Left ventricular mass increase is associated with cognitive decline and dementia in the elderly independently of blood pressure

Aims Left ventricular (LV) mass increase is considered part of composite target organ damage in hypertension and an independent risk factor for cardiovascular (CV) events. This study was designed to explore whether left ventricular mass index (LVMI) is associated with cognitive decline and dementia in elderly subjects, independently of blood pressure (BP) levels. Methods and results Four hundred subjects (mean age 79 ± 6 years) were studied. Left ventricular mass was measured echocardiographically in accordance with American Society of Echocardiography and normalized for body height to the 2.7 (LVMI). Global cognitive function was evaluated with the mini-mental state examination (MMSE) (maximum score 30). Dementia was defined as an MMSE score <21. Arterial stiffness was evaluated as carotid–femoral pulse wave velocity by Complior®. Prevalence of hypertension was 70% and diabetes mellitus was diagnosed in 25%. No significant differences in traditional CV risk factors were observed across LVMI quartiles. Mini-mental state examination showed an inverse trend across LVMI quartiles (the higher the LVMI, the lower the MMSE, P for trend <0.05); systolic and diastolic BP levels were not different across LVMI quartiles. In multivariable logistic regression models, including age, sex, BP levels, and use of antihypertensive drugs as covariates, the highest LVMI was found to be independently associated with a two-fold higher likelihood of having dementia. The association persisted significant even after adjustment for arterial stiffness. Conclusion In elderly subjects, LVMI is associated with a progressive cognitive decline. This association is independent of BP levels and/or large artery stiffness

Carotid beta stiffness association with thyroid function

Background: Thyroid hormone modulation of cardiovascular function has been associated with cardiovascular disease. Recent evidence suggests that free thyroxine (FT4) levels are associated with an increase in systemic arterial stiffness, but little is known about the effects of FT4 at the local level of the common carotid artery. β-stiffness index is a local elastic parameter usually determined by carotid ultrasound imaging. Methods: We conducted a cross-sectional analysis in the ProgeNIA cohort, including 4846 subjects across a broad age range. For the purpose of this study, we excluded subjects with increased thyrotropin (TSH) levels and those treated with levothyroxine or thyrostatic. We assessed β stiffness, strain, wall–lumen ratio, carotid cross-sectional area (CSA), and stress and flow in the right common carotid artery. We tested whether FT4, heart rate, and their interactions were associated with carotid parameters. Results: FT4 was positively and independently associated with β stiffness index (β = 0.026, p = 0.041), and had a negative association with strain (β = −0.025, p = 0.009). After adding heart rate and the interaction between FT4 and heart rate to the model, FT4 was still associated with the β stiffness index (β = 0.186, p = 0.06), heart rate was positively associated with the stiffness index (β = 0.389, p &lt; 0.001) as well as their interaction (β = 0.271, p = 0.007). Conclusion: This study suggests that higher FT4 levels increase arterial stiffness at the common carotid level, consistent with a detrimental effect on elastic arteries. The effect of FT4 is likely to be primarily attributable to its effect on heart rate

Comparison of amsler–krumeich and sandali classifications for staging eyes with keratoconus

Keratoconus (KC) is the most common corneal ectasia characterized by progressive corneal thinning, protrusion, and irregular astigmatism. The Amsler–Krumeich classification based on the analysis of corneal topography, corneal thickness, refraction and biomicroscopy is the most commonly used; recently, a new classification based on anterior segment Optical Coherence Tomography was introduced by Sandali and colleagues. Since there is no information about the possible agreement between these two classifications, the aim of this study is to compare the stratification of consecutive KC patients using the Amsler–Krumeich and Sandali classifications, and to further ascertain KC cases in which one classification is preferred over the other. Overall, 252 eyes of 137 patients (41.45 ± 16.93 years) were analyzed: in 156 eyes (61.9%), the Amsler and Sandali staging differed in one stage while in 75 cases (29.8%) it differed in two or more stages. In 222 eyes (88.1%), the Sandali staging was higher compared to the Amsler one. These results show that the two classifications are not fully interchangeable: the Amsler–Krumeich classification is more appropriate in identifying and longitudinally monitoring patients with early stages of KC, while the Sandali classification for the diagnosis and follow-up of patients with more advanced stages, particularly when a surgical planning has to be chosen

Effect of Gabapentin in a Neuropathic Pain Model in Mice Overexpressing Human Wild-Type or Human Mutated Torsin A

Background: DYT1 dystonia is the most common form of early-onset inherited dystonia, which is caused by mutation of torsin A (TA) belonging to the "ATPases associated with a variety of cellular activities" (AAA + ATPase). Dystonia is often accompanied by pain, and neuropathic pain can be associated to peripherally induced movement disorder and dystonia. However, no evidence exists on the effect of gabapentin in mice subjected to neuropathic pain model overexpressing human normal or mutated TA. Methods: Mice subjected to L5 spinal nerve ligation (SNL) develop mechanical allodynia and upregulation of the alpha 2 delta-1 L-type calcium channel subunit, forming a validated experimental model of neuropathic pain. Under these experimental conditions, TA is expressed in dorsal horn neurons and astrocytes and colocalizes with alpha 2 delta-1. Similar to this subunit, TA is overexpressed in dorsal horn 7 days after SNL. This model has been used to investigate (1) basal mechanical sensitivity; (2) neuropathic pain phases; and (3) the effect of gabapentin, an alpha 2 delta-1 ligand used against neuropathic pain, in non-transgenic (NT) C57BL/6 mice and in mice overexpressing human wild-type (hWT) or mutant (hMT) TA. Results: In comparison to non-transgenic mice, the threshold for mechanical sensitivity in hWT or hMT does not differ (Kruskal-Wallis test = 1.478; p = 0.4777, although, in the latter animals, neuropathic pain recovery phase is delayed. Interestingly, gabapentin (100 mg/Kg) reduces allodynia at its peak (occurring between post-operative day 7 and day 10) but not in the phase of recovery. Conclusions: These data lend support to the investigation on the role of TA in the molecular machinery engaged during neuropathic pain

Increase of ribavirin dose improves sustained virological response in HCV-genotype 1 patients with a partial response to peg-interferon and ribavirin

Background and aim. In patients with chronic hepatitis C receiving Peg interferon/ribavirin (PEG-IFN/RBV) who do not achieve ≥ 2log-reduction in HCV-RNA at week 12 (null responders, NR) and in those with ≥ 2log-decrease but detectable at week 24 (partial responders, PR) the probability to achieve the sustained virological response (SVR) is almost null. The aim of this study was to investigate the efficacy of individualized schedule of progressively increased RBV doses in the setting of PEG-IFN/RBV treatment. Material and methods. PR or NR to PEG-IFN/RBV instead of discontinuing treatment were enrolled to receive increasing doses of RBV until a target theoretical concentration ([tRBV]) of ≥ 15 μmol/L (by pharmacokinetic formula based on glomerular filtration rate). HCV-RNA was assessed every 4 weeks and, if detectable, RBV dose was gradually increased until negativization. Twelve weeks later, patients with detectable HCV-RNA discontinued therapy while those with undetectable HCV-RNA continued for further 48 weeks. Results. Twenty genotype-1 patients (8 NR and 12 PR) were enrolled. After 12 weeks 9 (45%) were still HCV-RNA positive and were discontinued, while remaining 11 had undetectable HCV-RNA. One stopped treatment for side effects. Ten completed treatment. Five (all PR) achieved SVR. Side effects incidence was similar to that observed during PEG-IFN/RBV. Conclusions. In conclusion, RBV high doses, according to individualized schedule, increase SVR in PR on a similar extent to that of triple therapy but without increase of side effects. Such treatment should be considered in PR with no access or intolerant to protease inhibitors (PI)

Association of FTO With Obesity-Related Traits in the Cebu Longitudinal Health and Nutrition Survey (CLHNS) Cohort

OBJECTIVE—The underlying genetic component of obesity-related traits is not well understood, and there is limited evidence to support genetic association shared across multiple studies, populations, and environmental contexts. The present study investigated the association between candidate variants and obesity-related traits in a sample of 1,886 adult Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) cohort

Combination of anti-CGRP/CGRP-R mAbs with onabotulinumtoxin A as a novel therapeutic approach for refractory chronic migraine: a retrospective study of real-world clinical evidence and a protocol for a double-blind, randomized clinical trial to establish the efficacy and safety

Chronic migraine is a disabling neurovascular disorder that ranks amongst the top causes of years lived with disability worldwide. The duration and the frequency of migraine affect cognitive and affective domains, inducing worsening of memory, executive functions, orientation and causing anxiety. Population-based studies report a worrying level of resistance to treatments. Therefore, this study aims: 1) to assess efficacy of monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) or its receptor (CGRP-R) for chronic migraine resistant to current preventatives; 2) to design a clinical trial protocol to evaluate the efficacy and safety of combination therapy utilizing anti-CGRP/CGRP-R together with onabotulinumtoxin A in patients suffering from resistant chronic migraine; 3) to provide a molecular rationale for combination therapy. A controlled trial is warranted as pooled analysis of real-world data from our group highlighted that combined treatment provides ≥50% reduction vs. baseline (onabotulinumtoxin A) of monthly headache days (MHDs) in up to 58.8% of patients, but there has been only sparse application of this combined therapy to date. The mAbs chosen are: erenumab, because its combination effect with onabotulinumtoxin A improved symptoms in 65% of patients; eptinezumab, due to its faster action. The results highlight that early diagnosis of migraine improves therapeutic outcomes with mAbs alone, confirming their effectiveness and the need for an adequately powered clinical trial evaluating the safety and potential superior effectiveness of eptinezumab/erenumab and onabotulinumtoxin A together

Pain and agitation treatment in severe dementia patients: The need for Italian Mobilization-Observation-Behavior-Intensity-Dementia (I-MOBID2) pain scale translation, adaptation and validation with psychometric testing

The 97% of dementia patients develops fluctuant neuropsychiatric symptoms often related to under-diagnosed and unrelieved pain. Up to 80% severe demented nursing home residents experiences chronic pain due to age-related comorbidities. Patients lacking self-report skills risk not to be appropriately treated for pain. Mobilization-Observation-Behavior-Intensity-Dementia (MOBID2) is the sole pain scale to consider the frequent co-occurrence of musculoskeletal and visceral pain and to unravel concealed pain through active guided movements. Accordingly, the Italian real-world setting can benefit from its translation and validation. This clinical study provides a translated, adapted and validated version of the MOBID2, the Italian I-MOBID2. The translation, adaptation and validation of the scale for non-verbal, severe demented patients was conducted according to current guidelines in a cohort of 11 patients over 65 with mini-mental state examination ≤&nbsp;12. The I-MOBID2 proves: good face and scale content validity index (0.89); reliable internal consistency (Cronbach's α&nbsp;=&nbsp;0.751); good to excellent inter-rater (Intraclass correlation coefficient, and test-retest (ICC&nbsp;=&nbsp;0.902) reliability. The construct validity is high (Rho&nbsp;=&nbsp;0.748 p&nbsp;&lt;&nbsp;0.05 for 11 patients, Spearman rank order correlation of the overall pain intensity score with the maximum item score of I-MOBID2 Part 1; rho=0.895 p&nbsp;&lt;&nbsp;0.01 for 11 patients, for the overall pain intensity score with the maximum item score of I-MOBID2 Part 2) and a good rate of inter-rater and test-retest agreement was demonstrated by Cohen's K&nbsp;=&nbsp;0.744. The average execution time is of 5.8&nbsp;min, thus making I-MOBID2 a useful tool suitable also for future development in community setting with administration by caregivers

Gender specific profiles of white coat and masked hypertension impacts on arterial structure and function in the SardiNIA study

Background: There is no definite consensus on the CV burden associated to Masked hypertension (MH) or White Coat Hypertension (WCH)-conditions that can be detected by out-of-office blood pressure measurements (24 hour Ambulatory Blood Pressure Monitoring, 24 h ABPM). Methods: We investigated the association of WCH and MH with arterial aging, indexed by a range of parameters of large artery structure and function in 2962 subjects, taking no antihypertensive medications, who are participating in a large community-based population of both men and women over a broad age range (14-102 years). Results: The overall prevalence of WCH was 9.5% and was 5.0% for MH, with 54.9% of subjects classified as true normotensive and 30.6% as true hypertensive. Both WCH and MH were associated with a stiffer aorta, a less distensible and thicker common carotid artery, and greater central BP than true normotensive subjects. Notably, the profile of arterial alterations in WCH and MH did not significantly differ from what was observed in true hypertensive subjects. The arterial changes accompanying WCH and MH differed in men and women, with women showing a greater tendency towards concentric remodeling, greater parietal wall stress, and PWV than men. Conclusion: Both WCH, and MH are associatedwith early arterial aging, and therefore, neither can be regarded as innocent conditions. Future studies are required to establish whether measurement of arterial aging parameters in subjects with WCH or MHwill identify subjects at higher risk of CV events and cognitive impairment, who may require more clinical attention and pharmacological intervention