Neonatal Platelet Function Del Vecchio, Antonio; Motta, Mario; Romagnoli, Costantino
Clinics in perinatology,
09/2015, Volume:
42, Issue:
3
Journal Article
Peer reviewed
Similarly to the development of the plasma coagulation system, which matures during the early weeks and months of life, age-dependent mechanisms and developmental changes influence platelet ...production and function in neonates. Platelet function testing on cord blood and peripheral blood demonstrates a generalized platelet hyporeactivity, during the first days of life. This reactivity reaches normal adult levels between the fifth and ninth day of life. The persistence of hyporeactivity after the tenth day of life might indeed suggest a platelet disorder.
Background To minimize event rates in patients with elevated cardiovascular surgical risk, we investigated a new therapeutic strategy consisting of simultaneous hybrid revascularization by carotid ...artery stenting (CAS), immediately followed by coronary artery bypass grafting (CABG). Methods The study included 37 patients with severe carotid and coronary artery disease and a European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 5 or higher. Immediately after CAS, patients underwent CABG. The primary end point was the incidence of stroke, myocardial infarction, or death at 30 days. Secondary end points were a combination of transient ischemic attack, major local complications, bleeding, and systemic complications within the 30 days after treatment, and any stroke, acute myocardial infarction, or death from day 31 through to the end of the follow-up. All clinical outcomes were assessed by an independent monitoring board. Results The rate of procedural success was 97.3%. The 30-day cumulative incidence of disabling stroke, myocardial infarction, or death was 8.1%: 2 patients (5.4%) died, and 1 patient had a stroke immediately after carotid stenting. Another patient died between day 31 and 6 months after the intervention. Conclusions Our findings indicate that in elevated-surgical-risk patients with carotid stenosis and coronary artery disease suitable for CABG, hybrid revascularization by CAS, immediately followed by CABG, is a feasible and promising therapeutic strategy.
Purpose
Aim of the present study was to develop and validate a nomogram to accurately predict the risk of chronic kidney disease (CKD) upstaging at 3 years in patients undergoing robot-assisted ...partial nephrectomy (RAPN).
Methods
A multi-institutional database was queried to identify patients treated with RAPN for localized renal tumor (cT1-cT2, cN0, cM0). Significant CKD upstaging (sCKD-upstaging) was defined as development of newly onset CKD stage 3a, 3b, and 4/5. Model accuracy was calculated according to Harrell C-index. Subsequently, internal validation using bootstrapping and calibration was performed. Then nomogram was depicted to graphically calculate the 3-year sCKD-upstaging risk. Finally, regression tree analysis identified potential cut-offs in nomogram-derived probability. Based on this cut-off, four risk classes were derived with Kaplan–Meier analysis tested this classification.
Results
Overall, 965 patients were identified. At Kaplan–Meier analysis, 3-year sCKD-upstaging rate was 21.4%. The model included baseline (estimated glomerular filtration rate) eGFR, solitary kidney status, multiple lesions, R.E.N.A.L. nephrometry score, clamping technique, and postoperative acute kidney injury (AKI). The model accurately predicted 3-year sCKD-upstaging (C-index 84%). Based on identified nomogram cut-offs (7 vs 16 vs 26%), a statistically significant increase in sCKD-upstaging rates between low vs intermediate favorable vs intermediate unfavorable vs high-risk patients (1.3 vs 9.2 vs 22 vs 54.2%, respectively,
p
< 0.001) was observed.
Conclusion
Herein we introduce a novel nomogram that can accurately predict the risk of sCKD-upstaging at 3 years. Based on this nomogram, it is possible to identify four risk categories. If externally validated, this nomogram may represent a useful tool to improve patient counseling and management.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The insulin receptor (IR) form hybrids with the closely related insulin-like growth factor-I (IGF-I) receptor (IGF-I-R). Because
most human breast carcinomas overexpress both the IR and the IGF-I-R, ...we evaluated whether the insulin/IGF-I hybrid receptor
(Hybrid-R) is also overexpressed in these tumors and what role it plays in breast cancer biology.
Using specific ELISAs and Western blots, we measured Hybrid-R content and function in 8 human cultured breast cancer cell
lines and 39 human breast cancer specimens. Hybrid-R content and function were also compared to the content and function of
the IR and the IGF-I-R. Hybrid-R content exceeded the IGF-I-R content in >75% of breast cancer specimens and was directly
related to the molar ratio of both the IR and IGF-I-R content, suggesting that Hybrid-R formation occurred by random assembly
of IR and IGF-I-R half-receptors. Hybrid-Rs became tyrosine autophosphorylated when breast cancer cells were exposed to IGF-I
but not when they were exposed to insulin.
In cells with an elevated Hybrid-R content, Hybrid-R autophosphorylation in response to IGF-I exceeded IGF-I-R autophosphorylation,
suggesting that most of the IGF-I effect occurred via the Hybrid-R. Furthermore, Hybrid-Rs mediated growth in response to
IGF-I, as indicated by experiments with blocking antibodies to the IGF-I-R.
These data indicated therefore that: ( a ) Hybrid-Rs are present and play a major role in mediating the IGF-I signal in breast cancer; ( b ) their expression is directly related to IR overexpression; and ( c ) potential therapies designed to block IGF-I actions in breast cancer must take into account the role of these Hybrid-Rs.
Hypertension (HTN) is a global public health issue. There are limited data regarding the effects of HTN in patients undergoing partial nephrectomy (PN) for renal tumors. To address this void, we ...tested the association between HTN and renal function after minimally invasive PN (MIPN).
Using a multi-institutional database (2007-2017), we identified patients aged ≥ 18 years with a diagnosis of cT1 renal tumors treated with MIPN. Kaplan-Meier plots and Cox regression models addressed newly-onset CKD stage ≥ 3b or higher (sCKD). All analyses were repeated after 1:1 propensity score matching (PSM).
Overall, 2144 patients were identified. Of those, 35% (
= 759) were yes-HTN. Yes-HTN patients were older, more frequently male and more often presented with diabetes. Yes-HTN patients harbored higher RENAL nephrometry scores and higher cT stages than no-HTN patients. Conversely, yes-HTN patients exhibited lower preoperative eGFRs. In the overall cohort, five-year sCKD-free survival was 86% vs. 94% for yes-HTN vs. no-HTN, which translated into a multivariable HR of 1.67 (95% CI: 1.06-2.63,
= 0.026). After 1:1 PSM, virtually the same results were observed (HR 1.86, 95% CI: 1.07-3.23,
= 0.027).
Yes-HTN patients exhibited worse renal function after MIPN when compared to their no-HTN counterparts. However, these observations need to be further tested in a prospective cohort study.
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Chronic kidney disease-mineral bone disorder is frequent in patients with renal failure. It is characterized by abnormalities in mineral and bone metabolism with resulting hyperphosphatemia, low ...serum vitamin D, secondary hyperparathyroidism, altered bone morphology and strength, higher risk of bone fractures, and development of vascular or other soft tissue calcifications. Besides the recommendation to reduce phosphorus dietary intake, many drugs are currently available for the treatment of calcium/phosphate imbalance. Among them, phosphate binders represent a milestone. Calcium-based binders (calcium carbonate, calcium acetate) are effective in lowering serum phosphate, but their use has been associated with an increased risk of hypercalcemia and calcifications. Calcium-free binders (sevelamer hydrochloride, sevelamer carbonate, and lanthanum carbonate) are equally or slightly less effective than calcium-containing compounds. They would not induce an increase in calcium levels but may have relevant side effects, including gastrointestinal symptoms for sevelamer and risk of tissue accumulation for lanthanum. Accordingly, new phosphate binders are under investigation and some of them have already been approved. A promising option is sucroferric oxyhydroxide (Velphoro(®), PA21), an iron-based phosphate binder consisting of a mixture of polynuclear iron(III)-oxyhydroxide, sucrose, and starches. The present review is focused on pharmacology, mode of action, and pharmacokinetics of sucroferric oxyhydroxide, with a discussion on comparative efficacy, safety, and tolerability studies of this drug in chronic kidney disease and patient perspectives such as quality of life, satisfaction, and acceptability. Sucroferric oxyhydroxide has proven to be as effective as sevelamer in reducing phosphatemia with a similar safety profile and lower pill burden. Experimental and clinical studies have documented a minimal percentage of iron absorption without inducing toxicity. In conclusion, the overall benefit-risk balance of sucroferric oxyhydroxide is deemed to be positive, and this new drug may therefore represent a good alternative to traditional phosphate binders for the treatment of hyperphosphatemia in dialysis patients.
Abstract Recently, mutations in the TANK-binding kinase 1 ( TBK1 ) gene were identified as a cause for amyotrophic lateral sclerosis (ALS) with or without comorbid frontotemporal dementia. We have ...assessed the frequency and clinical characteristics of TBK1 mutations in a cohort of ALS patients of Sardinian ancestry. Whole-exome sequencing was performed on Hiseq2000 platform (Illumina). Genome analysis Toolkit was used to align and to code variants according to Human Genome (UCSC hg19). Mutation was confirmed with Sanger sequence. In our screening of 186 Sardinian ALS cases, we found 3 (1.6%) patients carrying 3 distinct novel genetic variants: a nonsynonymous SNV c.1150C>T leading to a p.Arg384Thr change in exon 9; a nonsynonymous SNV c.1331G>A causes a p.Arg444Gln change in exon 11; and a frameshift deletion c.2070delG (p.Met690fs) at the exon 20 of the gene leading to a stop at 693 codon. The latter patients also carried missense mutation c.98C>T of the SQSTM1 gene causing a substitution of an arginine with a valine at the position 33 (p.Arg33Val). All variants were found to be deleterious according to in silico predictions. All cases were apparently sporadic and one of them showed frontotemporal dementia associated to ALS. These mutations were not found in 2 cohorts of 6780 ethnic-matched controls. We have found that TBK1 mutations account for 1.6% of Sardinian ALS cases. Our data support the notion that TBK1 is a novel ALS gene, providing important evidence complementary to the first descriptions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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