A familial case of aortic dilatation with p.Tyr470Cys in TGFBR2 in which the phenotype included only vascular lesions.

Hereditary connective tissue diseases have different risks of aortic dissection depending on the causative gene. We report a family with no extravascular phenotype and a clinical diagnosis of familial thoracic aortic aneurysm and dissection, but genetic testing confirmed p.Tyr470Cys in TGFBR2, which is typically the responsible gene for Loeys-Dietz syndrome. Validation of the clinical diagnosis by genetic testing is warranted.

Impact of pre-existing dementia on neurosurgical intervention and outcomes in older patients with head injury: an analysis of a nationwide trauma registry in Japan.

BACKGROUND: Dementia is a common comorbidity in older patients with traumatic brain injury (TBI), potentially affecting their care processes and outcomes. However, the impact of pre-existing dementia on TBI remains unclear as research on TBI often excludes older adults with comorbidities. This study aimed to investigate the association between pre-existing dementia and outcomes in older patients admitted to hospitals after TBI. METHODS: This observational study included patients aged ≥ 65 years with TBI who were identified from the Japan Trauma Data Bank between January 1, 2019, and December 31, 2021. Associations between pre-existing dementia and outcomes were assessed using multivariable logistic regression analysis. The primary outcome was survival at discharge. Secondary outcomes were neurosurgical interventions and discharge to home. RESULTS: In total, 16,270 patients from 175 hospitals were analyzed. Of these, 1,750 (10.8%) had pre-existing dementia, and 13,520 (83.1%) survived to discharge. No significant association was observed between pre-existing dementia and neurosurgical interventions and survival at discharge. In contrast, pre-existing dementia was associated with a significantly lower likelihood of being discharged to home. Subgroup analysis revealed interactions between pre-existing dementia and the subgroups, showing adverse impact in relatively younger patients and those without severe head injury. CONCLUSIONS: Patients with pre-existing dementia had similar chances for neurosurgical intervention and survival at discharge than their counterparts without dementia. However, pre-existing dementia was associated with a significantly lower likelihood of being discharged to home, especially in relatively younger patients and those without severe head injury. Therefore, recognizing the risks within this population and taking measures to facilitate social reintegration is necessary.

Prognosis, risk factors, and scoring model of patients resuscitated from traumatic cardiac arrest: A multicenter observational study in Japan.

BACKGROUND: A subset of patients with traumatic cardiac arrest is salvageable when the reversible causes of cardiac arrest are promptly treated. However, prognosis and risk factors of survivors upon hospital admission after traumatic cardiac arrest remain unclear. We aimed to describe the outcomes, identify risk factors, and develop a simple risk-scoring model for patients resuscitated from traumatic cardiac arrest. METHODS: This observational multicenter study analyzed data from the Japan Trauma Data Bank from January 1, 2019, to December 31, 2021. Patients who underwent cardiopulmonary resuscitation in the emergency department and survived to the day after hospital admission for traumatic cardiac arrest were included. Factors associated with survival to hospital discharge were determined using mixed-effects multivariable logistic regression analysis. A simple scoring model was developed to stratify the probability of survival to hospital discharge. RESULTS: In total, 452 patients from 119 hospitals (median age, 64 years; 334 [74.4%] men) were included in the analysis. Of these, 130 (28.8%) survived until discharge. Penetrating injury, signs of life upon hospital arrival, and Injury Severity Score were significantly associated with survival at hospital discharge. A scoring model that assigned 1 point each for penetrating injury and signs of life upon hospital arrival effectively stratified the probability of survival to hospital discharge, with scores of 0, 1, and 2 corresponding to survival probabilities of 12.2%, 35.2%, and 83.3%, respectively. CONCLUSION: This study described the outcomes and risk factors of patients resuscitated from traumatic cardiac arrest. Our simple scoring model effectively stratified the likelihood of survival to hospital discharge. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Transient Arginine Vasopressin Deficiency Induced by Valproic Acid Intoxication: A Case Report.

Valproic acid is commonly used for treating seizures and psychiatric disorders. Valproic acid is a common anticonvulsant drug causing overdose for suicidal purposes. The most common symptom of valproic acid poisoning is central nervous system damage. Most cases result in mild to moderate drowsiness, while in severe cases, fatal cerebral edema and coma have been reported. Other complications include respiratory depression, hepatotoxicity, thrombocytopenia, and multi-organ failure resulting in circulatory collapse. Herein, we present a case of a 42-year-old woman who ingested an overdose of 600 mg nitrazepam, 50 mg olanzapine, and 35,600 mg valproic acid. The maximum daily doses for nitrazepam, olanzapine, and valproic acid are 15, 20, and 1200 mg, respectively. This overdose led to reversible arginine vasopressin (AVP) deficiency as a rare but significant complication. The deficiency led to polyuria with dilute urine, which was effectively suppressed by AVP administration. This case highlights the potential for reversible AVP deficiency as a rare but significant complication of valproic acid overdose. Early diagnosis and appropriate management are crucial for favorable outcomes.

Incidence, risk factors, and impact of post-return of spontaneous circulation events in patients with out-of-hospital cardiac arrest: A population-based study in Tokyo, Japan.

AIM: Patients with the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) are unstable and often experience rearrest, after which ROSC may be reattained. This study investigated the incidence and risk factors of post-ROSC events (rearrest and subsequent reattainment of ROSC) and their impact on outcomes in patients with prehospital ROSC following OHCA. METHODS: Patients with OHCA and prehospital ROSC were identified from the Tokyo Fire Department database between 1 January 2018 and 31 December 2022. The factors associated with post-ROSC events and their impact on 1-month favourable neurological outcome (cerebral performance category scale: 1 or 2) were assessed using multivariable logistic regression analysis. RESULTS: Overall, 64,000 individuals experienced OHCA, and 6,190 (9.7%) had ROSC. Rearrest was confirmed in 28.4% of patients with ROSC, and was associated with age, time of emergency call, location of cardiac arrest, dispatcher instruction regarding cardiopulmonary resuscitation, first recorded cardiac rhythm, bystander cardiopulmonary resuscitation, defibrillation by a bystander, response time, and prehospital interventions. ROSC reattainment was confirmed in 34.5% of patients with rearrest and associated with the first recorded cardiac rhythm and defibrillation by a bystander. Patients without rearrests had the highest proportion of favourable neurological outcomes, followed by those with solved and unsolved rearrests (38.6% vs. 22.4% and 4.4%, P < 0.001). The difference remained significant after adjustment for confounders. CONCLUSION: This study revealed population-based incidence and risk factors of post-ROSC events. Rearrest was common, leading to unfavourable neurological outcome; however, its deleterious impact may be mitigated by successful resuscitation efforts.

The impact of injuries at the time of cardiac arrest on the prognosis of extracorporeal cardiopulmonary resuscitation (ECPR) in out-of-hospital cardiac arrest patients.

Aim: Extracorporeal cardiopulmonary resuscitation (ECPR) is an effective treatment for out-of-hospital cardiac arrest and refractory ventricular fibrillation. Despite the success of this intervention, trauma is a potential complication that may adversely impact patient outcomes. This study assessed the incidence and impact of trauma in patients who underwent ECPR. We hypothesized that all trauma incurred until the conclusion of ECPR would have a significant negative effect on survival and neurological outcomes. Methods: This retrospective observational study examined all ECPR patients admitted to a tertiary emergency medical center between January 2015 and December 2021. All patients underwent pan-scan computed tomography (CT) before admission to the intensive care unit. The head and body trauma were assessed from CT images taken after ECPR. Trauma was defined as all trauma affecting post-ECPR management. In other words, all trauma caused by collapse, trauma caused by resuscitative actions such as chest compressions, and vascular injuries associated with ECPR were included. Univariate analysis of neurological prognosis and 30-day survival due to complicated trauma was performed. Results: A total of 189 patients (mean age 55.2 ± 13.4 years; 85.2% male) were included in this study. Four patients (2.1%) had head trauma, and 31 patients (16.4%) had torso trauma. All patients with head trauma died during extracorporeal membrane oxygenation management. In patients with torso trauma, 30-day survival was not significantly different compared with that in those without trauma (31.5% vs. 41.9%, P = 0.60); good neurological outcomes were almost the same (26.0% vs. 25.8%, P = 1.00). Approximately half of the patients with torso trauma (48%) underwent transarterial embolization. Conclusion: Patients treated with ECPR can suffer a variety of traumatic injuries from the time of collapse to the establishment of ECMO. Head trauma may be lethal and warrants caution. With appropriate treatment, patients with torso trauma may have an equivalent prognosis to those without traumatic complications.

Dysbiosis of gut microbiota in patients with protein-losing enteropathy after the Fontan procedure.

BACKGROUND: There is a lack of predictive biomarkers for the onset or activity of protein-losing enteropathy (PLE), a Fontan procedure-associated complication. Here, we aimed to identify the gut microbiota composition of patients with active PLE and investigate its relationship with PLE activity. METHODS: This multicenter case-control study involved patients who developed PLE (n = 16) after the Fontan procedure and those who did not (non-PLE; n = 20). Patients with PLE who maintained a serum albumin level of ≥3 g/dL for >1 year were included in the remissive-stage-PLE group (n = 9) and those who did not maintain this level were included in the active-PLE group (n = 7). 16S rRNA gene sequencing analysis of fecal samples was performed using QIIME2 pipeline. Alpha (Shannon and Faith's phylogenetic diversity indices) and beta diversity was assessed using principal coordinate analysis based on unweighted UniFrac distances. RESULTS: Shannon and Faith's phylogenetic diversity indices were lower in the active-PLE group than in the remissive-stage- (q = 0.028 and 0.025, respectively) and non-PLE (q = 0.028 and 0.017, respectively) groups. Analysis of beta diversity revealed a difference in the microbiota composition between the active-PLE and the other two groups. Linear discriminant effect size analysis demonstrated differences in the relative abundance of Bifidobacterium and Granulicatella spp., and Ruminococcus torques between patients with active- and those with remissive-stage-PLE. CONCLUSIONS: Gut microbiota dysbiosis was observed in patients with active PLE. Changes in the bacterial composition of the gut microbiota and decreased diversity may be associated with the severity of PLE.

Peripheral VA-ECMO and pericardial drainage connected to the ECMO circuit for cardiac tamponade from blowout rupture: a case report.

BACKGROUND: Left ventricular free wall rupture, particularly the blowout type, is still one of the most lethal complications of myocardial infarction and can cause catastrophic cardiac tamponade. Extracorporeal membrane oxygenation (ECMO) is often used to treat haemodynamic instability due to cardiac tamponade. However, elevated pericardial pressure can cause collapse of the right atrium, resulting in inadequate ECMO inflow and preventing the stabilisation of the circulation. Further, it can interfere with the venous return from the superior vena cava (SVC), increasing the intracranial pressure and reducing cerebral perfusion levels. CASE PRESENTATION: A 65-year-old man was hospitalised for out-of-hospital cardiac arrest. We used ECMO for cardiopulmonary resuscitation. After the establishment of ECMO, transthoracic echocardiography and left ventriculography revealed massive pericardial effusion. The treatment was supplemented with pericardial drainage since ECMO flow was frequently hampered by suction events. However, the blowout rupture led to the requirement of constant drainage from the pericardial catheter. To tend to this leak, we connected the venous cannula of ECMO and the pericardial drainage catheter. The surgery was performed with stable circulation without suction failure of ECMO. During the course of the intensive care management, the neurological prognosis of the patient was revealed to be poor, and the patient was shifted to palliative care. Unfortunately, the patient died on day 10 of hospitalisation. CONCLUSION: We present a case wherein the combination of pericardial drainage and ECMO was used to maintain circulation in a patient with massive pericardial effusion due to cardiac rupture.

An electrocardiographic score to predict pulmonary hypertension in children with atrial septal defect.

BACKGROUND: In limited resource settings, identification of factors that predict the occurrence of pulmonary hypertension(PH) in children with atrial septal defect(ASD) is important to decide which patients should be prioritized for defect closure to prevent complication. Echocardiography and cardiac catheterization are not widely available in such settings. No scoring system has been proposed to predict PH among children with ASD. We aimed to develop a PH prediction score using electrocardiography parameters for children with ASD in Indonesia. METHODS: A cross-sectional study reviewing medical record including ECG record was conducted among all children with newly diagnosed isolated ASD admitted to Dr Sardjito Hospital in Yogyakarta, Indonesia during 2016-2018. Diagnosis of ASD and PH was confirmed through echocardiography and/or cardiac catheterization. Spiegelhalter Knill-Jones approach was used to develop PH prediction score. Accuracy of prediction score was performed using a receiver operating characteristic (ROC) curve. RESULTS: Of 144 children, 50(34.7%) had PH. Predictors of pulmonary hypertension were QRS axis ≥120°, P wave ≥ 3 mm at lead II, R without S at V1, Q wave at V1, right bundle branch block (RBBB), R wave at V1, V2 or aVR > normal limit and S wave at V6 or lead I > normal limit. ROC curve from prediction scores yielded an area under the curve (AUC) 0.908(95% CI 0.85-0.96). Using the cut-off value 3.5, this PH prediction score had sensitivity of 76%(61.8-86.9), specificity 96.8%(91.0-99.3), positive predictive value 92.7%(80.5-97.5), negative predictive value 88.4%(82.2-92.6), and positive likelihood ratio 23.8(7.7-73.3). CONCLUSIONS: A presence of PH in children with ASD can be predicted by the simple electrocardiographic score including QRS axis ≥120°, P wave ≥3 mm at lead II, R without S at V1, Q wave at V1, RBBB, R wave at V1, V2 or aVR > normal limit and S wave at V6 or lead I > normal limit. A total score ≥ 3.5 shows a moderate sensitivity and high specificity to predict PH among children with ASD.

Identifying individuals satisfying the termination of resuscitation rule but having potential to achieve favourable neurological outcome following out-of-hospital cardiac arrest.

AIM: To develop a simple scoring model that identifies individuals satisfying the termination of resuscitation (TOR) rule but having potential to achieve favourable neurological outcome following out-of-hospital cardiac arrest (OHCA). METHODS: This study analysed the All-Japan Utstein Registry from 1 January 2010 to 31 December 2019. We identified patients satisfying basic life support (BLS) and advanced life support (ALS) TOR rules and determined factors associated with favourable neurological outcome (cerebral performance category scale of 1 or 2) for each cohort using multivariable logistic regression analysis. Scoring models were derived and validated to identify patient subgroups that might benefit from continued resuscitation efforts. RESULTS: Among 1,695,005 eligible patients, 1,086,092 (64.1%) and 409,498 (24.2%) satisfied BLS and ALS TOR rules, respectively. One month post-arrest, 2038 (0.2%) and 590 (0.1%) patients in the BLS and ALS cohorts, respectively, achieved favourable neurological outcome. A scoring model derived for the BLS cohort (2 points for age <17 years or ventricular fibrillation/ventricular tachycardia rhythm; 1 point for age <80 years, pulseless electrical activity rhythm, or transport time <25 min) effectively stratified the probability of achieving 1-month favourable neurological outcome, with patients scoring <4 having a probability of <1%, whereas those scoring 4, 5, and 6 having probabilities of 1.1%, 7.1%, and 11.1%, respectively. In the ALS cohort, the probability increased with scores; however, it remained <1%. CONCLUSION: A simple scoring model comprising age, first documented cardiac rhythm, and transport time effectively stratified the likelihood of achieving favourable neurological outcome in patients satisfying the BLS TOR rule.

The edemiological state of blunt diaphragmatic injury: An analysis of a nationwide trauma registry in Japan.

BACKGROUND: Little is known about blunt traumatic diaphragmatic injury (BTDI). This study aimed to investigate the epidemiological state of BTDI, using a nationwide trauma registry in Japan. METHODS: Data of patients aged ≥18 years who experienced blunt injury between January 2004 and May 2019 were extracted from the Japan Trauma Data Bank. Demographics, cause of trauma, mechanism of injury, physiological parameters, organ injuries, and bone fractures were compared between patients with and those without BTDI. Multivariable logistic regression analysis was performed to identify factors associated with BTDI. RESULTS: A total of 305,141 patients from 244 hospitals were analyzed. The median patient age (interquartile range) was 65 (44-79) years, and 185,750 (60.9%) were men. BTDI was diagnosed in 868 patients (0.3%). The prevalence of BTDI was stable, between 0.2 and 0.6%, over the study period. Among the 868 patients with BTDI, 408 (47.0%) fatalities were recorded. Mortality rates in each year were 42.5-68.2%, with no significant trend toward an improved outcome (P = 0.925). Our multivariable logistic regression analysis found that mechanism of injury, Glasgow Coma Scale score (9-12 or 3-8) on hospital arrival, hypotension (systolic blood pressure <90 mmHg) on hospital arrival, organ injuries (lung, heart, spleen, bladder, kidney, pancreas, stomach, and liver), and bone fractures (rib, pelvis, lumbar spine, and upper extremities) were independently associated with BTDI. CONCLUSION: Using a nationwide trauma registry, this study revealed the epidemiological state of BTDI in Japan. BTDI was found to be a very rare but devastating injury, with high in-hospital mortality. Some clinical factors, such as mechanism of injury, Glasgow Coma Scale score, organ injuries, and bone fractures, were independently associated with BTDI.

Bystander cardiopulmonary resuscitation and cardiac rhythm change over time in patients with out-of-hospital cardiac arrest.

BACKGROUND: Whether and how bystander cardiopulmonary resuscitation (CPR) modifies the cardiac rhythm after out-of-hospital cardiac arrest (OHCA) over time remains unclear. We investigated the association between bystander CPR and the likelihood of ventricular fibrillation (VF) or ventricular tachycardia (VT) as the first documented cardiac rhythm. METHODS: We identified individuals with witnessed OHCA of cardiac origin from a nationwide population-based OHCA registry in Japan between 1 January 2005 and 31 December 2019. The first documented cardiac rhythm was compared between patients who received bystander CPR and those who did not, using a 1:2 propensity score-matched analysis. RESULTS: Of 309 900 patients with witnessed OHCA of cardiac origin, 71 887 (23.2%) received bystander CPR. Propensity score matching paired 71 882 patients who received bystander CPR with 143 764 who did not. The likelihood of detecting a VF/VT rhythm was significantly higher among patients who received bystander CPR than among those who did not (OR 1.66; 95% CI 1.63 to 1.69; p<0.001). Comparing the two groups at each time point, the difference in the proportions of patients with VF/VT rhythms peaked at 15-20 min but was insignificant at 30 min postcollapse (15 min after collapse; 20.9% vs 13.9%; p<0.001). The likelihood of a pulseless electrical activity rhythm was significantly lower in patients who received bystander CPR during the first 25 min postcollapse (15 min after collapse; 26.2% vs 31.5%; p<0.001). The two groups had no significant difference in the likelihood of asystole (15 min after collapse; 51.0% vs 53.3%; p=0.078). CONCLUSION: Bystander CPR was associated with a higher VF/VT likelihood and a lower likelihood of pulseless electrical activity at first documented rhythm analysis. Our results support early CPR for OHCA and highlight the need for further research to understand whether and how CPR modifies the cardiac rhythm after arrest.

Case report: High-dose epoprostenol therapy in pediatric patients with pulmonary hypertension and developmental lung disease.

Pulmonary hypertension (PH) with developmental lung disease is a life-threatening disease and accounts for 10%-12% of pediatric PH patients. Administration of specific pulmonary vasodilators to pediatric PH patients has brought about improvement of their long-term prognosis. Intravenous epoprostenol therapy is a gold standard therapy for severe idiopathic pulmonary arterial hypertension (IPAH), but there are few reports demonstrating the efficacy of epoprostenol for pediatric PH patients with developmental lung disease, especially when treating with high doses of epoprostenol. Two cases of pediatric PH patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) and congenital diaphragmatic hernia (CDH) with bronchopulmonary dysplasia (BPD), respectively, treated with epoprostenol above 100 ng/kg/min are presented. In these two cases, severe PH was improved significantly by an aggressive increase of the epoprostenol infusion rate with administration of oral pulmonary vasodilators and appropriate respiratory management, without any significant adverse effects. High-dose epoprostenol therapy may be one of the therapeutic options in pediatric PH patients with developmental lung disease.

Analysis of Coronary Arterial Aneurysm Regression in Patients With Kawasaki Disease by Aneurysm Severity: Factors Associated With Regression.

Background Coronary arterial aneurysms (CAAs) associated with Kawasaki disease (KD) significantly affect prognosis. However, the clinical course of CAAs and factors associated with CAA regression have not been well analyzed. Methods and Results The cohort of the Z-Score 2nd Project Stage study, a multicenter, retrospective, cohort study involving 44 institutions in Japan including 1006 patients with KD, was examined. CAAs were classified by the z score of their internal diameter in the acute phase: small (z<5), medium (5≤z<10), and large (z≥10). The lower limit of small CAA was based on the Japanese Ministry of Health, Labour and Welfare criteria. In the right coronary artery, the CAA regression rates 10 years after diagnosis were 95.5% for small, 83.2% for medium, and 36.3% for large. In the proximal left anterior descending artery, the regression rates 10 years after diagnosis were 95.3% for small, 80.1% for medium, and 28.8% for large. Cox regression analysis showed that diagnosis under the age of 1 year and onset of KD in 2010 to 2012 for the right coronary artery and the left anterior descending artery, and female for the right coronary artery were significantly associated with a high regression rate, whereas large CAAs for the right coronary artery and the left anterior descending artery were significantly associated with a low regression rate. Conclusions The current study, the largest Japanese study of its kind, found that small aneurysm, recent onset, and diagnosis under the age of 1 year predict regression, and that even giant aneurysms could regress. These data may contribute to long-term management of coronary aneurysms. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000010606.

Fifteen-year secular changes in the care and outcomes of patients with out-of-hospital cardiac arrest in Japan: a nationwide, population-based study.

AIMS: Countries have implemented initiatives to improve the outcomes of patients with out-of-hospital cardiac arrest (OHCA). However, secular changes in care and outcomes at the national level have not been extensively investigated. This study aimed to determine 15-year secular changes in the outcomes of such patients in Japan. METHODS AND RESULTS: Using population-based data of patients with OHCA, covering all populations in Japan (2005-19), patients for whom resuscitation was attempted were identified. The primary outcome was a favourable neurological outcome (Cerebral Performance Category 1 or 2: sufficient cerebral function for independent activities of daily life and work in a sheltered environment). Secular changes in outcomes were determined using a mixed-level multivariate logistic regression analysis. Overall, 1 764 440 patients (42.4% women; median age, 78 years) were examined. The incidence, median age, and proportion of patients who received bystander cardiopulmonary resuscitation (CPR) and dispatcher instructions for resuscitation increased significantly during the study period (P  < 0.001). A significant trend was noted toward improved outcomes over time (P for trend < 0.001); favourable neurological outcome proportions 1 month after arrest increased from 1.7-3.0% (odds ratio, 1.03 per 1-incremental year). A remarkable increase was noted in favourable neurological outcomes in younger patients and patients with initial shockable cardiac rhythm, while improvement varied among prefectures. CONCLUSION: In Japan, collaborative efforts have yielded commendable achievements in the care and outcomes of patients with OHCA over 15 years through to 2019, while the improvement depended on patient characteristics. Further initiatives are needed to improve OHCA outcomes.

Conception by assisted reproductive technology in infants with critical congenital heart disease in Japan.

RESEARCH QUESTION: What is the proportion of infants born as a result of assisted reproductive technology ART across different types of neonatal critical congenital heart disease (CCHD) in a Japanese population? DESIGN: A retrospective analysis of 418 consecutive infants with CCHD that required catheter treatment or surgery within the first 28 days of life or ductal-dependent lesions, in two paediatric centres in Japan, between January 2014 and December 2019. The proportion of ART in infants with each type of CCHD was evaluated. The proportion of ART in infants with univentricular heart defect (UVH) compared with those with biventricular heart defect (BVH) was evaluated. RESULTS: The study group included 229 boys and 189 girls, with a gestational age of 38 ± 2 weeks. Overall, 61 infants (14.6%) were conceived by fertility treatment with 46 (11.0%) conceived by ART. Univentricular heart defect and BVH were identified in 111 infants (26.6%) and 307 infants (73.4%), respectively. The proportion of infants conceived by ART was significantly higher in UVH (16.2%) than in BVH (9.1%) (OR 2.28, 95% CI 1.11 to 4.68, P = 0.025), regardless of maternal age and maternal history of miscarriage. CONCLUSIONS: The proportion of ART in infants with CCHD, especially UVH, was high. These findings could form the basis of a rationale for carrying out fetal echocardiography in fetuses conceived by ART.