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Pompe disease, an autosomal recessive disorder caused by deficient lysosomal acid α-glucosidase (GAA), is characterized by accumulation of intra-lysosomal glycogen in skeletal and oftentimes cardiac muscle. The c.1935C>A (p.Asp645Glu) variant, the most frequent GAA pathogenic mutation in people of Southern Han Chinese ancestry, causes infantile-onset Pompe disease (IOPD), presenting neonatally with severe hypertrophic cardiomyopathy, profound muscle hypotonia, respiratory failure, and infantile mortality. We applied CRISPR-Cas9 homology-directed repair (HDR) using a novel dual sgRNA approach flanking the target site to generate a Gaaem1935C>A knock-in mouse model and a myoblast cell line carrying the Gaa c.1935C>A mutation. Herein we describe the molecular, biochemical, histological, physiological, and behavioral characterization of 3-month-old homozygous Gaaem1935C>A mice. Homozygous Gaaem1935C>A knock-in mice exhibited normal Gaa mRNA expression levels relative to wild-type mice, had near-abolished GAA enzymatic activity, markedly increased tissue glycogen storage, and concomitantly impaired autophagy. Three-month-old mice demonstrated skeletal muscle weakness and hypertrophic cardiomyopathy but no premature mortality. The Gaaem1935C>A knock-in mouse model recapitulates multiple salient aspects of human IOPD caused by the GAA c.1935C>A pathogenic variant. It is an ideal model to assess innovative therapies to treat IOPD, including personalized therapeutic strategies that correct pathogenic variants, restore GAA activity and produce functional phenotypes.

A sesquiterpenoid with an unprecedented 5/5/4 tricyclic skeleton (

The rapid emergence of SARS-CoV-2 variants raised public health questions concerning the capability of diagnostic tests to detect new strains, the efficacy of vaccines, and how to map the geographical distribution of variants to understand transmission patterns and loads on healthcare resources. Next-generation sequencing (NGS) is the primary method for detecting and tracing new variants, but it is expensive, and it can take weeks before sequence data are available in public repositories. This article describes a customizable reverse transcription PCR (RT-PCR)-based genotyping approach which is significantly less expensive, accelerates reporting, and can be implemented in any lab that performs RT-PCR. Specific single-nucleotide polymorphisms (SNPs) and indels were identified which had high positive-percent agreement (PPA) and negative-percent agreement (NPA) compared to NGS for the major genotypes that circulated through September 11, 2021. Using a 48-marker panel, testing on 1,031 retrospective SARS-CoV-2 positive samples yielded a PPA and NPA ranging from 96.3 to 100% and 99.2 to 100%, respectively, for the top 10 most prevalent World Health Organization (WHO) lineages during that time. The effect of reducing the quantity of panel markers was explored, and a 16-marker panel was determined to be nearly as effective as the 48-marker panel at lineage assignment. Responding to the emergence of Omicron, a genotyping panel was developed which distinguishes Delta and Omicron using four highly specific SNPs. The results demonstrate the utility of the condensed panel to rapidly track the growing prevalence of Omicron across the US in December 2021 and January 2022.

Introduction: VNS is an adjunctive neuromodulation therapy for patients with drug-refractory epilepsy. The antiseizure effect of VNS is thought to be related to a diffuse modulation of functional connectivity but remains to be confirmed. Aim: To investigate electroencephalographic (EEG) metrics of functional connectivity in patients with drug-refractory epilepsy treated by vagus nerve stimulation (VNS), between VNS-stimulated “ON” and nonstimulated “OFF” periods and between responder (R) and nonresponder (NR) patients. Methods: Scalp-EEG was performed for 35 patients treated by VNS, using 21 channels and 2 additional electrodes on the neck to detect the VNS stimulation. Patients were defined as VNS responders if a reduction of seizure frequency of ∼50% was documented. We analyzed the synchronization in EEG time series during “ON” and “OFF” periods of stimulation, using average phase lag index (PLI) in signal space and phase-locking value (PLV) between 10 sources. Based on graph theory, we computed brain network models and analyzed minimum spanning tree (MST) for responder and nonresponder patients. Results: Among 35 patients treated by VNS for a median time of 7 years (range 4 months to 22 years), 20 were R and 15 were NR. For responder patients, PLI during ON periods was significantly lower than that during OFF periods in delta (p = 0.009), theta (p = 0.02), and beta (p = 0.04) frequency bands. For nonresponder patients, there were no significant differences between ON and OFF periods. Moreover, variations of seizure frequency with VNS correlated with the PLI OFF/ON ratio in delta (p = 0.02), theta (p = 0.04), and beta (p = 0.03) frequency bands. Our results were confirmed using PLV in theta band (p

The goal of this study is to generate and characterize a knock-in model of Pompe disease (PD) – a rare, progressive, fatal disorder primarily affecting the cardiac and musculoskeletal systems. While a murine model of PD exists, it bears a Cre/loxP induced exonic insertion of a neomycin cassette and does not completely recapitulate severe human PD - displaying nonfatal hypertrophic cardiomyopathy only late in its natural history. We therefore designed a CRISPR-Cas9 knock-in system targeting the Gaa gene to introduce the known pathogenic CRIM negative Gaa mutation c.1826insA (p.Y609*). Following optimization of our knock-in strategy in cultured murine myoblasts, we successfully generated a Gaac1826insA mouse model using a dual sgRNA with ssODN donor template approach. Whole genome sequencing and analysis of the Gaac1826insA murine model establishes that our system is highly specific for the Gaac1826 target locus and does not induce any off-target mutations or genomic rearrangements. Next, we examined GAA mRNA transcript, protein expression and enzymatic activity levels in our PD knock-in mice. Gaac1826insA mice display significantly reduced levels of GAA expression and enzymatic activity relative to wild-type mice. We performed echocardiography on Gaac1826insA mice to assess cardiac structure and function. Gaac1826insA mice exhibit early-onset, progressive cardiac hypertrophy as measured by significant increases in left ventricular wall thickness and mass index by 3 months of age. We also conducted functional tests – grip strength, inverted screen, gait analysis – on Gaac1826insA mice every 3 months to assess overall motor performance. Gaac1826insA mice display impaired motor strength and coordination relative to wild-type mice. Altogether, our results demonstrate that the Gaac1826insA murine model recapitulates human infantile-onset Pompe disease and is better suited for evaluation of therapeutic strategies such as genome correction.

Cardiac hepatopathy has generally been used to describe any liver damage caused by cardiac disorders in the absence of other possible causes of liver damage. Although there is no consensus on the terminology used, cardiac hepatopathy can be examined as congestive hepatopathy (CH) and acute cardiogenic liver injury (ACLI). CH is caused by passive venous congestion of the liver that generally occurs in the setting of chronic cardiac conditions such as chronic HF, constrictive pericarditis, tricuspid regurgitation, or right-sided heart failure (HF) of any cause, and ACLI is most commonly associated with acute cardiocirculatory failure resulting from acute myocardial infarction, acute decompensated HF, or myocarditis. Histologically, CH is characterized by sinusoidal dilation, replacement of hepatocytes with red blood cells extravasating from the sinusoids, and necrosis/apoptosis of zone 3 of the Rappaport acinus, and it could progress to cirrhosis in advanced cases. In ACLI, however, massive necrosis of zone 3 is the main histological finding. Primary laboratory findings of CH are elevated serum cholestasis markers including bilirubin, alkaline phosphatase, and γ-glutamyl-transpeptidase levels, whereas those of ACLI are a striking elevation in transaminase and lactate dehydrogenase levels. Both CH and ACLI have a prognostic value for identifying cardiovascular events and mortality and have some special implications in the management of patients undergoing ventricular assist device implantation or cardiac transplantation. There is no specific treatment for CH or ACLI other than treatment of the underlying cardiac disorder.

Background and ObjectivesFocal cortical dysplasia type 2 (FCD2) in the central region can cause drug-resistant epilepsy for which surgery remains challenging because of subsequent functional deficits. Advances in imaging and surgical techniques have progressively improved outcome. We aimed to assess the benefits on epilepsy and the functional risks after FCD2 resections in these highly eloquent areas.MethodsWe retrospectively studied all consecutive patients with histologically confirmed FCD2 located in the central region operated on between 2000 and 2019 at a single center. We analyzed electroclinical and imaging features (including fMRI), seizure outcome, and early and late postoperative neurologic status correlating to anatomo-functional areas (primary motor cortex [PMC], paracentral lobule [PCL], supplementary motor area [SMA], precentral gyrus [PrCG], postcentral gyrus [PoCG], central operculum [COp]).ResultsSixty patients (35 female, age 7–65 years) were included in the study. Epilepsy was characterized by early onset, high seizure frequency with clusters (30–90/d), drop attacks, and status epilepticus. Ictal semiology included sensory-motor auras, motor and postural manifestations, and postictal motor deficits. EEG and stereo-EEG patterns were like those typically recorded in FCD2. MRI was positive in 63% and 18F-fluorodeoxyglucose-PET was positive in 86% of the patients. fMRI demonstrated activations close to the FCD2 (59%) or minor reorganization (41%) but none within the lesion. Seizure-free outcome (2- to 20-year follow-up) was obtained in 53 patients (88%), including 37 achieving Engel class IA (62%), correlating with complete FCD2 removal. Early transitory postoperative deficits occurred in 52 patients (87%), which were severe in 19, mostly after PMC, PCL, and SMA resections, while PrCG, PoCG, and COp resections were associated with minor/moderate deficits. Total recovery was observed in 21 of 52 patients (40%), while a permanent deficit (>2 years) persisted in 31 (minor 19, moderate 9, major 3). The best outcome (seizure freedom without deficit [48%] or with minor deficit (28%]) was significantly more frequent in children (p = 0.025). Antiseizure medications were discontinued in 28 patients (47%). Quality of life correlated with seizure-free outcome and absence of postoperative deficit; 43 patients (72%) reported a schooling or socio-professional improvement.DiscussionExcellent seizure outcome and low rates of major permanent disability can be achieved after central FCD2 resections despite functional risks.Classification of EvidenceDue to its retrospective nature, this study provides Class IV evidence that good seizure outcomes with minor additional deficits can be achieved after epilepsy surgery in the central region.

OBJECTIVE To assess factors associated with favorable outcome in refractory insular epilepsy treated by volume-based stereotactic radiofrequency thermocoagulation (RFTC). METHODS We performed volume-based RFTC in 19 patients (11 males, 7-44 years old). The volume for thermocoagulation was identified by multimodal data including electroencephalography (EEG)-video, magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (PET) in all patients, and epileptogenic zone (EZ) was assessed by stereo-electroencephalography (SEEG) in 16. MRI showed insular lesions in four patients (benign tumors, n = 2; focal cortical dysplasia [FCD], n = 1; polymicrogyria, n = 1). MRI was negative in 15 cases; however, PET was positive in 18, and FCD pattern was detected by SEEG in nine cases. The dominant hemisphere was involved in 12 cases. RFTC was performed as a separate procedure after SEEG, or as a single MRI-guided procedure. The insular volume to be coagulated was determined by a tridimensional identification of the epileptogenic cortex using MRI, PET, and SEEG, and was destroyed with coalescent thermal lesions. RESULTS Seizure-free outcome was achieved in 10 patients (53%), including Engel class IA in three (follow-up = 1-12 years, mean = 5.4). The responder rate (including Engel classes I-III) was 89%. Transient postoperative deficits (mild hemiparesia, dysarthria, hypoesthesia, dysgeusia) were observed in eight patients (42%), with rapid and total recovery in all but one with persistent mild dysarthria. Neurological deficits were related to higher number of RFTC procedures (P = .036) and greater volume of RFTC (P = .028). Neuropsychological status was unchanged or improved in all; however, psychiatric status transitorily worsened in three patients. Factors contributing to seizure-free outcome were the detection of FCD pattern (P = .009), localized EZ (P = .038), low RFTC volume (P = .002), low number of RFTC procedures (P = .001), and low RFTC volume/number ratio (P = .012). Optimal volume of RFTC around 2 cm3 offered the best compromise between efficacy and safety. SIGNIFICANCE RFTC may be curative in insular epilepsy after accurate localization of EZ with SEEG. Best outcome was associated with low volume of thermolesions.

The development of antibodies that target specific glycan structures on cancer cells or human pathogens poses a significant challenge due to the immense complexity of naturally occurring glycans. Automated glycan assembly enables the production of structurally homogeneous glycans in amounts that are difficult to derive from natural sources. Nanobodies (Nbs) are the smallest antigen-binding domains of heavy-chain-only antibodies (hcAbs) found in camelids. To date, the development of glycan-specific Nbs using synthetic glycans has not been reported. Here, we use defined synthetic glycans for alpaca immunization to elicit glycan-specific hcAbs, and describe the identification, isolation, and production of a Nb specific for the tumor-associated carbohydrate antigen Globo-H. The Nb binds the terminal fucose of Globo-H and recognizes synthetic Globo-H in solution and native Globo-H on breast cancer cells with high specificity. These results demonstrate the potential of our approach for generating glycan-targeting Nbs to be used in biomedical and biotechnological applications.

The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP).A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mmThe median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.Bu çalışmanın amacı kronik immün trombositopeni (ITP) hastalarında bir oral trombopoietin reseptör agonisti olan eltrombopagın etkinlik ve güvenirliliğini değerlendirmektir.Elli beş merkezde izlem altındaki toplam 285 kronik ITP hastası (187 kadın, %65,6) bu geriye dönük küme çalışmasına alınmıştır. Tedaviye yanıt trombosit sayısına göre değerlendirilmiş ve tam yanıt (100.000/mmTanı anında yaş ortalaması 43,9±20,6 (3-95) yıl olan hastalar ortalama 18,0±6,4 (6-28,2) ay izlenmiştir. Tam ve kısmi yanıtı içeren toplam yanıt %86,7 (n=247) bulundu. Sırasıyla 182 (%63,8) ve 65 (%22,8) hastada tam ve parsiyel tedavi yanıtları gözlenmiştir. Otuz sekiz hasta (%13,4) eltrombopag tedavisine yanıt vermemiştir. Altmış yaş üzerindeki hastalarda (n=68) toplam yanıt %89,7 (n=61) bulunurken, bu oran 80 yaş üzerindeki (n=12) hastalarda %83 (n=10) olmuştur. Tedavi öncesi trombosit sayısı göz önüne alındığında, eltrombopag, tedavinin 1., 2., 3., 4. ve 8. haftalarında trombosit sayısını anlamlı şekilde artırmıştır. Kısmi veya tam cevap için gereken süre arttıkça, tedaviye cevap önemli ölçüde azaldığı saptanmıştır. Eltrombopag tedavisinden sonra maksimum trombosit sayısı ne kadar yüksekse, yan etkilerin oluşabilme ihtimalinin o kadar yüksek olabildiği dikkati çekmiştir. En sık görülen yan etkiler baş ağrısı (%21,6), güçsüzlük (%13,7) ve hepatotoksisite (%11,8) ve trombozdur (%5,9).Mevcut çalışmanın sonuçları, eltrombopag tedavisinin kronik ITP’de, yaşlı hastalar dahil olmak üzere, etkili bir tedavi seçeneği olduğunu göstermektedir. Bununla birlikte, hastalar tedavi sırasında yanıt ve yan etkiler açısından yakından izlenmelidir. Hem cevap hem de yan etkiler, takip süresi boyunca değişken olabileceğinden, hastalar özellikle tromboz risk faktörleri açısından dinamik olarak değerlendirilmelidir.

This work presents a sensitive and rapid analytical method for the determination of oxcarbazepine in human plasma and urine samples. A vortex-assisted switchable hydrophilicity solvent-based liquid phase microextraction (VA-SHS-LPME) was used to preconcentrate oxcarbazepine from the samples before the determination by gas chromatography mass spectrometry. The switchable hydrophilicity solvent was synthesized by protonating N,N-dimethylbenzylamine with carbon dioxide to make it totally miscible with an equivalent volume of water. Parameters of the VA-SHS-LPME method including volume of switchable hydrophilicity solvent, concentration/volume of sodium hydroxide and vortex period were systematically optimized. Under the optimum conditions, good linearity ranging from 27.03 to 353.47 μg/kg was obtained for the analyte. Limit of detection and quantitation values were found to be 6.2 and 21 μg/kg (mass base), respectively. The relative standard deviation was calculated as 6.9% for six replicate measurements of the lowest concentration of the calibration plot. Satisfactory recovery results were calculated in the range of 97-100% for human plasma and urine samples spiked at five different concentrations.

Background Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counselling.Methods In this retrospective, multicentre, longitudinal, cohort study, patients who had epilepsy surgery between Jan 1, 2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18 European countries of the European Epilepsy Brain Bank consortium were assessed. We included patients of all ages with histopathology available after epilepsy surgery. Histopathological diagnoses and a minimal dataset of clinical variables were collected from existing local databases and patient records. The primary outcomes were freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2, and 5 years after surgery. Proportions of individuals who were Engel class 1 and drug-free were reported for the 11 main categories of histopathological diagnosis. We analysed the association between histopathology, duration of epilepsy, and age at surgery, and the primary outcomes using random effects multivariable logistic regression to control for confounding.Findings 9147 patients were included, of whom seizure outcomes were available for 8191 (89.5%) participants at 2 years, and for 5577 (61.0%) at 5 years. The diagnoses of low-grade epilepsy associated neuroepithelial tumour (LEAT), vascular malformation, and hippocampal sclerosis had the best seizure outcome at 2 years after surgery, with 77.5% (1027 of 1325) of patients free from disabling seizures for LEAT, 74.0% (328 of 443) for vascular malformation, and 71.5% (2108 of 2948) for hippocampal sderosis. The worst seizure outcomes at 2 years were seen for patients with focal cortical dysplasia type I or mild malformation of cortical development (50.0%, 213 of 426 free from disabling seizures), those with malformation of cortical development-other (52.3%, 212 of 405 free from disabling seizures), and for those with no histopathological lesion (53.5%, 396 of 740 free from disabling seizures). The proportion of patients being both Engel class 1 and drug-free was 0-14% at 1 year and increased to 14-51% at 5 years. Children were more often drug-free; temporal lobe surgeries had the best seizure outcomes; and a longer duration of epilepsy was associated with reduced chance of favourable seizure outcomes and drug freedom. This effect of duration was evident for all lesions, except for hippocampal sclerosis.Interpretation Histopathological diagnosis, age at surgery, and duration of epilepsy are important prognostic factors for outcomes of epilepsy surgery. In every patient with refractory focal epilepsy presumed to be lesional, evaluation for surgery should be considered. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

Three new elemanolides, named vernonilides D (1), E (2), and F (3), along with four known sesquiterpenoids, including two elemanolides (4, 5), a guaianolide (6), and a germacranolide (7) were isolated from the seeds of Vernonia anthelmintica. The structures of them were elucidated based on 1D and 2D NMR experiments and comparison with published data. Cytotoxicity of the compounds against four human tumor cell lines was assayed. 6 showed strongly inhibitory effect against HCT-15 and PC-3 cell lines with IC50 values of 0.56 and 0.69 μM, respectively. The new compounds showed moderate cytotoxicity against four cell lines with IC50 values ranging from 9.1 to 28.1 μM.

Comparison between the intended and performed motor action can be expected to occur in the final epoch of a voluntary movement. In search for electrophysiological correlates of this mental process the purpose of the current study was to identify intracerebral sites activated in final epoch of self-paced voluntary movement. Intracerebral EEG was recorded from 235 brain regions of 42 epileptic patients who performed self-paced voluntary movement task. Evoked potentials starting at 0 to 243ms after the peak of averaged, rectified electromyogram were identified in 21 regions of 13 subjects. The mean amplitude value of these late movement potentials (LMP) was 56.4±27.5μV. LMPs were observed in remote regions of mesiotemporal structures, cingulate, frontal, temporal, parietal, and occipital cortices. Closely before the LMP onset, a significant increase of phase synchronization was observed in all EEG record pairs in 9 of 10 examined subjects; p

Introduction Dysembryoplastic neuroepithelial tumors and gangliogliomas are developmental glioneuronal tumors usually revealed by partial epilepsy. High epileptogenicity, childhood epilepsy onset, drug-resistance, temporal location, and seizure freedom after complete resection are common characteristics of both tumors. We report the specificity of surgical management, functional results and seizure outcome in cases of a tumor location in eloquent areas. Methods Among 150 patients (88 males, 3–55 years) operated on for refractory epilepsy due to a glioneuronal tumor (1990–2015), 30 (20%, dysembryoplastic neuroepithelial tumors = 21; gangliogliomas = 9) had a tumor located in an eloquent cortex (sensory-motor, insular or language areas). Surgery was performed after a preoperative work-up, including stereo-electroencephalography in 48 patients (26%) and functional MRI in 100 (67%). MRI-guided lesionectomy was mainly performed in extra-temporal location, whereas an additional corticectomy was performed in a temporal location. Tumor microsurgical resections were guided using neuronavigation and cortical/subcortical electrical stimulations. Multiple stereotactic thermocoagulations were performed in two insular tumors. Results New motor/language deficits related to eloquent areas occurred postoperatively in 6/30 patients (20%) without any major permanent disability. Minor sensorimotor ( n = 2) and moderate language disturbance ( n = 1) persisted in three of them. Postoperative seizure-free outcome (mean follow-up > 5 years) was obtained in 81% of the entire series, but significantly decreased to 60% in eloquent areas. Incomplete tumor resection was the main cause of surgical failure. However, unfavorable seizure outcome was also observed despite complete tumor resection. Malignant transformation occurred in one ganglioglioma. Conclusion Epilepsy surgery for benign glioneuronal tumors in eloquent areas provides acceptable results regarding the functional risks. Complete tumor resection is crucial for long-term favorable outcome.

Aim: Tp-e/QT ratio is a novel marker of ventricular repolarization. The aim of the study is to evaluate the Tp-e interval and Tp-e/QT ratio before and after radiofrequency ablation (RFA) for patients with frequent premature ventricular complexes (PVCs). Patients & methods: The study included 151 consecutive patients who underwent RFA for treatment of symptomatic frequent PVCs. Results: Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio (all p < 0.001) were significantly different before and after RFA. After the procedure, mean left ventricular ejection fraction of the population were significantly increased than before RFA (p < 0.001). There was a significant correlation between preprocedural Tp-e/QTc ratio and PVC burden in patients (p = 0.023). Conclusion: Our study shows that PVCs may have a negative effect on ventricular repolarization.

Objective To analyze the outcome of epileptic patients who had redo surgery involving the vagus nerve stimulation's lead. Methods We reviewed the clinical and surgical records of all patients who had a complete vagus nerve stimulation (VNS) removal or replacement or any redo surgical procedure involving the system lead at Sainte-Anne Hospital in Paris, France. Results Between the years 1999 and 2016, 41 redo surgical procedures involving the lead or electrode were achieved, of which 23 were complete VNS explantations, 12 were complete system replacements, 5 were lead changes only, and 1 was isolated lead removal. 41% of the surgical procedures were achieved in female patients. This population has a median age at VNS implantation of 33.6 years (interquartile range [IQR], [21.4–38.6]. Median time between the VNS implantation and the redo surgery involving the lead was 4.9 years (IQR, 2.9–8). The reason for VNS removal was mainly a lack of clinical effectiveness. No preoperative or postoperative complications occurred after complete VNS system removal or lead replacement. The effectiveness of the VNS therapy remained unchanged after lead replacement. No vagus nerve injury was reported, nor did symptoms suggest that it was disabled. Conclusions Complete removal or replacement of the VNS system including the lead and the electrode is feasible and safe. These procedures should be offered to patients who would no longer benefit from the VNS or when only a lead change is needed.

Objective: To develop and validate a scale to measure fear of activity in patients with coronary artery disease. Design: Psychometric study. Setting: Outpatient cardiology clinics. Participants: The scale was applied to patients who had myocardial infarction, coronary artery bypass grafting, or percutaneous coronary intervention within the last 12 months (N=250). Interventions: A scale for fear of activity in patients with coronary artery disease (Fact-CAD) was created through semistructured focus group interviews with patients. Face and content validity of Fact-CAD was verified. Main Outcome Measures: Psychometric analysis included model fit, unidimensionality, reliability, local dependency, differential item functioning, and external construct validity. Analyses were performed using the Rasch Analysis Model. Results: Fact-CAD scale was a reliable (high Person Separation Index of 0.89) and valid (unidimensional, no misfit, local independency supported, no residual correlations) measure of fear of activity. Three items showed differential item functioning according to employment status, marital status, and angina pectoris, which were not assigned as real item bias by experts and remained in the model. Conclusion: Fact-CAD was supported by Rasch analysis as a psychometrically valid scale to evaluate fear of activity in patients with coronary artery disease. (C) 2019 by the American Congress of Rehabilitation Medicine WOS:000520949900011 2-s2.0-85073748647 PubMed: 31562874

Aim: This study aims to assess the predictive role of the preprocedural circulating monocyte to high-density lipoprotein (HDL) cholesterol ratio (MHR) on the occurrence of stent restenosis (SR) in patients with stable and unstable angina pectoris undergoing successful bare-metal stenting (BMS). Patients & methods: Between February 2008 and June 2014, a total of 831 patients with stable and unstable angina pectoris who underwent successful BMS were retrospectively analyzed. Demographic and clinical characteristics of the patients were recorded. Left ventricular ejection fraction and laboratory data were also noted. Results: In the receiver operating characteristics curve analysis, MHR >14 had 71% sensitivity and 69% specificity in predicting SR. Conclusion: Our study results show that preprocedural MHR is an independent predictor of SR in this patient population.

Compared to pediatric age group, the prognosis of adult acute lymphoblastic leukemia (ALL) is still dismal even in patients receiving allogeneic hematopoietic cell transplantation (AHCT). We retrospectively analyzed 205 adults (male: 122; female: 83) with ALL who underwent AHCT. Median age of patients was 28 (18-59). Fifty-two patients had Ph+ ALL. The estimated relapse free and overall survival (OS) of the study cohort at 1, 2 and 3 years were 52.3%/63.9%, 42.9%/49.5% and 39.9%/45.6%, respectively. On multivariate analysis, first complete remission at the time of AHCT, TBI-based conditioning and development of chronic graft-versus-host disease were only factors, which were significantly associated with prolonged OS. (c) 2016 Elsevier Ltd. All rights reserved.

Hepatic sinusoidal obstruction syndrome (HSOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the incidence, risk factors, treatment and survival for HSOS after allo-HSCT in Turkey. We also reported our experience of defibrotide (DF) for HSOS prophylaxis in high-risk (HR) patients. Across Turkey, 1153 patients from 10 centers were enrolled in the study. We evaluated the medical records of patients who were treated with allo-SCT between January 2012 and December 2015. The study included 1153 patients (687 males/466 females) with median age of 38 (15?71) years. The incidence of HSOS was 7.5 % (n = 86). The incidences of HSOS in the HR/DF+, HR/DF- and standard risk (SR) group were 8%, 66.7 % and 6.2 %, respectively. The rate of HSOS development was not statistically different between HR/DF + and SR group (p = 0.237). HSOS prophylaxis (defibrotide) was significantly decreased HSOS-related mortality (p = 0.004). The incidence of HSOS was found similar to literature in this large Turkish cohort. Defibrotide prophylaxis appears to be associated with low incidence of HSOS development and reduced HSOS-related mortality. Although these results are promising, future studies are needed to support the efficacy of defibrotide prophylaxis in patients with risk of HSOS. © 2020 Elsevier Ltd, We thank to Raika Durusoy for statistical analysis and data interpretation.

International audience; The primary line of therapy for high-grade brain tumor is surgical resection, however, identifying tumor margins in vivo remains a major challenge. Despite the progress in computer-assisted imaging techniques, biopsy analysis remains the standard diagnostic tool when it comes to delineating tumor margins. Our group aims to answer this challenge by exploiting optical imaging of endogenous fluorescence in order to provide a reliable and reproducible diagnosis close to neuropathology. In this study, we first establish the ability of two-photon microscopy (TPM) to discriminate normal brain tissue from glioblastomas and brain metastasis using the endogenous fluorescence response of fresh human brain sample. Two-photon fluorescence images were compared to gold standard neuropathology. "Blind" diagnosis realized by a neuropathologist on a group of TPM images show a good sensitivity, 100%, and specificity, 50% to discriminate non tumoral brain tissue versus glioblastoma or brain metastasis. Quantitative analysis on spectral and fluorescence lifetime measurements resulted in building a scoring system to discriminate brain tissue samples.

The spliceosome catalyzes the removal of introns from pre-messenger RNA (mRNA) and subsequent pairing of exons with remarkable fidelity. Some exons are known to be skipped or included in the mature mRNA in a cell type- or context-dependent manner (cassette exons), thereby contributing to the diversification of the human proteome. Interestingly, splicing is initiated (and sometimes completed) co-transcriptionally. Here, we develop a kinetic mathematical modeling framework to investigate alternative co-transcriptional splicing (CTS) and, specifically, the control of cassette exons’ inclusion. We show that when splicing is co-transcriptional, default splice patterns of exon inclusion are more likely than when splicing is post-transcriptional, and that certain exons are more likely to be regulatable (i.e. cassette exons) than others, based on the exon–intron structure context. For such regulatable exons, transcriptional elongation rates may affect splicing outcomes. Within the CTS paradigm, we examine previously described hypotheses of co-operativity between splice sites of short introns (i.e. ‘intron definition’) or across short exons (i.e. ‘exon definition’), and find that models encoding these faithfully recapitulate observations in the fly and human genomes, respectively.

Contrast-induced nephropathy (CIN) after primary percutaneous coronary intervention (PPCI) is associated with adverse short- and long-term outcomes. The aim of this study was to evaluate the predictive value of gamma-glutamyl transferase (GGT) for risk of CIN in patients with ST-segment elevation myocardial infarction who underwent PPCI. A total of 473 patients were enrolled in the study. A relative increase in serum creatinine ≥25%, or an absolute increase ≥0.5 mg/dl, from the baseline within 72 hours of contrast exposure was defined as CIN. Patients were divided into 3 groups according to GGT tertiles (tertile 1, GGT19 U/L; tertile 2, GGT 19 to 33 U/L; and tertile 3, GGT33 U/L) on admission. Demographics, clinical risk factors, laboratory parameters, CIN incidence, and other inhospital clinical outcomes were compared among GGT tertiles. CIN incidence was significantly higher in tertile 3 (29%) compared with tertiles 1 (11%) and 2 (11%, p0.001). Inhospital death incidence was significantly increased across tertiles (from tertile 1 to tertiles 2 and 3, 1%, 4%, and 5%, respectively, p0.05). In receiver operating characteristic analysis, a threshold value of GGT26.5 U/L had 70% sensitivity and 60% specificity for CIN. After including variables found significant in univariate analysis, the presence of diabetes mellitus (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.22 to 2.31, p0.001), C-reactive protein (for each 1 mg/L increase; OR 1.01, 95% CI 1.00 to 1.02, p = 0.007), contrast volume (for each 1-ml increase; OR 1.01, 95% CI 1.00 to 1.02, p = 0.012), and GGT26.5 U/L (OR 2.59, 95% CI 1.48 to 4.53, p0.001) were found as independent associates of CIN in multivariate regression analysis. Each 1 U/L increase in GGT was also associated with CIN risk (OR 1.04, 95% CI 1.03 to 1.06, p0.001). In conclusion, GGT on admission was a significant and independent predictor of CIN after PPCI in patients with ST-segment elevation myocardial infarction.

Objective: Electrical storm (ES) is a life-threatening pathology that requires immediate and effective treatment due to increased morbidity and mortality. Catheter ablation (CA) is an effective therapeutic option, particularly in patients with drug resistant ventricular arrhythmia episodes. These procedures should only be performed in highly specialized and experienced centers. Here we aimed to assess safety and efficacy of CA in a relatively large cohort with ES in our tertiary center hospital. Methods: A total of 44 patients (90.9% male; mean age: 59.7±10.3 years) with ischemic cardiomyopathy undergoing CA for drug-refractory ES were prospectively evaluated. Procedures were performed using non-contact and electro-anatomic mapping systems. Long-term follow-up analysis addressed the predictors of ES recurrence and cardiac mortality. Results: Acute success rates for clinical and non-clinical VTs were 90.8% and 55.5%, respectively. A mean follow-up at 28±11 months revealed cardiac mortality in 8 (18%) patients, 39 (88.6%) patients were free from the ES, and 24 (55%) patients remained free from both ES and paroxysmal VT episodes. In multivariate regression analysis, recurrence of ES (OR=3.11, 95% CI: 1.65-4.62, p=0.001), LVEF, and serum creatinine were found as independent predictors of cardiac mortality. In addition, substrate based ablation, implantation of ICD for secondary prophylaxis, LVEF, and serum creatinine were good predictors of ES recurrence. Conclusion: Catheter ablation for ventricular arrhythmias in the course of ES in patients with ischemic cardiomyopathy is safe with an acceptable success rate. (Anatol J Cardiol 2016; 16: 159-64)

Polycyclic aromatic hydrocarbons are known for their carcinogenic and mutagenic effects on human health. This therefore calls for the regulation of their concentrations in air, water, and soil. Naphthalene as the simplest in structure of the polycyclic aromatic hydrocarbons is mainly used as a starter material for other chemicals but also has impacts on human health. A method is therefore proposed for the determination of naphthalene in water samples by gas chromatography mass spectrometry after liquid-liquid extraction. The extraction method was optimized to improve the extraction output, thereby lowering the limit of detection. The limits of detection and quantification obtained for naphthalene were 4.4 and 14.6 ng mL−1, respectively. Deuterated anthracene was used as internal standard to enhance the precision of the method, for which a relative standard deviation of 4.3% was obtained. The percent recovery of naphthalene obtained from tap water was ranged between 93.8 and 102.2.

Sainte-Anne Hospital is the largest psychiatric hospital in Paris. Its long and fascinating history began in the 18th century. In 1952, it was at Sainte-Anne Hospital that Jean Delay and Pierre Deniker used the first neuroleptic, chlorpromazine, to cure psychiatric patients, putting an end to the expansion of psychosurgery. The Department of Neuro-psychosurgery was created in 1941. The works of successive heads of the Neurosurgery Department at Sainte-Anne Hospital summarized the history of psychosurgery in France.Pierre Puech defined psychosurgery as the necessary cooperation between neurosurgeons and psychiatrists to treat the conditions causing psychiatric symptoms, from brain tumors to mental health disorders. He reported the results of his series of 369 cases and underlined the necessity for proper follow-up and postoperative re-education, illustrating the relative caution of French neurosurgeons concerning psychosurgery.Marcel David and his assistants tried to follow their patients closely postoperatively; this resulted in numerous publications with significant follow-up and conclusions. As early as 1955, David reported intellectual degradation 2 years after prefrontal leucotomies.Jean Talairach, a psychiatrist who eventually trained as a neurosurgeon, was the first to describe anterior capsulotomy in 1949. He operated in several hospitals outside of Paris, including the Sarthe Psychiatric Hospital and the Public Institution of Mental Health in the Lille region. He developed stereotactic surgery, notably stereo-electroencephalography, for epilepsy surgery but also to treat psychiatric patients using stereotactic lesioning with radiofrequency ablation or radioactive seeds of yttrium-90.The evolution of functional neurosurgery has been marked by the development of deep brain stimulation, in particular for obsessive-compulsive disorder, replacing the former lesional stereotactic procedures.The history of Sainte-Anne Hospital’s Neurosurgery Department sheds light on the initiation—yet fast reconsideration—of psychosurgery in France. This relatively more prudent attitude toward the practice of psychosurgery compared with other countries was probably due to the historically strong collaboration between psychiatrists and neurosurgeons in France.

International audience; Delineating tumor margins as accurately as possible is of primordial importance in surgical oncology: extent of resection is associated with survival but respect of healthy surrounding tissue is necessary for preserved quality of life. The real-time analysis of the endogeneous fluorescence signal of brain tissues is a promising tool for defining margins of brain tumors. The present study aims to demonstrate the feasibility of multimodal optical analysis to discriminate fresh samples of gliomas, metastases and meningiomas from their appropriate controls. Tumor samples were studied on an optical fibered endoscope using spectral and fluorescence lifetime analysis and then on a multimodal set-up for acquiring spectral, one and two-photon fluorescence images, second harmonic generation signals and two-photon fluorescence lifetime datasets. The obtained data allowed us to differentiate healthy samples from tumor samples. These results confirmed the possible clinical relevance of this real-time multimodal optical analysis. This technique can be easily applied to neurosurgical procedures for a better delineation of surgical margins.

Increased circulating D-dimer levels have been correlated with adverse outcomes in various clinical conditions. To our knowledge, the association of on-admission D-dimer and in-hospital mortality in infective endocarditis (IE) has not been investigated. We hypothesized that increased on-admission D-dimer levels would correlate with adverse outcomes when prospectively studied in patients with IE.In this prospective study, a total of 157 consecutive patients with the definite IE diagnosis met the inclusion criteria and underwent testing for on-admission D-dimer and CRP assays. The outcome measure was in-hospital death from any cause.In-hospital mortality occurred in 40 (26%) patients. Increased levels of plasma D-dimer (5.1 ± 1.7 vs 1.9 ± 0.8, p0.001), CRP [45(13-98) vs 12(5-28), p0.001] were found in dead patients compared with those survived. In addition to S. aureus infection, increased leukocyte count, end-stage renal disease, LVEF50%, vegetation size of10mm, perivalvular abscess, on-admission D-dimer (HR: 1.32; 95% CI: 1.24-1.40; p0.001) and CRP (HR: 1.18; 95% CI: 1.09-1.36; p=0.001) levels were significantly associated with in-hospital mortality. Furthermore, the sensitivity and specificity of D-dimer ≥ 4.2mg/L in predicting in-hospital death in IE were 86% and 85%, respectively. Moreover, the sensitivity and specificity of CRP levels ≥ 13.6 mg/L were 72% and 69%, respectively.Our findings suggest that on-admission D-dimer level may be a simple, available and valuable biomarker that allows us to identify high-risk IE patients for in-hospital mortality. D-dimer ≥ 4.2mg/L, CRP ≥ 13.6 mg/L were independently associated with IE related in-hospital death.

Early morning blood pressure surge (MBPS) is a risk factor for cardiovascular events (CVEs), but the relationship with uric acid is not well understood. The authors aimed to determine the association between MBPS and increased uric acid and the effect of elevated MBPS and uric acid combination on CVEs. A total of 921 patients underwent 24-hour ambulatory blood pressure monitoring and were followed for a median of 40 months. During this period, 103 (11.2%) CVEs occurred. There was a significant relationship between increasing quartiles of serum uric acid level and increasing values of MBPS (P

Objectives: Increased epicardial adipose tissue (EAT) thickness is a risk factor for cardiovascular diseases. Previous studies have demonstrated that EAT thickness is increased in patients with hypertension compared with normotensive individuals. In the current study, we aimed to evaluate whether echocardiographically measured EAT thickness differs among patients with normotension, prehypertension, hypertension, and the relation between EAT thickness and blood pressure levels in prehypertensives. Study design: Patients with prehypertension (n=50) and hypertension (n=50) and normotensive healthy subjects (n=50) according to the American Hypertension Guidelines (Joint National Committee 7) were enrolled in the study. All participants underwent transthoracic echocardiographic examination. EAT thickness was measured from the parasternal long-axis view at end-systole. Results: Compared with normotensives, EAT thickness was significantly increased in subjects with prehypertension and hypertension (4.1+-1.1 mm, 5.4+-1.3 mm and 6.6+-1.5 mm, respectively, p

Subvalvular apparatus preservation is an important concept in mitral valve replacement (MVR) surgery that is performed to remedy mitral regurgitation. In this study, we sought to determine the effects of papillary muscle repositioning (PMR) on clinical outcomes and echocardiographic left ventricular function in rheumatic mitral stenosis patients who had normal left ventricular systolic function. We prospectively assigned 115 patients who were scheduled for MVR surgery with mechanical prosthesis to either PMR or MVR-only groups. Functional class and echocardiographic variables were evaluated at baseline and at early and late postoperative follow-up examinations. All values were compared between the 2 groups. The PMR group consisted of 48 patients and the MVR-only group of 67 patients. The 2 groups’ baseline characteristics and surgery-related factors (including perioperative mortality) were similar. During the 18-month follow-up, all echocardiographic variables showed a consistent improvement in the PMR group; the mean left ventricular ejection fraction deteriorated significantly in the MVR-only group. Comparison during follow-up of the magnitude of longitudinal changes revealed that decreases in left ventricular end-diastolic and end-systolic diameters and in left ventricular sphericity indices, and increases in left ventricular ejection fractions, were significantly higher in the PMR group than in the MVR-only group. This study suggests that, in patients with rheumatic mitral stenosis and preserved left ventricular systolic function, the addition of papillary muscle repositioning to valve replacement with a mechanical prosthesis improves left ventricular dimensions, ejection fraction, and sphericity index at the 18-month follow-up with no substantial undesirable effect on the surgery-related factors.

Objectives The association of QRS duration (QRSd) with ventricular dyssynchrony is well-known in systolic heart failure (HF). However, there are no data regarding the relationship between QRSd and atrial dyssynchrony in patients with HF. We aimed to investigate the association of QRSd with intra-atrial and inter-atrial dyssynchrony in patients with systolic HF by using color tissue Doppler imaging (TDI). Methods The study consisted of 70 systolic HF patients and 35 healthy controls. According to QRSd, HF patients were categorized into 2 subgroups as narrow QRS (n = 35) and wide QRS (n = 35) groups. Time intervals between the onset of P-wave and the onset of A-wave on color TDI from the right atrium (P-RA), inter-atrial septum (P-IAS) and left atrium (P-LA) were measured. Atrial dyssynchrony was defined as differences between P-RA and P-IAS (RA dyssynchrony), between P-LA and P-IAS (LA dyssynchrony) and between P-RA and P-LA (inter-atrial dyssynchrony). Results In patients with either HF groups, we observed significant impairment in intra-atrial and inter-atrial synchronicity compared with the controls (P

Serum uric acid (SUA) level is known as a significant predictor for cardiovascular diseases, partly through increased inflammatory response and smooth muscle cell proliferation. Inflammation and smooth muscle cells play a crucial role in the pathogenesis of in-stent restenosis (ISR). However, the relation between SUA and ISR has not been studied. The aim of the present study was to investigate the predictive value of preprocedural SUA on the development of ISR in patients who undergo coronary bare-metal stent implantation. Clinical, biochemical, and angiographic data from 708 consecutive patients (mean age 60.3 ± 9.3 years, 71% men) who had undergone bare-metal stent implantation and additional control coronary angiography for stable or unstable angina pectoris were analyzed. Patients were divided into tertiles on the basis of preprocedural SUA levels. Stent restenosis was observed in 54 patients (23%) in the lowest tertile, in 79 (34%) in the middle tertile, and in 109 (46%) in the highest tertile (p0.001). Using multiple logistic regression analysis, diabetes mellitus, smoking, high-density lipoprotein cholesterol, stent length, C-reactive protein level, and preprocedural SUA level emerged as independent predictors of ISR. On receiver-operating characteristics curve analysis, SUA level5.5 mg/dl had 75% sensitivity and 71% specificity (area under the curve 0.784, p0.001) in predicting ISR. In conclusion, higher preprocedural SUA is a powerful and independent predictor of bare-metal stent restenosis in patients with stable and unstable angina pectoris.

The use of αβ+ T-cell-depleted grafts is a novel approach to prevent graft failure, graft-versus-host disease (GVHD), and non-relapse mortality (NRM) in patients undergoing haploidentical hematopoietic stem cell transplantation.Thirty-four patients with acute leukemia and lacking a match donor were treated with αβ T-cell-depleted allografts from haploidentical family donors. A total of 24 patients had acute myeloid leukemia (AML) and 10 had acute lymphoblastic leukemia. 84.4% of patients were in the high-risk group, and 55.9% were not in remission. The preparative regimen included thiotepa, melphalan, fludarabine, and anti-thymocyte globulin-Fresenius. Grafts were peripheral blood stem cells engineered by TcR-alpha/beta depletion.Neutrophil and platelet engraftment was achieved on days +12 (range, 10.5-15) and +11 (range, 10-12). All but three patients were engrafted with full donor chimerism. Grade III-IV acute GVHD occurred in two (5.9%) patients and chronic GVHD in two (6.1%). Disease-free survival and overall survival were 42 and 54% at 1 year, respectively. AML as disease type (HR: 4.87, 95% CI: 1.50-15.87) and mother as donor (HR: 1.05, 95% CI: 1.00-1.11) were found to be independent risk factors on patient survival. Mortality and NRM in the first 100 days were 5 of 34 (14.7%) and 4 of 34 (11.7%). Relapse was the main cause of death (56.3%). T-cell reconstitution appears to be faster than that reported in published data with CD3/CD19-depleted grafts.αβ T-cell-depleted haploidentical transplantation may be a good alternative for high-risk patients if there are no human leukocyte antigen matched donors.

Background The neutrophil-to-lymphocyte ratio is an independent predictor of worse prognosis in both infectious and cardiovascular disease. We hypothesized that an increased neutrophil-to-lymphocyte ratio at admission would predict in-hospital unfavourable outcomes in patients with infective endocarditis (IE). Methods We retrospectively analyzed clinical, laboratory, and echocardiographic data in a total of 121 consecutive adult patients (64 men; mean age, 54.7 ± 14.2 years) with definite IE. Results Among all patients, the prespecified clinical outcomes were experienced in 46 patients (38%). In-hospital mortality and central nervous system (CNS) events occurred in 29 (24%) and 21 patients (17%), respectively. The neutrophil-to-lymphocyte ratio at admission was found to be significantly higher for either composite end point. On using multiple Cox regression analysis, vegetation size ≥ 10 mm, end-stage renal disease, Staphylococcus aureus infection, low hemoglobin level, increased C-reactive protein (CRP) level, and high neutrophil-to-lymphocyte ratio at admission emerged as independent predictors of in-hospital unfavourable outcomes. In the receiver operating characteristics (ROC) curve analysis, a neutrophil-to-lymphocyte ratio > 7.1 had 80% sensitivity and 83% specificity in predicting adverse outcomes. Conclusion High neutrophil-to-lymphocyte ratio at admission is an independent predictor of in-hospital mortality and CNS events in patients with IE. However, prospective validation of these findings is required.

BACKGROUND: Hypertension (HT) is one of the main conditions associated with left ventricular (LV) diastolic dysfunction. Epicardial fat tissue (EFT) serves as a source of a plenty of proinflammatory cytokines and is associated with increased cardiovascular events. The aim of the current study was to evaluate the relation among echocardiographically measured EFT thickness, systemic inflammation, and LV diastolic dysfunction in patients with essential HT. PATIENTS AND METHODS: The study included 135 newly diagnosed and untreated hypertensive outpatients. On the basis of conventional Doppler and tissue Doppler imaging-derived parameters, patients were divided into two groups: 60 patients with normal diastolic function and 75 patients with LV diastolic dysfunction. EFT thickness was measured from the parasternal long-axis view at end-systole and high-sensitivity C-reactive protein (hs-CRP) was assessed using the latex-enhanced immunoturbidimetric method. RESULTS: In patients with LV diastolic dysfunction, EFT thickness was significantly increased compared with the normal diastolic function group (7.9 ± 1.7 vs. 6.3 ± 1.5 mm; P < 0.001, respectively). Serum hs-CRP level was also significantly higher in the LV diastolic dysfunction group (P < 0.001) and was correlated with EFT thickness (r = 0.442, P < 0.001). In stepwise multivariate logistic regression analysis, EFT thickness (odds ratio 1.27, 95% confidence interval 1.12-1.43; P = 0.006) and hs-CRP level (odds ratio 1.42, 95% confidence interval 1.18-1.72; P = 0.003) emerged as independent positive predictors of LV diastolic dysfunction. CONCLUSION: In patients with newly diagnosed and untreated essential HT, increased EFT thickness and hs-CRP level are significantly related to impaired LV diastolic function independent from other factors, including age, waist circumference, and 24-h systolic blood pressure.

Objectives Left ventricular (LV) synchronous contraction is impaired in patients with hypertension (HT). The deleterious effects of HT on cardiovascular system are more evident in patients with nondipper HT than dippers. In this study, we aimed to investigate the effect of nondipping HT on LV systolic synchronicity compared with dippers and controls. Methods One hundred patients with newly diagnosed essential HT and 50 normotensive subjects were enrolled in this study. The hypertensive patients were assigned 2 groups comprising 55 dippers and 45 nondippers. Each subject underwent a comprehensive transthoracic echocardiographic examination. The evaluation of systolic dyssynchrony was performed by tissue synchronization imaging, and the time to regional peak systolic tissue velocity (Ts) in LV was measured on the basis of 12 segmental models. The standard deviation (SD) of the 12 LV segments (Ts-SD-12) and maximal difference in Ts between any two of the 12 LV segments (Ts-12) were calculated. Results Compared with the control group, the synchronicity indexes were significantly prolonged in the hypertensive patients. Furthermore, Ts-SD-12 and Ts-12 values were found to be significantly impaired in patients with nondipper HT, compared with dippers: Ts-SD-12 (38.1 ± 18.7 vs. 31.8 ± 15.4, P ≤ 0.001); Ts-12 (123.0 ± 50.6 vs. 98.4 ± 42.3, P ≤ 0.001). Stepwise multivariate logistic regression analysis revealed a significant negative association between LV dyssynchrony indices and percentage decline in BP level from day to night. Conclusion Synchronous systolic contraction of LV is found to be significantly impaired in patients with nondipping circadian pattern of HT compared with dippers and the controls.

Red cell distribution width (RDW) is a strong prognostic marker for systolic left heart failure regardless of the anemia status, and heart rate variability (HRV) is negatively associated with mortality and sudden cardiac death in patients with systolic left heart failure. Their relationship has not been investigated in the previous literature.One hundred eighty four patients who had been previously diagnosed with systolic left heart failure (with ischemic or non-ischemic etiology) were retrospectively enrolled in our study. Patients underwent 24-h electrocardiographic monitoring, and blood samples for RDW and other variables were analyzed. Study population was grouped into tertiles of RDW (Tertile 1: 13.4 ± 1.4%, Tertile 2: 14.6 ± 1.4%, and Tertile 3: 17.1 ± 1.2%).Most of the characteristics of patients were similar among RDW tertiles. Standard deviation of all normal RR intervals (SDNN), standard deviation of the averages of RR intervals in all 5-min segments (SDANN) and root-mean square of difference of successive RR intervals (RMSSD) values significantly differed among groups (p0.001). The highest RDW tertile had the lowest HRV values, and Pearson correlation analysis yielded a negative correlation between HRV parameters and RDW (for SDNN, SDANN, RMSSD; r = 0.373, 0.340, 0.362, respectively, p0.001 for all). In stepwise multivariate analysis HRV was independently associated with RDW.The HRV parameters were independently associated with RDW in patients with systolic left heart failure.

Myocardial clefts are defined as narrow, deep blood-filled invaginations within the left ventricular myocardium. They occur in hypertrophic cardiomyopathy patients with different frequency and represent a distinctive morphological expression of hypertrophic cardiomyopathy. Although two-dimensional transthoracic echocardiography is able to detect myocardial clefts in some cases, cardiovascular magnetic resonance imaging with its high spatial resolution can detect myocardial clefts not visualized with echocardiography. In this report, we represent multimodality imaging of a septal myocardial cleft in a hypertrophic cardiomyopathy patient.

Aim: To determine the association of monocyte count-to-high-density lipoprotein (HDL)-cholesterol ratio, a recently emerged inflammatory marker, with abdominal aortic aneurysm (AAA) size. Patients & methods: A total of 120 asymptomatic AAA subjects (99 male, mean age: 67.1 ± 10.2 years) were enrolled into the study. All data were compared between patients with low and high admission monocyte/HDL ratio. Multivariate linear regression analysis was performed to study the relationship between different variables and AAA size. Results: Compared to patients with below-median monocyte/HDL ratio, aneurysm diameter was significantly higher in above-median monocyte/HDL ratio group (54.3 ± 10.6 mm vs 62.0 ± 12.4 mm, p < 0.001, respectively). Hypertension, coronary artery disease, monocyte/HDL ratio and C-reactive protein were independently associated with AAA diameter. Conclusion: Monocyte/HDL ratio is independently associated with AAA size.

Objective Thyroid hormones have both direct and indirect effects on thermogenesis such as modulating vascular smooth muscle cell proliferation. However, the influence of more subtle changes in thyroid hormones on coronary atherosclerosis remains a matter of speculation. Smooth muscle cells play a crucial role in the pathogenesis of in-stent restenosis (ISR). However, the relationship between free thyroxine (fT4) and ISR has not been studied. In the present study, we aimed to assess the role of preprocedural serum fT4 level on the development of ISR in patients undergoing coronary bare metal stent (BMS) implantation. Materials and methods We enrolled and analyzed clinical, biochemical, and angiographic data from 705 consecutive patients without a history of primary thyroid disease [mean age 60.3 ± 9.3 years, 505 (72%) male]; all patients had undergone BMS implantation and further control coronary angiography owing to stable or unstable angina pectoris. Patients were divided into 3 tertiles based on preprocedural serum fT4 levels. Results ISR was observed in 53 (23%) patients in the lowest tertile, 82 (35%) patients in the second tertile, and 107 (46%) patients in the highest fT4 tertile (p < 0.001). Using multiple logistic regression analysis, five characteristics emerged as independent predictors of ISR: diabetes mellitus, smoking, HDL-cholesterol, stent length, and preprocedural serum fT4 level. In receiver operating characteristics curve analysis, fT4 level > 1.23 mg/dL had 70% sensitivity and 73% specificity (AUC: 0.75, p < 0.001) in predicting ISR. Conclusion Higher preprocedural serum fT4 is a powerful and independent predictor of BMS restenosis in patients with stable and unstable angina pectoris.

Triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) has been suggested as a simple method to identify unfavorable cardiovascular outcomes in the general population. The effect of the TG/HDL-C ratio on essential hypertensive patients is unclear. About 900 consecutive essential hypertensive patients (mean age 52.9 +/- 12.6 years, 54.2% male) who visited our outpatient hypertension clinic were analyzed. Participants were divided into quartiles based on baseline TG/HDL-C ratio and medical records were obtained periodically for the occurrence of fatal events and composite major adverse cardiovascular events (MACEs) including transient ischemic attack, stroke, aortic dissection, acute coronary syndrome, and death. Participants were followed for a median of 40 months (interquartile range, 35-44 months). Overall, a higher quartile of TG/HDL-C ratio at baseline was significantly linked with higher incidence of fatal and nonfatal cardiovascular events. Using multivariate Cox regression analysis, plasma TG/HDL-C ratio was independently associated with increased risk of fatal events (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.13-1.37; P

Background: It has been shown that psychological status is associated with the likelihood of atrial fibrillation (AF). Prolongation of the duration of atrial electromechanical delay (AEMD) is known to be a precursor for AF development. Aim: Therefore, we aimed to evaluate AEMD in patients with anxiety disorder. Methods: In this prospective study, a total of 82 anxiety disorder and 80 healthy subjects were enrolled. Symptoms of anxiety were evaluated by using the Hamilton Anxiety Rating Scale (HAM-A). P-wave dispersion (PWD) was measured on a 12-lead electrocardiogram. Both intra- and inter-AEMD were measured with tissue Doppler imaging. Results: Basal characteristics were similar between the two groups. PWD, inter- and right intra-AEMD were significantly prolonged in patients with anxiety disorders, compared to the control group (p < 0.05). In the correlation analysis, HAM-A was significantly and moderately correlated with right intra- and inter-AEMD, and PWD. Conclusions: Patients suffering from anxiety disorders are characterised by prolonged AEMD, which can provide significant contributions to evaluate the risk for AF development in this group.