Relationship between extravascular leakage and clinical outcome on computed tomography of isolated traumatic brain injury.

Aim: This study investigated whether contrast extravasation on computed tomography (CT) angiography in patients with traumatic brain injury (TBI) is associated with death or surgical procedures. Methods: Patients over 18 years old, directly brought in by ambulance with an isolated head injury and confirmed to have acute intracranial hemorrhage on a CT scan upon admission between 2010 and 2020, were included. The primary outcome was mortality, and the secondary outcome was neurosurgical procedures performed from admission to discharge from the intensive care unit. Multivariable logistic regression analyses were performed to evaluate the association between these outcomes and contrast extravasation. Results: The analysis included 188 patients with a median age of 65 years, 123 men (65.4%), 34 deaths (18.1%), and 91 surgeries (48.4%). Among the 66 patients with contrast extravasation, 22 (33.3%) died and 47 (71.2%) required surgery. Among the 122 patients with no contrast extravasation, 12 (9.8%) died, and 44 (36.1%) required surgery. The presence or absence of extravascular leakage was associated with death (odds ratio, 3.6 [95% CI: 1.2-12.2]) and surgery (odds ratio, 7.6 [95% CI: 2.5-22.7]). Conclusion: Contrast extravasation was associated with mortality and performance of surgery in patients with an isolated head injury.

Long-Term Outcomes Over 20 Years in Persons With Persistent Disorders of Consciousness After Traumatic Brain Injury.

The long-term outcomes of patients with disorders of consciousness after traumatic brain injury (TBI) is unclear. We investigated the long-term outcomes over 20 years in patients who were in a persistent vegetative state (VS). We conducted a retrospective cohort study using a review of medical records and collected data by telephone and written interviews with patients and their families. We included patients who were treated for TBI at our hospital, between October 1996 and January 2003 and who were in a persistent VS, defined as a Disability Rating Scale (DRS) score of ≥22 at 1 month after TBI. The DRS was administered at 1 month, 6 months, 1 year, and then annually out to 20 years. We evaluated their clinical course until July 2021 with the DRS. We analyzed 35 patients in a persistent VS attributable to TBI. We were able to confirm the 20-year outcomes for 26 of the 35 patients (74%); at 20 years post-TBI, 19 (54%) patients were found to be deceased and 7 (20%) were alive. Over the 20-year study period, 23 of the 35 patients (65.7%) emerged from a persistent VS. Among the 35 patients in a persistent VS at 1 month post-TBI, 20 (57%) emerged from a persistent VS within 1 year, and 3 patients (8.6%) emerged from a persistent VS after more than a year after injury. DRS scores improved up to 9 years post-injury, whereas the change in DRS scores from 10 to 20 years post-injury was within ±1 point in all patients. We found that patients with persistent VS attributable to TBI may show improvement in functional disability up to 10 years post-injury. On the other hand, no substantial improvement in functional disability was observed after the 10th year.

Association of Extravascular Leakage on Computed Tomography Angiography with Fibrinogen Levels at Admission in Patients with Traumatic Brain Injury.

Extravascular leakage on computed tomography (CT) angiography in patients with traumatic brain injury (TBI) is associated with hematoma expansion, functional prognosis, subsequent surgery, and death. Fresh frozen plasma (FFP) administration is often necessary to treat coagulation disorders associated with TBI. This study aimed to determine the relationship between the presence of extravascular leakage on contrast-enhanced head CT, fibrinogen level at admission, and FFP administration in patients with TBI. The medical records of patients with TBI ≥18 years of age referred to our hospital between January 2010 and December 2020 were examined retrospectively. Patients who underwent contrast-enhanced CT immediately after admission were selected, and the presence or absence of extravascular leakage, fibrinogen level at admission, and percentage of patients who required FFP administration within 24 h of admission were examined; 172 patients were included. Multi-variable linear regression analysis was performed to determine the effects of contrast extravasation on fibrinogen levels at admission and was adjusted for age, sex, systolic blood pressure, time from injury to admission, Marshall CT score, Glasgow Coma Scale score at admission, Injury Severity Score, and need for emergency surgery; the regression coefficient was -19.8. The effect of extravasation on FFP administration within 24 h of admission was analyzed using logistic regression while adjusting for age, systolic blood pressure, Marshall CT score, need for emergency surgery, and fibrinogen level at admission. The odds ratio of contrast extravasation was 7.08 after adjustment. Extravascular leakage is associated with fibrinogen levels at admission and FFP administration within 24 h of admission.

Vertebral artery occlusion associated with blunt traumatic cervical spine injury.

AIM: Vertebral artery injury associated with blunt traumatic cervical spine injury sometimes causes severe cerebellar and brain stem infarction. No treatment guidelines for vertebral artery injury aimed at preventing stroke have been decided. We have conducted endovascular embolization in patients with up to Denver grade IV cerebrovascular injury complicated by unstable cervical spine injury before open reduction and fixation surgery. The purpose of this study was to validate the clinical course of vertebral artery injury and especially endovascular treatment for grade IV patients in our hospital. METHODS: Participants comprised of patients diagnosed as having traumatic cervical spine injury in our hospital between January 2015 and April 2018. Among these patients, we selected those with vertebral artery injury and retrospectively examined the background characteristics of the patients, details of treatment, and complications with or without stroke. RESULTS: Traumatic cervical spine injury was diagnosed in 89 patients. Among these patients, 15 (16.7%) showed a complicating vertebral artery injury. Mean age was 62.6 years, and almost 50% of the patients were injured in falls. Three types of cervical spine injury caused vertebral artery injury: subluxation, Jefferson fracture, and fracture involving the foramen transversarium. Vertebral artery injury was classified as grade IV in 12 patients, of whom nine required spinal surgery. All patients who needed spinal surgery underwent endovascular therapy before surgery, and none experienced a stroke. CONCLUSION: Endovascular embolization of the vertebral artery occlusion in patients with unstable cervical spine injury before open reduction and fixation surgery can be a treatment option to prevent stroke.

Serial change of C1 inhibitor in patients with sepsis: a prospective observational study.

BACKGROUND: C1 inhibitor (C1-INH), which belongs to the superfamily of serine protease inhibitors, regulates the complement system and also the plasma kallikrein-kinin, fibrinolytic, and coagulation systems. The biologic activities of C1-INH can be divided into the regulation of vascular permeability and anti-inflammatory functions. The objective of this study was to clarify the serial change of C1-INH in patients with sepsis and evaluate the relationship with the shock severity. METHODS: This was a single-center, prospective, observational study. We serially examined C1-INH activity values (normal range 70-130%) in patients with sepsis admitted into the intensive care unit of the Trauma and Acute Critical Care Center at Osaka University Hospital (Osaka, Japan) during the period between January 2014 and August 2015. We defined "refractory shock" as septic shock unresponsive to conventional therapy such as adequate fluid resuscitation and vasopressor therapy to maintain hemodynamics. RESULTS: Serial changes of C1-INH were evaluated in 40 patients with sepsis (30 men, 10 women; 30 survivors, 10 non-survivors; mean age, 70 ± 13.5 years). We divided the patients into three groups: non-shock group (n = 14), non-refractory shock group (n = 13), and refractory shock group (n = 13: 3 survivors, 10 non-survivors). In the non-shock group, C1-INH was 107.3 ± 26.5% on admission and 104.2 ± 22.3% on day 1, and it increased thereafter to 128.1 ± 26.4% on day 3, 138.3 ± 21.2% on day 7, and 140.3 ± 12.5% on day 14 (p < 0.0001). In the non-refractory shock group, C1-INH was 113.9 ± 19.2% on admission, 120.2 ± 23.0% on day 1, 135.7 ± 19.9% on day 3, 138.8 ± 17.2% on day 7, and 137.7 ± 10.7% on day 14 (p < 0.0001). In the refractory shock group, C1-INH was 96.7 ± 15.9% on admission, 88.9 ± 22.3% on day 1, 119.8 ± 39.6% on day 3, 144.4 ± 21.1% on day 7, and 140.5 ± 24.5% on day 14 (p < 0.0001). The difference between these three groups was statistically significant (p < 0.0001). C1-INH in non-survivors did not increase significantly during their clinical course (p = 0.0690). CONCLUSIONS: In refractory shock patients with sepsis, the values of C1-INH activity were lower (especially in non-survivors) on admission and day 1 as compared with non-shock and non-refractory shock patients.

Serial change of C1 inhibitor in patients with sepsis--a preliminary report.

OBJECTIVE: C1 inhibitor (C1INH) regulates not only the complement system but also the plasma kallikrein-kinin, fibrinolytic, and coagulation systems. The biologic activities of C1INH can be divided into the regulation of vascular permeability and anti-inflammatory functions. The objective was to clarify the serial change of C1INH in patients with sepsis. METHODS: We serially examined C1INH activity values (reference range, 70%-130%) and quantitative values (reference range, 160-330 µg/mL) in patients with sepsis admitted into the intensive care unit of the Trauma and Acute Critical Care Center at Osaka University Hospital (Osaka, Japan) during the period between December 2012 and February 2013. We also analyzed their clinical course. We defined "refractory shock" as septic shock requiring steroid administration to maintain hemodynamics. RESULTS: The serial change of C1INH was evaluated in 5 patients (4 survivors and 1 nonsurvivor). Two patients were diagnosed as having refractory shock. In the nonsurvivor after refractory shock, C1INH activity on admission was 97.2%, and the quantitative value was 133.1 µg/mL. In the other patient with refractory shock, C1INH activity on admission was 94.4%, and the quantitative value was 126.7 µg/mL. This patient's general condition had improved by day 6, with increases in C1INH activity (139.9%) and quantitative value (250.1 µg/mL). In the 3 nonrefractory shock patients, C1INH activity on admission was 130.6%±8.7%, and the quantitative value was 215±26.5 µg/mL. CONCLUSIONS: Enhancement of C1INH activity was not observed in the refractory shock patients, and the C1INH quantitative values were low. Further evaluation of the serial change of C1INH and the validity of C1INH replacement therapy in patients with septic shock may lead to a new strategy for sepsis management.

The clinical meaning of mucin phenotype and Epstein-Barr virus infection in gastric cancer.

BACKGROUND/AIMS: Differentiated type adenocarcinomas producing gastric type mucin are receiving much attention because of their degree of clinical malignancy. Most Epstein-Barr virus (EBV)-associated gastric cancers are undifferentiated type, and correlate with gastric type mucin. We analyzed the clinical meaning of mucin phenotypes and the detection of EBV in gastric cancers. METHODOLOGY: The objects of study were 120 consecutive gastric cancer lesions, resected endoscopically (EMR group, n=54) or surgically (surgery group, n=66). The mucin phenotypes were determined using immunostaining for human gastric mucin (HGM), MUC2, and CD10. Changes in histological type within the lesions were examined. The presence of EBV was determined using in situ hybridization for EBV-encoded small RNA 1 (EBER-1). RESULTS: The incomplete intestinal phenotype accounted for 83% of the EMR group, and the gastric phenotype for only 13%. None of the EMR group lesions had changes in the degree of differentiation, and there was no EBER-1-positive lesion. In the surgery group, the gastric phenotype accounted for 29%, significantly more than in the EMR group (p=0.0363). The incomplete intestinal phenotype accounted for 64% of surgically resected lesions. Changes in the degree of differentiation were significantly more common in the surgery group (16/66) than in the EMR group (0/54) (p=0.0001), tending to be more common in the gastric phenotype lesions. There were 3 EBER-1-positive lesions in the surgery group, accounting for 5%, and all were HGM positive. CONCLUSIONS: There appears to be little need to determine the mucin phenotype or EBV status of endoscopically resected lesions. In cases of gastric cancer where surgical resection is indicated, however, where the preoperative findings indicate a depth of invasion to SM or greater, and/or an undifferentiated lesion, then mucin phenotyping of biopsy specimens may be useful in predicting the predominant histological type of the tumor.

Mucin and differentiation in Epstein-Barr virus-associated gastric carcinoma.

BACKGROUND/AIMS: Epstein-Barr virus (EBV) is present in roughly 1 in 10 cases of gastric carcinoma, particularly in undifferentiated adenocarcinomas. To clarify the histological developmental processes in EBV-associated gastric carcinoma, we investigated the presence of EBV infection, changes in the degree of differentiation within lesions, and mucin phenotypes of gastric carcinomas. METHODOLOGY: We had already examined 124 gastric carcinomas using in situ hybridization for EBV-encoded small RNA1 (EBER-1) and 12 lesions were EBER-1-positive. From these lesions we selected 8 carcinomas positive for EBER-1, and then chose 16 EBER-1-negative carcinomas as controls. Hematoxylin and eosin (H&E) stained specimens were examined for changes in histological type within each lesion. Mucin phenotypes of the specimens were determined using human gastric mucin (HGM), MUC2 and CD10 immunostaining. RESULTS: Of the EBER-1-positive lesions, 50% exhibited the gastric type mucin phenotype, whereas only 19% of the EBER-1-negative lesions were of the gastric phenotype. Changes in the histological type were seen within 75% of the EBER-1-positive lesions and within 62.5% of the EBER-1-negative lesions. CONCLUSIONS: The gastric mucin phenotype tended to be more common in the EBV-associated gastric carcinomas. The influence of EBV infection on the change in the histological type within the lesion was considered to be slight.

Endoscopic findings potentially predictive of gastric cancer in borderline lesions diagnosed by forceps biopsy.

BACKGROUND/AIMS: When a benign-malignant borderline lesion is diagnosed by the usual small gastric biopsy, there is sometimes difficulty in making a clinical decision. To clarify potentially useful findings to predict the existence of gastric cancer in borderline lesions diagnosed by forceps biopsy, we retrospectively analyzed endoscopic features. METHODOLOGY: We diagnosed 68 consecutive gastric benign-malignant borderline lesions (57 cases) by forceps biopsy and endoscopically resected them. The final diagnosis for 24 lesions (35.3%) was adenocarcinoma (adenocarcinoma group), and for 40 lesions (58.8%) was adenoma (adenoma group). Comparison with endoscopic findings for the groups was carried out using digitally filed endoscopic photos. RESULTS: We found six endoscopic findings (distal location, reddish surface color, lack of smoothness, lack of glossiness, focal roughness, and focal redness) having statistically significant relationships with adenocarcinoma at the final pathological diagnosis. In multivariate analysis, focal redness (p<0.01) and lack of glossiness (p<0.05) were found to have a significant relationship to gastric cancer. CONCLUSIONS: Endoscopic findings such as focal redness and lack of glossiness were potentially predictive of gastric cancer in borderline lesions diagnosed by forceps biopsy.

Clinical impact of strip biopsy for early gastric cancer.

BACKGROUND: The impact of EMR (strip biopsy method) on the selection of subsequent treatment for early gastric cancer was analyzed retrospectively. METHODS: A total of 163 consecutive patients with gastric epithelial tumors (186 lesions) underwent strip biopsy. On the basis of pretherapeutic findings, the indications for strip biopsy were classified into 4 groups: benign-malignant borderline group (93 lesions), curative indication group (65), diagnostic indication group (22), and palliative indication group (6). The clinical impact of the strip biopsy result on the subsequent treatment strategy was assessed. RESULTS: Of the lesions in the benign-malignant borderline group, 36.6% were intramucosal cancer. In the curative indication group, the results of strip biopsy differed from the pretherapeutic findings for 7.7% of the lesions. Strip biopsy was effective treatment for all lesions in the benign-malignant borderline group and for 92.3% of those in the curative indication group. Strip biopsy avoided unnecessary surgery in 50% of patients in the diagnostic indication group and 16.7% of those in the palliative indication group. After the strip biopsy results were explained, 50% of the patients in the palliative indication group reversed their initial decision and opted for surgery. Strip biopsy results reversed the decision for surgery, which had been based on inaccurate pretherapeutic information, in 20% of cases of early gastric cancer. CONCLUSIONS: Strip biopsy has a major clinical impact, because it provides an accurate diagnosis, aids in the selection of an appropriate treatment strategy, and reduces unnecessary surgery.

Increased expression of matrix metalloproteinase-7 in invasive early gastric cancer.

BACKGROUND: Matrix metalloproteinase-7 (MMP-7), a proteolytic enzyme, is suspected to play an important role in the progression of various cancers. To clarify the clinical importance of MMP-7, we retrospectively analyzed MMP-7 expression in gastric epithelial tumors. METHODS: We tested 201 lesions (from 172 patients) of surgically or endoscopically resected gastric epithelial tumors (gastric cancer, 158 lesions; gastric adenoma, 32 lesions; hyperplastic polyp, 11 lesions). MMP-7 expression was immunohistochemically examined. Sections with immunostaining signals in more than 30% of tumor cells were judged to show positive expression. RESULTS: MMP-7 was expressed in 33.3% (67/201) of all lesions. MMP-7-positive tumors were significantly more frequent in diffuse-type adenocarcinomas (62.2%; 28/45) compared with intestinal-type lesions (31.9%; 36/113; P < 0.001). Cancers invading the submucosa or deeper (60.5%; 46/76) were showed positivity significantly more frequently than mucosal cancers (22.0%; 18/82; P < 0.001). MMP-7-positive lesions increased with the progression of gastric epithelial tumors, including adenomas, mucosal cancers, and cancers invading the submucosal layer or deeper (P < 0.001). MMP-7 expression occurred significantly more often in lymphatic invasion-positive cancers (65.1%; 41/63) than in lymphatic invasion-negative cancers (24.2%; 23/95; P < 0.001). CONCLUSIONS: The MMP-7-positive rate increased with the progression of gastric epithelial tumors, such as adenoma, mucosal cancer, and cancer invading the submucosal layer or deeper. MMP-7 was significantly associated with aggressive pathological phenotypes of cancer. The detection of the MMP-7 protein may be useful in pretherapeutic diagnosis.

The pilot experience of immunotherapy-combined photodynamic therapy for advanced gastric cancer in elderly patients.

BACKGROUND: Therapeutic efficacy of endoscopic photodynamic therapy (PDT) for advanced gastric cancer is limited. Recent animal studies have clarified the very important role of host immune cells in PDT. We expected a potential cooperative effect of PDT and immunotherapy, and developed immunotherapycombined PDT (I-PDT) for advanced gastric cancer. METHODS AND MATERIALS: We applied I-PDT for two elderly patients with complicated advanced gastric cancer (92- and 89-yr-old males). Tumor bleeding prevented them from leading an ordinary home life. Initial simple PDT was not effective. Patients received over 109 activated T-lymphocyte-predominant autologous immune cells, mainly intravenously, 5x for one course. PDT was performed endoscopically on the day of the third infusion. RESULTS: Two or three courses of I-PDT safely stopped tumor bleeding, and the initial poor prognoses of a few months of survival seemed to be improved (patient 1, over 32 mo; patient 2, 14 mo). CONCLUSIONS: I-PDT was found to be a safe, feasible treatment that could improve symptoms resulting from advanced gastric cancer.