Analysis of Clinical and Laboratory Risk Factors of Post-Traumatic Intracranial Hemorrhage in Patients on Direct Oral Anticoagulants with Mild Traumatic Brain Injury: An Observational Multicenter Cohort.

BACKGROUND: Assessing the risk of intracranial hemorrhage (ICH) in patients with a mild traumatic brain injury (MTBI) who are taking direct oral anticoagulants (DOACs) is challenging. Currently, extensive use of computed tomography (CT) is routine in the emergency department (ED). OBJECTIVE: This study aims to investigate whether the clinical and laboratory characteristics presented at the ED evaluation can also estimate the risk of post-traumatic ICH in DOAC-treated patients with MTBI. METHODS: A retrospective observational study was conducted in three EDs in Italy from January 1, 2016 to March 15, 2020. All patients treated with DOACs who were evaluated for an MTBI in the ED were enrolled. The primary outcome of the study was the presence of post-traumatic ICH in the head CT performed in the ED. RESULTS: Of 930 patients on DOACs with MTBI who were enrolled, 6.8% (63 of 930) had a post-traumatic ICH and 1.5% (14 of 930) were treated with surgery or died as a result of the ICH. None of the laboratory factors were associated with an increased risk of ICH. On multivariate analysis, previous neurosurgical intervention, major trauma dynamic, post-traumatic loss of consciousness, post-traumatic amnesia, Glasgow Coma Scale score of 14, and evidence of trauma above the clavicles were associated with a higher risk of post-traumatic ICH. The net clinical benefit provided by risk factor assessment appears superior to the strategy of performing CT on all DOAC-treated patients. CONCLUSIONS: Assessment of the clinical characteristics presented at ED admission can help identify DOAC-treated patients with MTBI who are at risk of ICH.

Decision tree analysis to predict the risk of intracranial haemorrhage after mild traumatic brain injury in patients taking DOACs.

BACKGROUND: Although the preliminary evidence seems to confirm a lower incidence of post-traumatic bleeding in patients treated with direct oral anticoagulants (DOACs) compared to those on vitamin K antagonists (VKAs), the recommended management of mild traumatic brain injury (MTBI) in patients on DOACs is the same as those on the older VKAs, risking excessive use of CT in the emergency department (ED). AIM: To determine which easily identifiable clinical risk factors at the first medical evaluation in the ED may indicate an increased risk of post-traumatic intracranial haemorrhage (ICH) in patients on DOACs with MTBI. METHODS: Patients on DOACs who were evaluated in the ED for an MTBI from 2016 to 2020 at four centres in Northern Italy were considered. A decision tree analysis using the chi-square automatic interaction detection (CHAID) method was conducted to assess the risk of post-traumatic ICH after an MTBI. Known pre- and post-traumatic clinical risk factors that are easily identifiable at the first medical evaluation in the ED were used as input predictor variables. RESULTS: Among the 1146 patients on DOACs in this study, post-traumatic ICH was present in 6.5% (75/1146). Decision tree analysis using the CHAID method found post-traumatic TLOC, post-traumatic amnesia, major trauma dynamic, previous neurosurgery and evidence of trauma above the clavicles to be the strongest predictors associated with the presence of post-traumatic ICH in patients on DOACs. The absence of a concussion seems to indicate subgroups at very low risk of requiring neurosurgery. CONCLUSIONS: The machine-based CHAID model identified distinct prognostic groups of patients with distinct outcomes based on clinical factors. Decision trees can be useful as guides for patient selection and risk stratification.

Risk factors associated with intracranial bleeding and neurosurgery in patients with mild traumatic brain injury who are receiving direct oral anticoagulants.

BACKGROUND: The established clinical risk factors for post-traumatic intracranial bleeding have not been evaluated in patients receiving DOACs yet. AIM: Evaluating the association between clinic and patient characteristics and post-traumatic intracranial bleeding (ICH) in patients with mild traumatic brain injury (MTBI) and DOACs. METHODS: This is a retrospective observational study conducted on three Emergency Departments. Multivariate analysis provided association in terms of OR with the risk of ICH. The performance of the multivariate model, described in a nomogram, has been tested with discrimination and decision curve analysis. RESULTS: Of 473 DOACs patients with MTBI, 8.5% had post-traumatic ICH. On multivariable analysis, major dynamics (odds ratio [OR] 6.255), post-traumatic amnesia (OR 3.961), post-traumatic loss of consciousness (LOC, OR 7.353), Glasgow Coma Scale (GCS) score < 15 (OR 3.315), post-traumatic headache (OR 4.168) and visible trauma above the clavicles (OR 3.378) were associated with a higher likelihood of ICH. The multivariate model, used for the nomogram construction, showed a good performance (AUC bias corrected with 5000 bootstraps resample 0.78). The DCAs showed a net clinical benefit of the prognostic model. CONCLUSIONS: Clinical risk factors can be used in DOACs patients to better define the risk of post-traumatic ICH.

Thirty-day mortality in atrial fibrillation patients with gastrointestinal bleeding in the emergency department: differences between direct oral anticoagulant and warfarin users.

More clinical data are required on the safety of direct oral anticoagulants (DOACs). Although patients treated with warfarin and DOACs have a similar risk of bleeding, short-term mortality after a gastrointestinal bleeding (GIB) episode in DOAC-treated patients has not been clarified. The objective of this study was to assess differences in 30-day mortality in patients treated with DOACs or warfarin admitted to the emergency department (ED) for GIB. This was a multicentre retrospective study conducted over 2 years. The study included patients evaluated at three different EDs for GIB. The baseline characteristics were included. Subsequently, we assessed the differences in past medical history and clinical data between the two study groups (DOAC and warfarin users). Differences between the two groups were evaluated using Kaplan-Meier curves. Among the 284 patients presenting GIB enrolled in the study period, 39.4% (112/284) were treated with DOACs and 60.6% (172/284) were treated with warfarin. Overall, 8.1% (23/284) of patients died within 30 days. Among the 172 warfarin-treated patients, 8.7% (15/172) died within 30 days from ED evaluation. In the 112 DOAC-treated patients, the mortality rate was 7.1% (8/112). The Cox regression analysis, adjusted for possible clinical confounders, and the Kaplan-Meier curves did not outline differences between the two treatment groups. The present study shows no differences between DOACs and warfarin in short-term mortality after GIB.

Direct Oral Anticoagulant Treatment and Mild Traumatic Brain Injury: Risk of Early and Delayed Bleeding and the Severity of Injuries Compared with Vitamin K Antagonists.

BACKGROUND: The risk of intracranial hemorrhage (ICH) in patients taking direct oral anticoagulants (DOACs) after mild traumatic brain injury (MTBI) is unclear. OBJECTIVES: To assess the differences in the risk of developing early, delayed, and comprehensive bleeding after MTBI among patients treated with DOACs as compared with those treated with vitamin K antagonists (VKAs). METHODS: All MTBI patients taking oral anticoagulants in our emergency department between June 2017 and August 2018 were included. All patients on oral anticoagulants underwent immediate cerebral computed tomography (CT) and a second CT scan after 24 h of clinical observation. RESULTS: There were 451 patients enrolled: 268 were on VKAs and 183 on DOACs. Of the DOAC-treated patients, 7.7% (14/183) presented overall intracranial bleeding, compared with 14.9% (40/268) of VKA-treated patients (p = 0.026). Early bleeding was present in 5.5% (10/183) of DOAC-treated patients and in 11.6% (31/268) of VKA-treated patients (p = 0.030). Multivariable analysis showed that VKA therapy (odds ratio [OR] 2.327), high-energy impact (OR 11.229), amnesia (OR 2.814), loss of consciousness (OR 5.286), Glasgow Coma Scale score < 15 (OR 4.719), and the presence of lesion above the clavicles (OR 2.742) were associated with significantly higher risk of global ICH. A nomogram was constructed to predict ICH using these six variables. Discrimination of the nomogram revealed good predictive abilities (area under the receiver operating characteristic curve: 0.817). CONCLUSIONS: DOAC-treated patients seem to have lower risk of posttraumatic intracranial bleeding compared with VKA-treated patients.

Association of Short- and Medium-Term Particulate Matter Exposure with Risk of Mortality after Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: We investigated the association of short- and medium-term particulate matter (PM) exposure with risk of mortality in patients with spontaneous intracerebral hemorrhage (ICH) identified according to strict etiologic criteria. METHODS: We conducted a retrospective analysis of prospectively collected data from consecutive patients with spontaneous ICH admitted to the emergency department of the University Hospital of Verona from March 2011 to December 2014. Outcome measures were mortality within 1 month after ICH and significant hematoma expansion (HE) defined as an absolute growth of more than 12.5 mL or a relative increase of more than 50% from baseline to follow-up computed tomography scan. RESULTS: A final number of 308 patients were included. In the adjusted model, higher PM2.5 and PM10 values in the last 3 days (odds ratio [OR] 1.827, 95% confidence interval [CI] 1.057-3.159, P = .031 and OR 1.949, 95% CI 1.025-3.704, P = .042, respectively) and in the last 4 weeks (OR 4.975, 95% CI 2.174-11.381, P < .001 and OR 9.781, 95% CI 3.425-27.932, P < .001, respectively) before ICH were associated with higher mortality rate. No association was found between PM exposure and significant HE. CONCLUSIONS: PM exposure in the short- and medium-term before spontaneous ICH was associated with risk of 1-month mortality, independent of predictors such as age, sex, stroke severity, intraventricular hemorrhage, ICH volume, ICH location, ICH etiologic subtype, significant HE, antithrombotic therapy, atrial fibrillation, and blood glucose levels.

Association between short- and medium-term air pollution exposure and risk of mortality after intravenous thrombolysis for stroke.

The exposure to air pollutants may increase both incidence and mortality of stroke. We aimed to investigate the association of short- and medium-term exposure to particulate matter (PM) and nitrogen dioxide (NO2) with the outcome of intravenous thrombolysis (IVT) for stroke. We conducted a retrospective analysis based on data prospectively collected from 944 consecutive IVT-treated stroke patients. The main outcome measure was 3-month mortality. The secondary outcome measures were causes of neurological deterioration (≥ 1 NIHSS point from baseline or death < 7 days), including intracerebral hemorrhage, cerebral edema (CED), and persistence or new appearance of hyperdense cerebral artery sign. In the adjusted model, higher PM2.5 and PM10 values in the last 3 days and 4 weeks before stroke were independently associated with higher mortality rate [hazard ratio (HR) 1.014, 95% confidence intervals (CI) 1.005-1.024, p = 0.003; HR 1.079, 95% CI 1.055-1.103, p = 0.001; HR 1.019, 95% CI 1.005-1.032, p = 0.008; and HR 1.015, 95% CI 1.004-1.027, p = 0.007; respectively]. Higher PM2.5 and PM10 values in the last 4 weeks were associated with higher CED rate [odd ratio (OR) 1.023, 95% CI 1.007-1.040, p = 0.006; and OR 1.017, 95% CI 1.003-1.032, p = 0.021; respectively]. No significant association between PM or NO2 and other causes of neurological deterioration was observed. Higher exposure to PM in the last 3 days and 4 weeks before stroke may be independently associated with 3-month mortality after IVT. Higher exposure to PM in the last 4 weeks before stroke may also be independently associated with CED after IVT.

The Role of Red Blood Cell Distribution Width for Predicting 1-year Mortality in Patients Admitted to the Emergency Department with Severe Dyspnoea.

BACKGROUND: Universally accepted and validated instruments for predicting the outcome of patients presenting to the emergency department (ED) with severe dyspnoea do not exist so far, nor are they regularly used by the emergency physicians. This study hence aimed to establish whether red blood cell distribution width (RDW) may be a predictive parameter of 1-year mortality in a population of patients admitted to the ED with severe dyspnoea attributable to different underlying disorders. METHODS: We retrospectively evaluated all the patients undergoing arterial blood gas analysis for severe dyspnoea (irrespective of the cause) during admission to ED of University Hospital of Verona from September 1, 2014 to November 31, 2014. RESULTS: The final study population consisted of 287 patients for whom complete clinical and laboratory information was available. Overall, 36 patients (12.5%) died after a 1-year follow-up. The RDW value was found to be considerably increased in patients who deceased during the follow-up compared to those who survived (17.2% versus 14.8%; p<0.001). In both univariate and multivariate analyses, the RDW value was found to be a significant predictor of 1-year mortality. In particular, patients with RDW ≥ 15.0% displayed a 72% increased risk of 1-year mortality after multiple adjustments. CONCLUSIONS: The measurement of RDW, a very simple and inexpensive laboratory parameter, may represent an important factor for predicting medium-term mortality in patients presenting to the ED with severe dyspnoea.

Early in-hospital variation of red blood cell distribution width predicts mortality in patients with acute heart failure.

BACKGROUND: Some studies showed that the value of red blood cell distribution width (RDW) at admission may predict clinical outcomes in patients with acutely decompensated heart failure (ADHF). Therefore, this study was planned to investigate whether in-hospital variations of RDW may also predict mortality in this condition. METHODS: The final study population consisted of 588 patients admitted to the local Emergency Department (ED), who were hospitalized for ADHF. The RDW was measured at ED admission and after 48h and 96h of hospital stay. In-hospital variations from admission value, expressed as absolute variation (DeltaRDW) or percent variation (Delta%RDW), were then correlated with 30- and 60-day mortality. RESULTS: Overall, 87 (14.8%) and 118 (20.1%) patients with ADHF died at 30 or 60days of follow-up. Delta%RDW after 96h of hospital stay independently predicted 30-day mortality (odds ratio, 1.12; 95% CI, 1.07-1.18). An increase >1% of Delta%RDW after 96h of hospital stay independently predicted both 30-day (odds ratio, 2.86; 95% CI, 1.67-4.97) and 60-day (odds ratio, 3.06; 95% CI, 1.89-4.96) mortality. A similar trend was observed for DeltaRDW, since an increase after 96h of hospital stay was associated with a nearly 4-fold higher 30-day mortality (odds ratio, 3.65; 95% CI, 2.02-6.15). CONCLUSION: Despite it remains unclear whether RDW is a real risk factor or an epiphenomenon in ADHF, these results suggest that more aggressive management may be advisable in ADHF patients with increasing anisocytosis during the first days of hospitalization.

Early function decline after ischemic stroke can be predicted by a nomogram based on age, use of thrombolysis, RDW and NIHSS score at admission.

The availability of prediction tools for risk stratification after acute stroke is seen as a valuable perspective for tailored clinical management. This retrospective study was aimed to identify significant predictors of poor outcome in patients presenting with acute ischemic stroke, which could then be used for constructing a prediction model. The study population consisted of 837 patients admitted to the Stoke Unit of University Hospital of Verona (Italy) for acute ischemic stroke within 12 h of symptoms onset. In multivariate analysis, age, use of thrombolysis, red blood cell distribution width (RDW) and NIHSS score at admission were found to be significant predictors of 3-month functional decline. A nomogram constructed by integrating these four variables exhibited an area under the curve of 0.832 for predicting functional impairment. The >80% risk cut-off derived from the nomogram was associated with 0.91 positive predictive value, whereas a risk probability <10% displayed 0.93 negative predictive value for predicting functional impairment. These results demonstrate that a prediction tool integrating some important clinical, laboratory and demographic variables may enable an efficient risk stratification of poor outcome after acute stroke.

Red Blood Cell Distribution Width Is an Independent Predictor of Outcome in Patients Undergoing Thrombolysis for Ischemic Stroke.

An appropriate and timely management, including early diagnosis and accurate prognostication, is the mainstay for managed care of patients with acute ischemic stroke. Since red blood cell distribution width (RDW) was found to be an independent predictor of clinical outcomes in patients with thrombotic disorders, we designed a retrospective observational study to investigate whether the RDW value may also retain predictive significance in stoke patients undergoing thrombolytic therapy. This retrospective study was based on all patients admitted to the Emergency Department (ED) of the University Hospital of Verona (Italy) with a diagnosis of ischemic stroke, who underwent systemic thrombolysis between January 2013 and June 2015. The RDW value along with basal clinical characteristics was recorded at ED admission. The final study population consisted of 316 patients. A significant association was found between stroke severity (NIHSS score) and RDW (r = 0.322; p < 0.001). The median RDW value in patients with clinical improvement after thrombolysis was significantly lower than in patients without (13.4 vs. 14.1%; p < 0.001). The diagnostic accuracy (area under the curve) of RDW for predicting the lack of neurological improvement was 0.667. In univariate analysis, RDW >14.5% was associated with increased rate of no neurological improvement (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.37-4.13), an association remaining significant also in multivariate analysis (OR, 1.85; 95% CI, 1.13-3.32). Survivor curve analysis showed that patients with RDW values ≥14.5% had a higher risk of 1-year mortality and shorter survival. These results suggest that RDW assessment at ED admission may provide valuable diagnostic and prognostic information in patients with acute ischemic stroke.

Hydroxocobalamin treatment of acute cyanide poisoning from apricot kernels.

Clinical experience with hydroxocobalamin in acute cyanide poisoning via ingestion remains limited. This case concerns a 35-year-old mentally ill woman who consumed more than 20 apricot kernels. Published literature suggests each kernel would have contained cyanide concentrations ranging from 0.122 to 4.09 mg/g (average 2.92 mg/g). On arrival, the woman appeared asymptomatic with a raised pulse rate and slight metabolic acidosis. Forty minutes after admission (approximately 70 min postingestion), the patient experienced headache, nausea and dyspnoea, and was hypotensive, hypoxic and tachypnoeic. Following treatment with amyl nitrite and sodium thiosulphate, her methaemoglobin level was 10%. This prompted the administration of oxygen, which evoked a slight improvement in her vital signs. Hydroxocobalamin was then administered. After 24 h, she was completely asymptomatic with normalised blood pressure and other haemodynamic parameters. This case reinforces the safety and effectiveness of hydroxocobalamin in acute cyanide poisoning by ingestion.

Hydroxocobalamin treatment of acute cyanide poisoning from apricot kernels.

Clinical experience with hydroxocobalamin in acute cyanide poisoning via ingestion remains limited. This case concerns a 35-year-old mentally ill woman who consumed more than 20 apricot kernels. Published literature suggests each kernel would have contained cyanide concentrations ranging from 0.122 to 4.09 mg/g (average 2.92 mg/g). On arrival, the woman appeared asymptomatic with a raised pulse rate and slight metabolic acidosis. Forty minutes after admission (approximately 70 min postingestion), the patient experienced headache, nausea and dyspnoea, and was hypotensive, hypoxic and tachypnoeic. Following treatment with amyl nitrite and sodium thiosulphate, her methaemoglobin level was 10%. This prompted the administration of oxygen, which evoked a slight improvement in her vital signs. Hydroxocobalamin was then administered. After 24 h, she was completely asymptomatic with normalised blood pressure and other haemodynamic parameters. This case reinforces the safety and effectiveness of hydroxocobalamin in acute cyanide poisoning by ingestion.

Tryptase serum level as a possible indicator of scombroid syndrome.

INTRODUCTION: Scombroid syndrome (histamine fish poisoning--HFP) is a complex of symptoms caused by biogenic amines, mainly histamine, contained in seafood. The diagnosis of HFP is quite difficult as the symptoms of this particular condition are similar to the symptoms of a normal allergic syndrome. MATERIALS AND METHODS: We have collected 10 cases (3 male and 7 female) of HFP and 50 non-HFP patients (35 female and 15 male) with allergic disorders, all from the Emergency Department of Ospedale Civile Maggiore in Verona. RESULTS: As expected, tryptase serum concentrations of most of the patients with allergic or anaphylactic disorders were increased above normal value (24.4+/-8.0 ng/mL mean+/-SD, normal value<11 ng/mL), whereas the tryptase serum concentrations of all the 10 patients with HFP were within the normal range (8.1+/-1.8 ng/mL). DISCUSSION: Our data suggest that tryptase serum concentrations can discriminate between the allergic and HFP syndromes. As the tryptase half-life is 90-120 min, blood samples must be taken 1-2 h from the beginning of symptoms. CONCLUSIONS: Finding a biomarker could help physicians to formulate a correct diagnosis and thus in choosing the best therapeutic strategy. In this work, we analyzed the role of tryptase serum concentrations to differentiate real allergic syndromes from the HFP syndrome, which causes similar histamine-mediated effects by a different mechanism.

Effects of nebivolol and atenolol on small arteries and microcirculatory endothelium-dependent dilation in hypertensive patients undergoing isometric stress.

OBJECTIVE: To examine the effects on small arteries and on the cutaneous microcirculatory system of nebivolol and atenolol in hypertensive patients. DESIGN: Twenty hypertensive patients were randomly assigned to receive nebivolol or atenolol in a single-blind, placebo-controlled cross-over study. Piezoelectric plethysmography on the third finger, laser Doppler on the third finger at rest and after iontophoretic administration of acetylcholine, and pressure-heart rate monitoring, were carried out both at rest and during handgrip. The tests were performed 45 min after 5 mg nebivolol or 100 mg atenolol administration, then repeated 2 days later with a placebo and, after a further 2 days, with atenolol or nebivolol again. RESULTS: Both atenolol and nebivolol reduced diastolic blood pressure values and heart rate, as well the increase of blood pressure and heart rate during handgrip. No change was recorded after placebo. Piezoelectric plethysmography showed a significant increase in the ratio between time to peak and total time (PT/TT), calculated on the sphygmic wave, during handgrip (0.295 0.005 versus 0.231 0.015, P<0.005). After nebivolol, a decrease was recorded in rest conditions (0.185 0.008 versus 0.231 0.015, P<0.005) with no statistically significant increase during handgrip, whereas atenolol showed an increase in the PT/TT ratio at rest, with a sustained response during handgrip. Laser Doppler showed an increased response to acetylcholine only after nebivolol. CONCLUSIONS: Nebivolol and atenolol significantly reduced diastolic blood pressure and heart rate, favourably modulating response to handgrip. Nebivolol improved small artery distensibility index. Endothelium-dependent cutaneous vasodilation after acetylcholine demonstrated a lack of response with atenolol whereas nebivolol favourably acts on endothelial function.

Effect of glutathione infusion on leg arterial circulation, cutaneous microcirculation, and pain-free walking distance in patients with peripheral obstructive arterial disease: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the effects of glutathione on pain-free walking distance (PFWD) and hemodynamic parameters in patients with peripheral artery disease. PATIENTS AND METHODS: Forty patients with Fontaine stage II peripheral artery disease who were seen between September 2000 and March 2001 at the vascular laboratory and ward of the Division of Vascular Medicine and Rehabilitation at Verona University were studied in a double-blind, placebo-controlled trial. The patients were randomly assigned (20 per group) to treatment with intravenous glutathione twice a day or saline solution twice a day for 5 days. Treatments were administered in a double-blind manner. The 2 groups of patients underwent measurement of PFWD by strain-gauge plethysmography and laser Doppler flowmetry (with postischemic test) of the symptomatic leg at rest and after treadmill test. All measurements and tests were repeated 12 hours after the last infusion. RESULTS: Between the 2 groups, hemodynamic tests showed no differences in baseline values and at rest after treatment. At rest, no differences were observed between basal and posttreatment values; findings in the saline group were similar during tests before and after the infusion period. In the glutathione group, we observed increases in PFWD (196+/-15 vs 143+/-11 m; P<.04), macrocirculatory flow after treadmill test with plethysmography at the end of treatment (9.3+/-2 vs 2.8+/-0.5 mL per 100 mL/min; P<.002), and postischemic hyperemia with laser Doppler flowmetry, registered as perfusion units (PU), at the end of infusions (14.4+/-3.2 vs 6.18+/-1.5 PU; P<.005), with a greater area under the curve after treatment (705+/-103 vs 508+/-45 PU/s; P<.001) and reduced time to flow motion (32+/-4 vs 48+/-11 seconds; P<.05). CONCLUSION: In patients with peripheral artery disease, glutathione prolongs PFWD and shows an improvement of macrocirculatory and microcirculatory parameters.