Relation of chelation regimes to cardiac mortality and morbidity in patients with thalassaemia major: an observational study from a large Greek Unit

Objectives: Cardiac complications because of transfusional iron overload are the main cause of death in thalassaemia major. New chelators and iron monitoring methods such as cardiac magnetic resonance (CMR) became available after the year 2000. We evaluated the impact of these new management options on cardiac mortality and morbidity. Methods: The risk of cardiac death during 1990–1999 and 2000–2008 was compared. Furthermore, after 1999, morbidity, mortality and reversal of heart failure were evaluated according to chelation regime: desferrioxamine (DFO), deferiprone (DFP) and combination therapy of DFO and DFP. We also present preliminary results for deferasirox (DFX), a new oral chelator. Results: Three hundred and fifty‐four patients were included in the de novo cardiac event evaluation, while 86 were included in the improvement component. The annual risk of cardiac death in patients aged between 20–30 and 30–40 reduced from 1.52% to 0.67% and 1.87% to 0.56%, respectively, before and after the year 2000. The risk for a de novo cardiac event for DFO was 9.1 times greater than that of DFP and 23.6 than with the combination of DFP and DFO. For DFX, there was one cardiac event over 269 patient‐years. The risk of cardiac death was 9.5 per 1000 patient‐years for DFO, 2.5 on DFP, 1.4 on combination. In the DFX group no cardiac deaths were recorded. The odds of improvement were 8.5 times greater with DFP and 6.1 with combination therapy compared to DFO. Conclusions: The new chelation regimes, together with CMR have contributed significantly to the reduction in cardiac morbidity and mortality in patients with thalassaemia major.     

The proprioceptive and agonist roles of gastrocnemius, soleus and tibialis anterior muscles in maintaining human upright posture

Humans can stand using sensory information solely from the ankle muscles. Muscle length and tension in the calf muscles (gastrocnemius and soleus) are unlikely to signal postural sways on account of balance-related modulation in agonist activity. These facts pose two questions: (1) Which ankle muscles provide the proprioceptive information? (2) Which peripheral mechanism could modulate agonist activity? To address these issues, subjects were asked to stand normally on two force plates. Ultrasound and surface EMG were recorded from the calf and tibialis anterior (TA) muscles. For all nine subjects, changes in muscle length of TA were mainly (84 ± 9% whole trial duration) orthodoxly correlated with bodily sway (centre of gravity, CoG), i.e. in accordance with passive ankle rotation. When orthodox, TA had the highest correlation with CoG (−0.66 ± 0.07, deep compartment, P < 0.001). For five subjects, the superficial TA compartment showed counter-intuitive changes in muscle length with CoG, probably due to the flattening of the foot and proximal attachment geometry. Gastrocnemius and soleus were usually (duration 71 ± 23 and 81 ± 16%, respectively) active agonists (paradoxically correlated with CoG) but, for short periods of time, they could be orthodox and then presented a moderate correlation (0.38 ± 0.16 and 0.28 ± 0.09, respectively) with CoG. Considering the duration and extent to which muscle length is orthodox and correlated with CoG, TA may be a better source of proprioceptive information than the active agonists (soleus and gastrocnemius). Therefore, if a peripheral feedback mechanism modulates agonist activity then reciprocal inhibition acted by TA on the calf muscles is more likely to be effective than the autogenic pathway.     

Pseudomonas fluorescens infections in clinical practice

Pseudomonas fluorescens was isolated from an elderly immunocompromized patient with fever. Treatment with ceftazidime was successful, after empirical therapy failed. Pseudomonas fluorescens is 1 of the less virulent members of the Pseudomonadaceae family. The epidemiology of the infection and the difficulties in isolation and susceptibility assessment are further discussed.     

Snake venom poisoning in Greece. Experiences with 147 cases

BACKGROUND: Snake venom poisoning is a medical emergency requiring immediate attention. Bites from poisonous European snakes can lead to local tissue damage and systemic symptoms. Vipera ammodytes accounts for the most envenomation in Greece. METHODS: The demographic and epidemiological characteristics, clinical symptoms and signs, laboratory findings, treatment, and outcome of 147 consecutive victims of V. ammodytes admitted to our hospital from 1988 to 2003 were reviewed and analyzed. RESULTS: The most common symptoms and signs included fang marks (100%), pain (100%), swelling (98.64%), ecchymosis (60.54%), tachycardia (32.65%), fainting or dizziness (29.93%), fever (23.13%), enlargement of regional lymph nodes (17.69%), nausea (16.33%), hypotension (13.61%), and vomiting (12.93%). The main complications were reduced range of motion, thrombophlebitis, local hemorrhagic blister formation, skin bleeding, rhabdomyolysis, reduced sensation, acute renal failure, necrosis with tissue loss, carpal tunnel syndrome, compartment syndrome, Kounis syndrome, and digit amputation. CONCLUSIONS: A V. ammodytes bite is a potentially serious event that requires immediate hospital care. Yet, the majority of victims can be treated successfully with conservative methods. No deaths occurred in our series.     

Strength and speed characteristics of elite, subelite, and recreational young soccer players

The purpose of the present study was to compare maximal isometric force, force-time curve characteristics, pedaling rate, vertical jump, and sprint performance among young soccer players from different competition levels. Fifty-four (54) young soccer players were divided into three groups according to competition level: the elite group (n=18) consisted of soccer players from the national youth soccer team of Greece, the subelite group (n=18) consisted of youth soccer players who participated in the local championship, and the recreational group (n=18) consisted of recreational soccer players. All groups were evaluated for maximal isometric force, explosive force at 100 msec, peak force relative to body mass, rate of force development, squat and drop jump heights, 10 m sprint time, and pedaling rate. The elite group presented significantly (p < 0.05) higher maximal isometric force, vertical jump height, and pedaling rate, and lower 10 m sprint time in comparison with the subelite and recreational groups. No significant differences were observed in strength and speed characteristics between the subelite and recreational young soccer players. The findings of the present study suggest that the elite young soccer players can be distinguished from subelite and recreational young soccer players in strength and speed characteristics. These strength and speed measures can be used for strength and speed diagnosis, and for designing and evaluating training programs.     

Covered Stent-Graft Treatment of Traumatic Internal Carotid Artery Pseudoaneurysms: A Review

Objective To review the literature concerning the management with placement of covered stent-grafts of traumatic pseudoaneurysms of the extracranial internal carotid artery (ICA) resulting from penetrating craniocervical injuries or skull base fractures. Method We have reviewed, from the Medline database, all the published cases in the English literature since 1990 and we have added a new case. Results We identified 20 patients with traumatic extracranial ICA pseudoaneurysms due to penetrating craniocervical injuries or skull base fractures who had been treated with covered stent-graft implantation. Many discrepancies have been ascertained regarding the anticoagulation therapy. In 3 patients the ICA was totally occluded in the follow-up period, giving an overall occlusion rate 15%. No serious complication was reported as a result of the endovascular procedure. Conclusion Preliminary results suggest that placement of stent-grafts is a safe and effective method of treating ICA traumatic pseudoaneurysms resulting from penetrating craniocervical injuries or skull base fractures. The immediate results are satisfactory when the procedure takes place with appropriate anticoagulation therapy. The periprocedural morbidity and mortality and the early patency are also acceptable. A surveillance program with appropriate interventions to manage restenosis may improve the long-term patency.     

Molecular predictors of response to tyrosine kinase inhibitors in patients with Non-Small-Cell Lung Cancer

Introduction

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have become a treatment option in non-small-cell lung cancer (NSCLC) patients. However, despite their use in this disease, a significant number of patients will eventually develop resistance and relapse. In this study, we aimed to characterize several molecular events involved in potential resistance mechanisms to anti-EGFR treatment and correlate our findings with clinical outcome.

Material and methods

The medical records of patients with NSCLC who received anti-EGFR TKIs in any line within the participating centers were reviewed and available paraffin embedded tissue was retrieved. Mutational analysis for EGFR, KRAS, BRAF and intron-exon 14 deletions of MET; FISH analysis for chromosomal gain or amplification for EGFR, MET and the deletion marker D7S486 were performed. Furthermore, the expression of EGFR and MET were analysed by immunohistochemistry. All results were correlated with treatment outcomes.

Results

Between 10/2001 and 12/2009 from an initial cohort of 72 treated patients, 59 cases (28 gefitinib/ 31 erlotinib) were included in the analysis. The majority had adenocarcinoma histology (68%), and received treatment in the second line setting (56%). Disease control rate (DCR) was 25.4% for all patients. EGFR and RAS mutational rates were 33% and 10% respectively, no other mutations were identified. High EGFR expressing tumors were found in 7 of 45 cases and pEGFR positivity (IHC) was found in 56% of the cases; MET expression was found in 48% of tumors. EGFR gene amplification was found in 4 cases, two cases showed high polysomy; overall, 13% cases were FISH positive for EGFR. High polysomy of MET gene was detected in 1/43 cases tested. D7S486 locus deletion was detected in 15/37 (40%) of cases. EGFR mutational status and gene gain were both associated with more favorable DCR. No other associations between examined biomarkers and DCR or survival were noted.

Conclusions

EGFR mutational status is a predictor for disease control in patients with NSCLC treated with anti-EGFR TKIs. The predictive role of several other molecules involved in potential resistance to anti-EGFR TKIs is worthy of additional investigation.