBBR for patients undergoing SSM or NSM for prevention or treatment of breast cancer. Secondary objectives will compare prepectoral versus subpectoral IBBR in terms of safety, QoL and patient satisfaction, aesthetic outcomes and burden on patients. Total number of patients to be included: 372 (186 per arm). ETHICS AND DISSEMINATION: This study will be conducted in compliance with the Declaration of Helsinki. Ethical approval has been obtained for the lead investigator's site by the Ethics Committee 'Ethikkommission Nordwest- und Zentralschweiz' (2020-00256, 26 March 2020). The results of this study will be published in a peer-reviewed medical journal, independent of the results, following the Consolidated Standards of Reporting Trials standards for RCTs and good publication practice. Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on public repositories adhering to the FAIR (Findability, Accessibility, Interoperability, and Reuse) principles. TRIAL REGISTRATION NUMBER: NCT04293146.