Multiple surgical resections for progressive IDH wildtype glioblastoma-is it beneficial?

PURPOSE: The role of repeat resection for recurrent glioblastoma (rGB) remains equivocal. This study aims to assess the overall survival and complications rates of single or repeat resection for rGB. METHODS: A single-centre retrospective review of all patients with IDH-wildtype glioblastoma managed surgically, between January 2014 and January 2022, was carried out. Patient survival and factors influencing prognosis were analysed, using Kaplan-Meier and Cox regression methods. RESULTS: Four hundred thirty-two patients were included, of whom 329 underwent single resection, 83 had two resections and 20 patients underwent three resections. Median OS (mOS) in the cohort who underwent a single operation was 13.7 months (95% CI: 12.7-14.7 months). The mOS was observed to be extended in patients who underwent second or third-time resection, at 22.9 months and 44.7 months respectively (p < 0.001). On second operation achieving > 95% resection or residual tumour volume of < 2.25 cc was significantly associated with prolonged survival. There was no significant difference in overall complication rates between primary versus second (p = 0.973) or third-time resections (p = 0.312). The use of diffusion tensor imaging (DTI) guided resection was associated with reduced post-operative neurological deficit (RR 0.37, p = 0.002), as was use of intraoperative ultrasound (iUSS) (RR 0.45, p = 0.04). CONCLUSIONS: This study demonstrates potential prolongation of survival for rGB patients undergoing repeat resection, without significant increase in complication rates with repeat resections. Achieving a more complete repeat resection improved survival. Moreover, the use of intraoperative imaging adjuncts can maximise tumour resection, whilst minimising the risk of neurological deficit.

A Murine Model of Maternal Micronutrient Deficiencies and Gut Inflammatory Host-microbe Interactions in the Offspring.

BACKGROUND & AIMS: Micronutrient deficiency (MND) (ie, lack of vitamins and minerals) during pregnancy is a major public health concern. Historically, studies have considered micronutrients in isolation; however, MNDs rarely occur alone. The impact of co-occurring MNDs on public health, mainly in shaping mucosal colonization by pathobionts from the Enterobacteriaceae family, remains undetermined due to lack of relevant animal models. METHODS: To establish a maternal murine model of multiple MND (MMND), we customized a diet deficient in vitamins (A, B12, and B9) and minerals (iron and zinc) that most commonly affect children and women of reproductive age. Thereafter, mucosal adherence by Enterobacteriaceae, the associated inflammatory markers, and proteomic profile of intestines were determined in the offspring of MMND mothers (hereafter, low micronutrient [LM] pups) via bacterial plating, flow cytometry, and mass spectrometry, respectively. For human validation, Enterobacteriaceae abundance, assessed via 16s sequencing of 3-month-old infant fecal samples (n = 100), was correlated with micronutrient metabolites using Spearman's correlation in meconium of children from the CHILD birth cohort. RESULTS: We developed an MMND model and reported an increase in colonic abundance of Enterobacteriaceae in LM pups at weaning. Findings from CHILD cohort confirmed a negative correlation between Enterobacteriaceae and micronutrient availability. Furthermore, pro-inflammatory cytokines and increased infiltration of lymphocyte antigen 6 complex high monocytes and M1-like macrophages were evident in the colons of LM pups. Mechanistically, mitochondrial dysfunction marked by reduced expression of nicotinamide adenine dinucleotide (NAD)H dehydrogenase and increased expression of NAD phosphate oxidase (Nox) 1 contributed to the Enterobacteriaceae bloom. CONCLUSION: This study establishes an early life MMND link to intestinal pathobiont colonization and mucosal inflammation via damaged mitochondria in the offspring.

Prevalence and clinical associations of mitral and aortic regurgitation in patients with aortic stenosis.

BACKGROUND: Most guidelines directing clinicians to manage valve disease are directed at single valve lesions. Limited data exists to direct our understanding of how concomitant valve disease impacts the left ventricle (LV). METHODS: We identified 2817 patients with aortic stenosis (AS) from the echocardiography laboratory database between September 2012 and June 2018 who had a LV ejection fraction (EF) ≥50%. LV mass, LV mass index, LV systolic pressure (systolic blood pressure + peak aortic gradient). Covariates were collected from the electronic medical record. Multi-variate analysis of covariance was used to generate adjusted comparisons. RESULTS: Our population was 66% female, 17% African-American with a mean age of 65 years. Of note, 7.3% were noted to have significant (moderate/severe) aortic regurgitation (AR), and 11% had significant (moderate/severe) mitral regurgitation (MR). Adjusting for covariates at different levels, significant MR had a much stronger association with heart failure compared to those with significant AR (p < .001 vs. p = .313, respectively) at all levels of adjustment. Both significant mitral and AR exhibited an association with increasing left ventricular mass, even with adjustment for baseline demographics and clinical features (p < .001 vs. p = .007, respectively). CONCLUSION: In patients with AS, 16% also experience at least moderate MR or AR. Further, significant MR has a stronger association with heart failure than significant AR, even though both increase left ventricular mass. Those with moderate AS and significant MR or AR experience similar or higher levels of heart failure compared to severe AS without regurgitation. Mixed valve disease merits further studies to direct longitudinal management.

Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex.

Diverse neocortical GABAergic neurons specialize in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III mGluRs by L-AP4 changes GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in 2 distinct dendritic spine-innervating GABAergic interneurons recorded in vitro in human neocortex. Calbindin-positive double bouquet cells (DBCs) had columnar "horsetail" axons descending through layers II-V innervating dendritic spines (48%) and shafts, but not somata of pyramidal and nonpyramidal neurons. Parvalbumin-expressing dendrite-targeting cell (PV-DTC) axons extended in all directions innervating dendritic spines (22%), shafts (65%), and somata (13%). As measured, 20% of GABAergic neuropil synapses innervate spines, hence DBCs, but not PV-DTCs, preferentially select spine targets. Group III mGluR activation paradoxically increased the frequency of sIPSCs in DBCs (to median 137% of baseline) but suppressed it in PV-DTCs (median 92%), leaving the amplitude unchanged. The facilitation of sIPSCs in DBCs may result from their unique GABAergic input being disinhibited via network effect. We conclude that dendritic spines receive specialized, diverse GABAergic inputs, and group III mGluRs differentially regulate GABAergic synaptic transmission to distinct GABAergic cell types in human cortex.

Hypertension Across a Woman's Life Cycle.

PURPOSE OF REVIEW: We reviewed the effects of hypertension and the means to prevent and treat it across the spectrum of a woman's lifespan and identified gaps in sex-specific mechanisms contributing to hypertension in women that need to be addressed. RECENT FINDINGS: Hypertension continues to be an important public health problem for women across all life stages from adolescence through pregnancy, menopause, and older age. There remain racial, ethnic, and socioeconomic differences in hypertension rates not only overall but also between the sexes. Blood pressure cutoffs during pregnancy have not been updated to reflect the 2017 ACC/AHA changes due to a lack of data. Additionally, the mechanisms behind hypertension development in menopause, including sex hormones and genetic factors, are not well understood. In the setting of increasing inactivity and obesity, along with an aging population, hypertension rates are increasing in women. Screening and management of hypertension throughout a women's lifespan are necessary to reduce the burden of cardiovascular disease, and further research to understand sex-specific hypertension mechanisms is needed.

Surgical and oncological score to estimate the survival benefit of resection and chemoradiotherapy in elderly (≥70 years) glioblastoma patients: A preliminary analysis.

Background: Elderly patients with glioblastoma are perceived to face a poor prognosis with perceptions surrounding older age and a relative lack of randomized data contributing. This study evaluated survival prognosticators in elderly glioblastoma patients to more accurately guide their treatment. Methods: The records of 169 elderly (≥70 years) patients with a new diagnosis of glioblastoma who had undergone neurosurgical intervention were retrospectively examined for patient sex, age, performance status, comorbidities, MGMT promoter methylation, surgical intervention, and chemoradiation regime. The adjusted survival impact of these factors was determined using Cox proportional hazards model and used to devise a two-stage scoring system to estimate patient survival at the stage of surgical (Elderly Glioblastoma Surgical Score, EGSS) and oncological management (Elderly Glioblastoma Oncological Score, EGOS). Results: The median overall survival (mOS) of the cohort was 28.8 weeks. Gross-total and subtotal resection were associated with improved survival compared to biopsy alone (respective mOS 65.3 and 28.1 vs 15.7 weeks, P < .001). Hypofractionated radiotherapy (40Gy in 15 fractions) with Temozolomide was noninferior to the Stupp protocol, P = .72. Exploratory subgroup analysis revealed a significant benefit of Temozolomide-based approaches in MGMT-methylated patients as well as a trend towards improved survival in MGMT-unmethylated patients. Our EGSS and EGOS scores successfully estimated survival in this retrospective cohort with 65% and 73% accuracy. Conclusions: Where appropriate and safe, elderly glioblastoma patients may benefit from surgical resection and combined chemoradiotherapy with Temozolomide. The proposed EGSS and EGOS scores take into account important prognostic factors to help guide which patients should receive such treatment.

Newer Drugs to Reduce High Blood Pressure and Mitigate Hypertensive Target Organ Damage.

PURPOSE OF REVIEW: This review aims to investigate the blood pressure (BP)-lowering effects of emerging drugs developed to treat diabetic kidney disease and heart failure (HF). We summarize the potential pathophysiological mechanisms responsible for mitigating hypertensive target organ damage and evaluating the available clinical data on these newer drugs. RECENT FINDINGS: Nonsteroidal dihydropyridine-based mineralocorticoid receptor antagonists (MRAs), dual angiotensin II receptor-neprilysin inhibitors (valsartan with sacubitril), sodium-glucose cotransporter 2 inhibitors (SGLT2i), and soluble guanylate cyclase stimulators are new classes of chemical agents that have distinct mechanisms of action and have been shown to be effective for the treatment of cardiovascular (CV) disease (CVD), HF, and type 2 diabetes mellitus (T2D). These drugs can be used either alone or in combination with other antihypertensive and CV drugs. Among these, SGLT2i and valsartan with sacubitril offer new avenues to reduce CVD mortality. SGLT2i have a mild-to-moderate effect on BP lowering with a favorable effect on CV and renal hemodynamics and have been shown to produce a significant reduction in the incidence of major adverse CVD events (as monotherapy or add-on therapy) compared with controls (placebo or non-SGLT2i treatment). Most of the participants in these studies had hypertension (HTN) at baseline and were receiving antihypertensive therapy, including renin-angiotensin system blockers. The combination of valsartan with sacubitril also lowers BP in the short term and has demonstrated a striking reduction in CVD mortality and morbidity in HF patients with a reduced left ventricular ejection fraction. If widely adopted, these novel therapeutic agents hold significant promise for reducing the public health burden posed by HTN and CVD. Based on the results of several clinical trials and considering the high prevalence of HTN and T2D, these new classes of agents have emerged as powerful therapeutic tools in managing and lowering the BP of patients with diabetic kidney disease and HF.

Tonic GABAA Receptor-Mediated Currents of Human Cortical GABAergic Interneurons Vary Amongst Cell Types.

Persistent anion conductances through GABAA receptors (GABAARs) are important modulators of neuronal excitability. However, it is currently unknown how the amplitudes of these currents vary among different cell types in the human neocortex, particularly among diverse GABAergic interneurons. We have recorded 101 interneurons in and near layer 1 from cortical tissue surgically resected from both male and female patients, visualized 84 of them and measured tonic GABAAR currents in 48 cells with an intracellular [Cl-] of 65 mm and in the presence of 5 µm GABA. We compare these tonic currents among five groups of interneurons divided by firing properties and four types of interneuron defined by axonal distributions; rosehip, neurogliaform, stalked-bouton, layer 2-3 innervating and a pool of other cells. Interestingly, the rosehip cell, a type of interneuron only described thus far in human tissue, and layer 2-3 innervating cells exhibit larger tonic currents than other layer 1 interneurons, such as neurogliaform and stalked-bouton cells; the latter two groups showing no difference. The positive allosteric modulators of GABAARs allopregnanolone and DS2 also induced larger current shifts in the rosehip and layer 2-3 innervating cells, consistent with higher expression of the δ subunit of the GABAAR in these neurons. We have also examined how patient parameters, such as age, seizures, type of cancer and anticonvulsant treatment may alter tonic inhibitory currents in human neurons. The cell type-specific differences in tonic inhibitory currents could potentially be used to selectively modulate cortical circuitry.SIGNIFICANCE STATEMENT Tonic currents through GABAA receptors (GABAARs) are a potential therapeutic target for a number of neurologic and psychiatric conditions. Here, we show that these currents in human cerebral cortical GABAergic neurons display cell type-specific differences in their amplitudes which implies differential modulation of their excitability. Additionally, we examine whether the amplitudes of the tonic currents measured in our study show any differences between patient populations, finding some evidence that age, seizures, type of cancer, and anticonvulsant treatment may alter tonic inhibition in human tissue. These results advance our understanding of how pathology affects neuronal excitability and could potentially be used to selectively modulate cortical circuitry.

Diffusion tractography for awake craniotomy: accuracy and factors affecting specificity.

INTRODUCTION: Despite evidence of correspondence with intraoperative stimulation, there remains limited data on MRI diffusion tractography (DT)'s sensitivity to predict morbidity after neurosurgical oncology treatment. Our aims were: (1) evaluate DT against subcortical stimulation mapping and performance changes during and after awake neurosurgery; (2) evaluate utility of early post-operative DT to predict recovery from post-surgical deficits. METHODS: We retrospectively reviewed our first 100 awake neurosurgery procedures using DT- neuronavigation. Intra-operative stimulation and performance outcomes were assessed to classify DT predictions for sensitivity and specificity calculations. Post-operative DT data, available in 51 patients, were inspected for tract damage. RESULTS: 91 adult brain tumor patients (mean 49.2 years, 43 women) underwent 100 awake surgeries with subcortical stimulation between 2014 and 2019. Sensitivity and specificity of pre-operative DT predictions were 92.2% and 69.2%, varying among tracts. Post-operative deficits occurred after 41 procedures (39%), but were prolonged (> 3 months) in only 4 patients (4%). Post-operative DT in general confirmed surgical preservation of tracts. Post-operative DT anticipated complete recovery in a patient with supplementary motor area syndrome, and indicated infarct-related damage to corticospinal fibers associated with delayed, partial recovery in a second patient. CONCLUSIONS: Pre-operative DT provided very accurate predictions of the spatial location of tracts in relation to a tumor. As expected, however, the presence of a tract did not inform its functional status, resulting in variable DT specificity among individual tracts. While prolonged deficits were rare, DT in the immediate post-operative period offered additional potential to monitor neurological deficits and anticipate recovery potential.

Associations between physical activity, sedentary behaviour and left ventricular structure and function from the Echocardiographic Study of Latinos (ECHO-SOL).

OBJECTIVE: The cross-sectional association between accelerometer-measured physical activity (PA), sedentary behaviour (SB) and cardiac structure and function is less well described. This study's primary aim was to compare echocardiographic measures of cardiac structure and function with accelerometer measured PA and SB. METHODS: Participants included 1206 self-identified Hispanic/Latino men and women, age 45-74 years, from the Echocardiographic Study of Latinos. Standard echocardiographic measures included M-mode, two-dimensional, spectral, tissue Doppler and myocardial strain. Participants wore an Actical accelerometer at the hip for 1 week. RESULTS: The mean±SE age for the cohort was 56±0.4 years, 57% were women. Average moderate to vigorous PA (MVPA) was 21±1.1 min/day, light PA was 217±4.2 min/day and SB was 737±8.1 min/day. Both higher levels of light PA and MVPA (min/day) were associated with lower left ventricular (LV) mass index (LVMI)/end-diastolic volume and a lower E/e' ratio. Higher levels of MVPA (min/day) were associated with better right ventricular systolic function. Higher levels of SB were associated with increased LVMI. In a multivariable linear regression model adjusted for demographics and cardiovascular disease modifiable factors, every 10 additional min/day of light PA was associated with a 0.03 mL/m2 increase in left atrial volume index (LAVI) (p<0.01) and a 0.004 cm increase in tricuspid annular plane systolic excursion (p<0.01); every 10 additional min/day of MVPA was associated with a 0.18 mL/m2 increase in LAVI (p<0.01) and a 0.24% improvement in global circumferential strain (p<0.01). CONCLUSIONS: Our findings highlight the potential positive association between the MVPA and light PA on cardiac structure and function.

Frequent Assembly of Chimeric Complexes in the Protein Interaction Network of an Interspecies Yeast Hybrid.

Hybrids between species often show extreme phenotypes, including some that take place at the molecular level. In this study, we investigated the phenotypes of an interspecies diploid hybrid in terms of protein-protein interactions inferred from protein correlation profiling. We used two yeast species, Saccharomyces cerevisiae and Saccharomyces uvarum, which are interfertile, but yet have proteins diverged enough to be differentiated using mass spectrometry. Most of the protein-protein interactions are similar between hybrid and parents, and are consistent with the assembly of chimeric complexes, which we validated using an orthogonal approach for the prefoldin complex. We also identified instances of altered protein-protein interactions in the hybrid, for instance, in complexes related to proteostasis and in mitochondrial protein complexes. Overall, this study uncovers the likely frequent occurrence of chimeric protein complexes with few exceptions, which may result from incompatibilities or imbalances between the parental proteomes.

Raman spectroscopy to differentiate between fresh tissue samples of glioma and normal brain: a comparison with 5-ALA-induced fluorescence-guided surgery.

OBJECTIVE: Raman spectroscopy is a biophotonic tool that can be used to differentiate between different tissue types. It is nondestructive and no sample preparation is required. The aim of this study was to evaluate the ability of Raman spectroscopy to differentiate between glioma and normal brain when using fresh biopsy samples and, in the case of glioblastomas, to compare the performance of Raman spectroscopy to predict the presence or absence of tumor with that of 5-aminolevulinic acid (5-ALA)-induced fluorescence. METHODS: A principal component analysis (PCA)-fed linear discriminant analysis (LDA) machine learning predictive model was built using Raman spectra, acquired ex vivo, from fresh tissue samples of 62 patients with glioma and 11 glioma-free brain samples from individuals undergoing temporal lobectomy for epilepsy. This model was then used to classify Raman spectra from fresh biopsies from resection cavities after functional guided, supramaximal glioma resection. In cases of glioblastoma, 5-ALA-induced fluorescence at the resection cavity biopsy site was recorded, and this was compared with the Raman spectral model prediction for the presence of tumor. RESULTS: The PCA-LDA predictive model demonstrated 0.96 sensitivity, 0.99 specificity, and 0.99 accuracy for differentiating tumor from normal brain. Twenty-three resection cavity biopsies were taken from 8 patients after supramaximal resection (6 glioblastomas, 2 oligodendrogliomas). Raman spectroscopy showed 1.00 sensitivity, 1.00 specificity, and 1.00 accuracy for predicting tumor versus normal brain in these samples. In the glioblastoma cases, where 5-ALA-induced fluorescence was used, the performance of Raman spectroscopy was significantly better than the predictive value of 5-ALA-induced fluorescence, which showed 0.07 sensitivity, 1.00 specificity, and 0.24 accuracy (p = 0.0009). CONCLUSIONS: Raman spectroscopy can accurately classify fresh tissue samples into tumor versus normal brain and is superior to 5-ALA-induced fluorescence. Raman spectroscopy could become an important intraoperative tool used in conjunction with 5-ALA-induced fluorescence to guide extent of resection in glioma surgery.

Relation of Low Normal Left Ventricular Ejection Fraction to Heart Failure Hospitalization in Blacks (From the Jackson Heart Study).

There is no clear consensus on a lower cutoff value for normal left ventricular ejection fraction (EF) and the prognostic implications of low normal EF (LNEF) are poorly understood, particularly in Blacks. Therefore, we investigated the association of LNEF and incident heart failure (HF) in a community-based cohort of Blacks. We studied 3,669 participants (mean age 54 years, 63% women) of the Jackson Heart Study without prevalent HF or coronary heart disease (CHD). Participants were divided into three groups: (1) Reduced EF (<50%), (2) LNEF (≥50%, <55%), and (3) Normal EF (≥55%). There were 197 cases of incident HF hospitalizations over a median follow-up of 10 years (interquartile range 9.4 to 10). After adjustment for conventional risk factors and incident CHD, the LNEF group had a higher rate of incident HF hospitalization than the Normal EF group (HR 1.58, 95% CI 1.04 to 2.38, p<0.05). Furthermore, this relation remained statistically significant after additionally adjusting for LV mass index but was not significant after adjusting for LV diastolic dysfunction grade. In participants with LNEF with incident HF, 63% developed HF with reduced EF and 37% developed HF with preserved EF. In conclusion, LNEF is associated with higher risk of incident HF hospitalization in comparison with normal EF in a community-based cohort of Blacks. In those with LNEF who went on to develop HF, most cases were HF with reduced EF. These findings suggest that strategies are needed for risk stratification and management to improve outcomes in patients with LNEF.

Obstructive coronary artery disease with a coronary artery calcium score of 0: A case report.

Coronary artery calcium (CAC) scoring has emerged as a useful tool in identifying patients who may benefit from more aggressive risk factor modification and for prognostication. Although a CAC score of 0 is associated with a very low prevalence of obstructive epicardial coronary artery disease and low event rates, it can also provide a false sense of reassurance. We present a case of a 39-year-old woman with a CAC score of 0 obtained as part of a coronary computerized tomography angiography study that was ultimately found to have significant left anterior descending artery disease requiring percutaneous coronary intervention and a stent.

Impact of anatomical variations of the left ventricular outflow tract on stroke volume calculation by Doppler echocardiography in aortic stenosis.

BACKGROUND: Accurate calculation of stroke volume (SV) by Doppler echocardiography is important for the assessment of aortic stenosis (AS), which may be impacted by anatomical variations of left ventricular outflow tract (LVOT). METHODS: Patients with AS (n = 64) were studied using computed tomography (CT) and transthoracic echocardiography (TTE). Anatomical variations of LVOT areas were measured at (a) the aortic annulus (Aa ); (b) 5 mm (A5 ); and (c) 10 mm below the annulus (A10 ) by CT. LVOT diameters were also measured by 2D TTE at these three levels for calculation of LVOT areas. Stroke volumes (SV) were calculated using continuity equation. The impacts of anatomical variations of LVOT on SV calculation were evaluated. RESULTS: Anatomical LVOT area increased from Aa to A10 (5.0 ± 0.9 cm2 vs 5.8 ± 1.9 cm2 , P < .01). Differences between TTE-calculated LVOT areas and anatomical areas were most significant at A10 due to elongation of mediolateral diameters with variable changes in anteroposterior diameters (5.8 ± 1.9 cm2 vs 3.4 ± 1.1 cm2 , P < .001). Although mean calculated SV by TTE was not significant at different LVOT levels (Aa 69 ± 22 mL, vs A5 66 ± 21 mL, vs A10 66 ± 28 ± 22 mL, P > .05), the most significant variations in individuals were at A10 levels (ΔSV: 8.2 ± 6.4 mL, 12 ± 9%). CONCLUSION: Variations of LVOT anatomy in individuals with AS significantly impact the SV calculated by Doppler echocardiography. These features should be taken into account for AS diagnosis and a clinical decision-making for intervention.

Electrocardiographic myocardial injury and stroke mortality in the general population.

BACKGROUND: Recent evidence suggests a link between myocardial infarction and stroke risk, but it is unclear whether such risk exists with electrocardiographic myocardial injury in otherwise healthy individuals. Therefore, we explored the association of myocardial injury with stroke mortality in participants free of cardiovascular disease. METHODS: This analysis included 6017 participants (58.4 ± 13.4 years, 54.1% women, 50.3% white) from the Third National Health and Nutrition Examination Survey. Cardiac infarction/injury score (CIIS), a weighted scoring system composed of several electrocardiographic waveform components related to myocardial injury and ischemia, was used to define myocardial injury. Stroke mortality was ascertained using the National Death Index during follow-up. Multivariable adjusted Cox proportional hazard analysis was used to examine the association between baseline myocardial injury and risk of stroke mortality. RESULTS: Over a median follow-up of 14 years, 152 stroke deaths occurred. Stroke mortality was more common in those with than those without myocardial injury (3.8% vs. 2.1%, respectively; p = 0.0003). In a model adjusted for potential confounders, the myocardial injury was associated with a 44% increased risk of stroke mortality (HR (95%CI):1.44(1.02-2.03)). In a similar model, each 1 CIIS score point increase was associated with a 2% increase in the risk of stroke mortality (HR (95%CI):1.02 (1.00-1.04), p = 0.01). CONCLUSIONS: Electrocardiographic myocardial injury in cardiovascular disease-free adults is associated with an increased risk of stroke mortality suggesting a potential link between asymptomatic myocardial injury and risk of cardiac thromboembolism. Whether screening and management of myocardial injury would reduce such risk requires further investigation.

Impact of the Location of ST-T Abnormalities Accompanying Minor Q-Waves on the Definition of Prior Myocardial Infarction.

According to the Fourth Universal Definition of myocardial infarction (MI), the likelihood of a previous MI is increased when ST-T abnormalities exist with minor Q-waves in the same leads. Therefore, we examined whether differences in location of ST-T abnormalities in relation to minor Q-waves as part of the old MI definition impact the prevalence and prognostic significance of MI. This analysis included 7,878 participants with available baseline electrocardiogram (ECG) and follow-up data from the third National Health and Nutrition Examination Survey. Two ECG MI definitions were utilized; both were based on the standards of the Minnesota Code (MC) ECG Classification, and both incorporated major Q-waves but differed in whether major ST-T abnormalities and minor Q waves, as part of the definition, were in the same lead group (Standard MC-MI) or not (Fourth Universal MI). All-cause mortality and cardiovascular disease mortality were ascertained during 14 years (median). We found no difference between baseline prevalence of Standard MC-MI (3.48%; n = 274) and Fourth Universal MI (3.27%; n = 258), p = 0.46. Also, Standard MC-MI and Fourth Universal MI were similarly associated with increased risk of all-cause mortality (hazard ratio [95% confidence interval] 1.64 [1.42 to 1.90] and 1.61 [1.38 to 1.87], respectively; p value for differences in associations = 0.86), and cardiovascular disease mortality (hazard ratio [95% confidence interval] 1.99 [1.61 to 2.48] and 1.94 [1.56 to 2.42], respectively; p value for differences in associations = 0.84). In conclusion, the location of ST-T abnormalities accompanying minor Q-waves does not impact the prevalence or prognostic significance of a prior MI which raise doubts about the clinical impact of considering the location of ST-T in relation to minor Q-waves when defining an old MI.