Oncological outcomes of unsuspected pN2 in patients with non-small-cell lung cancer: a systematic review and meta-analysis.

Objectives: Optimal treatment of stage IIIA (N2) non-small-cell lung cancer (NSCLC) is controversial. Guidelines advise induction therapy before surgical resection. A proportion of patients with cN0 NSCLC are postoperatively upstaged due to unsuspected N2 disease.

Oncologic Outcomes of Surgery Versus SBRT for Non-Small-Cell Lung Carcinoma: A Systematic Review and Meta-analysis.

Background: The optimal treatment of stage I non-small-cell lung carcinoma is subject to debate. The aim of this study was to compare overall survival and oncologic outcomes of lobar resection (LR), sublobar resection (SR), and stereotactic body radiotherapy (SBRT).

Methods: A systematic review and meta-analysis of oncologic outcomes of propensity matched comparative and noncomparative cohort studies was performed.

A validation study for a clinical decision rule for acute wrist injury.

Purpose: Acute wrist injury is a common reason for visiting the emergency department. To date, there are no implemented clinical decision rules to predict a fracture in this group of patients. We previously identified six clinical predictors in adult patients with acute wrist trauma.

A Shared Decision Approach to Chronic Abdominal Pain Based on Cine-MRI: A Prospective Cohort Study.

Objectives: Chronic abdominal pain develops in 11-20% of patients undergoing abdominal surgery, partly owing to post-operative adhesions. In this study we evaluate results of a novel diagnostic and therapeutic approach for pain associated with adhesions.

Methods: Prospective cohort study including patients with a history of abdominal surgery referred to the outpatient clinic of a tertiary referral center for the evaluation of chronic abdominal pain.

Resection of a bony tumour of the chest wall with direct reconstruction using a sandwich technique: a standard technique for closure of large chest wall defects.

Bony tumours of the chest wall are rare and radical surgical resection forms the cornerstone of treatment. Closure of the defect following radical resection can be challenging. We report the case of a 59-year-old woman with a large tumour of the thoracic wall, which was surgically resected with direct reconstruction using a sandwich technique with a Palacos(®) patch placed in a double-layer Marlex mesh.

A pilot study to identify clinical predictors for wrist fractures in adult patients with acute wrist injury.

Background: To date, no clinical decision rules for acute wrist injuries are available. In the past, clinical decision rules for the knee, ankle and spine injuries have been developed and validated. Implementation of these rules resulted in standardised clinical assessment at the emergency department and a substantial reduction of radiographic diagnostics.

Pain and its interference with daily activities in medical oncology outpatients.

Background: Pain prevalence at various stages of cancer ranges from 27% to 60% for outpatients. Yet, how pain is managed in this patient group is poorly understood.

Objectives: The primary objective was to assess pain prevalence and intensity, and its interference with daily activities, in medical oncology outpatients.

Platelet activation by oxidized low density lipoprotein is mediated by CD36 and scavenger receptor-A.

Objective: The interaction of platelets with low density lipoprotein (LDL) contributes to the development of cardiovascular disease. Platelets are activated by native LDL (nLDL) through apoE Receptor 2' (apoER2')-mediated signaling to p38(MAPK) and by oxidized LDL (oxLDL) through lysophosphatidic acid (LPA) signaling to Rho A and Ca2+. Here we report a new mechanism for platelet activation by oxLDL.

Novel molecular defect in the platelet ADP receptor P2Y12 of a patient with haemorrhagic diathesis.

Background: The platelet adenosine 5'-diphosphate (ADP) receptor P2Y(12) plays a crucial role in haemostasis. Only a few patients with haemorrhagic diathesis due to molecular defects in the P2Y(12) receptor have been described so far. We report a novel molecular defect in the gene coding for P2Y(12) in a patient with a history of epistaxis, easy bruising and excessive posttraumatic blood loss.

Impaired platelet adhesion to lysed fibrin, whereas neutrophil adhesion remains intact under conditions of flow.

Vessel wall injury induces the formation of a haemostatic plug. Restoration of vascular integrity should involve cessation of further platelet and fibrin deposition and subsequent removal of these thrombi by both the fibrinolytic system and proteases delivered by infiltrating inflammatory cells. We hypothesized that adhesion of platelets and inflammatory cells [polymorphonuclear leucocyte (PMN)] to fibrin is differently supported after exposure of fibrin during fibrinolysis.

A tripeptide mimetic of von Willebrand factor residues 981-983 enhances platelet adhesion to fibrinogen by signaling through integrin alpha(IIb)beta3.

Background: RGD is a major recognition sequence for ligands of platelet alpha(IIb)beta3.

Objective And Methods: To identify potential binding sites for alpha(IIb)beta3 apart from RGD, we screened phage display libraries by blocking the enrichment of RGD-containing phages with a GRGDS peptide and identified a novel integrin recognition tripeptide sequence, VPW.

Results: Platelets adhered to an immobilized cyclic VPW containing peptide in a alpha(IIb)beta3-dependent manner; platelets and alpha(IIb)beta3-expressing CHO cells adhered faster to immobilized alpha(IIb)beta3-ligands in the presence of soluble VPW.

The effect of recombinant IgG antibodies against the leucine-33 form of the platelet beta3 integrin (HPA-1a) on platelet function.

Recombinant HPA-1a antibodies with Fc, mutated to remove destructive effector functions, have been developed as a potential therapy for fetomaternal alloimmune thrombocytopenia (FMAIT), via blockade of binding of human HPA-1a polyclonal antibodies to fetal HPA-1a1b platelets. We have assessed the effect of the IgG1 HPA-1a antibody B2G1 and two mutated derivatives in various functional assays in resting and agonist-stimulated platelets of the three HPA-1 genotypes. With HPA-1a1b platelets (fetal genotype), the antibodies did not activate signalling or CD62P expression in resting platelets, did not change in vitro bleeding time (IVBT), and did not inhibit platelet adhesion to collagen in flowing blood.

Identification of the primary collagen-binding surface on human glycoprotein VI by site-directed mutagenesis and by a blocking phage antibody.

Glycoprotein (GP) VI is the major receptor responsible for platelet activation by collagen, but the collagen-binding surface of GPVI is unknown. To address this issue we expressed, from insect cells, the immunoglobulin (Ig)-like ectodomains (residues 1-185) of human and murine GPVI, called hD1D2 and mD1D2, respectively. Both proteins bound specifically to collagen-related peptide (CRP), a GPVI-specific ligand, but hD1D2 bound CRP more strongly than did mD1D2.

Thrombopoietin increases platelet adhesion under flow and decreases rolling.

Thrombopoietin (TPO) is known to sensitize platelets to other agonists at 20 ng/ml, and above 100 ng/ml it is an independent activator of aggregation and secretion. In studies with a perfusion chamber, TPO, between 0.01 ng/ml and 1 ng/ml, increased platelet adhesion to surface-coated fibrinogen, fibronectin and von Willebrand Factor (VWF) but not to a collagen-coated surface.

The low-frequency allele of the platelet collagen signaling receptor glycoprotein VI is associated with reduced functional responses and expression.

Interaction of platelets with collagen under conditions of blood flow is a multi-step process with tethering via glycoprotein IbIXV (GPIbIXV) over von Willebrand factor, adhesion by direct interaction with the integrin GPIaIIa, and signaling via GPVI. GPVI can be specifically agonized by cross-linked collagen-related peptide (CRP-XL), which results in a signaling cascade very similar to that evoked by native collagen. The GPVI gene has 2 common alleles that differ by 3 replacements in the glycosylated stem and 2 in the cytoplasmic domain.

Reduced platelet adhesion in flowing blood to fibrinogen by alterations in segment gamma316-322, part of the fibrin-specific region.

The interaction of platelets with fibrinogen is a key event in the maintenance of a haemostatic response. It has been shown that the 12-carboxy-terminal residues of the gamma-chain of fibrinogen mediate platelet adhesion to immobilized fibrinogen. These studies, however, did not exclude the possibility that other domains of fibrinogen are involved in interactions with platelets.

Role of ADP receptor P2Y(12) in platelet adhesion and thrombus formation in flowing blood.

ADP plays a central role in regulating platelet function. It induces platelet aggregation via the activation of 2 major ADP receptors, P2Y(1) and P2Y(12). We have investigated the role of P2Y(12) in platelet adhesion and thrombus formation under physiological flow by using blood from a patient with a defect in the gene encoding P2Y(12).

Absence of fibrinogen in afibrinogenemia results in large but loosely packed thrombi under flow conditions.

We studied the role of fibrinogen in platelet thrombus formation under flow on adhesive proteins using afibrinogenemic blood (LMWH anticoagulated) in a perfusion system. Perfusions with afibrinogenemic blood showed strong increased surface coverage and thrombus volume that normalized upon addition of fibrinogen. Similar studies using citrate anticoagulated blood showed that this was due to fibrinogen and not fibrin.

Platelet adhesion to collagen in healthy volunteers is influenced by variation of both alpha(2)beta(1) density and von Willebrand factor.

Platelet thrombus formation on collagen is initiated by platelet GPIb interaction with von Willebrand factor (vWF) bound to collagen, followed by firm attachment of the platelet to collagen by the integrin alpha(2)beta(1). Platelet and plasma vWF levels and alpha(2)beta(1) density on the platelet surface are highly variable among normal subjects; however, little is known about the consequences of this variability on platelet adhesion to collagen. A population of 32 normal subjects was studied to evaluate the relation between genetic and phenotypic variations of alpha(2)beta(1) density on the platelet surface, plasma vWF levels, platelet vWF levels, and adenosine diphosphate and adenosine triphosphate concentrations on the one hand and platelet adhesion to collagen under flow on the other hand.

Platelet thrombus formation on collagen at high shear rates is mediated by von Willebrand factor-glycoprotein Ib interaction and inhibited by von Willebrand factor-glycoprotein IIb/IIIa interaction.

We studied the role of von Willebrand Factor (vWF) in platelet thrombus formation in flowing blood by using a perfusion system and mutant forms of vWF lacking either interaction with glycoprotein Ib (GpIb) or with glycoprotein IIb/IIIa (alphaIIb-beta3). These mutants were added to the blood of patients with severe von Willebrand's disease (vWD) or to normal blood reconstituted with a human albumin solution instead of plasma. This blood was then perfused over collagen type III spray-coated on a glass surface and preincubated for 2 hours with 20 microg/mL plasma vWF.

Fibronectin in an extracellular matrix of cultured endothelial cells supports platelet adhesion via its ninth type III repeat : A comparison with platelet adhesion to isolated fibronectin.

We investigated the involvement of different domains of fibronectin in mediating platelet adhesion to fibronectin in the extracellular matrix (ECM) of cultured endothelial cells under flow conditions. Polyclonal anti-fibronectin antibodies were absorbed with Sepharose to which no protein, intact fibronectin, or different fibronectin fragments had been coupled to obtain supernatants (Sups) (Sup(0), Sup(FN), and Sup(name of the fragment), respectively) from which a specific part of the antibodies had been removed. Treatment of the ECM before perfusion with Sup(0) resulted in a 36% decrease in platelet coverage, whereas treatment with Sup(FN) resulted in maximal adhesion.

Adhesive domains in the collagen III fragment alpha1(III)CB4 that support alpha2beta1- and von Willebrand factor-mediated platelet adhesion under flow conditions.

Seven overlapping peptides derived from the bovine alpha1(III)CB4 fragment of collagen III support static platelet adhesion, and an integrin alpha2beta1-recognition site has been assigned within this fragment to residues 522-528 of the collagen alpha1(III) chain; (25). In this study we found that two of the peptides, CB4(III)-6 and -7, were able to support platelet adhesion under flow conditions, whereas the other peptides showed either very little (CB4(III)-1 and -4) or no platelet adhesion at all (CB4(III)-2, -3 and -5). Using the recombinant leech anti-platelet protein (rLAPP), known to prevent both alpha2beta1 integrin- and von Willebrand factor (vWF)-binding to collagen, we observed almost complete inhibition of platelet adhesion to peptides CB4(III)-6 and -7.