Use of perampanel oral suspension for the treatment of refractory and super-refractory status epilepticus.

INTRODUCTION: Status epilepticus (SE) is a medical emergency associated with a significant risk of disability and death. The treatment of SE follows a step-wise approach, with limited data on ideal antiseizure medications (ASMs) for refractory and super refractory SE (RSE/SRSE). Perampanel (PER), an AMPA receptor antagonist, has shown promise in animal models but still has limited data in humans. This study tried to evaluate optimal dosage and safety of PER in RSE and SRSE patients. MATERIALS AND METHODS: We retrospectively analysed 17 adult patients with RSE (1) or SRSE (16) treated with PER. Demographic and clinical data, including EEG patterns, ASMs administered, PER dosages, and PER plasma concentrations, were collected. For patients receiving a 24 mg PER loading dose (full dose group), the following treatment regimen was applied: 24 mg per day for 48 h following by 16 mg per day. The response to PER was assessed based on electroencephalographic (EEG) improvement from high to low epileptiform activity or from low to the absence of epileptiform activities. Safety was evaluated monitoring hepatic and renal function. RESULTS: A response rate of 58.82 % was observed, with significantly higher responses in the full dose group (81.82 %) compared to those receiving PER doses below 24 mg (low dose group) (16.67 %) (p-value = 0.004; OR 0.044, 95 % CI 0.003 to 0.621, p = 0.021). No other clinical factors significantly influenced treatment response. Hepatic enzymes become elevated in most patients (70.59 %) but spontaneously decreased. DISCUSSION: Our findings suggest that a 24 mg PER dose administered for 48 h may be more effective in managing RSE and SRSE compared to doses below 24 mg, potentially due to pharmacokinetic factors. CONCLUSION: More robust data on PER in RSE and SRSE, including standardized dosing procedures and plasma level monitoring are needed. PER's potential benefits should be explored further, particularly in patients with RSE and SRSE.

Time course of ischemic and bleeding burden in consecutive patients undergoing transcatheter aortic valve replacement (FOCUS-ONE Registry).

BACKGROUND AND AIMS: Ischemic or bleeding events might occur after transcatheter aortic valve replacement (TAVR), with the potential to hamper clinical outcomes. This study aimed to characterize the average daily ischemic risks (ADIRs) and the average daily bleeding risks (ADBRs) over 1-year in all consecutive patients undergoing TAVR. METHODS: ADBR included all bleeding events according to VARC-2 definition, and ADIR included cardiovascular deaths, myocardial infarction and ischemic stroke. ADIRs and ADBRs were assessed within different timeframes post TAVR: acute (0-30 days), late (31-180 days), and very late (>181 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparison of ADIRs and ADBRs. Our analysis was performed in the overall cohort and according to antithrombotic strategy (LT-OAC vs No LT-OAC). RESULTS: Ischemic burden was higher than bleeding burden, independently from the indication to LT-OAC, and in all timeframes examined. In the overall population, ADIRs were three-fold ADBRs (0.0467 [95% CI, 0.0431-0.0506] vs 0.0179 [95% CI, 0.0174-0.0185]; p < 0.001*). While ADIR was significantly higher in the acute phase, ADBR was relatively stable in all timeframes analysed. Of note, in LT-OAC population, OAC + SAPT group showed lower ischemic risk and higher bleeding events compared with OAC alone (ADIR: 0.0447 [95% CI: 0.0417-0.0477] vs 0.0642 [95% CI: 0.0557-0.0728]; p < 0.001*, ADBR 0.0395 [95% CI: 0.0381-0.0409] vs 0.0147 [95% CI: 0.0138-0.0156]; p < 0.001*). CONCLUSIONS: In patients undergoing TAVR Average daily risk fluctuates over time. However, ADIRs overcome ADBRs in all timeframes, especially in the acute phase and regardless of antithrombotic strategy adopted.

Targeted association analysis identified japonica rice varieties achieving Na(+)/K (+) homeostasis without the allelic make-up of the salt tolerant indica variety Nona Bokra.

During the last decade, a large number of QTLs and candidate genes for rice tolerance to salinity have been reported. Using 124 SNP and 52 SSR markers, we targeted 14 QTLs and 65 candidate genes for association mapping within the European Rice Core collection (ERCC) comprising 180 japonica accessions. Significant differences in phenotypic response to salinity were observed. Nineteen distinct loci significantly associated with one or more phenotypic response traits were detected. Linkage disequilibrium between these loci was extremely low, indicating a random distribution of favourable alleles in the ERCC. Analysis of the function of these loci indicated that all major tolerance mechanisms were present in the ERCC although the useful level of expression of the different mechanisms was scattered among different accessions. Under moderate salinity stress some accessions achieved the same level of control of Na(+) concentration and Na(+)/K(+) equilibrium as the indica reference variety for salinity tolerance Nona Bokra, although without sharing the same alleles at several loci associated with Na(+) concentration. This suggests (a) differences between indica and japonica subspecies in the effect of QTLs and genes involved in salinity tolerance and (b) further potential for the improvement of tolerance to salinity above the tolerance level of Nona Bokra, provided the underlying mechanisms are complementary at the whole plant level. No accession carried all favourable alleles, or showed the best phenotypic responses for all traits measured. At least nine accessions were needed to assemble the favourable alleles and all the best phenotypic responses. An effective strategy for the accumulation of the favourable alleles would be marker-assisted population improvement.

Clinical impact and evolution of mitral regurgitation after TAVI using the new generation self-expandable valves.

BACKGROUND: Concomitant mitral regurgitation (MR) impaired prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). It has been suggested that the use of first generation self-expandable valve in patients with significant MR is associated with worse outcome as compared with balloon expandable valve. However, the impact of newer generation transcatheter devices on MR has not been investigated so far. We aim to assess the prognostic impact of MR in patients undergoing TAVI with the first-generation vs. the latest generation of self-expandable valves. METHODS: We analyzed 2964 consecutive patients who underwent TAVI. Patients were classified into 4 groups according to the degree of baseline MR and the generation of self expandable valve implanted. RESULTS: Of 1234 patients with moderate or severe MR, 817 were treated with first generation and 417 patients with second generation valves. Whereas, of 1730 patients with no or mild MR, 1130 were treated with first generation and 600 patients with second generation valves. Although, concomitant moderate-severe MR was found to be an independent predictor of mortality after TAVI, the use of newer generation self expandable valves was associated with higher survival rate at 1 year irrespective of the degree of preprocedural MR. At multivariable analysis the use of newer generation valve was associated with MR improvement throughout 1 year follow-up. CONCLUSION: Baseline moderate-severe MR is associated with an increase in mortality after TAVI. However, the degree of preprocedural MR doesn't impact survival when a second generation self expandable valve is used.

Materials characterization of explanted mechanical heart valves and comparison to patients' clinical data.

In the present study, twelve explanted mechanical heart valves (MHVs)with pyrolitic carbon tilting disc and 14 bileaflet MHVs were analyzed to investigate the effects of material properties on valve performance and patients' general health conditions. Optical and scanning electron microscopy was used to investigate material imperfections, wear patterns or damages to housing and occluder components. All analyzed tilting disc valves exhibited wear effects, particularly due to abrasion and impact to both disc and housing. Wear of pyrolitic carbon disc and housing did not influence their in vivo performance. In the bileaflet MHVs, breakaway of the pyrolitic carbon coating sometimes caused malfunctioning and required surgical retrieval of the valve. In all cases, occurrence of clinical symptoms was more likely when wear effects were located in critical areas. The study supports a correlation between the properties of the MHVs material and patients' symptoms.

Similarities of essential and spontaneous hypertension. Volume and number of blood cells.

Spontaneously hypertensive rats have long been used as an animal counterpart of human essential hypertension. The validation of this strain as a model rests mainly on the "clinical" similarity of the two syndromes, but it has scarcely been founded on numerical comparison of measurable parameters. We investigated three hematological indexes previously recognized to be altered in spontaneously hypertensive rats: the single-cell volume of erythrocytes, the single-cell volume of platelets, and the erythrocyte number. Erythrocyte volume was lower by 7%, platelet volume was higher by 12%, and erythrocyte count was higher by 22% in spontaneously hypertensive rats in comparison with Wistar-Kyoto controls. More unexpectedly, it was found that erythrocyte volume is lower by 2%, platelet volume is higher by 3%, and erythrocyte number is higher by 6% in essential hypertensive subjects when compared with normotensive healthy subjects. These results, combined with previously reported blood cell alterations in subjects and rats, reinforce the evidence of a biological similarity between essential and spontaneous hypertension.

Dietary sodium change in primary aldosteronism. Atrial natriuretic factor, hormonal, and vascular responses.

Atrial natriuretic factor (ANF) may be physiopathologically involved in several clinical conditions including human hypertension. However, few data are available regarding this putative hormone and its relationship to aldosterone, blood pressure, and vascular responsiveness to alpha-adrenergic receptor stimulation in primary aldosteronism, a volume-expanded, low-renin model of human hypertension. For this reason, the behavior of supine and upright plasma ANF as related to aldosterone, blood pressure, and forearm alpha-adrenergic sensitivity (plethysmographic technique) to intra-arterial norepinephrine infusion was studied in eight patients with primary aldosteronism (five with adenomas, three with hyperplasia) before and at the end of two sequential 1-week low (20 mmol/day) and high sodium (200 mmol/day) diet periods. Basal, predict ANF concentrations decreased and increased after low and high sodium intakes, respectively. Furthermore, highly significant postural ANF decrements after 1 hour of standing occurred with each diet, although they were lower after the low than after the high sodium diet. Plasma aldosterone, either supine or upright, was insensitive to dietary sodium manipulations, suggesting the absence of ANF-mediated control of aldosterone secretion in our patients. In spite of about twofold higher ANF concentrations during the high than during the low sodium diet, forearm vascular sensitivity to intra-arterial norepinephrine infusion did not change during the study. Furthermore, systemic arterial blood pressure rose to a highly significant extent after dietary sodium content was increased, thus casting doubt on a role for ANF as an endogenous long-term modulator of systemic blood pressure and peripheral alpha-adrenergic sensitivity in patients with primary aldosteronism.

Use of Fourier shape descriptors to improve the reproducibility of echographic measurements of arterial intima-media thickness.

BACKGROUND: A major source of error in the longitudinal assessment of the intima-media thickness (IMT) is the difficulty in retrieving the same echographic view of the vessel. OBJECTIVE: To present a method for increasing the reproducibility of IMT measurements by ultrasound in large arteries. METHOD: The Fourier descriptor is a well-known means of describing an object's shape. By means of the discrete Fourier transform (DFT), the shape was represented in a frequency domain; the computational advantages of the DFT then permitted a measure of unlikeness between different shapes (the 'distance' measure; DM) to be defined and used as a criterion for reproducing the contour. When the sonographer compared successive images of a complex vascular segment, like the carotid bifurcation, the identity of the echographic cut was deduced from the identity of the vessel's contour. The best match of the baseline image was the view that minimized the contour DM. RESULTS: Preliminary studies in the carotid artery bifurcations of eight subjects showed that the DM responds to systematic variations in the ultrasound interrogation angle and reveals minimal changes in transducer position. Duplicate scans of 12 subjects were performed by three sonographers with different strategies for acquisition of the same images: a low DM was associated with a low difference in pairs of IMT measurements. Data were classified into two groups (normal or borderline vessels with a pooled mean IMT of 0.62 mm and overtly thickened segments with a pooled mean IMT of 1.31 mm). When minimization of the DM was the criterion for the acquisition of replicate scans, the mean absolute difference of paired data for the mean IMT of the distal common carotid artery was 0.03 +/- 0.02 mm for the first group and 0.06 +/- 0.03 mm for the second group. This is a significant reduction in comparison with non-quantitative alternative criteria for image reproduction. For the maximum IMT of the same segments the mean absolute differences were 0.07 +/- 0.03 and 0.13 +/- 0.06 mm in the first and second groups, respectively. CONCLUSION: This method can be applied to the serial assessment of single atherosclerotic segments. The computational time is negligible. By reducing the scatter in sequential IMT data, longitudinal investigations (e.g. of the results of antihypertensive therapy) with shorter durations and smaller sample groups may be rendered feasible.

Topoisomerase I inhibitors combination chemotherapy in non-small cell lung cancer.

In the last years, the main topoisomerase I inhibitors (TP1-I) (i.e. topotecan and irinotecan) have been used in combination chemotherapy in non-small cell lung cancer. Several drugs (also alternative to cisplatin) have been used in combination with TP1-I, but to date the higher remission rate obtained with combinations is not translated into a more prolonged survival in comparison with TP1-I given alone. On the other hand, the toxicity of TP1-I combinations is greater than those of TP1-I used alone. The superior efficacy of combinations versus TP1-I used alone remains an open question. Furthermore, the best schedule for TP1-I has not been completely elucidated. Randomised studies are few (only two phase III trials) and only controlled studies will be able to clarify the best TP1-I combination regimen.

First successful Italian clinical experience with DeBakey VAD.

The growing number of patients waiting for heart transplantation more than tripled between 1989 and 1998. Various non-pulsatile mechanical circulatory support devices have been developed as bridge to heart transplantation in recent years. We report the first successful Italian clinical experience with an axial-flow pump, DeBakey VAD, in a patient supported as bridge to transplantation for 55 days.

Modified pericardial closure technique in patients with ventricular assist device.

The use of Gore-Tex (W.L. Gore & Assoc, Flagstaff, AZ) sheet for pericardial closure in patients with left ventricular assist device as a bridge to transplant allows easy dissection of epicardial adhesions and safe resternotomy at the moment of heart transplantation, with no complications or significant cost increase related to the Gore-Tex itself.

Aorto-atrial fistula through the septum in recurrent aortic dissection.

A case of aortic dissection (De Bakey type I) with a fistula to the right atrium through the interatrial septum, diagnosed by transthoracic and transesophageal echocardiography is reported. The patient presented with cardiac failure and a continuous murmur in the right second and third intercostal spaces. The patient underwent successful operative repair.

Regional sympathetic activity in pre-hypertensive phase of spontaneously hypertensive rats.

Imbalances in central and peripheral sympathetic nervous system (SNS) activity have been observed in essential and experimental hypertension. This study was carried out in order to evaluate SNS activity in two distinct tissue types of spontaneously hypertensive rats (SHR), compared to Wistar-Kyoto normotensive (WKY) rats, in the pre-hypertensive phase (4-5 weeks of age). Interstitial concentrations of norepinephrine (NE) and other catecholamines were measured by microdialysis in striated muscle, whose tone is controlled by baroreflexes, and in the subcutaneous adipose tissue where sympathetic output mainly controls metabolism. Two groups of SHR and WKY male rats were studied, aged 4-5 weeks, with a mean body weight of 92 and 86 g respectively. Systolic blood pressure (SBP, tail-cuff) values were 113 mm Hg (SD +/- 6.2) in SHR and 108 mm Hg (SD +/- 7.3) in WKY rats (p=0.28,t test). Two microdialysis probes were positioned in the subcutaneous fatty tissue and in the striated muscle of the parascapular region and perfused with Ringers' solution. The dialysate was collected every thirty minutes for 3 hours and analyzed in HPLC-ED to determine the content of NE and other catecholamines. Interstitial levels of NE were higher in SH than in WKY rats in both tissues. Mean NE values from subcutaneous adipose tissue in 4-5 week-old SHR were 1162 +/- 193 pg/ml compared to 496 + 188 pg/ml in WKY rats (p<0.001, t test). Muscle tissue NE levels in SHR were 1241 +/- 337 pg/ml vs. 521 +/- 138 pg/ml in WKY rats (p<0.001, t test). Plasma NE concentrations (279 +/- 61 pg/ml in SHR vs 246 + 69 pg/ml in WKY P = 0.65, t test) were not significantly different between the two strains at this young age. These findings suggest SNS hyperactivity in young SHR, though still normotensive, possibly dissociated from regional components of regulation (baroreceptor control in striated muscle and metabolic control in subcutaneous adipose tissue).

Intracellular free [Ca2+] in circulating lymphocytes of spontaneously hypertensive rats.

In the light of previous reports suggesting a common abnormality of Ca handling in most tissues of hypertensive humans and rats, we applied a novel technique using the fluorescent probe Quin 2 for measurement of cytosolic free Ca2+ in lymphocytes of spontaneously hypertensive rats (SHR). (Ca2+)i is increased in SHR (122.1 +/- 7.4 nM) versus normotensive Wistar-Kyoto (WKY) control rats (81.1 +/- 6.3 nM) Membrane exchange, as challenged by varying the extracellular Ca concentration over a 10(5)-fold range proved to be relatively unimportant in regulating (Ca2+)i and did not significantly affect the difference between SHR and WKY. Catecholamines and ouabain had no appreciable effect on (Ca2+)i. The mechanisms of increased (Ca2+)i in SHR lymphocytes remain to be fully elucidated.

Papillary muscle rupture and pericardial injuries after blunt chest trauma.

Non-penetrating cardiac trauma resulting in mitral valve rupture is uncommon, requiring a high degree of suspicion for diagnosis. Sudden and severe mitral regurgitation, unless surgically corrected rapidly lead to congestive heart failure and death. We report a patient with traumatic rupture of the antero-lateral papillary muscle of the mitral valve and pericardial injury, after a lateral blunt chest trauma, who successfully underwent emergency mitral valve replacement.

The kinetics of aminosidine in renal patients with different degrees of renal failure.

The plasma concentration and urinary excretion after a single 500 mg dose of Aminosidine have been studied in 12 patients with different degrees of renal failure and 4 normal subjects. In normal subjects the plasma half-life is 2.47 hr; in patients with creatinine clearance (Ccr) of 30-60 ml/min, its 6.7 hrs.; in patients with Ccr of 10-30 ml/min, it is 16.7hrs.; in patients with Ccr less than 10 ml/min, it is 36.6 hrs. A dose of 0.5 g of Aminosidine should be given to normal subjects every 12 hr. When renal function is reduced, the interval (in hr) between doses should be the following: Ccr 60-40 ml/min: 19-28;Ccr 40-30 ml/min; 28-35; Ccr 30-20 ml/min: 35-47; Ccr 20-10 ml/min: 47; Ccr less than 10 ml/min: 76.

Localized management of sinus floor with simultaneous implant placement: a clinical report.

Localized management of sinus floor (LMSF) achieves implant placement and sinus lifting simultaneously. LMSF is a further application of the principles of the edentulous ridge expansion (ERE) technique. It comprises the dissection of a partial-thickness flap, the buccal expansion of the residual alveolar bone, and the fracture and elevation of the sinus floor with simultaneous implant placement. Three hundred three patients were treated with 499 implants placed using the LMSF between April 1988 and December 1993. The selected patients, who showed no signs of sinus pathology, exhibited insufficient vertical alveolar bone dimensions for the placement of dental implants with the traditional technique. The minimal residual alveolar bone height was between 5 and 7 mm. Based on the criteria established by Albrektsson and his coworkers in 1986, the success rate of the 499 implants placed with the LMSF was 97.5%.

Mechanical circulatory support in severe heart failure: single-center experience.

Ventricular assist devices (VADs) have become important therapeutic tools to treat patients with end-stage cardiac failure. VADs are an essential component of transplantation programs as they successfully bridge individuals who would otherwise die. Recently left ventricular VAD (LVAD) therapy has been proposed as alternative to heart transplantation (HTx) for patients who are not transplant candidates. Other indications have now expanded into areas such as postcardiotomy failure, acute myocarditis, and acute massive myocardial infarction. From 1988 to May 2003, 80 patients received left or biventricular mechanical circulatory support including 78 as a bridge to and two as an alternative to HT. All patients survived the operation. Mean duration of VAD support was 77 +/- 150 days. Fifty-one points (63.8%) underwent heart transplantation; 3 (3.8%) recovered and were weaned from VADs. Major bleeding episodes occurred in 11 patients (13.8%) and major neurologic events occurred in 8 (10%). Sixteen patients (20%) were discharged home while waiting for HTx. Twenty-two patients (27.5%) died on VAD. In conclusion, VAD therapy proved effective in bridging patients with end-stage heart failure to HTx. While on LVAD support patients who were assisted with implantable wearable devices could be discharged at home, improving their quality of life.

Impella recover 100 microaxial left ventricular assist device: the Niguarda experience.

BACKGROUND: The Impella Recover 100 (IR100) is an intravascular microaxial blood pump used to support blood circulation for a maximum of 7 days in cases of reduced left ventricular function, for example in postcardiotomy low output syndrome or in cardiogenic shock after acute myocardial infarction. MATERIALS AND METHODS: We supported five patients with the IR100. The mean age, cardiac index (CI), and ejection fraction (EF) of our population were 42 years, 1.83 L/min/m(2), and 20%, respectively. Two patients (group A) with ischemic dilated cardiomyopathy were bridged to heart transplant. Two patients (group B) with fulminan myocarditis and septic shock were bridged to recovery. One patient, with severe valvular cardiomyopathy who underwent aortic valve replacement and mitral valve annuloplasty, was supported to weaning from ECC. RESULTS: Mean support time was 9.8 +/- 2.3 days. Only one acute myocarditis patient died from a severe vasoplegic syndrome despite maximal inotropic and vasoactive support. Both group A patients were successfully transplanted. Among group B, the second patient resolved the septic status and was slowly weaned from the device and discharged home with moderate improvement of LV function (EF = 40%). Patient C was weaned from the IR100 and electively placed on the heart transplant recipient list. CONCLUSIONS: IR100 is a device that in our experience can be utilized for various indications for short-term support. In compromised patients where a traditional LVAD is contraindicated, the IR100 showed good results, for it is minimally invasive and does not need ECC or systemic anticoagulation.