Association of early oral intake after extubation and independent activities of daily living at discharge among intensive care unit patients: A single centre retrospective cohort study.

PURPOSE: We investigated the association between the time to first post-extubation oral intake, barriers to oral intake, and the rate of activities of daily living (ADL) independence at discharge (Barthel Index score <70). METHOD: Consecutive patients admitted to the intensive care unit, aged ≥18 years, and mechanically ventilated for ≥48 hr were retrospectively enrolled. The time to first oral intake, barriers to oral intake, daily changes, and clinical outcomes were assessed. Multiple logistic regression analysis adjusted for baseline characteristics was used to determine the association between time to first post-extubation oral intake and ADL independence. RESULT: Among the 136 patients, 74 were assigned to the ADL independence group and 62 to the dependence group. The time to first post-extubation oral intake was significantly associated with ADL independence (adjusted p = < 0.001) and was a predictor of ADL independence at discharge. Respiratory and dysphagia-related factors (odds ratio [OR] 0.35; 95% confidence interval [CI] 0.15-0.82, p = 0.015 and OR 0.07; CI 0.01-0.68, p = 0.021, respectively) were significantly associated with the ADL independence at discharge. CONCLUSION: Respiratory and dysphagia-related factors, as barriers to the initiation of oral intake after extubation, were significantly associated with ADL independence at discharge.

Gender-related differences in the coagulofibrinolytic responses and long-term outcomes in patients with isolated traumatic brain injury: A 2-center retrospective study.

Coagulation function differs by gender, with women being characterized as more hypercoagulable. Even in the early stages of trauma, women have been shown to be hypercoagulable. Several studies have also examined the relationship between gender and the prognosis of trauma patients, but no certain conclusions have been reached. Patients with isolated traumatic brain injury (iTBI) are known to have coagulopathy, but no previous studies have examined the gender differences in detail. This is a retrospective analysis of a prospective registry conducted at 2 centers. The study included adult patients with iTBI enrolled from April 2018 to March 2021. Coagulofibrinolytic markers were measured in each patient at 1 hour, 24 hours, 3 days, and 7 days after injury, and neurological outcomes were assessed with the Glasgow Outcome Scale Extended at 6 months. Subgroup analysis was also performed by categorizing patients into groups according to neurological prognosis or age at 50 years. Males (n = 31) and females (n = 21) were included in the analysis. In males, there was a significant difference in the levels of activated partial thromboplastin time (P = .007), fibrin/fibrinogen degradation products (P = .025), D-dimer (P = .034), α2-plasmin inhibitor (P = .030), plasmin-α2-plasmin inhibitor complex (P = .004) at 1 hour after injury between favorable and unfavorable long-term neurological outcome groups, while in females there was no significant difference in these markers between 2 groups. In the age group under 50 years, there were significant gender differences in fibrinogen (day 3: P = .018), fibrin/fibrinogen degradation products (1 hour: P = .037, day 3: P = .009, day 7: P = .037), D-dimer (day 3: P = .005, day 7: P = .010), plasminogen (day 3: P = .032, day 7: P = .032), and plasmin-α2-plasmin inhibitor complex (day 3: P = .001, day 7: P = .001), and these differences were not evident in the age group over 50 years. There were differences in coagulofibrinolytic markers depending on gender in patients with iTBI. In male patients, aggravation of coagulofibrinolytic markers immediately after traumatic brain injury may be associated with poor neurologic outcome 6 months after injury.

Hyperfibrinolysis and fibrinolysis shutdown in patients with traumatic brain injury.

Traumatic brain injury (TBI) is associated with coagulation/fibrinolysis disorders. We retrospectively evaluated 61 TBI cases transported to hospital within 1 h post-injury. Levels of thrombin-antithrombin III complex (TAT), D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were measured on arrival and 3 h, 6 h, 12 h, 1 day, 3 days and 7 days after injury. Multivariate logistic regression analysis was performed to identify prognostic factors for coagulation and fibrinolysis. Plasma TAT levels peaked at admission and decreased until 1 day after injury. Plasma D-dimer levels increased, peaking up to 3 h after injury, and decreasing up to 3 days after injury. Plasma PAI-1 levels increased up to 3 h after injury, the upward trend continuing until 6 h after injury, followed by a decrease until 3 days after injury. TAT, D-dimer, and PAI-1 were elevated in the acute phase of TBI in cases with poor outcome. Multivariate logistic regression analysis showed that D-dimer elevation from admission to 3 h after injury and PAI-1 elevation from 6 h to 1 day after injury were significant negative prognostic indicators. Post-TBI hypercoagulation, fibrinolysis, and fibrinolysis shutdown were activated consecutively. Hyperfibrinolysis immediately after injury and subsequent fibrinolysis shutdown were associated with poor outcome.

Neurointensive Care of Traumatic Brain Injury Patients Based on Coagulation and Fibrinolytic Parameter Monitoring.

Coagulopathy, a common complication of traumatic brain injury (TBI), is characterized by a hypercoagulable state developing immediately after injury, with hyperfibrinolysis and bleeding tendency peaking 3 h after injury, followed by fibrinolysis shutdown. Reflecting this timeframe, the coagulation factor fibrinogen is first consumed and then degraded after TBI, its concentration rapidly decreasing by 3 h post-TBI. The fibrinolytic marker D-dimer reaches its maximum concentration at the same time. Hyperfibrinolysis in the acute phase of TBI is associated with poor prognosis via hematoma expansion. In the acute phase, the coagulation and fibrinolysis parameters must be monitored to determine the treatment strategy. The combination of D-dimer plasma level at admission and the level of consciousness upon arrival at the hospital can be used to predict the patients who will "talk and deteriorate." Fibrinogen and D-dimer levels should determine case selection and the amount of fresh frozen plasma required for transfusion. Surgery around 3 h after injury, when fibrinolysis and bleeding diathesis peak, should be avoided if possible. In recent years, attempts have been made to estimate the time of injury from the time course of coagulation and fibrinolysis parameter levels, which has been particularly useful in some cases of pediatric abusive head trauma patients.

Antithrombin activity levels for predicting long-term outcomes in the early phase of isolated traumatic brain injury.

Coagulopathy management is an important strategy for preventing secondary brain damage in patients with traumatic brain injury (TBI). Antithrombin (AT) is a natural anticoagulant that controls coagulation and inflammation pathways. However, the significance of AT activity levels for outcomes in patients with trauma remains unclear. This study aimed to investigate the relationship between AT activity levels and long-term outcomes in patients with TBI; this was a sub-analysis of a prior study that collected blood samples of trauma patients prospectively in a tertiary care center in Kawaguchi City, Japan. We included patients with isolated TBI (iTBI) aged ≥16 years admitted directly to our hospital within 1 h after injury between April 2018 and March 2021. General coagulofibrinolytic and specific molecular biomarkers, including AT, were measured at 1, 3, 6, 12, and 24 h after injury. We analyzed changes in the AT activity levels during the study period and the impact of the AT activity levels on long-term outcomes, the Glasgow Outcome Scale-Extended (GOSE), 6 months after injury. 49 patients were included in this study; 24 had good neurological outcomes (GOSE 6-8), and 25 had poor neurological outcomes (GOSE 1-5). Low AT activity levels were shown within 1 h after injury in patients in the poor GOSE group; this was associated with poor outcomes. Furthermore, AT activity levels 1 h after injury had a strong predictive value for long-term outcomes (area under the receiver operating characteristic curve of 0.871; 95% CI: 0.747-0.994). Multivariate logistic regression analysis with various biomarkers showed that AT was an independent factor of long-term outcome (adjusted odds ratio: 0.873; 95% CI: 0.765-0.996; p=0.043). Another multivariate analysis with severity scores showed that low AT activity levels were associated with poor outcomes (adjusted odds ratio: 0.909; 95% CI: 0.822-1.010; p=0.063). We demonstrated that the AT activity level soon after injury could be a predictor of long-term neurological prognosis in patients with iTBI.

A case of cribriform plate dural arteriovenous fistulas with a rare complication after endovascular therapy.

Background: Cribriform plate dural arteriovenous fistulas (dAVFs) are rarely encountered. Here, we report a case of cribriform plate dAVF with a rare complication after endovascular therapy. Case Description: A 60-year-old man presented with severe sudden headache. Head computed tomography showed right subdural hematoma, and magnetic resonance angiography showed dilated bilateral frontal cortical vein. Digital subtraction angiography revealed cribriform plate dAVF fed by the anterior and posterior ethmoidal branches of the bilateral ophthalmic arteries. Transarterial embolization with liquid embolic material was performed and the fistula disappeared. Although magnetic resonance imaging showed the disappearance of the cribriform plate dAVF and subdural hematoma, the patient complained of anosmia after the procedure. Conclusion: Endovascular embolization is an effective treatment option for treating cribriform plate dAVFs. However, anosmia is a possible complication, and endovascular surgeons should take care of this complication, especially in cribriform plate dAVFs supplied with blood bilaterally.

Association between Early Mobilization in the ICU and Psychiatric Symptoms after Surviving a Critical Illness: A Multi-Center Prospective Cohort Study.

This is a prospective multicenter cohort study aiming to investigate the association between early mobilization (EM), defined as a rehabilitation level of sitting at the edge of the bed or higher within 72 h of ICU admission, and psychiatric outcome. Consecutive patients, admitted to the ICU for more than 48 h, were enrolled. The primary outcome was the incidence of psychiatric symptoms at 3 months after hospital discharge defined as the presence of any of three symptoms: depression, anxiety, or post-traumatic stress disorder (PTSD). Risk ratio (RR) and multiple logistic regression analysis were used. As a sensitivity analysis, two methods for inverse probability of treatment weighting statistics were performed. Of the 192 discharged patients, 99 (52%) were assessed. The patients who achieved EM had a lower incidence of psychiatric symptoms compared to those who did not (25% vs. 51%, p-value 0.008, odds ratio (OR) 0.27, adjusted p = 0.032). The RR for psychiatric symptoms in the EM group was 0.49 [95% Confidence Interval, 0.29-0.83]. Sensitivity analysis accounting for the influence of death, loss to follow-up (OR 0.28, adjusted p = 0.008), or potential confounders (OR 0.49, adjusted p = 0.046) consistently showed a lower incidence of psychiatric symptoms in the EM group. EM was consistently associated with fewer psychiatric symptoms.

Association between timing of speech and language therapy initiation and outcomes among post-extubation dysphagia patients: a multicenter retrospective cohort study.

BACKGROUND: Post-extubation dysphagia (PED) is recognized as a common complication in the intensive care unit (ICU). Speech and language therapy (SLT) can potentially help improve PED; however, the impact of the timing of SLT initiation on persistent PED has not been well investigated. This study aimed to examine the timing of SLT initiation and its effect on patient outcomes after extubation in the ICU. METHODS: We conducted this multicenter, retrospective, cohort study, collecting data from eight ICUs in Japan. Patients aged ≥ 20 years with orotracheal intubation and mechanical ventilation for longer than 48 h, and those who received SLT due to PED, defined as patients with modified water swallowing test scores of 3 or lower, were included. The primary outcome was dysphagia at hospital discharge, defined as functional oral intake scale score < 5 or death after extubation. Secondary outcomes included dysphagia or death at the seventh, 14th, or 28th day after extubation, aspiration pneumonia, and in-hospital mortality. Associations between the timing of SLT initiation and outcomes were determined using multivariable logistic regression. RESULTS: A total of 272 patients were included. Of them, 82 (30.1%) patients exhibited dysphagia or death at hospital discharge, and their time spans from extubation to SLT initiation were 1.0 days. The primary outcome revealed that every day of delay in SLT initiation post-extubation was associated with dysphagia or death at hospital discharge (adjusted odds ratio (AOR), 1.09; 95% CI, 1.02-1.18). Similarly, secondary outcomes showed associations between this per day delay in SLT initiation and dysphagia or death at the seventh day (AOR, 1.28; 95% CI, 1.05-1.55), 14th day (AOR, 1.34; 95% CI, 1.13-1.58), or 28th day (AOR, 1.21; 95% CI, 1.07-1.36) after extubation and occurrence of aspiration pneumonia (AOR, 1.09; 95% CI, 1.02-1.17), while per day delay in post-extubation SLT initiation did not affect in-hospital mortality (AOR, 1.04; 95% CI, 0.97-1.12). CONCLUSIONS: Delayed initiation of SLT in PED patients was associated with persistent dysphagia or death. Early initiation of SLT may prevent this complication post-extubation. A randomized controlled study is needed to validate these results.

Effects of Mobilization among Critically Ill Patients in the Intensive Care Unit: A Single-center Retrospective Study.

Objectives: This study investigated the effect of early mobilization [EM; physical rehabilitation with the intensity needed to sit on the edge of the bed started within 5 days of intensive care unit (ICU) admission] in relation to improvements in gait independence and other clinical outcomes. Methods: This retrospective single-center study evaluated patients aged at least 18 years who stayed in the ICU for at least 48 h and were categorized into EM and late mobilization (LM; physical rehabilitation started more than 5 days after ICU admission) groups. Outcomes were compared after adjusting for 20 background factors by propensity score matching and inverse probability of treatment weighting. The primary outcome was independent gait at discharge. The secondary outcomes were medical costs, 90-day survival, and durations of ICU and hospital stays. Results: Of 177 patients, 85 and 92 were enrolled in the EM and LM groups, respectively. Propensity score matching created 37 patient pairs. There was no significant difference in the 90-day survival rate (P=0.308) or medical costs (P=0.054), whereas independent gait at discharge (P=0.025) and duration of hospital stay (P=0.013) differed significantly. Multivariate logistic regression analysis showed that EM was independently associated with independent gait at discharge (P=0.011) and duration of hospital stay (P=0.010) but was not associated with 90-day survival (odds ratio: 2.64, 95% confidence interval: 0.67-13.12, P=0.169). Conclusions: Early mobilization in the ICU did not affect 90-day survival and did not lower medical costs but was associated with independent gait at discharge and shorter hospital stays.

Acoustic Neurinoma with Synchronous Ipsilateral Cerebellopontine Angle Lipoma: A Case Report and Review of the Literature.

Lipomas of the cerebellopontine angle (CPA) and internal auditory canal (IAC) are relatively rare tumors. Acoustic neurinoma is the most common tumor in this location, which often causes hearing loss, vertigo, and tinnitus. Occasionally, this tumor compresses the brainstem, prompting surgical resection. Lipomas in this area may cause symptoms similar to neurinoma. However, they are not considered for surgical treatment because their removal may result in several additional deficits. Conservative therapy and repeated magnetic resonance imaging examinations for CPA/IAC lipomas are standard measures for preserving cranial nerve function. Herein, we report a case of acoustic neurinoma and CPA lipoma occurring in close proximity to each other ipsilaterally. The main symptom was hearing loss without facial nerve paralysis. Therefore, facial nerve injury had to be avoided. Considering the anatomical relationships among the tumors, cranial nerves, and CPA/IAC lipoma, we performed total surgical removal of the acoustic neurinoma. We intentionally left the lipoma untreated, which enabled facial nerve preservation. This report may be a useful reference for the differential diagnosis of similar cases in the future.

Trends in Isolated Pelvic Fracture and 30-Day Survival during a Recent 15-Year Period: A Nationwide Study of the Japan Trauma Data Bank.

BACKGROUND: The epidemiology and treatment of isolated pelvic fracture in Japan are not well understood. This study evaluated epidemiological trends in isolated pelvic trauma and in-hospital survival rates during a recent 15-year period. METHODS: This retrospective cohort study analyzed data from the Japan Trauma Data Bank for 2004-2018. Patients of any age with isolated pelvic fracture were grouped according to time period, as follows: 2004-2008 (Phase 1), 2009-2013 (Phase 2), and 2014-2018 (Phase 3). The main outcome was 30-day in-hospital survival rate. The data were analyzed using the chi-square, Kruskal-Wallis, and Mantel-Haenszel trend tests. We analyzed change in the main outcome over time in multiple logistic regression analysis fitted with a generalized estimating equation, accounting for within-cluster association. RESULTS: In total, 5,348 isolated pelvic fractures were identified during the study period. There was no significant between-phase difference in proportions of patients who underwent resuscitative balloon occlusion of the aorta or external fixation. The proportion of patients who underwent transcatheter arterial embolization significantly increased with time (p=0.003), as did the survival rate (Phase 1, 77%; Phase 2, 86%; and Phase 3, 91%; p<0.001). The 30-day in-hospital mortality rate was significantly lower in Phase 3 than in Phase 1 and Phase 2, even after adjustment for hospital clustering and other confounders (p<0.01). CONCLUSIONS: The 30-day in-hospital survival rate after isolated pelvic fracture improved over a 15-year period in Japan.

Changes in barriers to implementing early mobilization in the intensive care unit: a single center retrospective cohort study.

This study was undertaken to investigate the rate of mobilization, defined as a rehabilitation level of sitting on the edge of a bed or higher, and its association with changes in barriers in the intensive care unit (ICU). Consecutive patients from January 2016 to March 2019 admitted to the ICU, 18 years old or older, who did not meet exclusion criteria, were eligible. The primary outcome was the rate of mobilization. Barriers, their changes on a daily basis, and clinical outcomes, such as walking independence at hospital discharge, were also investigated. The association between the barriers and mobilization, and walking independence were analyzed by multivariate logistic regression analysis. During the study period, 177 patients were enrolled. Mobilization was achieved by 116 patients (66%) by the 7th ICU day. The barrier to mobilization was circulatory status on days 1 and 2, consciousness level on days 3 to 5, and medical staff factors on days 6 and 7. Multivariate analysis showed that consciousness level (OR: 0.38, p=0.01), and medical staff factors (OR: 0.49, p=0.01) were significantly associated with mobilization. By hospital discharge 125 patients (71%) could walk independently. Consciousness level was associated (OR: 0.52, p=0.04) with walking independence. In this study, over half of patients could achieve mobilization within the first 7 days. Barriers to mobilization in the ICU change over time. Consciousness level is significantly associated with both mobilization and independent walking at discharge.

Time course of coagulation and fibrinolytic parameters in pediatric traumatic brain injury.

OBJECTIVE: Coagulopathy is a well-recognized risk factor for poor outcomes in patients with traumatic brain injury (TBI). Differences in the time courses of coagulation and fibrinolytic parameters between pediatric and adult patients with TBI have not been defined. METHODS: Patients with TBI and an Abbreviated Injury Scale of the head score ≥ 3, in whom the prothrombin time (PT)-international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen concentration, and plasma D-dimer levels were measured on arrival and at 3, 6, and 12 hours after injury, were retrospectively analyzed. Propensity score-matched analyses were performed to adjust baseline characteristics between pediatric patients (aged < 16 years) and adult patients (aged ≥ 16 years). RESULTS: A total of 468 patients (46 children and 422 adults) were included. Propensity score matching resulted in a matched cohort of 46 pairs. Higher PT-INR and APTT values at 1 to 12 hours after injury and lower fibrinogen concentrations at 1 to 6 hours after injury were observed in the pediatric group compared with the adult group. Plasma levels of D-dimer were elevated in both groups at 1 to 12 hours after injury, but no significant differences were seen between the groups. Multivariate logistic regression analysis of the initial coagulation and fibrinolytic parameters in the pediatric group revealed no prognostic significance of the coagulation parameter values, but elevation of the fibrinolytic parameter D-dimer was an independent negative prognostic factor. CONCLUSIONS: In the acute phase of TBI, pediatric patients were characterized by prolongation of PT-INR and APTT and lower fibrinogen concentrations compared with adult patients, but these did not correlate with outcome. D-dimer was an independent prognostic outcome factor in terms of the Glasgow Outcome Scale in pediatric patients with TBI.

Treatment of Geriatric Traumatic Brain Injury: A Nationwide Cohort Study.

BACKGROUND: Because of the aging of the Japanese population, traumatic brain injuries (TBI) have increased in elderly adults. However, the effectiveness and prognosis of intensive treatment for geriatric TBI have not yet been determined. Thus, we used nationwide data from the Japan Neurotrauma Data Bank (JNTDB) projects to analyze prognostic factors for intensive and aggressive treatments. METHODS: We analyzed 1,879 geriatric TBI cases (age ≥65 years) registered in four JNTDB projects: Project 1998 (P1998) to Project 2015 (P2015). Clinical features, use of aggressive treatment, and 6-month outcomes on the Glasgow Outcome Scale (GOS) were compared among study projects. Logistic regression was used to identify prognostic factors in aggressively treated patients. RESULTS: The percentage of geriatric TBI cases significantly increased with time-P1998: 30.1%; Project 2004 (P2004): 34.6%; Project 2009 (P2009): 43.9%; P2015: 53.6%, p<0.0001). Use of aggressive treatment also significantly increased, from 67.0% in P1998 to 69.3% in P2015 (p<0.0001). Less invasive methods, such as trepanation and normothermic targeted temperature management, were more often chosen for geriatric patients. These efforts resulted in a significant decrease in the 6-month mortality rate, from 76.2% in P1998 to 63.1% in P2015 (p=0.0003), although the percentage of severely disabled patients increased, from 8.9% in P1998 to 11.1% in P2015 (p=0.0003). Intraventricular hemorrhage was the factor most strongly associated with unfavorable 6-month outcomes (OR 3.79, 95% CI 1.78-8.06, p<0.0001). CONCLUSIONS: Less invasive treatments reduced mortality in geriatric TBI but did not improve functional outcomes. Patient age was not the strongest prognostic factor; thus, physicians should consider characteristics other than age.

Age-Related Differences in the Time Course of Coagulation and Fibrinolytic Parameters in Patients with Traumatic Brain Injury.

Coagulopathy and older age are common and well-recognized risk factors for poorer outcomes in traumatic brain injury (TBI) patients; however, the relationships between coagulopathy and age remain unclear. We hypothesized that coagulation/fibrinolytic abnormalities are more pronounced in older patients and may be a factor in poorer outcomes. We retrospectively evaluated severe TBI cases in which fibrinogen and D-dimer were measured on arrival and 3-6 h after injury. Propensity score-matched analyses were performed to adjust baseline characteristics between older patients (the "elderly group," aged ≥75 y) and younger patients (the "non-elderly group," aged 16-74 y). A total of 1294 cases (elderly group: 395, non-elderly group: 899) were assessed, and propensity score matching created a matched cohort of 324 pairs. Fibrinogen on admission, the degree of reduction in fibrinogen between admission and 3-6 h post-injury, and D-dimer levels between admission and 3-6 h post-injury were significantly more abnormal in the elderly group than in the non-elderly group. On multivariate logistic regression analysis, independent risk factors for poor prognosis included low fibrinogen and high D-dimer levels on admission. Posttraumatic coagulation and fibrinolytic abnormalities are more severe in older patients, and fibrinogen and D-dimer abnormalities are negative predictive factors.

Early outcome prediction with quantitative pupillary response parameters after out-of-hospital cardiac arrest: A multicenter prospective observational study​.

We aimed to determine the characteristics of quantitative pupillary response parameters other than amplitude of pupillary light reflex (PLR) early after return of spontaneous circulation (ROSC) and their implications for predicting neurological outcomes early after cardiac arrest (CA). Fifty adults resuscitated after non-traumatic out-of-hospital CA from four emergency hospitals were enrolled. Pupil diameters, PLR, constriction velocity (CV), maximum CV (MCV), dilation velocity (DV), latency of constriction, and Neurological Pupil index (NPi) were quantitatively measured at 0, 6, 12, 24, 48, and 72 h post-ROSC using an automated pupillometer. Change over time of each parameter was compared between favorable (Cerebral Performance Category [CPC] 1 or 2) and unfavorable neurological outcome (CPC 3-5) groups. Prognostic values of 90-day favorable outcome by these parameters and when combined with clinical predictors (witness status, bystander cardiopulmonary resuscitation, initial shockable rhythm, implementation of target temperature management) were tested. Thirteen patients achieved favorable outcome. CV, MCV, DV (P < 0.001), and NPi (P = 0.005) were consistently greater in the favorable group than in the unfavorable outcome group. Change over time was not statistically different between the groups in all parameters. CV, MCV, DV (ρ = 0.96 to 0.97, P < 0.001, respectively), and NPi (ρ = 0.65, P < 0.001) positively correlated with PLR. The prognostic value of 0-hour CV (area under the curve, AUC [95% confidence interval]: 0.92 [0.80-1.00]), DV (0.84 [0.68-0.99]), and NPi (0.88 [0.74-1.00]) was equivalent to that of PLR (0.84 [0.69-0.98]). Prognostic values improved to AUC of 0.95-0.96 when 0-hour PLR, CV, DV, or NPi was combined with clinical predictors. The 0-hour CV, MCV, and NPi showed equivalent prognostic values to PLR alone/in combination with clinical predictors. Using PLR among several quantitative pupillary response parameters for early neurological prognostication of post-CA patients is a simple and effective strategy.

A retrospective study of the effect of fibrinogen levels during fresh frozen plasma transfusion in patients with traumatic brain injury.

BACKGROUND: The association between traumatic brain injury (TBI) and coagulopathy is well established. While coagulopathy prophylaxis in TBI involves replenishing coagulation factors with fresh frozen plasma (FFP), its effectiveness is controversial. We investigated the relationship between plasma fibrinogen concentration 3 h after initiating FFP transfusion and outcomes and evaluated the correlation with D-dimer levels at admission. METHODS: We retrospectively examined data from 380 patients with severe isolated TBI with blood samples collected a maximum of 1 h following injury. Plasma fibrinogen and D-dimer concentrations were obtained at admission, and plasma fibrinogen concentration was again assessed 3-4 h following injury. The patients were divided into two groups based on whether or not they received FFP transfusion. Patients were also divided into subgroups according their fibrinogen level: ≥ 150 mg/dL (high-fibrinogen subgroup) or < 150 mg/dL (low-fibrinogen subgroup) 3 h after injury. Demographic, clinical, radiological and laboratory data were compared between these subgroups. RESULTS: Glasgow Outcome Scale (GOS) scores at discharge and 3 months after injury were significantly lower in the FFP transfusion group than in the FFP non-transfusion group. Among patients who received FFP, GOS scores at discharge and 3 months after injury were significantly higher in the high-fibrinogen subgroup than in the low-fibrinogen subgroup. Elevated admission D-dimer predicted subsequent fibrinogen decrease. CONCLUSIONS: In FFP transfusion, fibrinogen level ≥ 150 mg/dL 3 h after injury was associated with better outcomes in TBI patients. Assessing the admission D-dimer and tracking the fibrinogen are crucial for optimal coagulopathy prophylaxis in TBI patients.

Feasibility of Human Neural Stem Cell Transplantation for the Treatment of Acute Subdural Hematoma in a Rat Model: A Pilot Study.

Human neural stem cells (hNSCs) transplantation in several brain injury models has established their therapeutic potential. However, the feasibility of hNSCs transplantation is still not clear for acute subdural hematoma (ASDH) brain injury that needs external decompression. Thus, the aim of this pilot study was to test feasibility using a rat ASDH decompression model with two clinically relevant transplantation methods. Two different methods, in situ stereotactic injection and hNSC-embedded matrix seating on the brain surface, were attempted. Athymic rats were randomized to uninjured or ASDH groups (F344/NJcl-rnu/rnu, n = 7-10/group). Animals in injury group were subjected to ASDH, and received decompressive craniectomy and 1-week after decompression surgery were transplanted with green fluorescent protein (GFP)-transduced hNSCs using one of two approaches. Histopathological examinations at 4 and 8 weeks showed that the GFP-positive hNSCs survived in injured brain tissue, extended neurite-like projections resembling neural dendrites. The in situ transplantation group had greater engraftment of hNSCs than matrix embedding approach. Immunohistochemistry with doublecortin, NeuN, and GFAP at 8 weeks after transplantation showed that transplanted hNSCs remained as immature neurons and did not differentiate toward to glial cell lines. Motor function was assessed with rotarod, compared to control group (n = 10). The latency to fall from the rotarod in hNSC in situ transplanted rats was significantly higher than in control rats (median, 113 s in hNSC vs. 69 s in control, P = 0.02). This study first demonstrates the robust engraftment of in situ transplanted hNSCs in a clinically-relevant ASDH decompression rat model. Further preclinical studies with longer study duration are warranted to verify the effectiveness of hNSC transplantation in amelioration of TBI induced deficits.

Quantitative pupillometry and neuron-specific enolase independently predict return of spontaneous circulation following cardiogenic out-of-hospital cardiac arrest: a prospective pilot study.

This study aimed to identify neurological and pathophysiological factors that predicted return of spontaneous circulation (ROSC) among patients with out-of-hospital cardiac arrest (OHCA). This prospective 1-year observational study evaluated patients with cardiogenic OHCA who were admitted to a tertiary medical center, Nippon Medical School Hospital. Physiological and neurological examinations were performed at admission for quantitative infrared pupillometry (measured with NPi-200, NeurOptics, CA, USA), arterial blood gas, and blood chemistry. Simultaneous blood samples were also collected to determine levels of neuron-specific enolase (NSE), S-100b, phosphorylated neurofilament heavy subunit, and interleukin-6. In-hospital standard advanced cardiac life support was performed for 30 minutes.The ROSC (n = 26) and non-ROSC (n = 26) groups were compared, which a revealed significantly higher pupillary light reflex ratio, which was defined as the percent change between maximum pupil diameter before light stimuli and minimum pupil diameter after light stimuli, in the ROSC group (median: 1.3% [interquartile range (IQR): 0.0-2.0%] vs. non-ROSC: (median: 0%), (Cut-off: 0.63%). Furthermore, NSE provided the great sensitivity and specificity for predicting ROSC, with an area under the receiver operating characteristic curve of 0.86, which was created by plotting sensitivity and 1-specificity. Multivariable logistic regression analyses revealed that the independent predictors of ROSC were maximum pupillary diameter (odds ratio: 0.25, 95% confidence interval: 0.07-0.94, P = 0.04) and NSE at admission (odds ratio: 0.96, 95% confidence interval: 0.93-0.99, P = 0.04). Pupillary diameter was also significantly correlated with NSE concentrations (r = 0.31, P = 0.027). Conclusively, the strongest predictors of ROSC among patients with OHCA were accurate pupillary diameter and a neuronal biomarker, NSE. Quantitative pupillometry may help guide the decision to terminate resuscitation in emergency departments using a neuropathological rationale. Further large-scale studies are needed.