Acceptance and transfer to a regional severe respiratory failure and veno-venous extracorporeal membrane oxygenation (ECMO) service: predictors and outcomes.

The use of extracorporeal membrane oxygenation for respiratory failure is high risk and resource intensive. In England, five centres provide this service and patients who are referred have four possible outcomes: declined transfer due to perceived futility; accepted in principle but remain at the referring centre with ongoing surveillance; retrieved using conventional ventilation; or retrieved on extracorporeal support. The decision-making process leading to these outcomes has not previously been examined. We evaluated referrals to one centre and identified factors associated with each decision outcome. Five hundred and sixty-four patients were analysed from January 2012 to October 2015. One hundred and fifty-seven patients were declined; multivariate analysis demonstrated associated factors to be: age (odds ratio (95% confidence interval) 1.05 (1.04-1.07)); immunocompromise (4.95 (2.58-9.67)); lactate (1.11 (1.01-1.22)); duration of ventilation (1.08 (1.04-1.14)); and cardiac failure (3.22 (1.04-10.51)). Factors associated with the decision to retrieve an accepted patient were: plateau pressure (1.05 (1.01-1.10)); ratio of arterial oxygen partial pressure to fractional inspired oxygen (0.89 (0.85-0.93)); partial pressure of carbon dioxide in arterial blood (1.13 (1.03-1.25)); and the absence of non-pulmonary infection (0.31 (0.15-0.61)). Only pH was independently associated with the decision to transfer on extracorporeal support (0.020 (0.002-0.017)). Six-month survival in the declined, non-retrieved, conventionally retrieved and extracorporeal-retrieved groups was 16.6%, 71.1%, 76.7% and 72.1%, respectively, substantially supporting the decision-making model. Survival in the accepted group exceeds that reported previously. However, a proportion of those declined do survive and some remotely managed patients die. This suggests the approach does not account for some important survival-determining factors.

International survey on the management of mechanical ventilation during ECMO in adults with severe respiratory failure.

BACKGROUND: No consensus exists on the optimal settings of mechanical ventilation during veno-venous extracorporeal membrane oxygenation (ECMO). Our aim was to describe how mechanical ventilation and related interventions are managed by adult ECMO centres. METHODS: A cross-sectional, multi-centre, international survey of 173 adult respiratory ECMO centres. The survey was generated through an iterative process and assessed for clarity, content and face validity. RESULTS: One hundred thirty-three centres responded (76.8%). Pressure control was the most commonly used mechanical ventilation mode (64.4%). Although the median PEEP was 10 cmH2O, 22.6% set PEEP <10 cmH2O and 15.5% used 15-20 cmH2O. In 63% of centres PEEP was fixed and not titrated. Recruitment maneuvres, were never used in 34.1% of centres, or used daily in 13.2%. Centres reported using either a "lung rest" (45.7%), or an "open lung" strategy (44.2%). Only 24.8% used chest CT to guide mechanical ventilation. Adjunctive treatments were never or occasionally used. Only 10% of centres extubated patients on ECMO, mainly in more experienced centres. 71.3% of centres performed tracheostomy on ECMO, with large variability in timing (most frequent on days 6-10). Only 27.1% of ECMO centres had a protocol for mechanical ventilation on ECMO. CONCLUSION: We found large variability in ventilatory practices during ECMO. The clinicians' training background and the centres' experience had no influence on the approach to ventilation. This survey shows that well conducted studies are necessary to determine the best practice of mechanical ventilation during ECMO and its impact on patient outcome.

Capabilities of a mobile extracorporeal membrane oxygenation service for severe respiratory failure delivered by intensive care specialists.

We conducted a single-centre observational study of retrievals for severe respiratory failure over 12 months. Our intensivist-delivered retrieval service has mobile extracorporeal membrane oxygenation capabilities. Sixty patients were analysed: 34 (57%) were female and the mean (SD) age was 44.1 (13.6) years. The mean (SD) PaO2 /FI O2 ratio at referral was 10.2 (4.1) kPa and median (IQR [range]) Murray score was 3.25 (3.0-3.5 [1.5-4.0]). Forty-eight patients (80%) required veno-venous extracorporeal membrane oxygenation at the referring centre. There were no cannulation or extracorporeal membrane oxygenation-related complications. The median (IQR [range]) retrieval distance was 47.2 (14.9-77.0 [2.3-342.0]) miles. There were no major adverse events during retrieval. Thirty-seven patients (77%) who received extracorporeal membrane oxygenation survived to discharge from the intensive care unit and 36 patients (75%) were alive after six months. Senior intensivist-initiated and delivered mobile extracorporeal membrane oxygenation is safe and associated with a high incidence of survival.

Anti-tumour activity of afatinib, an irreversible ErbB family blocker, in human pancreatic tumour cells.

BACKGROUND: The combination of the reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib with gemcitabine obtained FDA approval for treating patients with pancreatic cancer. However, duration of response is often limited and there is currently no reliable predictive marker. METHODS: We determined the sensitivity of a panel of human pancreatic tumour cell lines to treatment with afatinib, erlotinib, monoclonal antibody (mAb) ICR62, and gemcitabine, using the Sulforhodamine B colorimetric assay. The effect of these agents on cell signalling and cell-cycle distribution was determined by western blot and flow cytometry, respectively. RESULTS: At 200 nM, ICR62 had no effect on growth of these tumour cells with the exception of BxPC-3 cells. BxPC-3 cells were also sensitive to treatment with afatinib and erlotinib with respective IC(50) values of 11 and 1200 nM. Compared with erlotinib, afatinib was also more effective in inhibiting the growth of the other human pancreatic tumour cell lines and in blocking the EGF-induced phosphorylation of tyrosine, EGFR, MAPK, and AKT. When tested in BxPC-3 xenografts, afatinib induced significant delay in tumour growth. CONCLUSION: The superiority of afatinib in this study encourages further investigation on the therapeutic potential of afatinib as a single agent or in combination with gemcitabine in pancreatic cancer.

RET proto-oncogene mutations are restricted to codon 618 in Cypriot families with multiple endocrine neoplasia 2.

BACKGROUND: RET germline mutations predispose to the development of inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN2). Several variants of the RET proto-oncogene including G691S and S904S have been suggested to act as genetic modifiers at the age of onset ofMEN2. AIM: The aim of this study is to characterize clinically and molecularly 7 Cypriot patients with familial medullary thyroid carcinoma (FMTC) and 1 with MEN2A and also to determine the allelic frequencies of the RET variants G691S and S904S. SUBJECTS AND METHODS: Seven probands from FMTC families and 1 from MEN2A were screened for the presence of RET mutations and the G691S and S904S variants. Additionally, 226 healthy Cypriots, who served as controls were analysed in an attempt to compare the frequencies of G691S and S904S RET variants to those observed in the 8 patients. RESULTS: The clinical diagnosis of the probands was based on clinical presentation and supported with biochemical findings. The germline C618R mutation of exon 10 was identified in all 8 probands and in 15 relatives from 7 different families. No significant difference in the G691S/S904S variants allele frequencies between patients (4/16 or 25%) and controls (124/452 or 27.4%) was found. CONCLUSIONS: Mutational screening of the RET gene identified a common mutation (C618R) in all 8 (7 FMTC and 1 MEN2A) unrelated Cypriot patients which may be explained by a founder effect. Additionally, no association of the G691S/S904S variants was linked with the disease.

A real-time PCR assay to differentiate the B and Q biotypes of the Bemisia tabaci complex in Cyprus.

A real-time PCR assay based on TaqMan technology was developed and evaluated for the rapid detection of the B and Q biotypes of Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae). A survey was conducted during 2005-2007 in order to identify the distribution and prevalence of B. tabaci biotypes in Cyprus using the real-time PCR assay. More than 700 adult whiteflies collected from 35 cultivated and weed plant species were individually haplotyped using TaqMan PCR, and the results of the assay were validated by restriction fragment length polymorphism analysis and DNA sequencing of the mitochondrial cytochrome oxidase I (mtCOI) gene. Two biotypes, B and Q, were identified in the collected plant species on the island. The real-time PCR and RFLP assay consistently yielded the same results, although the real-time assay was more sensitive and less time consuming. Phylogenetic analysis of the mtCOI DNA sequences corroborated the identity of the B and Q biotypes 100% of the time and by phylogenetic analysis the haplotypes grouped, as expected, in the major North African-Mediterranean-Middle Eastern clade of the B. tabaci complex.

Open subintimal angioplasty of the superficial femoral and distal arteries.

PURPOSE: To describe an open approach to subintimal angioplasty. TECHNIQUE: Through a subinguinal incision and arteriotomy over the superficial femoral artery origin, the opening of a subintimal channel is created surgically. The subintimal plane is advanced distally with a guidewire, and this neolumen is expanded with sequential balloon dilations. The atherosclerotic core is dissected proximally in the common femoral artery and tacked down to ensure inflow. A patch graft closes the arteriotomy. CONCLUSIONS: Open subintimal angioplasty is a simple, minimally invasive alternative treatment for complete SFA occlusion. Long-term follow-up in a large group of patients will be necessary to determine the durability of the false arterial lumen.

Concurrent multivessel stenting in a patient with multifocal arterial disease.

PURPOSE: To report the concurrent endovascular treatment of multiple stenoses in different vascular territories. METHODS AND RESULTS: A 45-year-old male presented with an aortic arch syndrome, renovascular hypertension, and Leriche syndrome. Intra-arterial digital arteriography disclosed occlusion of the left subclavian artery and stenoses in the left common carotid artery (CCA), the right CCA at the bifurcation, the left renal artery, and both iliac arteries. In a single procedure, the patient received 5 stents in 2 carotid, 1 renal, and 2 iliac arteries. At 3-month follow-up, color flow duplex imaging confirmed continued patency of all stented arteries. CONCLUSIONS: This case illustrates the feasibility, safety, and cost effectiveness of treating multivessel stenoses using a single-session endovascular approach executed by experienced interventionists.

Determination of glutamate by high-performance liquid chromatography with fluorescence detection in superfusates of rat brain preparations.

A method is described for the determination of glutamate in superfusates of cortical or hippocampal rat brain slices. This method is based on the precolumn derivatization of amino acids with orthopthaldialdehyde and mercaptopropionic acid, separation by high-performance liquid chromatography, and detection by fluorescence. By adjusting the concentrations of reagents and with the minimum dilution of the sample, it was possible to reproducibly measure the Ca2+-dependent K+-evoked release of neurotransmitter glutamate in superfusates of brain slices.

Surgical treatment of spontaneous internal carotid dissection.

Spontaneous dissection of the internal carotid artery is rarely submitted to surgery. We report a case successfully operated on with complete restoration of the cerebral blood flow. A 43-year-old male was admitted to our hospital 10 days after an episode of amaurosis fugax of the left eye, left sided headache and paresis of the right arm of a few hours duration. A diagnosis of dissection of the left internal carotid artery was made by duplex and triplex ultrasound examination and was confirmed by cerebral arteriography in contrast to magnetic resonance angiography which was misleading. Due to the slow arterial flow from the right to the left cerebral hemisphere through only the posterior communicating arteries we envisaged the possibility of a cerebral infarction if the dissection were to be extended. For this reason a surgical procedure was performed by excising the dissected segment and inserting a venous graft for the re-establishment of the arterial flow. Surgical treatment of spontaneous internal carotid dissection should be considered very carefully when the clinical and laboratory findings suggest the possibility of an impending stroke.

Fatalities from non-use of seat belts and helmets in Greece: a nationwide appraisal. Hellenic Road Traffic Police.

It has been established that seat belt use by car occupants and helmet use by motorcycle riders substantially reduces the risk of serious and fatal injuries following accidents. No study, however, has evaluated the motor vehicle deaths that could be prevented in Greece by general use of these devices, even though this country has the highest mortality from motor vehicle accidents in the European Union. We have estimated the odds ratios (OR) for death rather than injury in a motor vehicle accident by seat belt use among occupants of passenger cars or helmet use among motorcycle riders, using a nationwide database in which persons killed or injured in road traffic accidents in 1985 and 1994 were recorded. The study base included 910 dead and 19,511 injured persons for 1985 and 1203 dead and 22,186 injured persons for 1994. The OR and 95% confidence intervals (CI) for death rather than injury was 0.69 (CI: 0.58 to 0.81, p < 10(-5)) for seat belt users versus non-users and 0.64 (CI: 0.51 to 0.81; p < 10(-3)) for helmet users versus non-users. There was evidence that the protective effect of these passive safety devices increased from 1985 to 1994 probably reflecting technological improvements. The proportion of all deaths that could have been avoided if all car occupants used seat belts was estimated to 27%, whereas 38% of motorcycle deaths could have been avoided if all motorcycle riders used helmets. These proportions translate to about 500 deaths per year, mostly deaths among young men.

Is cerebral arteriography necessary for decision making in carotid endarterectomy?

The development of ultrasonic diagnostic imaging technics has recently been a competitive diagnostic method in cerebral arteriography. Many vascular surgeons, based on the high specificity and sensitivity of the ultrasonic imaging technics in carotid artery disease, have been performing carotid endarterectomy without arteriography with satisfactory results. In the last four years we have performed in our Department 62 carotid endarterectomies on 57 patients without using cerebral arteriography. In this paper diagnostic ultrasonic imaging and transcranial Doppler technics are presented and the immediate results of carotid endarterectomy in the above series of patients are reported. From our and other authors' experience it is concluded that carotid endarterectomy in patients with carotid artery disease is a safe procedure. Larger series of patients are needed with a longer follow-up in order that carotid endarterectomy without arteriography be accepted by the medical profession as a safe procedure.

Ruptured abdominal aortic aneurysms. Clinical and surgical considerations.

Rupture of abdominal aortic aneurysms (AAA) is a life-threatening condition and a leading cause of death in various countries. In spite of increased awareness of most physicians for an early diagnosis of the rupture, the performance of surgery in an early stage and special care in the Intensive Care Unit, postoperative mortality is still high in most medical centers as well as in our Clinic. Two series of patients operated in our Clinic during the last 17 years are analysed. The applied surgical technics are presented and morbidity and mortality are analysed. A distinction between the general mortality was made based on all the inhospital deaths and the postoperative mortality rate including only the deaths after the operation during the postoperative period. Among the other conclusions it is also stressed that a real improvement in the mortality rate depends on elective surgery of all the disclosed AAA larger than 4 cm in diameter.

Somatostatin as adjuvant therapy in the management of obstructive ileus.

The adjuvant use of somatostatin in the clinical management of obstructive ileus was studied prospectively. Fifty-four consecutive patients suffering from total obstructive ileus were managed over a period of one year. A double-blind clinical trial involving the administration of somatostatin for two days was carried out. Twenty-seven non-selected patients received somatostatin, while the other twenty-seven did not. Of the 27 patients who did not receive somatostatin, 12 (44%) were operated on, while only 6 (22%) of those who had received the agent required surgery. As little as 16% of the patients who received somatostatin pre-operatively exhibited severe dilatation and necrosis of the intestine proximal to the area of destruction as compared with 83% of those patients who did not receive somatostatin before the operation. It was concluded that while the administration of somatostatin to patients suffering from obstructive ileus may not be directly related to a reduction in surgery, it does reduce the effects of intestinal dilatation on the healthy gut proximal to the area of destruction.

The effective treatment of multifocal atrial tachycardia with amiodarone.

Multifocal atrial tachycardia (MAT) was observed in 9 patients aged 60-85 (mean 72.1 +/- 8.6) years during exacerbation of their chronic lung and/or cardiac disease. Four, in whom the rapid heart rate caused symptoms of pulmonary congestion, were treated with intravenous amiodarone (450-900 mg over 2 hours) with restoration of sinus rhythm soon after the termination of the drug infusion. In 1, with recurrence of MAT, the same intravenous dosage was repeated for 2 consecutive days, with final achievement of stable sinus rhythm. Five patients, apart from the conventional management of their underlying disease (digitalis, diuretics, aminophylline) were treated with oral amiodarone (600 mg/day). Sinus rhythm was restored in all and remained stable during their hospitalization, under alpha maintenance dosage of 200-400 mg daily. Amiodarone may be the drug of choice for the treatment of MAT, for which up to now no effective therapy has been established.

Combination of disopyramide and propranolol in hypertrophic cardiomyopathy.

Fifteen patients were studied by echocardiography, apexcardiogram and carotid pulse tracings in four ways: basally; on propranolol 40 mg, three times daily; on disopyramide 200 mg single dose, three days after propranolol discontinuation; and on both drugs. The following data were measured: systolic anterior mitral motion slope, systolic anterior mitral distance from the septum, outflow tract diameter, the A wave to the total apexcardiographic excursion ratio, carotid pulse contour and left ventricular ejection time index. Propranolol did not produce any significant changes while disopyramide was much more effective in changing the data in a direction suggesting diminution of left ventricular outflow gradient. The combination of propranolol and disopyramide had the greatest influence. Fourteen patients received the two drugs for 12.3 +/- 4.3 months with improvement of NYHA class.

New criteria to increase the reliability of systolic time intervals in left bundle branch block and right ventricular pacing.

We measured the systolic time intervals (STI) in 14 patients (pts) with intermittent left bundle branch block (LBBB) in order to find correlations and comparisons in their values which might pertain to the individual patients, with (b) and without (a) LBBB. QS2I, PEP and the PEP/LVET ratio increased significantly (b) while the LVET I did not change. STI correlation was significant and improved further when the QS2 (b) was corrected by subtracting from it the QRS prolongation (b) in msec. All 7 pts with a PEP/LVET ratio (b) greater than 0.65 had an (a) ratio greater than 0.42 (normal limits for our laboratory), sensitivity 100%. Six of 7 patients with a PEP/LVET (b) less than 0.65 had an (a) ratio less than 0.42 (specificity 87.5%). For the individual patient with LBBB his STI can be quite accurately assessed by subtracting from his QS2 (b) the prolongation of the QRS (b) greater than 80 msec the length of the normal QRS duration. The above data were prospectively evaluated in 10 pts to whom intermittent right ventricular pacing was applied. We found that the correction of the QS2 interval for QRS prolongation permitted a very reliable calculation of the STI.

A study of the factors influencing the appearance of the Ashman phenomenon.

The electrocardiograms of 29 patients with atrial fibrillation and aberrancy (Ashman phenomenon) were studied. The length of the cycles manifesting aberrancy (R-RA) varied from 270 to 520 msec (mean 372 +/- 55). It correlated negatively with the heart rate (r-0.899, p less than 0.001) and for equal heart rates in separate persons it varied with the length of the preceding R-R cycle (p less than 0.01). Above a critical R-RA length of 520 msec and outside an R-R/R-RA ratio range of 1.5-3.6 aberrancy is never observed: this finding is important for the differentiation of aberrancy from ventricular ectopy.