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We evaluated the utility of left atrial volume index (LAVI) and markers of coagulation and hemostatic activation (MOCHA) in cryptogenic stroke (CS) patients to identify those more likely to have subsequent diagnosis of atrial fibrillation (AF), malignancy or recurrent stroke during follow-up.Consecutive CS patients who met embolic stroke of undetermined source (ESUS) who underwent transthoracic echocardiography and outpatient cardiac monitoring following stroke were identified from the Emory cardiac registry. In a subset of consecutive patients, d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex and fibrin monomer (MOCHA panel) were obtained ≥2 weeks post-stroke and repeated ≥4 weeks later if abnormal; abnormal MOCHA panel was defined as ≥2 elevated markers which did not normalize when repeated. We assessed the predictive abilities of LAVI and the MOCHA panel to identify patients with subsequent diagnosis of AF, malignancy, recurrent stroke or the composite outcome during follow-up.Of 94 CS patients (mean age 64 ± 15 years, 54% female, 63% non-white, mean follow-up 1.4 ± 0.8 years) who underwent prolonged cardiac monitoring, 15 (16%) had new AF. Severe LA enlargement (vs normal) was associated with AF (P < .06). In 42 CS patients with MOCHA panel testing (mean follow-up 1.1 ± 0.6 years), 14 (33%) had the composite outcome and all had abnormal MOCHA. ROC analysis showed LAVI and abnormal MOCHA together outperformed either test alone with good predictive ability for the composite outcome (AUC 0.84).We report the novel use of the MOCHA panel in CS patients to identify a subgroup of patients more likely to have occult AF, occult malignancy or recurrent stroke during follow-up. A normal MOCHA panel identified a subgroup of CS patients at low risk for recurrent stroke on antiplatelet therapy. Further study is warranted to evaluate whether the combination of an elevated LAVI and abnormal MOCHA panel identifies a subgroup of CS patients who may benefit from early anticoagulation for secondary stroke prevention.

While the capacity of the olfactory epithelium (OE) to generate sensory neurons continues into middle age in mice, it is presumed that this regenerative potential is present throughout all developmental stages. However, little experimental evidence exists to support the idea that this regenerative capacity remains in late adulthood, and questions about the functionality of neurons born at these late stages remain unanswered. Here, we extend our previous work in the VNO to investigate basal rates of proliferation in the OE, as well as after olfactory bulbectomy (OBX), a commonly used surgical lesion. In addition, we show that the neural stem cell retains its capacity to generate mature olfactory sensory neurons in aged animals. Finally, we demonstrate that regardless of age, a stem cell in the OE, the horizontal basal cell (HBC), exhibits a morphological switch from a flattened, quiescent phenotype to a pyramidal, proliferative phenotype following chemical lesion in aged animals. These findings provide new insights into determining whether an HBC is active or quiescent based on a structural feature as opposed to a biochemical one. More importantly, it suggests that neural stem cells in aged mice are responsive to the same signals triggering proliferation as those observed in young mice.

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Introduction: We previously reported that markers of coagulation and hemostatic activation (MOCHA) have been associated with malignancy, venous thromboembolism (VTE) and hypercoagulable states in embolic stroke of undetermined source (ESUS) patients. The objective of our study was to identify independent predictors of these endpoints. Methods: Consecutive ESUS patients seen at the Emory Clinic from January 1, 2017 to June 30, 2019 underwent a MOCHA profile (d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer) and were followed prospectively for new diagnoses of malignancy, VTE, other defined hypercoagulable states and the composite outcome. Abnormal MOCHA was defined as ≥ 2 elevated markers. Multivariable analyses were performed to identify predictors of the composite outcome. Results: Of 188 patients (mean age 63 ±16 years, 59% female, 50% Caucasian) included in the study period, 25 (13%) had the composite outcome. The median time between ESUS to MOCHA testing was 45 days (IQR 23-88). Abnormal MOCHA profile was the only independent predictor of the composite outcome (OR 2.34, 1.64-3.32, p<0.001) (AUC 0.824); age, sex, race, any history of tobacco use, hypertension, diabetes, history of stroke, cortical stroke, migraine, and left atrial size were not predictive. Abnormal MOCHA had a 96% sensitivity, 32% positive predictive value and 99% negative predictive value for the composite outcome. Conclusions: This study confirms that a normal MOCHA profile in the post-acute time period can rule out ESUS patients with malignancy, VTE or other underlying hypercoagulable states.