Detecting T-cell receptor clonality in patients with severe atopic dermatitis refractory to dupilumab.

BACKGROUND: Trials and real-life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis (AD) treated with the anti-IL-4RA-antibody dupilumab. However, misdiagnosis or confounding skin diseases in particular cutaneous T-cell lymphoma (CTCL) may lead to inadequate response. OBJECTIVE: To investigate the clinical and pathological features of patients with AD who showed insufficient response to dupilumab. METHODS: We reviewed the medical records of 371 patients treated with dupilumab for severe AD. Insufficient response was defined as failure to achieve an improvement of the eczema area severity index (EASI) of at least 50% (EASI-50) at Week 16 and of 75% (EASI-75) at Week 52. Among 46 patients with insufficient response, 35 patients consented to a re-evaluation including a full physical exam, biopsies and laboratory assessments including immunohistochemistry and T-cell receptor gene rearrangement analysis to differentiate CTCL. RESULTS: Of the 371 patients treated with dupilumab, 46 (12.3%) patients showed insufficient response to dupilumab. Of these, 35 underwent further evaluation, and 19 (54.2% of inadequate responders) were finally diagnosed with mycosis fungoides (MF). In these patients, transition to or addition of conventional MF treatment led to clinical improvements. CONCLUSION: Insufficient response to dupilumab treatment may help uncover early MF on an existing AD background.

Quantification of steal flow on Doppler ultrasound in patients with arteriovenous graft for hemodialysis.

PURPOSE: Arteriovenous fistula (AVF) is the preferred treatment for long-term hemodialysis patients to allow reliable vascular access. Arteriovenous graft (AVG) is monitored using Doppler sonography to check a vessel's condition and predict complications such as steal syndrome. In this study, we developed an analysis algorithm and method to quantify steal syndrome using Doppler sonography. METHODS: Doppler sonography was used to determine the pattern of anterograde and retrograde flow. The ratio of blood volumes was calculated with a vision analysis software. First, performance of the developed algorithm was validated by comparing it with commercial Doppler sonography data. Doppler sonography was performed for an artificial vessel to analyze the steal flow. RESULTS: A total of 58 patients with steal flow were enrolled in this study. Of these patients, 23 did not have a difference in fingertip temperature between both sides. The median difference in temperature of 35 patients was 0.8°C (range, 0.3-1.9°C). The ratio of retrograde flow volume/antegrade flow volume in patients with the presence of temperature difference was significantly higher compared to that in patients without the temperature difference (p < .001). The ROC curve for the difference in flow volume had an AUC of 0.770. The optimal cutoff of difference in the flow volume between the two groups was 0.24 (sensitivity of 91.4 % and specificity of 52.2%). The flow volume difference was significantly positively correlated to temperature difference (r = 0.487, p < .003). CONCLUSION: Our algorithm could measure steal flow volume of a bidirectional waveform by antegrade arterial flow and retrograde reversal flow.

Optimizing Rehabilitation Outcomes for Stroke Survivors: The Impact of Speed and Slope Adjustments in Anti-Gravity Treadmill Training.

Background and Objectives: This study explored the efficacy of customized anti-gravity treadmill (AGT) training, with adjustments in speed and incline, on rehabilitation outcomes for stroke patients, focusing on knee extensor muscle strength, joint angle, balance ability, and activities of daily living (ADLs). Materials and Methods: In this study, 30 individuals diagnosed with a stroke were divided into three groups. Experimental group 1 (EG1) underwent training without changes to speed and incline, experimental group 2 (EG2) received training with an increased incline, and experimental group 3 (EG3) underwent training with increased speed. Initially, all participants received AGT training under uniform conditions for two weeks. Subsequently, from the third to the sixth week, each group underwent their specified training intervention. Evaluations were conducted before the intervention and six weeks post-intervention using a manual muscle strength tester for knee strength, TETRAX for balance ability, Dartfish software for analyzing knee angle, and the Korean version of the Modified Barthel Index (K-MBI) for assessing activities of daily living. Results: Within-group comparisons revealed that AGT training led to enhancements in muscle strength, balance ability, joint angle, and ADLs across all participant groups. Between-group analyses indicated that EG2, which underwent increased incline training, demonstrated significant improvements in muscle strength and balance ability over EG1. EG3 not only showed significant enhancements in muscle strength, joint angle, and ADLs when compared to EG1 but also surpassed EG2 in terms of knee strength improvement. Conclusions: In conclusion, the application of customized AGT training positively impacts the rehabilitation of stroke patients, underscoring the importance of selecting a treatment method tailored to the specific needs of each patient.

A Comprehensive Review: Robot-Assisted Treatments for Gait Rehabilitation in Stroke Patients.

Robot-assisted gait training (RAGT) is at the cutting edge of stroke rehabilitation, offering a groundbreaking method to improve motor recovery and enhance the quality of life for stroke survivors. This review investigates the effectiveness and application of various RAGT systems, including both end-effector and exoskeleton robots, in facilitating gait enhancements. The selection process for this comprehensive analysis involved a meticulous review of the literature from databases such as PubMed, the Cochrane Library, and EMBASE, focusing on studies published between 2018 and 2023. Ultimately, 27 studies met the criteria and were included in the final analysis. The focus of these studies was on the various RAGT systems and their role in promoting gait and balance improvements. The results of these studies conclusively show that patients experience significant positive effects from RAGT, and when combined with other physiotherapy methods, the outcomes are notably superior in enhancing functional ambulation and motor skills. This review emphasizes RAGT's capability to deliver a more customized and effective rehabilitation experience, highlighting the importance of tailoring interventions to meet the specific needs of each patient.

General Treatments Promoting Independent Living in Parkinson's Patients and Physical Therapy Approaches for Improving Gait-A Comprehensive Review.

This study delves into the multifaceted approaches to treating Parkinson's disease (PD), a neurodegenerative disorder primarily affecting motor function but also manifesting in a variety of symptoms that vary greatly among individuals. The complexity of PD symptoms necessitates a comprehensive treatment strategy that integrates surgical interventions, pharmacotherapy, and physical therapy to tailor to the unique needs of each patient. Surgical options, such as deep brain stimulation (DBS), have been pivotal for patients not responding adequately to medication, offering significant symptom relief. Pharmacotherapy remains a cornerstone of PD management, utilizing drugs like levodopa, dopamine agonists, and others to manage symptoms and, in some cases, slow down disease progression. However, these treatments often lead to complications over time, such as motor fluctuations and dyskinesias, highlighting the need for precise dosage adjustments and sometimes combination therapies to optimize patient outcomes. Physical therapy plays a critical role in addressing the motor symptoms of PD, including bradykinesia, muscle rigidity, tremors, postural instability, and akinesia. PT techniques are tailored to improve mobility, balance, strength, and overall quality of life. Strategies such as gait and balance training, strengthening exercises, stretching, and functional training are employed to mitigate symptoms and enhance functional independence. Specialized approaches like proprioceptive neuromuscular facilitation (PNF), the Bobath concept, and the use of assistive devices are also integral to the rehabilitation process, aimed at improving patients' ability to perform daily activities and reducing the risk of falls. Innovations in technology have introduced robotic-assisted gait training (RAGT) and other assistive devices, offering new possibilities for patient care. These tools provide targeted support and feedback, allowing for more intensive and personalized rehabilitation sessions. Despite these advancements, high costs and accessibility issues remain challenges that need addressing. The inclusion of exercise and activity beyond structured PT sessions is encouraged, with evidence suggesting that regular physical activity can have neuroprotective effects, potentially slowing disease progression. Activities such as treadmill walking, cycling, and aquatic exercises not only improve physical symptoms but also contribute to emotional well-being and social interactions. In conclusion, treating PD requires a holistic approach that combines medical, surgical, and therapeutic strategies. While there is no cure, the goal is to maximize patients' functional abilities and quality of life through personalized treatment plans. This integrated approach, along with ongoing research and development of new therapies, offers hope for improving the management of PD and the lives of those affected by this challenging disease.

Epidemiologic and Clinical Features of Campylobacter Enteritis Before and During COVID-19 in Korea.

BACKGROUND: With the increase in meals at home due to coronavirus disease 2019 (COVID-19), the pattern and incidence of enteritis seemed to change. Some types of enteritis, such as Campylobacter enteritis, appear to have increased. Our study aimed to evaluate the change in the trend of enteritis, especially Campylobacter enteritis, before COVID-19 (2016-2019) and at the present time during COVID-19 in South Korea. METHODS: We analyzed data from the Health Insurance Review and Assessment Service. From 2016 to 2020, the International Classification of Diseases codes related to enteritis were examined to distinguish bacterial and viral enteritis and the trends of each were analyzed. The aspects of enteritis, before and after the COVID-19 outbreak, were compared. RESULTS: Both bacterial and viral enteritis declined in all age groups from 2016 to 2020 (P < 0.001). In 2020, the reduction rate of viral enteritis was higher than that of bacterial enteritis. However, unlike other causes of enteritis, even after COVID-19, Campylobacter enteritis increased in all age groups. An increase of Campylobacter enteritis in 2020 was particularly noticeable in children and adolescents. The prevalence of viral and bacterial enteritis was higher in urban areas than in rural areas (P < 0.001). Campylobacter enteritis was more common in the rural areas (P < 0.001). CONCLUSION: Although the prevalence of bacterial and viral enteritis have decreased in COVID-19, Campylobacter enteritis has increased in all age groups and in rural areas compared to urban areas. Recognizing that the trend of Campylobacter enteritis before and during COVID-19 is helpful for future public health measures and interventions.

Treatment of Sagittal Fracture of the Zygomatic Arch Root.

A sagittal fracture at the temporal root of the zygomatic arch (ZAR) often occurs as a component of zygomaticomaxillary complex (ZMC) fractures. However, this area is difficult to access, and anchorage is limited due to the unstable structure around it. Therefore, a preauricular approach using single-screw fixation is proposed, and this study reports its results and usefulness. Forty-four patients with sagittal fractures of ZAR occurring with ZMC fractures were evaluated from 2012 to 2021. Open reduction and internal fixation were performed on all patients with ZMC fractures. Closed reduction using Dingman incision and external finger pressure in group A (indirect approach; 30 patients) and single-screw fixation using a preauricular approach in group B (direct approach; 14 patients) were performed to address sagittal fractures in ZAR. For single-screw fixation, the additional mean operation time was 11.34±3.25 minutes. On postoperative 3-dimensional computed tomography and plain radiographs, group B showed more accurate reduction and less deformity and trismus ( P <0.05). Moreover, a normal diet was initiated more quickly in group B than in group A ( P <0.05). Some cases in group A showed nonunion or malunion. This study revealed that a direct approach (group B) toward sagittal fractures of ZAR is recommended due to more accurate results and fewer complications than those observed with the indirect approach (group A). Moreover, the total operation time and complications may be lesser than those with the bicoronal approach.

A Comprehensive Review of the Effects of Extracorporeal Shock Wave Therapy on Stroke Patients: Balance, Pain, Spasticity.

Stroke remains a leading cause of disability worldwide, with survivors often experiencing impairments in balance, pain, spasticity, and control that limit their ability to perform daily living activities. Extracorporeal shock wave therapy (ESWT) has emerged as a potential treatment modality to improve these outcomes in stroke patients. This review aims to provide a comprehensive examination of the effects of ESWT on stroke patients, focusing on the theoretical background, balance, pain reduction, muscle spasticity and control, and upper and lower extremities. This study reviewed the use of ESWT in treating balance, pain, and spasticity in stroke patients, focusing on articles published in PubMed between January 2003 and January 2023. Systematic reviews related to stroke were used to provide an overview of stroke, and a total of 33 articles related to balance, pain, and spasticity were selected. ESWT has several shock wave generation methods and application methods, and it has been shown to have positive therapeutic effects on various aspects of rehabilitation for stroke patients, such as improving balance, reducing pain, decreasing muscle spasticity and increasing control, and enhancing functional activities of the upper and lower extremities. The efficacy of ESWT may vary depending on the patient's condition, application method, and treatment area. Therefore, it is important to apply ESWT according to the individual characteristics of each patient in clinical practice to maximize its potential benefits.

Surface Accessibility of an Intrinsically Disordered Protein Probed by 2D Time-Resolved Laser-Assisted NMR Spectroscopy.

Probing the protein surface accessibility of different residues is a powerful way of characterizing the overall conformation of intrinsically disordered proteins (IDPs). We present a two-dimensional (2D) time-resolved photo-CIDNP (TR-CIDNP) experiment suitable for IDP analysis. Pulse stretching of high-power laser pulses, band-selective decoupling of 13Cα, and simultaneous application of radiofrequency and laser pulses were implemented to quantitatively analyze the IDP surface at ultrahigh resolution. Comparative analysis with other methods that measure protein surface accessibility validated the newly developed method and emphasized the importance of dye charge in photo-CIDNP. Using the neutral riboflavin dye, surface accessibilities were measured to be nearly identical for the four Tyr residues of α-synuclein (α-Syn), whose 1Hα-13Cα correlations were well-resolved in the 2D TR-CIDNP spectrum. Having confirmed the similarity between the time-resolved and steady-state photo-CIDNP results for α-Syn, we used the more sensitive latter method to show that divalent cations induce compaction of the C-terminal region and release of the N-terminal region of α-Syn. The photo-CIDNP method presented herein can be used as an orthogonal and independent method for investigating important biological processes associated with changes in the overall IDP conformation.

Hyaluronate-Black Phosphorus-Upconversion Nanoparticle Complex for Non-invasive Theranosis of Skin Cancer.

Despite the wide investigation on black phosphorus (BP) for biophotonic applications, the finite depth of light penetration has limited further development of BP-based photomedicines. Here, we developed a hyaluronate-BP-upconversion nanoparticle (HA-BP-UCNP) complex for near-infrared (NIR) light-mediated multimodal theranosis of skin cancer with photoacoustic (PA) bioimaging, photodynamic therapy (PDT), and photothermal therapy (PTT). In contrast to the conventional BP-based skin cancer theranosis, the HA-BP-UCNP complex could be non-invasively delivered into the tumor tissue to induce the cancer cell apoptosis upon NIR light irradiation. The PA imaging of BP successfully visualized the non-invasive transdermal delivery of the HA-BP-UCNP complex into the mice skin. HA in the complex facilitated the transdermal delivery of BP into the tumor tissue under the skin. Upon 980 nm NIR light irradiation, the UCNP converted the light to UV-blue light to generate reactive oxygen species by sensitizing BP in the HA-BP-UCNP complex for PDT. Remarkably, 808 nm NIR irradiation with PTT triggered the apoptosis of tumor cells. Taken together, we could confirm the feasibility of the HA-BP-UCNP complex for NIR light-mediated multimodal theranosis of skin cancers.

Seed-assembly-mediated fabrication and application of highly branched gold nanoshells having hollow and porous morphologies.

Highly branched gold nanoshells (BAuNSs) having hollow and porous morphologies have been fabricated via a seed-assembly-mediated strategy. Gold seed assemblies can be prepared by removal of SiO2nanotemplates with help of polyvinylpyrrolidone (PVP) molecules, which weakly link gold nanoparticles together even after SiO2etching. L-3,4-dihydroxy phenylalanine (L-DOPA) and AgNO3are employed as shape-directing agents to induce the anisotropic growth of gold. BAuNSs exhibit 7.4 and 4.4 times stronger activities than SiO2@Au nanoparticles in catalysis and surface-enhanced Raman scattering (SERS) applications, respectively, due to their large surface areas and numerous hot spots. It is necessary to find the optimal amount of gold deposition in fabrication to effectively utilize the hollow and porous morpologies of BAuNSs for catalysis and SERS applications. Overgrown nanobranches can fill the nanopores and nanogaps of BAuNSs, resulting in decrease of activities in applications. Overall, the seed-assembly-mediated fabrciation can be employed to produce plasmonic nanostructures having unique morphologies and high application activities.

The Flavonoid Baicalein Negatively Regulates Progesterone Target Genes in the Uterus in Vivo.

Baicalein is a flavonoid extracted from the root of Scutellaria baicalensis (Chinese skullcap) and is consumed as part of this botanical dietary supplement to reduce oxidative stress, pain, and inflammation. We previously reported that baicalein can also modify receptor signaling through the progesterone receptor (PR) and glucocorticoid receptor (GR) in vitro, which is interesting due to the well-established roles of both PR and GR in reducing inflammation. To understand the effects of baicalein on PR and GR signaling in vivo in the uterus, ovariectomized CD-1 mice were treated with DMSO, progesterone (P4), baicalein, P4 with baicalein, and P4 with RU486, a PR antagonist, for a week. The uteri were collected for histology and RNA sequencing. Our results showed that baicalein attenuated the antiproliferative effect of P4 on luminal epithelium as well as on the PR target genes HAND2 and ZBTB16. Baicalein did not change levels of PR or GR RNA or protein in the uterus. RNA sequencing data indicated that many transcripts significantly altered by baicalein were regulated in the opposite direction by P4. Similarly, a large portion of GO/KEGG terms and GSEA gene sets were altered in the opposite direction by baicalein as compared to P4 treatment. Treatment of baicalein did not change body weight, organ weight, or blood glucose level. In summary, baicalein functioned as a PR antagonist in vivo and therefore may oppose P4 action under certain conditions such as uterine hyperplasia, fibroids, and uterine cancers.

Correction of a Secondary Bilateral Cleft Lip Nasal Deformity in Adults Using Repositioning of Both Lower Lateral Cartilages and Nasal Tip Plasty Through an Open Bilateral Reverse-U Incision.

BACKGROUND: Correcting a secondary bilateral cleft lip nasal deformity is very complex with many challenges due to its complexity. This study presents the surgical results after correcting a secondary bilateral cleft lip nasal deformity using isolation and repositioning of the lower lateral cartilages, the columellar strut, and an onlay graft on the nasal tip. METHOD: Eighteen patients who had bilateral cleft lip nasal deformities and who had surgery performed between September 2013 and December 2019 were included in this study. The age of the patients ranged between 19 and 52 years. Open rhinoplasty with bilateral reverse-U incision was performed. The lower lateral cartilages were isolated and repositioned. Nasal tip support is provided using a columellar strut with a septal cartilage or Medpor strut. In the vertical component of the nasal tip, a conchal cartilage graft was used. The mean follow-up period was 2 years (ranging from 1 to 6 years). RESULTS: Fourteen of the 18 patients underwent photogrammetric evaluation. After surgery, the projection of the nasal tip and angle increased, but nasal bridge length decreased. The columella-labial angle significantly increased by 10.1% after surgery which was statistically significant (P < 0.05). The angle between the nostril axes significantly decreased by 46.2% postoperatively and also reached statistical significance (P < 0.05), indicating that the displaced alar base and lower nostril sill improved and the major axis of the nostril changed more vertically oblique. All patients were pleased with their surgical results. CONCLUSION: The proposed technique was highly effective in correcting secondary bilateral cleft lip nasal deformities in adults.

Intraoperative evaluation of DRUJ instability through dorsal stress radiography in distal radius fractures.

INTRODUCTION: Certain type of injury of the triangular fibrocartilage complex associated with distal radius fracture can result in distal radioulnar joint instability (DRUJ). Untreated DRUJ instability may lead to poor result in the treatment of acute distal radius fractures. The aim of this study was to evaluate DRUJ instability in distal radius fractures through dorsal stress radiography comparing the affected and unaffected wrists intraoperatively. MATERIALS AND METHODS: 49 patients with a distal radius fracture who were operatively treated with a volar locking plate were included. Dorsal stress radiography was used to evaluate both affected and unaffected wrists peri-operatively to detect DRUJ instability. Under general anesthesia, a dorsal stress test was performed on the unaffected wrist. Additionally, after fixation of the affected wrist, a dorsal stress test was performed. The ulnar translation ratio (UTR) was measured through the dorsal stress radiograph. Arthroscopic examination was performed on all affected wrists according to Palmer's and Atzei classification. RESULTS: The UTR of the affected wrist and the TFCC injury Palmer-type IB tendency were positively correlated (odds ratio: 1.18, p-value: 0.002). Additionally, as the UTR difference between the affected and unaffected wrists enlarged, it revealed a significant DRUJ instability tendency due to Palmer-type IB TFCC injury (p-value: 0.000006, Wilcoxon rank-sum test). CONCLUSIONS: Dorsal stress radiography is a reliable, simple procedure to evaluate DRUJ instability intraoperatively. UTR value from dorsal stress radiography could be useful for evaluating DRUJ instability associated with distal radius fracture.

Usefulness of Incisional Negative Pressure Wound Therapy for Decreasing Wound Complication Rates and Seroma Formation Following Prepectoral Breast Reconstruction.

BACKGROUND: Seroma is a common complication in prepectoral breast reconstruction. PICOTM dressing, a type of incisional negative pressure wound therapy (iNPWT), was used to reduce complications postoperatively. METHODS: This study was a retrospective cohort study that included patients who underwent prepectoral breast reconstruction between February 2017 and July 2019. There were two groups: one that received PICOTM dressing and a control group. The frequencies of overall complications, major seromas, and reoperations were analyzed. The durations and total amounts of seromas were also analyzed. RESULT: Sixty patients were included in this study (PICOTM : 37 and non-PICOTM patients: 23). The overall incidence of complications, major seromas, and frequency of reoperations were lower in the PICO group compared to the non-PICOTM group (18.9% vs. 52.2%, p = 0.007; 16.2% vs. 43.5%, p = 0.020; 2.7% vs. 26.1%, p = 0.006, respectively). Univariate analysis was used to analyze the risk factors for complications due to the application of PICOTM dressing and showed statistically significant results for any complication. When univariate analysis was performed on risk factors for seroma, the duration of seroma showed statistical significance in association with PICOTM dressing status and mastectomy volume. The total number of patients who developed seroma was statistically correlated with age, PICOTM dressing status, and mastectomy volume. CONCLUSIONS: PICOTM dressing after prepectoral breast reconstruction could be a useful tool for reducing the frequency of complications and major seroma, as well as the duration and total incidences of seroma. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Influence of Irradiation on Capsules of Silicone Implants Covered with Acellular Dermal Matrix in Mice.

BACKGROUND: In advanced breast cancer, radiotherapy is recommended as adjuvant therapy following breast reconstructive surgery. This inevitably led to growing concerns over possible complications of radiotherapy on implants. In this experimental animal study, we investigated the utility of acellular dermal matrix (ADM) wraps around implants as preventive management for radiotherapy complications. METHODS: Black mice (C57NL6; n = 32) were assigned to groups that either received radiation or did not: groups A and B underwent surgery using implants without radiotherapy; while groups C and D underwent surgery using implants with radiotherapy for one and three months, respectively. The hemispheric silicone implants with an 0.8-cm-diameter were inserted on the left back of each mouse, and implants wrapped by ADM were inserted on the right back. The Clinic 23EX LINAC model was used for irradiation at 10 Gy. The samples were evaluated by gross assessment, histological analysis, immunohistochemical analysis, and the Western blotting test. RESULTS: The H&E staining analysis showed that membrane thickness is smallest in group A, followed by groups C, D, and B. In a Masson trichrome histological analysis, collagen fibers became less dense and more widespread over time in the groups that received an ADM. Immunohistochemistry findings were similarly constant. However, the expression of TGF-ß1 was increased in the irradiated groups, whereas it was decreased in the non-irradiated groups as observed over time. CONCLUSIONS: Radiotherapy was shown to increase risk factors for capsular contracture, including inflammatory response, pseudoepithelium, thinning of membrane, and TGF-ß1 expression over time; however, the accompanying framework using an ADM as a barrier between implant and tissue was shown to be effective in alleviating these risks. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effect of Topical Tranexamic Acid on Seroma Formation in a Rat Mastectomy Model.

BACKGROUND: Seroma is the most common complication after mastectomy and reconstruction surgery. Therefore, this study aimed to determine whether the topical application of tranexamic acid would be useful to reduce seromas in a rat mastectomy model. METHODS: Forty-eight Sprague-Dawley rats were divided into four groups. After mastectomy and axillary lymph node dissection, 0.4 mL of normal saline was administered to group A in the dead space. In group B, 0.4 mL of a triamcinolone mixed solution was administered. In group C, 0.4 mL of a tranexamic acid (10 mg/kg) mixed solution was administered. In group D, 0.4 mL of a tranexamic acid (50 mg/kg) mixed solution was administered. Gross examination, assessment with micro-computed tomography (CT), quantitative analysis via aspiration, and histopathologic assessment were implemented 7 and 14 days postoperatively. RESULTS: No other complications such as wound infection and skin necrosis were observed. At postoperative week 1, groups B and C showed significantly lower seroma volume values on micro-CT (P < 0.001 and P < 0.05, respectively) and seroma volume values at aspiration (P < 0.01 and P < 0.001, respectively) than group A. According to histopathologic analysis, inflammation was observed more frequently in groups A and D than in the other groups, and angiogenesis was more active in groups B and C than in the other groups. CONCLUSIONS: Topical application of tranexamic acid was as effective as topical application of triamcinolone to prevent seroma formation. The stability of tranexamic acid was confirmed when the high dose of tranexamic acid was used. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Zinc Deficiency Induces Autophagy in HT-22 Mouse Hippocampal Neuronal Cell Line.

Zinc is a trace metal vital for various functions in nerve cells, although the effect of zinc deficiency on neuronal autophagy remains unclear. This study aimed to elucidate whether zinc deficiency induced by treatment with N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a zinc chelator, affects and alters autophagy activity. In cell viability assays, TPEN showed cytotoxicity in HT-22 cells. TPEN treatment also increased LC3-II levels and the ratio of LC3-II to LC3-I. Western blot analysis showed that phospho-AMP-activated protein kinase levels and the ratio of phospho-AMP-activated protein kinase to total AMP-activated protein kinase increased. Protein levels of the mammalian target of rapamycin and sirtuin 1 decreased following TPEN treatment. When TPEN-treated HT-22 cells were cotreated with autophagy inhibitors, 3-methyladenine (1 mM), or bafilomycin A1 (3 nM), the TPEN-induced decrease in cell viability was exacerbated. Cotreatment with chloroquine (10 µM) partially restored cell viability. The study showed that zinc deficiency induces autophagy and may be cytoprotective in neurons. We expect our results to add a new perspective to our understanding of the neuronal pathology related to zinc deficiency.

Serial Change of Endotoxin Tolerance in a Polymicrobial Sepsis Model.

Immune suppression is known to occur during sepsis. Endotoxin tolerance is considered a mechanism of immune suppression in sepsis. However, the timing and serial changes in endotoxin tolerance have not been fully investigated. In this study, we investigated serial changes in endotoxin tolerance in a polymicrobial sepsis model. Herein, we used a rat model of fecal slurry polymicrobial sepsis. After induction of sepsis, endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was measured at various time points (6 h, 12 h, 24 h, 48 h, 72 h, 5 days, and 7 days), through the measurement of TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. At each time point, we checked for plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 levels. Moreover, we analyzed reactive oxygen species (ROS) as measured by 2',7'-dichlorodihydrofluorescein, plasma lactate, serum alanine aminotransferase (ALT), and creatinine levels. Nuclear factor (NF)-κB, IL-1 receptor-associated kinase (IRAK)-M, and cleaved caspase 3 levels were measured in the spleen. Endotoxin tolerance, measured by TNF-α production stimulated through LPS in PBMCs and splenocytes, was induced early in the sepsis model, starting from 6 h after sepsis. It reached a nadir at 24 to 48 h after sepsis, and then started to recover. Endotoxin tolerance was more prominent in the severe sepsis model. Plasma cytokines peaked at time points ranging from 6 to 12 h after sepsis. ROS levels peaked at 12 h and then decreased. Lactate, ALT, and serum creatinine levels increased up to 24 to 48 h, and then decreased. Phosphorylated p65 and IRAK-M levels of spleen increased up to 12 to 24 h and then decreased. Apoptosis was prominent 48 h after sepsis, and then recovered. In the rat model of polymicrobial sepsis, endotoxin tolerance occurred earlier and started to recover from 24 to 48 h after sepsis.

Metformin Augments Anti-Inflammatory and Chondroprotective Properties of Mesenchymal Stem Cells in Experimental Osteoarthritis.

Mesenchymal stem cells (MSCs) can protect against cartilage breakdown in osteoarthritis (OA) via their immunomodulatory capacities. However, the optimization strategy for using MSCs remains challenging. This study's objective was to identify the in vivo effects of metformin-stimulated adipose tissue-derived human MSCs (Ad-hMSCs) in OA. An animal model of OA was established by intra-articular injection of monosodium iodoacetate into rats. OA rats were divided into a control group and two therapy groups (treated with Ad-hMSCs or metformin-stimulated Ad-hMSCs). Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Our data show that metformin increased IL-10 and IDO expression in Ad-hMSCs and decreased high-mobility group box 1 protein, IL-1ß, and IL-6 expression. Metformin increased the migration capacity of Ad-hMSCs with upregulation of chemokine expression. In cocultures, metformin-stimulated Ad-hMSCs inhibited the mRNA expression of RUNX2, COL X, VEGF, MMP1, MMP3, and MMP13 in IL-1ß-stimulated OA chondrocytes and increased the expression of TIMP1 and TIMP3. The antinociceptive activity and chondroprotective effects were greater in OA rats treated with metformin-stimulated Ad-hMSCs than in those treated with unstimulated Ad-hMSCs. TGF-ß expression in subchondral bone of OA joints was attenuated more in OA rats treated with metformin-stimulated Ad-hMSCs. Our findings suggest that metformin offers a promising option for the clinical application of Ad-hMSCs as a cell therapy for OA.