The development of cell therapies to treat peripheral vascular disease has proven difficult because of the contribution of multiple cell types that coordinate revascularization. We characterized the ...vascular regenerative potential of transplanted human bone marrow (BM) cells purified by high aldehyde dehydrogenase (ALDHhi) activity, a progenitor cell function conserved between several lineages. BM ALDHhi cells were enriched for myelo-erythroid progenitors that produced multipotent hematopoietic reconstitution after transplantation and contained nonhematopoietic precursors that established colonies in mesenchymal-stromal and endothelial culture conditions. The regenerative capacity of human ALDHhi cells was assessed by intravenous transplantation into immune-deficient mice with limb ischemia induced by femoral artery ligation/transection. Compared with recipients injected with unpurified nucleated cells containing the equivalent of 2- to 4-fold more ALDHhi cells, mice transplanted with purified ALDHhi cells showed augmented recovery of perfusion and increased blood vessel density in ischemic limbs. ALDHhi cells transiently recruited to ischemic regions but did not significantly integrate into ischemic tissue, suggesting that transient ALDHhi cell engraftment stimulated endogenous revascularization. Thus, human BM ALDHhi cells represent a progenitor-enriched population of several cell lineages that improves perfusion in ischemic limbs after transplantation. These clinically relevant cells may prove useful in the treatment of critical ischemia in humans.
Abstract
Background
Intravascular lithotripsy (IVL) is a promising balloon-based technique to treat calcified coronary lesions. The evidence of its use in LM disease is scarce and there are no ...studies reporting a comparison between IVL and conventional techniques for calcified lesions, especially in LM PCI that represented an exclusion criteria of the DISRUPT-CAD trials.
Methods
The aim of this study is to evaluate safety and efficacy of IVL to treat moderate-severe calcified LM disease from January 2018 to December 2022. We stratified our cohort into two groups 1) patients who underwent LM PCI with IVL treatment (bail-out or upfront) and 2) LM PCI with conventional techniques excluding IVL (cutting balloons, NC/OPN balloons, rotational atherectomy). Efficacy endpoint: device success and stent expansion evaluated either by intravascular imaging or angiographic criteria. Safety endpoint: peri-procedural complications (coronary dissection, perforation, no-slow flow, peri-procedural MI, pericardial effusion) and in hospital death or target vessel failure.
Results
87 patients were enrolled, 43 (49.4%) underwent LM PCI with IVL (group A), while 44 (50.6%) were treated with conventional techniques (35 NC balloons, 7 RA, 2 cutting balloons). Intravascular imaging was performed in 69% of cases, the 2 groups were similar in terms of age (77.4±9.63, p=0.94), comorbidity, clinical presentation and angiographic characteristics. Both groups presented severe calcifications in terms of calcium length (11.9±10.3, p=0.87), arc (270° 144-350, p = 0.76, and thickness (1.3 ±0.7 p =0.99) assessed by intravascular imaging. IVUS calcium score was similar between 2 groups (1.53±0.7, p = 0.7).
Target vessel was distal LM-proximal LAD in 56.6%. IVL most used balloon was 3.5mm (55%), followed by 4.00mm (38.2%). Impella CP was implanted to support 4 PCI and removed at the end of the procedure. Provisional stenting was performed in 55.1% of cases, while two-stents technique was used in 26.4% (mainly represented by DK-crush). Good stent expansion (>80%) was achieved in 85% of cases, with a certain prevalence for patients treated with IVL. Optimal stent expansion (>90%) was higher in patients treated with IVL (9 in group A vs 3 in group B), although it did not reach a statistically significative difference (p=0.06). No differences in terms of complications and peri-procedural myocardial infarction occurred between the two groups.
Conclusions
This is the first description of a comparison between IVL and conventional techniques in LM calcified PCI. IVL appeared to be safe and effective with good stent expansion and low rate of peri-procedural complications and in-hospital MACE. LM lesions treated with IVL appeared to reach greater stent expansion compared to other techniques, although it was not statistically significative. Certainly, further trials are warranted to establish longer term outcomes and the benefit of IVL over existing calcium-modification therapies.
Purpose
To study the possible association of CT-derived quantitative epicardial adipose tissue (EAT) and glycemia at the admission, with severe outcomes in patients with COVID-19.
Methods
Two hundred ...and twenty-nine patients consecutively hospitalized for COVID-19 from March 1st to June 30th 2020 were studied. Non contrast chest CT scans, to confirm diagnosis of pneumonia, were performed. EAT volume (cm
3
) and attenuation (Hounsfield units) were measured using a CT post-processing software. The primary outcome was acute respiratory distress syndrome (ARDS) or in-hospital death.
Results
The primary outcome occurred in 56.8% patients. Fasting blood glucose was significantly higher in the group ARDS/death than in the group with better prognosis 114 (98–144) vs. 101 (91–118) mg/dl,
p
= 0.001. EAT volume was higher in patients with vs without the primary outcome 103 (69.25; 129.75) vs. 78.95 (50.7; 100.25) cm
3
,
p
< 0.001 and it was positively correlated with glycemia, PCR, fibrinogen,
P
/
F
ratio. In the multivariable logistic regression analysis, age and EAT volume were independently associated with ARDS/death. Glycemia and EAT attenuation would appear to be factors involved in ARDS/death with a trend of statistical significance.
Conclusions
Our findings suggest that both blood glucose and EAT, easily measurable and modifiable targets, could be important predisposing factors for severe Covid-19 complications.
The primary objective of this study was to determine sharps disposal practices among people with diabetes in a community care clinic. Secondary objectives were to identify patterns of sharps use and ...barriers to proper use.
Surveys were distributed to patients at a community care clinic in person and via mail. Survey questions focused on how sharps are used and disposed of, the frequency of sharps changes, sharps disposal training, sharps identification, and confidence in sharps disposal. Participant demographics and diabetes profiles were also collected.
Among 89 respondents, mean age was 60 years (range 29-93 years), 61.8% were Caucasian, 88.8% had type 2 diabetes, and 60.7% had had a diabetes diagnosis for ≤10 years, with diverse diabetes management methods; 57.3% did not receive or were unsure of sharps training, 25.8% discarded used sharps without a designated sharps container, and 37.1% properly disposed of sharps containers at sharps disposal facilities. Barriers to proper sharps practices included perceived safety of reusing sharps and waste with single use, cost, and the hassle of disposal. Those with prior sharps training were more likely to properly use and discard sharps; however, gaps in knowledge were still evident in this population.
Results indicate gaps in proper sharps use and disposal knowledge among people with diabetes. Responses revealed sharps practices that are inconsistent with current federal and state regulations and are potentially dangerous for those handling improperly discarded sharps. Targeted sharps usage and disposal education resources are needed for individuals with and without prior sharps training.
There is considerable interest in the potential of cell-based approaches to mediate therapeutic angiogenesis for acute and chronic vascular syndromes. Using a mouse model of HLI, we showed previously ...that adoptive transfer of a small number of donor monocytes enhanced revascularization significantly. Herein, we provide data suggesting that the BM resident monocytes sense systemic signals that influence their future functional capacity. Specifically, following induction of distant ischemia, the angiogenic capacity of BM resident monocytes is reduced markedly. We provide evidence that G-CSF and IL-6 represent such "conditioning" signals. Systemic levels of G-CSF and IL-6 are increased significantly following induction of HLI. Accordingly, BM resident monocytes from ischemic mice exhibited increased pSTAT3 and STAT3 target gene expression. Finally, G-CSFR(-/-) and IL-6(-/-) mice were resistant to the deleterious effects of ischemic conditioning on monocyte angiogenic potential. RNA expression profiling suggested that ischemia-conditioned monocytes in the BM up-regulate the well-described M2 polarization markers Chi3l4 and Lrg1. Consistent with this observation, M2-skewed monocytes from SHIP(-/-) mice also had impaired angiogenic capacity. Collectively, these data show that G-CSF and IL-6 provide signals that determine the angiogenic potential of BM resident monocytes.
In addition to the well-known involvement of macrophages and neutrophils, other cell types have been recently reported to substantially contribute to the onset and progression of inflammatory bowel ...diseases (IBD). Enteric glial cells (EGC) are the equivalent cell type of astrocyte in the central nervous system (CNS) and share with them many neurotrophic and neuro-immunomodulatory properties. This short review highlights the role of EGC in IBD, describing the role played by these cells in the maintenance of gut homeostasis, and their modulation of enteric neuronal activities. In pathological conditions, EGC have been reported to trigger and support bowel inflammation through the specific over-secretion of S100B protein, a pivotal neurotrophic factor able to induce chronic inflammatory changes in gut mucosa. New pharmacological tools that may improve the current therapeutic strategies for inflammatory bowel diseases (IBD), lowering side effects (i.e. corticosteroids) and costs (i.e. anti-TNFα monoclonal antibodies) represent a very important challenge for gastroenterologists and pharmacologists. Novel drugs capable to modulate enteric glia reactivity, limiting the pro-inflammatory release of S100B, may thus represent a significant innovation in the field of pharmacological interventions for inflammatory bowel diseases.
Chronic inflammation is a major risk factor for cancer, including gastric cancers and other gastrointestinal cancers. For example, chronic inflammation caused by autoimmune gastritis (AIG) is ...associated with an increased risk of gastric polyps, gastric carcinoid tumors, and possibly adenocarcinomas. In this study, we characterized the progression of gastric cancer in a novel mouse model of AIG. In this model, disease was caused by CD4(+) T cells expressing a transgenic T-cell receptor specific for a peptide from the H(+)/K(+) ATPase proton pump, a protein expressed by parietal cells in the stomach. AIG caused epithelial cell aberrations that mimicked most of those seen in progression of human gastric cancers, including chronic gastritis followed by oxyntic atrophy, mucous neck cell hyperplasia, spasmolytic polypeptide-expressing metaplasia, dysplasia, and ultimately gastric intraepithelial neoplasias. Our work provides the first direct evidence that AIG supports the development of gastric neoplasia and provides a useful model to study how inflammation drives gastric cancer.
The metabolic syndrome is a long-term process, explained by the interaction of genetic and environmental factors, that starts early in life and is involved in the pathophysiology of a large ...percentage of cases with type 2 diabetes and atherosclerosis. A number of clinical studies have demonstrated the importance of fat distribution and especially the contribution of visceral fat accumulation to the development of metabolic disorders. Visceral adipose tissue can be studied through different imaging techniques. The accumulation of visceral adipose tissue, as opposed to subcutaneous fat, increases the risk of developing metabolic disease and cardiovascular diseases (CVD). Visceral adipocytes secrete a variety of cytokines known as adipocytokines suggesting that adipose tissue is an endocrine organ that may affect the function of other organs. Weight loss, particularly a reduction in waist circumference, improves insulin sensitivity, lipid profile, and serum adipocytokines, reducing the risk of developing chronic disease and CVD. Waist circumference is a required component of metabolic syndrome under the International Diabetes Federation (IDF) criteria, rather than an optional component as used by other previous classifications. Studies have shown that using a lower waist circumference threshold within the context of metabolic syndrome increases the prevalence, but decreases the risk of mortality and type 2 diabetes. It is possible that waist circumference acts as a marker for other risk factors. These findings reinforce the notion that reductions in visceral adipose tissue should be a primary aim of strategies designed to reduce health risks associated with metabolic syndrome.
Circulating endothelial progenitor cells (EPCs) are thought to contribute to angiogenesis following vascular injury, stimulating interest in their ability to mediate therapeutic angiogenesis. ...However, the number of EPCs in the blood is low, limiting endogenous repair, and a method to rapidly mobilize EPCs has not been reported. In this study, healthy donors were mobilized sequentially with the CXCR4 antagonist, AMD3100, and G-CSF. The number of EPCs and circulating angiogenic cells (CACs) in the blood and pheresis product was determined and the angiogenic capacity of each cell population assessed. Compared with baseline, treatment with AMD3100 or G-CSF increased the number of blood CACs 10.0-fold ± 4.4-fold and 8.8-fold ± 3.7-fold, respectively. The number of EPCs in the blood increased 10.2-fold ± 3.3-fold and 21.8-fold ± 5.4-fold, respectively. On a percell basis, CACs harvested from G-CSF–mobilized blood displayed increased in vivo angiogenic potential compared with AMD3100-mobilized CACs. Mobilized EPCs displayed a greater proliferative capacity than EPCs isolated from baseline blood. Both CACs and EPCs were efficiently harvested by leukapheresis. Cryopreserved CACs but not EPCs retained functional activity after thawing. These data show that AMD3100 is a potent and rapid mobilizer of angiogenic cells and demonstrate the feasibility of obtaining and storing large numbers of angiogenic cells by leukapheresis.
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