Targeting the High-Density Lipoprotein Proteome for the Treatment of Post-Acute Sequelae of SARS-CoV-2.

Here, we target the high-density lipoprotein (HDL) proteome in a case series of 16 patients with post-COVID-19 symptoms treated with HMG-Co-A reductase inhibitors (statin) plus angiotensin II type 1 receptor blockers (ARBs) for 6 weeks. Patients suffering from persistent symptoms (post-acute sequelae) after serologically confirmed SARS-CoV-2 infection (post-COVID-19 syndrome, PCS, n = 8) or following SARS-CoV-2 vaccination (PVS, n = 8) were included. Asymptomatic subjects with corresponding serological findings served as healthy controls (n = 8/8). HDL was isolated using dextran sulfate precipitation and the HDL proteome of all study participants was analyzed quantitatively by mass spectrometry. Clinical symptoms were assessed using questionnaires before and after therapy. The inflammatory potential of the patients' HDL proteome was addressed in human endothelial cells. The HDL proteome of patients with PCS and PVS showed no significant differences; however, compared to controls, the HDL from PVS/PCS patients displayed significant alterations involving hemoglobin, cytoskeletal proteins (MYL6, TLN1, PARVB, TPM4, FLNA), and amyloid precursor protein. Gene Ontology Biological Process (GOBP) enrichment analysis identified hemostasis, peptidase, and lipoprotein regulation pathways to be involved. Treatment of PVS/PCS patients with statins plus ARBs improved the patients' clinical symptoms. After therapy, three proteins were significantly increased (FAM3C, AT6AP2, ADAM10; FDR < 0.05) in the HDL proteome from patients with PVS/PCS. Exposure of human endothelial cells with the HDL proteome from treated PVS/PCS patients revealed reduced inflammatory cytokine and adhesion molecule expression. Thus, HDL proteome analysis from PVS/PCS patients enables a deeper insight into the underlying disease mechanisms, pointing to significant involvement in metabolic and signaling disturbances. Treatment with statins plus ARBs improved clinical symptoms and reduced the inflammatory potential of the HDL proteome. These observations may guide future therapeutic strategies for PVS/PCS patients.

Heterogeneity in Clinical Practices for Post-Cardiotomy Extracorporeal Life Support: a Pilot Survey from the PELS-1 Multicenter Study.

BACKGROUND: High-quality evidence for post-cardiotomy extracorporeal life support (PC-ECLS) management is lacking. This study investigated the real-world PC-ECLS clinical practices. METHODS: This cross-sectional, multi-institutional, international pilot survey explored center organization, anticoagulation management, left ventricular unloading, distal limb perfusion, PC-ECLS monitoring and transfusions practices. Twenty-nine questions were distributed among 34 hospitals participating in the Post-cardiotomy Extra-Corporeal Life Support Study. RESULTS: Of the 32 centers [16 low-volume (50%); 16 high-volume (50%)] that responded, 16 (50%) had dedicated ECLS specialists. Twenty-six centers (81.3%) reported using additional mechanical circulatory supports. Anticoagulation practices were highly heterogeneous: 24 hospitals (75%) reported using patient's bleeding status as a guide, without a specific threshold in 54.2% of cases. Transfusion targets ranged 7-10 g/dL. Most centers used cardiac venting on a case-by-case basis (78.1%) and regular distal limb perfusion (84.4%). Nineteen (54.9%) centers reported dedicated monitoring protocols including daily echocardiography (87.5%), Swan-Ganz catheterization (40.6%), cerebral near-infrared spectroscopy (53.1%) and multimodal assessment of limb ischemia. Inspection of the circuit (71.9%), oxygenator pressure drop (68.8%), plasma free hemoglobin (75%), d-dimer (59.4%), lactate dehydrogenase (56.3%) and fibrinogen (46.9%) are used to diagnose hemolysis and thrombosis. CONCLUSIONS: This study shows remarkable heterogeneity in clinical practices for PC-ECLS management. More standardized protocols and better implementation of available evidence are recommended.

Gender differences in adverse outcomes after contemporary percutaneous coronary intervention: an analysis from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) percutaneous coronary intervention registry.

BACKGROUND: Prior studies have shown a relationship between female gender and adverse outcomes after percutaneous coronary interventions (PCIs). Whether this relationship still exists with contemporary PCI remains to be determined. METHODS: We evaluated gender differences in clinical outcomes in a large registry of contemporary PCI. Data were prospectively collected from 22,725 consecutive PCIs in a multicenter regional consortium (Blue Cross Blue Shield of Michigan Cardiovascular Consortium) between January 2002 and December 2003. The primary end point was in-hospital all-cause mortality; other clinical outcomes evaluated included in-hospital death, vascular complications, transfusion, postprocedure myocardial infarction, stroke, and a combined major cardiovascular adverse event (MACE) end point including myocardial infarction, death, stroke, emergency coronary artery bypass grafting, and repeated PCI at the same site. Independent predictors of adverse outcomes were identified using multivariate logistic regression analysis. RESULTS: Compared with men, women were older, had a higher prevalence of comorbidities, and had a significantly higher frequency of adverse outcomes after PCI. After adjustment for baseline demographics, comorbidities, clinical presentation, and lesion characteristics, female gender was associated with an increased risk of in-hospital death, vascular complication, blood transfusion, stroke, and MACE. The relationship between female gender and increased risk of death and MACE was no longer present after further adjustment for kidney function and low body surface area. CONCLUSIONS: Differences in mortality rates between men and women no longer exist after PCI. However, our data suggest that technological advancements have not completely offset the relationship between gender and adverse outcomes after PCI.

Biliary stent clogging solved by nanotechnology? In vitro study of inorganic-organic sol-gel coatings for teflon stents.

BACKGROUND & AIMS: The major drawback of plastic stents for biliary drainage is the occlusion by sludge. Sludge is accrued because the stent surface allows for the adherence of proteins, glycoproteins, or bacteria and the bile flow is insufficient to clean the surface. In this study, experience from nanotechnology to achieve a clean surface by improved soil-release characteristics is used to optimize biliary stent surface. The aim of this study was to examine sludge accumulation in relation to surface characteristics designed by nanotechnology. METHODS: A variety of inorganic-organic sol-gel-coated stents were incubated in sterilized human bile and enzyme-active Escherichia coli for 35 days. Materials were Teflon (DuPont, Wilmington, DE) coated with hydrophobic Clearcoat (NTC, Tholey, Germany), Teflon with sol-gel coating synthesized of organic epoxides of 190 g/mol or 500 g/mol, and propylaminosilane without or with fluorsilanes for increased hydrophobicity. Scanning electron microscopy and semiquantitative analysis, blinded to the type of coating, were used to determine the amount of sludge accumulated on the surface. RESULTS: Sludge deposition was reduced on the designed surfaces as compared with uncoated Teflon and Clearcoat. The performance of high molecular (500 g/mol) was superior to that of low molecular (190 g/mol) epoxide ligand. However, increasing hydrophobicity by adding fluoraminosilanes resulted in increased adherence of sludge. Less than a micrometer-thin sol-gel coating is inexpensive because very little coating material is required. This is the first published data comparing systematically modified surfaces of biliary stents using nanotechnology. CONCLUSIONS: Optimized soil release by sol-gel nanocoating of plastic stents may prevent biliary plastic stents from clogging.

[Mental health and performance of medical students with high and low test anxiety]. / Seelische Gesundheit und Studienerfolg von Studierenden der Medizin mit hoher und niedriger Prüfungsängstlichkeit.

UNLABELLED: About 10 % of students suffer from test anxiety to such an extent that treatment is warranted. The correlation of high test anxiety with other mental disorders and study success is rarely investigated. OBJECTIVE: Do students with high test anxiety differ from students with low test anxiety regarding mental health and success in their studies? METHODS: Out of 945 medical students of all semesters 115 test persons were selected which scored either very high or very low for test anxiety. They were subjected to a clinical interview and two personality tests (NEO-FFI, TAS-20). The analysed sample contained 109 men und women. RESULTS: Students with high test anxiety suffered in a much higher proportion from social anxieties. Also, specific isolated anxieties and other mental disorders appeared in this group more often. They had a higher score of neuroticism, lower scores of extraversion and conscientiousness and they consumed more medication. In the high test anxiety group were more long-term students than in the low test anxiety group. Only 7 % of the students with high test anxiety were in psychotherapeutic treatment. Study finances, family status, cultural and gender affiliation were without or of minor significance. CONCLUSIONS: Students with high test anxiety are to a significant extent compromised in their performance and emotional wellbeing. They most likely would benefit from a low threshold psychotherapeutic outreach program offered by the university focusing among others their social anxieties.

[Integrative psychosomatics: contributions to a reform of medical training]. / Integrierte Psychosomatik: Beiträge zu einer Reform des Medizinstudiums.

Medical training has so far mainly emphasised teaching of knowledge and neglected fostering of theoretical and practical competence in doctors' occupation. The consequences of these deficits are often experienced as "practice shock" when young doctors start working. New concepts of teaching moduls in psychosocial subjects may enhance medical competence. We present some of the contents and didactic concepts which we have implemented in the medical curriculum of Cologne University.