Newly Developed Sex-Specific Z Score Model for Coronary Artery Diameter in a Pediatric Population.

BACKGROUND: This study aimed to generate a Z score calculation model for coronary artery diameter of normal children and adolescents to be adopted as the standard calculation method with consensus in clinical practice. METHODS: This study was a retrospective, multicenter study that collected data from multiple institutions across South Korea. Data were analyzed to determine the model that best fit the relationship between the diameter of coronary arteries and independent demographic parameters. Linear, power, logarithmic, exponential, and square root polynomial models were tested for best fit. RESULTS: Data of 2,030 subjects were collected from 16 institutions. Separate calculation models for each sex were developed because the impact of demographic variables on the diameter of coronary arteries differs according to sex. The final model was the polynomial formula with an exponential relationship between the diameter of coronary arteries and body surface area using the DuBois formula. CONCLUSION: A new coronary artery diameter Z score model was developed and is anticipated to be applicable in clinical practice. The new model will help establish a consensus-based Z score model.

Pediatric Extracorporeal Membrane Oxygenation in Korea: A Multicenter Retrospective Study on Utilization and Outcomes Spanning Over a Decade.

BACKGROUND: Over the last decade, extracorporeal membrane oxygenation (ECMO) use in critically ill children has increased and is associated with favorable outcomes. Our study aims to evaluate the current status of pediatric ECMO in Korea, with a specific focus on its volume and changes in survival rates based on diagnostic indications. METHODS: This multicenter study retrospectively analyzed the indications and outcomes of pediatric ECMO over 10 years in patients at 14 hospitals in Korea from January 2012 to December 2021. Four diagnostic categories (neonatal respiratory, pediatric respiratory, post-cardiotomy, and cardiac-medical) and trends were compared between periods 1 (2012-2016) and 2 (2017-2021). RESULTS: Overall, 1065 ECMO runs were performed on 1032 patients, with the annual number of cases remaining unchanged over the 10 years. ECMO was most frequently used for post-cardiotomy (42.4%), cardiac-medical (31.8%), pediatric respiratory (17.5%), and neonatal respiratory (8.2%) cases. A 3.7% increase and 6.1% decrease in pediatric respiratory and post-cardiotomy cases, respectively, were noted between periods 1 and 2. Among the four groups, the cardiac-medical group had the highest survival rate (51.2%), followed by the pediatric respiratory (46.4%), post-cardiotomy (36.5%), and neonatal respiratory (29.4%) groups. A consistent improvement was noted in patient survival over the 10 years, with a significant increase between the two periods from 38.2% to 47.1% (P = 0.004). Improvement in survival was evident in post-cardiotomy cases (30-45%, P = 0.002). Significant associations with mortality were observed in neonates, patients requiring dialysis, and those treated with extracorporeal cardiopulmonary resuscitation (P < 0.001). In pediatric respiratory ECMO, immunocompromised patients also showed a significant correlation with mortality (P < 0.001). CONCLUSION: Pediatric ECMO demonstrated a steady increase in overall survival in Korea; however, further efforts are needed since the outcomes remain suboptimal compared with global outcomes.

Intradural Extramedullary Ependymoma with Hemorrhage: A Case Report.

In adults, spinal ependymomas are usually found in intramedullary locations. However, intradural extramedullary spinal ependymomas are rare. Additionally, spinal ependymomas usually show iso to hypointensity on T1-weighted images without hemorrhage. Herein, we present a rare case of a 43-year-old female with a pathologically confirmed intradural extramedullary ependymoma that showed hyperintensity on T1-weighted imaging accompanied by hemorrhage.

A selective ER-phagy exerts neuroprotective effects via modulation of α-synuclein clearance in parkinsonian models.

The endoplasmic reticulum (ER) is selectively degraded by ER-phagy to maintain cell homeostasis. α-synuclein accumulates in the ER, causing ER stress that contributes to neurodegeneration in Parkinson's disease (PD), but the role of ER-phagy in α-synuclein modulation is largely unknown. Here, we investigated the mechanisms by which ER-phagy selectively recognizes α-synuclein for degradation in the ER. We found that ER-phagy played an important role in the degradation of α-synuclein and recovery of ER function through interaction with FAM134B, where calnexin is required for the selective FAM134B-mediated α-synuclein clearance via ER-phagy. Overexpression of α-synuclein in the ER of the substantia nigra (SN) resulted in marked loss of dopaminergic neurons and motor deficits, mimicking PD characteristics. However, enhancement of ER-phagy using FAM134B overexpression in the SN exerted neuroprotective effects on dopaminergic neurons and recovered motor performance. These data suggest that ER-phagy represents a specific ER clearance mechanism for the degradation of α-synuclein.

Rat Model of Normothermic Ex-Situ Perfused Heterotopic Heart Transplantation.

Heart transplantation is the most effective therapy for end-stage heart failure. Despite the improvements in therapeutic approaches and interventions, the number of heart failure patients waiting for transplantation is still increasing. The normothermic ex situ preservation technique has been established as a comparable method to the conventional static cold storage technique. The main advantage of this technique is that donor hearts can be preserved for up to 12 h in a physiologic condition. Moreover, this technique allows resuscitation of the donor hearts after circulatory death and applies required pharmacologic interventions to improve donor function after implantation. Numerous animal models have been established to improve normothermic ex situ preservation techniques and eliminate preservation-related complications. Although large animal models are easy to handle compared to small animal models, it is costly and challenging. We present a rat model of normothermic ex situ donor heart preservation followed by heterotopic abdominal transplantation. This model is relatively cheap and can be accomplished by a single experimenter.

Hypoalbuminemia and Albumin Replacement during Extracorporeal Membrane Oxygenation in Patients with Cardiogenic Shock.

Background: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with cardiorespiratory failure. The serum albumin level is an important prognostic marker in critically ill patients. We evaluated the efficacy of using pre-ECMO serum albumin levels to predict 30-day mortality in patients with cardiogenic shock (CS) who underwent venoarterial (VA) ECMO. Methods: We reviewed the medical records of 114 adult patients who underwent VA-ECMO between March 2021 and September 2022. The patients were divided into survivors and non-survivors. Clinical data before and during ECMO were compared. Results: Patients' mean age was 67.8±13.6 years, and 36 (31.6%) were female. The proportion of survival to discharge was 48.6% (n=56). Cox regression analysis showed that the pre-ECMO albumin level independently predicted 30-day mortality (hazard ratio, 0.25; 95% confidence interval [CI], 0.11-0.59; p=0.002). The area under the receiver operating characteristic curve of albumin levels (pre-ECMO) was 0.73 (standard error [SE], 0.05; 95% CI, 0.63-0.81; p<0.001; cut-off value=3.4 g/dL). Kaplan-Meier survival analysis showed that the cumulative 30-day mortality was significantly higher in patients with a pre-ECMO albumin level ≤3.4 g/dL than in those with a level >3.4 g/dL (68.9% vs. 23.8%, p<0.001). As the adjusted amount of albumin infused increased, the possibility of 30-day mortality also increased (coefficient=0.140; SE, 0.037; p<0.001). Conclusion: Hypoalbuminemia during ECMO was associated with higher mortality, even with higher amounts of albumin replacement, in patients with CS who underwent VA-ECMO. Further studies are needed to predict the timing of albumin replacement during ECMO.

Extracorporeal circulation models in small animals: beyond the limits of preclinical research.

Extracorporeal membrane oxygenation (ECMO) use has remarkably increased in recent years. Although ECMO has become essential for patients with refractory cardiac and respiratory failure, extracorporeal circulation (ECC) is associated with significant complications. Small-animal models of ECC have been developed and widely used to better understand ECC-induced pathophysiology. This review article summarizes the development of small-animal ECC models, including the animal species, circuit configuration, priming, perioperative procedures, cannulation, and future perspectives of small-animal ECMO models.

Cryo-EM structures of human Cx36/GJD2 neuronal gap junction channel.

Connexin 36 (Cx36) is responsible for signal transmission in electrical synapses by forming interneuronal gap junctions. Despite the critical role of Cx36 in normal brain function, the molecular architecture of the Cx36 gap junction channel (GJC) is unknown. Here, we determine cryo-electron microscopy structures of Cx36 GJC at 2.2-3.6 Å resolutions, revealing a dynamic equilibrium between its closed and open states. In the closed state, channel pores are obstructed by lipids, while N-terminal helices (NTHs) are excluded from the pore. In the open state with pore-lining NTHs, the pore is more acidic than those in Cx26 and Cx46/50 GJCs, explaining its strong cation selectivity. The conformational change during channel opening also includes the α-to-π-helix transition of the first transmembrane helix, which weakens the protomer-protomer interaction. Our structural analyses provide high resolution information on the conformational flexibility of Cx36 GJC and suggest a potential role of lipids in the channel gating.

Rapid remodeling observed at mid-term in-vivo study of a smart reinforced acellular vascular graft implanted on a rat model.

BACKGROUND: The poor performance of conventional techniques used in cardiovascular disease patients requiring hemodialysis or arterial bypass grafting has prompted tissue engineers to search for clinically appropriate off-the-shelf vascular grafts. Most patients with cardiovascular disease lack suitable autologous tissue because of age or previous surgery. Commercially available vascular grafts with diameters of < 5 mm often fail because of thrombosis and intimal hyperplasia. RESULT: Here, we tested tubular biodegradable poly-e-caprolactone/polydioxanone (PCL/PDO) electrospun vascular grafts in a rat model of aortic interposition for up to 12 weeks. The grafts demonstrated excellent patency (100%) confirmed by Doppler Ultrasound, resisted aneurysmal dilation and intimal hyperplasia, and yielded neoarteries largely free of foreign materials. At 12 weeks, the grafts resembled native arteries with confluent endothelium, synchronous pulsation, a contractile smooth muscle layer, and co-expression of various extracellular matrix components (elastin, collagen, and glycosaminoglycan). CONCLUSIONS: The structural and functional properties comparable to native vessels observed in the neoartery indicate their potential application as an alternative for the replacement of damaged small-diameter grafts. This synthetic off-the-shelf device may be suitable for patients without autologous vessels. However, for clinical application of these grafts, long-term studies (> 1.5 years) in large animals with a vasculature similar to humans are needed.

Frequency of serous tubal intraepithelial carcinoma (STIC) in patients with high grade serous ovarian cancer.

OBJECTIVE: Serous tubal intraepithelial carcinoma (STIC) is a known precursor of high-grade serous ovarian cancer (HGSOC). This study aimed to evaluate the proportion of STIC in patients with HGSOC and analyze the STIC-related prognosis in patients with HGSOC. MATERIALS AND METHODS: All pathology reports at our institution that included bilateral salpingectomies of patients with HGSOC from January 2013 to December 2018 were reviewed by two experienced pathologists. The specimens from the ovaries and the salpinx including fimbria were examined. We analyzed the correlation between STIC and HGSOC and compared the clinical characteristics and STIC-related prognostic outcomes in patients with HGSOC. RESULTS: Eleven of the 76 cases were STIC. BRCA mutations were found in 16.9% of patients with HGSOC. STIC was observed in 30.0% of patients with BRCA mutations and in 14.3% of patients without BRCA mutations. The incidence of STIC in patients with BRCA mutations was approximately twice that in patients without BRCA mutations; however, the difference was not statistically significant (P = 0.231). Further, the 5-year survival rate of patients without STIC appeared to be high; nevertheless, the difference was not statistically significant (59.7% vs. 47.4%, P = 0.633). Moreover, there was no significant difference in disease-free survival rate according to STIC (36.4% vs. 33.1%, P = 0.956). CONCLUSION: STIC was identified in patients with HGSOC, and STIC incidence was prominent in HGSOC related to BRCA mutation. Although low frequency, STIC was detected in patients without BRCA mutation. Therefore, prophylactic salpingectomy may be useful for prevention of HGSOC.

Multiple ectopic germinomas presenting as focal dystonia of fingers: a case report and literature review.

BACKGROUND: Intracranial primary germinomas predominantly develop on or near the midline structure in children and young adults and are diagnosed by brain imaging and biopsy. However, if brain imaging and pathology show unusual findings, it becomes difficult to make an accurate diagnosis. CASE REPORT: Herein, we report the case of a 14-year-old boy who presented with focal dystonia of the fingers as an initial symptom. Magnetic resonance imaging of the brain showed multifocal heterogeneous lesions with solid and cystic components involving the right frontal lobe, corpus callosum, left basal ganglia, and left corona radiata. A stereotactic biopsy of the right frontal lesion revealed several granulomatous areas with abundant inflammatory cells. After immunohistochemical staining, the patient was diagnosed with germinoma and treated with chemoradiotherapy according to the Korean Society for Pediatric Neuro-Oncology protocol. The patient has been in complete remission for five years. CONCLUSION: Germinomas can develop in intracranial off-midline structures, with unusual clinical, radiological, and pathological presentations. It is important to include intracranial germinomas in the differential diagnosis of infiltrative parenchymal tumors, especially in children.

Effect of the respiratory motion of pulmonary nodules on CT-guided percutaneous transthoracic needle biopsy.

BACKGROUND: Computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) is highly affected by respiratory motion; however, respiratory motion of target nodule during the PTNB and its effect on CT-guided lung biopsy have not been studied. PURPOSE: To investigate the effect of the respiratory motion of pulmonary nodules on CT-guided PTNB. MATERIAL AND METHODS: We retrospectively reviewed the procedural CT scans of 426 pulmonary nodules that underwent PTNB during quiet breathing. Maximal and average respiratory motions were measured using the difference of table position of the targeted nodule between multiple procedural scans. Diagnostic performance, complications, and technical factors of PTNB in nodules with large motion (maximal motion >1 cm) were compared with those in nodules with small motion (≤1 cm). RESULTS: The mean maximal and average respiratory motions between tidal volume breathing were 5.4 ± 4.4 and 2.7 ± 2.6 mm, respectively. Sensitivity and accuracy were 93.1% and 96.1% in nodules with large motion, compared with 94.7% and 95.9% in nodules with small motion, respectively. Respiratory targeting (P < 0.001), needle modulation (P < 0.001), motion artifact of target (P < 0.001), target disappearance from scans (P < 0.001), and number of performed CT scans (P < 0.001) were significantly higher in the large motion group, with no significant difference in radiation dose and complications between the groups. CONCLUSION: The respiratory motion of pulmonary nodules during CT-guided PTNB may cause technical difficulties but does not affect diagnostic performance nor complications associated with PTNB.

Prognostic roles of leptin-signaling proteins, PD-L1, and tumor-infiltrating lymphocytes in surgically-resected biliary tract cancers.

BACKGROUND: Biliary tract cancers are rare, with a poor patient prognosis. Leptin and programmed death-ligand 1 (PD-L1) influence CD8+ and forkhead box P3 (FOXP3)+ lymphocytes, and thus, cancer cell growth. We aimed to define the prognostic implications of these variables and the clinicopathological features of biliary tract cancers. METHODS: Immunohistochemistry for leptin signaling-related proteins (leptin, leptin receptor, pSTAT3, extracellular-regulated kinase, mammalian target of rapamycin), PD-L1, CD8, and FOXP3 and in situ hybridization for Epstein-Barr virus-encoded small RNAs were performed in 147 cases of surgically-resected biliary tract cancers. RESULTS: Immune cell PD-L1-positivity, tumor size < 3 cm, adjuvant chemotherapy, no recurrence, and early-stage tumors were correlated with better 5-year survival in the tumoral PD-L1(-) and leptin(-) subgroups, and extrahepatic cholangiocarcinoma through multivariate analysis (all p < 0.05). Immune cell PD-L1 and adjuvant chemotherapy lost its prognostic significance in the tumoral PD-L1+ and leptin+ subgroups. CONCLUSIONS: The prognostic implication of the variables may depend upon tumoral protein expression and the anatomical site. Immune cell PD-L1-positivity and the administration of adjuvant chemotherapy may indicate the favorable survival of patients with surgically-resected biliary tract cancers, specifically, in the tumoral PD-L1(-) or tumor leptin(-) subgroups and extrahepatic cholangiocarcinoma. PD-L1- or leptin-targeted therapy combined with conventional chemotherapy may benefit the tumoral PD-L1+ or leptin+ subgroups.

Combined effects of sepsis and extracorporeal membrane oxygenation on left ventricular performance in a murine model.

Extracorporeal membrane oxygenation (ECMO) may be a viable salvage therapy in selected patients with septic shock. As ECMO use increases, we studied left ventricular (LV) performance during sepsis with and without ECMO using a pressure-volume (PV) loop in a murine model and aimed to understand LV hemodynamics in septic shock with ECMO. The rats were divided into Group 1 (ECMO applied to healthy rats), Group 2 (ECMO for septic rats), Group 3 (Controls, n = 20) and Group 4 (Sepsis induction only, n = 20). The cardiac parameters include end-diastolic volume (EDV), end-systolic volume (ESV), end-diastolic pressure (EDP), and end-systolic pressure (ESP), ejection fraction (EF), end-systolic elastance (Ees), diastolic time constant (Tau) index, arterial elastance (Ea), pressure-volume area (PVA), stroke work (SW), and potential energy (PE). We compared the changes of parameters in all groups. A total of 74 rats were included in the analyses. After 2 h on ECMO, Group 2 was associated with significant increases in ESP, EDV, ESV, PVA, PE, and SW. The difference ratio of PE and PVA was significantly higher in Group 2 compared to Group 1 (P < 0.01). In conclusion, myocardial oxygen consumption was higher in septic shock with ECMO than in controls.

Digital Media Influence on Adolescents' Behavior during the COVID-19 Pandemic: Self-Intravenous Injection of Lactobacilli Drinking Yogurt.

During the coronavirus disease 2019 (COVID-19) pandemic, widened physical distance and social deprivation are being replaced with digital media use. The media's social function has tremendously increased following the COVID-19 era and adolescents living in a media-saturated world are the most vulnerable subjects of all. Social media use can encourage risky behavior in adolescents. Posting videos related to risk behaviors on social media has been linked to jeopardizing not only mental health but also physical safety. Herein, we report a case of a 12-year-old boy who intravenously self-injected Lactobacilli drinking yogurt for the purpose of filming a video to post on social media. He was treated with antibiotics based on Lactobacilli sepsis that cured him without any complications. In order to reduce the risk-taking behavior of adolescents, social norms need to be straightened up, and the social responsibility of hosts is strongly recommended.

A Case of Pathologically Confirmed Corticobasal Degeneration Initially Presenting as Progressive Supranuclear Palsy Syndrome.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) overlap clinically with parkinsonism or extrapyramidal signs and pathologically with tauopathy. Asymmetric parkinsonism and cortical dysfunctions are classical features of CBD. However, symmetric parkinsonism, frequent falls, and supranuclear gaze palsy are key features of PSP. Despite biochemically classified as 4R tauopathies, tufted astrocytes of PSP and astrocytic plaque of CBD show pathologically important differences. Herein, we report a 68-year-old man with pathologically confirmed CBD. He was clinically suspected to have PSP because of progressive gait disturbances, frequent falls, and vertical saccade limitation. Neurological examination performed at age 71 revealed symmetrical bradykinesia, axial rigidity, and postural instability with worsening of early existing symptoms. Magnetic resonance imaging of the brain taken at age 70 detected midbrain and left frontotemporal atrophy and right middle cerebral artery infarction. Left frontotemporoparietal hypometabolism and asymmetrically decreased fluoro-propyl-carbomethoxy-iodophenyl-tropane uptake in the basal ganglia were observed. The autopsy was performed at the time of his death (at age 72), which revealed severe pallor of the substantia nigra and mildly hypopigmented locus ceruleus. AT8 immunohistochemistry and Gallyas staining revealed tau-positive neuronal and glial inclusions, astrocytic plaques, ballooned neurons, and numerous threads in both gray and white matter. No abnormal inclusions were revealed by beta-amyloid, α-synuclein and TDP-43 immunohistochemistry. In our case, cerebral infarction, periventricular and deep white matter ischemic changes, and midbrain atrophy were likely to produce PSP-CBD overlapping symptoms. However, our patient was finally confirmed to have CBD based on pathological findings such as astrocytic plaques.

One Autopsy Proved Neocortical Lewy Body Disease Without the Involvement of the Olfactory Bulb and Brainstem.

Lewy bodies (LBs) and Lewy neurites (LNs) are pathological hallmarks of Parkinson's disease (PD) or dementia with LBs (DLB). Incidental Lewy body disease (iLBD) is defined when LBs and LNs are found in the brain of normal elderly individuals. A 65-year-old man presented with autopsy-proven Lewy body pathology (LBP). He had never complained of cognitive impairments or parkinsonian motor symptoms, and he had always maintained independence in activities of daily living. Hypopigmentations in the locus coeruleus and substantia nigra were discovered during the autopsy. The patient showed severe-to-extremely severe LBs in the neocortex and limbic areas, except in the nucleus basalis of Meynert, amygdala, and brainstem, according to microscopic findings. Hence, using several of the previously known staging systems, it was difficult to classify the patient's LBP type. Furthermore, these findings were unique because they had never been observed before in iLBD.

Chest Pain and Suspected Myocarditis Related to COVID-19 Vaccination in Adolescents-A Case Series.

As adolescents started to be vaccinated against coronavirus disease 2019 (COVID-19), suspected myocarditis and pericarditis related to the vaccine were reported in adolescents. According to the Korea Disease Control and Prevention Agency (KDCA), 2,796,270 persons aged 12−18 years were fully vaccinated by December 8. Among these, 9223 adverse events were reported (0.33%). We aimed to elucidate the clinical courses and short-term outcomes for adolescents aged 12−18 with cardiac symptoms and suspected myo- or peri-carditis related to COVID-19 vaccination in South Korea. Methods: We retrospectively collected data on patients ≤ 18 years of age who had suspected myocarditis or pericarditis within 30 days of COVID-19 vaccination, from July 2021 to January 2022. Results: We reported on 40 adolescents in different South Korean provinces at two centers. Twenty-six cases (65%) were male, and the median age was 16 years (range, 13−18; IQR 14.5−17). Twenty-five cases (62.5%) occurred at the first dose, and fifteen (37.5%) occurred after the second dose. Symptoms started at a median of 2 days (range 0−29 days; IQR 1−5 days) after vaccination. The patients were treated with nonsteroidal anti-inflammatory drugs (77.5%), intravenous immunoglobulin (2.5%), glucocorticoids (20%), colchicine (5%), or no therapy (15%). Five patients (12.5%) required intensive care unit admission; one patient needed inotropic/vasoactive support. No patients required extracorporeal membrane oxygenation or died. The median hospital stay was one day (range 0−8 days; IQR 0−2 days). Twenty-one patients (52.5%) had an abnormal electrocardiogram; among these, seven patients had an elevated ST segment, six patients (15%) had decreased ejection fraction (<55%), and LV function was completely recovered in all of them. Conclusions: Most cases of suspected myocarditis after COVID-19 vaccination in adolescents ≤ 18 years had mild symptoms and clinical courses, as well as a complete recovery. Further studies are needed to evaluate long-term outcomes.