Antiangiogenic therapy combined with immune checkpoint blockade in renal cancer

Antiangiogenic therapy with vascular endothelial growth factor (VEGF) inhibitors is the current first-line treatment in metastatic renal cell carcinoma (mRCC). Immunotherapy with checkpoint inhibitor has been recently added to the armamentarium of mRCC treatment. These therapies are based on treatment with antibodies that block programmed cell death-1 (PD-1), programmed cell death ligand 1 (PD-L1) pathways, demonstrating impressive response rates and improved survival in several tumour types. So far, nivolumab is the only approved anti-PD-1 monoclonal antibody after VEGF therapy in mRCC. According to preclinical and clinical studies, combination therapies with VEGF- and checkpoint inhibitors have synergistic effect achieving improved response rates. However, toxicity in some combinations is high. In this article, we present a review of the ongoing trials with these drug combinations for RCC.     

Genetic heterogeneity of platelet glycoproteins Ia and IIIa and the risk of spontaneous miscarriages

Objective: The aim of this study was to investigate the association between the genetic heterogeneity of platelet glycoproteins Ia (GpIa-C807T) and IIIa (GpIIIa-PlA1/PlA2) and spontaneous abortions.

Study design: Two hundred and twenty two women with a history of unexplained spontaneous miscarriages and no successful pregnancy, and 60 fertile women serving as controls were genotyped for the GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms by pyrosequencing.

Results: In comparison with the common alleles homozygotes, GpIa-807T and GpIIIa-PlA2 carriers had an increased risk of fetal loss (OR?=?3.36, 95%CI: 1.85–6.11, p?p?=?0.006, respectively). For subjects who were combined carriers of the GpIa-807T and GpIIIa-PlA2 alleles, the risk increased further (OR?=?9.13, 95%CI: 2.99–27.82, p?Conclusions: The GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and more pronouncedly their combination are associated with increased risk of spontaneous abortions. The correlations were stronger for younger patients. Our results indicate that GpIa-807T and GpIIIa-PlA2 are susceptibility alleles for fetal loss in the Greek population.     

Prediction of atrial fibrillation development and progression:current perspectives

Atrial fibrillation(AF) is the most common arrhythmia in clinical practice. Several conventional and novel predictors of AF development and progression(from paroxysmal to persistent and permanent types) have been reported. The most important predictor of AF progression is possibly the arrhythmia itself. The electrical, mechanical and structural remodeling determines the perpetuation of AF and the progression from paroxysmal to persistent and permanent forms. Common clinical scores such as the hypertension, age ≥ 75 years, transient ischemic attack or stroke, chronic obstructive pulmonary disease, and heart failure and the congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category scores as well as biomarkers related to inflammation may also add important information on this topic. There is now increasing evidence that even in patients with so-called lone or idiopathic AF, the arrhythmia is the manifestation of a structural atrial disease which has recently been defined and described as fibrotic atrial cardiomyopathy. Fibrosis results from a broad range of factors related to AF inducing pathologies such as cell stretch, neurohumoral activation, and oxidative stress. The extent of fibrosis as detected either by late gadolinium enhancement-magnetic resonance imaging or electroanatomic voltage mapping may guide the therapeutic approach based on the arrhythmia substrate. The knowledge of these risk factors may not only delay arrhythmia progression, but also reduce the arrhythmia burden in patients with first detected AF. The present review highlights on the conventional and novel risk factors of development and progression of AF.     

Nonoperable Recurrent Renal Cell Carcinoma: Management with Embolization and CT-Guided RF Ablation

We report the case of a 59-year-old male who underwent embolization and computed-tomography-guided radiofrequency ablation of a recurrent renal cell carcinoma that developed after radical nephrectomy in contiguity to the inferior vena cava. The alternative of a new operation was rejected because of the proximity of the tumor to the vessel and percutaneous approach seemed to be the better solution.     

Cervical joint position sense: an intra- and inter-examiner reliability study

OBJECTIVES: To evaluate the intra- and inter-examiner reliability of neck active joint position sense measurements in different head movements. METHODS: Participants had to reproduce actively a specific angle-target in all movements (flexion, right/left rotation, right/left side flexion) from two initial positions, sitting and standing by using a 3D ultrasound-based motion analysis device. Three tests were employed to assess intra-examiner reliability and two examiners used for the inter-examiner reliability. Absolute error (AE) and variable error (VE) indices were used to assess the repositioning accuracy. Intraclass correlation coefficient (I.C.C.(1,1)), standard error of measurement (S.E.M.), smallest detectable difference (S.D.D.) indices were calculated for the analysis of the results. RESULTS: Both AE and VE yielded poor to moderate I.C.C.s in any movement and position (-0.01 to 0.50 and 0.01-0.25, respectively). AE presented higher I.C.C.s estimates than the VE but the S.D.D.s were similar for both indices. Regarding the AE, the standing position yielded higher I.C.C. estimates (0.15-0.68) than the sitting position (-0.01 to 0.43) but the S.E.M. (1.2-3.0 degrees and 1.5-3.5 degrees, respectively) and S.D.D. values (123.3-191.8% and 139.9-203.8%, respectively) showed no specific trend in favour of any position. The VE reliability indices showed that standing position was more reliable with less error than sitting. The inter-examiner data showed similar results to the intra-examiner study. CONCLUSIONS: The statistical analysis of the present experiments showed that the method employed for measuring cervical joint position sense is unreliable. However, it needs further research to identify the discriminatory power of these tests or if they are clinically unacceptable.     

Procollagen-I, collagen telopeptide I, CEA, CA 15-3 as compared to bone scintigraphy in patients with breast cancer

The most common metastases of breast cancer (BC) are bone metastases. Serum pro-Iota collagen peptide (PICP) and I collagen telopeptide (ICTP) levels indicate the rate of bone collagen synthesis and bone resorption respectively and therefore indicate metastatic activity in the bone. We have studied the clinical importance of serum PICP and ICTP as well as CA 15-3 and CEA and compared them to bone scintigraphy findings indicating metastases from BC. Ninety seven women of mean age 58+/-8 years with BC were examined. The diagnosis of BC was histologically confirmed. Bone metastases were diagnosed in 68 of them by bone scans performed after the intravenous injection of 925 MBq of technetium-99m methylendiphosphonate, while 29 patients were free from bone metastases. We also examined 52 women of similar age, as controls. Serum PICP, ICTP, CA 15-3 and CEA were measured in both patients and controls. Serum levels of ICTP and CA 15-3 were significantly higher in patients with BC and bone metastases compared to patients without metastases (P<0.05), while PICP and CEA were only marginally higher. A statistically significant correlation was observed between the existence of bone metastases and ICTP serum levels (P<0.05). The sensitivity of PICP, ICTP, CEA and CA 15-3 was 28.1%, 48.6%, 78%, 42% respectively and their specificity was 83.9%, 94%, 65% and 86% respectively. In conclusion: ICTP and CA 15-3 are the most reliable markers of those studied for the diagnosis of bone metastases in BC. PICP alone or combined with ICTP were not sensitive enough. CA 15-3 showed sensitivity 78% and specificity 86%. When combining CA 15-3, ICTP and CEA the sensitivity and specificity increased to 82% and 96% accordingly.     

Add-on lamotrigine treatment and plasma glutamate levels in epilepsy: relation to treatment response

We investigated the effects of add-on lamotrigine treatment on plasma glutamate (Glu) levels, in 29 epileptic patients. Plasma Glu levels were determined by high-performance liquid chromatography at baseline and at 1 and 3 months post-treatment. In patients with a seizure reduction of ≥66% a decrease of Glu at month 1 was noted, followed by return to baseline levels at month 3. In the remaining patients a gradual increase of Glu was noted throughout the 3 months of the study. The above findings indicate that an excellent clinical response to add-on lamotrigine may be characterized by a statistically significant, yet transient decrease of plasma Glu levels, while increasing Glu levels may accompany a response that is moderate at best. The combination of lamotrigine with valproate was more frequent in patients with excellent clinical response and tended to result in glutamate decrease.