Mild Cognitive Impairment among Type II Diabetes Mellitus Patients Attending University Teaching Hospital

BACKGROUND: Type II diabetes mellitus (TIIDM) has been associated with structural and functional changes in the brain. TIIDM is commonly associated with obesity, insulin resistance, hypertension, and dyslipidemia, all of which can have negative impact on brain. AIM: The aim of the study was to study the risk of mild cognitive impairment (MCI) among both diabetics and non-diabetics and to identify risk factors to MCI among both groups. METHODS: Two comparative cross-sectional studies were carried out enrolling 100 diabetics and 100 age, sex, and education matching non-diabetics. Cognitive function was assessed using Montreal Cognitive Assessment (MoCA) test and risk factors for MCI were assessed. RESULTS: The subjective complaint of memory impairment among diabetics was significantly higher (34%) compared to non-diabetics (13.0%), p < 0.05. The mean of objective MoCA score was significantly lower among diabetics (25.9 ± 2.5) compared to non-diabetics (27.4 ± 2.4), p < 0.001. The rate of MCI was significantly higher among TIIDM patients (22%) compared to non-diabetics (9%), p < 0.01 and odds ratio (OR) 2.8 (95% confidence interval 1.2–6.5). Among the two studied groups, the rate of MCI was significantly higher among those aged over 50 years compared to younger age as well as among hypertensive compared to non-hypertensive persons, (p < 0.05). Among diabetics, the MCI was significantly higher among those with secondary education, having heart diseases, longer duration of DM, or repeated hypoglycemia attack, p < 0.05. A healthy diet, brain training, and social activities were found to be significantly associated with normal cognition. Logistic analysis revealed that diabetics aged above 50 was the only significant predicting factor for MCI with an OR 2.9 (95% CI: 3.8–123.3), p < 0.001. CONCLUSION: TIIDM is significantly associated with 3-times increasing risk of having MCI compared to non-diabetics. The age, hypertension, cardiovascular diseases, duration of diabetes, and frequency of hypoglycemic episodes are risk factors for cognitive impairment. A healthy diet, brain training, and social activities were associated with better cognitive function

Calpain cleavage of Junctophilin-2 generates a spectrum of calcium-dependent cleavage products and DNA-rich NT1-fragment domains in cardiomyocytes

Calpains are calcium-activated neutral proteases involved in the regulation of key signaling pathways. Junctophilin-2 (JP2) is a Calpain-specific proteolytic target and essential structural protein inside Ca2+ release units required for excitation-contraction coupling in cardiomyocytes. While downregulation of JP2 by Calpain cleavage in heart failure has been reported, the precise molecular identity of the Calpain cleavage sites and the (patho-)physiological roles of the JP2 proteolytic products remain controversial. We systematically analyzed the JP2 cleavage fragments as function of Calpain-1 versus Calpain-2 proteolytic activities, revealing that both Calpain isoforms preferentially cleave mouse JP2 at R565, but subsequently at three additional secondary Calpain cleavage sites. Moreover, we identified the Calpain-specific primary cleavage products for the first time in human iPSC-derived cardiomyocytes. Knockout of RyR2 in hiPSC-cardiomyocytes destabilized JP2 resulting in an increase of the Calpain-specific cleavage fragments. The primary N-terminal cleavage product NT1 accumulated in the nucleus of mouse and human cardiomyocytes in a Ca2+-dependent manner, closely associated with euchromatic chromosomal regions, where NT1 is proposed to function as a cardio-protective transcriptional regulator in heart failure. Taken together, our data suggest that stabilizing NT1 by preventing secondary cleavage events by Calpain and other proteases could be an important therapeutic target for future studies

Performance of a novel left ventricular lead with short bipolar spacing for cardiac resynchronization therapy: Primary results of the Attain Performa Quadripolar Left Ventricular Lead Study

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A Leadless Ventricular Pacemaker Providing Atrioventricular Synchronous Pacing in the Real-World Setting: 12-Month Results from the Micra AV Post-Approval Registry.

BACKGROUND Advances in leadless pacemaker technology have enabled accelerometer-based atrioventricular (AV) synchronous pacing by sensing atrial mechanical contraction. OBJECTIVES To report performance of the Micra AV leadless pacemaker from the worldwide Micra AV post-approval registry (PAR) through 12-months. METHODS The Micra AV PAR is a prospective single-arm observational registry designed to assess safety and effectiveness of Micra AV in a real-world setting. For the present interim analysis, major complications and system revisions through 12-months were summarized and compared to a historical cohort of 2,667 transvenous dual-chamber pacing patients. RESULTS The device was successfully implanted in 796 of 801 patients (99.4%) at 97 centers in 19 countries. Micra AV patients were older (74.1 vs. 71.1 years, P90%. CONCLUSIONS The Micra AV leadless pacemaker was implanted with a high rate of success in patients with multiple co-morbidities, with a significantly lower rate of complications and system revisions through 12-months compared to a historical cohort of patients with transvenous dual-chamber pacemakers

Cardiac injuries in blunt chest trauma

Blunt chest traumas are a clinical challenge, both for diagnosis and treatment. The use of cardiovascular magnetic resonance can play a major role in this setting. We present two cases: a 12-year-old boy and 45-year-old man. Late gadolinium enhancement imaging enabled visualization of myocardial damage resulting from the trauma

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)