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0049). Hispanic and Black children also had distinct alterations in myeloid cells, with a significant increase in a population of non-classical activated HLA-DR +CD16+myeloid cells, previously implicated in disease progression, compared with NHW counterparts. Racial background also correlated with altered expression of inhibitory checkpoint PD-L1 on myeloid cells.
There are surprisingly substantial race/ethnicity-based differences in innate immune cells of children with newly diagnosed B-ALL. These differences urge the need to enhance accrual of children from minorities background in immunetherapy trials and may impact their outcome following such therapy.
There are surprisingly substantial race/ethnicity-based differences in innate immune cells of children with newly diagnosed B-ALL. These differences urge the need to enhance accrual of children from minorities background in immunetherapy trials and may impact their outcome following such therapy.
Immune checkpoint inhibitors (ICIs) have revolutionized treatment of advanced hepatocellular carcinoma. Integrated use of transarterial chemoembolization (TACE), a locoregional inducer of immunogenic cell death, with ICI has not been formally assessed for safety and efficacy outcomes.
From a retrospective multicenter dataset of 323 patients treated with ICI, we identified 31 patients who underwent >1 TACE 60 days before or concurrently, with nivolumab at a single center. We derived a propensity score-matched cohort of 104 patients based on Child-Pugh Score, portal vein thrombosis, extrahepatic metastasis and alpha fetoprotein (AFP) who received nivolumab monotherapy. We described overall survival (OS), progression-free survival (PFS), objective responses according to modified RECIST criteria and safety in the multimodal arm in comparison to monotherapy.
Over a median follow-up of 9.3 (IQR 4.0-16.4) months, patients undergoing multimodal immunotherapy with TACE achieved a significantly longer median (d patients.
TACE can be safely integrated with programmed cell death 1 blockade and may lead to a significant delay in tumor progression and disease downstaging in selected patients.The Sonic hedgehog (Shh) signaling pathway is an essential pathway in the human body that plays an important role in embryogenesis and tissue homeostasis. Aberrant activation of this pathway has been linked to the development of different diseases, ranging from cancer to immune dysregulation and infections.Uncontrolled activation of the pathway through sporadic mutations or other mechanisms is associated with cancer development and progression in various malignancies, such as basal cell carcinoma, medulloblastoma, pancreatic cancer, breast cancer and small-cell lung carcinoma. Targeted inhibition of the pathway components has therefore emerged as an attractive and validated therapeutic strategy for the treatment of a wide range of cancers. Currently, two main components of the pathway, the smoothened receptor and the glioma-associated oncogene homolog transcriptional factors, have been investigated for the development of targeted drugs, leading to the marketing authorization of three smoothened receptor inhibitors for the treatment of basal cell carcinoma and acute myeloid leukemia.The Shh pathway also seems to be involved in regulating the immune response, possibly playing a role in immune system evasions by tumors, development of autoimmune diseases, such as rheumatoid arthritis and Crohn's disease, airway inflammation, and diseases related to aberrant activation of T-helper 2 cellular response, such as allergy, atopic dermatitis, and asthma.Finally, the Shh pathway is involved in pathogen-mediated infection, including influenza-A and, more recently, SARS-CoV-2 viruses. Therefore, agents that inhibit the Shh signaling pathway might be used to treat pathogenic infections, shifting the therapeutic approach from strain-specific treatments to host-based strategies that target highly conserved host targets.
To conduct a meta-analysis of randomised controlled trials (RCTs) to evaluate the impact of ILR use on occurrence of recurrent stroke.
PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched from 1966 to November 2021 to identify RCTs comparing ILR versus non-ILR in patients with ischaemic stroke. Relative risk (RR) with 95% CI was used as a measure of the effect of ILR versus non-ILR on recurrent stroke, recurrent ischaemic stroke, AF detection and oral anticoagulant (OAC) initiation. A fixed-effect estimate based on the Mantel-Haenszel method was computed.
We identified three RCTs with 1233 patients with ischaemic stroke. Among three included RCTs, 54 recurrent stroke events were reported in two RCTs and 84 recurrent ischaemic stroke events were reported in three RCTs. Pooled results showed that patients who received ILR versus no ILR was not associated with a significantly reduced risk of recurrent stroke (5.6% vs 8.0%; RR 0.70; 95% CI 0.42 to 1.19) or recurrent ischaemic stroke (5.7% vs 7.9%; RR 0.72; 95% CI 0.48 to 1.10). Compared to non-ILR patients, ILR patients had higher rates of AF detection (12.9% vs 2.4%; RR 5.31; 95% CI, 3.10 to 9.11) and OAC initiation (15.2% vs 5.5%; RR 2.77; 95% CI 1.90 to 4.03).
Patients assigned to ILR vs non-ILR did not have a significantly reduced risk of recurrent stroke or recurrent ischaemic stroke despite higher rates of AF detection and OAC initiation. Sufficiently powered RCTs of ILR to assess the risk of recurrent stroke are warranted.
Patients assigned to ILR vs non-ILR did not have a significantly reduced risk of recurrent stroke or recurrent ischaemic stroke despite higher rates of AF detection and OAC initiation. Sufficiently powered RCTs of ILR to assess the risk of recurrent stroke are warranted.
To investigate temporal trends of chronic kidney disease (CKD) among patients with incident aortic stenosis (AS) and to compare these trends with that of a matched control population.
Using the Quebec Integrated Chronic Disease Surveillance System, we performed a population-based nested case-control study including 108 780 patients newly hospitalised with AS and 543 900 age-matched, sex-matched and fiscal year-matched patients without AS from 2000 to 2016 in Quebec (Canada). Three subgroups were considered. Dialysis subgroup had at least two outpatient billing codes of dialysis. The predialysis subgroup had at least one hospital or two billing diagnostic codes of CKD. The remaining individuals were included in the non-CKD subgroup. We estimated overall and sex-specific standardised annual proportions of CKD subgroups through direct standardisation using the 2016-2017 age structure of the incident AS cohort. The trends overtime were estimated through fitting robust Poisson regression models. Age-specific derventions targeting CKD risk factors may influence AS incidence in the future.
Over time, the proportion of patients with CKD increased significantly and remained consistently higher in incident AS individuals compared with controls. Our results highlight the need to investigate whether interventions targeting CKD risk factors may influence AS incidence in the future.Intracardiac and intravascular thrombi are associated with significant morbidity and mortality. Although surgery remains the gold standard treatment option, these patients often have multiple comorbidities that can make surgical options challenging. With advancements in catheter-based technologies, there are now percutaneous treatment options for these patients. The AngioVac is a percutaneous vacuum-assisted thrombectomy device FDA-approved for removal of intravascular debris that uses a venovenous extracorporeal membranous oxygenation circuit with a filter. Use of this device has now been reported in the removal of right atrial or iliocaval thrombi, debulking tricuspid vegetations, removal of vegetations from implantable cardiac devices, and pulmonary embolism.Acute ischemic stroke (AIS) is one of the major causes of death worldwide and a leading cause of disability. Until recently treatment of AIS was supportive, and in a minority of patients intravenous thrombolysis was available but with marginal clinical benefit. With the advent of stent retrievers, distal aspiration catheters as well as improved patient selection neurologic outcomes have greatly improved. However, the care of patients with AIS is still challenging and requires the early recognition of stroke symptoms, extensive diagnostic testing, early intervention, and advanced nursing and critical care.The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious pathogen resulting in the 2019 coronavirus disease (COVID-19) pandemic with direct impact on cardiac catheterization laboratory (CCL) operations. Initially, major challenges in limiting the spread of aerosolized pathogens existed until protocols were implemented to limit infectivity to staff and patients. COVID-19 increases the risk of myocardial infarctions and cardiogenic shock requiring acute management in the CCL. In this review, we specify best practices in the CCL for the management of infected patients in the preprocedure, intraprocedure, and postprocedure environments harmonizing available evidence, recommendations from international heart associations, and consensus opinion.Pelvic venous disorders are inter-related pathologic conditions caused by reflux and obstruction in the pelvic veins. selleck chemical It can present a spectrum of clinical features based on the route of transmission of venous hypertension to either distal or caudal venous reservoirs. Imaging can help to visualize pelvic vascular and visceral structures to rule out other gynecologic, gastrointestinal, and urologic diseases. Endovascular treatment, owing to its low invasive nature and high success rate, has become the mainstay in the management of pelvic venous disorders. This article reviews the pathophysiology, clinical presentations, and diagnostic and therapeutic approaches to pelvic venous disorders.Pulmonary arterial hypertension is a common and highly morbid medical problem resulting in elevated pulmonary arterial pressures and pulmonary vascular resistance. Medical therapies are costly, and not always well-tolerated. Surgical therapies such as pulmonary endarterectomy and lung transplantation are limited to a small subset of patients due to various patient, disease, or institutional factors. Over the past decade, there has been growing investigation into endovascular interventional therapies for patients with pulmonary hypertension such as balloon pulmonary angioplasty and pulmonary denervation. In this review, we describe the current status, future directions, and our recommendations on technical considerations with these therapies.Refractory angina (RA) is defined as chest pain caused by coronary ischemia in patients on maximal medical therapy and is not amenable to revascularization despite advanced coronary artery disease (CAD). The long-term prognosis has improved with optimal medical therapy including risk factor modification. Still, patients are left with major impairment in quality of life and have high resource utilization with limited treatment options. We review the novel invasive and noninvasive therapies under investigation for RA.
