The impact of COVID‐19 on clinical outcomes among acute myocardial infarction patients undergoing early invasive treatment strategy

BackgroundThe implications of coronavirus disease 2019 (COVID‐19) infection on outcomes after invasive therapeutic strategies among patients presenting with acute myocardial infarction (AMI) are not well studied.HypothesisTo assess the outcomes of COVID‐19 patients presenting with AMI undergoing an early invasive treatment strategy.MethodsThis study was a cross‐sectional, retrospective analysis of the National COVID Cohort Collaborative database including all patients presenting with a recorded diagnosis of AMI (ST‐elevation myocardial infarction (MI) and non‐ST elevation MI). COVID‐19 positive patients with AMI were stratified into one of four groups: (1a) patients who had a coronary angiogram with percutaneous coronary intervention (PCI) within 3 days of their AMI; (1b) PCI within 3 days of AMI with coronary artery bypass graft (CABG) within 30 days; (2a) coronary angiogram without PCI and without CABG within 30 days; and (2b) coronary angiogram with CABG within 30 days. The main outcomes were respiratory failure, cardiogenic shock, prolonged length of stay, rehospitalization, and death.ResultsThere were 10 506 COVID‐19 positive patients with a diagnosis of AMI. COVID‐19 positive patients with PCI had 8.2 times higher odds of respiratory failure than COVID‐19 negative patients (p = .001). The odds of prolonged length of stay were 1.7 times higher in COVID‐19 patients who underwent PCI (p = .024) and 1.9 times higher in patients who underwent coronary angiogram followed by CABG (p = .001).ConclusionThese data demonstrate that COVID‐19 positive patients with AMI undergoing early invasive coronary angiography had worse outcomes than COVID‐19 negative patients.     

Low-quality employment trajectories and the risk of common mental health disorders among individuals with Swedish and foreign background – a register-based cohort study

ObjectiveThis study aimed to examine the effects of low-quality employment trajectories on severe common mental disorders (CMD) according to Swedish and foreign background.MethodsIn this longitudinal study based on Swedish population registries (N=2 703 687), low- and high-quality employment trajectories were the main exposures observed across five years (2005–2009), with severe CMD as outcome variable (2010–2017). Adjusted hazard ratios (HR) were calculated by means of Cox regression models and stratified according to Swedish and foreign background [first-generation (i) EU migrants, (ii) non-EU migrants, (iii) second-generation migrants, (iv) Swedish-born of Swedish background] and sex. The reference group was Swedish-born of Swedish background in a constant high-quality employment trajectory.ResultsSecond-generation migrants had an increased risk of CMD compared to Swedish-born of Swedish background when following low-quality employment trajectories [eg, male in constant low-quality HR 1.54, 95% confidence interval (CI) 1.41–1.68]. Female migrant workers, especially first-generation from non-EU countries in low-quality employment trajectories (eg, constant low-quality HR 1.66, 95% CI 1.46–1.88), had a higher risk of CMD compared to female Swedish-born of Swedish background. The risk for CMD according to employment trajectories showed little differences between first- and second-generation migrants.ConclusionLow-quality employment trajectories appear to be determinants of risk for CMD in association with Swedish or foreign background of origin and sex. Our study shows a higher risk for severe CMD in second-generation and non-EU migrant compared to Swedish-born of Swedish background in constant low-quality employment. Further qualitative research is recommended to understand the mechanism behind the differential mental health impact of low-quality employment trajectories according to foreign background.     

The impact of visual dysfunctions in recent-onset psychosis and clinical high-risk state for psychosis

Subtle subjective visual dysfunctions (VisDys) are reported by about 50% of patients with schizophrenia and are suggested to predict psychosis states. Deeper insight into VisDys, particularly in early psychosis states, could foster the understanding of basic disease mechanisms mediating susceptibility to psychosis, and thereby inform preventive interventions. We systematically investigated the relationship between VisDys and core clinical measures across three early phase psychiatric conditions. Second, we used a novel multivariate pattern analysis approach to predict VisDys by resting-state functional connectivity within relevant brain systems. VisDys assessed with the Schizophrenia Proneness Instrument (SPI-A), clinical measures, and resting-state fMRI data were examined in recent-onset psychosis (ROP, n = 147), clinical high-risk states of psychosis (CHR, n = 143), recent-onset depression (ROD, n = 151), and healthy controls (HC, n = 280). Our multivariate pattern analysis approach used pairwise functional connectivity within occipital (ON) and frontoparietal (FPN) networks implicated in visual information processing to predict VisDys. VisDys were reported more often in ROP (50.34%), and CHR (55.94%) than in ROD (16.56%), and HC (4.28%). Higher severity of VisDys was associated with less functional remission in both CHR and ROP, and, in CHR specifically, lower quality of life (Qol), higher depressiveness, and more severe impairment of visuospatial constructability. ON functional connectivity predicted presence of VisDys in ROP (balanced accuracy 60.17%, p = 0.0001) and CHR (67.38%, p = 0.029), while in the combined ROP + CHR sample VisDys were predicted by FPN (61.11%, p = 0.006). These large-sample study findings suggest that VisDys are clinically highly relevant not only in ROP but especially in CHR, being closely related to aspects of functional outcome, depressiveness, and Qol. Findings from multivariate pattern analysis support a model of functional integrity within ON and FPN driving the VisDys phenomenon and being implicated in core disease mechanisms of early psychosis states.Subject terms: Predictive markers, Psychosis     

Cocktails of Mycotoxins,Phytoestrogens, and Other Secondary Metabolites in Diets of Dairy Cows in Austria: Inferences from Diet Composition and Geo-Climatic Factors

Dairy production is a pivotal economic sector of Austrian and European agriculture. Dietary toxins and endocrine disruptors of natural origin such as mycotoxins and phytoestrogens can affect animal health, reproduction, and productivity. This study characterized the profile of a wide spectrum of fungal, plant, and unspecific secondary metabolites, including regulated, emerging, and modified mycotoxins, phytoestrogens, and cyanogenic glucosides, in complete diets of lactating cows from 100 Austrian dairy farms. To achieve this, a validated multi-metabolite liquid chromatography/electrospray ionization–tandem mass spectrometric (LC/ESI–MS/MS) method was employed, detecting 155 of >800 tested metabolites. Additionally, the most influential dietary and geo-climatic factors related to the dietary mycotoxin contamination of Austrian dairy cattle were recognized. We evidenced that the diets of Austrian dairy cows presented ubiquitous contamination with mixtures of mycotoxins and phytoestrogens. Metabolites derived from Fusarium spp. presented the highest concentrations, were the most recurrent, and had the highest diversity among the detected fungal compounds. Zearalenone, deoxynivalenol, and fumonisin B1 were the most frequently occurring mycotoxins considered in the EU legislation, with detection frequencies >70%. Among the investigated dietary factors, inclusion of maize silage (MS) and straw in the diets was the most influential factor in contamination with Fusarium-derived and other fungal toxins and metabolites, and temperature was the most influential among the geo-climatic factors.     

Celastrol regulates innate immunity response via NF-κB and Hsp70 in human retinal pigment epithelial cells

Elevated nuclear factor kappa B (NF-κB) activity and interleukin-6 (IL-6) secretion participates in the pathology of several age and inflammatory-related diseases, including age-related macular degeneration (AMD), in which retinal pigment epithelial cells are the key target. Recent findings reveal that heat shock protein 70 (Hsp70) may affect regulation of NF-κB. In the current study, effects of Hsp70 expression on NF-κB RelA/p65 activity were evaluated in human retinal pigment epithelial cells (ARPE-19) by using celastrol, a novel anti-inflammatory compound. Anti-inflammatory properties of celastrol were determined by measuring expression levels of IL-6 and endogenous NF-κB levels during lipopolysaccharide (LPS) exposure by using enzyme-linked immunosorbent assays (ELISA). Cell viability was measured by MTT and LDH assay, and Hsp70 expression levels were analyzed by Western blotting. ARPE-19 cells were transfected with hsp70 small interfering RNA (siRNA) in order to attenuate Hsp70 expression and activity of NF-κB RelA/p65 was measured using NF-κB consensus bound ELISA.Simultaneous exposures to LPS and celastrol reduced IL-6 expression levels as well as activity of phosphorylated NF-κB at serine 536 (Ser536) in ARPE-19 cells when compared to LPS exposure alone. In addition, inhibition of NF-κB RelA/p65 activity by celastrol was attenuated when Hsp70 response was silenced by siRNA. Favorable anti-inflammatory concentrations of celastrol showed no signs of cytotoxic response. Our findings reveal that celastrol is a novel plant compound which suppresses innate immunity response in human retinal pigment epithelial cells via NF-κB and Hsp70 regulation, and that Hsp70 is a critical regulator of NF-κB.     

Malignant Struma Ovarii: Two Case Reports and a Review of the Literature

Struma ovarii consists of thyroid tissue derived from germ cells in a mature teratoma. Malignant transformation is very rare, with clinically evident metastatic disease reported in approximately 20 cases. The rarity of this disease renders evaluation of treatment modalities difficult. There is evidence that these tumors behave like their thyroid counterparts, and cytoreductive surgery followed by ablation with radioactive iodine has been advocated. We report the diagnosis and treatment of 2 patients with metastatic malignant struma ovarii treated with a combination of surgery and radiation therapy.     

Molecular diagnostic alterations in squamous cell carcinoma of the head and neck and potential diagnostic applications

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that continues to be difficult to treat and cure. In many organ systems and tumor types, there have been significant advances in the understanding of the molecular basis for tumorigenesis, disease progression and genetic implications for therapeutics. Although tumorigenesis pathways and the molecular etiologies of HNSCC have been extensively studied, there are still very few diagnostic clinical applications used in practice today. This review discusses current clinically applicable molecular markers, including viral detection of Epstein–Barr virus and human papillomavirus, and molecular targets that are used in diagnosis and management of HNSCC. The common oncogenes EGFR, RAS, CCND1, BRAF, and PIK3CA and tumor suppressor genes p53, CDKN2A and NOTCH are discussed for their associations with HNSCC. Discussion of markers with potential future applications is also included, with a focus on molecular alterations associated with targeted therapy resistance.     

Paraneoplastic syndromes in patients with laryngeal neuroendocrine carcinomas: clinical manifestations and prognostic significance

Paraneoplastic syndromes are associated with a variety of malignant neoplasms and are systemic and non-metastatic manifestations that develop in a minority of cancer patients. This review examines all published cases of paraneoplastic syndromes associated with neuroendocrine carcinomas of the larynx. There are a total of ten patients reported with paraneoplastic syndromes associated with laryngeal neuroendocrine carcinomas in the literature. Of these, nine died and the tenth is alive with liver metastases. There were five cases of small-cell neuroendocrine carcinoma, four cases of moderately differentiated neuroendocrine carcinoma, and one case of well-differentiated neuroendocrine carcinoma associated with paraneoplastic syndromes. As these syndromes have significant clinical relevance, physicians should be aware of the possible presence of paraneoplastic syndromes in the diagnostic process of patients with neuroendocrine carcinoma of the larynx.