Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1−CD8+ Tumor-Infiltrating T Cells

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Is multiple sclerosis a risk factor for atherosclerosis?

BackgroundMultiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. We aimed to discuss possible predisposing factors to atherosclerosis such as carotid intima-media thickness (CIMT) and high-sensitivity C-reactive protein (Hs-CRP) levels in MS.MethodsThirty-five ambulatory patients with relapsing-remitting MS (RRMS) (22 females and 13 males) and 34 healthy controls (21 females and 13 males) with similar demographic variables were included. Blood cell counts, cholesterol levels, vitamin D and B12, Hs-CRP levels, body mass index (BMI), history of smoking, and CIMT of both groups, Expanded Disability Status Scale (EDSS) scores, and disease duration of patients were recorded. Patients with a history of other vascular diseases such as hypertension, diabetes mellitus, peripheral artery disease, and acute relapses were excluded.ResultsSixty-nine participants were included. The mean age of the study population was 35.8 ± 7.1 years. Right CIMT was significantly greater in the patient population (P < 0.001). Spearman's correlation coefficient between age and right CIMT was r = 0.41, P = 0.01. When we compared the Hs-CRP with a cut-off value of ≤ 3, the right, left, and mean CIMT levels were not statistically significant (P = 0.17; P = 0.22; P = 0.15). The mean serum vitamin D levels were higher in the patient group and this was statistically significant (P < 0.001). The statistically significant factors identified with univariate analysis with P < 0.2 were further entered into multivariate modelling.ConclusionCIMT seems to be affected in patients with MS by means of the disease itself and age. Thus, CIMT might reflect the predisposition to subclinical atherosclerosis more than Hs-CRP. Further investigation in a large MS population is still needed.     

Right ventricular involvement in anterior myocardial infarction: a tissue Doppler-derived strain and strain rate study

OBJECTIVE:

Strain and strain rate imaging is currently the most popular echocardiographic technique that reveals subclinical myocardial damage. There are currently no available data on this imaging method with regard to assessing right ventricular involvement in anterior myocardial infarction. Therefore, we aimed to evaluate right ventricular regional functions using a derived strain and strain rate imaging tissue Doppler method in patients who were successfully treated for their first anterior myocardial infarction.

METHODS:

The patient group was composed of 44 patients who had experienced their first anterior myocardial infarction and had undergone successful percutaneous coronary intervention. Twenty patients were selected for the control group. The right ventricular myocardial samplings were performed in three regions: the basal, mid, and apical segments of the lateral wall. The individual myocardial velocity, strain, and strain rate values of each basal, mid, and apical segment were obtained.

RESULTS:

The right ventricular myocardial velocities of the patient group were significantly decreased with respect to all three velocities in the control group. The strain and strain rate values of the right mid and apical ventricular segments in the patient group were significantly lower than those of the control group (excluding the right ventricular basal strain and strain rate). In addition, changes in the right ventricular mean strain and strain rate values were significant.

CONCLUSION:

Right ventricular involvement following anterior myocardial infarction can be assessed using tissue Doppler based strain and strain rate     

"The end of good luck'--long-term survival without anticoagulation: a case report and review of the literature

Long-term anticoagulation in patients with metallic prosthetic valve disease is required according to current guidelines. We describe a patient with a functioning mitral mechanical valve without anticoagulation for 27 years. A 46-year-old man admitted to the emergency department with complains of palpitation. The patient had a mitral valve replacement because of severe mitral stenosis. He discontinued warfarin treatment 1 month after surgery because of the unavailability of this drug in Turkey. Transthoracic echocardiography revealed functioning metalic mitral valve with a mean gradient of 9 mm Hg. Fluoroscopy showed normal excursions of the mechanical mitral valve. Transesophageal echocardiography was performed and revealed fresh thrombus formation in the left atrial appendix. Admission international normalized ration (INR) level was 1.79. Due to the higher INR level and long-term survival, genetic analysis of warfarin polymorphism was performed. There was a homozygous mutation in the vitamin K epoxide reductase complex 1 (VKORC1) 1173C>T and 1639G>A genotypes. The possible explanations of long-term survival and baseline higher INR level were linked to the mutation in warfarin metabolism. We also briefly review the literature.     

A lasting post-stimulus activation on dorsolateral prefrontal cortex is produced when processing valence and arousal in visual affective stimuli

This paper introduces a new paradigm in the study of emotional processes through functional neuroimaging. We study whether the valence and arousal of visual stimuli influence neuroimaging of the evoked hemodynamic changes. Using functional near-infrared spectroscopy (fNIRS), we investigate evoked-cerebral blood oxygenation (CBO) changes in dorsolateral prefrontal cortex (DLPFC) during direct exposure to different emotion-eliciting stimuli ('on' period), and during the period directly following stimulus cessation ('off' period). We hypothesize that the evoked-CBO, rather than return to baseline after stimulus cessation, would show either overshoot or undershoot. The study includes 30 healthy subjects and a total of 9 stimuli, which consist of video-clips with different emotional content. The total sample of trials studied (270) is classified according to the valence and arousal ratings given by the subjects. Results show a more robust activation in DLPFC during the 'off' period than during the 'on' period, depending on the subjective degree of arousal given to the stimulus. Our findings provide the first fNIRS evidence showing that an increment in subjective arousal leads to activation in DLPFC which persists after stimulus cessation and this does not occur with non-arousing stimuli. Neuroimaging studies must consider the duration and affective dimensions of the stimulus as well as the duration of the scanning to specify how much of the recorded response is analyzed. Not accounting for this difference may contribute to confusion in the data interpretation.     

Exercise does not increase QTcmax and QTcd in diabetic patients with autonomic neuropathy

BACKGROUND: The purpose of this study was to examine the effects of exercise on maximum QTc interval (QTcmax) and QTc dispersion (QTcd) in diabetic patients without clinically evident heart disease. METHODS: Seventy-six diabetic patients who had no coronary artery disease or hypertension (group I; mean age 48 +/- 9 years old) and 40 healthy volunteers (group II; mean age 46 +/- 13 years old) were enrolled in the study. Cases with clinically evident heart disease were excluded from the study. Resting 12-lead electrocardiogram (ECG) and maximal treadmill exercise test (according to Bruce protocol) were performed in all cases. The QTcmax interval was determined at rest (RQTcmax) and during peak exercise (PQTcmax). Also, the QTcd was measured at rest (RQTcd) and during peak exercise (PQTcd). Autonomic neuropathy was assessed by measuring the heart rate variability (HRV). RESULTS: There was no significant difference between clinical characteristics of two groups. In group I, HRV parameters were significantly lower than group II. RQTcd, PQTcd, RQTcmax, and PQTcmax were significantly longer in group I (56 +/- 16 vs 34 +/- 11; P< 0.001, 62 +/- 22 vs 40 +/- 15; P < 0.001, respectively). In diabetic patients, there was no significant difference between RQTcmax and PQTcmax (428 +/- 19 vs 420 +/- 31; P > 0.05), and no significant difference was present between RQTcd and PQTcd (56 +/- 16 vs 62 +/- 22; P > 0.05, respectively). CONCLUSION: Exercise does not affect QTcd in patients with diabetes mellitus and without clinically evident heart disease.