The Use of Episodic Memory Tests for Screening in Clinical Trials for Early Alzheimer's Disease: A Comparison of the Free and Cued Selective Reminding Test (FCSRT) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

BACKGROUND: Screening procedures for early Alzheimer's disease (AD) trials seek to efficiently identify participants who fulfill clinical and biomarker criteria for AD and enrich for those most likely to experience significant clinical progression during the study. Episodic memory performance is often assessed in screening, but the utility of different memory tests for optimizing screening efficiency and/or rates of clinical progression remains uncertain. OBJECTIVES: Cross-study comparisons of the effects of inclusion criteria based on performance on the Free and Cued Selective Reminding Test (FCSRT) or the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) on screen-failure rates for episodic memory and ß-amyloid (Aß) positivity (by CSF or PET) and on subsequent rates of clinical disease progression in randomized participants across three clinical trials in early (prodromal-to-mild) AD. DESIGN: Secondary analyses of cross-sectional and longitudinal clinical trial data. SETTING: Multi-center international clinical trials. PARTICIPANTS: Individuals with prodromal-to-mild AD screened and/or randomized in clinical trials for crenezumab (CREAD, CREAD2) or semorinemab (Tauriel). Cross-sectional analyses of screening data for episodic memory impairment included participants from CREAD2 (n=2897) and Tauriel (n=887) and for Aß positivity included participants from CREAD (n=1138), CREAD2 (n=1119), and Tauriel (n=483). Longitudinal analyses of rates of clinical progression included participants from CREAD (n=779), CREAD2 (n=773), and Tauriel (n=331). MEASUREMENTS: Cross-sectional analyses examined eligibility rates per cutoffs defined for the FCSRT (CREAD, CREAD2) or RBANS (Tauriel) and per Aß positivity using CSF and/or PET biomarkers. Longitudinal analyses examined rates of clinical progression on the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the 13-item version of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), and Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL). RESULTS: Lower rates of study eligibility per episodic memory criteria were seen with the FCSRT (CREAD2) relative to the RBANS (Tauriel), but similar rates of eligibility per Aß positivity criteria were seen amongst participants with episodic memory impairment per the cutoffs used on either assessment. Similar rates of clinical decline over 18 months on the CDR-SB, ADAS-Cog13, and ADCS-ADL were observed in study populations enriched using the FCSRT (CREAD, CREAD2) or the RBANS (Tauriel). CONCLUSIONS: Cutoffs for episodic memory impairment on the FCSRT used in the CREAD and CREAD2 studies are more stringent than those on the RBANS used in the Tauriel study, resulting in lower rates of eligibility. However, given that study enrichment with either test yields similar rates of Aß positivity and clinical progression, considerations beyond these factors may drive the decision of which assessment to use for screening in early AD clinical trials.

Cassava starch fermentation wastewater: characterization and preliminary toxicological studies.

Cassava starch fermentation wastewater is an industrial residue composed mainly of lactic acid bacteria with predominance of the genera Lactobacillus, and organic acids. To evaluate the safety of this residue for possible production of probiotic beverages, acute in mice and sub-chronic (28-day repeated dose) toxicity studies in rats were carried. The administration of a single dose of 5 g/kg/body weight did not produce mortality in mice. Rats treated with water containing 0 (control), 25%, 50%, and 100% of the residue for 28 days, did not present alterations in behaviour or in food and water consumption. There were no treatment-related changes of toxicological significance in the relative weight of the organs neither in the haematological nor in the biochemical parameters. Histopathologic alterations observed in the small intestine did not seem to be associated with the treatment.

[General balanced anesthesia and propofol in ablation of the arterioventricular junction]. / Anestesia generale bilanciata e propofol nella folgorazione della giunzione atrio-ventricolare.

The Authors compare the results of general balanced anaesthesia and propofol in the anaesthetic management of closed-chest ablation of A-V junction. The best results were obtained with propofol because of the lower incidence of cardiovascular complications. Therefore propofol is a suitable agent in the anaesthetic management of closed-chest ablation of the A-V junction.

[Propofol in single bolus for treatment of elevated intracranial hypertension]. / Il propofol in singolo bolo nel trattamento della ipertensione endocranica.

Eleven patients with intracranial pressure (ICP) above 20 mmHg despite hyperventilation and neurosedation were treated with a bolus of propofol (1.5 mg/kg) i.v. At baseline and 1-2-5-10-15-30-45 minutes after propofol administration we recorded the values of PIC, systolic arterial pressure (SAP) and mean arterial pressure (MAP), heart rate (HR) and cerebral perfusion pressure (CPP), calculated as MAP less PIC. In the first ten minutes after propofol we observed a statistically significant (p less than 0.05) decrease of ICP and SAP. MAP decreased in the first five minutes only. Consequently HR increased at the same time. CPP decreased in the first two minutes after administration of the drug, but without statistical evidence. We conclude that propofol, in our opinion, can be used to treat intracranial hypertension but the hemodynamic effects in hypovolemic patients must be taken into consideration.

Intra-operative monitoring by means of somatosensory evoked potentials during cerebral aneurysms surgery.

During cerebral aneurysms surgery, brain tissue may suffer for global or local ischemia due to deliberate hypotension and surgical manoeuvres. Somatosensory evoked potentials (SEPs) can detect functional derangements consequent to hypoxia, before a permanent brain damage is produced. Forty two patients, undergoing cerebral aneurysms surgery for treatment of SAH, were evaluated intraoperatively with SEP recordings. It has been stressed that no permanent neurological damage is to be expected if the absolute value of Central Conduction Time (CCT) does not exceed 9.5 ms for 10 min at least and the cortical waves are visible throughout the whole procedure. SEP changes are strictly related with MAP decrease and surgical handlings.

[Anesthesiologic problems in transluminal balloon dilatation of esophageal stenosis in children]. / Problematiche anestesiologiche nella dilatazione delle stenosi esofagee con sonda a palloncino nei bambini.

The authors report their anesthesiological experience in 88 cases of transluminal balloon dilatation of esophageal strictures in children. The most serious problems are caused by the need to repeat the dilatation process (up to a maximum of 24 times in one patient) and to the risk of extrinsic mechanical compression of the trachea with consequent transient anoxia. Good sedation was achieved using premedication with haloperidol and diazepam, but was not sufficient to avoid the child's anxiety on entering the operating theatre. Anesthesia using ketamine plus fentanyl, combined with tracheal intubation gave good results in almost all cases, but marked bradycardia was observed in several patients during balloon dilatation. In conclusion, although the technique itself is simple to perform, very careful anesthesia is required to avoid the risk of serious intraoperative complications.

[Transcatheter fulguration of the atrioventricular junction in supraventricular hyperkinetic arrhythmia. Immediate and long-term results]. / Folgorazione transcatetere della giunzione atrio-ventricolare nelle aritmie ipercinetiche sopraventricolari. Risultati immediati e a distanza.

Transcatheter direct-current ablation of the atrio-ventricular junction is a recently developed technique in the treatment of medically refractory supraventricular tachycardia. Twenty patients underwent this procedure between July 1987 and May 1989 and were followed-up for a mean period of 8.3 +/- 6 months (range 1-23). Indication for ablation included atrial flutter in 4 patients, atrial fibrillation in 8, atrial tachycardia in 1, atrio-ventricular nodal re-entrant tachycardia in 4, atrioventricular re-entrant tachycardia (concealed pathway) in 2, permanent junctional reciprocating tachycardia in 1. These arrhythmias were resistant to a mean of 3.3 +/- 1.7 antiarrhythmic drugs. A mean of 1.4 +/- 0.59 (range 1-3) electrical shocks, with a mean energy of 285 +/- 135J (range 200-700), were delivered during 1-2 sessions. In all patients a persistent complete atrio-ventricular block was achieved. Immediate complications included transient hypotension in 2 pts, acute pulmonary edema in 1, premature ventricular complexes in 4, non sustained ventricular tachycardia in 4, sustained ventricular tachycardia in 1. Late complications included thrombophlebitis of the right femoral vein in 2 pts; one of them died suddenly as a result of massive pulmonary embolism 10 days after the procedure. Follow-up evaluation reveals chronic complete atrio-ventricular block in all patients. Symptoms related to pre-existing arrhythmia are absent in all pts and none of them is currently taking antiarrhythmic drugs. Two patients with DDD pacing had pacemaker mediated re-entrant tachycardia and 1 patient with VVIR pacing developed a pacemaker syndrome. This experience confirms that transcatheter fulguration of atrio-ventricular junction is an effective technique. However, possible severe complications related to the procedure suggest this approach be restricted to patients with very symptomatic and drug-refractory supraventricular tachyarrhythmias.

[Value of serial electropharmacologic tests in the treatment of sustained ventricular arrhythmias]. / Valore dei tests elettrofarmacologici seriati nel trattamento delle tachiaritmie ventricolari sostenute.

The value of electropharmacological testing in patients (pts) with sustained ventricular tachyarrhythmias was studied in 46 consecutive pts (24 with sustained ventricular tachycardia (SVT) and 22 with cardiac arrest due to a ventricular tachyarrhythmia. Forty-two pts underwent a baseline electrophysiological study. The ventricular stimulation protocol included up to 3 extrastimuli during spontaneous rhythm and during paced ventricular rhythm at 100/min, 130/min, 160/min and brief bursts pacing at 2 ventricular sites. Ventricular tachycardia was induced in 37/42 pts (88%) (sustained in 32 pts and non sustained in 5 pts). Twenty nine pts underwent 79 trials of different drug regimens (mean 2.72 per pt, range 1-8). A totally successful drug regimen was found in 15/29 pts (51.7%) and a partially successful drug regimen in 11/29 pts (37.9%). Twenty-three pts were discharged on a drug regimen successful during serial electropharmacological testing (Group I) and 23 pts were discharged on an empiric drug regimen (Group II). Each pt was followed-up for a mean period of 15 months (range 1-74). Group I pts had fewer arrhythmia recurrence (SVT and/or sudden death) than Group II pts (2/23 vs 13/23 p less than 0.01). In conclusion electropharmacological testing is an useful tool in the therapy of pts with sustained ventricular tachyarrhythmias.

[Deep hypothermia and cardiocirculatory arrest with the technic of central cooling in patients with simple transposition of the great arteries]. / L'ipotermia profonda e l'arresto cardiocircolatorio con la tecnica del raffreddamento centrale in pazienti affetti da TGA semplice.

The deep hypothermia and cardiocirculatory arrest are employed mainly for two reasons; to reduce as much as possible the extra corporeal circulation time in patients more suitable to present the deleterious effects of the by-pass circulation, and to have surgical field completely free from the blood, making easier some surgical procedures. In the classic description of Hykasa the deep hypothermia necessary to have a safe cardiocirculatory arrest is obtained by means of surface cooling and an extracorporeal heat exchanger. In our experience deep hypothermia and cardiocirculatory arrest were achieved only by means of core cooling technique; 64 patients with TGA weighing less than 10 kg were operated upon by this method with a mortality rate of 3.1%. The most important mortality risk factors were associated to the low weight of the patients and to the age. The major criticism against core cooling is represented by the thought that this type of cooling can impair cerebral function. In 2 patients we had neurological complications but were unrelated to the technique. We conclude that, when is necessary to perform a cardiocirculatory arrest, the core cooling deep hypothermia is a good, simple and useful technique, with a low danger of neurological complications.