Pharmacodynamic Comparison of Two Aspirin Formulations in the Caribbean: The ARC Study.

INTRODUCTION: This prospective, single-arm, crossover pharmacodynamic study assessed the effect of Bayer® low-dose enteric-coated aspirin 81 mg tablets (LD EC-ASA) (Bayer AG, Leverkusen, North Rhine-Westphalia, Germany) compared to Vazalore® low-dose phospholipid-aspirin liquid-filled 81 mg capsules (LD PL-ASA) (PLx Pharma Inc., Sparta, NJ, USA) on platelet reactivity with respect to aspirin reaction units (ARU). METHODS: Forty-seven healthy volunteers were recruited. Platelet function was evaluated with the VerifyNow™ ARU assay (Werfen, Bedford, MA, USA) and assessed post-initiation of Bayer® LD EC-ASA daily for 14 days, with a washout period of 28 days, followed by Vazalore® LD PL-ASA daily for 14 days, again followed by ARU testing. RESULTS: Participants on LD EC-ASA had a mean ARU score of 426, with 19.1% of participants having an ARU > 550; patients on LD PL-ASA derived a mean ARU score of 435, with 14.9% achieving an ARU > 550. There were no significant differences in aspirin resistance (ARU > 550) according to the formulation (Bayer® LD EC-ASA vs. Vazalore® LD PL-ASA) used. Aspirin resistance was independent of ethnicity regardless of the formulation used. In addition, there were no significant associations between body surface area (BSA) and Bayer® LD EC-ASA ARU value (p value 0.788) or Vazalore® LD PL-ASA ARU value (p value 0.477). No patients experienced any serious adverse events or treatment-emergent adverse events. CONCLUSIONS: There were no significant differences in aspirin resistance between Bayer® LD EC-ASA and Vazalore® LD PL-ASA. This dedicated pharmacodynamic study could potentially be informative and applicable for Trinidadian patients on dual antiplatelet therapy (DAPT). Further studies are required to confirm these exploratory findings. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT06228820, prospectively registered 1/18/2024.

Effectiveness and Safety of Left Distal Transradial Access in Coronary Procedures in the Caribbean.

INTRODUCTION: This retrospective study investigated the effectiveness and safety of left distal transradial access (LDTRA) in patients with cardiovascular disease in Trinidad undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). METHOD: Procedural parameters, including technical success and safety outcomes such as vascular complications and radial artery occlusion (RAO), were assessed in 111 consecutive patients undergoing CAG or PCI from January 2023 to June 2023 at the Eric Williams Medical Sciences Complex, Trinidad and Tobago. Eighty-eight patients underwent LDTRA, while 23 received left transradial access (LTRA). RESULTS: There was no difference in procedural success with LDTRA compared to LTRA, 90.9% vs. 100%, p-value 0.202, non-significant (ns). LDTRA was associated with shorter fluoroscopy times (8.4 ± 6.8 minutes vs. 12.4 ± 7.7 minutes, p-value = 0.02), procedural duration (26.7 ± 18 minutes vs. 35.8 ± 20 minutes, p-value = 0.04), and hemostasis time (142 ± 41 minutes vs. 186 ± 44 minutes, p-value < 0.05). There were no significant differences in procedural-related complications (8% for LDTRA vs. 4.3% for LTRA, p-value = 0.476, ns). There were no reported cases of RAO. In the subgroup of patients with prior coronary artery bypass grafting (CABG), the fluoroscopy and procedure times were similar for both access sites; however, LDTRA was associated with a shorter hemostasis time (128 ± 30 minutes vs. 194 ± 39 minutes, p-value = 0.01). CONCLUSIONS: LDTRA is effective and safe for coronary procedures and is associated with a shorter hemostasis time. This study may prove clinically pertinent in a limited-resource Caribbean setting.

Correlation of RETINAL Artery Diameter with Coronary Artery Disease: The RETINA CAD Pilot Study-Are the Eyes the Windows to the Heart?

INTRODUCTION: This study aimed to determine whether there was any correlation between coronary artery disease (CAD) and retinal artery diameter at an academic tertiary medical center in Trinidad and Tobago. METHODS: This prospective study evaluated patients (n = 77) with recent invasive coronary angiography (CAG) and the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score who subsequently underwent optical coherence tomography-angiography (OCT-A) at the Eric Williams Medical Sciences Complex (EWMSC) from January 2021 to March 2021. Routine medical history and cardiovascular medications were also recorded. Spearman's rank correlation coefficient and Mann-Whitney U-tests were used to compare correlations and medians between groups. RESULTS: The average patient age was 57.8 years old, with the majority being male [n = 55 (71.4%)] and of South Asian ethnicity [n = 53 (68.8%)]. Retinal artery diameter was negatively correlated with the SYNTAX score (-0.332 for the right eye, p = 0.003 and -0.237 for the left eye, p = 0.038). A statistically significant relationship was also demonstrated in females and diabetic patients. There were no serious adverse events (SAEs). CONCLUSION: A significantly negative correlation was observed between retinal artery diameter and SYNTAX score. This study alludes to the practical use of optical coherence tomography-angiography (OCT-A) as a noninvasive diagnostic modality for patients with cardiovascular disease (CVD). Further large-scale, multicentric studies are required to confirm these exploratory findings. TRIAL REGISTRATION NUMBER: NCT04233619.

Effect of cocoa (Theobroma cacao L.) on platelet function testing profiles in patients with coronary artery disease: ECLAIR pilot study.

INTRODUCTION: This prospective pharmacodynamic nutraceutical study assessed the effect of a 1-week trial of 30 g/day of 65% cocoa (dark chocolate) (Theobroma cacao L.) consumption intervention on platelet reactivity. METHODS: Patients with stable coronary artery disease (CAD) (n=20) who were on maintenance dual antiplatelet therapy of aspirin (ASA) 81 mg/day and clopidogrel 75 mg/day were recruited. Platelet function was evaluated with the VerifyNow P2Y12 reaction unit (PRU) and aspirin reaction unit (ARU) assays (Werfen, Bedford, Massachusetts, USA) and assessed prior to initiation of and after a 1-week trial of 30 g/day of 65% cocoa consumption intervention. Results were compared with a paired t-test. RESULTS: Cocoa augmented the inhibitory effect of clopidogrel, demonstrated by a reduction of 11.9% (95% CI 5.7% to 18.0%, p value 0.001), significantly decreasing the PRU by 26.85 (95% CI 12.22 to 41.48, p value 0.001). The inhibitory effect of ASA was not impacted by cocoa, reflected by a non-significant reduction in ARU of 17.65 (95% CI 21.00 to 56.3, p value 0.351). No patients experienced any serious adverse events. CONCLUSIONS: Cocoa augmented the inhibitory effect of clopidogrel but not ASA. This nutraceutical study could be potentially informative and applicable for patients with stable CAD. Further long-term studies are required to confirm these exploratory findings. TRIAL REGISTRATION NUMBER: NCT04554901.

Africanised honey bee sting-induced ischaemic stroke.

The Africanised honey bee, vernacularly known as the 'killer bee', is a hybrid of the western honey bee species. These bees tend to be more aggressive with a greater tendency for swarm formation. Their stings are frequently encountered with a broad spectrum of clinical manifestations, ranging from local to systemic effects, even with recorded fatalities. We report a case of an elderly man, who experienced a cerebrovascular event confirmed by neuroimaging within 24 hours after a multitude of Africanised honey bee stings.

Clinical approach to the diagnosis and successful management of anti-NMDA receptor encephalitis when antibody testing is not possible.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a multistage illness that progresses from psychosis, memory deficits, seizures and language disintegration to a state of unresponsiveness with catatonic features often associated with abnormal movements, and autonomic and breathing instability. While the disorder predominantly affects children and young adults, and occurs with or without tumour association, the presence of a tumour (usually an ovarian teratoma) is dependent on the age, sex and ethnicity.Teratomas present more frequently in women older than 18 years, and are more predominant in black women than Caucasians. Here we present the case of a patient with probable anti-NMDA receptor encephalitis. She was subsequently found to have a mature teratoma of the ovary (dermoid cyst). Despite immune-modulated therapy, surgery was eventually performed to remove the cyst. This was met with a good clinical recovery.

Amyloid pathology and axonal injury after brain trauma.

OBJECTIVE: To image ß-amyloid (Aß) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and Aß are correlated, and compare the spatial distribution of Aß to Alzheimer disease (AD). METHODS: Patients 11 months to 17 years after moderate-severe TBI underwent (11)C-Pittsburgh compound B ((11)C-PiB)-PET, structural and diffusion MRI, and neuropsychological examination. Healthy aged controls and patients with AD underwent PET and structural MRI. Binding potential (BPND) images of (11)C-PiB, which index Aß plaque density, were computed using an automatic reference region extraction procedure. Voxelwise and regional differences in BPND were assessed. In TBI, a measure of white matter integrity, fractional anisotropy, was estimated and correlated with (11)C-PiB BPND. RESULTS: Twenty-eight participants (9 with TBI, 9 controls, 10 with AD) were assessed. Increased (11)C-PiB BPND was found in TBI vs controls in the posterior cingulate cortex and cerebellum. Binding in the posterior cingulate cortex increased with decreasing fractional anisotropy of associated white matter tracts and increased with time since injury. Compared to AD, binding after TBI was lower in neocortical regions but increased in the cerebellum. CONCLUSIONS: Increased Aß burden was observed in TBI. The distribution overlaps with, but is distinct from, that of AD. This suggests a mechanistic link between TBI and the development of neuropathologic features of dementia, which may relate to axonal damage produced by the injury.

Thalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage.

BACKGROUND: Traumatic brain injury can trigger chronic neuroinflammation, which may predispose to neurodegeneration. Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo. FINDINGS: Using [(11)C]-PK11195 positron emission tomography, a marker of microglial activation, we previously demonstrated thalamic inflammation up to 17 years after traumatic brain injury. Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage. CONCLUSIONS: These findings support a link between axonal damage and persistent inflammation after brain injury.

Increased microglia activation in neurologically asymptomatic HIV-infected patients receiving effective ART.

BACKGROUND: Neuroinflammation plays an important role in HIV-associated neurological disorders; however, its role prior to the onset of symptomatic disease is unclear. We imaged microglial activation, the hallmark of neuroinflammation, in asymptomatic HIV-infected patients on effective combination ART. METHODS: Seven neurologically and cognitively asymptomatic adults with chronic HIV-infection and nine healthy volunteers were investigated with [11C]-PK11195 PET, a marker of translocator protein (TSPO) expressed by activated microglia. In the HIV-infected patients, cognitive speed, accuracy and executive function were also assessed. Between-group differences in [11C]-PK11195 binding potential were localized throughout the brain with statistical parametric mapping (SPM) and associations between levels of [11C]-PK11195 binding and cognitive performance were interrogated using linear regression modelling. RESULTS: In HIV-infected patients, Statistical parametric mapping detected clusters of significantly increased [11C]-PK11195 binding in corpus callosum (P = 0.001), anterior cingulate (P = 0.001), posterior cingulate (P = 0.008) and temporal (P = 0.026) and frontal (P = 0.038) areas. Cognitive functions were intact in the HIV group, however, a significant association between greater [11C]-PK11195 binding and poorer executive function performance was observed in the anterior cingulate (P = 0.031), corpus callosum and posterior cingulate (P = 0.001). CONCLUSION: Despite effective control of HIV infection, neuroinflammation, as evidenced by the presence of focal cortical areas of activated microglia, occurs in asymptomatic HIV-infected patients and levels correlate with poorer executive performance. Further studies are needed to establish whether detection of activated microglia in HIV-infected patients represents a marker of future neurocognitive decline.

Reference region automatic extraction in dynamic [(11)C]PIB.

The positron emission tomography (PET) radiotracer [(11)C]Pittsburgh Compound B (PIB) is a marker of amyloid plaque deposition in brain, and binding potential is usually quantified using the cerebellum as a reference where the specific binding is negligible. The use of the cerebellum as a reference, however, has been questioned by the reported cerebellar [(11)C]PIB retention in familial Alzheimer's disease (AD) subjects. In this work, we developed a supervised clustering procedure for the automatic extraction of a reference region in [(11)C]PIB studies. Supervised clustering models each gray matter voxel as the linear combination of three predefined kinetic classes, normal and lesion gray matter, and blood pool, and extract reference voxels in which the contribution of the normal gray matter class is high. In the validation with idiopathic AD subjects, supervised clustering extracted reference voxels mostly in the cerebellum that indicated little specific [(11)C]PIB binding, and total distribution volumes of the extracted region were lower than those of the cerebellum. Next, the methodology was applied to the familial AD cohort where the cerebellar amyloid load had been demonstrated previously, resulting in higher binding potential compared with that obtained with the cerebellar reference. The supervised clustering method is a useful tool for the accurate quantification of [(11)C]PIB studies.

First reported case of posterior reversible encephalopathy syndrome occurring in a weightlifter.

Posterior reversible encephalopathy syndrome (PRES) is an increasingly well recognised clinical and radiological condition. Here we report on the first known published case of PRES in a weightlifter. We present a 34-year-old man with acute onset visual disturbance and expressive dysphasia which occurred after an intensive gym session.

Acute HCV/HIV coinfection is associated with cognitive dysfunction and cerebral metabolite disturbance, but not increased microglial cell activation.

BACKGROUND: Microglial cell activation and cerebral function impairment are described in both chronic hepatitis C viral (HCV) and Human-Immune-Deficiency viral (HIV) infections. The aim of this study was to investigate the effect of acute HCV infection upon cerebral function and microglial cell activation in HIV-infected individuals. METHODS: A case-control study was conducted. Subjects with acute HCV and chronic HIV coinfection (aHCV) were compared to matched controls with chronic HIV monoinfection (HIVmono). aHCV was defined as a new positive plasma HCV RNA within 12 months of a negative RNA test. Subjects underwent neuro-cognitive testing (NCT), cerebral proton magnetic resonance spectroscopy ((1)H-MRS) and positron emission tomography (PET) using a (11)C-radiolabeled ligand (PK11195), which is highly specific for translocator protein 18 kDA receptors on activated microglial cells. Differences between cases and controls were assessed using linear regression modelling. RESULTS: Twenty-four aHCV cases completed NCT and (1)H-MRS, 8 underwent PET. Of 57 HIVmono controls completing NCT, 12 underwent (1)H-MRS and 8 PET. Subjects with aHCV demonstrated on NCT, significantly poorer executive function (mean (SD) error rate 26.50(17.87) versus 19.09(8.12), p = 0.001) and on (1)H-MRS increased myo-inositol/creatine ratios (mI/Cr, a marker of cerebral inflammation) in the basal ganglia (ratio of 0.71(0.22) versus 0.55(0.23), p = 0.03), compared to subjects with HIVmono. On PET imaging, no difference in (11)C-PK11195 binding potential (BP) was observed between study groups (p>0.10 all cerebral locations), however lower BPs were associated with combination antiretroviral therapy (cART) use in the parietal (p = 0.01) and frontal (p = 0.03) cerebral locations. DISCUSSION: Poorer cognitive performance and disturbance of cerebral metabolites are observed in subjects with aHC,V compared to subjects with HIVmono. Higher (11)C-PK11195 BP was not observed in subjects with aHCV, but was observed in subjects not on cART.

Inflammation after trauma: microglial activation and traumatic brain injury.

OBJECTIVE: Patient outcome after traumatic brain injury (TBI) is highly variable. The underlying pathophysiology of this is poorly understood, but inflammation is potentially an important factor. Microglia orchestrate many aspects of this response. Their activation can be studied in vivo using the positron emission tomography (PET) ligand [11C](R)PK11195 (PK). In this study, we investigate whether an inflammatory response to TBI persists, and whether this response relates to structural brain abnormalities and cognitive function. METHODS: Ten patients, studied at least 11 months after moderate to severe TBI, underwent PK PET and structural magnetic resonance imaging (including diffusion tensor imaging). PK binding potentials were calculated in and around the site of focal brain damage, and in selected distant and subcortical brain regions. Standardized neuropsychological tests were administered. RESULTS: PK binding was significantly raised in the thalami, putamen, occipital cortices, and posterior limb of the internal capsules after TBI. There was no increase in PK binding at the original site of focal brain injury. High PK binding in the thalamus was associated with more severe cognitive impairment, although binding was not correlated with either the time since the injury or the extent of structural brain damage. INTERPRETATION: We demonstrate that increased microglial activation can be present up to 17 years after TBI. This suggests that TBI triggers a chronic inflammatory response particularly in subcortical regions. This highlights the importance of considering the response to TBI as evolving over time and suggests interventions may be beneficial for longer intervals after trauma than previously assumed.

Glutamate NMDA receptor dysregulation in Parkinson's disease with dyskinesias.

Levodopa-induced dyskinesias are a common complication of long-term therapy in Parkinson's disease. Although both pre- and post-synaptic mechanisms seem to be implicated in their development, the precise physiopathology of these disabling involuntary movements remains to be fully elucidated. Abnormalities in glutamate transmission (over expression and phosphorylation of N-methyl-D-aspartate receptors) have been associated with the development of levodopa-induced dyskinesias in animal models of Parkinsonism. The role of glutamate function in dyskinetic patients with Parkinson's disease, however, is unclear. We used (11)C-CNS 5161 [N-methyl-3(thyomethylphenyl)cyanamide] positron emission tomography, a marker of activated N-methyl-D-aspartate receptor ion channels, to compare in vivo glutamate function in parkinsonian patients with and without levodopa-induced dyskinesias. Each patient was assessed with positron emission tomography twice, after taking and withdrawal from levodopa. Striatal and cortical tracer uptake was calculated using a region of interest approach. In the 'OFF' state withdrawn from levodopa, dyskinetic and non-dyskinetic patients had similar levels of tracer uptake in basal ganglia and motor cortex. However, when positron emission tomography was performed in the 'ON' condition, dyskinetic patients had higher (11)C-CNS 5161 uptake in caudate, putamen and precentral gyrus compared to the patients without dyskinesias, suggesting that dyskinetic patients may have abnormal glutamatergic transmission in motor areas following levodopa administration. These findings are consistent with the results of animal model studies indicating that increased glutamatergic activity is implicated in the development and maintenance of levodopa-induced dyskinesias. They support the hypothesis that blockade of glutamate transmission may have a place in the management of disabling dyskinesias in Parkinson's disease.

Lesion identification using unified segmentation-normalisation models and fuzzy clustering.

In this paper, we propose a new automated procedure for lesion identification from single images based on the detection of outlier voxels. We demonstrate the utility of this procedure using artificial and real lesions. The scheme rests on two innovations: First, we augment the generative model used for combined segmentation and normalization of images, with an empirical prior for an atypical tissue class, which can be optimised iteratively. Second, we adopt a fuzzy clustering procedure to identify outlier voxels in normalised gray and white matter segments. These two advances suppress misclassification of voxels and restrict lesion identification to gray/white matter lesions respectively. Our analyses show a high sensitivity for detecting and delineating brain lesions with different sizes, locations, and textures. Our approach has important implications for the generation of lesion overlap maps of a given population and the assessment of lesion-deficit mappings. From a clinical perspective, our method should help to compute the total volume of lesion or to trace precisely lesion boundaries that might be pertinent for surgical or diagnostic purposes.