COVID-19 vaccine acceptance among medical students in Romania.

Vaccination against COVID-19 is a highly debated subject that brings confusion due to contradictory information coming from the scientific community and the media. Our aim was to focus on a homogeneous group of students in the healthcare field to assess their intention to vaccinate and the drivers behind this decision. A cross-sectional study was performed in the spring of 2021 in a Medical University in Romania. 725 of the undergraduates that completed an online questionnaire regarding their intention to vaccinate against COVID-19 were included in the study. Univariable analysis and logistic regression were performed on several variables to analyze factors affecting the willingness to vaccinate against COVID-19. In our study sample, 93.1% of students presented a strong intention to vaccinate, out of which the highest proportion belonged to subjects studying general medicine (96%). On logistic regression, we identified the following predictor factors: previous infection with coronavirus, prior vaccination refusal, VAX score, scientifically oriented sources of information and preference for RNA-based technology. Medical students have an increased willingness towards vaccination. Even for them, a highly educated and informed group of subjects, the general attitude towards vaccinations has a strong impact on the choice of COVID-19 vaccination.

Outcomes of patients with cancer infected with SARS-CoV-2: results from the Ion Chiricuta Oncology Institute series.

BACKGROUND: The evolution of COVID-19 is a controversial topic in cancer patients. They have been designated by international organizations as a vulnerable population at greater risk for contracting SARS-CoV-2 and having a more severe clinical outcome. PATIENTS AND METHODS: Active screening at our institution became routine early in the pandemic. We have examined the clinical data of 341 cancer patients, with a positive RT-PCR SARS-CoV-2 test between April 2020 and February 2021, in the prevaccination era. RESULTS: During the infection, 40.5% remained asymptomatic, 27.6% developed a mild form, 20.5% had a moderate form, and 11.4% a severe/critical form of COVID-19 that led to death in 7.6% of cases. Treatment was adapted to disease severity according to national guidelines. In our series, the incidence of COVID-19 infection was lower in cancer patients compared with the general population (P < 0.001), however, the mortality rate was higher in cancer patients in comparison with the general population (7.6% versus 2.9%, P < 0.001). The prognostic factors were assessed by three distinct univariate and multivariate analyses: (i) evolution to a moderate or severe/critical clinical manifestation, (ii) clinical worsening (severe/critical form or death), and (iii) overall survival. In the multivariate analysis, the prognostic factors associated with the evolution to a moderate or severe/critical clinical manifestation were: performance status (PS) (P < 0.0001) and no active treatment in the previous 3 months (P = 0.031). Factors associated with clinical worsening were: PS (P < 0.0001), peripheral arterial disease (P = 0.03), and chronic liver disease (P = 0.04). Factors associated with impaired overall survival were PS (P < 0.0001), ischemic cardiac disease (P = 0.0126), chronic liver disease (P = 0.001), and radiotherapy (P = 0.0027). CONCLUSION: Our series confirms a more severe evolution for COVID-19 infection in cancer patients, with PS as the most prominent prognostic factor in all three multivariate analyses. By active screening, efforts should be in place to keep cancer units as coronavirus-free sanctuaries.

Higher-order correction terms to the nonlinear amplification or absorption, the nonlinear refractive index, and the intrapulse Raman scattering.

In this paper we have investigated through the numerical solution of the basic equation as well as through the dynamic model the influence of higher-order correction terms to the nonlinear amplification (absorption) and to the nonlinear refractive index on the self-frequency shift of Raman dissipative solitons. We have found a nonlinear dependence of the self-frequency shift of Raman dissipative solitons on the parameter describing intrapulse Raman scattering in the presence of the saturation of the nonlinear gain. With the increase of the absolute value of the saturation of the nonlinear gain, the maximum absolute value of the frequency shift decreases and its position moves to larger values of the parameter describing intrapulse Raman scattering. The increase in the value of the nonlinear gain leads to an increase in the maximum absolute value of the frequency shift, without changing its position. We have also observed the nonlinear dependence of the absolute value of the frequency shift on the parameter describing intrapulse Raman scattering in the presence of higher-order correction term to the nonlinear refractive index. The discovered nonlinear dependence of the self-frequency shift on the value of the saturation of the nonlinear gain as well as on the higher-order correction term to the nonlinear refractive index can be used for the better understanding and control of the spectral characteristics of Raman dissipative solitons. The dynamic model correctly describes all the features of the observed phenomena.

Transitions of stationary to pulsating solutions in the complex cubic-quintic Ginzburg-Landau equation under the influence of nonlinear gain and higher-order effects.

In this paper we study the transitions of stationary to pulsating solutions in the complex cubic-quintic Ginzburg-Landau equation (CCQGLE) under the influence of nonlinear gain, its saturation, and higher-order effects: self-steepening, third-order of dispersion, and intrapulse Raman scattering in the anomalous dispersion region. The variation method and the method of moments are applied in order to obtain the dynamic models with finite degrees of freedom for the description of stationary and pulsating solutions. Having applied the first model and its bifurcation analysis we have discovered the existence of families of subcritical Poincaré-Andronov-Hopf bifurcations due to the intrapulse Raman scattering, as well as some small nonlinear gain and the saturation of the nonlinear gain. A phenomenon of nonlinear stability has been studied and it has been shown that long living pulsating solutions with relatively small fluctuations of amplitude and frequencies exist at the bifurcation point. The numerical analysis of the second model has revealed the existence of Poincaré-Andronov-Hopf bifurcations of Raman dissipative soliton under the influence of the self-steepening effect and large nonlinear gain. All our theoretical predictions have been confirmed by the direct numerical solution of the full perturbed CCQGLE. The detailed comparison between the results obtained by both dynamic models and the direct numerical solution of the perturbed CCQGLE has proved the applicability of the proposed models in the investigation of the solutions of the perturbed CCQGLE.

BODY MASS INDEX AS A PROGNOSTIC FACTOR FOR DISEASE PROGRESSION IN PATIENTS WITH METASTATIC COLORECTAL CANCER TREATED WITH BEVACIZUMAB BASED SYSTEMIC THERAPY.

CONTEXT: Epidemiological data have shown that obesity increases the risk of developing colorectal cancer and also an increased body mass index (BMI) is associated with a worse prognosis. Bevacizumab based systemic therapy, an antiVEGF targeted therapy, is an important treatment option for metastatic colorectal cancer (mCRC) patients. Obesity is associated with high level of vascular endothelial growth factor (VEGF), that might provoke resistance to antiVEGF monoclonal antibody. OBJECTIVE: To evaluate the efficacy in terms of progression free survival (PFS) and overall survival (OS) of bevacizumab systemic therapy in patients with mCRC. DESIGN: Retrospective cohort, single center study. SUBJECTS AND METHODS: Between January 2007 and December 2012, 112 patients with mCRC, who followed bevacizumab based systemic therapy in the "Ion Chiricuta" Oncology Institute in Cluj-Napoca, were included in our analysis. RESULTS: Values of BMI ≥ or <27 kg/sqm was found that PFS is statistically significant superior in patients with BMI<27 kg/sqm (n=77) than in those with BMI ≥ 27 kg/sqm (n=35), 24 months versus 17.9 months (p = 0.04). Five years OS was not influenced by the BMI, 35% vs 30% (p=0.29). In patients with liver metastases with values of BMI ≥ 27 kg/sqm have PFS lower than patients with a BMI <27 kg/sqm, 17.5 months versus 24.5 months (p = 0.02). Five years OS was not influenced by the BMI, 39% (BMI <27 kg/sqm) vs. 22% (BMI ≥ 27 kg/sqm) (p = 0.09). CONCLUSIONS: This study demonstrated the negative influence of BMI on both PFS on the entire sample of patients and in patients with liver metastases only, BMI cut-off value proved to be 27 kg/square meter and shows that the BMI may be an important prognostic factor with a high clinical relevance in patients with mCRC.

Left Atrial Size and Function in a Canine Model of Chronic Atrial Fibrillation and Heart Failure.

BACKGROUND: Our aim was to assess how atrial fibrillation (AF) induction, chronicity, and RR interval irregularity affect left atrial (LA) function and size in the setting of underlying heart failure (HF), and to determine whether AF effects can be mitigated by vagal nerve stimulation (VNS). METHODS: HF was induced by 4-weeks of rapid ventricular pacing in 24 dogs. Subsequently, AF was induced and maintained by atrial pacing at 600 bpm. Dogs were randomized into control (n = 9) and VNS (n = 15) groups. In the VNS group, atrioventricular node fat pad stimulation (310 µs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. LA volume and LA strain data were calculated from bi-weekly echocardiograms. RESULTS: RR intervals decreased with HF in both groups (p = 0.001), and decreased further during AF in control group (p = 0.014), with a non-significant increase in the VNS group during AF. LA size increased with HF (p<0.0001), with no additional increase during AF. LA strain decreased with HF (p = 0.025) and further decreased after induction of AF (p = 0.0001). LA strain decreased less (p = 0.001) in the VNS than in the control group. Beat-by-beat analysis showed a curvilinear increase of LA strain with longer preceding RR interval, (r = 0.45, p <0.0001) with LA strain 1.1% higher (p = 0.02) in the VNS-treated animals, independent of preceding RR interval duration. The curvilinear relationship between ratio of preceding and pre-preceding RR intervals, and subsequent LA strain was weaker, (r = 0.28, p = 0.001). However, VNS-treated animals again had higher LA strain (by 2.2%, p = 0.002) independently of the ratio of preceding and pre-preceding RR intervals. CONCLUSIONS: In the underlying presence of pacing-induced HF, AF decreased LA strain, with little impact on LA size. LA strain depends on the preceding RR interval duration.

Influence of intrapulse Raman scattering on stationary pulses in the presence of linear and nonlinear gain as well as spectral filtering.

We examine numerically the influence of intrapulse Raman scattering (IRS) on the stable stationary pulses in the presence of constant linear and nonlinear gain as well as spectral filtering. Numerical results show that the small change of the value of the parameter describing IRS leads to qualitatively different behavior of the evolution of pulse amplitudes. We prove that the strong dependence of the pulse dynamics on the parameter describing IRS is related to the existence of the Poincaré-Andronov-Hopf bifurcation and the appearance of the unstable limit cycle.

Impact of vagal nerve stimulation on left atrial structure and function in a canine high-rate pacing model.

BACKGROUND: Cervical vagal nerve stimulation (VNS) can improve left ventricular dysfunction in the setting of heart failure (HF). However, little is known about the impact of VNS on left atrial (LA) function. The aim of this study was to compare LA mechanics and histology between control and VNS-treated animals during HF development. METHODS AND RESULTS: Fifteen mongrel dogs were randomized into control (n=7) and VNS (n=8) groups. All dogs underwent 8 weeks of high-rate ventricular pacing (at 220 beats per minute for the first 4 weeks to develop HF and another 4 weeks at 180 beats per minute to maintain HF). LA contractile function (LA negative peak strain), conduit function (LA positive peak strain), and reservoir function (LA total strain) were measured from speckle tracking in 2 groups. At the end of the terminal study, the LA appendage was obtained. Baseline LA strains were comparable in the control and VNS-treated dogs. At 4 and 8 weeks of ventricular pacing, all LA strains were decreased and LA volumes were increased in the control group compared with the VNS group (P<0.05). Histological evaluation of the left atrium revealed that percent fibrosis was significantly lower in the VNS versus the control group (8±1% versus 13±1%; P<0.001). Finally, transmitral flow showed decreased atrial contribution to left ventricular filling in the control group (P<0.05). CONCLUSIONS: VNS improved LA function and volumes and suppressed LA fibrosis in the canine high-rate ventricular pacing model. VNS is a novel and potentially useful therapy for improving LA function during HF.

Left ventricular strain distribution in healthy dogs and in dogs with tachycardia-induced dilated cardiomyopathy.

BACKGROUND: Recently, left ventricular (LV) strain distribution pattern has been assessed in several cardiac disease states. Tachycardia-induced cardiomyopathy (TIC) is an animal model of non-ischemic cardiomyopathy well characterized in terms of global LV dysfunction but with poor understanding of regional variability in LV function. We hypothesized that TIC induces specific changes in LV strain distribution pattern. METHODS: Twenty five adult mongrel conscious dogs were trained to lie down calmly for echocardiography. In seven selected dogs, we implanted pacing system for TIC induction under general anesthesia. We measured LV geometry and function, strains, and torsion before and after the development of TIC in awake non-sedated state. RESULTS: In 25 healthy dogs, all three types of normal strain significantly increased from base to apex (p <0.05), while a definite and recognizable twist could be measured due to presence of shear strain. In 7 dogs with TIC, marked changes in LV mechanics occurred throughout the cardiac cycle, resulting in decrease of strain (p <0.001), twist (p <0.05), and negative peak twist rate (p <0.05). Interestingly, the relative decrease of strain due to TIC was more pronounced in the apex (p < 0.001), with the radial strain decreasing the most (p < 0.05). CONCLUSION: TIC is accompanied by decreased systolic LV strain and twist deformation, as well as loss of early diastolic recoil. In addition, the decrease of strain was more profound in the apex. This "reverse" distribution of LV strain may help us understand LV dysfunction in the presence of nonischemic etiology.

What is the significance of a microscopically positive resection margin in the curative-intent treatment of rectal adenocarcinoma? A retrospective study.

PURPOSE: The aim of this study was to analyze the characteristics of patients with rectal cancer operated with a microscopic positive margin (R1) and thus avoid these situations or adapt treatment in these particular cases. METHODS: We reviewed all the pathology data of resected specimens from patients with rectal or recto-sigmoid cancer operated with curative intent at the Institute of Oncology "Prof. Dr. Ion Chiricuta" between 2000-2011 (763 patients in 12 years) and the pathology files of patients from other institutions referred for adjuvant treatment to our hospital (318 patients). We included patients with anterior resection, Hartmann's procedure and abdomino-perineal resection, but we excluded patients with local excision and patients with R2/R1 at first, but R0 after re-resection (56 patients). We have identified 31 patients with R1, but had to exclude one case from analysis because this patient was lost to follow-up. RESULTS: With surgery alone the local relapse (LR) was unavoidable. In the neoadjuvant chemoradiation (CRT) group 85.7% of the patients did not develop LR despite of R1. In the adjuvant CRT cohort 50% of the patients were LR-free at 2 years after conventional radiotherapy (p<0.01). CONCLUSION: Based on these results it is concluded that a clear resection margin is extremely important for the local control of rectal cancer, because it cannot be always compensated by adjuvant CRT. In R1 cases neoadjuvant CRT seems to offer better prognosis than adjuvant CRT. To avoid R1 and its consequences a good quality control of total mesorectal excision (TME) is needed and CRT should be done before and not after surgery. R1 after primary surgery needs to be compensated by re-resection if possible, otherwise probably high dose radiotherapy with chemotherapy is needed.

Can the epirubicin cardiotoxicity in cancer patients be prevented by angiotensin converting enzyme inhibitors?

PURPOSE: The aim of this study was to assess whether treatment with angiotensin converting enzyme inhibitors (ACEI) can prevent the alteration of left ventricular systolic and diastolic performance in cancer patients treated with different chemotherapy regimens containing epirubicin. METHODS: In this prospective study , 68 patients with different malignant tumors treated with epirubicin and perindopril in different chemotherapy protocols (study group), and a gender- and age-matched group of 68 patients with different malignant tumors treated with epirubicin without perindopril in different chemotherapy protocols (control group), were assessed by Doppler echocardiography. Left ventricular systolic function was assessed by measuring left ventricular ejection fraction (EF). Left ventricular diastolic function was assessed by Doppler ultrasound by evaluating the transmitral flow. We also assessed the QTc on the 12 lead electrocardiograms. RESULTS: At the end of chemotherapy the left ventricular systolic function was less altered in the study group compared to the control group and was superior in the study group (epirubicin+ACEI) compared to the control group (epirubicin alone). We documented a significantly deteriorated left ventricular diastolic function in both groups at the completion of chemotherapy. QTc time in both arms was also significantly prolonged. CONCLUSION: In the present echo-Doppler study we documented a preserved left ventricular systolic performance in patients with various malignancies treated with epirubicin plus perindopril. Although co-treatment with ACEI prevented the alteration of systolic performance, it failed to prevent the deterioration of the left ventricular diastolic performance impairment due to poor left ventricular compliance.

Therapeutic effects of selective atrioventricular node vagal stimulation in atrial fibrillation and heart failure.

INTRODUCTION: Atrial fibrillation (AF) and heart failure (HF) frequently coexist. We have previously demonstrated that selective atrioventricular node (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during AF. Due to withdrawal of vagal activity in HF, the therapeutic effects of AVN-VS may be compromised in the combined condition of AF and HF. Accordingly, this study was designed to evaluate the therapeutic effects of AVN-VS to control ventricular rate in AF and HF. METHODS AND RESULTS: A combined model of AF and HF was created by implanting a dual chamber pacemaker in 24 dogs. A newly designed bipolar electrode was inserted into the ganglionic AVN fat pad and connected to a nerve stimulator for delivering AVN-VS. In all dogs, HF was induced by high rate ventricular pacing at 220 bpm for 4 weeks. AF was then induced and maintained by rapid atrial pacing at 600 bpm after discontinuation of ventricular pacing. These HF + AF dogs were randomized into control (n = 9) and AVN-VS (n = 15) groups. In the latter group, vagal stimulation (310 µs, 20 Hz, 3-7 mA) was delivered continuously for 6 months. Compared with the control, AVN-VS had a consistent effect on ventricular rate slowing (by >50 bpm, all P < 0.001) during the entire 6-month observation period that was associated with left ventricular functional improvement. Moreover, AVN-VS was well tolerated by the treated animals. CONCLUSIONS: AVN-VS achieved consistent rate slowing, which was associated with improved ventricular function in a canine AF and HF model. Thus, AVN-VS may be a novel, effective therapeutic option in the combined condition of AF and HF.

Atrioventricular node functional remodeling induced by atrial fibrillation.

BACKGROUND: The atrioventricular node (AVN) plays a vital role in determining the ventricular rate during atrial fibrillation (AF). AF results in profound electrophysiological and structural remodeling in the atria as well as the sinus node. However, it is unknown whether AVN undergoes remodeling during AF. OBJECTIVE: To determine whether AVN undergoes functional remodeling during AF. METHODS: AVN conduction properties were studied in vitro in 9 rabbits with AF and 10 normal controls. A previously validated index of AVN dual-pathway electrophysiology, His-electrogram alternans, was used to monitor fast-pathway or slow-pathway (SP) AVN conduction in these experiments. AVN conduction properties were further studied in vivo in 7 dogs with chronic AF and 8 controls. RESULTS: Compared with the control rabbits, the rabbits with AF had a longer AVN conduction time (83 ± 16 ms vs 68 ± 7 ms; P <.01), longer AVN effective refractory period (141 ± 27 ms vs 100 ± 9 ms; P <.01), an earlier transition from fast-pathway to SP conduction (at a longer prematurity, 249 ± 60 ms vs 171 ± 24 ms; P <.01), and a slower ventricular rate during simulated AF (RR interval 249 ± 42 ms vs 202 ± 12 ms; P <.01). Notably, a larger proportion of conducted beats utilized the SP in AF preparations (92% ± 12% vs 63% ± 32%; P <.05). Long-term AF in dogs resulted in a longer atrioventricular conduction time and AVN effective refractory period and a slower ventricular rate during AF compared with the controls. CONCLUSIONS: Pronounced AVN functional electrophysiological remodeling occurs after long-term AF, which could lead to a spontaneous slowing of the ventricular rate. Furthermore, the SP dominance during AF underscores the effectiveness of its modification by ablation for ventricular rate control during AF.

Suppression of the soliton self-frequency shift and compression in the presence of bandwidth-limited amplification.

We study numerically the suppression of the soliton self-frequency shift as well as the compression in the presence of bandwidth-limited optical amplification (BLA). Our results confirm the existence of equilibrium points (stable focuses) for the soliton amplitude and speed identified by the soliton perturbation theory. Analyzing the equilibrium amplitudes as a function of physical parameters, maximum compression factor in the amplification of short pulses is revealed. The results of linear stability analysis allow estimation of the necessary distance for the appearance of equilibrium states from different initial conditions. It has been shown that the shape of the perturbed stationary solution in the presence of intrapulse Raman scattering and BLA can be described by the earlier derived analytic expressions.

Botulinum toxin injection in epicardial autonomic ganglia temporarily suppresses vagally mediated atrial fibrillation.

BACKGROUND: Autonomic denervation may suppress atrial fibrillation (AF) vulnerability. This study was designed to assess the short- to mid-term effects of botulinum toxin, a cholinergic neurotransmission blocker, on AF inducibility. METHODS AND RESULTS: A total of 23 mongrel dogs were studied. The sinus node and atrioventricular node epicardial fat pads were exposed through a right lateral thoracotomy. Botulinum toxin (Botox, 50 U per fat pad) or 0.9% normal saline (control) was injected into the center of each of the 2 fat pads. The electrophysiological effects were evaluated at 1, 2, and 3 weeks (7 to 8 animals at each time point) with and without cervical vagal stimulation. The vagal stimulation effects on the sinus and atrioventricular nodes were inhibited, and dispersion of atrial effective refractory period was lower at 1 week in the Botox group. Significant suppression of AF inducibility was observed at 1 week but disappeared at 2 and 3 weeks. These changes were not observed in the control group. CONCLUSIONS: Temporary suppression of vagally mediated AF, for at least 1 week, was achieved with botulinum toxin injection in this canine model. This effect might be associated with reduced dispersion of effective refractory period. A temporary autonomic block using botulinum toxin might be a novel therapeutic option for several clinical conditions such as post-cardiac surgery AF.

AV nodal dual pathway electrophysiology and Wenckebach periodicity.

INTRODUCTION: The precise mechanism(s) governing the phenomenon of AV nodal Wenckebach periodicity is not fully elucidated. Currently 2 hypotheses, the decremental conduction and the Rosenbluethian step-delay, are most frequently used. We have provided new evidence that, in addition, dual pathway (DPW) electrophysiology is directly involved in the manifestation of AV nodal Wenckebach phenomenon. METHODS AND RESULTS: AV nodal cellular action potentials (APs) were recorded from 6 rabbit AV node preparations during standard A1A2 and incremental pacing protocols. His electrogram alternans, a validated index of DPW electrophysiology, was used to monitor fast (FP) and slow (SP) pathway conduction. The data were collected in intact AV nodes, as well as after SP ablation. In all studied hearts the Wenckebach cycle started with FP propagation, followed by transition to SP until its ultimate block. During this process complex cellular APs were observed, with decremental foot formations reflecting the fading FP and second depolarizations produced by the SP. In addition, the AV node cells exhibited a progressive loss in maximal diastolic membrane potential (MDP) due to incomplete repolarization. The pause created with the blocked Wenckebach beat was associated with restoration of MDP and reinitiation of the conduction cycle via the FP wavefront. CONCLUSION: DPW electrophysiology is dynamically involved in the development of AV nodal Wenckebach periodicity. In the intact AV node, the cycle starts with FP that is progressively weakened and then replaced by SP propagation, until block occurs. AV nodal SP modification did not eliminate Wenckebach periodicity but strongly affected its paradigm.

Expression of VEGF, VEGFR, EGFR, COX-2 and MVD in cervical carcinoma, in relation with the response to radio-chemotherapy.

INTRODUCTION: Despite the improvement in the treatment results due to modern irradiation techniques and to the association of chemo-radiotherapy, cervical cancer remains an unsolved problem of oncology both due to the increased rate of local failures and of the distant metastasis. Efforts to implement new therapeutic strategies in order to obtain better results in patients with cervical cancer appear justified. Neovascularization is an important step in the tumor progression and the therapeutic targeting of the tumor blood vessels appears to be a good strategy to follow in the anti-cancer treatment. Thus, even in an incipient phase of the clinical research process, the combination between the anti-angiogenic aimed therapies and the current radio-chemotherapy seems to represent a new, feasible and promising approach. The aim of the present study was to determine the prognostic and/or predictive value of some biological markers of tumor angiogenesis and of their implication in increasing the efficacy of current treatments for this cancer. MATERIALS AND METHODS: So far, 54 women were included in a prospective trial: 44 having an advanced cervical carcinoma and 10 healthy women, as controls. A tumor biopsy and a blood sample were obtained from each patient before the start of therapy. The density of microvascularization was assessed using CD34 monoclonal antibody (hot spot technique), the expression of angiogenic factors VEGFR, EGFR and COX-2 were determined in tumor biopsies by specific immunohistochemistry techniques, using primary antibodies anti-EGFR, anti-VEGF and anti-COX-2 respectively. The quantitative polymerase chain reaction (Real Time PCR) was employed for assessing the expression level of the genes involved. Serum VEGF was determined by quantitative ELISA technique. RESULTS: Among the studied clinical and molecular factors, we found to be predictive for the type of response the following factors: tumor size at diagnosis (p=0.01), VEGFR2 expression (p=0.02) and a tendency to significance for patients' age (p=0.06). From the large panel of studied markers it was observed correlation between MVD expression with stromal COX-2 (p=0.01) and a tendency with epithelial COX-2 (p=0.06). Stromal COX-2 has higher correlation with VEGFR2 (p=0.01) and MVD (p=0.01) and also has a lower correlation with tumor size (p=0.08). CONCLUSIONS: Univariate analysis demonstrates that the response to radio-chemotherapy in cervical cancer is related to a set of clinical and molecular factors as: the tumor size, the expression of VEGFR2 as mRNA level and the patients' age. Unfortunately, the multivariate analysis by logistic model selects only VEGFR2 expression for prediction of tumor response. The interrelations between the different biomarkers demonstrate the complexity of the tumor progression process and the necessity of further studies to identify new therapeutic targets.

Arrhythmias and vagus nerve stimulation.

Enhancing vagal tone by delivering electrical stimulation to the vagal nerves (VNS) is emerging as a promising novel therapy in heart failure. In addition, VNS is already an FDA-approved therapy for refractory epilepsy and depression. Besides its well-known negative chronotropic, inotropic, and dromotropic effects, VNS has profound effects on cardiac electrophysiology and arrhythmogenesis. This review summarizes current knowledge about the complex relationship between VNS and cardiac arrhythmias. Specifically, the focus is on VNS capability to become a therapeutic strategy along with important electrophysiological alterations that may constitute a potential arrhythmogenic substrate and become a clinical concern.

Functional model of dual AV nodal pathway physiology.

Role of dual AV nodal pathway physiology in the atrioventricular nodal (AVN) conduction during atrial arrhythmias remains unclear. By using His electrogram alternans (HEA), we have developed a functional model of the atrioventricular conduction that incorporates the dual AV nodal pathway physiology. Experiments performed on 5 rabbit atrial-AVN preparations were used to develop and test the presented AV nodal functional model. HEAs from the inferior margin of the His bundle were used to identify fast and slow wavefront propagations (FP and SP). Conduction curves were calculated by using the model and compared with the real experiments, the root mean square error of the FP and SP were 7 ± 4ms and 3 ± 3 ms respectively. In addition, the model has been used for illustrating the effects of the atrioventricular node modification, which has emerged as one of the alternatives for ventricular rate control during atrial fibrillation. The presented model can help in understanding some of the unclear AV node conduction mechanisms and should be considered as a step forward in understanding the AV node and specifically its dual pathway physiology.

Oxaliplatin in patients with metastatic colorectal cancer: efficacy and pharmacokinetics parameters.

PURPOSE: The aim of this study was to investigate the efficiency of the FOLFOX-4 regimen and to evaluate the pharmacokinetics of oxaliplatin in untreated patients with metastatic colorectal cancer. METHODS: 43 patients were enrolled in the study. Patients received oxaliplatin 85 mg/m(2) as 2-h i.v. infusion, on day 1, and bolus 5-fluorouracil (5FU) 400 mg/m(2) plus leucovorin (LV) 200 mg/m(2) followed by 5FU 600 mg/m(2) as 22-h infusion on day 1 and 2, every 2 weeks. The pharmacokinetics of oxaliplatin evaluated in 4 patients was performed in blood, plasma and ultrafiltered plasma (UFT) by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: The overall response rate and the median time to progression (TTP) were 53.49% and 7.1 months, respectively. Grade 3-4 toxic effects were observed in 11 (25.5%) patients. Grade 3 neuropathy was observed in 13.95% of the cases. In univariate analysis only Eastern Cooperative Oncology Group (ECOG) performance status (PS) was correlated with response. No correlation was found between grade 3-4 adverse events and the patient characteristics. The area under the time-concentration curve (AUC) in UFT was 4.8 + or - 0.72 standard deviation (SD) microg h/ml and the total clearance 30.17 + or - 7.75 l/min. The values for volume of distribution and the maximum concentration were 567 + or - 20 liters and 0.38 + or - 0.17 ug/ml, respectively. CONCLUSION: FOLFOX-4 was an effective regimen with good tolerability in previously untreated metastatic colorectal cancer patients. The pharmacokinetics of oxaliplatin was triphasic with a short initial distribution phase and a long terminal elimination phase.