Genomic analysis of bladder urothelial carcinoma with osteoclast­like giant cells: A case report.

Urothelial carcinoma of the bladder with osteoclast-like giant cells (UCOGCs) is rare among the subtypes of poorly differentiated urothelial carcinoma. Its clinical significance and optimal treatment are unknown, and few reports on genomic analysis of UCOGCs have been reported. Detailed analysis including genetic analysis for rare type variants of cancer could be a foothold for further research. The present case describes the case of a 75-year-old man who presented with a non-papillary bladder tumor 56 mm in diameter showing gross hematuria and pain on voiding. Following transurethral resection of the bladder tumor, the pathological diagnosis was invasive UCOGCs. Neoadjuvant chemotherapy and radical cystectomy were performed with the resected tumor pathologically diagnosed as invasive UCOGCs, high grade, pT3b, pN1. The present study also analyzed the genomic features using a cancer panel test. The panel test noted six gene alterations (PIK3CA p.E542K, HRAS p.G13R, ARAF copy number amplification, CDKN2A copy number loss, TP53 p.E285V, ARID1A p.S90Pfs*11) and telomerase reverse transcriptase (TERT) promoter variant. Accumulation of knowledge from molecular-based testing is anticipated to determine precise treatment for rare cancer.

Clinical and Diagnostic Utility of Genomic Profiling for Digestive Cancers: Real-World Evidence from Japan.

The usefulness of comprehensive genomic profiling (CGP) in the Japanese healthcare insurance system remains underexplored. Therefore, this large-scale study aimed to determine the usefulness of CGP in diagnosing digestive cancers. Patients with various cancer types recruited between March 2020 and October 2022 underwent the FoundationOne® CDx assay at the Keio PleSSision Group (19 hospitals in Japan). A scoring system was developed to identify potentially actionable genomic alterations of biological significance and actionable genomic alterations. The detection rates for potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to companion diagnosis (CDx), as well as the signaling pathways associated with these alterations in each digestive cancer, were analyzed. Among the 1587 patients, 547 had digestive cancer. The detection rates of potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to CDx were 99.5%, 62.5%, and 11.5%, respectively. APC, KRAS, and CDKN2A alterations were frequently observed in colorectal, pancreatic, and biliary cancers, respectively. Most digestive cancers, except esophageal cancer, were adenocarcinomas. Thus, the classification flowchart for digestive adenocarcinomas proposed in this study may facilitate precise diagnosis. CGP has clinical and diagnostic utility in digestive cancers.

Fluid balance during acute phase extracorporeal cardiopulmonary resuscitation and outcomes in OHCA patients: a retrospective multicenter cohort study.

OBJECTIVE: The association between fluid balance and outcomes in patients who underwent out-of-hospital cardiac arrest (OHCA) and received extracorporeal cardiopulmonary resuscitation (ECPR) remains unknown. We aimed to examine the above relationship during the first 24 h following intensive care unit (ICU) admission. METHODS: We performed a secondary analysis of the SAVE-J II study, a retrospective multicenter study involving OHCA patients aged ≥ 18 years treated with ECPR between 2013 and 2018 and who received fluid therapy following ICU admission. Fluid balance was calculated based on intravenous fluid administration, blood transfusion, and urine output. The primary outcome was in-hospital mortality. The secondary outcomes included unfavorable outcome (cerebral performance category scores of 3-5 at discharge), acute kidney injury (AKI), and need for renal replacement therapy (RRT). RESULTS: Overall, 959 patients met our inclusion criteria. In-hospital mortality was 63.6%, and the proportion of unfavorable outcome at discharge was 82.0%. The median fluid balance in the first 24 h following ICU admission was 3673 mL. Multivariable analysis revealed that fluid balance was significantly associated with in-hospital mortality (odds ratio (OR), 1.04; 95% confidence interval (CI), 1.02-1.06; p < 0.001), unfavorable outcome (OR, 1.03; 95% CI, 1.01-1.06; p = 0.005), AKI (OR, 1.04; 95% CI, 1.02-1.05; p < 0.001), and RRT (OR, 1.05; 95% CI, 1.03-1.07; p < 0.001). CONCLUSIONS: Excessive positive fluid balance in the first day following ICU admission was associated with in-hospital mortality, unfavorable outcome, AKI, and RRT in ECPR patients. Further investigation is warranted.

A case of fatal fulminant fat embolism syndrome saved by VA-ECMO in the acute phase of multiple trauma.

Fat embolism syndrome (FES) is a rare complication of long bone fractures, with fulminant FES developing within 12 h of injury and often proving fatal (Shaikh, 2009 [1]). Here, we present a case of fulminant FES in a patient who developed sudden right heart failure after undergoing external fixation of a lower leg fracture and required veno-arterial extracorporeal membrane oxygenation (VA-ECMO). A 79-year-old woman injured in a traffic accident was transferred to our emergency department. Upon arrival, her level of consciousness deteriorated, and she developed circulatory failure. We promptly performed transcatheter arterial embolization for the pelvic fracture and external fixation of the tibiofibular fracture. Within four hours of the injury, she was admitted to our intensive care unit (ICU). Two hours after ICU admission, her hemodynamic status worsened, necessitating the administration of maximum catecholamine dose. Echocardiography revealed petechial hemorrhage of the palpebral conjunctiva and enlargement of the right ventricle. Despite maximal supportive care, the patient remained cardiovascularly unstable. Therefore, VA-ECMO was initiated to stabilize her hemodynamic status. Thereafter, her hemodynamics stabilized, and ECMO support was weaned off and removed on day 3. Subsequent magnetic resonance imaging revealed evidence of cerebral fat embolism. On day 9, she underwent open reduction of the left lower leg with internal fixation and was transferred to another hospital on day 29. This report documents the successful management of fulminant FES during the acute phase of multiple traumas. Clinicians should consider VA-ECMO when suspecting uncontrolled circulatory failure due to fulminant FES, even in the acute phase of multiple trauma.

Acute Mesenteric Ischemia Secondary to Candida Endocarditis: A Case Report.

A 36-year-old man presented with abdominal pain, vomiting, and diarrhea. On arrival, his vital signs were remarkable for fever (39.3 °C) and tachycardia (127 beats/min, regular). His abdomen was distended, and a blood test showed elevations of inflammatory markers. Contrast-enhanced computed tomography revealed a superior mesenteric artery thrombus, ischemic colitis, ascites, and infarctions in the spleen and right kidney. He was diagnosed with bowel necrosis due to acute mesenteric ischemia (AMI). An emergent laparotomy was performed. The following day, Candida tropicalis was identified in the blood culture. In addition, transthoracic echocardiography revealed vegetation on the mitral valve leaflet. These findings were suggestive of infective endocarditis (IE) caused by C. tropicalis (Candida endocarditis); thus, the patient underwent surgical mitral valve replacement with the administration of antifungal therapy. Following postoperative intensive care and a prolonged course of antifungal treatment, he achieved a full recovery. AMI is only rarely caused by IE, and this case is the first reported instance of AMI secondary to Candida endocarditis. When encountering patients with AMI without any risk factors for thromboembolism, clinicians should be aware that IE may cause AMI.

Multicenter, randomized, double-blind, placebo-controlled phase 3 study of mogamulizumab with open-label extension study in a minimum number of patients with human T-cell leukemia virus type-1-associated myelopathy.

Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. This multicenter, randomized phase 3 study evaluated the efficacy and safety of 0.3 mg/kg intravenous mogamulizumab, a monoclonal antibody targeting-CC chemokine receptor 4, every 12 weeks in HAM/TSP patients. This study comprised a 24-week double-blind, placebo-controlled period, 24-week open-label period, and extension treatment period. The primary endpoint was the proportion of patients with a ≥ 1-grade improvement in the Osame motor disability score (OMDS). Secondary endpoints were changes in HTLV-1 proviral load, 10-m timed walk, cerebrospinal fluid (CSF) neopterin levels, and safety. The exploratory endpoint was CSF chemokine C-X-C motif ligand 10 (CXCL10) levels. Thirty-four and 33 patients were randomized to mogamulizumab and placebo arms, respectively. At the end of the double-blind period, no significant difference was found in the OMDS improvement rate or other secondary efficacy endpoints assessing motor activities. However, the mogamulizumab arm showed a significant decrease in HTLV-1 proviral load (- 59.39 ± 29.91% vs. placebo 2.32 ± 36.31%) and CSF neopterin (p < 0.001)/CXCL10 levels (p = 0.004). The baseline OMDS pattern and the 60-80% HTLV-1 proviral load reduction were sustained through the open-label and extension treatment periods. Although a higher incidence of rash (69.2%) was reported, the safety profile was similar compared with a previous phase 1/2a study. We found no significant difference in clinical benefit; however, mogamulizumab may provide long-term clinical benefit by preventing disease progression, as CSF neopterin/CXCL10 levels are associated with long-term prognosis in HAM/TSP.Clinical Trial Registration Number: NCT03191526 (registered date: 6-June-2017).

Impact of Tumor Grade Distribution on Genetic Alterations in Clear Cell Renal Cell Carcinoma and Prostate Cancer.

BACKGROUND/AIM: A genomic analysis based on next-generation sequencing is important for deciding cancer treatment strategies. Cancer tissue sometimes displays intratumor heterogeneity and a pathologic specimen may contain more than two tumor grades. Although tumor grades are very important for the cancer prognosis, the impact of higher tumor grade distribution in a specimen used for a genomic analysis is unknown. PATIENTS AND METHODS: We retrospectively analyzed the data of 61 clear cell carcinoma and 46 prostate cancer patients that were diagnosed between December 2018 and August 2022 using the GeneRead Human Comprehensive Cancer Panel or SureSelect PrePool custom Tier2. Genome annotation and curation were performed using the GenomeJack software. RESULTS: Tumor mutation burden (TMB) was increased in proportion to the higher tumor grade distribution in grade 2 clear cell renal cell carcinoma (ccRCC). In PC, Grade Group 3/4 specimens that included an increased distribution of Gleason pattern 4 had more frequent gene mutations. CONCLUSION: Our results suggest the importance of selecting the maximum distribution of higher tumor grade areas to obtain results on the precise gene alterations for genomics-focused treatments.

Early prediction for massive fresh frozen plasma transfusion based on fibrinogen/fibrin degradation products and D-dimer in patients with blunt trauma: a single-center, retrospective cohort study.

PURPOSE: This study aimed to examine the association of fibrinogen/fibrin degradation product (FDP) values in comparison with D-dimer and fibrinogen (Fib) values and the need for massive fresh frozen plasma (FFP) transfusion in patients with blunt trauma. METHODS: This retrospective study included patients with blunt trauma aged ≥ 18 years who were transported directly to the tertiary care hospital between April, 2012, and March, 2021. Massive FFP transfusion was defined as a composite outcome of at least 10 units of FFP or death for any cause except for cerebral herniation, within 24 h after hospital arrival. We evaluated the diagnostic accuracy of predicting the need for massive FFP transfusions using FDP, D-dimer, and Fib levels at the time of hospital arrival. RESULTS: A total of 2160 patients were eligible for the analysis, of which 167 fulfilled the criteria for the composite outcome. The area under the curve and 95% confidence interval for FDP, D-dimer, and Fib levels were 0.886 (0.865-0.906), 0.885 (0.865-0.906), and 0.771 (0.731-0.810), respectively. When the cutoff values of FDP and D-dimer were set at 90 µg/mL and 45 µg/mL, the sensitivity values were 77% and 78%, the positive predictive values were 28% and 27%, and the negative predictive values were both 98%, respectively. In contrast, the sensitivity of Fib was low regardless of the cutoff value. CONCLUSION: FDP and D-dimer levels at the time of hospital arrival showed a higher predictive accuracy for the need for massive FFP transfusion than Fib.

The association between blood glucose levels on arrival at the hospital and patient outcomes after out-of-hospital cardiac arrest: A multicenter cohort study.

BACKGROUND: This study aimed to investigate the association between blood glucose levels on arrival at the hospital and 1-month survival and favorable neurological outcomes in patients with OHCA using a large Japanese dataset. METHODS: This study was a secondary analysis of data from the JAAM-OHCA Registry. Adult (≥18 years) patients with witnessed OHCA transported to emergency departments and registered in the database from June 2014 to December 2019 were included in the study. The primary and secondary endpoints were 1-month survival and 1-month favorable neurological outcomes (Glasgow-Pittsburgh Cerebral Performance Category score 1 or 2), respectively. Patients were categorized into the following four groups based on blood glucose levels on arrival at the hospital: <80 mg/dL, 80-179 mg/dL, 180-299 mg/dL, and ≥300 mg/dL. RESULTS: This study included 11,387 patients. Survival rates were 1.3%, 3.1%, 7.0%, and 5.7% in the <80 mg/dL, 80-179 mg/dL, 180-299 mg/dL, and ≥ 300 mg/dL blood glucose groups, respectively. The rates of favorable neurological outcomes in each group were 0.4%, 1.5%, 3.3%, and 2.5%, respectively. Multivariable analysis showed that 180-299 mg/dL glucose was significantly associated with 1-month survival and favorable neurological outcomes compared with 80-179 mg/dL glucose (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.34-2.31; p < 0.001 and OR, 1.52; 95 % Cl, 1.02-2.25; p = 0.035, respectively). In this study, blood glucose levels with the best outcomes likely ranged from 200 to 250 mg/dL based on the cubic spline regression model. CONCLUSIONS: Blood glucose level of 180-299 mg/dL on arrival at the hospital was significantly associated with 1-month survival and favorable neurological outcomes compared to blood glucose level of 80-179 mg/dL in patients with OHCA.

Intra-aortic balloon pump in patients with extracorporeal cardiopulmonary resuscitation after cardiac arrest caused by acute coronary syndrome.

BACKGROUND: This study evaluated the association between intra-aortic balloon pump (IABP) use in patients with out-of-hospital cardiac arrest (OHCA) caused by acute coronary syndrome (ACS) who received extracorporeal cardiopulmonary resuscitation (ECPR) and 30-day outcomes. METHODS: This study was a secondary analysis of data from the SAVE-J II study, a retrospective, multicenter registry study involving 36 participating institutions in Japan. Patients with cardiac arrest caused by ACS who received ECPR were divided into two groups depending on whether or not they received IABP. The primary outcome was 30-day survival. Subgroup analysis was performed to detect what type of patients were mostly associated with improved outcomes. RESULTS: Of 2,157 patients registered in the SAVE-J II study, 877 patients were enrolled in this study, 702 patients in the IABP group and 175 patients in the non-IABP group. Multivariable logistic regression analysis did not reveal a significant difference in 30-day survival (OR 1.37, 95% CI 0.91-2.07, p = 0.13). In the subgroup analysis, 30-day survival among patients without percutaneous coronary intervention (PCI) and stenosis of multiple coronary vessels were associated with IABP use. CONCLUSIONS: IABP use in patients with OHCA with ACS who received ECPR is not associated with 30-day survival. The use of IABP in patients who did not have PCI and have multiple coronary vessel stenoses warrants further study.

Cardiac arrest with retropharyngeal hematoma caused by minor facial injuries from a ground level fall.

Background: Traumatic retropharyngeal hematoma followed by airway obstruction is extremely rare. In this report, we show unique images from two cases of out-of-hospital cardiac arrest due to airway obstruction caused by massive retropharyngeal hematoma after a minor facial injury. Case presentation: Case 1: A 78-year-old man was transferred to our emergency department due to cardiac arrest. He presented with respiratory insufficiency after a ground level fall. His neck was swollen, and the attending physician performed an emergent cricothyroidotomy to secure his airway and administered intravenous adrenaline. Computed tomography revealed a massive retropharyngeal hematoma and severe hypoxic encephalopathy. Despite a temporary return of spontaneous circulation (ROSC), the patient died on the admission day.Case 2: A 68-year-old woman presented with dyspnea, prompting her family to call an ambulance. On the way to the hospital, the ambulance crew determined the patient was in cardiac arrest. The patient's history revealed a ground level fall in which she hit her face. Computed tomography revealed a massive retropharyngeal hematoma compressing her upper airway. Although ROSC was obtained, the patient died on the 12th day of hospitalization due to hypoxic encephalopathy.Extension views of cervical spine images identified angular instability without cervical bone fracture in both cases, suggesting that possible injuries of the anterior longitudinal ligament contributed to the retropharyngeal hematoma. Conclusions: Patients presenting with asphyxia after a simple ground level fall accompanied by minor facial injuries should be assessed by emergency physicians for the possibility of a retropharyngeal hematoma. In both cases presented here, unique images indicate possible injuries of the anterior longitudinal ligament.

Singleton pregnancy using in vitro fertilization or intracytoplasmic sperm injection does not increase risk of bleeding in cesarean delivery: a retrospective cohort study.

PURPOSE: Several studies indicate that assisted reproductive technology (ART) including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies carries increased risk of complications including postpartum hemorrhage (PPH). However, the association between IVF/ICSI and the bleeding risk particularly in cesarean delivery has not been systematically assessed. The aim of this study was to evaluate bleeding risk during and after cesarean delivery in parturients who conceived using IVF or ICSI. METHODS: This is a retrospective observational study analyzing data from 310 parturients who underwent cesarean delivery: 155 who had conceived using IVF or ICSI (IVF/ICSI group) and 155 age and year of delivery matched controls who had conceived spontaneously (control group). The primary outcome measure was the amount of blood lost during and within 24 h after cesarean delivery. Secondary outcome measure was the incidence of severe PPH. With 132 parturients in each group, we had 90% power to detect a 200 mL difference in the bleeding amount, at a 0.05 two-sided significance level. RESULTS: The amount of bleeding in the IVF/ICSI group was 1234 ± 669 mL, which was 124 mL (11.2%) greater than that in the control group (95% CI - 34 to 282; p = 0.12). The incidence of severe PPH in the IVF/ICSI group and in the control group was 23.9% and 16.8%, respectively (p = 0.16), and the unadjusted odds ratio was 1.6 (95% CI, 0.9-2.7; p = 0.12). No significant independent effect of IVF/ICSI on the bleeding amount and the incidence of severe PPH was observed in multivariable regression analyses (p = 0.22, p = 0.16). CONCLUSION: In this study, IVF and ICSI were not associated with increasing risk of bleeding in cesarean delivery.

Comparison of outcomes of out-of-hospital cardiac arrest patients: Emergency calls placed from mobile phones vs. landline phones.

Background: Until recently, calls to the emergency medical service (EMS) from landline phones, which display the caller's exact location at the dispatch center, had been common. Since the use of mobile phones has become widespread, many emergency calls are now made from mobile phones. Differences in outcomes of out-of-hospital cardiac arrest (OHCA) patients for whom EMS was called from mobile versus landline phones has not yet been fully elucidated. Methods: We performed a retrospective, population-based analysis in Kobe, Japan to examine whether EMS calls from mobiles improved the prognosis of OHCA patients over EMS calls placed from landlines. The primary outcome was favorable neurological outcome, defined as Cerebral Performance Category (CPC) scores of 1 or 2 at discharge. Secondary outcomes were survival at one-month, survival at discharge, and time durations between call and EMS activities. Results: Of 4,231 OHCA cases, 2,194 cases (706 landline cases vs. 1,488 mobile cases) were included in this study. The percentages of favorable neurological outcomes were 0.7% (5/706) in the landline group and 3.8% (56/1,488) in the mobile group. Adjusted multivariable logistic regression revealed that favorable neurological outcomes (odds ratio [OR] 3.03, 95% confidence interval [CI] 1.12-8.17, p = 0.03) were better in the mobile group, while one-month survival (OR 1.30, 95% CI 0.80-2.14, p = 0.29) was not significantly different. Bystander CPR was more frequently administered in the mobile group (landlines 61.3% vs. mobiles 68.4%, p < 0.01). Time durations between call to EMS dispatch (184.5 [IQR 157-220 s] vs. 205 [IQR 174-248 s], p < 0.01) and EMS arrival (476.5 [IQR 377-599 s] vs. 491 [IQR 407.5-611.5 s], p < 0.01) were shorter in the landline group. Conclusions: Although the landline caller location display system seems effective for shorter times between EMS call and EMS arrival, mobile phone use was associated with better neurological outcomes.

Current animal models of extracorporeal cardiopulmonary resuscitation: A scoping review.

Aim: Animal models of Extracorporeal Cardiopulmonary Resuscitation (ECPR) focusing on neurological outcomes are required to further the development of this potentially life-saving technology. The aim of this review is to summarize current animal models of ECPR. Methods: A comprehensive database search of PubMed, EMBASE, and Web of Science was undertaken. Full-text publications describing animal models of ECPR between January 1, 2000, and June 30, 2022, were identified and included in the review. Data describing the conduct of the animal models of ECPR, measured variables, and outcomes were extracted according to pre-defined definitions. Results: The search strategy yielded 805 unique reports of which 37 studies were included in the final analysis. Most studies (95%) described using a pig model of ECPR with the remainder (5%) describing a rat model. The most common method for induction of cardiac arrest was a fatal ventricular arrhythmia through electrical stimulation (70%). 10 studies reported neurological assessment of animals using physical examination, serum biomarkers, or electrophysiological findings, however, only two studies described a multimodal assessment. No studies reported the use of brain imaging as part of the neurological assessment. Return of spontaneous circulation was the most reported primary outcome, and no studies described the neurological status of the animal as the primary outcome. Conclusion: Current animal models of ECPR do not describe clinically relevant neurological outcomes after cardiac arrest. Further work is needed to develop models that more accurately mimic clinical scenarios and can test innovations that can be translated to the application of ECPR in clinical medicine.

Bilateral video-assisted thoracic surgery for esophageal cancer with left inferior pulmonary vein invasion following chemoradiation therapy.

BACKGROUND: The surgical strategy for thoracic esophageal cancer that invades the lungs is controversial. In particular, invasion of the pulmonary vein is often regarded unresectable. We successfully applied bilateral video-assisted thoracic surgery (VATS) in esophagectomy for esophageal cancer with left inferior pulmonary vein invasion following induction chemoradiotherapy (CRT), with a favorable response. CASE PRESENTATION: A 64-year-old woman was diagnosed with squamous cell carcinoma of the lower third of the esophagus. Computed tomography (CT) revealed that the tumor was suspected to be invading the main trunk of the left lower pulmonary vein and left lower lung. We initiated induction CRT comprising 5-fluorouracil, cisplatin, and concurrent radiotherapy at 50.4 Gy/28Fr. CT revealed shrinkage of the tumor, and the main trunk of the left inferior pulmonary vein was released from the tumor invasion. We considered the tumor to be completely resectable. VATS esophagectomy is usually performed using a right-sided approach. However, the right-sided approach is inappropriate for evaluating tumors around the left inferior pulmonary vein. We started with left-sided VATS to determine tumor resectability and dissected between the esophagus and the main trunk of the left inferior pulmonary vein. We only needed to perform partial resection of the left lower lobe. We then performed a right-sided VATS esophagectomy and lymphadenectomy with partial en bloc resection of the left lower lobe. Following this, we performed hand-assisted laparoscopic proximal gastrectomy and reconstruction using the gastric remnant. The postoperative course was uneventful. The patient was discharged on postoperative day 14. Histopathological examination of the surgical specimen revealed a complete pathological response without any remnant tumor or lymph node metastasis. There were no signs of recurrence or metastasis at the 1-year follow-up. CONCLUSIONS: Curative resection for thoracic esophageal cancer that invades the pulmonary vein could be possible via the bilateral VATS approach following induction CRT with a favorable response.

Delayed Tension Hemothorax With Nondisplaced Rib Fractures After Blunt Thoracic Trauma.

Blunt thoracic trauma often causes rib fractures, hemothorax, and pneumothorax. Although there is no established definition regarding the duration and management of delayed hemothorax, it commonly occurs in a few days and exhibits at least one displaced rib fracture. Moreover, delayed hemothorax rarely develops tension hemothorax. A 58-year-old male who had a motorcycle accident received conservative treatment from his orthopedic doctor. He felt a sudden severe chest pain 19 days after the accident. Contrast-enhanced computed tomography (CT) of the chest revealed multiple left-sided rib fractures without displacement, left pleural effusion, and extravasation near the intercostal space of the seventh rib fracture. After transfer to our hospital and a plain CT scan, which showed a more mediastinal shift toward the right, his condition deteriorated with cardiorespiratory embarrassment, such as restlessness, hypotension, and neck vein distention. We diagnosed him with obstructive shock due to tension hemothorax. Immediate chest drainage ameliorated restlessness and elevated blood pressure. Here, we report an extremely rare and atypical case of delayed tension hemothorax after blunt thoracic trauma without displaced rib fractures.

Machine Learning to Predict Three Types of Outcomes After Traumatic Brain Injury Using Data at Admission: A Multi-Center Study for Development and Validation.

The difficulty of accurately identifying patients who would benefit from promising treatments makes it challenging to prove the efficacy of novel treatments for traumatic brain injury (TBI). Although machine learning is being increasingly applied to this task, existing binary outcome prediction models are insufficient for the effective stratification of TBI patients. The aim of this study was to develop an accurate 3-class outcome prediction model to enable appropriate patient stratification. To this end, retrospective balanced data of 1200 blunt TBI patients admitted to six Japanese hospitals from January 2018 onwards (200 consecutive cases at each institution) were used for model training and validation. We incorporated 21 predictors obtained in the emergency department, including age, sex, six clinical findings, four laboratory parameters, eight computed tomography findings, and an emergency craniotomy. We developed two machine learning models (XGBoost and dense neural network) and logistic regression models to predict 3-class outcomes based on the Glasgow Outcome Scale-Extended (GOSE) at discharge. The prediction models were developed using a training dataset with n = 1000, and their prediction performances were evaluated over two validation rounds on a validation dataset (n = 80) and a test dataset (n = 120) using the bootstrap method. Of the 1200 patients in aggregate, the median patient age was 71 years, 199 (16.7%) exhibited severe TBI, and emergency craniotomy was performed on 104 patients (8.7%). The median length of stay was 13.0 days. The 3-class outcomes were good recovery/moderate disability for 709 patients (59.1%), severe disability/vegetative state in 416 patients (34.7%), and death in 75 patients (6.2%). XGBoost model performed well with 69.5% sensitivity, 82.5% accuracy, and an area under the receiver operating characteristic curve of 0.901 in the final validation. In terms of the receiver operating characteristic curve analysis, the XGBoost outperformed the neural network-based and logistic regression models slightly. In particular, XGBoost outperformed the logistic regression model significantly in predicting severe disability/vegetative state. Although each model predicted favorable outcomes accurately, they tended to miss the mortality prediction. The proposed machine learning model was demonstrated to be capable of accurate prediction of in-hospital outcomes following TBI, even with the three GOSE-based categories. As a result, it is expected to be more impactful in the development of appropriate patient stratification methods in future TBI studies than conventional binary prognostic models. Further, outcomes were predicted based on only clinical data obtained from the emergency department. However, developing a robust model with consistent performance in diverse scenarios remains challenging, and further efforts are needed to improve generalization performance.