Fatigue, depression and health-related quality of life in patients with post-myocardial infarction during the COVID-19 pandemic: results from the Augsburg Myocardial Infarction Registry

The interplay between fatigue and depression and their association with health-related quality of life (HRQoL) after acute myocardial infarction (AMI) has received little attention during the COVID-19 pandemic. Therefore, this study evaluated the frequency of fatigue and depression in post-AMI patients during the COVID-19 pandemic and investigated the cross-sectional associations between fatigue, depression and HRQoL. Methods: The analysis was based on population-based Myocardial Infarction Registry Augsburg data. All survivors of AMI between 1 June 2020 and 15 September 2021 were included (n = 882) and received a postal questionnaire containing questions about fatigue (Fatigue Assessment Scale), depression (Patient Health Questionnaire), and HRQoL (MacNew Heart Disease HRQoL questionnaire) on 17 November 2021. The questionnaire was returned by 592 patients (67.1%), and 574 participants could be included in the analysis. Multivariable linear regression models were performed to investigate the associations between fatigue and depression (both exposures) and HRQoL (outcome). Results: Altogether, 273 (47.6%) participants met the criteria for the presence of fatigue, about 16% showed signs of moderate to severe depression. Both fatigue and depression were significantly associated with a decreased HRQoL (total score and emotional, social, and physical subscales; all p-values < 0.0001). In particular, a combined occurrence of fatigue and depression was associated with a significantly reduced HRQoL. Conclusions: It seems necessary to screen post-MI patients for the presence of fatigue and depression in clinical practice on a routine basis to provide them with adequate support and treatment and thus also to improve their HRQoL

Shock index and modified shock index are predictors of long-term mortality not only in STEMI but also in NSTEMI patients

BACKGROUND: Shock index (SI) and modified shock index (mSI) are useful instruments for early risk stratification in acute myocardial infarction (AMI) patients. They are strong predictors for short-term mortality. Nevertheless, the association between SI or mSI and long-term mortality in AMI patients has not yet been sufficiently examined. MATERIAL AND METHODS: For this study, a total of 10,174 patients with AMI was included. All cases were prospectively recorded by the population-based Augsburg Myocardial Infarction Registry from 2000 until 2017. Endpoint was all-cause mortality with a median observational time of 6.5 years [IQR: 3.5–7.4]. Using ROC analysis and calculating Youden-Index, the sample was dichotomized into a low and a high SI and mSI group, respectively. Moreover, multivariable adjusted COX regression models were calculated. All analyses were performed for the total sample as well as for STEMI and NSTEMI cases separately. RESULTS: Optimal cut-off values were 0.580 for SI and 0.852 for mSI (total sample). AUC values were 0.6382 (95% CI: 0.6223–0.6549) for SI and 0.6552 (95% CI: 0.6397–0.6713) for mSI. Fully adjusted COX regression models revealed significantly higher long-term mortality for patients with high SI and high mSI compared to patients with low indices (high SI HR: 1.42 [1.32–1.52], high mSI HR: 1.46 [1.36–1.57]). Furthermore, the predictive ability was slightly better for mSI compared to SI and more reliable in NSTEMI cases compared to STEMI cases (for SI and mSI). CONCLUSION: High SI and mSI are useful tools for early risk stratification including long-term outcome especially in NSTEMI cases, which can help physicians to make decision on therapy. NSTEMI patients with high SI and mSI might especially benefit from immediate invasive therapy. KEY MESSAGES: Shock index and modified shock index are predictors of long-term mortality after acute myocardial infarction. Both indices predict long-term mortality not only for STEMI cases, but even more so for NSTEMI cases

Association between acute myocardial infarction symptoms and short- and long-term mortality after the event

Background In this study we investigated the associations between various acute myocardial infarction (AMI) symptoms and their associations with short-term (28 day) - and long-term mortality. Methods The analysis was based on 5,900 patients aged 25 to 84 years with a first-time AMI recorded by the population-based Myocardial Infarction Registry Augsburg between 2010 and 2017. Median follow-up time was 3.8 years [IQR: 1.1-6.3]. As part of a face-to-face interview, the presence (yes/no) of 11 most commonly AMI symptoms at the acute event was assessed. Using multivariable-adjusted logistic regression and COX regression models the association between various symptoms and all-cause mortality was investigated. P values of the regression models were FDR-adjusted. Results Pain in various body parts (chest pain, left and right shoulder/arm/hand, between shoulder blades), sweating, nausea/vomiting, dizziness and fear of death/feeling of annihilation were significantly associated with a decreased 28-day mortality after AMI. The pain symptoms and sweating were also significantly associated with a decreased long-term mortality. Shortness of breath was significantly associated with a higher long-term mortality. Conclusions The absence of several symptoms, including typical chest discomfort (chest pain or retrosternal pressure/tightness), is associated with unfavorable outcomes after AMI. This finding has implications for patient management and public health measures designed to encourage appropriate and prompt medical consultation of patients with atypical AMI symptoms

Can inflammatory plasma proteins predict Long COVID or fatigue severity after SARS-CoV-2 infection?

Objective To investigate whether specific immune response plasma proteins can predict an elevated risk of developing Long COVID symptoms or fatigue severity after SARS-CoV-2 infection. Methods This study was based on 257 outpatients with test-confirmed SARS-CoV-2 infection between February 2020 and January 2021. At least 12 weeks after the acute infection, 92 plasma proteins were measured using the Olink Target 96 immune response panel (median time between acute infection and venous blood sampling was 38.8 [IQR: 24.0–48.0] weeks). The presence of Long COVID symptoms and fatigue severity was assessed 115.8 [92.5–118.6] weeks after the acute infection by a follow-up postal survey. Long COVID (yes/no) was defined as having one or more of the following symptoms: fatigue, shortness of breath, concentration or memory problems. The severity of fatigue was assessed using the Fatigue Assessment Scale (FAS). In multivariable-adjusted logistic and linear regression models the associations between each plasma protein (exposure) and Long COVID (yes/no) or severity of fatigue were investigated. Results Nine plasma proteins were significantly associated with Long COVID before, but not after adjusting for multiple testing (FDR-adjustment): DFFA, TRIM5, TRIM21, HEXIM1, SRPK2, PRDX5, PIK3AP1, IFNLR1 and HCLS1. Moreover, a total of 10 proteins were significantly associated with severity of fatigue before FDR-adjustment: SRPK2, ITGA6, CLEC4G, HEXIM1, PPP1R9B, PLXNA4, PRDX5, DAPP1, STC1 and HCLS1. Only SRPK2 and ITGA6 remained significantly associated after FDR-adjustment. Conclusions This study demonstrates that certain immune response plasma proteins might play an important role in the pathophysiology of Long COVID and severity of fatigue after SARS-CoV-2 infection

Fundamental in vitro 3D human skin equivalent tool development for assessing biological safety and biocompatibility – towards alternative for animal experiments

Nowadays, human skin constructs (HSCs) are required for biomaterials, pharmaceuticals and cosmetics in vitro testing and for the development of complex skin wound therapeutics. In vitro three-dimensional (3D) dermal-epidermal based interfollicular, full-thickness, human skin equivalent (HSE) was here developed, recapitulating skin morphogenesis, epidermal differentiation, ultra-structure, tissue architecture, and barrier function properties of human skin. Different 3D cell culture conditions were tested to optimize HSE maturation, using various commercially available serum/animal component-free and/or fully defined media, and air-liquid interface (ALI) culture. Optimized culture conditions allowed the production of HSE by culturing normal human dermal fibroblasts (NHDFs) for 5–7 days in CELLnTEC-Prime Fibroblast (CnT-PR-F) medium and then culturing normal human epidermal keratinocytes (NHEKs) for 3 days in CELLnTEC-Prime Epithelial culture (CnT-PR) medium on them. Co-culture was then submerged overnight in CELLnTEC-Prime-3D barrier (CnT-PR-3D) medium to stimulate cell-cell contact formation and finally placed at ALI for 15–20 days using CnT-PR-3D medium. Histological analysis revealed uniform distribution of NHDFs in the dermal layer and their typical elongated morphology with filopodia. Epidermal compartment showed a multi-layered structure, consisting of stratum basale, spinosum, granulosum, and corneum. NHDFs and keratinocytes of basal layer were positive for the proliferation marker Kiel 67 (Ki-67) demonstrating their active state of proliferation. The presence of typical epidermal tissue proteins (keratins, laminins, filaggrin, loricin, involucrin, and β-tubulin) at their correct anatomical position was verified by immunohistochemistry (IHC). Moreover, transmission electron microscopy (TEM) analyses revealed basement membrane with lamina lucida, lamina densa, hemidesmosomes and anchoring fibers. The epidermal layers showed abundant intracellular keratin filaments, desmosomes, and tight junction between keratinocytes. Scanning electron microscopy (SEM) analyses showed the interwoven network of collagen fibers with embedded NHDFs and adjacent stratified epidermis up to the stratum corneum similar to native human skin. HSE physiological static contact angle confirmed the barrier function. The developed HSE represents a fundamental in vitro tool to assess biocompatibility of biomaterials, pharmacotoxicity, safety and effectiveness of cosmetics, as well as to investigate skin biology, skin disease pathogenesis, wound healing, and skin infection

Depression mediates the association between health literacy and health-related quality of life after myocardial infarction

IntroductionSo far, health literacy (HL) and its related factors in patients with acute myocardial infarction received little attention. Thus, the objective of this study was to investigate the associations between the different dimensions of HL and disease-specific health-related quality of life (HRQOL), and factors that may affect these relations in patients after acute myocardial infarction (AMI).MethodsAll survivors of AMI between June 2020 and September 2021, from the Myocardial Infarction Registry Augsburg (n=882) received a postal questionnaire on HL [Health Literacy Questionnaire (HLQ)], HRQOL (MacNew Heart Disease HRQOL questionnaire) and depression (Patient Health Questionnaire). From the 592 respondents, 546 could be included in the analysis. Multivariable linear regression models were performed to investigate the associations between the nine subscales of the HLQ and the total score and three subscales of the MacNew questionnaire. A mediation analysis was performed to estimate direct and indirect effects of HL on HRQOL taking into account the mediating effect of depression.ResultsIn the sample of 546 patients (72.5% male, mean age 68.5 ± 12.2 years), patients with poor education showed significantly lower HLQ scores. Significant associations between the subscales of the HLQ and the MacNew were found, which remained significant after adjustment for sociodemographic variables with few exceptions. More than 50% of the association between HL and HRQOL was mediated by depression in seven HLQ subscales and a complete mediating effect was found for the HLQ subscales ‘Actively managing my health’ and ‘Appraisal of health information’.DiscussionDepression mediates the associations between HL and disease-specific HRQOL in patients with myocardial infarction