Verification of the termination of resuscitation rules in pediatric out-of-hospital cardiac arrest cases.

Aim: Pediatric out-of-hospital cardiac arrest has an unfavorable prognosis; therefore, making accurate predictions of outcomes is crucial for tailoring treatment plans. The termination of resuscitation rules must accurately predict unfavorable outcomes. In this study, we aimed to assess if the current termination of resuscitation rules for adults can predict factors associated with unfavorable outcomes in pediatric out-of-hospital cardiac arrest and examine the relationship between these factors and unfavorable outcomes. Methods: A retrospective nationwide cohort study of pediatric cases registered in the Japanese Association for Acute Medicine Multicenter Out-of-Hospital Cardiac Arrest Registry from June 1, 2014, to December 31, 2020, was conducted. The association between the current termination of resuscitation rules and outcomes, such as 30-day mortality and unfavorable 30-day neurological outcomes following out-of-hospital cardiac arrest, was evaluated. Results: A total of 1,216 participants were included. The positive predictive value for predicting 30-day mortality for each termination of resuscitation rule exceeded 0.9. The specificity and positive predictive value for predicting unfavorable 30-day neurological outcomes were 1.00, indicating that no rules identified favorable outcomes. Factors such as no bystander witness, no return of spontaneous circulation before hospital arrival, no automated external defibrillator or defibrillator use, and no bystander cardiopulmonary resuscitation were associated with poor 30-day mortality and neurological outcomes. Conclusion: Adult termination of resuscitation rules had a high positive predictive value for predicting pediatric out-of-hospital cardiac arrest. However, surviving cases make it challenging to use these rules for end-of-resuscitation decisions, indicating the need for identifying new rules to help predict neurological outcomes.

Characteristics and Risk Factors for the Fracture of One-Piece Implants.

Objective: The one-piece dental implant was originally designed to overcome the structural weaknesses of the two-piece implant. However, a fractured one-piece implant requires removal because the abutment cannot be repaired or replaced to support new prosthetic restorations. The aim of this study was to clarify the features and risk factors for fracture of the one-piece implant. Methods: This study was designed as a retrospective case series research. The subjects were patients who were treated for fractures of the one-piece implant at a clinic in Japan between 2012 and 2021. Fractures of the one-piece implant were diagnosed by cone-beam computed tomography, and the association between age and duration from implant placement to fracture was analyzed by one-way ANOVA followed by the Tukey test. Results: Eighteen patients and 20 one-piece implants (under 39 years: 5 patients and 6 implants; 40-59 years: 7 patients and 7 implants; over 60 years: 6 patients and 7 implants) had fractures in their one-piece implants. Of the fractured implants, 11 had a diameter of 3 mm, and 9 had a diameter of 4 mm. The mean durations up to implant fracture were 662 days in the younger group, 1467 days in the middle group, and 1239 days in older group, and the duration was significantly shorter in the younger group. In addition, 83.3% of fracture implants in the younger group were in the molar region. All fractures of the one-piece implants occurred under the bone margin. Two patients had torus mandibularis, and 1 patient was had bruxism. Conclusions: One-piece implants in younger patients that are located in the lower molar position are the most susceptible to implant fracture, and the fracture occurred under the bone margin in all cases.

Extracellular vesicle-based liquid biopsies in cancer: Future biomarkers for oral cancer.

Oral cancer is the sixth most common cancer worldwide, with approximately 530,000 new cases and 300,000 deaths each year. The process of carcinogenesis is complex, and survival rates have not changed significantly in recent decades. Early detection of cancer, prognosis prediction, treatment selection, and monitoring of progression are important to improve survival. With the recent significant advances in analytical technology, liquid biopsy has made it possible to achieve these goals. In this review, we report new results from clinical and cancer research applications of liquid biopsy, focusing on extracellular vesicles (EVs) among the major targets of liquid biopsy, namely, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and EVs. In addition, the potential application of EVs derived from gram-negative bacteria (outer membrane vesicles; OMVs) among oral bacteria, which have recently attracted much attention, to liquid biopsy for oral cancer will also be addressed.

Association Between Thrombin-Antithrombin Complex and Acute Kidney Injury After Pediatric Cardiopulmonary Bypass Surgery: A Single-Center Retrospective Observational Study.

Vascular endothelial damage may activate hypercoagulation and contribute to the development of acute kidney injury (AKI). This study aimed to investigate whether early alteration in coagulation was associated with AKI onset following surgeries involving cardiopulmonary bypass (CPB) in children. This single-center retrospective cohort study included 154 infants and toddlers who underwent cardiovascular surgery with CPB. At admission to the pediatric intensive care unit, the absolute thrombin-antithrombin complex (TAT) level in each patient was measured. Moreover, the presence or absence of AKI onset in the early postoperative period was observed. Of the total participants, 55 (35%) developed AKI. A comparison within the toddler group based on the TAT cut-off value showed that both univariate and multivariable associations were found between increased absolute TAT level and AKI onset (odds ratio, 4.70; 95% confidence interval [1.20-17.90]; P = .023). The increase in absolute TAT level in toddlers during the early postoperative period following CPB was associated with AKI onset. However, a further prospective multicenter study with a larger sample size is required for validating these findings.

Pediatric fulminant malignant hyperthermia with severe electroencephalographic abnormality and brain damage: a case report.

BACKGROUND: Malignant hyperthermia is an extremely dangerous condition that can occur with exposure to volatile inhalant anesthetics and depolarizing muscle relaxants, and that requires immediate intervention. Neurological complications have rarely been reported, with no reports of electroencephalographic abnormalities or encephalopathy. Here, we report a case of severe electroencephalographic abnormality in the acute phase of malignant hyperthermia that eventually led to diffuse cerebral cortical damage. CASE PRESENTATION: A 15-month-old Japanese boy underwent a Rastelli procedure to correct a double-outlet right ventricle and pulmonary atresia. Sevoflurane was used for induction and maintenance of anesthesia during surgery. After withdrawal from the heart-lung machine, his body temperature rose at a rate of 0.1 â„ƒ/minute, and when he left the operating room, his core body temperature had reached 42 â„ƒ. After admission to the intensive care unit, tachycardia, high PaCO2, and progressive metabolic acidosis were observed. A clinical grading scale score of 63 indicated malignant hyperthermia, and dantrolene was administered. The pupils were dilated, and the electroencephalogram showed persistent generalized continuous multifocal spikes. Midazolam, levetiracetam, and fosphenytoin were administered without improvement, and thiamylal and ketamine were infused continuously. After the electroencephalogram shifted to burst suppression, the epileptic firing gradually decreased, and the background electroencephalogram became lower in amplitude. Magnetic resonance imaging of the head performed after the patient was hemodynamically stable suggested diffuse cerebral cortical damage. Severe mental retardation, hypertonia, and quadriplegia were observed as neurological complications. CONCLUSIONS: In this case, despite the use of high-dose anticonvulsants, the patient showed severe electroencephalogram abnormality, resulting in diffuse cortical damage. Hyperthermia is known to damage the central nervous system by causing increased brain pressure and cerebral edema, which may have triggered the severe neuronal excitation that we observed in this case. The presence of systemic inflammatory response syndrome and the patient's background, including young age and ethnicity, might also have been factors. Malignant hyperthermia can be complicated by encephalopathy, and continuous electroencephalogram monitoring should be considered.

VCAM-1 and GFPT-2: Predictive markers of osteoblast differentiation in human dental pulp stem cells.

INTRODUCTION: Dental pulp stem cells (DPSCs) have high proliferative and multilineage differentiation potential in mesenchymal stem cells. However, several studies have indicated that there are individual differences in the potential for osteogenic differentiation of DPSCs, and the factors determining these differences are unknown. OBJECTIVE: To identify the genes responsible for the individual differences in the osteogenic differentiation ability of DPSCs. METHODS: We divided DPSCs into high and low osteogenic differentiation ability groups (HG or LG) with ALP and von Kossa stain, and compared the gene expression patterns using RNA-seq. In addition, genes that may affect osteogenic differentiation were knocked down using small interfering RNA (siRNA) and their effects were investigated. RESULTS: The RNA-seq patterns revealed that VCAM1 and GFPT2 were significantly expressed at higher levels in the HG than in the LG. The results of siRNA analysis showed that VCAM1 and GFPT2 knockdown significantly reduced the expression of osteogenic markers. Furthermore, we analyzed the involvement of these two genes in cell signaling in DPSC differentiation. The results indicated that the VCAM1-mediated Ras-MEK-Erk and PI3K/Akt pathways are involved in the osteogenic differentiation of DPSCs, and that GFPT2-mediated HBP signaling influences the osteogenic differentiation of DPSCs. CONCLUSIONS: These findings indicate that DPSCs that highly express VCAM1 and GFPT2 have a high capacity for osteogenic differentiation. Evaluation of VCAM1 and GFPT2 expression in undifferentiated DPSCs may predict the outcome of bone regenerative therapy using DPSCs. Moreover, the expression levels of VCAM1 and GFPT2 in DPSCs may be useful in setting criteria for selecting donors for allogeneic cell transplantation for bone regeneration.

Utility of dual-energy computed tomography in the association of COVID-19 pneumonia severity.

Aim: Coronavirus disease 2019 pneumonia differs from ordinary pneumonia in that it is associated with lesions that reduce pulmonary perfusion. Dual-energy computed tomography is well suited to elucidate the etiology of coronavirus disease 2019 pneumonia, because it highlights changes in organ blood flow. In this study, we investigated whether dual-energy computed tomography could be used to determine the severity of coronavirus disease 2019 pneumonia. Methods: Patients who were diagnosed with coronavirus disease 2019 pneumonia, admitted to our hospital, and underwent dual-energy computed tomography were included in this study. Dual-energy computed tomography findings, plane computed tomography findings, disease severity, laboratory data, and clinical features were compared between two groups: a critical group (18 patients) and a non-critical group (30 patients). Results: The dual-energy computed tomography results indicated that the percentage of flow loss was significantly higher in the critical group compared with the non-critical group (P < 0.001). Additionally, our data demonstrated that thrombotic risk was associated with differences in clinical characteristics (P = 0.018). Receiver operating characteristic analysis revealed that the percentage of flow loss, evaluated using dual-energy computed tomography, could predict severity in the critical group with 100% sensitivity and 77% specificity. However, there were no significant differences in the receiver operating characteristic values for dual-energy computed tomography and plane computed tomography. Conclusion: Dual-energy computed tomography can be used to associate the severity of coronavirus disease 2019 pneumonia with high accuracy. Further studies are needed to draw definitive conclusions.

Methylprednisolone pulse therapy for critically ill patients with coronavirus disease 2019: A single-center retrospective observational study.

Aim: This study compared the clinical outcomes of critically ill patients with coronavirus disease (COVID-19) pneumonia treated with high-dose methylprednisolone and other steroids. Methods: This retrospective observational study included critically ill COVID-19 pneumonia adult patients with tracheal intubation treated between April 1, 2020, and September 15, 2021. Of the 46 patients who met the inclusion criteria, 36 received steroid pulse therapy (Group P) and 10 received steroids without pulse therapy (Group NP). Subgroup analyses in Group P by methylprednisolone dose of 1000 or 500 mg for 3 days during intensive care unit stay were carried out. The primary and secondary outcomes were 28-day mortality and steroid-associated complications, respectively. Results: In the Kaplan-Meier curve analysis, there was no difference in the 28-day survival between P and NP groups (log-rank P = 0.046). Univariate Cox proportional hazard model also showed that Group P had a decreased 28-day mortality (hazard ratio 0.30; [95% confidence interval, 0.20-0.44]; P < 0.01). After adjusting for covariates (age, sex, remdesivir, baricitinib, and favipiravir), using the multivariate Cox proportional hazards model, Group P had improved 28-day mortality (0.50 [0.30-0.85], P = 0.01). Conclusion: Steroid pulse therapy might improve the 28-day and in-hospital mortality in critically ill patients with COVID-19 pneumonia.

Two cases of post-traumatic inferior vena cava thrombosis.

BACKGROUND: Inferior vena cava thrombosis is a rare blunt abdominal trauma complication often associated with severe liver injury. We present two cases of inferior vena cava thrombosis due to mild liver injuries. CASE PRESENTATION: Case 1 was a 25-year-old woman taking oral contraceptives for dysmenorrhea who was injured in a motorcycle accident. Contrast-enhanced computed tomography revealed hepatic contusion of the sixth segment. At 1 week after the accident, inferior vena cava thrombosis was detected. Case 2 was a 58-year-old man injured in a motorcycle accident. Contrast-enhanced computed tomography showed traumatic subarachnoid hemorrhage, right hemothorax, and liver injury with hepatic contusion of the sixth segment. At 1 week after the accident, inferior vena cava thrombosis was observed. CONCLUSION: Inferior vena cava thrombosis can occur following liver injury, regardless of damage severity. When there are thrombogenic factors and damage near the inferior vena cava, follow-up examinations should be carried out.

DUAL-energy computed tomography findings in a case of COVID-19.

BACKGROUND: COVID-19 pneumonia has lesions with a decreased blood flow. Dual-energy computed tomography is suitable to elucidate the pathogenesis of COVID-19 pneumonia because it highlights the blood flow changes in organs. We report the dual-energy computed tomography findings of a successfully treated case of COVID-19 pneumonia. CASE PRESENTATION: An obese 49-year-old man with COVID-19 pneumonia was transferred from another hospital on day 11 after onset of illness. Although he was hypoxemic (PaO2/FiO2 = 100), tracheal intubation was not performed after anticipating difficulty in weaning from mechanical ventilation. Prone position therapy and nasal high flow therapy were administered, and the patient was discharged after his condition improved. Dual-energy computed tomography was performed three times during hospitalization, and it revealed improvement in the blood flow defect, unlike plain computed tomography that did not show much improvement. CONCLUSION: Dual-energy computed tomography can assess perfusion in COVID-19 pneumonia in real time and may be able to predict its severity.

Neutrophil gelatinase-associated lipocalin as a biomarker for short-term outcomes among trauma patients: A single-center observational study.

BACKGROUND: Urinary biomarkers for organ dysfunction could predict the outcomes of severe trauma patients. However, the use of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of trauma is not well studied. OBJECTIVES: To evaluate the association between the short-term prognosis of trauma patients and NGAL levels. METHODS: We conducted a single center study and compared predictive performances between NGAL levels and the trauma severity. RESULTS: A total of 104 patients were included in the study. Patients were divided into two groups based on ISS score of 16. There was no significant difference in patient characteristics based on trauma severity. However, the lactate level was significantly higher in the more severe group. There was a significant association between urinary NGAL levels and trauma severity indicators, such as intensive care unit stay (ICU) (p = 0.005) and emergency care unit (ECU) stay (p = 0.049). In addition, receiver operating curve analysis showed that as a predictor, NGAL could be used for detecting severity with moderate precision, especially for short-term outcomes (specificity 70.6 for ICU and 69.0 for ECU stay). CONCLUSION: In this study, we revealed that the level of NGAL could predict the degree of invasiveness in trauma patients with moderate precision and estimate the duration of treatment during the acute phase. It is necessary to examine the validity of the findings of this study using a prospective, cohort, and multi-center collaborative study design.

Individuals with progranulin haploinsufficiency exhibit features of neuronal ceroid lipofuscinosis.

Heterozygous mutations in the GRN gene lead to progranulin (PGRN) haploinsufficiency and cause frontotemporal dementia (FTD), a neurodegenerative syndrome of older adults. Homozygous GRN mutations, on the other hand, lead to complete PGRN loss and cause neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease usually seen in children. Given that the predominant clinical and pathological features of FTD and NCL are distinct, it is controversial whether the disease mechanisms associated with complete and partial PGRN loss are similar or distinct. We show that PGRN haploinsufficiency leads to NCL-like features in humans, some occurring before dementia onset. Noninvasive retinal imaging revealed preclinical retinal lipofuscinosis in heterozygous GRN mutation carriers. Increased lipofuscinosis and intracellular NCL-like storage material also occurred in postmortem cortex of heterozygous GRN mutation carriers. Lymphoblasts from heterozygous GRN mutation carriers accumulated prominent NCL-like storage material, which could be rescued by normalizing PGRN expression. Fibroblasts from heterozygous GRN mutation carriers showed impaired lysosomal protease activity. Our findings indicate that progranulin haploinsufficiency caused accumulation of NCL-like storage material and early retinal abnormalities in humans and implicate lysosomal dysfunction as a central disease process in GRN-associated FTD and GRN-associated NCL.

SIRT1 deficiency in microglia contributes to cognitive decline in aging and neurodegeneration via epigenetic regulation of IL-1ß.

Aging is the predominant risk factor for neurodegenerative diseases. One key phenotype as the brain ages is an aberrant innate immune response characterized by proinflammation. However, the molecular mechanisms underlying aging-associated proinflammation are poorly defined. Whether chronic inflammation plays a causal role in cognitive decline in aging and neurodegeneration has not been established. Here we report a mechanistic link between chronic inflammation and aging microglia and a causal role of aging microglia in neurodegenerative cognitive deficits. We showed that SIRT1 is reduced with the aging of microglia and that microglial SIRT1 deficiency has a causative role in aging- or tau-mediated memory deficits via IL-1ß upregulation in mice. Interestingly, the selective activation of IL-1ß transcription by SIRT1 deficiency is likely mediated through hypomethylating the specific CpG sites on IL-1ß proximal promoter. In humans, hypomethylation of IL-1ß is strongly associated with chronological age and with elevated IL-1ß transcription. Our findings reveal a novel epigenetic mechanism in aging microglia that contributes to cognitive deficits in aging and neurodegenerative diseases.

Early retinal neurodegeneration and impaired Ran-mediated nuclear import of TDP-43 in progranulin-deficient FTLD.

Frontotemporal dementia (FTD) is the most common cause of dementia in people under 60 yr of age and is pathologically associated with mislocalization of TAR DNA/RNA binding protein 43 (TDP-43) in approximately half of cases (FLTD-TDP). Mutations in the gene encoding progranulin (GRN), which lead to reduced progranulin levels, are a significant cause of familial FTLD-TDP. Grn-KO mice were developed as an FTLD model, but lack cortical TDP-43 mislocalization and neurodegeneration. Here, we report retinal thinning as an early disease phenotype in humans with GRN mutations that precedes dementia onset and an age-dependent retinal neurodegenerative phenotype in Grn-KO mice. Retinal neuron loss in Grn-KO mice is preceded by nuclear depletion of TDP-43 and accompanied by reduced expression of the small GTPase Ran, which is a master regulator of nuclear import required for nuclear localization of TDP-43. In addition, TDP-43 regulates Ran expression, likely via binding to its 3'-UTR. Augmented expression of Ran in progranulin-deficient neurons restores nuclear TDP-43 levels and improves their survival. Our findings establish retinal neurodegeneration as a new phenotype in progranulin-deficient FTLD, and suggest a pathological loop involving reciprocal loss of Ran and nuclear TDP-43 as an underlying mechanism.