Lambl's Excrescences: Association with Cerebrovascular Disease and Pathogenesis.

BACKGROUND: Lambl's excrescences (LEx) are detected by transesophageal echocardiography (TEE) and are characterized as thin, elongated, and hypermobile structures located at the leaflets' coaptation point of the heart valves. The association of LEx with cerebrovascular disease (CVD) is still undefined and yet patients with LEx and suspected CVD receive unproven effective antiplatelet or anticoagulant therapy or even undergo valve surgery. Also, the association of LEx with aging and atherogenic, inflammatory, or thrombogenic parameters has not been reported. METHODS: Seventy-seven patients with systemic lupus erythematosus (SLE) (71 women, age 37 ± 12 years) and 26 age- and sex-matched healthy controls (22 women, age 34 ± 11 years) prospectively underwent routine history and physical exam, transcranial Doppler, brain MRI, TEE, carotid duplex, and clinical and laboratory evaluations of atherogenesis, inflammation, platelet activity, coagulation, and fibrinolysis. Subjects without stroke/TIA on enrollment (with and without LEx) had a median follow-up of 57 months. RESULTS: On enrollment, 33 (43%) of 77 patients had CVD manifested as acute stroke/TIA (23 patients), cerebromicroembolism by transcranial Doppler (17 patients), or cerebral infarcts by MRI (14 patients). Mitral or aortic valve LEx were equally frequent in healthy controls (46%) as in patients with and without any CVD (39 and 43%), stroke/TIA (35 and 43%), cerebromicroembolism (41 and 42%), or cerebral infarcts (36 and 43%) (all p ≥ 0.72). Also, other mechanisms for CVD other than LEx such as Libman-Sacks vegetations, patent foramen ovale or interatrial septal aneurysm, aortic or carotid atherosclerosis, or thrombogenesis were found in ≥94% of patients with CVD. In addition, 36 subjects with and 44 without LEx had similar low incidence of stroke/TIA (1 (1.3%) and 2 (2.5%), respectively, p = 1.0) during follow-up. Finally, LEx were not associated with aging, atherogenic risk factors, atherosclerosis, inflammation, or thrombogenesis. CONCLUSIONS: In this study, LEx are similarly prevalent in healthy controls and SLE patients, are not associated with CVD, and are not associated with pathogenic risk factors. Therefore, the study findings suggest that LEx may not be cardioembolic substrates, may not represent pathologic valve structures, and may not require therapy.

Development and validation of prediction rules to target care intensification in veteran patients with diabetes.

BACKGROUND: Diabetes affects 30.3 million people in the USA. Among these people, a major risk factor for microvascular complications is having a glycated haemoglobin (HbA1c) value of ≥75 mmol/mol; therefore, it would be helpful to identify patients who will obtain future HbA1c values of <75 mmol/mol. OBJECTIVES: To develop and validate two prediction rules among patients with diabetes having a baseline HbA1c value of ≥75 mmol/mol: (1) HbA1c measurement ever <75 mmol/mol and (2) final HbA1c measurement of <75 mmol/mol. METHODS: Retrospective cohort study using a registry extracting data from the Department of Veterans Affairs's (VA's) electronic health records system. Baseline was 1 Jul 2013-30 June 2014; patients were followed up until 31 July 2016. RESULTS: Our population consisted of 145 659 patients. Across models, predictors were age, sex, minority status, baseline HbA1c value, time, HbA1c≥75 mmol/mol, receiving insulin treatment and consecutive number of HbA1c values of 75 mmol/mol. The overall likelihood of a patient ever having an HbA1c<75 mmol/mol was 73.65%; with the rule, predicted probabilities were 38.94%, 50.75% and 78.88%. The overall likelihood of patients having a final HbA1c measurement of <75 mmol/mol was 55.35%; the rule provided predicted probabilities of 29.93%, 50.17% and 68.58%. CONCLUSIONS: Within each rule, there were similar observed and predicted tertile probabilities; maintaining HbA1c values of <75 mmol/mol resulted in probability shifts in the majority of patients. We recommend psychosocial screening for 15% of patients for whom there is less than one-third chance of maintaining HbA1c<75 mmol/mol. We plan to conduct additional research to see whether this approach helps.

Hypoxemia and acute mountain sickness: which comes first?

Hypoxemia is usually associated with acute mountain sickness (AMS), but most studies have varied in time and magnitude of altitude exposure, exercise, diet, environmental conditions, and severity of pulmonary edema. We wished to determine whether hypoxemia occurred early in subjects who developed subsequent AMS while resting at a simulated altitude of 426 mmHg (approximately 16,000 ft or 4880 m). Exposures of 51 men and women were carried out for 8 to 12 h. AMS was determined by Lake Louise (LL) and AMS-C scores near the end of exposure, with spirometry and gas exchange measured the day before (C) and after 1 (A1), 6 (A6), and last (A12) h at simulated altitude and arterial blood at C, A1, and A12. Responses of 16 subjects having the lowest AMS scores (nonAMS: mean LL=1.0, range=0-2.5) were compared with the 16 having the highest scores (+AMS: mean LL=7.4, range=5-11). Total and alveolar ventilation responses to altitude were not different between groups. +AMS had significantly lower PaO2 (4.6 mmHg) and SaO2 (4.8%) at A1 and 3.3 mmHg and 3.1% at A12. Spirometry changes were similar at A1, but at A6 and A12 reduced vital capacity (VC) and increased breathing frequency suggested interstitial pulmonary edema in +AMS. The early hypoxemia in +AMS appears to be the result of diffusion impairment or venous admixture, perhaps due to a unique autonomic response affecting pulmonary perfusion. Early hypoxemia may be useful to predict AMS susceptibility.

Plasma volume by Evans blue: effects of eating and comparison with other methods at altitude.

HYPOTHESIS: Measurements of plasma volume (PV) and its changes (delta%PV) by Evans blue (EB) dye are presumed to be valid only in fasting subjects. In addition, delta%PVEB with acute altitude exposure has not been compared with other methods employing the concentration or dilution of naturally occurring blood (hematocrit (Hct), hemoglobin (Hb)) and plasma (density, proteins) components, but should be similar if capillary permeability and the sampled vein/whole body Hct ratio remain unchanged. METHODS: PVEB was determined in six subjects while fasting or eating on different days, with injection and sampling in the same arm, 4-h extrapolation to time zero and correcting readings with the 620-740 A method. For 93 experiments at altitude, delta%PVEB was obtained similarly from a 3-h extrapolation near the end of a 12-h chamber exposure to 426 mm Hg (-4,880 m =16,000 ft) and at the same time on the preceding control day. RESULTS: Mean PVEB with and without eating was not significantly different (SE of absolute difference = +/- 2.8%). The EB decay curves had significantly more scatter with eating than fasting. The fasting vs. non-fasting values for the single 20-min post-injection point also gave a close comparison (r = +0.97). At altitude the loss in PV measured with EB was significantly greater (delta%PVEB = -6.3%) than losses estimated from Hct-Hb (-2.9%), plasma protein (-3.7%), and plasma density (-3.9%). The expected larger PV loss in subjects tolerant to altitude sickness compared with intolerant ones was most clearly shown by delta%PVEB (8.8%). CONCLUSIONS: Obtaining more samples can offset reproducibility lost by eating. The delta%PVEB were largest and nearest to values previously reported at altitude, perhaps because the single baseline and altitude samples utilized by the other methods are more sensitive to subtle, transient fluctuations in body water and vasomotor tone associated with apprehension, vomiting, fluid intake, and regional vasodilation and constriction.

Libman-Sacks endocarditis and embolic cerebrovascular disease.

OBJECTIVES: The aim of this study was to determine whether Libman-Sacks endocarditis is a pathogenic factor for cerebrovascular disease (CVD) in systemic lupus erythematosus (SLE). BACKGROUND: A cardioembolic pathogenesis of SLE CVD manifested as: 1) neuropsychiatric systemic lupus erythematosus (NPSLE), including stroke and transient ischemic attacks (TIA); 2) neurocognitive dysfunction; and 3) magnetic resonance imaging of focal brain lesions has not been established. METHODS: A 6-year study of 30 patients with acute NPSLE (27 women, 38 ± 12 years of age), 46 age- and sex-matched SLE controls without NPSLE (42 women, 36 ± 12 years of age), and 26 age- and sex-matched healthy controls (22 women, 34 ± 11 years of age) who underwent clinical and laboratory evaluations, transesophageal echocardiography, carotid duplex ultrasound, transcranial Doppler ultrasound, neurocognitive testing, and brain magnetic resonance imaging/magnetic resonance angiography. Patients with NPSLE were re-evaluated after 4.5 months of therapy. All patients were followed clinically for a median of 52 months. RESULTS: Libman-Sacks vegetations (87%), cerebromicroembolism (27% with 2.5 times more events per hour), neurocognitive dysfunction (60%), and cerebral infarcts (47%) were more common in NPSLE than in SLE (28%, 20%, 33%, and 0%) and healthy controls (8%, 0%, 4%, and 0%, respectively) (all p ≤ 0.009). Patients with vegetations had 3 times more cerebromicroemboli per hour, lower cerebral blood flow, more strokes/TIA and overall NPSLE events, neurocognitive dysfunction, cerebral infarcts, and brain lesion load than those without (all p ≤ 0.01). Libman-Sacks vegetations were independent risk factors of NPSLE (odds ratio [OR]: 13.4; p < 0.001), neurocognitive dysfunction (OR: 8.0; p = 0.01), brain lesions (OR: 5.6; p = 0.004), and all 3 outcomes combined (OR: 7.5; p < 0.001). Follow-up re-evaluations in 18 of 23 (78%) surviving patients with NPSLE demonstrated improvement of vegetations, microembolism, brain perfusion, neurocognitive dysfunction, and lesion load (all p ≤ 0.04). Finally, patients with vegetations had reduced event-free survival time to stroke/TIA, cognitive disability, or death (p = 0.007). CONCLUSIONS: The presence of Libman-Sacks endocarditis in patients with SLE was associated with a higher risk for embolic CVD. This suggests that Libman-Sacks endocarditis may be a source of cerebral emboli.