Impact of Early Intravenous Haemostatic Drugs on Brain Haemorrhage Patients and Their Image Segmentation Based on RGB-D Images

Cerebral haemorrhage is a serious subtype of stroke, with most patients experiencing short-term haematoma enlargement leading to worsening neurological symptoms and death. The main hemostatic agents currently used for cerebral haemorrhage are antifibrinolytics and recombinant coagulation factor VIIa. However, there is no clinical evidence that patients with cerebral haemorrhage can benefit from hemostatic treatment. We provide an overview of the mechanisms of haematoma expansion in cerebral haemorrhage and the progress of research on commonly used hemostatic drugs. To improve the semantic segmentation accuracy of cerebral haemorrhage, a segmentation method based on RGB-D images is proposed. Firstly, the parallax map was obtained based on a semiglobal stereo matching algorithm and fused with RGB images to form a four-channel RGB-D image to build a sample library. Secondly, the networks were trained with 2 different learning rate adjustment strategies for 2 different structures of convolutional neural networks. Finally, the trained networks were tested and compared for analysis. The 146 head CT images from the Chinese intracranial haemorrhage image database were divided into a training set and a test set using the random number table method. The validation set was divided into four methods: manual segmentation, algorithmic segmentation, the exact Tada formula, and the traditional Tada formula to measure the haematoma volume. The manual segmentation was used as the “gold standard,” and the other three algorithms were tested for consistency. The results showed that the algorithmic segmentation had the lowest percentage error of 15.54 (8.41, 23.18) % compared to the Tada formula method.

Implementing a Goal-Directed Care Bundle after Acute Intracerebral Haemorrhage: Process Evaluation for the Third INTEnsive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial Study in China

<b><i>Background:</i></b> The third INTEnsive care bundle with blood pressure Reduction in Acute Cerebral Haemorrhage Trial is an ongoing international, multicentre, stepped wedge, cluster-randomized trial to determine the effectiveness of a goal-directed care bundle (early intensive blood pressure [BP] lowering, glycaemic control, treatment of pyrexia, and reversal of anticoagulation), as compared to standard of care, on patient-centred outcomes after acute intracerebral haemorrhage (ICH). An embedded process evaluation aims to identify factors related to the uptake and implementation of the intervention. Herein, we present the process evaluation results for hospital sites in China. <b><i>Methods/Design:</i></b> A mixed methods approach, including surveys, focused group discussions and interviews with clinicians, routine monitoring, and recruitment logs were used to collect data across purposively sampled hospitals. Medical Research Council guidance and normalization process theory were used as theoretical frameworks for design, data analysis, and synthesis. <b><i>Results:</i></b> Twenty quantitative surveys were completed with clinicians, and 26 interviews and 2 focus group discussions were conducted during 2019–2020. The care bundle was generally delivered as planned and acceptable by doctors and nurses, but difficulties were reported in achieving the protocol-defined target levels of BP and glycaemic control. Resistance to implementing the care bundle occurred for patients perceived to be at high risk of adverse effects. Common organizational contextual factors that impeded implementation included delayed processes and limited medication supply, while established background care procedures, expertise, and capacity influenced its integration into routine practice. Areas to facilitate implementation included optimizing workflow within available resources, having a dedicated team, and recognizing the potential benefits of the intervention. <b><i>Conclusions:</i></b> Varied established care protocols across sites, different levels of background expertise, and lack of staff capacity impeded the integration of goal-directed care bundle into routine practice for ICH patients in China. Ready identification, and efforts to address, these barriers could facilitate uptake of future guideline-recommended interventions for the management of patients with ICH.

Association of Direct Oral Anticoagulants (DOACs) and Warfarin With Haemorrhagic Risk by Applying Correspondence Analysis to Data From the Italian Pharmacovigilance Database – A Case Study

Introduction: Post-marketing data on the risks associated with direct oral anticoagulants (DOACs) are conflicting and only few studies evaluated a comparison between each different DOAC. Real-world data from pharmacovigilance databases can help to better define the safety profile of each DOAC and warfarin. However, Correspondence Analysis (CA) could represent a useful tool in this context.Objective: In the attempt to assess the usefulness of CA as a signal detection pharmacovigilance tool, we applied this method to the Italian Pharmacovigilance Database (RNF, Rete Nazionale di Farmacovigilanza), by comparing with disproportionality analysis on warfarin and DOACs.Methods: Study based on AEs sent to RNF by Campania Region from 2008 to 2021, in which warfarin, dabigatran, apixaban, edoxaban or rivaroxaban were reported as suspected drug. AEs were clustered into three Standardized MedDRA Queries (SMQs): Central Nervous System Haemorrhages and Conditions (CNSH), GastroIntestinal Perforation, Ulceration, Obstruction or Haemorrhages (GIPUOH) and other Haemorrhages (HH). Non-haemorrhagic AEs were included in a fourth cluster (nHH).Results: We retrieved 1,161 reports: 41.5% are associated to warfarin, 21.0% to dabigatran, 17.8% to rivaroxaban, 13.9% to apixaban and 5.8% to edoxaban. No significant differences in age distribution were observed. Results of CA showed that dabigatran and warfarin have the highest contribution (44.910 and 47.656, respectively) to the inertia of Dimension 1 as well as apixaban and dabigatran to the inertia of Dimension 2 (53.768 and 30.488, respectively). Edoxaban and rivaroxaban showed a negligible total contribution. CA biplot showed positive associations between warfarin and HH, apixaban and CNSH and dabigatran and nHH.Conclusion: Results seem to confirm that DOACs are not interchangeable. Apixaban was surprisingly associated with a higher risk of cerebral haemorrhage. As expected, our data support the better safety profile of DOACs than warfarin in terms of skin and respiratory tract hemorrhagic risks. Finally, we showed how CA could play a complementary role in analyzing data from pharmacovigilance databases.

Factors associated with symptomatic intracranial haemorrhage after intravenous thrombolysis in severe white matter lesions: a retrospective analysis

Background and purposeWhite matter lesions (WMLs) are thought to cause damage to the blood–brain barrier, thereby aggravating bleeding after intravenous thrombolysis. However, the risk factors for symptomatic cerebral haemorrhage after thrombolysis are still unclear. This study explored the risk factors for bleeding in patients with severe WMLs after intravenous thrombolysis to prevent bleeding as soon as possible.MethodsA large single-centre observational study conducted a retrospective analysis of intravenous thrombolysis in patients with severe WMLs from January 2018 to March 2021. According to whether symptomatic cerebral haemorrhage occurred, the patients were divided into two groups, and then statistical analysis was performed.ResultsAfter a retrospective analysis of the data of nearly 1000 patients with intravenous thrombolysis and excluding invalid information, 146 patients were included, of which 23 (15.8%) patients had symptomatic cerebral haemorrhage. Univariate analysis showed that a history of hypertension (20% vs 4.9%, p=0.024), hyperlipidaemia (38.7% vs 9.6%, p<0.001), the National Institutes of Health Stroke Scale (NIHSS) score before thrombolysis (median 17 vs 6, p<0.001), low-density lipoprotein levels (median 2.98 vs 2.44, p=0.011), cholesterol levels (mean 4.74 vs 4.22, p=0.033), platelet count (median 161 vs 191, p=0.031), platelet distribution width (median 15.2 vs 12.1, p=0.001) and sodium ion levels (median 139.81 vs 138.67, p=0.043) were significantly associated with symptomatic cerebral haemorrhage. Further multivariate logistic regression analysis showed that hyperlipidaemia (OR=9.069; 95% CI 2.57 to 32.07; p=0.001) and the NIHSS score before thrombolysis (OR=1.33; 95% CI 1.16 to 1.52; p<0.001) were comprehensive risk factors for symptomatic cerebral haemorrhage.ConclusionHyperlipidaemia and the NIHSS score before thrombolysis are independent risk factors for bleeding after intravenous thrombolysis in patients with severe WMLs. Delaying the onset of white matter and preventing risk factors for bleeding will help improve the prognosis of cerebral infarction and reduce mortality. These risk factors need to be further evaluated in future studies.

Leukocyte neutrophil ratio (NLR) as biomarker for neuroinflammation in patients with intracerebral haemorrhage and traumatic brain injury

Circulating inflammatory markers may predict the broad clinical spectrum of traumatic brain injury (TBI). The present study aimed to illustrate the role of leukocytes, precisely neutrophil and lymphocytes, in neuroinflammation as a new vista in neuro-critical care. Search terms were: elevations in peripheral blood leukocytes counts, neutrophil, lymphocyte with precisely neutrophil to lymphocyte ratios, associated with adverse outcomes of traumatic brain injury, pre and post-operative conditions of intracerebral haemorrhage, seizures, delirium, non-convulsive status epilepticus, confusion, aphasia, agitation, coma, disability and death. As a result, we identified 16 publications describing leukocyte biomarkers associated with neuroinflammation following TBI from PubMed, Cochrane Registry of Controlled Trials, Medline and Embase (Ovid) on randomised controlled trials (RCTs), non-RCTs and cohort studies published in the last decade. This study concluded that elevations in peripheral blood leukocyte and neutrophil to lymphocyte ratios could predict adverse outcomes of a cerebral haemorrhage.

Heart valve disease in hypocomplementemic urticarial vasculitis syndrome. From immune mediated degeneration to embolic complications of infective endocarditis. A case report

Introduction Hypocomplementemic Urticarial Vasculitis Syndrome is a rare disease due to small vessel inflammation and characterized by chronic urticarial vasculitis and arthritis. Multi-organ manifestations may include glomerulonephritis, ocular inflammation (uveitis, episcleritis), and recurrent abdominal pain. To our knowledge, just other nine cases of HUVS with cardiac valvular involvement have been reported in the literature. Case summary A 32-year-old woman presented to the emergency department because of a cerebral Haemorrhage. She suffered from a severe HUVS form with cardiac valvular involvement. In the previous years, she underwent cardiac surgery twice for aortic and mitral valves immune-mediated degeneration. The neurologic event was secondary to Listeria monocytogenes aortic endocarditis, complicated by a cerebral embolism and periaortic abscess. Discussion Patients with HUVS rarely present valvular heart disease. The latter is mostly secondary to an inflammatory process. Valve degeneration and immunosuppressive therapy increase the risk of infective endocarditis, with dramatic consequences for the prognosis of these patients. Valvular involvement is a sporadic but potentially fatal complication of HUVS, which should be taken in mind in the multidisciplinary evaluation of these patients.

Rivaroxaban Causing Thrombocytopenia in a Case of Deep Vein Thrombosis (DVT)

Novel oral anticoagulants (NOACs) are used as alternative to intravenous anticoagulants. It includes apixaban, dabigatran, rivaroxaban and edoxaban.1 Some of the complications induced by these drugs are gastrointestinal haemorrhage, cerebral haemorrhage and rarely thrombocytopenia. We present a rare case report of a selective factor Xa inhibitor rivaroxaban, which induced thrombocytopenia in a case of deep vein thrombosis (DVT) of right lower limb. Drugs commonly used to prevent embolization of systemic circulation are warfarin and novel oral anticoagulants, such as rivaroxaban and dabigatran.

Postverta, Agrippa, Caesarea

The frequency of breech presentation at term is 3% among singletons. Greek physicians dreaded those births, as they frequently led to the death of mother, infant, or both. In Rome, surviving infants were named Agrippa (born with difficulty), and the goddess Postverta was revered for presiding over breech deliveries. To the antique procedures of embryotomy and hook for the dead infant, the Middle Ages added manoeuvres to turn and extract a living, albeit often traumatized infant. These manoeuvres were associated with asphyxia from cord prolapse or compression, fracture of legs, arms, or clavicles, cerebral haemorrhage, trauma to the cerebellum, tentorium, or pituitary stalk, and with torticollis and arm plexus palsy. The prototype of difficult birth, infants born feet-first were considered dangerous, and were neglected or killed in many cultures. Even after Caesarean section had lost most of its risk, conservative obstetricians still propagated vaginal delivery from breech presentation. Finally, at the beginning of the 21st century, large randomized trials and population-based studies proved that Caesarean delivery was safe for the mother and highly beneficial for the child, making vaginal delivery from breech presentation obsolete.

ASSESSMENT OF ASSOCIATION OF DEMOGRAPHIC CHARACTERISTICS, DIET AND DISEASE WITH HAEMORRHAGIC STROKE AND FACTORS CAUSING STROKE LEADING TO CEREBRAL HAEMORRHAGE IN MALE PATIENTS IN QUETTA, BALOCHISTAN, PAKISTAN

Objectives. This study aimed to assess and make a pattern of factors causing stroke leading to cerebral haemorrhage in male patients as well as to assess association of demographic characteristics, diet and disease with haemorrhagic stroke in Quetta, Balochistan, Pakistan. Methods. In a cross sectional questionnaire based interviewing study, a questionnaire was designed to access the pattern of factors causing stroke leading to cerebral haemorrhage in male patients. Total 339 cases (adult male who had haemorrhagic stroke) were identified from two government and four private hospitals in Quetta City, Province Balochistan, Pakistan. The study was conducted within the time period of 9 months, from March to November, 2015. The data was piloted and then final data was analysed by using IBM SPSS 22. Results. In demographic characteristic study of patients, majority 219 (64.6%) were among the age group between 51 years and above, 330 (97.3%) were married, majority 186 (54.9%) were having urban residence and 277 (81.7%) were having own residence ownership, 127 (37.5%) were having addiction to smoking and 120 (35.4%) were addicted to tobacco and snuff. 124 (36.6%) were reluctant to mention whether their patients were either smokers or not. Among total 339 patients, majority 284 (83.8%) were not doing physical exercise routinely or if they were recommended by the physician. Among the 339 patients, all 339 (100%) of patients selected the multiple options among all given options (headache, unconscious/loss of consciousness, pain in neck). Conclusions. Demographic characteristics, low level of education, low income, urban residence in combined family setup, married, increased number of children are associated with hemorrhagic stroke. Smoking, tobacco and snuffing may also cause stroke. Lack of physical exercise, past history of stroke, diabetes mellitus, cardiovascular disease, hypertension (personal or family) of any type does not significantly cause stroke but may increase the risk of stroke. The order of events suddenly happened to the hemorrhagic patients are headache, pain in neck, vomiting and finally state of unconsciousness.

Risk of Thromboembolic Disease and Hemorrhage in Patients with Multiform Glioblastoma

Introduction: Glioblastoma Multiforme (GBM) is the most frequent malignant brain tumor, with an aggressive course and a short life expectancy despite standard treatment (chemotherapy and radiotherapy). The possibility of the development of Thrombotic Events (VTE) with this type of cancer is frequent. We designed this study to determine the risk of presenting VTE and hemorrhagic events in patients affected by GBM. Methods: Observational retrospective study of patients with GBM diagnosis at the General University Hospital of Ciudad Real between 2012 and 2015. The demographic characteristics of patients were studied, predictive models were compared, and a survival analysis was performed. Results: 77 patients were studied, 42 (55.3%)/34 (44.7%), men and women respectively, with an average age of 66.42 years. 13 (16.9%) presented VTE; of which 10 (61.54%) in the form of Deep Venous Thrombosis (DVT), 3 (23.08%) Pulmonary Embolism (PE) and 2 (15.38%) mixed events. The quality of life according to the performance status ECOG scale at the moment of diagnosis was 1 in 42 (15.38%) patients, and at the time of VTE, 5 (41.7%) had a value of 2, and 4 (33.3.3 %) registered 3. In the group that developed VTE according to the predictive model of risk for thrombosis in Khorana 5 (38.5%) had low risk and 8 (61.5%) intermediate; on the ASCO 2013 modified scale 5 (38.5%) had an Intermediate risk and 8 (61.5%) high. With a median, 1 year follow-up, 64 (84.2%) patients died, with an average time after the diagnosis of 279.09 days (216.6-341.6) (SE 31,8). 2 (2.6%) of the patients presented a greater haemorrhagic event and 7 (7.9%) cerebral haemorrhage, of which 4 (44.4%) had prophylactic Low Molecular Weight Heparins (LMWHs). In the survival analysis of Kaplan Meyer, patients who received prophylactic treatment with LMWHs had a higher survival rate with an average of 298.5 days compared to 239.3 of those who did not (p >0.05). There were no significant variables in the multivariate analysis for thrombotic or haemorrhagic events. Conclusion and Discussion: The demographic and clinical characteristics of our patients were similar to those reported in other international publications. The predictive scale of Khorana was not validated in our study, in contrast, the modified ASCO 2013 scale was closer to our results. The creation of a precise predictive model would help to delineate the benefit of prophylactic anticoagulation in high-risk patients. Long-term prophylaxis with LMWHs has demonstrated a reduction of thrombotic events without significantly increasing the fatal haemorrhagic episodes, also demonstrating greater long-term survival, independent of thrombotic events. Randomized prospective studies are needed to demonstrate its benefits.