Delipidation Destresses Drosophila.

Stress responses at an organism level are complex and poorly understood. In this issue of Immunity, Li et al. demonstrate that Drosophila kidney excretes blood lipids to minimize damage by reactive oxygen species and that this function is essential for animal survival.

Bacterial-derived uracil as a modulator of mucosal immunity and gut-microbe homeostasis in Drosophila.

All metazoan guts are subjected to immunologically unique conditions in which an efficient antimicrobial system operates to eliminate pathogens while tolerating symbiotic commensal microbiota. However, the molecular mechanisms controlling this process are only partially understood. Here, we show that bacterial-derived uracil acts as a ligand for dual oxidase (DUOX)-dependent reactive oxygen species generation in Drosophila gut and that the uracil production in bacteria causes inflammation in the gut. The acute and controlled uracil-induced immune response is required for efficient elimination of bacteria, intestinal cell repair, and host survival during infection of nonresident species. Among resident gut microbiota, uracil production is absent in symbionts, allowing harmonious colonization without DUOX activation, whereas uracil release from opportunistic pathobionts provokes chronic inflammation. These results reveal that bacteria with distinct abilities to activate uracil-induced gut inflammation, in terms of intensity and duration, act as critical factors that determine homeostasis or pathogenesis in gut-microbe interactions.

Response of the microbiome-gut-brain axis in Drosophila to amino acid deficit.

A balanced intake of macronutrients-protein, carbohydrate and fat-is essential for the well-being of organisms. An adequate calorific intake but with insufficient protein consumption can lead to several ailments, including kwashiorkor1. Taste receptors (T1R1-T1R3)2 can detect amino acids in the environment, and cellular sensors (Gcn2 and Tor)3 monitor the levels of amino acids in the cell. When deprived of dietary protein, animals select a food source that contains a greater proportion of protein or essential amino acids (EAAs)4. This suggests that food selection is geared towards achieving the target amount of a particular macronutrient with assistance of the EAA-specific hunger-driven response, which is poorly understood. Here we show in Drosophila that a microbiome-gut-brain axis detects a deficit of EAAs and stimulates a compensatory appetite for EAAs. We found that the neuropeptide CNMamide (CNMa)5 was highly induced in enterocytes of the anterior midgut during protein deprivation. Silencing of the CNMa-CNMa receptor axis blocked the EAA-specific hunger-driven response in deprived flies. Furthermore, gnotobiotic flies bearing an EAA-producing symbiotic microbiome exhibited a reduced appetite for EAAs. By contrast, gnotobiotic flies with a mutant microbiome that did not produce leucine or other EAAs showed higher expression of CNMa and a greater compensatory appetite for EAAs. We propose that gut enterocytes sense the levels of diet- and microbiome-derived EAAs and communicate the EAA-deprived condition to the brain through CNMa.

How microbiomes influence metazoan development: insights from history and Drosophila modeling of gut-microbe interactions.

Since Metchnikoff developed his views on the intestinal microflora, much effort has been devoted to understanding the role of gut microbiomes in metazoan physiology. Despite impressive data sets that have been generated by associating a phenotype-causing commensal community with its corresponding host phenotype, the field continues to suffer from descriptive and often contradictory reports. Hence, we cannot yet draw clear conclusions as to how the modifications of microbiomes cause physiological changes in metazoans. Unbiased, large-scale genetic screens to identify key genes, on both microbial and host sides, will be essential to gain mechanistic insights into gut-microbe interactions. The Drosophila genome-commensal microbiome genetic model has proven to be well suited to dissect the complex reciprocal cross talk between the host and its microbiota. In this review, we present a historical account, current views, and novel perspectives for future research directions based on the insights gleaned from the Drosophila gut-microbe interaction model.

SEC22B inhibition attenuates colorectal cancer aggressiveness and autophagic flux under unfavorable environment.

Autophagy has bidirectional functions in cancer by facilitating cell survival and death in a context-dependent manner. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are a large family of proteins essential for numerous biological processes, including autophagy; nevertheless, their potential function in cancer malignancy remains unclear. Here, we explored the gene expression patterns of SNAREs in tissues of patients with colorectal cancer (CRC) and discovered that SEC22B expression, a vesicle SNARE, was higher in tumor tissues than in normal tissues, with a more significant increase in metastatic tissues. Interestingly, SEC22B knockdown dramatically decreased CRC cell survival and growth, especially under stressful conditions, such as hypoxia and serum starvation, and decreased the number of stress-induced autophagic vacuoles. Moreover, SEC22B knockdown successfully attenuated liver metastasis in a CRC cell xenograft mouse model, with histological signs of decreased autophagic flux and proliferation within cancer cells. Together, this study posits that SEC22B plays a crucial role in enhancing the aggressiveness of CRC cells, suggesting that SEC22B might be an attractive therapeutic target for CRC.

Impact of boost sequence in concurrent chemo-radiotherapy on newly diagnosed IDH-wildtype glioblastoma multiforme.

BACKGROUND: The standard of care for glioblastoma multiforme (GBM) is maximal surgical resection followed by conventional fractionated concurrent chemoradiotherapy (CCRT) with a total dose of 60 Gy. However, there is currently no consensus on the optimal boost technique for CCRT in GBM. METHODS: We conducted a retrospective review of 398 patients treated with CCRT between 2016 and 2021, using data from two institutional databases. Patients were divided into two groups: those receiving sequential boost (SEB, N = 119) and those receiving simultaneous integrated boost (SIB, N = 279). The primary endpoint was overall survival (OS). To minimize differences between the SIB and SEB groups, we conducted propensity score matching (PSM) analysis. RESULTS: The median follow-up period was 18.6 months. Before PSM, SEB showed better OS compared to SIB (2-year, 55.6% vs. 44.5%, p = 0.014). However, after PSM, there was no significant difference between two groups (2-year, 55.6% vs. 51.5%, p = 0.300). The boost sequence was not associated with inferior OS before and after PSM (all p-values > 0.05). Additionally, the rates of symptomatic pseudo-progression were similar between the two groups (odds ratio: 1.75, p = 0.055). CONCLUSIONS: This study found no significant difference in OS between SEB and SIB for GBM patients treated with CCRT. Further research is needed to validate these findings and to determine the optimal boost techniques for this patient population.

Radotinib Decreases Prion Propagation and Prolongs Survival Times in Models of Prion Disease.

The conversion of cellular prion protein (PrPC) into pathogenic prion isoforms (PrPSc) and the mutation of PRNP are definite causes of prion diseases. Unfortunately, without exception, prion diseases are untreatable and fatal neurodegenerative disorders; therefore, one area of research focuses on identifying medicines that can delay the progression of these diseases. According to the concept of drug repositioning, we investigated the efficacy of the c-Abl tyrosine kinase inhibitor radotinib, which is a drug that is approved for the treatment of chronic myeloid leukemia, in the treatment of disease progression in prion models, including prion-infected cell models, Tga20 and hamster cerebellar slice culture models, and 263K scrapie-infected hamster models. Radotinib inhibited PrPSc deposition in neuronal ZW13-2 cells that were infected with the 22L or 139A scrapie strains and in cerebellar slice cultures that were infected with the 22L or 263K scrapie strains. Interestingly, hamsters that were intraperitoneally injected with the 263K scrapie strain and intragastrically treated with radotinib (100 mg/kg) exhibited prolonged survival times (159 ± 28.6 days) compared to nontreated hamsters (135 ± 9.9 days) as well as reduced PrPSc deposition and ameliorated pathology. However, intraperitoneal injection of radotinib exerted a smaller effect on the survival rate of the hamsters. Additionally, we found that different concentrations of radotinib (60, 100, and 200 mg/kg) had similar effects on survival time, but this effect was not observed after treatment with a low dose (30 mg/kg) of radotinib. Interestingly, when radotinib was administered 4 or 8 weeks after prion inoculation, the treated hamsters survived longer than the vehicle-treated hamsters. Additionally, a pharmacokinetic assay revealed that radotinib effectively crossed the blood-brain barrier. Based on our findings, we suggest that radotinib is a new candidate anti-prion drug that could possibly be used to treat prion diseases and promote the remission of symptoms.

Insensitive Effects of Inflammatory Cytokines on the Reference Genes of Synovial Fluid Resident-Mesenchymal Stem Cells Derived from Rheumatoid Arthritis Patients.

Mesenchymal stem cells derived from rheumatoid arthritis patients (RA-MSCs) provide an understanding of a variety of cellular and immunological responses within the inflammatory milieu. Sustained exposure of MSCs to inflammatory cytokines is likely to exert an influence on genetic variations, including reference genes (RGs). The sensitive effect of cytokines on the reference genes of RA-SF-MSCs may be a variation factor affecting patient-derived MSCs as well as the accuracy and reliability of data. Here, we comparatively evaluated the stability levels of nine RG candidates, namely GAPDH, ACTB, B2M, EEF1A1, TBP, RPLP0, PPIA, YWHAZ, and HPRT1, to find the most stable ones. Alteration of the RG expression was evaluated in MSCs derived from the SF of healthy donors (H-SF-MSCs) and in RA-SF-MSCs using the geNorm and NormFinder software programs. The results showed that TBP, PPIA, and YWHAZ were the most stable RGs for the normalization of H-SF-MSCs and RA-SF-MSCs using RT-qPCR, whereas ACTB, the most commonly used RG, was less stable and performed poorly. Additionally, the sensitivity of RG expression upon exposure to proinflammatory cytokines (TNF-α and IL-1ß) was evaluated. RG stability was sensitive in the H-SF-MSCs exposed to TNF-α and IL-1ß but insensitive in the RA-SF-MSCs. Furthermore, the normalization of IDO expression using ACTB falsely diminished the magnitude of biological significance, which was further confirmed with a functional analysis and an IDO activity assay. In conclusion, the results suggest that TBP, PPIA, and YWHAZ can be used in SF-MSCs, regardless of their exposure to inflammatory cytokines.

Combined endoscopic endonasal and transorbital multiportal approach for complex skull base lesions involving multiple compartments.

PURPOSE: This study defines the specific areas that connect the surgical corridors of the endoscopic endonasal (EEA) and transorbital approach (TOA) to identify adequate clinical applications and perspectives of this combined multiportal approach. METHODS: Consecutive patients who underwent combined EEA and TOA procedures for various pathologies involving multiple compartments of the skull base were enrolled. RESULTS: A total of eight patients (2 chondrosarcomas, 2 meningiomas, 2 schwannomas, 1 glioma, and 1 traumatic optic neuropathy) were included between August 2016 and April 2021. The cavernous sinus (CS) was targeted as the connection area of the combined approach in four patients with tumors infiltrating the middle cranial fossa (MCF) and central skull base through the CS. For two patients with MCF tumors extending into the infratemporal fossa (ITF), the horizontal portion of the greater sphenoid wing and the foramen ovale were utilized as the connection area. In the remaining 2 patients, connection was achieved through the optic canal (OC). Gross total and near total resection was achieved in 5 patients with tumors, and circumferential removal of bone composing the OC was performed in one patient with traumatic compressive optic neuropathy. Postoperative complications included one cardiac arrest due to underlying cardiovascular disease and one case of oculomotor nerve palsy. CONCLUSIONS: The combined EEA and TOA procedure is a useful strategy for complex lesions involving multiple compartments of the skull base. Herein, we identified the specific areas connecting the two surgical approaches, allowing a common path for EEA and TOA procedures.

Development of an Inertial Sensor Module for Categorizing Anomalous Kicks in Taekwondo and Monitoring the Level of Impact.

In this study, an inertial measurement unit (IMU) sensor module and software algorithm were developed to identify anomalous kicks that should not be given scores in Taekwondo competitions. The IMU sensor module was manufactured with dimensions of 3 cm × 3 cm × 1.5 cm and consists of a high-g sensor for high acceleration measurement, a 9-DOF sensor, and a Wi-Fi module for wireless communication. In the experiment, anomalous kicks and normal kicks were collected by the IMU sensor module, and an AI model was trained. The anomalous kick determination accuracy of the trained AI model was found to be 97.5%. In addition, in order to check whether the strength of a blow can be distinguished using the IMU sensor module, an impact test was performed with a pendulum under the same test conditions as the impact sensor installed in the impact test setup, and the correlation coefficient was 0.99. This study is expected to contribute to improving scoring reliability by suggesting the possibility of discriminating anomalous kicks, which were difficult to judge in Taekwondo competitions, through the analysis of Taekwondo kicks using inertial data and impulses.

Comparison of Breast Cancer and Cervical Cancer in Uzbekistan and Korea: The First Report of The Uzbekistan-Korea Oncology Consortium.

In general, as a country's economy, education level, and life expectancy increase, the incidence of cancer increases. This is because the peak incidence of cancer occurs in individuals in their 70s and 80s, and the health proportion of non-communicable diseases increases with the development of the living environment. Changes in diet, lifestyle and enhanced methods of detection contribute to an increase in cancer incidence as well. Recently, Uzbekistan has grown rapidly, and its incidence of cancer is also increasing. In the health management of cancer, not only treatment but also the identification and prevention of causes and effective screening should be considered. South Korea has a common ethnicity with Uzbekistan and has successfully performed national screening for seven major cancers over the past 20 years. The 5-year survival rate after cancer diagnosis in Korea was only 42.9% 20 years ago, but recently it has improved to 70.7%. We formed an advisory consortium in which oncologists from Uzbekistan and Korea could cooperate for cancer management in Uzbekistan. This advisory consortium intends to present the necessary considerations and recommendations for cancer management in Uzbekistan by examining the literature and cancer statistics of Uzbekistan and South Korea. In addition to the overall analysis, we identified and reviewed the major cancers with high morbidity in three categories in Uzbekistan: gynecological cancer (breast and cervical cancer), cancer common in men (lung and liver cancer), and gastrointestinal cancer (stomach and colorectal cancer). This review covers the general cancer statistics of Uzbekistan and a detailed review of gynecological cancer between two countries, and relevant recommendations.

Coordination of multiple dual oxidase-regulatory pathways in responses to commensal and infectious microbes in drosophila gut.

All metazoan guts are in permanent contact with the microbial realm. However, understanding of the exact mechanisms by which the strength of gut immune responses is regulated to achieve gut-microbe mutualism is far from complete. Here we identify a signaling network composed of complex positive and negative mechanisms that controlled the expression and activity of dual oxidase (DUOX), which 'fine tuned' the production of microbicidal reactive oxygen species depending on whether the gut encountered infectious or commensal microbes. Genetic analyses demonstrated that negative and positive regulation of DUOX was required for normal host survival in response to colonization with commensal and infectious microbes, respectively. Thus, the coordinated regulation of DUOX enables the host to achieve gut-microbe homeostasis by efficiently combating infection while tolerating commensal microbes.

Identification and characterization of GAL4 drivers that mark distinct cell types and regions in the Drosophila adult gut.

The gastrointestinal tract in the adult Drosophila serves as a model system for exploring the mechanisms underlying digestion, absorption and excretion, stem cell plasticity, and inter-organ communication, particularly through the gut-brain axis. It is also useful for studying the cellular and adaptive responses to dietary changes, alterations in microbiota and immunity, and systematic and endocrine signals. Despite the various cell types and distinct regions in the gastrointestinal tract, few tools are available to target and manipulate the activity of each cell type and region, and their gene expression. Here, we report 353 GAL4 lines and several split-GAL4 lines that are expressed in enteric neurons (ENs), progenitors (ISCs and EBs), enterocytes (ECs), enteroendocrine cells (EEs), or/and other cell types that are yet to be identified in distinct regions of the gut. We had initially collected approximately 600 GAL4 lines that may be expressed in the gut based on RNA sequencing data, and then crossed them to UAS-GFP to perform immunohistochemistry to identify those that are expressed selectively in the gut. The cell types and regional expression patterns that are associated with the entire set of GAL4 drivers and split-GAL4 combinations are annotated online at http://kdrc.kr/index.php (K-Gut Project). This GAL4 resource can be used to target specific populations of distinct cell types in the fly gut, and therefore, should permit a more precise investigation of gut cells that regulate important biological processes.

Stereotactic radiosurgery for orbital cavernous venous malformation: a single center's experience for 15 years.

BACKGROUND: Stereotactic radiosurgery such as Gamma Knife radiosurgery (GKRS) has been shown to have a good treatment effect for orbital cavernous venous malformation (CVM). However, radiation-induced retinopathy or optic neuropathy is a vision-threatening complication of orbital irradiation. Predicting the post-treatment visual outcome is critical. METHODS: Clinical and radiological outcomes were investigated in 30 patients who underwent GKRS for orbital CVM between July 2005 and February 2020. Measurement of peripapillary retinal nerve fiber layer (pRNFL) thickness using optical coherence tomography (OCT) was obtained in 14 patients. RESULTS: The median clinical and radiological follow-up periods were 46.6 months (range, 15.9-105.8) and 27.5 months (range, 15.4-105.8), respectively. Twenty-eight patients underwent multisession (4 fractions) GKRS. The median cumulative marginal dose was 20 Gy (range, 16-24). Two patients underwent single-session GKRS. Marginal doses were 15 Gy and 10.5 Gy in each patient. The volume of CVM decreased in 29 (97%) patients. Visual acuity was improved in 6 (20%) patients and was stable in 22 (73%) patients. Visual field defect and exophthalmos were improved in all patients. Serial investigation of OCT showed no statistically significant difference in pRNFL thickness after GKRS. Patients with normal average pRNFL thickness showed better visual recovery than patients with thin average pRNFL thickness. CONCLUSIONS: GKRS is an effective and safe treatment option for orbital CVM. The pRNFL thickness before GKRS can be a prognostic indicator for visual recovery in orbital CVM after GKRS.

Optimal Volume of the Residual Tumor to Predict Long-term Tumor Control Using Stereotactic Radiosurgery after Facial Nerve-preserving Surgery for Vestibular Schwannomas.

BACKGROUND: Intended subtotal resection (STR) followed by adjuvant gamma knife radiosurgery (GKRS) has emerged as an effective treatment option for facial nerve (FN) preservation in vestibular schwannomas (VSs). This study aimed to identify the optimal cut-off volume of residual VS to predict favorable outcomes in terms of both tumor control and FN preservation. METHODS: This retrospective study assessed the patients who underwent adjuvant GKRS for residual VS after microsurgery. A total of 68 patients who had been followed up for ≥ 24 months after GKRS were included. Tumor progression was defined as an increase in tumor volume (TV) of ≥ 20%. House-Brackmann grades I and II were considered to indicate good FN function. RESULTS: The median residual TV was 2.5 cm³ (range: 0.3-27.4). The median follow-up period after the first adjuvant GKRS was 64 months (range: 25.7-152.4). Eight (12%) patients showed tumor progression. In multivariate analyses, residual TV was associated with tumor progression (P = 0.003; hazard ratio [HR], 1.229; 95% confidence interval [CI], 1.075-1.405). A residual TV of 6.4 cm³ was identified as the cut-off volume for showing the greatest difference in progression-free survival (PFS). The 5-year PFS rates in the group with residual TVs of < 6.4 cm³ (54 patients) and that with residual TVs of ≥ 6.4 cm³ (14 patients) were 93.3% and 69.3%, respectively (P = 0.014). A good FN outcome was achieved in 57 (84%) patients. Residual TV was not associated with good FN function during the immediate postoperative period (P = 0.695; odds ratio [OR], 1.024; 95% CI, 0.908-1.156) or at the last follow-up (P = 0.755; OR, 0.980; 95% CI, 0.866-1.110). CONCLUSION: In this study, residual TV was associated with tumor progression in VS after adjuvant GKRS following STR. As preservation of FN function is not correlated with the extent of resection, optimal volume reduction is imperative to achieve long-term tumor control. Our findings will help surgeons predict the prognosis of residual VS after FN-preserving surgery.

Senescence Marker Protein 30 (SMP30): A Novel Pan-Species Diagnostic Marker for the Histopathological Diagnosis of Breast Cancer in Humans and Animals.

Senescence marker protein 30 (SMP30) is a cell survival factor playing an important role in vitamin C synthesis and antiapoptosis. Moreover, its cytoprotective role suggests a possibility to be related to cancer cell survival. Mammary carcinoma is a common cancer in both humans and animals. Because of its histopathological diversity, especially in the early stage, histopathological diagnosis may be complicated; therefore, a diagnostic marker is helpful for confirmation. The present study analyzed the expression pattern of SMP30 in mammary carcinoma in humans, dogs, and cats. Immunohistochemistry, immunofluorescence, and western blot analysis were used to investigate SMP30 expression patterns. The expression was specifically observed in neoplastic glandular epithelial cells. The expression increased with the malignancy of glandular epithelial cells with a highly proliferative status. However, SMP30 expression was low in normal mammary gland tissues or well-differentiated adenoma tissues. The patterns were consistently reproduced in canine primary mammary carcinoma cells and MCF-7 and MDA-MB-231 human carcinoma cell lines. This study provides useful information to understand SMP30 expression in various stages of mammary carcinoma and to suggest its utility as a pan-species diagnostic marker, thereby helping to establish strategies for diagnosing mammary carcinoma in several species.

Production of Minor Ginsenosides C-K and C-Y from Naturally Occurring Major Ginsenosides Using Crude ß-Glucosidase Preparation from Submerged Culture of Fomitella fraxinea.

Minor ginsenosides, such as compounds (C)-K and C-Y, possess relatively better bioactivity than those of naturally occurring major ginsenosides. Therefore, this study focused on the biotransformation of major ginsenosides into minor ginsenosides using crude ß-glucosidase preparation isolated from submerged liquid culture of Fomitella fraxinea (FFEP). FFEP was prepared by ammonium sulfate (30-80%) precipitation from submerged culture of F. fraxinea. FFEP was used to prepare minor ginsenosides from protopanaxadiol (PPD)-type ginsenoside (PPDG-F) or total ginsenoside fraction (TG-F). In addition, biotransformation of major ginsenosides into minor ginsenosides as affected by reaction time and pH were investigated by TLC and HPLC analyses, and the metabolites were also identified by UPLC/negative-ESI-Q-TOF-MS analysis. FFEP biotransformed ginsenosides Rb1 and Rc into C-K via the following pathways: Rd → F2 → C-K for Rb1 and both Rd → F2→ C-K and C-Mc1 → C-Mc → C-K for Rc, respectively, while C-Y is formed from Rb2 via C-O. FFEP can be applied to produce minor ginsenosides C-K and C-Y from PPDG-F or TG-F. To the best of our knowledge, this study is the first to report the production of C-K and C-Y from major ginsenosides by basidiomycete F. fraxinea.

Facile Synthetic Route To Prepare Ultrathin Silver Nanosheets by Reducing Silver Thiolates in Interlayer Surface of Layered Double Hydroxides.

Silver metal nanostructures have gained much interest, due to their utility in various fields, based on their unique properties at nanosize. Tremendous research efforts have been made to establish synthetic methods to manipulate their shape and size. The most challenging synthesis in silver nanostructures has been known as a plate-like shape having a few nanometers size thickness and high aspect ratio. Here, we demonstrate a novel and facile synthetic route for ultrathin (≤1 nm) silver nanosheets using silver carboxylthiolate as precursor. Such silver thiolate formed single-layered colloid in aqueous basic solution, due to the electrostatic repulsion between carboxylate groups. These single layers of silver thiolates were stabilized within the interlayer space of layered double hydroxide (LDH). When silver thiolates confined in LDHs were calcined under reductive atmosphere, the LDHs effectively suppressed the vertical growth of silver crystals.

Gamma Knife Radiosurgery as a Primary Treatment for Nonfunctioning Pituitary Adenoma Invading the Cavernous Sinus.

OBJECTIVES: Surgical resection of nonfunctioning pituitary adenoma (NFPA) invading the cavernous sinus (CS) remains a challenging and significant factor associated with incomplete resection. The residual tumor in CS is usually treated with adjuvant stereotactic radiosurgery (SRS), but there is little information concerning SRS as an initial treatment for CS-invading NFPA. In this study, we investigated the tumor control rate and clinical outcomes of the patients who received primary gamma knife radiosurgery (GKRS) for CS-invading NFPA. METHODS: This was a single-institute retrospective analysis of 11 patients. CS invasion of tumor was categorized using the modified Knosp grading system. The median tumor volume and maximal diameter were 1.6 cm3 (range 0.4-6.5) and 17.2 mm (range 11.6-23.3), respectively. The median clinical follow-up period was 48.5 months (range 16.4-177.8). The median prescription dose at tumor margin was 15 Gy (range 11-25) and median prescription isodose was 50% (range 45-50). The maximum radiation dose to optic chiasm and optic nerve were 7.2 Gy (range 3.4-9.2) and 7.5 Gy (range 4.5-11.5), respectively. RESULTS: Tumor control was achieved in all patients. The median tumor volume and maximal diameter at last follow-up were 0.4 cm3 (range 0.1-2.3) and 11.4 mm (range 4.7-19.5), respectively. The median volume reduction rate was 52% (range 33-88). Six patients showed downgrading of modified Knosp grade after GKRS. No patients developed GKRS-related complications such as hypopituitarism or visual disturbance. CONCLUSIONS: SRS may be an alternative primary treatment option for CS-invading NFPA if there is no urgent and absolute indication for surgery such as optic apparatus compression.

Incidence of Major Bleeding in Patients with Pulmonary Thromboembolism Treated with Fixed Dose Alteplase 100 mg.

BACKGROUND: Acute pulmonary thromboembolism (PTE) is a critical cardiopulmonary condition associated with high mortality and morbidity. In massive PTE, recently referred to as high risk PTE, the routine protocol for thrombolysis with recombinant tissue plasminogen activator (alteplase) is 100 mg over 2 hours. However, there are concerns about bleeding in patients with low body weight (< 50 kg), elderly patients, and Asians. METHOD: We performed a retrospective study in patients who were diagnosed with intermediate or high risk PTE, and who were treated with a fixed dose of alteplase (100 mg) in a single center at Chungbuk National University Hospital between July 2008 and April 2018. RESULTS: A total of 42 patients were reviewed, 4 patients dropped out, and 38 patients were included in the analysis. There were 18 males (47.4%), and the average age of the patients was 70.68 years (± standard deviation 13.15). Major bleeding was seen in 10/38 patients (26.3%), and 30/38 patients (78.9%) were successfully discharged. CONCLUSION: The major bleeding risk was higher in our study (26.3%) than in a previously published meta-analysis (9.24%). Therefore, we suggest reducing the dose of alteplase in patients who are elderly, Asian, or have cardiovascular disease. Further prospective studies of efficacy and bleeding rate after low dose alteplase should be considered.