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Circulation Jun 2024Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of...
BACKGROUND
Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of death worldwide. Although most mouse models of atherosclerosis develop lesions in the aorta and carotid arteries, they do not develop advanced coronary artery lesions. Moreover, they do not undergo spontaneous plaque rupture with MI and stroke or do so at such a low frequency that they are not viable experimental models to study late-stage thrombotic events or to identify novel therapeutic approaches for treating atherosclerotic disease. This has stymied the development of more effective therapeutic approaches for reducing these events beyond what has been achieved with aggressive lipid lowering. Here, we describe a diet-inducible mouse model that develops widespread advanced atherosclerosis in coronary, brachiocephalic, and carotid arteries with plaque rupture, MI, and stroke.
METHODS
We characterized a novel mouse model with a C-terminal mutation in the scavenger receptor class B, type 1 (SR-BI), combined with knockout (designated SR-BI/). Mice were fed Western diet (WD) for 26 weeks and analyzed for MI and stroke. Coronary, brachiocephalic, and carotid arteries were analyzed for atherosclerotic lesions and indices of plaque stability. To validate the utility of this model, SR-BI/ mice were treated with the drug candidate AZM198, which inhibits myeloperoxidase, an enzyme produced by activated neutrophils that predicts rupture of human atherosclerotic lesions.
RESULTS
SR-BI/ mice show high (>80%) mortality rates after 26 weeks of WD feeding because of major adverse cardiovascular events, including spontaneous plaque rupture with MI and stroke. Moreover, WD-fed SR-BI/ mice displayed elevated circulating high-sensitivity cardiac troponin I and increased neutrophil extracellular trap formation within lesions compared with control mice. Treatment of WD-fed SR-BI/ mice with AZM198 showed remarkable benefits, including >90% improvement in survival and >60% decrease in the incidence of plaque rupture, MI, and stroke, in conjunction with decreased circulating high-sensitivity cardiac troponin I and reduced neutrophil extracellular trap formation within lesions.
CONCLUSIONS
WD-fed SR-BI/ mice more closely replicate late-stage clinical events of advanced human atherosclerotic disease than previous models and can be used to identify and test potential new therapeutic agents to prevent major adverse cardiac events.
PubMed: 38881440
DOI: 10.1161/CIRCULATIONAHA.123.067931 -
Journal of Orthopaedic Surgery and... Jun 2024Postoperative pulmonary complications (PPCs) are among the most severe complications following total hip arthroplasty revision (THAR), imposing significant burdens on...
BACKGROUND
Postoperative pulmonary complications (PPCs) are among the most severe complications following total hip arthroplasty revision (THAR), imposing significant burdens on individuals and society. This study examined the prevalence and risk factors of PPCs following THAR using the NIS database, identifying specific pulmonary complications (SPCs) and their associated risks, including pneumonia, acute respiratory failure (ARF), and pulmonary embolism (PE).
METHODS
The National Inpatient Sample (NIS) database was used for this cross-sectional study. The analysis included patients undergoing THAR based on NIS from 2010 to 2019. Available data include demographic data, diagnostic and procedure codes, total charges, length of stay (LOS), hospital information, insurance information, and discharges.
RESULTS
From the NIS database, a total of 112,735 THAR patients in total were extracted. After THAR surgery, there was a 2.62% overall incidence of PPCs. Patients with PPCs after THAR demonstrated increased LOS, total charges, usage of Medicare, and in-hospital mortality. The following variables have been determined as potential risk factors for PPCs: advanced age, pulmonary circulation disorders, fluid and electrolyte disorders, weight loss, congestive heart failure, metastatic cancer, other neurological disorders (encephalopathy, cerebral edema, multiple sclerosis etc.), coagulopathy, paralysis, chronic pulmonary disease, renal failure, acute heart failure, deep vein thrombosis, acute myocardial infarction, peripheral vascular disease, stroke, continuous trauma ventilation, cardiac arrest, blood transfusion, dislocation of joint, and hemorrhage.
CONCLUSIONS
Our study revealed a 2.62% incidence of PPCs, with pneumonia, ARF, and PE accounting for 1.24%, 1.31%, and 0.41%, respectively. A multitude of risk factors for PPCs were identified, underscoring the importance of preoperative optimization to mitigate PPCs and enhance postoperative outcomes.
Topics: Humans; Arthroplasty, Replacement, Hip; Risk Factors; Postoperative Complications; Male; Female; Retrospective Studies; Incidence; Aged; Middle Aged; Cross-Sectional Studies; Databases, Factual; Pulmonary Embolism; Reoperation; Length of Stay; Lung Diseases; United States; Pneumonia; Adult; Aged, 80 and over; Respiratory Insufficiency; Inpatients
PubMed: 38877587
DOI: 10.1186/s13018-024-04836-3 -
PloS One 2024Acute kidney injury (AKI) is a common complication of septic shock and together these conditions carry a high mortality risk. In septic patients who develop severe AKI,... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Acute kidney injury (AKI) is a common complication of septic shock and together these conditions carry a high mortality risk. In septic patients who develop severe AKI, renal cortical perfusion is deficient despite normal macrovascular organ blood flow. This intra-renal perfusion abnormality may be amenable to pharmacological manipulation, which may offer mechanistic insight into the pathophysiology of septic AKI. The aim of the current study is to investigate the effects of vasopressin and angiotensin II on renal microcirculatory perfusion in a cohort of patients with septic shock.
METHODS AND ANALYSIS
In this single centre, mechanistically focussed, randomised controlled study, 45 patients with septic shock will be randomly allocated to either of the study vasopressors (vasopressin or angiotensin II) or standard therapy (norepinephrine). Infusions will be titrated to maintain a mean arterial pressure (MAP) target set by the attending clinician. Renal microcirculatory assessment will be performed for the cortex and medulla using contrast-enhanced ultrasound (CEUS) and urinary oxygen tension (pO2), respectively. Renal macrovascular flow will be assessed via renal artery ultrasound. Measurement of systemic macrovascular flow will be performed through transthoracic echocardiography (TTE) and microvascular flow via sublingual incident dark field (IDF) video microscopy. Measures will be taken at baseline, +1 and +24hrs following infusion of the study drug commencing. Blood and urine samples will also be collected at the measurement time points. Longitudinal data will be compared between groups and over time.
DISCUSSION
Vasopressors are integral to the management of patients with septic shock. This study aims to further understanding of the relationship between this therapy, renal perfusion and the development of AKI. In addition, using CEUS and urinary pO2, we hope to build a more complete picture of renal perfusion in septic shock by interrogation of the constituent parts of the kidney. Results will be published in peer-reviewed journals and presented at academic meetings.
TRIAL REGISTRATION
The REPERFUSE study was registered on Clinical Trials.gov (NCT06234592) on the 30th Jan 24.
Topics: Humans; Shock, Septic; Vasoconstrictor Agents; Microcirculation; Acute Kidney Injury; Kidney; Vasopressins; Angiotensin II; Male; Female; Norepinephrine; Renal Circulation; Middle Aged; Adult
PubMed: 38870103
DOI: 10.1371/journal.pone.0304227 -
Clinical Interventions in Aging 2024Renal impairment (RI) is associated with unfavourable outcome after acute ischaemic stroke with anterior circulation large vessel occlusion. We assessed the association... (Observational Study)
Observational Study
PURPOSE
Renal impairment (RI) is associated with unfavourable outcome after acute ischaemic stroke with anterior circulation large vessel occlusion. We assessed the association of RI with clinical outcomes in patients with acute basilar artery occlusion (ABAO), and the impact of RI on the effects of endovascular therapy (EVT) versus standard medical treatment (SMT).
PATIENTS AND METHODS
We used data from the BASILAR registry, an observational, prospective, nationwide study of patients with ABAO in routine clinical practice in China. Baseline estimated glomerular filtration rate (eGFR) was recorded at admission. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included favourable outcome (mRS score 0-3), mortality, and symptomatic intracranial haemorrhage (sICH). Multivariate logistic regression was used to assess the association of RI with mortality and functional improvement at 90 days.
RESULTS
Among 829 patients enrolled, 747 patients were analysed. The median baseline eGFR was 89 mL/min/1.73m (IQR, 71-100), and 350 (46.8%), 297 (39.8%), and 100 (13.4%) patients had baseline eGFR values of ≥90, 60-89, and <60 mL/min/1.73m, respectively. RI was associated with increased mortality (adjusted odds ratio [aOR], 1.97; 95% CI, 1.15-3.67) at 90 days and decreased survival probability (aOR 1.74; 95% CI, 1.30-2.33) within 1 year. EVT was associated with better functional improvement (common aOR, 2.50; 95% CI, 1.43-4.35), favourable outcome (aOR 5.42; 95% CI, 1.92-15.29) and lower mortality (aOR 0.47; 95% CI, 0.25-0.88) in ABAO patients with eGFR ≥90 mL/min/1.73m. However, RI was not modified the relationship of EVT with functional improvement (common aOR, 3.03; 95% CI, 0.81-11.11), favourable outcome (aOR 2.10; 95% CI, 0.45-9.79), and mortality (aOR 0.56; 95% CI, 0.15-2.06) by eGFR categories.
CONCLUSION
RI is associated with reduced efficacy of EVT and worse functional outcome and higher mortality at 3 months and lower survival probability at 1 year in patients with ABAO.
Topics: Humans; Male; Female; Endovascular Procedures; Aged; Middle Aged; Prospective Studies; Glomerular Filtration Rate; China; Treatment Outcome; Registries; Renal Insufficiency; Logistic Models; Basilar Artery; Vertebrobasilar Insufficiency; Ischemic Stroke; Aged, 80 and over
PubMed: 38860034
DOI: 10.2147/CIA.S462638 -
Urolithiasis Jun 2024To assess the impact of endoscopic stone surgeries on renal perfusion and blood flow in children. (Clinical Trial)
Clinical Trial
AIM
To assess the impact of endoscopic stone surgeries on renal perfusion and blood flow in children.
MATERIALS AND METHODS
Children who underwent percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), ureterorenoscopy (URS), endoscopic combined intrarenal surgery (ECIRS) were included to the study. Renal Doppler ultrasonography (RDUS) was performed one day before the operation, and on the postoperative 1st day and 1st month. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were measured, and resistive index (RI) was calculated with the (PSV-EDV)/PSV formula. RDUS parameters were compared before and after surgery and between ipsilateral and contralateral kidneys.
RESULTS
A total of 45 children with a median age was 8 (2-17) years were included (15 (33.3%) girls, 30 (66.7%) boys). PCNL was performed in 13 children (28.9%), RIRS 11 (24.4%), URS 12 (26.7%), and ECIRS 9 (20%). There was no significant difference in renal and segmental PSV, EDV and RI values of operated kidney in the preoperative, postoperative periods. There was no significant difference between RDUS parameters of the ipsilateral and contralateral kidneys in preoperative or postoperative periods. PSV and EDV values were significantly higher in the 1st postoperative month in the group without preoperative DJ stent than in the group with DJ stent (p = 0,031, p = 0,041, respectively). However, RI values were similar. The mean RI were below the threshold value of 0.7 in each period.
CONCLUSION
RDUS parameters didn't show a significant difference in children. Endoscopic surgeries can be safely performed in pediatric stone disease.
Topics: Humans; Child; Female; Male; Adolescent; Prospective Studies; Kidney Calculi; Child, Preschool; Ureteral Calculi; Ureteroscopy; Nephrolithotomy, Percutaneous; Ultrasonography, Doppler; Kidney; Renal Circulation; Blood Flow Velocity
PubMed: 38847881
DOI: 10.1007/s00240-024-01578-z -
Voprosy Virusologii May 2024The objective is to determine the complete nucleotide sequence and conduct a phylogenetic analysis of genome variants of the Puumala virus isolated in the Saratov region.
UNLABELLED
The objective is to determine the complete nucleotide sequence and conduct a phylogenetic analysis of genome variants of the Puumala virus isolated in the Saratov region.
MATERIALS AND METHODS
The samples for the study were field material collected in the Gagarinsky (formerly Saratovsky), Engelssky, Novoburassky and Khvalynsky districts of the Saratov region in the period from 2019 to 2022. To specifically enrich the Puumala virus genome in the samples, were used PCR and developed a specific primer panel. Next, the resulting PCR products were sequenced and the fragments were assembled into one sequence for each segment of the virus genome. To construct phylogenetic trees, the maximum parsimony algorithm was used.
RESULTS
Genetic variants of the Puumala virus isolated in the Saratov region have a high degree of genome similarity to each other, which indicates their unity of origin. According to phylogenetic analysis, they all form a separate branch in the cluster formed by hantaviruses from other subjects of the Volga Federal District. The virus variants from the Republics of Udmurtia and Tatarstan, as well as from the Samara and Ulyanovsk regions, are closest to the samples from the Saratov region.
CONCLUSION
The data obtained show the presence of a pronounced territorial confinement of strains to certain regions or areas that are the natural biotopes of their carriers. This makes it possible to fairly accurately determine the territory of possible infection of patients and/or the circulation of carriers of these virus variants based on the sequence of individual segments of their genome.
Topics: Phylogeny; Puumala virus; Humans; Genome, Viral; Russia; Genetic Variation; Hemorrhagic Fever with Renal Syndrome; Animals
PubMed: 38843022
DOI: 10.36233/0507-4088-224 -
Circulation Jun 2024A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-β...
BACKGROUND
A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-β peptides in the brain, some of which are neurotoxic and linked to Alzheimer-type dementia. To address this, we examined the effect of sacubitril/valsartan compared with valsartan on cognitive function in patients with heart failure with preserved ejection fraction in a prespecified substudy of PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction).
METHODS
In PARAGON-HF, serial assessment of cognitive function was conducted in a subset of patients with the Mini-Mental State Examination (MMSE; score range, 0-30, with lower scores reflecting worse cognitive function). The prespecified primary analysis of this substudy was the change from baseline in MMSE score at 96 weeks. Other post hoc analyses included cognitive decline (fall in MMSEs score of ≥3 points), cognitive impairment (MMSE score <24), or the occurrence of dementia-related adverse events.
RESULTS
Among 2895 patients included in the MMSE substudy with baseline MMSE score measured, 1453 patients were assigned to sacubitril/valsartan and 1442 to valsartan. Their mean age was 73 years, and the median follow-up was 32 months. The mean±SD MMSE score at randomization was 27.4±3.0 in the sacubitril/valsartan group, with 10% having an MMSE score <24; the corresponding numbers were nearly identical in the valsartan group. The mean change from baseline to 96 weeks in the sacubitril/valsartan group was -0.05 (SE, 0.07); the corresponding change in the valsartan group was -0.04 (0.07). The mean between-treatment difference at week 96 was -0.01 (95% CI, -0.20 to 0.19; =0.95). Analyses of a ≥3-point decline in MMSE, decrease to a score <24, dementia-related adverse events, and combinations of these showed no difference between sacubitril/valsartan and valsartan. No difference was found in the subgroup of patients tested for apolipoprotein E ε4 allele genotype.
CONCLUSIONS
Patients with heart failure with preserved ejection fraction in PARAGON-HF had relatively low baseline MMSE scores. Cognitive change, measured by MMSE, did not differ between treatment with sacubitril/valsartan and treatment with valsartan in patients with heart failure with preserved ejection fraction.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.
PubMed: 38841854
DOI: 10.1161/CIRCULATIONAHA.124.068774 -
Catheterization and Cardiovascular... Jun 2024Randomized clinical trials failed to show additional benefit of renal artery stenting on top of medical therapy. Instead of writing an obituary on renal artery stenting,... (Review)
Review
Randomized clinical trials failed to show additional benefit of renal artery stenting on top of medical therapy. Instead of writing an obituary on renal artery stenting, we try to explain these disappointing results. A transstenotic pressure gradient is needed to reduce renal perfusion and to activate the renin-angiotensin-aldosterone system. In only a minority of patients included in trials, a transstenotic pressure gradient is measured and reported. Like the coronary circulation, integration of physiological lesion assessment will allow to avoid stenting of non-significant lesions and select those patients that are most likely to benefit from renal artery stenting. Renal artery interventions are associated with peri-procedural complications. Contemporary techniques, including radial artery access, no-touch technique to engage the renal ostium and the use of embolic protection devices, will minimize procedural risk. Combining optimal patient selection and meticulous technique might lead to a netto clinical benefit when renal artery stenting is added to optimal medical therapy.
PubMed: 38837309
DOI: 10.1002/ccd.31117 -
BMC Nephrology Jun 2024Long-term enzyme replacement therapy (ERT) may improve prognosis in the patients with Fabry disease (FD), however, detail psychosocial burden has not been focused on...
BACKGROUND
Long-term enzyme replacement therapy (ERT) may improve prognosis in the patients with Fabry disease (FD), however, detail psychosocial burden has not been focused on long life expectancy. We experienced a male case of FD under ERT, he was placed on hemodialysis and presented rapidly progressive cognitive function.
CASE PRESENTATION
A 51-year-old male patient with FD has been receiving ERT from age of 38 years. Hemodialysis was initiated at the age of 47 years. The patient experienced several attacks of cerebral infarction, and brain images demonstrated wide-spread asymptomatic ischemic lesions. His behavior became problematic at the age of 51 years. He often exhibited restlessness during hemodialysis sessions and failure to communicate effectively. The patient experienced impairment of attention and executive function, topographical disorientation, and amnesia. Consequently, it was necessary for medical staff and family members to monitor his behavior for safe extracorporeal circulation and daily life activities. Annual standardized neuropsychiatric testing revealed worsening of cognitive performance.
CONCLUSIONS
Despite treating with long-term ERT, it is necessary to determine the psychosocial burden derived from the progression of cognitive impairment in patients with FD undergoing hemodialysis.
Topics: Humans; Male; Fabry Disease; Renal Dialysis; Middle Aged; Cognitive Dysfunction; Enzyme Replacement Therapy; Disease Progression; Cost of Illness
PubMed: 38831308
DOI: 10.1186/s12882-024-03624-9 -
Annals of Internal Medicine Jun 2024Khan SS, Matsushita K, Sang Y, et al; Chronic Kidney Disease Prognosis Consortium and the American Heart Association Cardiovascular-Kidney-Metabolic Science Advisory...
Khan SS, Matsushita K, Sang Y, et al; Chronic Kidney Disease Prognosis Consortium and the American Heart Association Cardiovascular-Kidney-Metabolic Science Advisory Group. Circulation. 2024;149:430-449. 37947085.
Topics: Humans; Cardiovascular Diseases; Middle Aged; Risk Assessment; Aged; Adult; Male; Female; United States; Renal Insufficiency, Chronic; Risk Factors; Glomerular Filtration Rate; American Heart Association
PubMed: 38830213
DOI: 10.7326/ANNALS-24-00208-JC