Multi-modality imaging evaluation of recurrent Tako-tsubo syndrome in a patient with coronary artery fibromuscular dysplasia

Background

Integrated bedside and sophisticated cardiac imaging techniques help characterize the discrepancy between myocardial injury and mechanic dysfunction in acute myocardial infarction.

Case presentation

A 57 year-old woman presented with sudden onset chest pain and ventricular fibrillation after hearing of her brother’s death. The electrocardiography indicated “anterior wall ST segment elevation myocardial infarction”. Coronary angiography ruled out obstructive lesion in the major coronary arteries, but revealed fibromuscular dysplasia of the distal left anterior descending artery. The ventriculography showed remarkable ventricular dilation, which affected much broader myocardium than the culprit vessel supplied. In a subsequent cardiac magnetic resonance study, delayed contrast (gadolinium) image revealed a focal left ventricular (LV) apical infarction. Her LV systolic function normalized within 1 week, except for a residual apical hypokinesis. She developed recurrent chest pain and LV dilation when she was laid off 9 months later. After supportive therapy, her symptoms improved and LV dysfunction normalized again.

Conclusions

“Tako-tsubo” syndrome can occur recurrently in the heart with pre-existing localized myocardial infarction. Its molecular mechanism and clinical significance warrants further investigation.

     

Factors associated with pain level in non-cardiac chest pain patients with comorbid panic disorder

Background

Panic disorder (PD) is highly prevalent in patients with non-cardiac chest pain (NCCP). This study aims to explore the role of psychological factors (PD intensity, anxiety sensitivity, heart-related fear, attention and avoidance) common to NCCP and PD in predicting chest pain levels in patients with both conditions.

Methods

This association was investigated in emergency department patients with NCCP and PD receiving either evidence-based treatment of PD or treatment as usual. Patients were assessed at baseline and 14 weeks later for post-treatment.

Results

Only heart-focused fear and attention for cardiac sensations independently explained a significant portion of the variance in baseline pain (n?=?66). At 3 months follow-up (n?=?53), changes in heart-related fear was the only factor independently associated with changes in chest pain intensity. Even in patients with PD, fear specific to cardiac sensations seems to play a central role in determining NCCP intensity.

Conclusion

These results suggest that the efficacy of intervention for patients with PD and comorbid NCCP could be improved by targeting heart-related fear and attention.

Trial registration

NCT00736346

     

Clinical characteristics of patients with suspected cardiac chest pain and angiographically normal coronary arteries in a secondary care hospital

Background

An important number of patients with suspected cardiac chest pain have non-obstructive coronary artery disease. Our purpose was to describe the clinical characteristics of patients with normal or near-normal coronary arteries in routine cardiological practice in a secondary care hospital.

Methods

In 2013, consecutive patients referred for invasive coronary angiography with suspected cardiac chest pain were analysed at a single-centre (Westfriesgasthuis, Hoorn, the Netherlands). Coronary arteries were defined as normal or near-normal if they showed no stenosis or only slight wall irregularities on visual assessment. Patients with a final non-cardiac diagnosis for the chest pain were excluded.

Results

A total of 558 patients were included. Of these, 151 (27%) showed normal or near-normal coronary arteries on visual assessment. This group of patients were significantly more often female (p < 0.001), younger (p < 0.001) and non-diabetic (p = 0.002). Forty percent of hospitalised patients who had normal or near-normal coronary arteries at coronary angiography showed an elevated troponin.

Conclusion

In routine cardiological practice, around 1 out of 4 patients with suspected cardiac chest pain undergoing invasive angiography had normal or near-normal coronary arteries. We suggest that premenopausal women with suspected cardiac chest pain could be considered for non-invasive coronary imaging as a first step in clinical practice.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Genomic integration occurs in the packaging cell via unexported lentiviral precursors

Objective

To use HIV-1 based lentivirus components to produce gene integration and the formation of a stable cell line in the packaging cell line without viral infection.

Results

A co-transfection of a Human Embryonic Kidney (HEK) 293 packaging cell line with Gag–pol (GP) and a transfer vector, without the envelope vector, produces a stable cell line after 2 weeks of selection. Furthermore, a matrix protein deficient GP in the packaging vector enhances this integration. This supports that, in theory, unexported lentiviral cores produced within the packaging cell can infect itself without requiring the release of any lentiviral particles.

Conclusion

If the packaging cell is also the target cell, then gene integration leading to a stable cell line can be accomplished without viral particle infection.

     

A new technique to salvage myocardium following the failure of thrombus aspiration in acute myocardial infarction: a case report

Background

The failure of aspiration thrombectomy may negatively impact outcomes in patients with acute myocardial infarction (AMI), but the available options are limited.

Case presentation

A 41-year-old man with chest pain for 2?h presented with ST-segment elevation myocardial infarction. Coronary angiography revealed a large filling defect extending from the distal left main (LM) coronary artery into the proximal left circumflex (LCX) coronary artery. The whole thrombus moved and occluded the proximal left anterior descending (LAD) artery, while the guidewire crossed the lesion. Dedicated manual aspiration thrombectomy (MAT) and balloon dilation failed to reduce thrombus burden. We considered thrombus extraction as impossible when it moved forward to occlude the middle LAD. To reduce infarct size, a new balloon-pushing technique was successfully performed to move the thrombus to the terminal LAD based on the actual condition of the LAD. The final angiogram demonstrated no stenosis in the LM artery and stent deployment was not performed. A 1-week follow-up coronary angiography revealed the complete resolution of thrombus and flow restoration in the left coronary artery. Intravascular ultrasound (IVUS) showed nonsignificant residual stenosis of the LM artery. No adverse events occurred during a 12-month follow-up period.

Conclusion

This case suggests that the new balloon-pushing technique is a useful remedy if repeated MAT fails during AMI.

     

Iridoid and phenylethanoid/phenylpropanoid metabolite profiles of <Emphasis Type="Italic">Scrophularia</Emphasis> and <Emphasis Type="Italic">Verbascum</Emphasis> species used medicinally in North America

Introduction

Botanicals containing iridoid and phenylethanoid/phenylpropanoid glycosides are used worldwide for the treatment of inflammatory musculoskeletal conditions that are primary causes of human years lived with disability, such as arthritis and lower back pain.

Objectives

We report the analysis of candidate anti-inflammatory metabolites of several endemic Scrophularia species and Verbascum thapsus used medicinally by peoples of North America.

Methods

Leaves, stems, and roots were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and partial least squares-discriminant analysis (PLS-DA) was performed in MetaboAnalyst 3.0 after processing the datasets in Progenesis QI.

Results

Comparison of the datasets revealed significant and differential accumulation of iridoid and phenylethanoid/phenylpropanoid glycosides in the tissues of the endemic Scrophularia species and Verbascum thapsus.

Conclusions

Our investigation identified several species of pharmacological interest as good sources for harpagoside and other important anti-inflammatory metabolites.

     

Heart rate variability after radiofrequency ablation of epicardial ganglionated plexuses on the ovine left atrium

Background

Ganglionated plexuses (GP) are terminal parts of cardiac autonomous nervous system (ANS). Radiofrequency ablation (RFA) for atrial fibrillation (AF) possibly affects GP. Changes in heart rate variability (HRV) after RFA can reflect ANS modulation.

Methods

Epicardial RFA of GP on the left atrium (LA) was performed under the general anesthesia in 15 mature Romanov sheep. HRV was used to assess the alterations in autonomic regulation of the heart. A 24???hour ECG monitoring was performed before the ablation, 2 days after it and at each of the 12 following months. Ablation sites were evaluated histologically.

Results

There was an instant change in HRV parameters after the ablation. A standard deviation of all intervals between normal QRS (SDNN), a square root of the mean of the squared differences between successive normal QRS intervals (RMSSD) along with HRV triangular index (TI), low frequency (LF) power and high frequency (HF) power decreased, while LF/HF ratio increased. Both the SDNN, LF power and the HF power changes persisted throughout the 12???month follow???up. Significant decrease in RMSSD persisted only for 3 months, HRV TI for 6 months and increase in LF/HF ratio for 7 months of the follow???up. Afterwards these three parameters were not different from the preprocedural values.

Conclusions

Epicardial RFA of GP’s on the ovine left atrium has lasting effect on the main HRV parameters (SDNN, HF power and LF power). The normalization of RMSSD, HRV TI and LF/HF suggests that HRV after epicardial RFA of GPs on the left atrium might restore over time.

     

Corneal Collagen Cross-Linking for the Management of Mycotic Keratitis

Purpose

To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.

Design

Retrospective case series in a tertiary university hospital.

Participants

CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.

Methods

The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.

Main Outcome Measures

Grade of the corneal infection.

Results

Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).

Conclusions

The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.

     

Pregnancy-related myocardial infarction

Introduction

The risk of acute myocardial infarction in young women is low, but increases during pregnancy due to the physiological changes in pregnancy, including hypercoagulability. Ischaemic heart disease during pregnancy is not only associated with increased maternal morbidity and mortality, but also with high neonatal complications. Advancing maternal age and other risk factors for cardiovascular diseases may further increase the risk of ischaemic heart disease in young women.

Methods

We searched the coronary angiography database of a Dutch teaching hospital to identify women with acute myocardial infarction who presented during pregnancy or postpartum between 2011 and 2013.

Results

We found two cases. Both women were in their early thirties and both suffered from myocardial infarction in the postpartum period. Acute myocardial infarction was due to coronary stenotic occlusion in one patient and due to coronary artery dissection in the other patient. Coronary artery dissection is a relatively frequent cause of myocardial infarction during pregnancy. Both women were treated by percutaneous coronary intervention and survived.

Conclusion

Physicians should be aware of the increased risk of myocardial infarction when encountering pregnant or postpartum women presenting with chest pain.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Effect of everolimus on the glucose metabolic pathway in mouse skeletal muscle cells (C2C12)

Introduction

Everolimus selectively inhibits mammalian target of rapamycin complex 1 (mTORC1) and exerts an antineoplastic effect. Metabolic disturbance has emerged as a common and unique side effect of everolimus.

Objectives

We used targeted metabolomic analysis to investigate the effects of everolimus on the intracellular glycometabolic pathway.

Methods

Mouse skeletal muscle cells (C2C12) were exposed to everolimus for 48 h, and changes in intracellular metabolites were determined by capillary electrophoresis time-of-flight mass spectrometry. mRNA abundance, protein expression and activity were measured for enzymes involved in glycometabolism and related pathways.

Results

Both extracellular and intracellular glucose levels increased with exposure to everolimus. Most intracellular glycometabolites were decreased by everolimus, including those involved in glycolysis and the pentose phosphate pathway, whereas no changes were observed in the tricarboxylic acid cycle. Everolimus suppressed mRNA expression of enzymes related to glycolysis, downstream of mTOR signaling enzymes and adenosine 5′-monophosphate protein kinases. The activity of key enzymes involved in glycolysis and the pentose phosphate pathway were decreased by everolimus. These results show that everolimus impairs glucose utilization in intracellular metabolism.

Conclusions

The present metabolomic analysis indicates that everolimus impairs glucose metabolism in muscle cells by lowering the activities of glycolysis and the pentose phosphate pathway.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.

     

Extrahepatic cholangiocarcinoma with prolonged survival: a case report

Background

Cholangiocarcinoma has poor prognosis and short term-survival. Here, we report the case of a patient with unusually prolonged survival.

Case presentation

Our patient was a 56-year-old Arab man with a 6-month history of obstructive jaundice. A computed tomography scan of his abdomen revealed a mass at the confluence of the hepatic ducts with suspected malignant strictures on endoscopy. A positive tissue diagnosis was achieved more than 18 months after commencement of his symptoms. He remained functional throughout this period despite recurrent episodes of cholangitis.

Conclusions

Cholangiocarcinoma is a presumably fatal disease, especially because patients tend to present late with unresectable disease. Many patient-related and disease-related factors may alter survival.

     

Sensing acidosis: nociception or sngception?

Background

Sensing tissue acidosis is an important function of the somatosensory nervous system to response to noxious stimuli.

Main body

In the pain clinic, acid or soreness sensation is a characteristic sensory phenotype of various acute and chronic pain syndromes, such as delayed onset muscle soreness, fibromyalgia, and radicular pain. However, soreness sensation is a sign of successful analgesia for acupuncture and noxipoint therapy. Thus, the nature of acid or soreness sensation is not always nociceptive (or painful) and could be anti-nociceptive. To facilitate the investigation of the molecular and neurobiological mechanisms of soreness sensation, we propose a concept called “sngception (sng- ception)” to describe the response of the somatosensory nervous system to sense tissue acidosis and to distinguish it from nociception. “Sng” is a Taiwanese word that represents the state of soreness while at the same time imitates the natural vocalization of humans feeling sore.

Conclusion

Here we propose sngception as a specific somatosensory function that transmits the acid sensation from the peripheral to the central nervous system. Sngception could partially overlap with nociception, but it could also transmit antinociception, proprioception, and pruriception.

     

Untargeted metabolomics suffers from incomplete raw data processing

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.

     

A methodology for elucidating regulatory mechanisms leading to changes in lipid profiles

Introduction

It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.

Objectives

This work simplifies this process.

Methods

A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.

Results

The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.

Conclusion

This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.

     

Extraction of natural products from bark of <Emphasis Type="Italic">Betula pendula</Emphasis> using ionic liquids

Introduction

Aqueous–methanol mixtures have successfully been applied to extract a broad range of metabolites from plant tissue. However, a certain amount of material remains insoluble.

Objectives

To enlarge the metabolic compendium, two ionic liquids were selected to extract the methanol insoluble part of trunk from Betula pendula.

Methods

The extracted compounds were analyzed by LC/MS and GC/MS.

Results

The results show that 1-butyl-3-methylimidazolium acetate (IL-Ac) predominantly resulted in fatty acids, whereas 1-ethyl-3-methylimidazolium tosylate (IL-Tos) mostly yielded phenolic structures. Interestingly, bark yielded more ionic liquid soluble metabolites compared to interior wood.

Conclusion

From this one can conclude that the application of ionic liquids may expand the metabolic snapshot.