Female Protection Against Diabetic Kidney Disease Is Regulated by Kidney-Specific AMPK Activity.

Reduced kidney AMPK activity is associated with nutrient stress-induced chronic kidney disease (CKD) in male mice. In contrast, female mice resist nutrient stress-induced CKD. The role of kidney AMPK in sex-related organ protection against nutrient stress and metabolite changes was evaluated in diabetic kidney tubule-specific AMPKγ2KO (KTAMPKγ2ΚΟ) male and female mice. In wild-type (WT) males, diabetes increased albuminuria, urinary kidney injury molecule-1, hypertension, kidney p70S6K phosphorylation, and kidney matrix accumulation; these features were not exacerbated with KTAMPKγ2ΚΟ. Whereas WT females had protection against diabetes-induced kidney injury, KTAMPKγ2ΚΟ led to loss of female protection against kidney disease. The hormone 17ß-estradiol ameliorated high glucose-induced AMPK inactivation, p70S6K phosphorylation, and matrix protein accumulation in kidney tubule cells. The mechanism for female protection against diabetes-induced kidney injury is likely via an estrogen-AMPK pathway, as inhibition of AMPK led to loss of estrogen protection to glucose-induced mTORC1 activation and matrix production. RNA sequencing and metabolomic analysis identified a decrease in the degradation pathway of phenylalanine and tyrosine resulting in increased urinary phenylalanine and tyrosine levels in females. The metabolite levels correlated with loss of female protection. The findings provide new insights to explain evolutionary advantages to females during states of nutrient challenges.

Percutaneous Intra-arterial Hyaluronidase Injection for Hyaluronic Acid Filler Embolism Threatening Skin Barrier Integrity: Implementation of a Stepwise Treatment Protocol.

BACKGROUND: Hyaluronic acid (HA) filler-induced vascular embolism that threatens skin integrity is an urgent situation. There is increasing evidence that percutaneous intra-arterial hyaluronidase injection is an effective therapeutic technique for it. However, until now, there is a lack of a unifying protocol about the technique. OBJECTIVES: This study aims to provide a conclusion of percutaneous intra-arterial hyaluronidase injection along with adjunctive measures on the treatment of occlusions precipitated by HA-based filler and develop a stepwise treatment protocol. METHODS: We searched PubMed for peer-reviewed studies, consensus statements, case series, and case reports using a variety of keywords. RESULTS: High-dose, pulsed hyaluronidase is the mainstay for the treatment of HA filler-induced embolism, but percutaneous intra-arterial hyaluronidase injection is a more effective technique. Until now, hyaluronidase is injected into three arteries percutaneously, including facial artery, supratrochlear artery, and superficial temporal artery. Furthermore, the adjunctive measures that may optimize clearance of an occlusion and/or skin barrier repair such as the use of image guidance and CGF should be considered. CONCLUSION: Vascular occlusions that threaten skin integrity are an urgent matter which requires accurate diagnosis and effective intervention. Percutaneous intra-arterial hyaluronidase injection along with adjunctive measures performed in a stepwise manner is key to an optimal outcome. 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 .

Utilizing circulating tumour DNA as a prognostic predictor of gastric cancer: a meta-analysis.

Background: Circulating tumour DNA (ctDNA) has demonstrated robust diagnostic accuracy in several digestive cancers. However, the prognostic role of ctCDNA in gastric cancer (GC) is still controversial. This systematic review and meta-analysis aimed to evaluate the prognostic value of ctDNA in GC.Methods: PubMed, Web of Science and Cochrane databases were searched to identify studies reporting the use of ctDNA to predict GC outcome and all relevant studies published until November 2022 were enrolled for our analysis. Data were extracted by two authors independently and statistic analysis was conducted by R program with 'meta' and 'metafor' packages.Results: A total of 34 qualified articles with 5091 subjects were incorporated into our meta-analysis. The corresponding Hazard ratio (HR) of overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) were 2.74 (95% CI:2.24-3.35), 3.13 (95% CI:2.08-4.72) and 3.04 (95% CI:2.46-3.76), respectively, in GC patients.Conclusion: Blood-based ctDNA assay would be a potential novel biomarker for GC evaluation and prediction.Simple Summary: This is the integrated meta-analysis on the association of circulating tumour DNA (ctDNA) and prognosis of gastric cancer (GC) with an increasing number of studies exploring the prognostic value of GC in the last few years, which depicted that the detection of ctDNA could be a promising predictor in GC patients.

Role of Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) in the Diagnosis of Suspicious Malignant Esophageal Strictures.

(1) Background: The accurate diagnosis of esophageal strictures is quite critical for optimizing medical intervention. However, the diagnosis of suspicious malignant esophageal strictures with intact mucosa appearance and negative biopsy results is challenging. This study aimed to evaluate the role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of suspicious esophageal strictures. (2) Methods: We retrospectively analyzed the cases with suspicious malignant esophageal strictures that underwent EUS-FNA, with or without rapid on-site evaluation (ROSE), in our hospital from April 2017 to September 2022. Their clinical manifestations, imaging examinations, gastroscopic examinations, EUS-FNA results, and therapeutic strategies were retrospectively recorded and analyzed. (3) Results: A total of 23 patients (15 male and 8 female) were enrolled in this study. Based on EUS-FNA results, 18 patients were diagnosed with malignancies, including 16 cases of primary esophageal cancer (13 squamous carcinomas and 3 adenocarcinomas), 1 case of mediastinal cancer, and 1 case of metastatic esophageal cancer; 1 case of tuberculosis was also confirmed by EUS-FNA. Among 4 cases of ambiguous diagnosis with EUS-FNA, 1 was diagnosed with an esophageal glomus tumor after surgical removal, and 2 patients survived for several years without medical intervention, which hinted at the possibility of benign esophageal strictures. No major complications, including bleeding or perforation, were observed. (4) Conclusions: EUS-FNA may serve as a safe and effective diagnostic tool in suspicious malignant esophageal strictures with accurate specimen acquisition, especially for biopsy-negative cases.

Using Circulating Tumor DNA as a Novel Biomarker to Screen and Diagnose Colorectal Cancer: A Meta-Analysis.

(1) Background: Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for many kinds of tumors. However, whether ctDNA could be an accurate diagnostic biomarker in colorectal cancer (CRC) remains to be clarified. The aim of this study was to evaluate the diagnostic accuracy of ctDNA in CRC. (2) Methods: PubMed, Web of Science, and Cochrane databases were searched to identify studies reporting the use of ctDNA to screen and diagnose CRC, and all relevant studies published until October 2022 were enrolled for our analysis. These studies were divided into three primer subgroups: the subgroup of quantitative or qualitative analysis of ctDNA and the subgroup of septin9 (SEPT9) methylation assay. (3) Results: A total of 79 qualified articles with 25,240 subjects were incorporated into our meta-analysis. For quantitative studies, the combined sensitivity (SEN), specificity (SPE), and diagnostic odds ratio (DOR) were 0.723 (95% CI: 0.623-0.803), 0.920 (95% CI: 0.827-0.966), and 23.305 (95% CI: 9.378-57.906), respectively, yielding an AUC of 0.860. The corresponding values for qualitative studies were 0.610 (95% CI: 0.566-0.651), 0.891 (95% CI: 0.878-0.909), 12.569 (95% CI: 9.969-15.848), and 0.823, respectively. Detection of SEPT9 methylation depicted an AUC of 0.879, with an SEN of 0.679 (95% CI: 0.622-0.732), an SPE of 0.903 (95% CI: 0.878-0.923), and a DOR of 20.121 (95% CI:14.404-28.106), respectively. (4) Conclusion: Blood-based ctDNA assay would be a potential novel biomarker for CRC screening and diagnosis. Specifically, quantitative analysis of ctDNA or qualitative analysis of SEPT9 methylation exhibited satisfying diagnostic efficiency. Larger sample studies are needed to further confirm our conclusions and to make the ctDNA approach more sensitive and specific.

Efficacy of Percutaneous Superficial Temporal Arterial Hyaluronidase Injection for Hyaluronic Acid Filler-Induced Necrosis of Frontotemporal Skin and/or the Ipsilateral Scalp With Subsequent Alopecia.

BACKGROUND: Necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia after hyaluronic acid (HA) filler injection into the temple is rare complications with superficial temporal artery embolization are suspected as the major pathological mechanism. The main treatment currently is intralesional hyaluronidase (HAase) injection, but the effectiveness of percutaneous superficial temporal arterial HAase injection still lacks consensus. OBJECTIVES: To investigate the effectiveness of superficial temporal arterial HAase injection in dissolving HA filler-induced necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia. METHODS: Five recent clinical cases with necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia after HA filler injection into the temple were analyzed retrospectively. The patients underwent HAase injection via superficial temporal artery combined with adjunctive treatments, and the clinical progress was observed. RESULTS: Significant improvement was observed in terms of necrosis of frontotemporal skin and the ipsilateral scalp after treatment, and the patients were relieved of their clinical symptoms. Alopecia occurred approximately 1 to 2 weeks after HA filler injection, and the well-defined alopecia areas were formed 15 to 20 days after HAase injection. Patients were followed for 3 to 6 months. During follow-up, the skin lesions of all patients were restored to near normal appearance. Hair regrowth was observed 2 to 3 months after HAase treatment, and hair density nearly reached the normal level 3 to 4 months later. CONCLUSIONS: Percutaneous superficial temporal arterial HAase injection is an effective treatment option for HA filler-induced necrosis of frontotemporal skin and/or the ipsilateral scalp with subsequent alopecia.

The role of altered fatty acid in pathological scars and their dermal fibroblasts.

PURPOSE: The proposed pathological mechanism for scar formation is controversial, and increased attention has been paid to the fatty acids (FAs) in the formation of pathological scars. Notably, FAs are known to be important in inflammation and mechanotransduction, which is closely related to scar formation. Therefore, it is necessary to clarify the roles of FA in scar formation. METHODS: Hypertrophic scar and keloid formed for more than a year and without other treatment, as well as normal skin samples were obtained from patients who underwent plastic surgery. Finally, keloids (n = 10), hypertrophic scars (n = 10), and normal skin samples (n = 10) were collected under informed consent. Primary dermal fibroblasts were isolated and cultured. The amount and variety of FAs were detected by lipid chromatography-mass spectrometry. Immunohistochemistry, real-time PCR, and western blotting were used to verify the expression of sterol regulatory element-binding protein-1 (SREBP1) and fatty acid synthase (FASN) in the samples and their fibroblasts. Student's t-test, ANOVA, and orthogonal partial least square discriminant analysis were performed for statistical analysis (∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001). RESULTS: Compared with full-thickness normal skin, there were 27 differential FAs in keloids and 15 differential FAs in hypertrophic scars (∗p < 0.05 and variable influence on projection >1.0). The expression of SREBP1 and FASN was lower in pathological scars both at mRNA and protein levels (all ∗p < 0.05). However, the mRNA levels of SREBP1 (∗∗∗p = 0.0002) and FASN (∗∗∗p = 0.0021) in keloid-derived fibroblasts were higher than that in normal skin fibroblasts (NFBs), while the expression in hypertrophic scar-derived fibroblasts was lower than that in NFBs (both ∗p < 0.05). Whereas there was no significant difference in FASN protein expression between keloid-derived fibroblasts and NFBs (p > 0.05). CONCLUSION: FAs involved in pathological scars are abnormally changed in scar formation. Thus, fatty acid-derived inflammation and de novo synthesis pathway of FA may play a key role in the formation of pathological scars.

Astragaloside IV inhibits the progression of liver cancer by modulating macrophage polarization through the TLR4/NF-κB/STAT3 signaling pathway.

AIM: The purpose of the present research was to investigate the effect and mechanism of Astragaloside IV (AS-IV) on liver cancer progression in vivo and in vitro. Since M1 macrophages play an essential role in suppressing tumors, while M2 macrophages can accelerate the incidence and progression of tumors by promoting angiogenesis, increasing tumor cell invasion and inhibiting tumor immune response, the effect and mechanism of AS-IV on macrophage polarization and their role in the development of HCC was explored. METHODS: The effects of different concentrations of AS-IV (0, 50, 80, 100, 120, and 150 µM) on the capacity of hepatocellular carcinoma (HCC) cells to proliferate, migrate, and invade were detected. THP-1 cells were subjected to incubation in PMA for the purpose of stimulating differentiation into M0 macrophages. These macrophages were treated using LPS, IFN-γ, and PMA to produce M1 macrophages or treated using PMA, IL-13, and IL-4 to produce M2 macrophages. HCC cells and M1 or M2 macrophages were co-cultured for 48 hours, then the cell proliferation and migration were measured. The MTT assay was employed to determine cell viability. The capability of the cells to migrate and invade was investigated utilizing the Transwell assay and the wound healing assay. The expression of the M2 macrophage CD206 in macrophages treated with AS-IV was evaluated by flow cytometry. The expression of p-signal transducer and activator of transcription 3 (STAT3), phosphorylated (p)-NF-κB, and toll-like receptor 4 (TLR4) in macrophages was measured after treatment with AS-IV and M2 induction. To verify the function of the TLR4/NF-κB/STAT3 signaling pathway, TLR4 expression was knocked down in M2 macrophages, then the proliferation and migration and the M2 macrophage markers of HCC cells were measured. The effect of AS-IV on HCC in vivo was confirmed by a subcutaneous tumor mouse model. AS-IV was 2 was administered by gavage (0, 40, 80, and 100 mg/kg) for every 3 days. The tumor volume and weight were recorded. RESULTS: AS-IV suppressed the capacities of HCC cells to proliferate, migrate, and invade in a dose-dependent way. M2 macrophages could promote the proliferative, migratory, and invasive ability of Huh-7 cells, which were suppressed by AS-IV. AS-IV directly attenuated the expression of M2 macrophage markers, indicating that AS-IV can inhibit macrophage M2 polarization. M2 macrophages stimulated the expression of p-STAT3, p-NF-κB, and TLR4, while AS-IV decreased the expression compared to the M2 group, indicating that AS-IV can regulate the TLR4/NF-κB/STAT3 signaling pathway. TLR4 small interfering RNA (siRNA/si) inhibited the proliferation of Huh-7 cells. The tumor volume, as well as weight of mice, was significantly reduced by AS-IV, indicating the antitumor impact of AS-IV in vivo. CONCLUSION: AS-IV can inhibit the proliferative, invasive, and migratory ability of liver cancer through the suppression of the M2 polarization of macrophages, and the mechanism may involve the TLR4/NF-κB/STAT3 signaling pathway. The present study indicates that AS-IV could be an alternative drug to treat liver cancer, and the polarization of macrophages may be a novel treatment target for HCC.

Efficacy of Percutaneous Intraarterial Facial/Supratrochlear Arterial Hyaluronidase Injection for Treatment of Vascular Embolism Resulting From Hyaluronic Acid Filler Cosmetic Injection.

BACKGROUND: Vascular embolism is a serious complication of hyaluronic acid (HA) filler cosmetic injection, and hyaluronidase injection has been proposed as the treatment. Until now, there has been a lack of adequate clinical evidence regarding the benefits of treatment for HA filler-induced vascular embolism by percutaneous facial or supratrochlear arterial hyaluronidase injection. OBJECTIVES: The authors sough to evaluate the efficacy of percutaneous facial or supratrochlear arterial hyaluronidase injection as a rescue treatment for HA filler-induced vascular embolism. METHODS: We included 17 patients with vascular embolism after facial HA filler injection. Intraarterial injection of 1500 units hyaluronidase was performed via facial artery for 13 cases with skin necrosis and via supratrochlear arterial for 4 cases with severe ptosis and skin necrosis but no visual impairment. Simultaneously, general symptomatic treatment and nutritional therapy were performed. RESULTS: After hyaluronidase injection, facial skin necrosis in all cases was restored and ptosis in the 4 cases was also significantly relieved. Patients were subsequently followed-up for 1 month to 1 year. The skin necrosis in 16 patients completely healed, and only 1 patient had small superficial scars. CONCLUSIONS: It is effective to alleviate skin necrosis and ptosis resulting from HA filler embolism via percutaneous facial or supratrochlear arterial hyaluronidase injection.

Prognostic Significance of Tumor-Associated Macrophages in Chondroblastoma and Their Association with Response to Adjuvant Radiotherapy.

OBJECTIVE: Chondroblastoma (CB) is a rare and locally growing cartilage-derived tumor. Currently, clinical implications of tumor-associated macrophages (TAMs) in CB remain unclear. In this study, we sought to analyze the relationship between TAM parameters (including densities of CD68+ and CD163+ cells as well as the CD163+/CD68+ ratio) and clinicopathological characteristics and survival of patients. METHODS: Immunohistochemistry was used to assess TAM subtypes for CD68 and CD163, as well as the expression levels of p53, CD34, and Ki-67 on tumor cells in 132 tissue specimens retrieved between July 2002 and April 2020. Then, TAM parameters were retrospectively analyzed for their associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]) and clinicopathological features. RESULTS: TAM densities were significantly higher in axial chondroblastoma tissue than in extra-axial chondroblastoma tissue. Moreover, the number of CD163+ TAMs was positively correlated with tumor invasion of surrounding tissues and high expression of CD34 and Ki-67 on tumor cells, whereas CD163+ cell density and the CD163/CD68 ratio were negatively associated with patient response to adjuvant radiotherapy. Univariate Kaplan-Meier analysis revealed that the number of CD68+ and CD163+ lymphocytes was significantly associated with both LRFS and OS. Multivariate Cox regression analysis showed that CD163+ and CD68+ cell levels were independent prognostic factors of LRFS, while TAM data independently predicted OS. More importantly, in subgroup analysis based on three significant factors in univariate survival analysis (including tumor location, adjuvant radiotherapy, and surrounding tissue invasion by tumors), the TAM parameters still displayed good prognostic performance. CONCLUSION: These data suggest that TAM may significantly affect the biological behavior of CB. We hypothesize that modulating the TAM level or polarization status in the microenvironment may be an effective approach for CB treatment.

Dispersal history of Miniopterus fuliginosus bats and their associated viruses in east Asia.

In this study, we examined the role of the eastern bent-winged bat (Miniopterus fuliginosus) in the dispersion of bat adenovirus and bat alphacoronavirus in east Asia, considering their gene flows and divergence times (based on deep-sequencing data), using bat fecal guano samples. Bats in China moved to Jeju Island and/or Taiwan in the last 20,000 years via the Korean Peninsula and/or Japan. The phylogenies of host mitochondrial D-loop DNA was not significantly congruent with those of bat adenovirus (m2XY = 0.07, p = 0.08), and bat alphacoronavirus (m2XY = 0.48, p = 0.20). We estimate that the first divergence time of bats carrying bat adenovirus in five caves studied (designated as K1, K2, JJ, N2, and F3) occurred approximately 3.17 million years ago. In contrast, the first divergence time of bat adenovirus among bats in the 5 caves was estimated to be approximately 224.32 years ago. The first divergence time of bats in caves CH, JJ, WY, N2, F1, F2, and F3 harboring bat alphacoronavirus was estimated to be 1.59 million years ago. The first divergence time of bat alphacoronavirus among the 7 caves was estimated to be approximately 2,596.92 years ago. The origin of bat adenovirus remains unclear, whereas our findings suggest that bat alphacoronavirus originated in Japan. Surprisingly, bat adenovirus and bat alphacoronavirus appeared to diverge substantially over the last 100 years, even though our gene-flow data indicate that the eastern bent-winged bat serves as an important natural reservoir of both viruses.

Acute Myocardial Infarction among Young Adult Men in a Region with Warm Climate: Clinical Characteristics and Seasonal Distribution.

The aim of this cross sectional study was to investigate the influence of the seasons on acute myocardial infarction (AMI) among young adult among young adults aged <45 years compared to old adults aged ≥45 years. The seasonal distribution of AMI hospital admissions among young adult men in eastern Taiwan was assessed. Data were extracted from 1413 male AMI patients from January 1994 to December 2015, including onset date, the average temperature (Tave) on the date of AMI hospitalization (AMI-Tave), and conventional risk factors, notably smoking, diabetes, hypertension, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and body mass index (BMI). The 1413 cases were divided into two groups: the young group (n = 138, <45 y/o) and the older group (n = 1275, ≥45 y/o). The differences between groups were examined. Logistic regression analyses were used to evaluate the associations between the seasons and the AMI hospitalization among the young group. The young group showed significantly higher percentage of smokers, BMI, total cholesterol levels, and triglycerides levels but lower percentage of diabetes and hypertension than the older group (p < 0.05). AMI hospitalization in winter was significantly greater compared to the other seasons among the young group (p < 0.05). Winter hospitalization was significantly associated with the young group relative to the older group (adjusted OR 1.750; 95% CI 1.151 to 2.259), while winter AMI-Tave in the young group was similar to that in the older group. Young adult men diagnosed with AMI are more likely than older adult men to be smokers, obese, and show an onset dependent on winter but not low-temperature in a region with a warm climate.

Clinical feasibility of the augmented reality computer-assisted spine surgery system for percutaneous vertebroplasty.

PURPOSE: This study aimed to demonstrate that the augmented reality computer-assisted spine surgery (ARCASS) system is clinically feasible for percutaneous vertebroplasty (PVP). METHODS: This prospective case-control study included the patients undergoing PVP under the assistance of the ARCASS system between July 1, 2013, and October 31, 2014. The control group was the age- and gender-matched patients who underwent standard PVP and met the same eligible criteria as the case group. Primary outcome was the frequency of fluoroscopy. Secondary outcomes were the accuracy of bony entry point and operative time. RESULTS: Eighteen patients were included in this study: 9 patients with 11 levels of lesions in the ARCASS group and 9 patients with 10 levels of lesions in the control group. Compared with the control group, the ARCASS group had significantly less frequency of fluoroscopy (6 vs. 18, P < 0.001) and shorter operative time (78 vs. 205 s, P < 0.001) during the process of entry point identification and local anesthesia, which started from the registration of skin entry point at lesion site to the end of bony entry point identification. Regarding accuracy, the ARCASS group had significant greater proportion of 'good' entry point than the control group on lateral views (81.8% vs. 30.0%, P = 0.028) and anteroposterior views (72.7% vs. 20.0%, P = 0.020). CONCLUSION: This study revealed that the ARCASS system was clinically feasible for PVP. The guidance of ARCASS system provided more accurate bony entry point with reduced operative time and unnecessary radiation exposure.

NbCycB2 represses Nbwo activity via a negative feedback loop in tobacco trichome development.

The transcription factor Woolly (Wo) and its downstream gene CycB2 have been shown to regulate trichome development in tomato (Solanum lycopersicum). It has been demonstrated that only the gain-of-function allele of Slwo (SlWoV, the Slwo woolly motif mutant allele) can increase the trichome density; however, it remains unclear why the two alleles function differently in trichome development. In this study, we used Nicotiana benthamiana as a model and cloned the homologues of Slwo and SlCycB2 (named Nbwo and NbCycB2). We also constructed a Nbwo gain-of-function allele with the same mutation site as SlWoV (named NbWoV). We found that both Nbwo and NbWoV directly regulate NbCycB2 and their own expression by binding to the promoter of NbCycB2 and their own genomic sequences. As form of a feedback regulation, NbCycB2 negatively regulates trichome formation by repressing Nbwo activity at the protein level. We also found that mutations in the Nbwo woolly motif can prevent repression of NbWoV by NbCycB2, which results in a significant increase in the amount of active Nbwo proteins and in increases in trichome density and the number of branches. Our results reveal a novel reciprocal regulation mechanism between NbCycB2 and Nbwo during trichome formation in N. benthamiana.

Evaluation of Intraarterial Thrombolysis in Treatment of Cosmetic Facial Filler-Related Ophthalmic Artery Occlusion.

BACKGROUND: With an increase in recent years in the number of people receiving cosmetic facial injection treatments of hyaluronic acid, the incidence of hyaluronic acid embolism has also increased commensurately. Hyaluronic acid embolism leads to serious complications, including blindness, eye and eyelid movement disorders, skin necrosis, and cerebral embolism. However, there is a lack of robust clinical evidence regarding the benefits of treatment for hyaluronic acid embolism by intraarterial thrombolysis therapy. METHODS: This study included 24 patients with a decrease in visual acuity and other complications induced by facial hyaluronic acid injection. Patients underwent emergency intraarterial thrombolysis therapy by injection of hyaluronidase (500 to 1500 units) alone or hyaluronidase (750 to 1500 units) combined with urokinase (100,000 to 250,000 units), followed in both cases by a general symptomatic treatment and nutritional therapy. RESULTS: Ten (42 percent) of 24 patients ultimately had improvements to visual acuity, even when the clinical application of the thrombolytic treatments had passed the recommended window for optimal treatment. In all cases, patients' facial skin necrosis was restored to nearly normal appearance. In addition, the authors found that hyaluronidase combined with urokinase was a more effective therapy than hyaluronidase alone. CONCLUSIONS: The authors' results indicate that intraarterial thrombolysis therapy is beneficial to patients suffering from blindness induced by hyaluronic acid embolism. The therapy was shown to be worthy of clinical application because it alleviated the impairment to patients' vision and was also beneficial in the recovery from other serious complications, including eye movement disorder, eye edema, headaches, and skin necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Correlation of anti-acetylcholine receptor antibody levels and long-term outcomes of juvenile myasthenia gravis in Taiwan: a case control study.

BACKGROUND: Myasthenia gravis is the most common disease affecting the neuromuscular junction. The most common etiology among patients with juvenile myasthenia gravis is the production of antibodies against the acetylcholine receptor. However, the clinical outcome in relation to serum levels of anti-acetylcholine receptor antibodies in juvenile myasthenia gravis has rarely been discussed. We aimed to analyze the correlation between the presence of anti-acetylcholine receptor antibodies and outcome in juvenile myasthenia gravis. METHODS: Patients diagnosed with juvenile myasthenia gravis younger than of 20 years of age were retrospectively recruited from January 1995 to February 2017 in a tertiary referral medical center. According to the Myasthenia Gravis Foundation of America outcome scale, the primary outcome was complete symptom remission and cessation of medications for at least 1 year measured 2 years after diagnosis. Secondary outcome was complete symptom remission at the last outpatient clinic. RESULTS: A total of 54 patients were followed up for over 2 years. Nine patients (9/54, 16.7%) achieved complete remission without medication use at 2 years after diagnosis. Thirteen (24.1%) patients achieved complete remission during longer follow-up periods. Those with negative anti-acetylcholine receptor antibodies were more likely to achieve complete remission at 2 years (6/15 [40%] vs. 3/39 [7.7%], 95% Confidence interval [CI] 1.670 to 38.323) and at the last outpatient clinic follow-up (8/15 [53.3%] vs. 5/39 [12.8%], 95% CI 2.367 to 20.704). Thirteen patients with comorbid autoimmune thyroid diseases were older than those without disease (11.8 ± 5.8 years old vs. 8.0 ± 6.3 years old, 95% CI 0.018 to 7.33). Moreover, patients negative for anti-acetylcholine receptor antibodies were less likely comorbid with autoimmune thyroid disease (1/35 [2.9%] vs. 12/71 [16.9%], 95% CI 0.018 to 1.161). CONCLUSIONS: Juvenile myasthenia gravis patients without anti-acetylcholine antibodies exhibited significantly increased complete remission rates and a reduced likelihood of comorbid autoimmune thyroid diseases compared with those with anti-acetylcholine receptor antibodies among Chinese.