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Research and Practice in Thrombosis and... Mar 2024A State of the Art lecture titled "Cancer and Arterial Thrombosis: Therapeutic Options" was presented at the International Society on Thrombosis and Haemostasis Congress...
A State of the Art lecture titled "Cancer and Arterial Thrombosis: Therapeutic Options" was presented at the International Society on Thrombosis and Haemostasis Congress in 2023. This State of the Art review delves into the complex relationship between cancer and arterial thromboembolism (ATE), encompassing acute coronary syndrome, ischemic strokes, and peripheral arterial disease. The burden of cancer-associated ATE is not well defined, but studies indicate elevated risks, particularly in the 6 months after a cancer diagnosis. Incidence varies among cancer subtypes, with lung cancer displaying the highest rates. Additionally, the pathophysiology of cancer-associated ATE involves a multifaceted interplay of cancer-induced hypercoagulopathy, cancer therapy-related thrombosis, and personal risk factor contributors. ATEs are clinically heterogeneous and in the context of cancer have particular mechanistic differences compared with ATE patients without cancer. This requires modifications in approach and tailored management considerations. Specific etiologies contributing to ATE, such as coronary vasospasm and non-bacterial-thrombotic endocarditis, need to be considered. The diagnosis of cancer alone usually does not contraindicate patients to standard guideline-based therapies for the management of ATE, although nuances in treatment may need to be considered in light of the underlying cancer. Atrial fibrillation in cancer patients further complicates the thrombotic landscape. Cancer patients with atrial fibrillation are at a higher risk of ATE, necessitating careful consideration of anticoagulation therapy as clinical benefits and bleeding risks need to be weighed. ATE may also be a presenting sign of underlying malignancy, which requires increased awareness and focused clinical evaluation for cancer in selected cases. Finally, we summarize relevant new data on this topic presented during the 2023 International Society on Thrombosis and Haemostasis Congress.
PubMed: 38660456
DOI: 10.1016/j.rpth.2024.102393 -
Journal of Neurosurgery Nov 2023Cerebral arterial vasospasm is a dreaded sequela of aneurysm rupture and can result in significant narrowing of the surrounding vasculature and subsequent cerebral...
OBJECTIVE
Cerebral arterial vasospasm is a dreaded sequela of aneurysm rupture and can result in significant narrowing of the surrounding vasculature and subsequent cerebral ischemia. Treatment interventions are associated with distinct side effect profiles, including the risk of thrombosis and worsened ischemia, which may be associated with increased mortality-especially in older adults. An improved understanding of the likelihood of vasospasm in elderly patients would enable clinicians and patients to better consider the risks and benefits of vasospasm prophylaxis in this vulnerable population. This retrospective chart review aimed to assess the relationship between age at onset and the incidence of cerebral vasospasm among patients treated at the University of North Carolina Medical Center with spontaneous aneurysmal subarachnoid hemorrhage (aSAH).
METHODS
Electronic health record data from the Epic Systems Corp. database, compiled by the Carolina Data Warehouse for Health, were analyzed for patients older than 18 years who were previously treated for an SAH secondary to aneurysm at the University of North Carolina Medical Center within the past 10 years, ranging from June 2011 through June 2021. Logistic regression was used to calculate odds ratios and to determine the association of age with the occurrence of vasospasm following aSAH.
RESULTS
Of the 386 cases analyzed, 149 patients (38.6%) were older than 65 years at the time of aSAH. A total of 192 of the 386 patients (49.7%) developed vasospasm within the first 3-21 days following aSAH. Among the patients who developed vasospasm, only 31 of 192 patients (16.1%) were older than 65 years at the time of aneurysm rupture. Odds ratio calculations revealed that older adults (> 65 years) were 8 times less likely to develop vasospasm compared to their younger counterparts (p < 0.0001; 95% CI 5.0-13.0).
CONCLUSIONS
This study found that older patients are less likely to develop cerebral vasospasm following aSAH than are younger individuals. Age-associated changes in arteriosclerosis, inflammatory responses, and CSF dynamics may mitigate vascular narrowing in response to aSAH. This finding suggests that the aSAH treatment and vasospasm prevention paradigms should be revised to minimize potentially unnecessary interventions and avoid adverse outcomes for older adults.
Topics: Humans; Aged; Subarachnoid Hemorrhage; Retrospective Studies; Vasospasm, Intracranial; Cerebral Infarction; Aneurysm, Ruptured
PubMed: 37119113
DOI: 10.3171/2023.3.JNS222720 -
Nature Communications Oct 2023Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been...
Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p < 5 × 10). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.26; 95%-CI: 1.20-1.31; p < 9.6 × 10) and IRX1 (rs12653958, OR: 1.17; 95%-CI: 1.12-1.22, p < 4.8 × 10) as candidate causal genes through integration of gene expression in disease relevant tissues. We further identified a likely causal detrimental effect of low fasting glucose levels on RP risk (r = -0.21; p-value = 2.3 × 10), and systematically highlighted drug repurposing opportunities, like the antidepressant mirtazapine. Our results provide the first robust evidence for a strong genetic contribution to RP and highlight a so far underrated role of α-adrenoreceptor signalling, encoded at ADRA2A, as a possible mechanism for hypersensitivity to catecholamine-induced vasospasms.
Topics: Humans; Genome-Wide Association Study; Ulcer; Raynaud Disease; Pain; Transcription Factors; Homeodomain Proteins; Receptors, Adrenergic, alpha-2
PubMed: 37828025
DOI: 10.1038/s41467-023-41876-5 -
Journal of the American Heart... Jul 2023Background Recent evidence implicates inflammation as a key driver in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH). Inducible nitric oxide...
Background Recent evidence implicates inflammation as a key driver in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH). Inducible nitric oxide synthase (iNOS) is one of the known major mediators of inflammation. We previously showed that an inhalational anesthetic, isoflurane, provides strong protection against delayed cerebral ischemia after SAH. Our current study aims to define the role of iNOS in isoflurane conditioning-induced protection against delayed cerebral ischemia in a mouse model of SAH. Methods and Results The experiments used 10- to 14-week-old male wild-type (C57BL/6) and iNOS global knockout mice. Anesthetic conditioning was initiated 1 hour after SAH with isoflurane 2% for 1 hour. Isoflurane-induced changes in iNOS expression were measured. N-(3-(aminomethyl) benzyl) acetamidine, a highly selective iNOS inhibitor, was injected intraperitoneally immediately after SAH and then daily. Vasospasm, microvessel thrombosis, and neurological assessment was performed. Data were analyzed by 1-way ANOVA and 2-way repeated measures ANOVA followed by Student Newman Keuls comparison test. Statistical significance was set at <0.05. Isoflurane conditioning downregulated iNOS expression in naïve and SAH mice. N-(3-(aminomethyl) benzyl) acetamidine attenuated large artery vasospasm and microvessel thrombosis and improved neurological deficits in wild-type animals. iNOS knockout mice were significantly resistant to vasospasm, microvessel thrombosis, and neurological deficits induced by SAH. Combining isoflurane with N-(3-(aminomethyl) benzyl) acetamidine did not offer extra protection, nor did treating iNOS knockout mice with isoflurane. Conclusions Isoflurane conditioning-induced delayed cerebral ischemia protection appears to be mediated by downregulating iNOS. iNOS is a potential therapeutic target to improve outcomes after SAH.
Topics: Mice; Male; Animals; Nitric Oxide Synthase Type II; Subarachnoid Hemorrhage; Isoflurane; Mice, Inbred C57BL; Brain Ischemia; Cerebral Infarction; Mice, Knockout; Vasospasm, Intracranial
PubMed: 37449587
DOI: 10.1161/JAHA.123.029975 -
Frontiers in Neurology 2024Methamphetamine (meth) is a potent and addictive central nervous system stimulant with increasing use. Stroke is one severe possible complication of meth use. Due to... (Review)
Review
Methamphetamine (meth) is a potent and addictive central nervous system stimulant with increasing use. Stroke is one severe possible complication of meth use. Due to high levels of manufacturing in Mexico, the western United States has experienced greater consequences of meth use. The literature reviewed herein is comprised of case studies and series, and it suggests that hemorrhagic stroke (including hypertensive-like intracerebral hemorrhage and aneurysmal subarachnoid hemorrhage), as opposed to ischemic stroke, is the more common type of neurovascular complication of meth use. Meth-related strokes are a particular concern for younger patients with stroke and may be a partial explanation for increasing stroke rates in this age group. We describe two cases (one intraparenchymal hemorrhage and one ischemic stroke) in young patients (<50 years old) with recent meth use to illustrate clinical characteristics and therapeutic considerations. There are several proposed pathophysiological explanations for meth-associated hemorrhagic stroke including an induced hypertensive surge, vasospasm, blood brain barrier breakdown, chronic hypertension, aneurysm development and rupture, and very rarely associated vasculitis. The increased risk of ischemic stroke related to meth use is less well supported in the literature, but this may, in part, be related to a lack of appropriately designed and powered research studies. Proposed mechanisms for ischemic stroke complications of meth use include those affecting blood vessels such as accelerated atherosclerosis, chronic hypertension, vasospasm, and vasculitis, plus mechanisms that affect the heart including cardiomyopathy, arrhythmias, and infective endocarditis (especially with injection drug use). Standard therapeutic interventions for acute stroke and approaches to secondary stroke prevention seem appropriate for meth-associated strokes, with the addition of abstinence from continued meth use. There is no evidence for any meth-specific stroke treatments. Finally, the prolonged duration of meth withdrawal is described. Larger, prospective studies of meth-related strokes are needed to allow for a better understanding and improved care for this often-devastating consequence of an increasingly prevalent cause of strokes in young patients.
PubMed: 38721123
DOI: 10.3389/fneur.2024.1397677 -
Brain Sciences Jul 2023Early brain injury (EBI) subsequent to subarachnoid hemorrhage (SAH) is strongly associated with delayed cerebral ischemia and poor patient prognosis. Based on... (Review)
Review
Early brain injury (EBI) subsequent to subarachnoid hemorrhage (SAH) is strongly associated with delayed cerebral ischemia and poor patient prognosis. Based on investigations into the molecular mechanisms underlying EBI, neurovascular dysfunction resulting from SAH can be attributed to a range of pathological processes, such as microvascular alterations in brain tissue, ionic imbalances, blood-brain barrier disruption, immune-inflammatory responses, oxidative stress, and activation of cell death pathways. Research progress presents a variety of promising therapeutic approaches for the preservation of neurological function following SAH, including calcium channel antagonists, endothelin-1 receptor blockers, antiplatelet agents, anti-inflammatory agents, and anti-oxidative stress agents. EBI can be mitigated following SAH through neuroprotective measures. To enhance our comprehension of the relevant molecular pathways involved in brain injury, including brain ischemia-hypoxic injury, neuroimmune inflammation activation, and the activation of various cell-signaling pathways, following SAH, it is essential to investigate the evolution of these multifaceted pathophysiological processes. Facilitating neural repair following a brain injury is critical for improving patient survival rates and quality of life.
PubMed: 37509013
DOI: 10.3390/brainsci13071083 -
Medical Gas Research 2024Sevoflurane has become an important volatile anesthetic in clinic and has been widely studied in recent years. Numerous studies have demonstrated the efficacy of... (Review)
Review
Sevoflurane has become an important volatile anesthetic in clinic and has been widely studied in recent years. Numerous studies have demonstrated the efficacy of sevoflurane in safeguarding against brain damage across various domains. For example, it has played a neuroprotective role in subarachnoid hemorrhage (SAH), traumatic brain injury, and ischemia/reperfusion injury. The ensuing critique will focus on the significance of sevoflurane in experimental SAH and shed light on the underlying mechanisms. The findings of the current investigation demonstrate that sevoflurane possesses neuroprotective capabilities and clarify that it effectively attenuates secondary damage resulting from SAH through anti-inflammatory and anti-apoptotic pathways. More specifically, sevoflurane is observed to mitigate arterial vasospasm, diminish microvascular thrombosis, and alleviate cerebral edema. In light of these discoveries, we maintain that sevoflurane exhibits significant promise in the management of SAH, and it merits additional investigation to facilitate its prompt clinical implementation. Therefore, a thorough understanding of the neuroprotective properties of sevoflurane is beneficial to exploring novel therapeutic solutions for SAH and providing clinicians with alternative treatment modalities.
Topics: Humans; Sevoflurane; Subarachnoid Hemorrhage; Apoptosis; Brain Injuries; Anti-Inflammatory Agents
PubMed: 37721248
DOI: 10.4103/2045-9912.379167 -
Neurology India 2023
Topics: Humans; Nimodipine; Atrial Fibrillation; Vasodilator Agents; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 37929447
DOI: 10.4103/0028-3886.388097 -
Stroke and Vascular Neurology Dec 2023The clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate...
BACKGROUND AND AIM
The clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate current expert opinions in neurointervention and therapeutic strategies of iatrogenic vasospasm during EVT.
METHODS
We conducted an anonymous international online survey (4 April 2023 to 15 May 2023) addressing treatment standards of neurointerventionalists (NIs) practising EVT. Several illustrative cases of patients with vasospasm during EVT were shown. Two study groups were compared according to the NI's opinion regarding the potential influence of vasospasm on patient outcome after EVT using descriptive analysis.
RESULTS
In total, 534 NI from 56 countries responded, of whom 51.5% had performed >200 EVT. Vasospasm was considered a complication potentially influencing the patient's outcome by 52.6% (group 1) whereas 47.4% did not (group 2). Physicians in group 1 more often added vasodilators to their catheter flushes during EVT routinely (43.7% vs 33.9%, p=0.033) and more often treated severe large-vessel vasospasm with vasodilators (75.3% vs 55.9%; p<0.001), as well as extracranial vasospasm (61.4% vs 36.5%, p<0.001) and intracranial medium-vessel vasospasm (27.1% vs 11.2%, p<0.001), compared with group 2. In case of a large-vessel vasospasm and residual and amenable medium-vessel occlusion during EVT, the study groups showed different treatment strategies. Group 2 continued the EVT immediately more often, without initiating therapy to treat the vasospasm first (9.6% vs 21.1%, p<0.001).
CONCLUSION
There is disagreement among NIs about the clinical relevance of vasospasm during EVT and its management. There was a higher likelihood of use of preventive and active vasodilator treatment in the group that perceived vasospasm as a relevant complication as well as differing interventional strategies for continuing an EVT in the presence of a large-vessel vasospasm.
PubMed: 38164618
DOI: 10.1136/svn-2023-002788