Pulmonary embolism (PE) is a potentially life-threatening disorder. Beyond its usefulness in the prognostic stratification of heart failure, sST2 can represent a biomarker with high utility in ...several acute conditions. Our study was aimed to investigate whether sST2 can be used as a clinical marker of severity and prognostic outcome in acute PE. We enrolled 72 patients with documented PE and 38 healthy subjects; we measured the plasma concentrations of sST2 to evaluate the prognostic and severity performance of different levels of sST2 according to its association with the pulmonary embolism severity index (PESI) score and several parameters of respiratory function. PE patients had significantly higher levels of sST2 compared with healthy subjects (87.74 ± 17.1 vs. 17.1 ± 0.4 ng/mL,
< 0.001); we found higher PESI scores and serum lactate values in the group of patients with sST2 > 35 ng/mL compared with patients with sST2 < 35 ng/mL (138.7 ± 14.9 vs. 103.7 ± 15.1 and 2.43 ± 0.69 vs. 1.025 ± 0.05 mmol/L, respectively;
< 0.05). Patients with sST2 > 35 ng/mL showed higher radiological severity of PE compared with patients with sST2 < 35 ng/mL. Moreover, sST2 was the strongest parameter with a discriminative capacity for the development of acute respiratory failure and a PESI score >106 with respect to C reactive protein (CRP), creatinine, d-dimer, and serum lactate. We clearly demonstrated that sST2 significantly increased in PE and that its elevation was associated with disease severity. Therefore, sST2 may be used as a clinical marker in the evaluation of PE severity. However, further studies with larger patient populations are required to confirm these findings.
BACKGROUND AND AIMS:The adrenal mineralocorticoid system plays a key role in cardiovascular, metabolic and renal damage. This study aimed to assess the relationship between plasma aldosterone ...concentration (PAC) and some surrogate markers of subclinical atherosclerosis, such as carotid intima-media thickness (cIMT), ankle-brachial index (ABI) and biochemical parameters in patients with essential hypertension.
METHODS AND RESULTS:From January 2014 to December 2017, we consecutively enrolled 804 essential hypertensive patients (407 men and 397 women, mean age 50 ± 14 years) without cardiovascular complications, distinguishing patients in quartiles according to PAC. Compared with the first quartile, the highest PAC quartile was associated with the highest levels of serum uric acid (SUA) (5.3 ± 1.3 vs. 5.0 ± 1.0 mg/dl; P = 0.01), triglycerides (117.5 ± 15.7 vs. 106.8 ± 10.5 mg/dl; P < 0.05), 24-h urinary albumin excretion (UAE) (38.8 ± vs. 7.6 ± mg/24 h; P < 0.05), cIMT (0.87 ± 0.22 vs. 0.80 ± 0.21 mm; P = 0.001) and increased prevalence of carotid plaques (26 vs. 16%; P < 0.005). Moreover, we found that in patients with PAC more than 150 pg/ml, the ABI was significantly lower than those with PAC < 150 pg/ml (1.01 ± 0.09 vs. 1.10 ± 0.09; P < 0.022). PAC was also found to be an independent predictor of the presence of carotid plaques and pathological ABI (<0.9) in essential hypertensive individuals.
CONCLUSION:Our results revealed that higher PAC values are strongly associated with some metabolic variables, as triglycerides, UAE, cIMT, worse ABI and major prevalence of carotid plaques that, together with elevated blood pressure values, are strictly correlated with higher risk of atherosclerosis and cardiovascular complications.
Purpose
Adrenal incidentalomas (AI) are discovered after work-up unrelated to adrenal gland diseases; up to 30% of AI show subclinical endogenous cortisol excess (SH), frequently associated to ...hypertension, obesity, metabolic disorders and increased incidence of cardiovascular events (CVEs).
Methods
We analysed 628 AI patients divided into two groups: 471 non-functional adrenal adenoma (NFA) and 157 SH. All patients underwent complete examinations, 24-h ambulatory blood pressure monitoring, biohumoral parameters and vascular damage markers, such as c-IMT and ankle brachial index. After long-term follow-up, we registered newly onset of CVEs such as myocardial infarction (MI), percutaneous stenting and surgical bypass (PTA/CABG), stroke, overall/cardiovascular mortality. Moreover, SH patients underwent to surgical (SSH) or pharmacological treatment (MSH).
Results
SH patients showed higher prevalence of metabolic syndrome, diabetes mellitus, and previous CVEs respect NFA at baseline. After follow-up MSH group showed higher recurrence of major CV events compared with NFA and SSH (RR 2.27 MSH vs NFA for MI; RR 2.30 MSH vs NFA for PTA/CABG; RR 2.41 MSH vs NFA for stroke). In SSH there was a significant reduction of the number of antihypertensive medications needed to reach target blood pressure levels (2.3 ± 1.0 to 1.5 ± 0.4 drugs). None differences were found in SH patients, distinguished in relation to cortisol plasma levels after dexamethasone suppression test (1.8–5 µg/dL, above 5 µg/dL).
Conclusions
SH is linked to relevant cardiovascular and metabolic alterations, leading to worsen clinical outcomes. In eligible patients, adrenalectomy is valid and safe option to treat SH, reducing cardiometabolic abnormalities.
Cellular homeostasis is tightly connected to the broad variety of mitochondrial functions. To stay healthy, cells need a constant supply of nutrients, energy production and antioxidants defenses, ...undergoing programmed death when a serious, irreversible damage occurs. The key element of a functional integration of all these processes is the correct crosstalk between cell signaling and mitochondrial activities. Once this crosstalk is interrupted, the cell is not able to communicate its needs to mitochondria, resulting in oxidative stress and development of pathological conditions. Conversely, dysfunctional mitochondria may affect cell viability, even in the presence of nutrients supply and energy production, indicating the existence of feed-back control mechanisms between mitochondria and other cellular compartments. The ubiquitin proteasome system (UPS) is a multi-step biochemical pathway that, through the conjugation of ubiquitin moieties to specific protein substrates, controls cellular proteostasis and signaling, removing damaged or aged proteins that might otherwise accumulate and affect cell viability. In response to specific needs or changed extracellular microenvironment, the UPS modulates the turnover of mitochondrial proteins, thus influencing the organelle shape, dynamics and function. Alterations of the dynamic and reciprocal regulation between mitochondria and UPS underpin genetic and proliferative disorders. This review focuses on the mitochondrial metabolism and activities supervised by UPS and examines how deregulation of this control mechanism results in proliferative disorders and cancer.
CRC cells evolve a variety of strategies to limit or circumvent apoptosis cell death. RNA binding proteins (RBPs) regulate many of the molecular mechanisms that underlie the development of cancer. ...The insulin-like growth factor II mRNA-binding proteins (IMP) family are oncofoetal RBPs, consisting of IMP1, IMP2 and IMP3, which have an important role in RNA metabolism. IMP3 is highly expressed in colorectal cancer (CRC) tissue, where its expression often correlates with poor prognosis. However, the role of IMP3 in CRC is not fully understood. IMP3 expression was analysed using a public database and by Western blotting and immunohistochemistry in human colon samples derived from patients with sporadic CRC and healthy subjects. To address whether IMP3 controls cancer cell survival, we analysed cell death pathways in in vitro and in vivo experiments after IMP3 downregulation by siRNA or an antisense oligonucleotide. IMP3 was highly expressed in CRC samples compared to normal control tissues. The knockdown of IMP3 enhanced a caspase-independent cell death in CRC cell lines. Furthermore, the treatment of CRC cells with IMP3 siRNA did not alter the expression of GSDMD, GPX-4 and the activated form of RIP3, three key molecules that govern pyroptosis, ferroptosis and necroptosis, respectively. Abrogation of IMP3 in CRC significantly reduced Bcl-2 and Bcl-xL mRNA and was associated with an altered mitochondrial membrane potential that allowed the nuclear migration of the apoptosis-inducing factor (AIF). Moreover, specific immunoprecipitation experiments on CRC human cell lines indicated that IMP3 binds Bcl-2 and Bcl-xL mRNA, suggesting that IMP3 acts as a regulator of the intrinsic apoptotic pathway through the surveillance of anti-apoptotic Bcl mRNA metabolism. Finally, we showed that IMP3 block inhibited the growth of CRC cell lines in vivo after transplantation into immunodeficient mice. Altogether, these data support a novel role for IMP3 in controlling the intrinsic caspase-independent apoptotic pathway in CRC.
Primary cilia are microtubule-based, non-motile sensory organelles present in most types of growth-arrested eukaryotic cells. They are transduction hubs that receive and transmit external signals to ...the cells in order to control growth, differentiation and development. Mutations of genes involved in the formation, maintenance or disassembly of ciliary structures cause a wide array of developmental genetic disorders, also known as ciliopathies. The primary cilium is formed during G1 in the cell cycle and disassembles at the G2/M transition. Following the completion of the cell division, the cilium reassembles in G1. This cycle is finely regulated at multiple levels. The ubiquitin-proteasome system (UPS) and the autophagy machinery, two main protein degradative systems in cells, play a fundamental role in cilium dynamics. Evidence indicate that UPS, autophagy and signaling pathways may act in synergy to control the ciliary homeostasis. However, the mechanisms involved and the links between these regulatory systems and cilium biogenesis, dynamics and signaling are not well defined yet. Here, we discuss the reciprocal regulation of signaling pathways and proteolytic machineries in the control of the assembly and disassembly of the primary cilium, and the impact of the derangement of these regulatory networks in human ciliopathies.
•Stent-assisted coiling of ruptured intracranial aneurysms is a feasible option in selected cases.•Peri- and post-procedural medical treatment regimen is still controversial.•Bail-out AntiGP2b3a are ...extremely effective in achieving complete flow restoration after stent thrombosis without increasing overall complication rate.
To assess efficacy, safety and to discuss optimal medical therapy of stent-assisted coiling of ruptured intracranial aneurysms.
Ruptured intracranial aneurysms treated with stent-assisted coiling in eight different institutions were retrospectively reviewed. Medical treatment regimens varied among the centers, mainly regarding heparin administration and post-procedural single or double antiplatelet therapy. Clinical and angiographic results, including complications and outcomes were analyzed and related to the different therapies.
Sixty-one consecutive patients (male/female 23/38), aged 59.1 years (36–86) underwent stent-assisted coiling for ruptured intracranial aneurysm without antiplatelet pre-medication. Intravenous acetylsalicylic acid (ASA) 500mg was administered to all patients immediately after stent deployment. At the same time heparin was given as bolus in 15 patients (24.6%) as part of local protocol. Intravenous glycoprotein 2b/3a inhibitors (antiGP2b3a) were used as bail-out therapy for stent thrombosis. Stent thrombosis occurred in 22 patients (36.1%), of which 4 (6.5%) lead to incomplete and 18 (29.6) to complete occlusion of the stent. Heparin administration had no effect on thrombosis rate. Thrombosis resolution occurred in all cases with intravenous antiGP2b3a (7 tirofiban, 15 abciximab), without increasing overall complication rate. Single antiplatelet therapy with ASA (28 patients, 45.9%) or double antiplatelet therapy including ASA and clopidogrel (33 patients, 54.1%) were administered after procedure, depending on local protocols and on neurointerventionists’ experience. Overall complication rate, including ischemia and hemorrhage was higher in patients in which only ASA was administered (21.4% vs. 12.1%). No late stent thrombosis was seen, regardless of whether a single or double antiplatelet regimen was used. Nevertheless, the small sample size suggests caution in interpreting these results. Moreover, a possible bias may arise from the decision whether to modify the maintenance therapy or not depending on the severity of the intracranial hemorrhage in a case-by-case assessment. At three months, 34 out of 38 patients with HH grade 1-2 (89.4%), and 11 out of 23 with Hunt-Hess grade of 3-4 (47.8%) were independent (Modified Ranking Scale 0-2).
Stent assisted coiling of ruptured intracranial aneurysms is a feasible option when simple coiling is not possible. Optimal medical treatment is still controversial because balance between hemorrhagic and ischemic risks is difficult to evaluate. In our series, heparin bolus had no effect on subsequent stent thrombosis. In all cases peri-operative stent thrombosis was successfully managed using bail-out intravenous antiGP2b3a, which did not increase post-procedural hemorrhage rates. A non-significant trend towards increased complications rate was noticed in patients treated with single antiplatelet therapy versus double antiplatelet therapy.
Covid-19 infection is characterized by several acute complications, as well long-term sequelae, mostly sustained by endothelial dysfunction; several studies show that complications as pulmonary ...embolism (PE) are described both in the acute phase and after negativization. Aim of research was to evaluate anthropometric, bio-humoral, instrumental parameters in a group of patients affected by PE after recent Covid-19 infection compared to PE patients without previous Covid-19 infection. We enrolled 72 consecutive patients (35M, 37F) with acute PE, distinguished in relation to previous acute Covid-19 infection: 54 pts without previous acute Covid-19 infection and 18 pts with previous Covid-19 infection within negativity at least 2 months before PE diagnosis; 44 healthy subjects (21M, 23F) were recruited as control group. Patients who had previously developed Covid-19 needed hospitalization in high percentage (84%); this group showed significantly higher prevalence of diabetes mellitus than Covid-19-free PE patients, reduced serum levels of C-reactive protein, sST2 and PESI score. In post-Covid-19 PE group, we observed higher mean IMPROVE risk score, whereas in Covid-19-free group lower P/F ratio, higher radiological severity, and worse PESI score and severity index
.
Covid-19 infection affects not just the lung parenchyma but also other organs; endothelial damage plays pivotal role in long-term alterations; in high thrombotic risk group (recent hospitalization due to acute Covid-19 infection), we have described thrombotic complications characterized by persistent prothrombotic state after recovery, highlighted by well-known markers as PCR and D-Dimer as well as novel vascular marker (sST2).
The archaeological site of Notarchirico, chronologically placed at the end of MIS 17 and MIS 16 (675-610 ka), is a key site for studying Acheulean technology in southern Europe and gaining a better ...understanding of human occupation in that region during the Middle Pleistocene. It was excavated between 1979 and 1995 by Marcello Piperno and re-opened since 2016. Between 1990 and 1991, around forty remains of Palaeloxodon antiquus, mostly comprising the head of the animal, such as cranium, mandible and tusks fragments belonging to a sub-adult male were discovered as a result of the excavation of a lateral discontinuity of the level A, situated in an area known as the “elephant butchery area”. Remains of deer, mainly assigned to Dama sp., and 42 stone tools, including choppers, hand-axes, cores and some flakes were also identified in the surroundings. This accumulation was originally interpreted as a butchering site, reflecting a single event of processing of an elephant carcass, and the entire paleosurface was exposed to visitors in situ. This work re-evaluates the original archaeological materials, especially those still preserved on the paleosurface, in terms of stratigraphic distribution, taphonomy and technology, to critically evaluate the putative role of hominins in the exploitation of the megaherbivore. After a meticulous examination of each element's surface and its deposition, we conclude that there is no support for the previous interpretation of the so-called "elephant butchery area" of Notarchirico as the result a butchery event, as there is no evidence of human exploitation of the remains and the accumulation derives from at least two diverse and unrelated depositional events, one resulting in the deposition of the elephant remains, and the other of the majority of the fallow deer remains and the stone tools.
•In Notarchirico, a butchery an elephant was purposed in the “elephant butchery area”.•We re-evaluated the original faunal and lithics materials, and the spatial relationship.•There is no support for the previous interpretation of the "elephant butchery area".•Lithics and elephant remains seem to be placed in different paleosurfaces.•The accumulation derives from at least two diverse and unrelated depositional events.
