Physiological and angiographic outcomes of PCI in calcified lesions after rotational atherectomy or intravascular lithotripsy.

BACKGROUND: Percutaneous coronary interventions (PCI) in calcified coronary artery lesions are associated with impaired stent expansion, higher rate of periprocedural complications and cardiac mortality. Lesion preparation using calcium modifying techniques such as Rotational Atherectomy (RA) or Intravascular Lithotripsy (IVL) has been advocated. Studies comparing these technologies are lacking. We aimed to compare in-stent pressure gradients, evaluated by vessel fractional flow reserve (vFFR), in calcific lesions treated using either RA or IVL. METHODS: Patients undergoing either RA- or IVL-assisted PCI from two European centers were included. Propensity score matching (1:2) was performed to control for potential bias. Primary outcome was post-PCI in-stent pressure gradients calculated by vFFR (vFFRgrad). Secondary outcomes included the proportion of patients with complete functional revascularization defined as distal vFFR post-PCI (vFFRpost) ≥ 0.90. RESULTS: From a cohort of 210 patients, 105 matched patients (70 RA and 35 IVL) were included. Pre-PCI vFFR did not differ between groups (0.65 ± 0.13 RA and 0.67 ± 0.11 IVL). After PCI, in-stent pressure gradients were significantly lower in the IVL group (0.032 ± 0.026 vs 0.043 ± 0.026 in the RA group, p = 0.024). The proportions of vessels with functional complete revascularization was similar between the two groups (32.9% vs. 37.1% in the RA and IVL group, respectively; p = 0.669). CONCLUSIONS: Calcific lesions preparation with IVL is effective and resulted in lower in-stent pressure gradients compared to RA. Approximately one third of the patients undergoing PCI for a severely calcified lesion achieved functional revascularization with no difference between rotational RA and IVL.

Excimer laser technology in percutaneous coronary interventions: Cardiovascular laser society's position paper.

Excimer Laser Coronary Atherectomy (ELCA) is a well-established therapy that emerged for the treatment of peripheral vascular atherosclerosis in the late 1980s, at a time when catheters and materials were rudimentary and associated with the most serious complications. Refinements in catheter technology and the introduction of improved laser techniques have led to their effective use for the treatment of a wide spectrum of complex coronary lesions, such as thrombotic lesions, severe calcific lesions, non-crossable or non-expandable lesions, chronic occlusions, and stent under-expansion. The gradual introduction of high-energy strategies combined with the contrast infusion technique has enabled us to treat an increasing number of complex cases with a low rate of periprocedural complications. Currently, the use of the ELCA has also been demonstrated to be effective in acute coronary syndrome (ACS), especially in the context of large thrombotic lesions.

Nutritional status in post SARS-Cov2 rehabilitation patients.

BACKGROUND & AIMS: After prolonged hospitalization, the assessment of nutritional status and the identification of adequate nutritional support is of paramount importance. In this observational study, we aimed at assessing the presence of a malnutrition condition in SARS-Cov2 patients after the acute phase and the effects of a multidisciplinary rehabilitation program on nutritional and functional status. METHODS: We recruited 48 patients (26 males/22 females) admitted to our Rehabilitation Unit after discharge from acute Covid Hospitals in northern Italy with negative swab for SARS-Cov2. We used the Global Leadership Initiative on Malnutrition (GLIM) criteria to identify patients with different degrees of malnutrition. Patients underwent a 3 to 4-week individual multidisciplinary rehabilitation program consisting of nutritional intervention (energy intake 27to30 kcal/die/kg and protein intake 1-1.3 g/die/kg), exercise for total body conditioning and progressive aerobic exercise with cycle- and arm-ergometer (45 min, 5 days/week). At admission and discharge from our Rehabilitation Unit, body composition and phase angle (PhA) (BIA101 Akern), muscle strength (handgrip, HG) and physical performance (Timed-Up-and-Go, TUG) were assessed. RESULTS: At admission in all patients the mean weight loss, as compared to the habitual weight, was -12.1 (7.6)%, mean BMI was 25.9 (7.9) kg/m2, mean Appendicular Skeletal Muscle Index (ASMI) was 6.6 (1.7) kg/m2 for males and 5.4 (1.4) kg/m2 for females, mean phase angle was 2.9 (0.9)°, mean muscle strength (HG) was 21.1 (7.8) kg for males and 16.4 (5.9) kg for females, mean TUG value was 23.7 (19.2) s. Based on GLIM criteria 29 patients (60% of the total) showed a malnutrition condition. 7 out of those 29 patients (24%) presented a mild/moderate grade and 22 patients (76%) a severe grade. After a rehabilitation program of an average duration of 25 days (range 13-46) ASMI increased, with statistically significant differences only in females (p = 0.001) and HG improved only in males (p = 0.0014). In all of the patients, body weight did not change, CRP/albumin (p < 0.05) and TUG (p < 0.001) were reduced and PhA increased (p < 0.01). CONCLUSIONS: We diagnosed a malnutrition condition in 60% of our post SARS-Cov2 patients. An individualized nutritional intervention with adequate energy and protein intake combined with tailored aerobic and strengthening exercise improved nutritional and functional status.

Functional movement disorders.

Functional movement disorders (FMD) represent a complex and disabling entity characterized by a broad range of clinical symptoms not explained by a classical neurological disease. In 2013, the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) added a clinical criterion based on incongruence and inconsistency, supported by recent literature highlighting the role of "positive clinical signs". These clinical signs allow a "rule-in" procedure in making a diagnosis of FMD so that the diagnosis is no longer a "rule-out" or "by default" diagnosis made after exclusion of other neurological conditions. This review summarizes current evidence on common clinical features and highlights bedside signs in FMD, such as tremor, dystonia, myoclonus and parkinsonism. Tics, chorea and hemiballism are also briefly discussed.

Impact of salivary contamination during placement of implants with simultaneous bony augmentation in iliac bone in sheep.

Our aim was to investigate the possible impact of contamination with saliva on osseointegration during placement of implants with simultaneous bone augmentation. Six hemispheric shape bone defects (8mm in diameter×4mm deep) were prepared in each iliac bone of six sheep. A dental implant (2.9mm in diameter×10mm long) was placed in the centre of each defect, and then pairs of defects were filled with one of the following bone augmentation materials: autogenous bone, autogenous bone plus bovine bone, or resorbable biphasic ceramic bone substitute. One site in each augmentation group was impregnated with saliva (contaminated group), while the other was not (non-contaminated group). Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within implant threads were measured after a healing period of five weeks, both in respect of the implant inserted in the augmented bone and in that inserted in the residual bone. Overall results showed that there was a significant difference between the contaminated and non-contaminated group for BIC in the augmented implant (p=0.028), while there were no significant differences in the implant in residual bone (p=0.722). For BAFO, there were no significant differences between the contaminated and non-contaminated groups among the different augmentation materials. The results showed that contamination with saliva during placement of an implant with simultaneous bone augmentation had a serious deleterious effect on osseointegration of the aspect of the implant within the augmented defect. Contamination with saliva during placement of an implant with simultaneous bone augmentation should therefore be avoided.

Mast cells are critical for controlling the bacterial burden and the healing of infected wounds.

Skin wound infections are a significant health problem, and antibiotic resistance is on the rise. Mast cells (MCs) have been shown to contribute to host-defense responses in certain bacterial infections, but their role in skin wound superinfection is unknown. We subjected 2 MC-deficient mouse strains to Pseudomonas aeruginosa skin wound infection and found significantly delayed wound closure in infected skin wounds. This delay was associated with impaired bacterial clearance in the absence of MCs. Engraftment of MCs restored both bacterial clearance and wound closure. Bacterial killing was dependent on IL-6 released from MCs, and engraftment with IL-6-deficient MCs failed to control wound infection. Treatment with recombinant IL-6 enhanced bacterial killing and resulted in the control of wound infection and normal wound healing in vivo. Taken together, our results demonstrate a defense mechanism for boosting host innate immune responses, namely effects of MC-derived IL-6 on antimicrobial functions of keratinocytes.

Correction to: The effect of magnesium on early osseointegration in osteoporotic bone: a histological and gene expression investigation.

This article was originally published under a CC BY-NC-ND 4.0 license, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the paper have been modified accordingly.

The effect of magnesium on early osseointegration in osteoporotic bone: a histological and gene expression investigation.

Magnesium has a key role in osteoporosis and could enhance implant osseointegration in osteoporotic patients. Titanium implants impregnated with Mg ions were installed in the tibia of ovariectomized rats. The release of Mg induced a significant increase of bone formation and the expression of anabolic markers in the peri-implant bone. INTRODUCTION: The success of endosseous implants is highly predictable in patients possessing normal bone status, but it may be impaired in patients with osteoporosis. Thus, the application of strategies that adjuvate implant healing in compromized sites is of great interest. Magnesium has a key role in osteoporosis prevention and it is an interesting candidate for this purpose. In this study, the cellular and molecular effects of magnesium release from implants were investigated at the early healing stages of implant integration. METHODS: Osteoporosis was induced in 24 female rats by means of ovariectomy and low-calcium diet. Titanium mini-screws were coated with mesoporous titania films and were loaded with magnesium (test group) or left as native (control group). The implants were inserted in the tibia and femur of the rats. One, 2 and 7 days after implantation, the implants were retrieved and histologically examined. In addition, expression of genes was evaluated in the peri-implant bone tissue at day 7 by means of quantitative polymerase chain reactions with pathway-oriented arrays. RESULTS: The histological evaluation revealed that new bone formation started already during the first week of healing for both groups. However, around the test implants, new bone was significantly more abundant and spread along a larger surface of the implants. In addition, the release of magnesium induced a significantly higher expression of BMP6. CONCLUSIONS: These results provide evidence that the release of magnesium promoted rapid bone formation and the activation of osteogenic signals in the vicinity of implants placed in osteoporotic bone.

Use of the Needs Evaluation Questionnaire with cancer outpatients.

PURPOSE: The Needs Evaluation Questionnaire (NEQ) is a self-administered instrument with 23 dichotomous items that is used both in oncology clinical practice and in research. It was originally developed for use in setting of hospitalization. The aim of the present study was to assess the factor structure of the NEQ in an outpatient oncology sample and to compare the unmet needs of inpatients and outpatients in the Italian context. METHODS: In 6 Italian oncology departments, 783 patients completed the NEQ. Patients included in the study had different primary tumor sites and were in different phases of the disease and care process. There were 195 inpatients and 588 outpatients total. RESULTS: Confirmatory factor analysis (CFA) showed that, with outpatients, the NEQ retained the distribution of the items in five main areas previously described with inpatients. Cancer outpatients expressed high percentages of unmet needs primarily concerning "material needs" and "needs for psycho-emotional support." Our survey also suggested that, in addition to the 23 original items, four new items could be tested for specific use with outpatients. CONCLUSIONS: Our findings highlight the importance of establishing routine assessment of unmet needs also in clinical oncology settings different from wards-such as day hospitals, ambulatory rehabilitation, or follow-up ambulatory care-where, at least in the Italian context, the rate of unmet needs is currently considerably high. The NEQ could be an effective tool for this assessment.

Conventional and enantioselective gas chromatography with microfabricated planar columns for analysis of real-world samples of plant volatile fraction.

Within a project exploring the application of lab-on-chip GC to in-field analysis of the plant volatile fraction, this study evaluated the performance of a set of planar columns (also known as microchannels, MEMS columns, or microfabricated columns) of different dimensions installed in a conventional GC unit. Circular double-spiral-shaped-channel planar columns with different square/rectangular sections up to 2m long were applied to the analysis of both essential oils and headspace samples of a group of medicinal and aromatic plants (chamomile, peppermint, sage, rosemary, lavender and bergamot) and of standard mixtures of related compounds; the results were compared to those obtained with reference narrow-bore columns (l:5m, dc:0.1mm, df:0.1 µm). The above essential oils and headspaces were first analyzed quali-and quantitatively with planar columns statically coated with conventional stationary phases (5%-phenyl-polymethylsiloxane and auto-bondable nitroterephthalic-acid-modified polyethylene glycol), and then submitted to chiral recognition of their diagnostic markers, by enantioselective GC with a planar columns coated with a cyclodextrin derivative (30% 6(I-VII)-O-TBDMS-3(I-VII)-O-ethyl-2(I-VII)-O-ethyl-ß-cyclodextrin in PS-086). Column characteristics and analysis conditions were first optimized to obtain suitable retention and efficiency for the samples investigated. The planar columns tested showed performances close to the reference conventional narrow-bore columns, with theoretical plate numbers per meter (N/m) ranging from 6100 to 7200 for those coated with the conventional stationary phases, and above 5600 for those with the chiral selector.

Does crown/implant ratio influence the survival and marginal bone level of short single implants in the mandibular molar? A preliminary investigation consisting of 12 patients.

Crown/implant (C/I) ratio has been proven to not affect the survival of the implants; however, it is also a fact that no evidence exists with regard to the use of single short implants in the mandibular molar. The aim of this study was to determine whether the crown/implant ratios of single implant-supported fixed restorations on implants of 6-8 mm in the mandibular molar have an impact on the implant survival and marginal bone maintenance. Twelve short dental implants (6-8 mm) were installed and restored with single crowns, loaded after 3 months of healing. The restorations were divided according to crown-to-implant ratio into two groups: Group 1: C/I < 2.0 and Group 2: C/I ≧ 2.0. Alveolar bone loss was measured using CBCT scan, taken at the implant placement and after 12 months follow-up from loading. Reduced implant/crown ratio shown no statistic significant differences on implant survival and the alveolar bone level compared with recommended implant/crown ratio. Within the limitation of this study, it can be concluded that reduced C/I ratio could be used as a substitute for recommended C/I ratio in severely mandibular atrophic residual alveolar ridges.

MPLA shows attenuated pro-inflammatory properties and diminished capacity to activate mast cells in comparison with LPS.

BACKGROUND: Monophosphoryl lipid A (MPLA), a nontoxic TLR4 ligand derived from lipopolysaccharide (LPS), is used clinically as an adjuvant in cancer, hepatitis, and malaria vaccines and in allergen-specific immunotherapy. Nevertheless, its cell-activating effects have not been analyzed in a comprehensive direct comparison including a wide range of different immune cells. Therefore, the objective of this study was the side-by-side comparison of the immune-modulating properties of MPLA and LPS on different immune cells. METHODS: Immune-activating properties of MPLA and LPS were compared in human monocytes and mast cells (MCs), a mouse endotoxin shock model (ESM), and mouse bone marrow (BM)-derived myeloid dendritic cells (mDCs), T cells (TCs), B cells, and MCs. RESULTS: In a mouse in vivo ESM and a human ex vivo monocyte activation test (MAT), MPLA induced the same cytokine secretion pattern as LPS (ESM: IL-6, IL-12, TNF-α; MAT: IL-1ß, IL-6, TNF-α), albeit at lower levels. Mouse mDCs and ex vivo isolated B cells stimulated with MPLA required a higher threshold to induce TRIF-dependent cytokine secretion (IL-1ß, IL-6, IL-10, and TNF-α) than did LPS-stimulated cells. In mDC:DO11.10 CD4 TC cocultures, stimulation with MPLA, but not with LPS, resulted in enhanced OVA-specific IL-4 and IL-5 secretion from DO11.10 CD4 TCs. Unexpectedly, in both human and mouse MCs, MPLA, unlike LPS, did not elicit secretion of pro-inflammatory cytokines. CONCLUSIONS: Compared to LPS, MPLA induced a qualitatively similar, but less potent pro-inflammatory immune response, but was unable to activate human or mouse MCs.

Potential effector and immunoregulatory functions of mast cells in mucosal immunity.

Mast cells (MCs) are cells of hematopoietic origin that normally reside in mucosal tissues, often near epithelial cells, glands, smooth muscle cells, and nerves. Best known for their contributions to pathology during IgE-associated disorders such as food allergy, asthma, and anaphylaxis, MCs are also thought to mediate IgE-associated effector functions during certain parasite infections. However, various MC populations also can be activated to express functional programs--such as secreting preformed and/or newly synthesized biologically active products--in response to encounters with products derived from diverse pathogens, other host cells (including leukocytes and structural cells), damaged tissue, or the activation of the complement or coagulation systems, as well as by signals derived from the external environment (including animal toxins, plant products, and physical agents). In this review, we will discuss evidence suggesting that MCs can perform diverse effector and immunoregulatory roles that contribute to homeostasis or pathology in mucosal tissues.

Neuropeptide Y receptor Y5 as an inducible pro-survival factor in neuroblastoma: implications for tumor chemoresistance.

Neuroblastoma (NB) is a pediatric tumor of neural crest origin with heterogeneous phenotypes. Although low-stage tumors carry a favorable prognosis, >50% of high-risk NB relapses after treatment with a fatal outcome. Thus developing therapies targeting refractory NB remains an unsolved clinical problem. Brain-derived neurotrophic factor (BDNF) and its TrkB receptor are known to protect NB cells from chemotherapy-induced cell death, while neuropeptide Y (NPY), acting via its Y2 receptor (Y2R), is an autocrine proliferative and angiogenic factor crucial for maintaining NB tumor growth. Here we show that in NB cells, BDNF stimulates the synthesis of NPY and induces expression of another one of its receptors, Y5R. In human NB tissues, the expression of NPY and Y5R positively correlated with the expression of BDNF and TrkB. Functionally, BDNF triggered Y5R internalization in NB cells, whereas Y5R antagonist inhibited BDNF-induced p44/42 mitogen-activated protein kinase activation and its pro-survival activity. These observations suggested TrkB-Y5R transactivation that resulted in cross-talk between their signaling pathways. Additionally, NPY and Y5R were upregulated in a BDNF-independent manner in NB cells under pro-apoptotic conditions, such as serum deprivation and chemotherapy, as well as in cell lines and tissues derived from posttreatment NB tumors. Blocking Y5R in chemoresistant NB cells rich in this receptor sensitized them to chemotherapy-induced apoptosis and inhibited their growth in vivo by augmenting cell death. In summary, the NPY/Y5R axis is an inducible survival pathway activated in NB by BDNF or cellular stress. Upon such activation, Y5R augments the pro-survival effect of BDNF via its interactions with TrkB receptor and exerts an additional BDNF-independent anti-apoptotic effect, both of which contribute to NB chemoresistance. Therefore, the NPY/Y5R pathway may become a novel therapeutic target for patients with refractory NB, thus far an incurable form of this disease.

Bivalirudin use in patients undergoing percutaneous coronary intervention for acute myocardial infarction. Insights from the prospective, multi-centre EUROVISION registry.

BACKGROUND: The effectiveness of bivalirudin in patients undergoing percutaneous coronary intervention for acute myocardial infarction has been tested in clinical trials, but its use in a real-world scenario has never been reported. METHODS: From the total number of patients enrolled in the EUROVISION registry, 678 subjects affected by ST-elevation myocardial infarction were selected and included in the analysis. Posology and usage patterns of bivalirudin, as evaluated by dose and time of drug bolus and infusion administered, were evaluated. The 30-day outcome has been assessed by efficacy and safety endpoints. RESULTS: All patients received an initial intravenous bolus of bivalirudin (0.70±0.25 mg/kg) followed by an infusion (1.58±0.47 mg/kg/h; duration: 60 [30, 107] min) in 99.3% of cases. An additional bolus (0.49±0.06 mg/kg) was administered in 9.3% of patients. Bivalirudin infusion was prolonged after procedure in 62.2%. Death occurred in 2.1% of patients, non-fatal myocardial reinfarction in 0.3%, unplanned revascularization in 0.6% and non-fatal stroke in 0.4%. Acute stent thrombosis was not observed. Major bleeding occurred in 1.5% of patients. CONCLUSIONS: Bivalirudin usage in the setting of primary PCI provided excellent results in terms of 30-day outcome even in a real-world population.

Formaldehyde replacement with glyoxylic acid in semipermanent hair straightening: a new and multidisciplinary investigation.

OBJECTIVE: Formaldehyde is an effective and popular semipermanent hair straightener, but the severe consequences for human health due to its toxicity have prompted the search for safer alternatives. Different carbonyl compounds, including glyoxylic acid, have recently been proposed as promising candidates. Despite the interest in this topic, there is a lack of information about the interactions between hair keratin and straightener agents. This study addresses this issue to gain new insights useful in the development of new products for safe, semipermanent hair deformation. METHODS: The possible reactions occurring between carbonyl groups and nucleophilic sites on amino acid residues belonging to the keratin were investigated using as model compounds some aldehydes and amino acid derivatives. Raman and IR analyses on yak hair subjected to the straightening treatment with glyoxylic acid in different conditions were carried out. Scanning electron microscope (SEM) analyses were carried out on yak and curly human hair after each step of the straightening procedure. RESULTS: The reactions between aldehydes and N-α-acetyl-L-lysine revealed the importance of the carbonyl electrophilicity and temperature to form imines. Raman and IR analyses on yak hair subjected to the straightening treatment evidenced rearrangements in the secondary structure distribution, conformational changes to the disulphide bridges, a decrease of the serine residues and formation of imines. It was also indicated that straightening produced major conformational rearrangements within the hair fibre rather than on the cuticle. CONCLUSION: This investigation revealed the role played by the electrophilicity of the carbonyl on the straightener agent and of the temperature, closely related to the dehydration process. Raman and IR studies indicated the involvement of imine bonds and the occurrence of a sequence of conformational modifications during the straightening procedure. SEM analyses showed the effectiveness of the treatment at the cuticular level.

Identification of novel biomarkers in neuroblastoma associated with the risk for bone marroww metastasis: a pilot study

PURPOSE: Neuroblastoma is a common pediatric neoplasm with variable histopathological features that carry an inherent risk of developing distant metastases, in particular bone marrow metastasis. Nestin, X-linked inhibitor of apoptosis (XIAP) and vascular growth factors (VEGF) are biomarkers that are implicated in the tumorigenesis of various cancers. We studied the expression of these biomarkers in neuroblastoma, in relation to bone marrow (BM) metastasis and other histologic parameters. METHODS: Patients with neuroblastoma included seven with BM metastasis and 12 with non-metastatic tumors. Slides from the primary tumors were immunostained with antibodies against nestin, XIAP, VEGF-A, VEGF-B, VEGF-D, VEGF-R1, and VEGF-R2. Immunostaining results were evaluated by two pathologists, graded and statistically correlated with the risk of developing BM metastasis. RESULTS: Nestin was expressed in 16/19 cases with no significant difference between patients with BM metastasis and those without BM metastasis. XIAP was identified in 18/19 tumor cases; the staining density was significantly lower in patients with bone marrow metastasis and those with unfavorable histology. VEGF-R1, VEGF-R2, and VEGF-B were expressed while VEGF-A and VEGF-D were not. Significantly, higher expression of VEGF-B was noted in patients with BM metastasis. CONCLUSION: Expression of VEGF-B and XIAP in neuroblastoma may play a role in the development of bone marrow metastasis. Given the limited number of patients in this study, a larger cohort is needed to validate these findings (AU)

Siloxanes removal from biogas by high surface area adsorbents.

Biogas utilized for energy production needs to be free from organic silicon compounds, as their burning has damaging effects on turbines and engines; organic silicon compounds in the form of siloxanes can be found in biogas produced from urban wastes, due to their massive industrial use in synthetic product, such as cosmetics, detergents and paints. Siloxanes removal from biogas can be carried out by various methods (Mona, 2009; Ajhar et al., 2010 May; Schweigkofler and Niessner, 2001); aim of the present work is to find a single practical and economic way to drastically and simultaneously reduce both the hydrogen sulphide and the siloxanes concentration to less than 1 ppm. Some commercial activated carbons previously selected (Monteleone et al., 2011) as being effective in hydrogen sulfide up taking have been tested in an adsorption measurement apparatus, by flowing the most volatile siloxane (hexamethyldisiloxane or L2) in a nitrogen stream, typically 100-200 ppm L2 over N2, through an activated carbon powder bed; the adsorption process was analyzed by varying some experimental parameters (concentration, grain size, bed height). The best activated carbon shows an adsorption capacity of 0.1g L2 per gram of carbon. The next thermogravimetric analysis (TGA) confirms the capacity data obtained experimentally by the breakthrough curve tests. The capacity results depend on L2 concentration. A regenerative carbon process is then carried out by heating the carbon bed up to 200 °C and flushing out the adsorbed L2 samples in a nitrogen stream in a three step heating procedure up to 200 °C. The adsorption capacity is observed to degrade after cycling the samples through several adsorption-desorption cycles.