Application of the New Preoperative Frailty Risk Score in Elderly Patients Undergoing Emergency Surgery.

BACKGROUND: Predicting preoperative frailty risk in emergency surgery is difficult with limited information because preoperative evaluation is not commonly performed properly. A recent study attempted to predict preoperative frailty risk using only diagnostic and surgical codes that can be extracted from the electronic medical records system. OBJECTIVE: This study aimed to validate whether the prediction model of preoperative frailty risk presented in the previous study is well applied to other medical hospitals' data. METHODS: This is a retrospective cohort study including 1,557 patients (≥75 years old) who were admitted to a single institution for emergency operations between January 1, 2010, and December 31, 2019, for study analysis. The Charlson comorbidity index, Hospital Frailty Risk Score, and the recently developed Operation Frailty Risk Score (OFRS) were calculated using the patient's diagnostic and operation codes. The predictive performances of these calculated risk scores and the American Society of Anesthesiologists-Physical Status classification for postoperative 90-day mortality were compared by using the receiver operating characteristic curve analysis. FINDINGS: The predictive performance of the OFRS, Charlson comorbidity index, American Society of Anesthesiologists-Physical Status, and Hospital Frailty Risk Score for postoperative 90-day mortality was 0.81, 0.630, 0.699, and 0.549 on a c-statistics basis, respectively. CONCLUSIONS: The OFRS using diagnostic and operation codes may show the best predictive performance for 90-day mortality compared to other risk scores, and it can be the clinically applicable model to evaluate the preoperative frailty risk in elderly patients undergoing emergency surgery.

Correlation between the Perfusion Index and Intraoperative Hypothermia: A Prospective Observational Pilot Study.

Background and Objectives: We examined the association between the baseline perfusion index (PI) and changes in intraoperative body temperature during general anesthesia. The PI reflects the peripheral perfusion state. The PI may be associated with changes in body temperature during general anesthesia because the degree of redistribution of body heat from the central to the peripheral compartment varies depending on the peripheral perfusion state. Materials and Methods: Thirty-eight patients who underwent brain surgery were enrolled in this study. The baseline PI and body temperature of the patients were measured on entering the operating room. Body temperature was recorded every 15 min after induction of anesthesia using an esophageal temperature probe. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for intraoperative hypothermia. Results: Eighteen patients (47 %) developed hypothermia intraoperatively. The baseline PI was significantly lower among patients in the hypothermia group (1.8 ± 0.7) than among those in the normothermia group (3.0 ± 1.2) (P < 0.001). The baseline PI and body temperature were independently associated with intraoperative hypothermia (PI: odds ratio [OR], 0.270; 95% confidence interval [CI], 0.105-0.697; P = 0.007, baseline body temperature: OR, 0.061; 95% CI, 0.005-0.743; P = 0.028). Conclusions: This study showed that low baseline PI was the factor most related to the development of intraoperative hypothermia. Future studies should consider the PI as a predictor of intraoperative hypothermia.

Genome surgery using Cas9 ribonucleoproteins for the treatment of age-related macular degeneration.

RNA-guided genome surgery using CRISPR-Cas9 nucleases has shown promise for the treatment of diverse genetic diseases. Yet, the potential of such nucleases for therapeutic applications in nongenetic diseases is largely unexplored. Here, we focus on age-related macular degeneration (AMD), a leading cause of blindness in adults, which is associated with retinal overexpression of, rather than mutations in, the VEGFA gene. Subretinal injection of preassembled, Vegfa gene-specific Cas9 ribonucleoproteins (RNPs) into the adult mouse eye gave rise to mutagenesis at the target site in the retinal pigment epithelium. Furthermore, Cas9 RNPs effectively reduced the area of laser-induced choroidal neovascularization (CNV) in a mouse model of AMD. Genome-wide profiling of Cas9 off-target effects via Digenome-seq showed that off-target mutations were rarely induced in the human genome. Because Cas9 RNPs can function immediately after in vivo delivery and are rapidly degraded by endogenous proteases, their activities are unlikely to be hampered by antibody- and cell-mediated adaptive immune systems. Our results demonstrate that in vivo genome editing with Cas9 RNPs has the potential for the local treatment for nongenetic degenerative diseases, expanding the scope of RNA-guided genome surgery to a new dimension.

Genome-wide analysis of RopGEF gene family to identify genes contributing to pollen tube growth in rice (Oryza sativa).

BACKGROUND: In plants, the key roles played by RopGEF-mediated ROP signaling in diverse processes, including polar tip growth, have been identified. Despite their important roles in reproduction, a comprehensive analysis of RopGEF members has not yet been performed in rice (Oryza sativa). To determine whether RopGEF regulators are involved in rice pollen tube growth, we performed genome-wide analysis of this family in rice. RESULTS: Phylogenomic and meta-expression analysis of eleven RopGEFs in rice showed that four genes were preferentially expressed in mature pollen. These four genes contain the plant-specific Rop nucleotide exchanger (PRONE) domain and possible phosphorylated residues, suggesting a conserved role in polar tip growth with Arabidopsis thaliana. In subcellular localization analysis of the four RopGEFs through tobacco (Nicotiana benthamiana) infiltration, four proteins were predominantly identified in plasma membrane. Moreover, double mutants of RopGEF2/8 exhibited reduced pollen germination, causing partial male sterility. These genes possess unique cis-acting elements in their promoters compared with the other RopGEF genes. CONCLUSIONS: In this study, four RopGEF genes were identified as pollen-specific gene in eleven members of rice, and the expression pattern, promoter analysis, and evolutionary relationship of the RopGEF family were studied compared with Arabidopsis. Our study indicated that four RopGEF genes might function during pollen germination in distinct subcellular localization. Our study could provide valuable information on the functional study of RopGEF in rice.

Cellular retinoic acid binding protein 1 protects mice from high-fat diet-induced obesity by decreasing adipocyte hypertrophy.

OBJECTIVES: Obesity, an emerging global health issue, involves numerous factors; understanding its underlying mechanisms for prevention and therapeutics is urgently needed. Cellular retinoic acid binding protein 1 (Crabp1) knockout (CKO) mice exhibit an obese phenotype under normal diet (ND) feedings, which prompted us to propose that Crabp1 could play a role in modulating adipose tissue development/homeostasis. Studies were designed to elucidate the underlying mechanism of Crabp1's action in reducing obesity. SUBJECTS/METHODS: In animal studies, 6 weeks old male wild type and CKO mice were fed with ND or high-fat diet (HFD) for 10 weeks. Body weight and food intake were regularly monitored. Glucose tolerance test and biological parameters of plasma (glucose and insulin levels) were measured after 10 weeks of ND vs. HFD feedings. Visceral adipose tissues were collected for histological and molecular analyses to determine affected signaling pathways. In cell culture studies, the 3T3L1 adipocyte differentiation model was used to examine and validate relevant signaling pathways. RESULTS: CKO mice, compared to WT mice, gained more body weight, exhibited more elevated fasting plasma glucose levels, and developed more severe impaired glucose tolerance under both ND and HFD. Histological examination revealed readily increased adipocyte hypertrophy and adipose tissue inflammation under HFD feedings. In 3T3L1 adipocytes, Crabp1 silencing enhanced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, accompanied by elevated markers and signaling pathways of lipid accumulation and adipocyte hypertrophy. CONCLUSIONS: This study identifies Crabp1's physiological role against the development of obesity. The protective function of CRABP1 is likely attributed to its classically proposed (canonical) activity as a trap for RA, which will reduce RA availability, thereby dampening RA-stimulated ERK1/2 activation and adipocyte hypertrophy. The results suggest Crabp1 as a potentially new therapeutic target in managing obesity and metabolic diseases.

Pre-hospital modified shock index for prediction of massive transfusion and mortality in trauma patients.

BACKGROUND: Modified shock index (MSI) is a useful predictor in trauma patients. However, the value of prehospital MSI (preMSI) in trauma patients is unknown. The aim of this study was to investigate the accuracy of preMSI in predicting massive transfusion (MT) and hospital mortality among trauma patients. METHODS: This was a retrospective, observational, single-center study. Patients presenting consecutively to the trauma center between January 2016 and December 2017, were included. The predictive ability of both prehospital shock index (preSI) and preMSI for MT and hospital mortality was assessed by calculating the areas under the receiver operating characteristic curves (AUROCs). RESULTS: A total of 1007 patients were included. Seventy-eight (7.7%) patients received MT, and 30 (3.0%) patients died within 24 h of admission to the trauma center. The AUROCs for predicting MT with preSI and preMSI were 0.773 (95% confidence interval [CI], 0.746-0.798) and 0.765 (95% CI, 0.738-0.791), respectively. The AUROCs for predicting 24-hour mortality with preSI and preMSI were 0.584 (95% CI, 0.553-0.615) and 0.581 (95% CI, 0.550-0.612), respectively. CONCLUSIONS: PreSI and preMSI showed moderate accuracy in predicting MT. PreMSI did not have higher predictive power than preSI. Additionally, in predicting hospital mortality, preMSI was not superior to preSI.

Transforaminal Epiduroscopic Laser Ablation for Removal of a Postlaminectomy Synovial Cyst: A Case Report.

Background: Synovial cysts rarely occur after a laminectomy and are difficult to detect if there are no symptoms; however, they can cause lower back pain or symptoms of radiculopathy. Various methods are used to treat synovial cysts. Here, we will introduce the first case with treatment using the transforaminal epiduroscopic laser annuloplasty (TELA) system. Case report: A 64-year-old female patient visited the pain clinic with lower back pain and pain radiating from the left lower extremity. An MRI T2 image showed a synovial cyst of facet joint origin at the L4-L5 level; the patient had undergone a laminectomy 10 years ago at the same spinal level. The patient rated the pain an 8 on the numerical rating scale (NRS), and pain was reduced after epidural steroid injection, but symptoms recurred a month later. The cyst ablation was performed using the TELA system with a 1414 nm neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser, and after the procedure, pain decreased to 4 points immediately and was reduced to 2 points on the NRS after 1 week. Six months after the procedure, the pain level was measured on NRS 2 and cyst was not recurred in the additional MRI. Conclusion: We introduced the TELA system as a noninvasive therapy for treating synovial cysts. Ablation of cystic necks using a 1414 nm Nd:YAG laser could be a method to prevent cyst recurrence, but long-term follow-up and large scale control studies will be needed to verify the effectiveness of this method.

Correction to: Cellular retinoic acid binding protein 1 protects mice from high-fat diet-induced obesity by decreasing adipocyte hypertrophy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Life-threatening massive empyema: A novel complication of intrathoracic omental herniation.

Intrathoracic omental herniation (ITOH) is the herniation of the omentum through the esophageal hiatus without herniation of the stomach. It is a rare disease and serious complications due to ITOH have not been reported in the literature. Here, we reported the case of 47-year old man who presented to the emergency department with dyspnea and chest pain. Enhanced computed tomography (CT) demonstrated a large retrocardiac mass and ITOH was suspected. During the observation period in the emergency department, the patient's condition rapidly deteriorated. Follow-up CT showed large parapneumonic effusion and empyema. Emergency surgery was performed and the omental sac was removed. The patient's vital signs were restored and his symptoms were relieved. He was discharged on hospital day 15 without complications. Emergency physicians should be aware that severe complications of ITOH could develop and that if the patient's symptoms and vital signs worsen, emergency surgery should be considered.

An Unusual Delayed Onset of Systemic Toxicity After Fluoroscopy-Guided Cervical Epidural Steroid Injection With Levobupivacaine: A Case Report.

BACKGROUND: Cervical epidural steroid injection (CESI) with local anesthetics is commonly used to treat neck pain and radicular pain of the upper extremity. Local anesthetic systemic toxicity (LAST) occurs shortly after injection as a complication; however, delayed onset is a very rare event, especially in central nervous system (CNS) block. CASE REPORT: We present a case in which delayed onset of LAST occurred in a patient who received CESI for cervical and arm radiating pain due to a cervical disc protrusion. We performed the interlaminar approach for CESI using fluoroscopic guidance. After confirming the location of the epidural space using the loss of resistance technique and spreading of contrast agent (Telebrix® 30), a mixture of 0.25% levobupivacaine 12.5 mg (5 mL in volume), hyaluronidase 1,500 IU (1 mL), dexamethasone 5 mg (1 mL), and normal saline 3 mL was administrated. After 50 minutes of injection, the patient showed CNS toxicity (unconsciousness, seizure) with normal blood pressure and tachycardia; therefore, she was immediately sedated with intravenous midazolam (3 mg), and 15 L/min of oxygen was administered. The patient fully recovered after 30 minutes of sedation without any sequelae. CONCLUSION: Delayed onset of LAST is a rare complication of a common procedure in CESI, so it is important to be aware of this complication and the presentation of toxicity.

Preoperative EUS-guided FNA: effects on peritoneal recurrence and survival in patients with pancreatic cancer.

BACKGROUND AND AIMS: EUS-guided FNA (EUS-FNA) is an accurate and relatively safe tissue confirmation method for pancreatic cancer. However, there is concern that this procedure may spread tumor cells along the needle track or within the peritoneum. We aimed to estimate the effect of preoperative EUS-FNA on the risk of peritoneal recurrence and long-term outcomes in resected pancreatic cancer. METHODS: We retrospectively reviewed records of patients diagnosed with pancreatic cancer who had undergone curative resection between 2009 and 2013 to investigate the overall survival, cancer-free survival, and peritoneal recurrence. Peritoneal recurrence was diagnosed based on image findings or cytology-confirmed ascites. RESULTS: Of 411 patients, 90 underwent preoperative EUS-FNA (EUS-FNA group), whereas 321 did not (non-EUS-FNA group). The median length of follow-up was 16.2 months (range, 2-46). Peritoneal recurrence occurred in 131 patients: 30% (27/90) in the EUS-FNA group versus 32% (104/321) in the non-EUS-FNA group (P = .66). Cancer-free survival or overall survival was not significantly different between the 2 groups: median overall survival of 25.3 months in the EUS-FNA group versus 23.7 months in the non-EUS-FNA group (P = .36) and median cancer-free survival of 12.7 months in the EUS-FNA group versus 11.6 months in the non-EUS-FNA group (P = .38). CONCLUSIONS: Preoperative EUS-FNA for pancreatic cancer was not associated with an increased rate of peritoneal recurrence or mortality. Therefore, EUS-FNA is an accurate and safe method to obtain suspicious pancreatic mass tissue.

SUBFOVEAL CHOROIDAL THICKNESS AND VASCULAR DIAMETER IN ACTIVE AND RESOLVED CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To determine the subfoveal choroidal thickness and analyze Haller's layer, Sattler's layer, and large choroidal vessel diameter in eyes with active central serous chorioretinopathy (CSC) and after resolution of CSC. METHODS: Ocular and clinical features of 32 eyes with CSC were analyzed retrospectively from October 2014 to September 2015. Subfoveal choroidal thickness and thicknesses of Haller's layer and Sattler's layer were measured in the active and resolved states. The diameter of the subfoveal choroidal hyporeflective lumen (i.e., the large choroidal vessel in Haller's layer) was also measured. RESULTS: The mean subfoveal choroidal thickness, mean thickness of Haller's layer, and mean choroidal vessel diameter were significantly less after the resolution of CSC (P < 0.001). However, the thickness of Sattler's layer did not change after the resolution of CSC (P = 0.731). There were no significant differences among the different treatment modalities. CONCLUSION: After the resolution of CSC, the subfoveal choroidal thickness and thickness of Haller's layer declined, but the reduced diameter of subfoveal choroidal vessels accounted for only about half of the total thickness changes in the choroid. These results suggest that nonvascular smooth muscle cells might play a role in the thickening of the choroid during CSC and possibly in the pathogenesis and progression of CSC.

Effect of remifentanil during drug-induced sleep endoscopy in patients with obstructive sleep apnea.

PURPOSE: During drug-induced sleep endoscopy (DISE) in patients with obstructive sleep apnea, the increased depth of propofol anesthesia is related to the increased collapsibility of the upper airway with dose-dependent. We examined the effect of remifentanil on propofol concentration during DISE. METHODS: In a prospective randomized trial, 56 adult patients were divided into remifentanil-propofol (n = 28) and propofol alone (n = 28) groups. Anesthesia was administered using a target-controlled infusion system. In the remifentanil-propofol group, 0.5 ng/ml remifentanil was administered prior to propofol infusion and its concentration maintained; thereafter, in the propofol alone group, normal saline was injected instead of remifentanil. Propofol was infused at a concentration of 1.5 µg/ml after the target concentration of remifentanil was reached. In both groups, the concentration of propofol was increased by 0.5 µg/ml if the degree of sedation was not sufficient. The sedation level was targeted at observer's assessment of alertness/sedation (OAA/S) scale 3. RESULTS: The mean propofol concentration was 2.87 ± 0.60 µg/ml in the remifentanil-propofol group, which was lower than that in the propofol alone group (3.38 ± 0.72 µg/ml, P < 0.001). The time until sufficient sedation to perform DISE was shorter in the remifentanil-propofol group (P < 0.001). Apnea-hypopnea index and the lowest peripheral capillary oxygen saturation (SpO2) during polysomnography showed no statistical difference between groups (P > 0.05). The lowest SpO2 and VOTE classification during DISE were also not statistically different (P > 0.05). CONCLUSIONS: Use of remifentanil during DISE reduces the target concentration of propofol required for patient sedation to perform DISE without respiratory depression.

Synergistic activation of Arg1 gene by retinoic acid and IL-4 involves chromatin remodeling for transcription initiation and elongation coupling.

All-trans Retinoic acid (RA) and its derivatives are potent therapeutics for immunological functions including wound repair. However, the molecular mechanism of RA modulation in innate immunity is poorly understood, especially in macrophages. We found that topical application of RA significantly improves wound healing and that RA and IL-4 synergistically activate Arg1, a critical gene for tissue repair, in M2 polarized macrophages. This involves feed forward regulation of Raldh2, a rate-limiting enzyme for RA biosynthesis, and requires Med25 to coordinate RAR, STAT6 and chromatin remodeler, Brg1 to remodel the +1 nucleosome of Arg1 for transcription initiation. By recruiting elongation factor TFIIS, Med25 also facilitates transcriptional initiation-elongation coupling. This study uncovers synergistic activation of Arg1 by RA and IL-4 in M2 macrophages that involves feed forward regulation of RA synthesis and dual functions of Med25 in nucleosome remodeling and transcription initiation-elongation coupling that underlies robust modulatory activity of RA in innate immunity.

Continuously steerable second-order differential microphone arrays.

This paper proposes a second-order differential microphone array (DMA) that can continuously steer in the main lobe direction. First, a general response of the second-order DMA is derived as a linear combination of a monopole and dipoles. Nine- and seven-microphone systems are proposed to realize continuous steering of the second-order DMA. The proposed system synthesizes the steered beam pattern without requiring the phase shifter by using back-to-back cardioids. Simulation results show that the nine-microphone configuration yields a nearly constant and high white noise gain, but the seven-microphone configuration has the practical advantage that it requires fewer microphones.

Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy.

Vascular inflammation is characteristic feature of diabetic retinopathy. In diabetic retina, a variety of the pro-inflammatory cytokines are elevated and involved in endothelial dysfunction. STAT3 transcription factor has been implicated in mediating cytokine signaling during vascular inflammation. However, whether and how STAT3 is involved in the direct regulation of the endothelial permeability is currently undefined. Our studies revealed that IL-6-induced STAT3 activation increases retinal endothelial permeability and vascular leakage in retinas of mice through the reduced expression of the tight junction proteins ZO-1 and occludin. In a co-culture model with microglia and endothelial cells under a high glucose condition, the microglia-derived IL-6 induced STAT3 activation in the retinal endothelial cells, leading to increasing endothelial permeability. In addition, IL-6-induced STAT3 activation was independent of ROS generation in the retinal endothelial cells. Moreover, we demonstrated that STAT3 activation downregulates the ZO-1 and occludin levels and increases the endothelial permeability through the induction of VEGF production in retinal endothelial cells. These results suggest the potential importance of IL-6/STAT3 signaling in regulating endothelial permeability and provide a therapeutic target to prevent the pathology of diabetic retinopathy. J. Cell. Physiol. 232: 1123-1134, 2017. © 2016 Wiley Periodicals, Inc.

Diabetic retinopathy is associated with diastolic dysfunction in type 2 diabetic patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: To investigate the association between diabetic retinopathy (DR) and myocardial dysfunction in patients with type 2 diabetes and dilated cardiomyopathy (dCMP). METHODS: Data were collected retrospectively from 89 patients with dCMP (46 with type 2 diabetes and 43 without diabetes) and no evidence of coronary artery disease. Echocardiographic parameters and laboratory data, including lipid profiles and fundus findings, were obtained from medical records. A left ventricular ejection fraction (LVEF) less than 40% was considered impaired systolic function, while an E/E' ratio greater than 15 was considered elevated left ventricular (LV) filling pressure. RESULTS: Baseline characteristics show that LVEF was not significantly different between patients with and without diabetes or between diabetic patients with and without DR. Among the diastolic function parameters, patients with DR exhibited higher E/E' ratios (left ventricular filling pressures) than patients without DR (23.75 ± 13.37 vs 11.71 ± 3.50, P = 0.022). Logistic regression analysis revealed that statin use lowered the risk of impaired systolic dysfunction in all patients (odds ratio (OR) 0.33, 95% confidence interval (CI) 0.12-0.92, P = 0.034) and in patients with diabetes (OR 0.273, 95% CI 0.08-0.99, P = 0.049), while the presence of DR was associated with a higher risk of elevated LV filling filling pressure in patients with diabetes (OR 18.00, 95% CI 1.50-216.62, P = 0.023). CONCLUSIONS: In conclusion, DR was associated with elevated LV filling pressure in patients with dCMP. DR may not only represent microvascular long-term complications in patients with diabetes but may also be associated with more advanced form of diastolic dysfunction among diabetic patients with cardiomyopathy.

Association of statin use and hypertriglyceridemia with diabetic macular edema in patients with type 2 diabetes and diabetic retinopathy.

BACKGROUND: To investigate the effects of dyslipidemia and statin therapy on progression of diabetic retinopathy and diabetic macular edema in patients with type 2 diabetes. METHODS: The medical records of 110 patients with type 2 diabetes (70 statin users and 40 non-users) were retrospectively reviewed. The two outcome measures were progression of diabetic retinopathy by two or more steps on the early treatment diabetic retinopathy study scale and diabetic macular edema based on optical coherence tomography. Serum lipid profiles were analyzed from 6 months prior to diagnosis of diabetic macular edema. RESULTS: Diabetic retinopathy progressed in 23% of statin users and 18% of non-users (p = 0.506), but diabetic macular edema was present in 23% of statin users and 48% of non-users (p = 0.008). Statins reduced low-density lipoprotein cholesterol levels in patients with and without diabetic macular edema (p = 0.043 and p = 0.031, respectively). Among statin users, patients with diabetic macular edema had higher levels of triglycerides (p = 0.004) and lower levels of high-density lipoprotein cholesterol (p = 0.033) than those without diabetic macular edema. Logistic regression analysis showed that statin use significantly lowered the risk of diabetic macular edema [odds ratio (OR): 0.33, 95% confidence interval (CI) 0.12-0.91, p = 0.032]. Hypertriglyceridemia at 6 months prior to development of macular edema was significantly associated with central retinal thickness (OR: 1.52; 95% CI 1.14-2.02, p = 0.005). CONCLUSIONS: Lipid lowering therapy with statins protected against the development of diabetic macular edema and progression of diabetic retinopathy in patients with type 2 diabetes. Hypertriglyceridemia could be used as a surrogate marker for diabetic macular edema.

Minimal pneumothorax with dynamic changes in ST segment similar to myocardial infarction.

Pneumothorax can cause a variety of electrocardiographic changes. ST segment elevation, which is mainly observed in myocardial infarction, can also be induced by pneumothorax. The mechanism is presumed to be a decrease in cardiac output, due to increased intra-thoracic pressure. We encountered a patient with ST segment elevation with minimal pneumothorax. Coronary angiography with ergonovine provocation test and echocardiogram had normal findings. The ST segment elevation was normalized by decreasing the amount of pneumothorax. We reviewed the literature and present possible mechanisms for this condition.