This work presents the results of an investigation on how wave overtopping at a near-vertical seawall at the back of a sandy foreshore is influenced by sequences of erosive storms. The experiments ...were carried out in the Large Wave Flume (GWK) at Leibniz University, Hannover (Germany). The tested layout consisted of a near-vertical 10/1 seawall and a sandy foreshore with an initial 1/15 slope. Three sequences of idealised erosive storms were simulated. Within each storm both the incident wave conditions and still water level were varied in time to represent high and low tide conditions. Each sequence started from a 1/15 configuration and the beach was not restored in between storms. The measurements included waves, beach profile, wave overtopping volumes. The profile of the beach was measured after each sea state tested.
Wave overtopping at each stage of the tested storms was significantly influenced by bed changes. This was linked to the measured evolution of the beach. Measurements showed that a barred profile developed quickly at the start of each sequence, and scour developed at the toe of the structure during high water level conditions, while accretion or partial backfilling developed during low water level conditions. Due to these processes, the position of a sea state in the tested sequence is shown to be an important factor in determining the wave overtopping volume. Remarkably, when a weaker idealised storm followed a more energetic one, nearly the same level of overtopping was recorded. This is explained by the foreshore erosion, leading to increased water depths and wave heights at the toe of the structure. This finding allows to quantify and to explain the variability of wave overtopping in storms following one another at intervals shorter than the recovery time of the foreshore.
•Wave overtopping at a seawall at the back of a sandy foreshore is investigated.•Overtopping generated by sequences of sea states was measured in the laboratory.•Sea state position within a sequence is important in determining overtopping rate.
Background
Patients with coronavirus disease 2019 (Covid-19) may experience venous thrombosis while data regarding arterial thrombosis are sparse.
Methods
Prospective multicenter study in 5 hospitals ...including 373 patients with Covid-19-related pneumonia. Demographic data, laboratory findings including coagulation tests and comorbidities were reported. During the follow-up any arterial or venous thrombotic events and death were registered.
Results
Among 373 patients, 75 (20%) had a thrombotic event and 75 (20%) died. Thrombotic events included 41 venous thromboembolism and 34 arterial thrombosis. Age, cardiovascular disease, intensive care unit treatment, white blood cells, D-dimer, albumin and troponin blood levels were associated with thrombotic events. In a multivariable regression logistic model, intensive care unit treatment (Odds Ratio OR: 6.0; 95% Confidence Interval CI 2.8–12.6;
p
< 0.001); coronary artery disease (OR: 2.4; 95% CI 1.4–5.0;
p
= 0.022); and albumin levels (OR: 0.49; 95% CI 0.28–0.87;
p
= 0.014) were associated with ischemic events. Age, sex, chronic obstructive pulmonary disease, diabetes, heart failure, coronary heart disease, intensive care unit treatment, in-hospital thrombotic events, D-dimer, C-reactive protein, troponin, and albumin levels were associated with mortality. A multivariable Cox regression analysis showed that in-hospital thrombotic events (hazard ratio HR: 2.72; 95% CI 1.59–4.65;
p
< 0.001), age (HR: 1.035; 95% CI 1.014–1.057;
p
= 0.001), and albumin (HR: 0.447; 95% CI 0.277–0.723;
p
= 0.001) predicted morality.
Conclusions
Covid-19 patients experience an equipollent rate of venous and arterial thrombotic events, that are associated with poor survival. Early identification and appropriate treatment of Covid-19 patients at risk of thrombosis may improve prognosis.
In adult CNS, nerve/glial-antigen 2 (NG2) is expressed by oligodendrocyte progenitor cells (OPCs) and is an early marker of pericyte activation in pathological conditions. NG2 could, therefore, play ...a role in experimental autoimmune encephalomyelitis (EAE), a disease associated with increased blood–brain barrier (BBB) permeability, inflammatory infiltrates, and CNS damage. We induced EAE in NG2 knock-out (NG2KO) mice and used laser confocal microscopy immunofluorescence and morphometry to dissect the effect of NG2 KO on CNS pathology. NG2KO mice developed milder EAE than their wild-type (WT) counterparts, with less intense neuropathology associated with a significant improvement in BBB stability. In contrast to WT mice, OPC numbers did not change in NG2KO mice during EAE. Through FACS and confocal microscopy, we found that NG2 was also expressed by immune cells, including T cells, macrophages, and dendritic cells (DCs). Assessment of recall T cell responses to the encephalitogen by proliferation assays and ELISA showed that, while WT and NG2KO T cells proliferated equally to the encephalitogenic peptide MOG35-55, NG2KO T cells were skewed towards a Th2-type response. Because DCs could be responsible for this effect, we assessed their expression of IL-12 by PCR and intracellular FACS. IL-12-expressing CD11c+ cells were significantly decreased in MOG35-55-primed NG2KO lymph node cells. Importantly, in WT mice, the proportion of IL-12-expressing cells was significantly lower in CD11c+ NG2- cells than in CD11c+ NG2+ cells. To assess the relevance of NG2 at immune system and CNS levels, we induced EAE in bone-marrow chimeric mice, generated with WT recipients of NG2KO bone-marrow cells and vice versa. Regardless of their original phenotype, mice receiving NG2KO bone marrow developed milder EAE than those receiving WT bone marrow. Our data suggest that NG2 plays a role in EAE not only at CNS/BBB level, but also at immune response level, impacting on DC activation and thereby their stimulation of reactive T cells, through controlling IL-12 expression.
In fibromyalgia (FM), reduced habituation of laser-evoked potentials (LEPs) suggests a dysfunction of pain processing at a central level. In this study, we aimed to further examine the nociceptive ...pathways at the peripheral to the central level in a large group of FM patients by means of LEPs and skin biopsy, in light of healthy controls findings and main clinical features. One hundred and ninety-nine FM patients and 109 age- and sex-matched controls were submitted to LEPs by the dorsum of the right hand and the skin over the right chest and knee tender point stimulation. Skin biopsy was performed in 21 randomly selected FM patients and 60 age- and sex-matched controls. The mean N2–P2 amplitude was reduced in the whole FM group, with normal or even increased values in patients with migraine as comorbidity and reduced values in other patients including those presenting with distal sensory deficits. All patients had reduced N2–P2 habituation in respect to controls. In the FM group, LEPs habituation was correlated with pain at tender points and bad quality of life. Epidermal fiber density was significantly reduced in FM patients versus controls, and correlated with N2–P2 amplitude by the hand and chest tender-point stimulation. Dysfunction in the nociceptive system at both the central and peripheral levels may concur to explain phenotypical eterogeneity and clinical symptom complexity in fibromyalgia.
Tendon repair is a challenging procedure in orthopaedics. The use of mesenchymal stem cells (MSCs) and pulsed electromagnetic fields (PEMF) in tendon regeneration is still investigational. In this ...perspective, MSCs isolated from the human umbilical cord (UC) may represent a possible candidate for tendon tissue engineering. The aim of the study is to evaluate the effect of low-frequency PEMF on tenogenic differentiation of MSCs isolated from the human umbilical cord (UC-MSCs) in vitro. 15 fresh UC samples from women with healthy pregnancies were retrieved at the end of caesarean deliveries. UC samples were manually minced into small fragments (less than 4 mm length) and cultured in MSC expansion medium. Part of the UC-MSCs was subsequently cultured with PEMF and tenogenic growth factors. UC-MSCs were subjected to pulsed electromagnetic fields for 2 h/day, 4 h/day, or 8 h/day. UC-MSCs cultured with FGF-2 and stimulated with PEMF showed a greater production of collagen type I and scleraxis. The prolonged exposure to PEMF was also related to the greatest expression of tenogenic markers. Thus, the exposure to PEMF provides a positive preconditioning biophysical stimulus, which may enhance UC-MSC tenogenic potential.
To evaluate plasma vitamin D and cross-linked C-telopeptides of type I (CTx-I) and type II (CTx-II) collagen concentrations in males with lumbar intervertebral disc degeneration (IVD) compared to ...healthy controls. Improved knowledge might suggest to optimize the vitamin D status of IVD patients and contribute to clarify mechanisms of cartilage degradation.
79 Italian males with lumbar IVD assessed by Magnetic Resonance Imaging (MRI) and 79 age, sex and BMI-matched healthy controls were enrolled. Plasma 25hydroxyvitamin D (25(OH)D), CTx-I and CTx-II were measured by immunoassays. Circannual seasonality, correlation between biomarkers concentrations and clinical variables were assessed.
Overall subjects 25(OH)D and CTx-II showed month rhythmicity with acrophase in August/September and October/November, and nadir in February/March and April/May, respectively. An inverse correlation between 25(OH)D and CTx-I, and a direct correlation between CTx-II and CTx-I were observed.
IVD patients, particularly with osteochondrosis, showed higher CTx-II than healthy controls.
Month of sampling may affect plasma 25(OH)D and CTx-II concentrations. The correlation between CTx-I and CTx-II suggests an interplay between the osteo-cartilaginous endplate and the fibro-cartilaginous disc. The results of this study highlighted that osteochondrosis associates with increased cartilaginous catabolism. Vitamin D supplementation seems more necessary in winter for lumbar IVD patients.
•Month of sampling may affect plasma 25(OH)D and CTx-II concentrations.•CTx-I and CTx-II correlation suggests an interplay between endplate and disc.•Osteochondrosis associates with increased cartilaginous catabolism.•Vitamin D supplementation can counteract the type I collagen catabolism.•Degradation of type II collagen seems independent from vitamin D.
Adequate bowel preparation before colonoscopy is crucial. Unfortunately, 25% of colonoscopies have inadequate bowel cleansing. From a patient perspective, bowel preparation is the main obstacle to ...colonoscopy. Several low-volume bowel preparations have been formulated to provide more tolerable purgative solutions without loss of efficacy.
Investigate efficacy, safety, and tolerability of Sodium Picosulphate plus Magnesium Citrate (SPMC) vs. Polyethylene Glycol plus Ascorbic Acid (PEG-ASC) solutions in patients undergoing diagnostic colonoscopy.
In this phase 4, randomized, multicenter, two-arm trial, adult outpatients received either SPMC or PEG-ASC for bowel preparation before colonoscopy. The primary aims were quality of bowel cleansing (primary endpoint scored according to Boston Bowel Preparation Scale) and patient acceptance (measured with six visual analogue scales). The study was open for treatment assignment and blinded for primary endpoint assessment. This was done independently with videotaped colonoscopies reviewed by two endoscopists unaware of study arms. A sample size of 525 patients was calculated to recognize a difference of 10% in the proportion of successes between the arms with a two-sided alpha error of 0.05 and 90% statistical power.
Overall 550 subjects (279 assigned to PEG-ASC and 271 assigned to SPMC) represented the analysis population. There was no statistically significant difference in success rate according to BBPS: 94.4% with PEG-ASC and 95.7% with SPMC (
= 0.49). Acceptance and willing to repeat colonoscopy were significantly better for SPMC with all the scales. Compliance was less than full in 6.6 and 9.9% of cases with PEG-ASC and SPMC, respectively (
= 0.17). Nausea and meteorism were significantly more bothersome with PEG-ASC than SPMC. There were no serious adverse events in either group.
SPMC and PEG-ASC are not different in terms of efficacy, but SPMC is better tolerated than PEG-ASC. SPMC could be an alternative to low-volume PEG based purgative solutions for bowel preparation.
ClinicalTrials.gov, Identifier NCT01649674 and EudraCT 2011-000587-10.
The employment of anti-epidermal growth factor receptor (EGFR) antibodies represents a backbone of the therapeutic options for the treatment of metastatic colorectal cancer (mCRC). However, this ...therapy is poorly effective or ineffective in unselected patients. Mutations in KRAS, BRAF and PIK3CA genes have recently emerged as the best predictive factors of low/absent response to EGFR-targeted therapy. Due to the need for efficacious treatment options for mCRC patients bearing these mutations, in this short report we examined the antitumoral activity of the protease inhibitor gabexate mesilate, alone and in combination with the anti-EGFR monoclonal antibody cetuximab, in a panel of human CRC cell lines harbouring a different expression pattern of wild-type/mutated KRAS, BRAF and PIK3CA genes. Results obtained showed that gabexate mesilate significantly inhibited the growth, invasive potential and tumour-induced angiogenesis in all the CRC cells employed in this study (including those ones harbouring dual KRAS/PIK3CA or BRAF/PIK3CA mutation), while cetuximab affected these parameters only in CRC cells with KRAS, BRAF and PIK3CA wild-type. Notably, the antitumoral efficacy of gabexate mesilate and cetuximab in combination was found to be not superior than that observed with gabexate mesilate as single agent. Overall, these preliminary findings suggest that gabexate mesilate could represent a promising therapeutic option for mCRC patients, particularly for those harbouring KRAS, BRAF and PIK3CA mutations, either as mono-therapy or in addition to standard chemotherapy regimens. Further studies to better elucidate gabexate mesilate mechanism of action in CRC cells are therefore warranted.
In the endovascular era peripheral bypass surgery still plays a key role. In situ saphenous vein bypass is a standardized technique. The main limitation of this procedure is the vein diameter. A new ...hydrophylic valvulotome (HYDRO LeMaitre® Valvulotome; LeMaitre Vascular, Burlington, MA, USA) allows even to disrupt the valves in smaller veins. The aim of this study was to analyze the intraprocedural and technical successes of this new valvulotome.
In January 2018 in Italy a national, multicenter, observational, prospective registry based on the examination of treatment of critical limb ischemia with infragenicular bypass adopting in situ saphenous vein technique (LIMBSAVE registry) started the enrollment. Until December 2018 216 patients have been enrolled in the registry. All data concerning the procedures were prospectively collected in a dedicated database. The information included demographics, preoperative risk factors, clinical and diagnostic preoperative assessments, intraoperative features, and discharge outcomes, including the safety and effectiveness of the valvulotome during the surgical procedure.
Patients were predominantly male (160, 74.1%) with a mean age of 74.1 years (range 49-95). The mean diameter of the great saphenous vein was 3.7 mm (range 1.7-10) in the proximal part of the thigh, 3.4 mm (range 1.6-7) in the distal part of the thigh, and 3.1 mm in the proximal part of the leg (range 1.6-5). The technical success was obtained in all cases (the bypass pulsed after the utilization of the valvulotome). The valvulotome was able to reach the proximal anastomosis in all cases. The mean number of utilizations was 2.6 (range 1-5). No vein perforation has been detected. In 6 cases (2.8%) a vein adventitial damage occurred. In one case with uncontrolled bleeding (0.5%) the substitution of the deleted vein segment was necessary.
Preliminary intraprocedural outcomes of LIMBSAVE registry showed that HYDRO LeMaitre® Valvulotome was safe and effective in disrupting the valves and obtaining the pulsatility of the saphenous vein. The rate of complications related to the utilization of the valvulotome was low. Further examinations are needed to evaluate the long-term outcomes of the bypass in terms of patency, reinterventions, and limb salvage.
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