Experience of reassessing FBN1 variants of uncertain significance by gene-specific guidelines.

BACKGROUND: Despite the 2015 American College of Medical Genetics and Genomics (ACMG) and Association of Molecular Pathology (AMP) guideline, many variants of FBN1 gene remain inconclusive. In line with publication of the FBN1-specific variant interpretation guideline by ClinGen in 2022, we reassessed variants of uncertain significance (VUS) in FBN1 gene found in our institution. METHODS: VUS found in the course of FBN1 sequencing between December 2015 and April 2022 were reassessed based on FBN1-specific variant interpretation guideline, review of updated literatures and additional genetic tests including family study and/or RNA study if available. RESULTS: Out of 695 patients who underwent FBN1 sequencing, 61 VUS were found in 69 patients. Among them, 38 VUS in 43 patients (62.3%) were reclassified as pathogenic and likely pathogenic variant ((L)PV), including 20 novel (L)PV. Major causes of reclassification were: (1) gene-specific modification of ACMG/AMP criteria, (2) updated literatures and (3) additional genetic tests. The most important evidence for reclassification was clarification of critical amino acid residues. CONCLUSIONS: After reassessing FBN1 variants according to FBN1-specific guideline and up-to-date database, a significant number of VUS was reclassified. Clinical laboratories are encouraged to perform variant reassessment at regular intervals or when there is a major change in the principle of variant interpretation.

Overcoming challenges associated with identifying FBN1 deep intronic variants through whole-genome sequencing.

BACKGROUND: Marfan syndrome (MFS), caused by pathogenic variants of FBN1 (fibrillin-1), is a systemic connective tissue disorder with variable phenotypes and treatment responsiveness depending on the variant. However, a significant number of individuals with MFS remain genetically unexplained. In this study, we report novel pathogenic intronic variants in FBN1 in two unrelated families with MFS. METHODS: We evaluated subjects with suspected MFS from two unrelated families using Sanger sequencing or multiplex ligation-dependent probe amplification of FBN1 and/or panel-based next-generation sequencing. As no pathogenic variants were identified, whole-genome sequencing was performed. Identified variants were analyzed by reverse transcription-PCR and targeted sequencing of FBN1 mRNA harvested from peripheral blood or skin fibroblasts obtained from affected probands. RESULTS: We found causative deep intronic variants, c.6163+1484A>T and c.5788+36C>A, in FBN1. The splicing analysis revealed an insertion of in-frame or out-of-frame intronic sequences of the FBN1 transcript predicted to alter function of calcium-binding epidermal growth factor protein domain. Family members carrying c.6163+1484A>T had high systemic scores including prominent skeletal features and aortic dissection with lesser aortic dilatation. Family members carrying c.5788+36C>A had more severe aortic root dilatation without aortic dissection. Both families had ectopia lentis. CONCLUSION: Variable penetrance of the phenotype and negative genetic testing in MFS families should raise the possibility of deep intronic FBN1 variants and the need for additional molecular studies. This study expands the mutation spectrum of FBN1 and points out the importance of intronic sequence analysis and the need for integrative functional studies in MFS diagnosis.

Usefulness of cardiopulmonary exercise test combined with exercise stress echocardiography in mild chronic thromboembolic pulmonary disease.

PURPOSE: Chronic thromboembolic pulmonary disease (CTEPD) can lead to exercise limitations even without right ventricular (RV) dysfunction or pulmonary hypertension at rest. Combining exercise stress echocardiography with cardiopulmonary exercise testing (ESE-CPET) for RV function and pressure changes combined measuring overall function may be useful for CTEPD evaluation. This study aims to investigate CPET and ESE results to elucidate the mechanisms of exercise limitation in mild CTEPD cases. METHODS: Among our CTEPD registry, 50 patients who performed both right heart catheterization data of mild disease (less than 30 mm Hg of mean pulmonary arterial pressure (mPAP)) and ESE-CPET were enrolled. Echocardiography and CPET-derived parameters were compared with hemodynamic parameters measured through right heart catheterization. RESULTS: Peak VO2 (maximal oxygen consumption) was decreased in overall population (71.3 ± 16.3% of predictive value). Peak VO2 during exercise was negatively correlate with mPAP and pulmonary vascular resistance at rest. A substantial increase in RV systolic pressure (RVSP) was observed during exercise (RVSP: pre-exercise 37.2 ± 11.8 mm Hg, postexercise 64.3 ± 24.9 mm Hg, p-value < .001). Furthermore, RV function deteriorated during exercise when compared to the baseline (RV fractional area change: 31.5 ± 10.0% to 37.8 ± 7.0%, p-value < .001; RV global longitudinal strain: -17.1 ± 4.2% to -17.7 ± 3.3%, p-value < .001) even though basal RV function was normal. While an excessive increase in RVSP during exercise was noticed in both groups, dilated RV and RV dysfunction during exercise were demonstrated only in the impaired exercise capacity group. CONCLUSION: CTEPD patients with mild PH or without PH exhibited limited exercise capacity alongside an excessive increase in RVSP during exercise. Importantly, RV dysfunction during exercise was significantly associated with exercise capacity. ESE-CPET could aid in comprehending the primary cause of exercise limitation in these patients.

Evaluation of pulse oximeter at the nasal septum during general anesthesia: comparison with finger oximeter.

PURPOSE: Though the finger is generally recommended for pulse oxygen saturation (SpO2) monitoring site, its reliability may be compromised in conditions of poor peripheral perfusion. Therefore, we compared the performance of nasal septum SpO2 monitoring with finger SpO2 monitoring relative to simultaneous arterial oxygen saturation (SaO2) monitoring in generally anesthetized patients. METHODS: In 23 adult patients, comparisons of SpO2 measured at the nasal septum and finger with simultaneous SaO2 were made at four time points during the 90 min study period. A pulse oximetry monitoring failure was defined as a > 10 s continuous failure of in an adequate SpO2 data acquisition. Core temperature as well as finger-tip and nasal septum temperatures were simultaneously measured at 10 min intervals. RESULTS: A total of 92 sets of SpO2 and SaO2 measurements were obtained in 23 patients. The bias and precision for SpO2 measured at the nasal septum were - 0.8 ± 1.3 (95% confidence interval: - 1.1 to - 0.6), which was similar to those for SpO2 measured at the finger (- 0.6 ± 1.4; 95% confidence interval: - 0.9 to - 0.4) (p = 0.154). Finger-tip temperatures were consistently lower than other two temperatures at all time points (p < 0.05), reaching 33.5 ± 2.3 °C at 90 min after induction of anesthesia. While pulse oximetry monitoring failure did not occur for nasal septum probe, two cases of failure occurred for finger probe. CONCLUSIONS: Considering the higher stability to hypothermia with a similar accuracy, nasal septum pulse oximetry may be an attractive alternative to finger pulse oximetry. Trail registration This study was registered with Clinical Research Information Service (CRIS: https://cris.nih.go.kr/cris/en/ ; ref: KCT0008352).

Multiagent Q-Learning-Based Mobility Management for Multi-Connectivity in mmWAVE Cellular Systems.

Effective mobility management is crucial for efficient operation of next-generation cellular systems in the millimeter wave (mmWave) band. Massive multiple-input-multiple-output (MIMO) systems are seen as necessary to overcome the significant path losses in this band, but the highly directional beam makes the channels more susceptible to radio link failures due to blockages. To meet stringent capacity and reliability requirements, multi-connectivity has attracted significant attention. This paper proposes a multiagent distributed Q learning-based mobility management scheme for multi-connectivity in mmWave cellular systems. A hierarchical structure is adopted to address the model complexity and speed up the learning process. The performance is assessed using a realistic measurement data set collected from Wireless Insite in an urban area and compared with independent Q learning and a heuristic scheme in terms of handover probability and spectral efficiency.

Simulation Analysis of Flow Rate Variability During Microinfusions: The Effect of Vertical Displacement and Multidrug Infusion in Conventional Infusion Pumps Versus New Cylinder-Type Infusion Pumps.

BACKGROUND: Medication dosing errors can occur during microinfusions when there is vertical pump displacement or multidrug infusion through a single intravenous path. We compared flow rate variability between new-generation cylinder-type infusion pumps and conventional infusion pumps under simulated conditions. METHODS: We evaluated the flow rates during microinfusions using different infusion pumps (syringe pump with 10/30/50-mL syringes, peristaltic pump, and cylinder pump). Two visible dyes were used as model drugs. The study samples were quantified using spectrophotometry. For vertical displacement, the infusion pumps were moved up and down by 60 cm during microinfusions at 0.5 mL·h-1 and 2 mL·h-1. In the multi-infusion study, the second drug flow was added through 4 linearly connected stopcocks either upstream or downstream of the first drug. We compared the total error dose between the cylinder pump and the syringe pump with a Mann-Whitney U test and additionally estimated the effects of the infusion pumps on total error doses by linear regression analysis. RESULTS: There were repetitive patterns of temporary flow increases when the pump was displaced upward and flow decreases when the pump was displaced downward in all settings. However, the amount of flow irregularities was more pronounced at the lower infusion rate and in the syringe-type pump using larger volume syringes. The total error dose increased in the syringe pump loaded with a 50-mL syringe compared to that of the new cylinder pump (regression coefficient [ß] = 4.66 [95% confidence interval {CI}, 1.60-7.72]; P = .008). The initiation and cessation of a new drug during multidrug microinfusion in the same intravenous path affected the lower rate first drug leading to a transient flow rate increase and decrease, respectively. The change in flow rate was observed regardless of the port selected for addition of the second drug, and the total error dose of the first drug did not significantly vary when an upstream or a downstream port was selected. CONCLUSIONS: In the microinfusion settings, attention must be paid to the use of the syringe pump loaded with large-volume syringes. The novel cylinder pump could be considered as a practical alternative to syringe pumps with small syringes given its flow stability without the need for frequent drug replacement.

Implementation and Outcomes of a Difficult Airway Code Team Composed of Anesthesiologists in a Korean Tertiary Hospital: A Retrospective Analysis of a Prospective Registry.

BACKGROUND: In 2017, we established an airway call (AC) team composed of anesthesiologists to improve emergency airway management outside the operating room. In this retrospective analysis of prospectively collected data from the airway registry, we describe the characteristics of patients attended to and practices by the AC team during the first 4 years of implementation. METHODS: All AC team activations in which an airway intervention was performed by the AC team between June 2017 and May 2021 were analyzed. RESULTS: In all, 359 events were analyzed. Activation was more common outside of working hours (62.1%) and from the intensive care unit (85.0%); 36.2% of AC activations were due to known or anticipated difficult airway, most commonly because of acquired airway anomalies (n = 49), followed by airway edema or bleeding (n = 32) and very young age (≤ 1 years; n = 30). In 71.3% of the cases, successful intubation was performed by the AC team at the first attempt. However, three or more attempts were performed in 33 cases. The most common device used for successful intubation was the videolaryngoscope (59.7%). Tracheal intubation by the AC team failed in nine patients, who then required surgical airway insertion by otolaryngologists. However, there were no airway-related deaths. CONCLUSIONS: When coupled with appropriate assistance from an otolaryngologist AC system, an AC team composed of anesthesiologists could be an efficient way to provide safe airway management outside the operating room. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0006643.

Acute Pulmonary Embolism and Chronic Thromboembolic Pulmonary Hypertension: Clinical and Serial CT Pulmonary Angiographic Features.

In acute pulmonary embolism (PE), circulatory failure and systemic hypotension are important clinically for predicting poor prognosis. While pulmonary artery (PA) clot loads can be an indicator of the severity of current episode of PE or treatment effectiveness, they may not be used directly as an indicator of right ventricular (RV) failure or patient death. In other words, pulmonary vascular resistance or patient prognosis may not be determined only with mechanical obstruction of PAs and their branches by intravascular clot loads on computed tomography pulmonary angiography (CTPA), but determined also with vasoactive amines, reflex PA vasoconstriction, and systemic arterial hypoxemia occurring during acute PE. Large RV diameter with RV/left ventricle (LV) ratio > 1.0 and/or the presence of occlusive clot and pulmonary infarction on initial CTPA, and clinically determined high baseline PA pressure and RV dysfunction are independent predictors of oncoming chronic thromboembolic pulmonary hypertension (CTEPH). In this pictorial review, authors aimed to demonstrate clinical and serial CTPA features in patients with acute massive and submassive PE and to disclose acute CTPA and clinical features that are related to the prediction of oncoming CTEPH.

A Retrospective Population-Based Survival Study of Idiopathic Pulmonary Arterial Hypertension in Korea.

BACKGROUND: Few studies used nationwide data to assess the survival rates (SRs) and death risk for idiopathic pulmonary arterial hypertension (IPAH; ICD-10 I27.0) in Korea. METHODS: IPAH data (N = 9,017; female:male = 6:4) were collected from the National Health Insurance Service in Korea, from 2006 through 2017. The data consisted of primary diagnoses related to IPAH. The Kaplan-Meier method and Cox proportional-hazards analyses were carried out. RESULTS: The mean age was 62.3 (± 19.4) years, 64.2 (± 18.9) years in female and 59.4 (± 19.8) years in male (P < 0.001). The one-, three-, five- and 10-year SRs for IPAH were 89.0%, 79.8%, 72.3% and 57.0%, respectively. The adjusted hazard ratio (HR) of IPAH was 1.81 (95% confidence interval [CI], 1.26-2.59) in 60-69 age group, 3.42 (95% CI, 2.40-4.87) in 70-79, and 7.73 (95% CI, 5.43-11.0) in 80s. Other risk factors were male, low-income status, diabetes, myocardial infarction, atrial fibrillation, ischemic stroke, hemorrhagic stroke, and malignant neoplasm. CONCLUSION: The 10-year SR of IPAH was 57% in Korea. The HR for IPAH was significantly high in patients with older age and other risk factors.

Comparable surgical outcomes of abdominal aortic aneurysm repair in patients with and without Marfan syndrome.

OBJECTIVE: Marfan syndrome (MFS) affects the cardiovascular system. Aortic root aneurysm is a pathognomonic feature of MFS; however, the abdominal aorta is rarely affected. A consensus on surveillance for the abdominal aorta in patients with MFS has not been established. In the present study, we compared the outcomes after open surgical repair (OSR) of abdominal aortic aneurysms (AAAs) in patients with and without MFS. METHODS: We conducted a retrospective, single-center cohort study from 2003 to 2020. We reviewed and compared 28 patients with MFS and 426 patients without MFS who had undergone OSR for AAAs. The baseline characteristics, medical comorbidities, previous cardiovascular surgery, anatomic features of the AAAs, and surgical treatment outcomes were compared between the two groups. RESULTS: The patients with MFS were younger than those without MFS at the AAA diagnosis (47.2 ± 12.3 vs 70.6 ± 7.9 years; P < .001). The proportion of women was also greater for those with MFS (46.4% vs 15.7%; P < .001). The AAAs were most often located at the infrarenal aorta in both groups. However, thoracoabdominal AAAs were more often found among patients with MFS (10.7% vs 0.9%; P < .012). The proportion of symptomatic patients was lower in the MFS group (3.6% vs 21.6%; P = .022). The maximum median diameter of the AAA at surgery was smaller in the patients with MFS (52 mm vs 58 mm; P = .001). However, concomitant aortic dissection (32.1% vs 3.3%; P < .001) was more prevalent among the patients with MFS. Consequent aneurysmal changes in the iliac artery after AAA repair were more frequent in the patients with MFS (7.1% vs 0%; P = .004). No significant differences were found in 30-day or overall mortality between the patients with and without MFS during a median follow-up period of 71 months (interquartile range, 24.7-121.1 months) and 26.7 months (interquartile range, 7.4-69.5 months), respectively. CONCLUSIONS: The surgical outcomes of OSR for AAAs for patients with MFS were not significantly different from those for patients without MFS in a well-established surveillance program of MFS.

Factors associated with radiographic progression in patients with Takayasu's arteritis.

OBJECTIVES: To identify the factors related to radiographic progression in patients with Takayasu's arteritis (TAK). METHODS: A retrospective cohort study was conducted among patients with TAK who underwent computed tomography angiography (CTA) at least twice in a 2-5-year interval. Radiographic progression was defined as newly developed and/or aggravated (more than 20%) characteristic CTA findings. Correlation analysis was performed using a multivariate Cox regression model. RESULTS: The cohort included 153 TAK patients with a mean CTA interval of 3.53 years, and 24 (15.7%) showed radiographic progression. Those with progression showed higher acute-phase reactant levels (erythrocyte sedimentation rate [ESR], 26.06 vs. 35.72 mm/h, p=0.040; C-reactive protein [CRP], 0.45 vs. 1.13 mg/dL, p<0.001), were younger at the initial CTA (43.70 vs. 31.81 years, p<0.001), and were more likely to be receiving immunosuppressants (14 [10.9%] vs. 7 [29.2%] patients, p=0.038). Multivariate Cox regression analysis revealed age at the initial CTA (hazard ratio [HR]=0.945, confidence interval [CI]=0.898-0.995, p=0.030) and area under the curve (AUC) of CRP levels (HR=2.126, CI=1.046-4.319, p=0.037) as significant factors for radiographic progression. In a subgroup of patients with high CRP levels, 30.4% (14/24) showed progression; only age at the initial CTA was significantly different (37.03 vs. 27.10 years, p=0.012) between those with and without progression. CONCLUSIONS: Higher CRP levels and younger age were risk factors of radiographic progression in patients with TAK. In the high CRP group, younger patients are more prone to progression and may need aggressive anti-inflammatory treatment.

Culture-Negative Mycotic Aortic Aneurysms Probably Have a Less Severe Clinical Nature Than Culture-Positive Counterparts.

BACKGROUND: Mycotic aortic aneurysm constitutes a potentially devastating disease that necessitates prompt suspicion and diagnosis. There is no exact consensus for treatment, but removal of infected tissues and prolonged use of antimicrobials based on the identified causative microorganisms seem widely acceptable and have been similarly practiced worldwide. However, some patients still show no identified microorganisms. In this study, we sought to determine whether there are any clinical significance or differences of note in culture-negative mycotic aortic aneurysms. METHODS: Between October 2003 and August 2018, 71 patients were identified as treated for mycotic aortic aneurysms at a single tertiary institution. Review of medical records and imaging studies were completed to collect the following information: demographics, previous medical/surgical history regarding potential infection sources, laboratory and radiologic findings, clinical presentations, treatment method, and morbidity and mortality rates. For analysis, patients were categorized into two groups: the blood and/or tissue culture-positive (CP) group and the blood and/or tissue culture-negative (CN) group. The latter was further divided as CN with identified microorganism by molecular biologic methods [CN(+)] and CN with no identified microorganism [CN(-)]. RESULTS: More patients in the CP group were symptomatic than were in the CN(+) group (100% vs. 80%; P = 0.034). However, identification of causative microorganisms did not result in a difference in symptom status upon comparing the [CP + CN(+)] and [CN(-)] groups. Inflammatory markers were the most elevated in the CP group and least elevated in the CN(-) group. The aneurysm growth rate seemed slower in the CN(-) group than in the CN(+) and CP groups (1.3 vs. 3.4 vs. 9 mm/month respectively). Aneurysm rupture at initial presentation was more prevalent in the CP group (33.3%). 18F-Fluorodeoxyglucose-positron emission tomography showed increased uptake regardless of whether or not the microorganisms were identified. Early mortality and disease-specific mortality rates during the follow-up period were higher in the CP group but without statistical significance. CONCLUSIONS: Compared with the CP group, the CN groups appeared clinically less severe, and also exhibited a relatively less devastating course as exhibited by the slower aneurysm expansion rate and smaller number of ruptured aneurysms at the initial presentation.

Simulation study on flow rate accuracy of infusion pumps in vibration conditions during emergency patient transport.

Infusion pumps are frequently used when transferring critically ill patients via patient transport cart, ambulance, or helicopter. However, the performance of various infusion pumps under these circumstances has not been explored. The aim of this study was to evaluate the flow rate accuracy of infusion pumps under various clinical vibration conditions. Experiments were conducted with four different types of pumps, including two conventional syringe pumps (Injectomat MC Agilia, Fresenius Kabi and TE-331, Terumo), one conventional peristaltic pump (Volumed µVP7000; Arcomed), and one new cylinder pump (H-100, Meinntech). The flow rate was measured using an infusion pump analyzer on a stable table (0 m/s2) for 1 h with 1 ml/h and 5 ml/h. Experiments were repeated in mild vibration (2 m/s2) (representing vibration of patients in a moving stretcher or ambulance), and in moderate vibration (6 m/s2) (representing vibration in helicopter transport). Any accidental bolus occurrence in extreme vibration situations (20 m/s2) was also analyzed. Simulated vibrations were reproduced by a custom-made vibration table. In the resting state without vibration and in mild vibration conditions, all pumps maintained good performance. However, in moderate vibration, flow rates in syringe pumps increased beyond their known error ranges, while flow rates in peristaltic pumps remained stable. In extreme vibration, accidental fluid bolus occurred in syringe pumps but not in peristaltic pumps. The newly developed cylinder pump maintained stable performance and was unaffected by external vibration environments.

Nonoperating room anaesthesia for elderly patients.

PURPOSE OF REVIEW: The number of elderly patients receiving non-operating room anaesthesia (NORA) has substantially increased because of clinical, epidemiological, social and economic reasons. Considering the high risk of anaesthesia-related adverse events in this population, along with the limitations of NORA, more specific knowledge and skills are required. RECENT FINDINGS: Advanced age appears to be an independent risk factor for anaesthesia-related adverse events in a NORA setting, similar to the traditional operating room. As significant changes occur in the pharmacological effects of anaesthetic agents with aging, reducing dosage and carefully titrating drugs are essential. Because NORA-related injury is frequently related to airway obstruction/respiratory depression, non-invasive respiratory activity monitoring is more useful for sedation of elderly patients. Additionally, advanced age increases the risk of aspiration and cognitive complications, even during sedation. SUMMARY: Elderly patients may greatly benefit from the lower invasiveness and faster recovery offered by interventional procedures. However, as they represent a highly heterogeneous population with large variations in physiological reserves and comorbidities, anaesthesiologists should strive to maintain the same practice standards throughout all anaesthetizing locations. Knowledge of the unique hazards associated with NORA in elderly patients may further enhance patient safety.Video abstract: NORA for elderly patients.mp4: http://links.lww.com/COAN/A66.

Comparison of Operator Workloads Associated with the Single-unit Anyfusion® Pump and the Changeover from a Syringe Pump to an Infusion Pump.

BACKGROUND: A changeover from a syringe pump to an infusion pump may transiently interrupt drug administration and result in medication errors. A newly developed infusion device (Anyfusion®) that combines the functions of an infusion pump and a syringe pump in a single unit was recently commercialized. This study compared the operator workloads associated with the Anyfusion® pump and with the conventional method using two infusion devices (a syringe pump and an infusion pump). METHODS: This was a prospective, randomized, crossover-designed simulation study using an imitation arm with an intravascular line. We compared the two methods in terms of total execution time, total number of button clicks, and subjective difficulty using a numerical rating scale with a score from 0 (extremely easy) to 10 (extremely difficult). RESULTS: Twenty-two nurses successfully performed both interventions according to the allocated sequence. Total execution times did not differ between the two methods (129.5 ± 23.2 seconds for the conventional method vs. 121.2 ± 24.3 seconds for the Anyfusion® method; P = 0.244), although the total number of clicks was significantly fewer using the Anyfusion® than the conventional method (median [interquartile range]: 10.0 [9.0-12.0] vs. 21.0 [20.0-25.0], respectively; P < 0.001). Participants rated the Anyfusion® method as easier than the conventional method (1.7 ± 1.2 vs. 3.6 ± 1.6; P < 0.001, respectively). CONCLUSION: The introduction of Anyfusion® lessened the workload of practitioners required by the changeover process, which might reduce the risk of medication errors and subsequent patient harm. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0004172.

Mutations in DDX58, which encodes RIG-I, cause atypical Singleton-Merten syndrome.

Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.

Natural history of spontaneous isolated celiac artery dissection after conservative treatment.

OBJECTIVE: Optimal treatment of spontaneous isolated celiac artery dissection (SICAD) is not well established because the natural history of this rare disease is poorly understood. We analyzed the natural history of patients who underwent conservative treatment. METHODS: The study included 28 patients with SICAD from December 2008 to January 2017. Our institutional policy of first-line treatment for SICAD patients was conservative, and invasive procedures were reserved for unstable complications such as severe persistent pain, significant organ malperfusion, rapid aneurysmal change, and rupture or concealed rupture. Demographics, clinical features, morphologic characteristics on computed tomography, treatment modalities, and follow-up results of these patients were retrospectively reviewed. RESULTS: Mean age was 52 years, and 89% of patients were male; 86% presented with pain, mostly abdominal, and 14% of cases were detected incidentally on abdominal imaging. None of these patients had unstable complications on admission, and all underwent initial conservative treatment. During the follow-up period (22 ± 20 months), aneurysmal change and propagation of thrombosis were noted in one patient and two patients, respectively, all of whom were managed conservatively without adverse clinical events. No difference in clinical and morphologic outcomes was noted between patients who were treated with antihypertensive therapy and those who were not. Patients with intramural hematoma on initial images showed dynamic vascular remodeling (partial to complete resorption) during the follow-up period compared with patients who had dominant intimal flap on initial images. CONCLUSIONS: The clinical course of patients with SICAD was benign. Even progressive vascular changes during follow-up did not require invasive treatment. Antihypertensive therapy might not modify the clinical course. The short-term results of conservative management are encouraging, but further evaluation with long-term follow-up in a large population is needed.

Comparison of Safety Profiles between Non-operating Room Anesthesia and Operating Room Anesthesia: a Study of 199,764 Cases at a Korean Tertiary Hospital.

BACKGROUND: Despite expanding demands for non-operating room anesthesia (NORA) worldwide, studies in this field are scarce. We compared the overall characteristics and the nature of deaths occurring within 48 hours after surgery between NORA and operating room anesthesia (ORA) cases at a Korean tertiary hospital. METHODS: We retrospectively analyzed the medical records of patients who underwent surgical procedures under anesthesia services in and outside the operating room from January 2013 to November 2017. All of the mortalities were categorized by principal cause into groups such as patient disease or condition, surgery, anesthesia, and others. RESULTS: Overall, 16,383 NORA cases and 183,381 ORA cases were analyzed. Eighty-six deaths were identified. The mortality rate of NORA cases was similar to that of ORA cases (4.9 per 10,000 cases [95% confidence interval (CI), 2.1-9.6] vs. 4.3 per 10,000 cases [95% CI, 3.4-5.3], respectively). Similar to ORA cases, higher American Society of Anesthesiologists physical status and very young age (< 2 years) were significantly associated with mortality in NORA cases. A patient's disease or condition was the most important cause of mortality (65/86, 75.6%), followed by surgery-related causes (16/86, 18.6%). Two cases of anesthesia-related mortality were only identified in the ORA cases, resulting in an overall anesthesia-related mortality of 0.1 per 10,000 cases (95% CI, 0.0-0.4). CONCLUSION: Although NORA cases showed an equivalent perioperative mortality rate compared to ORA cases, there may be more room for improving patient safety when considering their favorable characteristics (healthier patients, less invasive and shorter procedures). Trial registry at Clinical Research Information Service, KCT0002719.

Impact of Balloon Pulmonary Angioplasty on Hemodynamics and Clinical Outcomes in Patients with Chronic Thromboembolic Pulmonary Hypertension: the Initial Korean Experience.

BACKGROUND: The treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). However, not all patients are eligible for PEA, and some patients experience recurrence of pulmonary hypertension even after PEA. METHODS: Patients who underwent balloon pulmonary angioplasty (BPA) between December 2015 and April 2017 were enrolled from the Samsung Medical Center CTEPH registry. Enrolled patients underwent right heart catheterization, echocardiography, and 6-minute walk distance (6MWD) at baseline, 4 and 24 weeks after their first BPA session. We compared clinical and hemodynamic parameters at the baseline and last BPA session. RESULTS: Fifty-two BPA sessions were performed in 15 patients, six of whom had a history of PEA. BPA resulted in improvements in World Health Organization (WHO) functional class (2.9 ± 0.8 to 1.7 ± 0.6, P = 0.002), 6MWD (387.0 ± 86.4 to 453.4 ± 64.8 m, P = 0.01), tricuspid annular plane systolic excursion (14.1 ± 3.6 to 15.6 ± 4.3 mm, P = 0.03) and hemodynamics, including a decline in mean pulmonary artery pressure (41.1 ± 13.1 to 32.1 ± 9.5 mmHg, P < 0.001) and in pulmonary vascular resistance (607.4 ± 452.3 to 406.7 ± 265.4 dyne.sec.cm⁻5, P = 0.01) but not in cardiac index (2.94 ± 0.79 to 2.96 ± 0.93 L/min/m², P = 0.92). Six cases of complications were recorded, including two cases of reperfusion injury. CONCLUSION: BPA might be a safe and effective treatment strategy for both inoperable CTEPH patients and patients with residual pulmonary hypertension after PEA.

Treatment strategy based on the natural course for patients with spontaneous isolated superior mesenteric artery dissection.

OBJECTIVE: The optimal treatment of spontaneous isolated superior mesenteric artery dissection (SISMAD) is still not known, and we sought to determine an optimal treatment strategy for patients with SISMAD based on its natural clinical course. METHODS: We retrospectively reviewed consecutive patients with SISMAD treated from 2001 through 2016. Diagnosis and angiographic type of SISMAD were determined with contrast-enhanced computed tomography (CT) scan, and the clinical features were obtained using a fixed form questionnaire. All patients were treated conservatively, except for five who unselectively underwent primary interventional treatment. For the follow-up examinations, clinical features and morphologic changes of superior mesenteric artery dissection were examined with CT angiography every 6 to 12 months. RESULTS: During the past 15 years, 116 patients with SISMAD (male, 92%; mean age, 54.7 ± 10.8 years; symptomatic, 76%) were encountered. Clinical features and morphologic changes on CT examinations were available in 100% and 88% of the patients, respectively, during the mean follow-up of 53 ± 39 months (range, 1-173 months). Of 83 symptomatic patients managed conservatively, 96% achieved pain resolution; 4% experienced prolonged pain, including one patient with bowel gangrene. After pain resolution, 20% of patients developed late recurrence of abdominal pain, which was relieved with conservative management, whereas two patients (12%) required surgery to treat bowel stricture. Follow-up examinations (n = 102) by CT angiography revealed no change in 34%, partial or complete remodeling in 63%, aneurysmal change in 2%, and dissection progression in 1% of the patients. Antithrombotic therapy offered no beneficial effects on either clinical or morphologic outcomes. CONCLUSIONS: With conservative treatment, the majority of patients with SISMAD showed clinical improvement and no morphologic changes during long-term follow-up. We thus recommend a conservative management strategy as the first-line treatment for patients with SISMAD, regardless of angiographic type.