Role of serum eosinophil cationic protein in distinct endotypes of chronic rhinosinusitis.

BACKGROUND: Serum eosinophil cationic protein (ECP) levels affect the surgical outcome of chronic rhinosinusitis (CRS) with nasal polyps. Primary CRS can be classified into type 2 (T2) and non-T2. We aimed to differentiate the role of serum ECP levels in surgical outcomes between the distinct endotypes of primary CRS. METHODS: We prospectively enrolled patients with bilateral primary CRS who underwent surgical treatment with postoperative follow-up for at least 12 months. Endotyping and serum parameter measurements were completed within 1 week before surgery. RESULTS: In total, 113 patients were enrolled, including 65 with T2 CRS and 48 with non-T2 CRS. Patients in the T2 CRS group with uncontrolled CRS had significantly higher serum ECP levels than those in patients in the non-T2 CRS group. An optimal cut-off value was obtained at 17.0 λg/L using the receiver operating characteristic curve, attaining a sensitivity of 91.7% and specificity of 56.6%. Multivariate logistic regression analysis showed that a higher serum ECP level was an independent factor for postoperative uncontrolled disease. The hazard ratio was 11.3 for the T2 group, with serum ECP levels over 17.0 λg/L. In the non-T2 group, no parameters were significantly correlated with postoperative uncontrolled CRS. CONCLUSIONS: Serum ECP levels appear to be a feasible predictor of postoperative uncontrolled disease in patients with T2 CRS as preoperative serum ECP levels >17.0 λg/L in these patients have an approximately 16.7-fold increased risk of postoperative uncontrolled disease and should be closely monitored.

Tissue eosinophilia and computed tomography features in paediatric chronic rhinosinusitis with nasal polyps requiring revision surgery.

BACKGROUND: Endoscopic sinus surgery (ESS) is an effective and safe treatment modality for medically recalcitrant chronic rhinosinusitis (CRS) in the paediatric population, especially in older children or those with nasal polyposis (CRSwNP). We aimed to elucidate the inflammatory pattern and clinical characteristics of CRSwNP related to revision surgery after ESS in a paediatric population. METHODS: We retrospectively enrolled 146 patients with bilateral CRSwNP. Twenty-two patients had recurrent nasal polyps that required revision surgery. The clinical characteristics, computed tomography (CT) features, tissue eosinophil count, and immunoactivity of signature cytokines in the two groups were analysed. RESULTS: Tissue eosinophil infiltration and immunoreactivity of eosinophilic cationic protein and IL-5 in the sinus mucosa were higher in patients that required revision surgery. The revision surgery group was significantly younger and had positive aeroallergen test results, higher total Lund-Mackay scores, and ethmoid/maxillary sinus ratio on CT images than those without revision surgery. A nomogram was developed to predict the probability of the requirement of revision surgery according to the logistic regression analysis results. CONCLUSIONS: We developed a nomogram model using clinical characteristics, tissue eosinophilia, and CT features for the preoperative identification of patients vulnerable to revision surgery in paediatric CRSwNP. This could help clinicians predict the probability of recurrence and perform intensive postoperative adjunct therapy and follow-up.

Identifying a sphenoid sinus fungus ball using a nomogram model.

BACKGROUND: Sphenoid sinus fungus ball (SSFB) is a rare entity and usually presents with non-specific symptoms. SSFB could potentially lead to serious orbital and intracranial complications. Computed tomography (CT) scan is usually the first imaging test of the diagnostic workup in patients with specific clinical symptoms. This study aimed to compare the clinical characteristics and CT features between SSFB and unilateral (non-fungus ball) chronic sphenoid rhinosinusitis (USRS) and help differentiate between these two most common inflammatory diseases of the sphenoid sinus. METHODS: By retrospective database review, 66 patients with a histopathologic diagnosis of isolated SSFB were recruited for analysis. Fifty-four patients who underwent endoscopic sinus surgery with clinical and histopathological diagnoses of USRS were enrolled as the control group. Clinical characteristics and CT features were evaluated. RESULTS: Headache, rhinorrhoea, nasal obstruction, postnasal dripping, and hyposmia were the most common symptoms in both groups. In the univariate analysis, older age, lower white blood cell counts, irregular surface, bony dehiscence, lateral wall sclerosis, and intralesional hyperdensity (IH) were significant predictors for SSFB. Older age, irregular surface, and IH remained statistically significant in the multivariate analysis. Based on the results of the regression analysis, a nomogram for predicting the probability of SSFB was plotted. CONCLUSIONS: We developed a nomogram model as a novel preoperative diagnostic tool for identifying SSFB according to the predictors both in clinical characteristics and on CT features. This could help the clinicians in predicting the probability of SSFB, to reduce ineffective or delayed treatment and occurrence of complications.

Sleep impairment in patients with empty nose syndrome.

BACKGROUND: Empty nose syndrome (ENS) is characterized by paradoxical nasal obstruction that usually occurs after turbinate surgery. Patients with ENS may also experience significant psychiatric symptoms and sleep dysfunction, which negatively affect the quality of life of affected subjects. This study aimed to evaluate sleep impairment and sleepiness in patients with ENS. METHODS: Patients with ENS and control participants were recruited prospectively. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Epworth Sleepiness Scale (EpSS), and modified sleep quality index (MSQI) were used to evaluate the participants before and after nasal surgery. RESULTS: Forty-eight patients with ENS and forty-eight age- and sex-matched control subjects were enrolled. The SNOT-25, ENS6Q, EpSS, and MSQI scores in the ENS group were all significantly higher than those in the control group before and after surgery. After surgery, ENS patients all exhibited significant improvements in SNOT-25, ENS6Q, EpSS, and MSQI scores. Regression analysis revealed that SNOT-25 score was a significant predictor of EpSS and MSQI in preoperative evaluations. ENS patients experiencing daytime sleepiness suffered from significantly more "dryness of nose" and "suffocation" than those not experiencing daytime sleepiness. CONCLUSIONS: Patients with ENS experienced significantly impaired sleep quality and sleepiness. Nasal reconstruction surgery improved the sleep quality of ENS patients. The severity of sleep dysfunction is associated with the severity of ENS symptoms. Recognizing individuals with significant sleep impairment and sleepiness and providing appropriate management are critical issues for ENS patients.

Left ventricle geometry, atrial strain, ventricle strain, and hemodynamics across aortic valve before and after transcatheter aortic valve replacements.

INTRODUCTION: Transcatheter aortic valve replacements (TAVRs) has become widespread throughout the world. To date, there are no echocardiographic studies of TAVR patients from Southeast Asia (SEA). We sought to evaluate (1) changes in echocardiographic and strain values pre- and post-TAVR (2) relationship between aortic stenosis (AS) severity and strain values, (3) left ventricle geometry in severe AS, (4) relationship of flow rate to dimensionless index (DVI) and acceleration time (AT), and (5) effect of strains on the outcome. MATERIALS AND METHODS: Retrospective study of 112 TAVR patients in our centre from 2009 to 2020. The echocardiographic and strain images pre (within 1 month), post (day after), and 6 months post-TAVR were analyzed by expert echocardiographer. RESULTS: The ejection fraction (EF) increased at 6 months (53.02 ± 12.12% to 56.35 ± 9.00%) (p=0.044). Interventricular septal thickness in diastole (IVSd) decreased (1.27 ± 0.21 cm to 1.21 ± 0.23 cm) (p=0.038) and left ventricle internal dimension in diastole (LVIDd) decreased from 4.77 ± 0.64 cm to 4.49 ± 0.65 cm (p=0.001). No changes in stroke volume index (SVI pre vs 6 months p=0.187), but the flow rate increases (217.80 ± 57.61 mls/s to 251.94 ± 69.59 mls/s, p<0.001). Global longitudinal strain (GLS) improved from -11.44 ± 4.23% to -13.94 ± 3.72% (p<0.001), left atrial reservoir strain (Lar-S) increased from 17.44 ± 9.16% to 19.60 ± 8.77% (p=0.033). Eight patients (7.5%) had IVSd < 1.0 cm, and 4 patients (3.7%) had normal left ventricle (LV) geometry. There was linear relationship between IVSd and mean PG (r=0.208, p=0.031), between GLS to aortic valve area (AVA) and aortic valve area index (AVAi) (r = - 0.305, p=0.001 and r= - 0.316, p= 0.001). There was also relationship between AT (r=-0.20, p=0.04) and DVI (r=0.35, p<0.001) with flow rate. Patients who died late (after 6 months) had lower GLS at 6 months. (Alive; -13.94 ± 3.72% vs Died; -12.43 ± 4.19%, p=0.001). CONCLUSION: At 6 months, TAVR cause reverse remodelling of the LV with the reduction in IVSd, LVIDd, and improvement in GLS and LAr-S. There is a linear relationship between GLS and AVA and between IVSd and AVA.

Olfaction after endoscopic surgery for sellar and parasellar disease: an updated systematic review and meta-analysis.

BACKGROUND: Whether endoscopic surgery for sellar/parasellar disease causes significant deficits in olfactory function remains unclear. We aimed to systematically review the olfactory outcomes in such settings based on the evidence up to date. METHODS: PubMed, EMBASE, and CENTRAL were searched through February 1, 2021. Included studies were limited to endoscopic surgery for sellar/parasellar disease with follow-up olfactory function measured by standardized olfactory testing methods or subjective assessment. The primary outcome was the change in olfactory function after surgery assessed by standardized olfactory testing methods. The secondary outcome was the change in subjective olfactory function. Random-effects model was used in obtaining combine effects. Study quality was assessed using the Newcastleâ€"Ottawa scale. Sensitivity analysis was carried out using the leave-one-out approach, and publication bias was assessed using Egger's test. RESULTS: The results show no significant difference in olfaction assessed by standardized olfactory testing methods at 1-3 months post-surgery (880 patients in 16 studies) or at 6-12 months post-surgery (1320 patients in 16 studies) compared to pre-surgery, whereas a significantly lower subjective olfaction at 3 months was observed. In addition, the lack of significant change in olfaction as assessed by standardized olfactory testing methods was observed regardless of whether patients were treated with or without the nasoseptal flap (NSF) harvesting. Heterogeneity and publication bias were observed, whereas sensitivity analysis showed the meta-analysis results are robust. CONCLUSION: The findings of this updated systematic review and meta-analysis support the conclusion that endoscopic surgery for sellar and parasellar pathology may pose no greater risk of olfactory dysfunction. In addition, the current evidence does not support there is an increased risk of diminished olfaction among patients treated with NSF during surgery.

Synchronised neural signature of creative mental imagery in reality and augmented reality.

Creativity, transforming imaginative thinking into reality, is a mental imagery simulation in essence. It can be incorporeal, concerns sophisticated and/or substantial thinking, and involves objects. In the present study, a mental imagery task consisting of creating a scene using familiar (FA) or abstract (AB) physical or virtual objects in real (RMI) and augmented reality (VMI) environments, and an execution task involving effectively creating a scene in augmented reality (VE), were utilised. The beta and gamma neural oscillations of healthy participants were recorded via a 32 channel wireless 10/20 international EGG system. In real and augmented environments and for both the mental imagery and execution tasks, the participants displayed a similar cortico-cortical neural signature essentially based on synchronous vs asynchronous beta and gamma oscillatory activities between anterior (i.e. frontal) and posterior (i.e. parietal, occipito-parietal and occipito-temporal) areas bilaterally. The findings revealed a transient synchronised neural architecture that appears to be consistent with the hypothesis according to which, creativity, because of its inherent complexity, cannot be confined to a single brain area but engages various interconnected networks.

Are water precautions necessary after tympanostomy tube placement? A cadaver study.

OBJECTIVES: To determine whether Armstrong pressure equalization tubes allow passage of water into the middle ear with complete submersion in water up to 76 cm for 2 min. METHODS: 10 adult cadaver heads were first assessed for the presence of fluid in both middle ears with zero-degree rigid endoscopes, after being submerged for 2 min in a plastic receptacle filled with 76 cm of water. A 25% perforation was then made in the tympanic membrane of one ear. A myringotomy was then made in the tympanic membrane of the contralateral ear, with the placement of a beveled Armstrong pressure equalization tube. The head was then submerged again for 2 min. Both ears were then examined for the presence of fluid in the middle ear using a rigid endoscope and with suction. RESULTS: Eight out of ten (80%) of the heads showed the presence of fluid in the middle ear on the perforation side after submersion, whereas none of the heads showed fluid in the middle ear on the side with the pressure equalization tube. CONCLUSIONS: At depths of 76 cm, total submersion in water for 2 min does not facilitate the passage of water into the middle ear via an Armstrong pressure equalization tube.

Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508 culture-supernatant ameliorate obesity by inducing thermogenesis in obese-mice.

Excessive body fat and the related dysmetabolic diseases affect both developed and developing countries. The aim of this study was to investigate the beneficial role of a bacterial culture supernatant (hereafter: BS) of Lactobacillus and Bifidobacterium and their potential mechanisms of action on white-fat browning and lipolysis. For selection of four candidates among 55 Lactic acid producing bacteria (LAB) from human infant faeces, we evaluated by Oil Red O staining and Ucp1 mRNA quantitation in 3T3-L1 preadipocytes. The expression of browning and lipolysis markers was examined along with in vitro assays. The possible mechanism was revealed by molecular and biological experiments including inhibitor and small interfering RNA (siRNA) assays. In a mouse model, physiological, histological, and biochemical parameters and expression of some thermogenesis-related genes were compared among six experimental groups fed a high-fat diet and one normal-diet control group. The results allow us to speculate that BS treatment promotes browning and lipolysis both in vitro and in vivo. Moreover, the BS may activate thermogenic programs via a mechanism involving PKA-CREB signaling in 3T3-L1 cells. According to our data, we can propose that two LAB strains, Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508, may be good candidates for a dietary supplement against obesity and metabolic diseases; however, further research is required for the development as dietary supplements or drugs.

Ex utero intrapartum treatment to extracorporeal membrane oxygenation: lifesaving management of a giant cervical teratoma.

BACKGROUND: Ex utero intrapartum treatment ('EXIT' procedure) is a well described method for maintaining maternal-fetal circulation in the setting of airway obstruction from compressive neck masses. When ex utero intrapartum treatment to airway is not feasible, ex utero intrapartum treatment to extracorporeal membrane oxygenation ('ECMO') has been described in fetal cardiopulmonary abnormalities. OBJECTIVE: This paper presents the case of a massively compressive midline neck teratoma managed with ex utero intrapartum treatment to extracorporeal membrane oxygenation, allowing for neonatal survival, with controlled airway management and subsequent resection. CASE REPORT: A 34-year-old-female presented with a fetal magnetic resonance imaging scan demonstrating a 15 cm compressive midline neck teratoma. Concern for failure of ex utero intrapartum treatment to airway was high. The addition of the ex utero intrapartum treatment to extracorporeal membrane oxygenation procedure provided time for the planned subsequent resection of the mass and tracheostomy. CONCLUSION: Ex utero intrapartum treatment procedures allow for securement of the difficult neonatal airway, while maintaining a supply of oxygenated blood to the newborn. Ex utero intrapartum treatment circulation lasts on average less than 30 minutes. The arrival of extracorporeal membrane oxygenation has enabled the survival of neonates with disease processes previously incompatible with life.

Zinc-depletion associates with tissue eosinophilia and collagen depletion in chronic rhinosinusitis.

BACKGROUND: Zinc plays an important role in many biological processes. Reduced zinc levels have been found in chronic rhinosinusitis (CRS) patients, however, its role in the pathophysiology of this disease remains unknown. This study examined zinc levels in the serum, mucus and tissue from CRS patients in relation to collagen content and eosinophil infiltration. The effect of zinc depletion on inflammatory cytokine production and collagen synthesis was assessed in vitro. METHODOLOGY: Zinc levels were determined in serum, mucus and tissue from controls, CRS with (CRSwNP) and without nasal polyps (CRSsNP) patients. Tissue zinc levels, collagen and inflammatory cell infiltration was examined using zinquin assays, immunofluorescence and histology on Tissue Micro Arrays. Cytokine expression and collagen synthesis was evaluated in zinc depleted primary human nasal epithelial cells (HNECs) and primary fibroblasts. RESULTS: CRSwNP patients showed reduced tissue zinc levels in correlation with a reduction in collagen content, and increased eosinophil numbers. Zinc depletion of HNECs and fibroblasts induced the production of pro-inflammatory cytokines and MUC5AC and reduced collagen secretion. CONCLUSIONS: These results suggest mucosal zinc depletion associates with tissue eosinophilia and collagen depletion in CRSwNP and induces pro-inflammatory cytokine expression and reduction of collagen synthesis in vitro.

What drives depression in empty nose syndrome? A Sinonasal Outcome Test-25 subdomain analysis.

BACKGROUND: Empty nose syndrome (ENS) is a debilitating disorder characterised by paradoxical nasal obstruction after excessive surgical excision of nasal tissues. ENS negatively impacts the quality of life (QOL) and psychological status of patients. This study aimed to determine the associations among disease-specific QOL impairments and the severity of anxiety and depression before and after surgery in ENS patients. METHODS: A total of 68 ENS patients were prospectively recruited and underwent submucosal Medpor implantation. QOL impairments and the severity of anxiety and depression were evaluated using the Sinonasal Outcome Test-25 (SNOT-25), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI) 1 day before and 6 months after surgery. RESULTS: The BDI-II and BAI scores were significantly associated with the total score and ear/facial symptoms, psychological dysfunction, sleep dysfunction, and empty nose symptoms domains of the SNOT-25. Surgery improved disease-specific and psychological symptoms. Post-operative changes in the BDI-II score were correlated with changes in the total score and sleep dysfunction and empty nose symptoms domains of the SNOT-25. A SNOT-25 total score of greater than 60, sleep dysfunction domain score of greater than 18, and empty nose symptoms domain score of greater than 14 were good predictors of moderate-to-severe depression. CONCLUSIONS: ENS symptoms are associated with psychological burden and could be good predictors of moderate-to-severe depression. Targeted symptom improvement could reduce the psychological burden.

A new technique for evaluating heel xerosis grade and the effects of moisturizer on heel skin dryness.

BACKGROUND: Dryness-related heel skin problems are common; however, there are very few studies about heel skin dryness. The objective of this study was to develop new assessment methods for evaluating heel skin dryness, to clarify the characteristics associated with heal skin dryness, and assess the effectiveness of moisturizer use according to dryness severity. MATERIALS AND METHODS: We investigated the heel skin of 150 Korean women (aged 20-78 years). Heel skin images were taken using a DSLR camera and the distribution or severity of flakes, scaling, cracking, and fissures were visually assessed. Skin properties such as hydration, transepidermal water loss (TEWL), amount of dead skin cells, and efficacy of moisturizer were evaluated according to heel xerosis grade. Furthermore, as conventional evaluation methods for desquamation are not appropriate for heel skin, we developed new techniques using binarization of magnified images. RESULTS: Skin hydration tended to decrease and TEWL tended to increase as heel dryness grade increased. The amount of dead skin cells increased with increasing dryness grade using the new technique. Subjects in the severe dryness group achieved similar hydration levels as normal subjects at baseline after 3 hours of moisturizer application. CONCLUSION: Our new methods of visually classifying heel dryness and quantifying dead skin cells using magnified images effectively evaluated heel skin properties. As heel skin is prone to dryness, daily repetitive application of moisturizer might be helpful for hydrating dry heel skin, and ultimately preventing complications.

Association between fetal fraction on cell-free DNA testing and first-trimester markers for pre-eclampsia.

OBJECTIVES: To evaluate the association between fetal fraction on cell-free DNA (cfDNA) testing and first-trimester markers for pre-eclampsia, and to investigate the possible association of low fetal fraction with increased risks for pre-eclampsia (PE) and fetal growth restriction (FGR). METHODS: This was a retrospective cohort study including all women with a singleton pregnancy who had risk calculation for PE and FGR between 11 + 0 and 13 + 6 weeks' gestation and who also had cfDNA as a primary or secondary screening test for chromosomal abnormalities at any gestational age at two fetal medicine clinics in Sydney and Melbourne, Australia, between March 2013 and May 2017. Logarithmically transformed fetal fraction results were adjusted for gestational age and maternal characteristics. Associations with mean arterial pressure (MAP), mean uterine artery pulsatility index (UtA-PI), pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), and risks for PE < 34 weeks, PE < 37 weeks and FGR < 37 weeks were analyzed using correlation analysis and univariable and multivariable linear regressions. RESULTS: In total, 4317 singleton pregnancies that underwent cfDNA testing with fetal fraction reported were included. Significant prediction of fetal fraction was provided by gestational age, conception by in-vitro fertilization, maternal age, body mass index, chronic hypertension, diabetes mellitus, South Asian ethnicity and being parous without history of PE or FGR. Fetal fraction was associated inversely with MAP and UtA-PI and associated positively with PAPP-A and PlGF. The lower the fetal fraction, the higher were the risks for PE < 34 weeks, PE < 37 weeks and FGR < 37 weeks (P < 0.001 for all). CONCLUSIONS: There is a significant association between fetal fraction result and first-trimester markers for adverse pregnancy outcome. Low fetal fraction is associated with an increased risk for pregnancy complication, but its capacity to act an as independent first-trimester marker in an algorithm for screening for PE and FGR requires further research. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

A novel technique for unilateral supraglottoplasty.

OBJECTIVES: Traditional supraglottoplasty for pediatric laryngomalacia is most commonly conducted with either CO2 laser or cold steel instruments. While the procedure enjoys high success rates, serious complications such as excessive bleeding, supraglottic stenosis and aspiration can occur. Unilateral coblation supraglottoplasty may reduce this risk, but data on respiratory and swallowing outcomes are lacking. This study reports our experiences with unilateral coblation supraglottoplasty. METHODS: Pediatric patients with severe congenital laryngomalacia who underwent unilateral supraglottoplasty at a single institution from 2013 to 2016 were retrospectively reviewed. Bipolar radiofrequency ablation (Coblation) was utilized with partial arytenoidectomy, aryepiglottoplasty, and advancement of mucosal flaps. Outcome measures included apnea-hypopnea index (AHI), weight-by-age percentile, and decannulation rate. RESULTS: Twelve patients were included with an average age of 13.1 months (range 2-28 months). In patients without tracheostomy, 88% had complete resolution of respiratory symptoms, while the remainder had significant improvement. In patients without gastrostomy tubes, there was an average increase in weight-age percentile of 6.1, 7.8, and 15.3 points at 1, 3, and 6 months postoperatively, respectively. Three patients had complete polysomnography data with a mean preoperative AHI of 19.3 and postoperative AHI of 4.0. Three of four patients with tracheostomy have been decannulated at a mean follow-up of 1.5 years. There were no early or late postoperative complications and no revision supraglottoplasty. CONCLUSION: Unilateral supraglottoplasty with bipolar radiofrequency ablation can improve respiratory symptoms and decrease OSA severity in severe congenital laryngomalacia. This technique is safe and can lead to substantial improvement in AHI in patients with OSA.

Ovo-vegetarian diet is associated with lower systemic blood pressure in Taiwanese women.

OBJECTIVE: This study was designed to investigate blood pressure (BP) profiles among Taiwanese women with different dietary patterns. STUDY DESIGN: Cross-sectional study. METHODS: A total of 269 non-hypertensive Taiwanese women, 40 years of age or older, were surveyed using structured questionnaires, and measurements of BP and physiological parameters were made. To assess differences among vegans, ovo-vegetarians, and meat eaters in terms of BP, demographic, and health behavior data, the chi-squared and Fisher's exact tests were employed for categorical variables, and analysis of variance and independent t-tests were performed for continuous variables. Multiple regression analysis was used to examine the relationship between BP and dietary patterns while controlling for potential confounding factors. RESULTS: A significant difference was found among the three test groups in terms of age, education, employment, stress, and waist-hip ratio. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) significantly differed among the three groups. After controlling for age, body weight, waist circumference, and hip circumference, the three groups were observed to be a significant risk factor of the SBP and DBP. The SBP and DBP of the ovo-vegetarian group were significantly lower than those of the meat-eater group. No significant differences were found between the vegan and meat-eater groups in terms of SBP and DBP. CONCLUSION: Dietary pattern is a likely risk factor for SBP and DBP outcomes in Taiwanese women. In particular, the SBP and DBP of ovo-vegetarians are the lowest among the values observed for all dietary patterns. This finding suggests that an ovo-vegetarian diet is beneficial for long-term BP control and prevention of hypertension in females.

LSD1 demethylates HIF1α to inhibit hydroxylation and ubiquitin-mediated degradation in tumor angiogenesis.

Lysine-specific demethylase 1 (LSD1), which has been considered as a potential therapeutic target in human cancer, has been known to regulate many biological functions through its non-histone substrates. Although LSD1-induced hypoxia-inducible factor alpha (HIF1α) demethylation has recently been proposed, the effect of LSD1 on the relationship between HIF1α post-translational modifications (PTMs) and HIF1α-induced tumor angiogenesis remains to be elucidated. Here, we identify a new methylation site of the HIF1α protein antagonized by LSD1 and the interplay between HIF1α protein methylation and other PTMs in regulating tumor angiogenesis. LSD1 demethylates HIF1α at lysine (K) 391, which protects HIF1α against ubiquitin-mediated protein degradation. LSD1 also directly suppresses PHD2-induced HIF1α hydroxylation, which has a mutually dependent interplay with Set9-mediated HIF1α methylation. Moreover, the HIF1α acetylation that occurs in a HIF1α methylation-dependent manner is inhibited by the LSD1/NuRD complex. HIF1α stabilized by LSD1 cooperates with CBP and MTA1 to enhance vascular endothelial growth factor (VEGF)-induced tumor angiogenesis. Thus, LSD1 is a key regulator of HIF1α/VEGF-mediated tumor angiogenesis by antagonizing the crosstalk between PTMs involving HIF1α protein degradation.

Lymphangioma Arising From the Ovary.

Primary lymphangioma arising from the ovary is a rare tumor, with only 24 cases reported to date. As it is often accompanied by ascites or recurrence, similar to a malignant tumor, an aggressive treatment approach is used for disease control. In this report, we describe a 75-year-old woman with a left ovarian lymphangioma that increased in size during the menopause period. Microscopic examination of the tumor showed thin-walled multilocular cystic spaces and immunoreactivity for D2-40, a specific marker for lymphatic endothelium, lining the cystic spaces. The patient has been doing well for 5 years postoperatively. Ovarian cystic lymphangioma should be included in the differential diagnosis of an ovarian cyst and long-term follow-up is recommended to exclude malignant behavior. We also summarize a total of 25 cases, including the case presented here.