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1.
Future Med Chem ; : 1-20, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39291539

ABSTRACT

Aim: Pulmonary fibrosis is a life threating disease which requires an immediate treatment and due to the limited medications, this study focused on synthesizing a series of quinoline-based pyrimidodiazepines 4a-f as a novel antifibrotic hit.Materials & methods: The target compounds were synthesized via a one-pot reaction then investigated in a rat model of lung fibrosis induced by bleomycin (BLM).Results: Results revealed significant attenuation of the tested pro-inflammatory cytokines, fibrotic genes and apoptotic markers; however, Bcl-2 was upregulated, indicating a protective effect against fibrosis. Moreover, the molecular docking studies highlighted promising interactions between compounds 4b and 4c and specific amino acids within the protein pockets of caspase-3 (ARG341 and THR177), malondialdehyde (LYS195, LYS118 and ARG188) and TNF-α (SER99 and NME102).Conclusion: Compounds 4b and 4c emerge as promising candidates for further preclinical investigation as pulmonary antifibrotic agents.


[Box: see text].

2.
J Autism Dev Disord ; 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39141271

ABSTRACT

Although affective irritability is a common and concerning problem for autistic youth, limited research has examined relations among core autism characteristics and irritability. Therefore, this study investigated potential associations among types of restricted/repetitive behaviors (RRBs) and social communication challenges and irritability in autistic children and adolescents. Participants were 107 autistic youth recruited from a university-based autism clinical research program. Two hierarchical multiple regressions were conducted with Affective Reactivity Index as the dependent variable. Covariates were entered at step 1, followed by the independent variables of interest at step 2. For the first model, independent variables of interest were Repetitive Behavior Scale-Revised subscales: stereotyped behavior, self-injurious behavior, compulsive behavior, ritualistic behavior, sameness behavior, and restricted behavior. For the second model, independent variables of interest were Social Responsiveness Scale, Second Edition subscales: social awareness, social cognitive, social communication, and social motivation. Irritability was significantly associated with several categories of RRBs (i.e., insistence on sameness, stereotypic behavior, and restricted interests/activities). Nonetheless, irritability was not associated with categories of social communication and interaction challenges in autistic youth. Results from this study indicated differing associations between core autism characteristics and affective irritability. Findings highlight the importance of differentiating types of restricted, repetitive behaviors and social communication and interaction challenges in conceptualizing mental health concerns in autistic youth.

3.
Article in English | MEDLINE | ID: mdl-38656040

ABSTRACT

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.


Subject(s)
Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , Immunocompromised Host , Immunogenicity, Vaccine , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antibodies, Viral/blood , BNT162 Vaccine/immunology , BNT162 Vaccine/administration & dosage , COVID-19/prevention & control , COVID-19/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Immunization, Secondary , Immunocompetence/immunology , Immunocompromised Host/immunology , Vaccines, Inactivated/immunology , Vaccines, Inactivated/administration & dosage
5.
Schizophr Res ; 264: 298-313, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38215566

ABSTRACT

BACKGROUND: Impairment in social cognition, particularly eye gaze processing, is a shared feature common to autism spectrum disorder (ASD) and schizophrenia. However, it is unclear if a convergent neural mechanism also underlies gaze dysfunction in these conditions. The present study examined whether this shared eye gaze phenotype is reflected in a profile of convergent neurobiological dysfunction in ASD and schizophrenia. METHODS: Activation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates across the whole brain to identify spatial convergence. Functional coactivation with regions emerging as significant was assessed using meta-analytic connectivity modeling. Functional decoding was also conducted. RESULTS: Fifty-six experiments (n = 30 with schizophrenia and n = 26 with ASD) from 36 articles met inclusion criteria, which comprised 354 participants with ASD, 275 with schizophrenia and 613 healthy controls (1242 participants in total). In ASD, aberrant activation was found in the left amygdala relative to unaffected controls during gaze processing. In schizophrenia, aberrant activation was found in the right inferior frontal gyrus and supplementary motor area. Across ASD and schizophrenia, aberrant activation was found in the right inferior frontal gyrus and right fusiform gyrus during gaze processing. Functional decoding mapped the left amygdala to domains related to emotion processing and cognition, the right inferior frontal gyrus to cognition and perception, and the right fusiform gyrus to visual perception, spatial cognition, and emotion perception. These regions also showed meta-analytic connectivity to frontoparietal and frontotemporal circuitry. CONCLUSION: Alterations in frontoparietal and frontotemporal circuitry emerged as neural markers of gaze impairments in ASD and schizophrenia. These findings have implications for advancing transdiagnostic biomarkers to inform targeted treatments for ASD and schizophrenia.


Subject(s)
Autism Spectrum Disorder , Schizophrenia , Humans , Schizophrenia/complications , Schizophrenia/diagnostic imaging , Likelihood Functions , Fixation, Ocular , Magnetic Resonance Imaging , Brain , Brain Mapping
6.
Rev Inst Med Trop Sao Paulo, v. 66, e24, abr. 2024
Article in English | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5311

ABSTRACT

Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.

7.
Article in English | LILACS-Express | LILACS | ID: biblio-1559107

ABSTRACT

ABSTRACT Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.

8.
Asian Cardiovasc Thorac Ann ; 31(9): 816-818, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37812397

ABSTRACT

We present a case of repeated child abuse causing left-sided hemothorax and cardiac tamponade on two separate occasions. A 14-year-old cerebral palsy male presented with left-sided hemothorax and multiple metallic foreign bodies in the chest wall managed by small limited incision, removal of the foreign bodies and chest tube. One week later, he came to our emergency department (ER) with multiple chest wall foreign bodies and tamponade managed by median sternotomy, removal of the foreign bodies, one of them was in the LAD. He had a smooth postoperative course and the case is under investigation.


Subject(s)
Cardiac Tamponade , Child Abuse , Foreign Bodies , Thoracic Wall , Adolescent , Humans , Male , Cardiac Tamponade/diagnostic imaging , Cardiac Tamponade/etiology , Cardiac Tamponade/surgery , Foreign Bodies/complications , Foreign Bodies/diagnostic imaging , Foreign Bodies/surgery , Hemothorax/diagnostic imaging , Hemothorax/etiology , Hemothorax/surgery , Thoracic Wall/diagnostic imaging , Thoracic Wall/surgery
9.
J Neurosci ; 43(23): 4365-4377, 2023 06 07.
Article in English | MEDLINE | ID: mdl-37055181

ABSTRACT

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disease characterized by progressive motor and cognitive impairments, with no disease-modifying therapies yet available. HD pathophysiology involves evident impairment in glutamatergic neurotransmission leading to severe striatal neurodegeneration. The vesicular glutamate transporter-3 (VGLUT3) regulates the striatal network that is centrally affected by HD. Nevertheless, current evidence on the role of VGLUT3 in HD pathophysiology is lacking. Here, we crossed mice lacking Slc17a8 gene (VGLUT3 -/-) with heterozygous zQ175 knock-in mouse model of HD (zQ175:VGLUT3 -/-). Longitudinal assessment of motor and cognitive functions from 6 to 15 months of age reveals that VGLUT3 deletion rescues motor coordination and short-term memory deficits in both male and female zQ175 mice. VGLUT3 deletion also rescues neuronal loss likely via the activation of Akt and ERK1/2 in the striatum of zQ175 mice of both sexes. Interestingly, the rescue in neuronal survival in zQ175:VGLUT3 -/- mice is accompanied by a reduction in the number of nuclear mutant huntingtin (mHTT) aggregates with no change in the total aggregate levels or microgliosis. Collectively, these findings provide novel evidence that VGLUT3, despite its limited expression, can be a vital contributor to HD pathophysiology and a viable target for HD therapeutics.SIGNIFICANCE STATEMENT Dysregulation of the striatal network centrally contributes to the pathophysiology of Huntington's disease (HD). The atypical vesicular glutamate transporter-3 (VGLUT3) has been shown to regulate several major striatal pathologies, such as addiction, eating disorders, or L-DOPA-induced dyskinesia. Yet, our understanding of VGLUT3's role in HD remains unclear. We report here that deletion of the Slc17a8 (Vglut3) gene rescues the deficits in both motor and cognitive functions in HD mice of both sexes. We also find that VGLUT3 deletion activates neuronal survival signaling and reduces nuclear aggregation of abnormal huntingtin proteins and striatal neuron loss in HD mice. Our novel findings highlight the vital contribution of VGLUT3 in HD pathophysiology that can be exploited for HD therapeutic management.


Subject(s)
Huntington Disease , Neurodegenerative Diseases , Mice , Male , Female , Animals , Huntington Disease/metabolism , Neurodegenerative Diseases/metabolism , Corpus Striatum/metabolism , Neostriatum/metabolism , Vesicular Glutamate Transport Proteins/metabolism , Disease Models, Animal , Mice, Transgenic , Huntingtin Protein/genetics
10.
Front Cardiovasc Med ; 10: 990373, 2023.
Article in English | MEDLINE | ID: mdl-36873389

ABSTRACT

Background: In patients with aortic stenosis treated by transcatheter aortic valve implantation (TAVI), mitral and tricuspid regurgitation (MR and TR) at baseline and after TAVI are likely to be of prognostic relevance, and questions such as whether and when treatment further improves prognosis in these patients arise. Aims: Against that background, the purpose of this study was to analyze a variety of clinical characteristics including MR and TR with respect to their potential value as predictors of 2-year mortality after TAVI. Methods: A cohort of 445 typical TAVI patients was available for the study and clinical characteristics were evaluated baseline, 6 to 8 weeks as well as 6 months after TAVI. Results: In 39% of the patients relevant (moderate or severe) MR and in 32% of the patients relevant (moderate or severe) TR could be detected at baseline. The rates were 27% for MR (p = 0.001, compared to baseline) and 35% for TR (p = n.s., compared to baseline) at the 6- to 8-week follow-up. After 6 months, relevant MR was observable in 28% (p = 0.036, compared to baseline) and relevant TR in 34% (p = n.s., compared to baseline) of the patients. As predictors of 2-year mortality, a multivariate analysis identified the following parameters for the different time points: sex, age, AS entity, atrial fibrillation, renal function, relevant TR, systolic pulmonary artery pressure (PAPsys), and 6-min walk distance at baseline; clinical frailty scale and PAPsys 6-8 weeks after TAVI and BNP and relevant MR 6 months after TAVI. There was a significantly worse 2-year survival in patients with relevant TR at baseline (68.4% vs. 82.6%, p < 0.001; whole population, n = 445) and in patients with relevant MR at 6 months (87.9% vs. 95.2%, p = 0.042; landmark analysis: n = 235). Conclusion: This real-life study demonstrated the prognostic relevance of repeated evaluation of MR and TR before and after TAVI. Choosing the right time point for treatment is a remaining clinical challenge, which should be further addressed in randomized trials.

11.
Infect Control Hosp Epidemiol ; 44(2): 302-304, 2023 02.
Article in English | MEDLINE | ID: mdl-35144717

ABSTRACT

We evaluated the interference of the mucosal barrier injury (MBI) laboratory-confirmed bloodstream infection (MBI-LCBI) criteria on the central-line-associated bloodstream infection (CLABSI) incidence density, and the proportion of catheter-related bloodstream infections (CRBSIs) among those classified as MBI. We detected 339 CLABSIs: 15.0% were classified as MBI-LCBIs, and among these, 19.6% were classified as CRBSIs.


Subject(s)
Catheter-Related Infections , Catheterization, Central Venous , Central Venous Catheters , Communicable Diseases , Hematologic Neoplasms , Neoplasms , Sepsis , Humans , Catheter-Related Infections/diagnosis , Catheter-Related Infections/epidemiology , Retrospective Studies , Sepsis/epidemiology , Hematologic Neoplasms/complications , Catheterization, Central Venous/adverse effects
12.
Focus Autism Other Dev Disabl ; 38(3): 168-176, 2023 Sep.
Article in English | MEDLINE | ID: mdl-38469453

ABSTRACT

Social adaptive functioning is notably compromised and may be further impaired by aggressive behavior in children with autism spectrum disorder (ASD). This study examined the association between aggressive behavior and social adaptive skills in children with ASD and the contribution of aggressive behavior to social adaptive skills in a combined sample of children with and without ASD. Participants consisted of children, ages 8 to 15 years, with ASD (n = 52) and who were typically developing (n = 29). Results indicate that aggressive behavior is negatively associated with social adaptive skills in children with ASD and that it contributes to reduced social adaptive functioning above and beyond ASD diagnosis. Findings underscore the importance of considering the role of aggressive behavior when evaluating and promoting social functioning in children with ASD.

13.
Eur Heart J Suppl ; 24(Suppl J): J25-J29, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36518888

ABSTRACT

Complete revascularization (CR) in patients with multi-vessel disease improves outcomes. The use of percutaneous left-ventricular assist devices, such as the Impella heart pump, is useful to minimize the risk of haemodynamic compromise in complex higher risk and clinically indicated patients. The recently published data from the PROTECT III trial suggest more CR during Impella-protected percutaneous coronary intervention with more extensive lesion preparation and treatment, resulting in the reduced need for repeat revascularization. To achieve CR and improve survival, procedural guidance by intravascular imaging, extensive lesion preparation, debulking with atherectomy devices, advanced chronic total occlusion revascularization techniques, and post-interventional treatment with modern anti-platelet medication are essential.

14.
Eur Heart J Suppl ; 24(Suppl J): J37-J42, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36518892

ABSTRACT

Despite the routine use of percutaneous mechanical circulatory support (pMCS) with the Impella heart pump, vascular and bleeding complications may occur during removal with or without pre-closure. To safely close the large-bore access (LBA), post-hoc selection of the appropriate treatment of vascular complications is critical to patient recovery and survival. Femoral artery access is typically utilized for LBA, and percutaneous axillary artery access is a common alternative, especially in the instance of severe peripheral artery disease. Optimization of patient outcomes and efficiency of pMCS can be achieved with adequate arterial access using state-of-the-art techniques. Impella removal techniques with or without pre-closure will be addressed as well as the management of large-bore femoral access complications. In addition, treatment strategies to manage patient deterioration during a protected high-risk percutaneous coronary intervention will be provided.

15.
Eur Heart J Suppl ; 24(Suppl J): J30-J36, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36518894

ABSTRACT

Protected percutaneous coronary intervention is considered a life-saving procedure for high-risk patients. Therefore it is important that the interventional cardiology team is prepared, the procedure is planned, and potential complications, as well as bail out strategies are considered. Throughout the procedure, it is critical to monitor the patient to identify any early signs of deterioration or changes in patient well-being to avoid any potential complications.

17.
AIDS Behav ; 26(12): 4144-4155, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35699860

ABSTRACT

We investigated changes in lifestyle, depressive symptoms, self-perception of health, and body weight changes of persons living with HIV (PLWH) during the COVID-19 social distancing (SD). In a Web-based cross-sectional survey, participants (n = 406) were questioned about lifestyle and health status before and during SD. Most responders were men, 50 + years old, high education level; 49.8% had their income reduced during SD. About 9% were diagnosed with COVID-19, of whom 13.5% required hospitalization. During SD: - most participants did not change their food intake, although 25% replaced healthy foods with unhealthy ones; -more than half mentioned poor sleep quality; -about 50% increased their sedentary behavior. Depressive symptoms (reported by 70.9%) were associated with sedentary behavior, poor sleep quality, and reduced income. About one-third had a negative perception of their health status, which was inversely associated with practicing physical exercises and positively associated with sedentarism and poor sleep quality. More than half increased their body weight, which was associated with a lower intake of vegetables. The older age reduced the odds of the three outcomes. Carefully monitoring PLWH regarding SD will enable early interventions toward health.


RESUMEN: En este trabajo investigamos los cambios en el estilo de vida, síntomas depresivos, autopercepción de salud y cambios en el peso corporal de las personas que viven con el VIH (PVCV) durante el distanciamiento social (DS) de COVID-19. En una encuesta transversal en línea, se preguntó a los participantes (n = 406) sobre el estilo de vida y el estado de salud antes y durante el DS. La mayoría de los encuestados eran hombres, mayores de 50 años, con alto nivel educativo. El 49,8% tuvo una disminución en sus ingresos durante el DS. El 9,1% fue diagnosticados con COVID-19, de los cuales 13,5% requirió hospitalización. Durante el DS: - la mayoría de los participantes no cambió su ingesta de alimentos, aunque el 25% reemplazó los alimentos saludables por los no saludables; más de la mitad mencionó mala calidad del sueño; cerca del 50% aumentó su comportamiento sedentario. Los síntomas depresivos (referidos por el 70,9%), fueron incrementados por el sedentarismo, la mala calidad del sueño y reducción de la renta. Cerca de un tercio tenía una percepción negativa de su estado de salud, que se redujo con la práctica de ejercicio físico y aumentó con el sedentarismo y la mala calidad del sueño. Más de la mitad aumentó su peso corporal, lo que se asoció con una menor ingesta de vegetales. Una edad más avanzada redujo las probabilidades de los tres desenlaces. El monitoreo cuidadoso de las PVCV con respecto al DS permitirá intervenciones tempranas para la salud.


Subject(s)
COVID-19 , HIV Infections , Sleep Initiation and Maintenance Disorders , Male , Humans , Middle Aged , Female , COVID-19/epidemiology , COVID-19/prevention & control , Physical Distancing , Cross-Sectional Studies , HIV Infections/epidemiology , HIV Infections/prevention & control , Life Style , Body Weight , Outcome Assessment, Health Care , Internet
18.
Mol Immunol ; 149: 48-58, 2022 09.
Article in English | MEDLINE | ID: mdl-35724581

ABSTRACT

The key players of the hypoxic response are the hypoxia-inducible factors (Hif), whose α-subunits are tightly regulated by Prolyl-4-hydroxylases (PHD), predominantly by PHD2. Monocytes/Macrophages are involved in atherosclerosis but also restenosis and were found at hypoxic and sites of the lesion. Little is known about the role of the myeloid PHD2 in atherosclerosis and neointima formation. The study aimed to investigate the consequences of a myeloid deficiency of PHD2 in the process of neointima formation using an arterial denudation model. LysM-cre mice were crossed with PHD2fl/fl, PHD2fl/fl/Hif1αfl/fl and PHD2fl/fl/Hif2αfl/fl to get myeloid specific knockout of PHD2 and the Hif-α subunits. Denudation of the femoral artery was performed and animals were fed a western type diet afterwards with analysis of neointima formation 5 and 35 days after denudation. Increased neointima formation in myeloid PHD2 knockouts was observed, which was blunted by double-knockout of PHD2 and Hif1α whereas double knockout of PHD2 and Hif-2α showed comparable lesions to the PHD2 knockouts. Macrophage infiltration was comparable to the neointima formation, suggesting a more inflammatory reaction, and was accompanied by increased intimal VEGF-A expression. Collagen-content inversely correlated to the extent of neointima formation suggesting a destabilization of the plaque. This effect might be triggered by macrophage polarization. Therefore, in vitro results showed a distinct expression pattern in differentially polarized macrophages with high expression of Hif-1α, VEGF and MMP-1 in proinflammatory M1 macrophages. In conclusion, the results show that myeloid Hif-1α is involved in neointima hyperplasia. Our in vivo and in vitro data reveal a central role for this transcription factor in driving plaque-vascularization accompanied by matrix-degradation leading to plaque destabilization.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Femoral Artery , Hypoxia-Inducible Factor-Proline Dioxygenases , Macrophages , Neointima , Plaque, Atherosclerotic , Animals , Atherosclerosis/genetics , Atherosclerosis/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Femoral Artery/injuries , Femoral Artery/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit , Hypoxia-Inducible Factor-Proline Dioxygenases/deficiency , Hypoxia-Inducible Factor-Proline Dioxygenases/genetics , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Macrophages/metabolism , Mice , Neointima/genetics , Neointima/metabolism , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Plaque, Atherosclerotic/genetics , Plaque, Atherosclerotic/metabolism , Procollagen-Proline Dioxygenase/genetics
19.
BMC Cardiovasc Disord ; 22(1): 271, 2022 06 16.
Article in English | MEDLINE | ID: mdl-35710343

ABSTRACT

BACKGROUND: Various randomized multicenter studies have shown that percutaneous left atrial appendage closure (LAAC) is not inferior in stroke prevention compared to vitamin K antagonists (VKA) and can be performed safely and effectively. AIMS: The prospective multicenter ORIGINAL registry in the Free State of Saxony (saxOnian RegIstry analyzinG and followINg left atrial Appendage cLosure) investigated the efficiency and safety of LAAC with Watchman or Amulet device in a real word setting. A special focus was put on the influence of LAAC frequency on periprocedural efficiency and safety. METHODS AND RESULTS: The total of 482 consecutive patients (Abbott Amulet N = 93 and Boston Scientific Watchman N = 389) were included in the periinterventional analyses. After 6 weeks, 353 patients completed the first follow-up including transoesophageal echocardiography (TEE) (73.2%). Successful LAAC could be performed in more than 94%. The complication rate does not significantly differ between device types (p = 0.92) according to Fischer test and comprised 2.2% in the Amulet and 2.3% in the Watchman group. The kind of device and the frequency of LAAC per study center had no influence on the success and complication rates. Device related thrombus could be revealed more frequently in the Watchman group (4.5%) than in the Amulet group (1.4%) but this difference is still not significant in Fisher test (p = 0.14). Same conclusion can be made about residual leakage 1.1% versus 0% [not significant in Fisher test (p = 0.26)]. Dual antiplatelet therapy followed the intervention in 64% and 22% of patients were discharged under a combination of an anticoagulant (VKA/DOAC/Heparin) and one antiplatelet agent. CONCLUSIONS: The ORIGINAL registry supports the thesis from large, randomized trials that LAAC can be performed with a very high procedural success rate in the everyday clinical routine irrespective of the used LAA device (Watchman or Amulet). The postprocedural antithrombotic strategy differs widely among the participating centers. Trial registration Name of the registry: "saxOnian RegIstry analyzinG and followINg left atrial Appendage cLosure", Trial registration number: DRKS00023803; Date of registration: 15/12/2020 'Retrospectively registered'; URL of trial registry record: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023803 .


Subject(s)
Atrial Appendage , Atrial Fibrillation , Stroke , Anticoagulants/adverse effects , Atrial Appendage/diagnostic imaging , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Fibrillation/therapy , Cardiac Catheterization/adverse effects , Fibrinolytic Agents/therapeutic use , Humans , Prospective Studies , Registries , Stroke/epidemiology , Stroke/etiology , Stroke/prevention & control , Treatment Outcome
20.
Data Brief ; 42: 108199, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35539024

ABSTRACT

A precise prognosis is of imminent importance in intensive care medicine. This article provides data showing the overestimation of intrahospital mortality by APACHE II score in various subgroups of cardiogenic shock patients treated with a percutaneous left ventricular assist device. The data set includes additional baseline characteristics regarding age, pre-existing diseases, characteristics of coronary artery disease, characteristics of cardiopulmonary resuscitation, and hemodynamic parameter not included in the APACHE II score. Further data were provided which characterize derivation and validation group. Both groups were used for adjustment of the APACHE II approach. The data are supplemental to our original research article titled "Predictive value of the APACHE II score in cardiogenic shock patients treated with a percutaneous left ventricular assist device" (Mierke et al., IJC Heart & Vasculature. 40 (2022) 101013. https://doi.org/10.1016/j.ijcha.2022.101013).

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