Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome.

BACKGROUND: The vasoconstrictor terlipressin is used for type 1 hepatorenal syndrome (HRS-1) in many parts of the world and is part of the clinical practice guidelines in Europe. METHODS: We conducted a phase 3 trial to confirm the efficacy and safety of terlipressin plus albumin in adults with HRS-1. The patients were randomly assigned in a 2:1 ratio to receive terlipressin or placebo for up to 14 days; in both groups, concomitant use of albumin was strongly recommended. The primary end point was verified reversal of HRS, defined as two consecutive serum creatinine measurements of 1.5 mg per deciliter or less at least 2 hours apart and survival without renal-replacement therapy for at least 10 days after the completion of treatment. Four prespecified secondary end points were analyzed with the Hochberg procedure to account for multiple comparisons. RESULTS: A total of 300 patients underwent randomization - 199 were assigned to the terlipressin group and 101 to the placebo group. Verified reversal of HRS was reported in 63 patients (32%) in the terlipressin group and 17 patients (17%) in the placebo group (P = 0.006). With respect to the prespecified secondary end points, HRS reversal, defined as any serum creatinine level of 1.5 mg per deciliter or less during the first 14 days, was reported in 78 patients (39%) in the terlipressin group and 18 (18%) in the placebo group (P<0.001); HRS reversal without renal-replacement therapy by day 30, in 68 (34%) and 17 (17%), respectively (P = 0.001); HRS reversal among patients with systemic inflammatory response syndrome (84 patients in the terlipressin group and 48 patients in the placebo group), in 31 (37%) and 3 (6%), respectively (P<0.001); and verified reversal of HRS without recurrence by day 30, in 52 (26%) and 17 (17%), respectively (P = 0.08). At day 90, liver transplantations had been performed in 46 patients (23%) in the terlipressin group and 29 patients (29%) in the placebo group, and death occurred in 101 (51%) and 45 (45%), respectively. More adverse events, including abdominal pain, nausea, diarrhea, and respiratory failure, occurred with terlipressin than with placebo. Death within 90 days due to respiratory disorders occurred in 22 patients (11%) in the terlipressin group and 2 patients (2%) in the placebo group. CONCLUSIONS: In this trial involving adults with cirrhosis and HRS-1, terlipressin was more effective than placebo in improving renal function but was associated with serious adverse events, including respiratory failure. (Funded by Mallinckrodt Pharmaceuticals; CONFIRM ClinicalTrials.gov number, NCT02770716.).

Decreased need for RRT in liver transplant recipients after pretransplant treatment of hepatorenal syndrome-type 1 with terlipressin.

Hepatorenal syndrome-acute kidney injury (HRS-AKI), a serious complication of decompensated cirrhosis, has limited therapeutic options and significant morbidity and mortality. Terlipressin improves renal function in some patients with HRS-1, while liver transplantation (LT) is a curative treatment for advanced chronic liver disease. Renal failure post-LT requiring renal replacement therapy (RRT) is a major risk factor for graft and patient survival. A post hoc analysis with a 12-month follow-up of LT recipients from a placebo-controlled trial of terlipressin (CONFIRM; NCT02770716) was conducted to evaluate the need for RRT and overall survival. Patients with HRS-1 were treated with terlipressin plus albumin or placebo plus albumin for up to 14 days. RRT was defined as any type of procedure that replaced kidney function. Outcomes compared between groups included the incidence of HRS-1 reversal, the need for RRT (pretransplant and posttransplant), and overall survival. Of the 300 patients in CONFIRM (terlipressin n = 199; placebo, n = 101), 70 (23%) underwent LT alone (terlipressin, n = 43; placebo, n = 27) and 5 had simultaneous liver-kidney transplant (terlipressin, n = 3, placebo, n = 2). The rate of HRS reversal was significantly higher in the terlipressin group compared with the placebo group (37%, n = 16 vs. 15%, n = 4; p = 0.033). The pretransplant need for RRT was significantly lower among those who received terlipressin ( p = 0.007). The posttransplant need for RRT, at 12 months, was significantly lower among those patients who received terlipressin and were alive at Day 365, compared to placebo ( p = 0.009). Pretransplant treatment with terlipressin plus albumin in patients with HRS-1 decreased the need for RRT pretransplant and posttransplant.

Suspected neurodevelopmental disorders in adult patients of memory clinics: Start at the beginning. GREDEV proposals for clinical practice.

Neurodevelopmental disorders are frequent but underestimated in adult populations, even though the cognitive profile of those affected remains atypical throughout adulthood and the disorders can cause significant impairment in activities of daily living. Retrospective diagnosis in this population is challenging. In this article, the GREDEV (working group for the assessment of neurodevelopmental disorders in adults) proposes a brief screening questionnaire for patients with suspected neurodevelopmental disorders, a checklist to facilitate taking the patient history, a list of self-administered questionnaires, and the different key steps of diagnosing neurodevelopmental disorders in adults.

Preoperative portal vein or portal and hepatic vein embolization: DRAGON collaborative group analysis.

BACKGROUND: The extent of liver resection for tumours is limited by the expected functional reserve of the future liver remnant (FRL), so hypertrophy may be induced by portal vein embolization (PVE), taking 6 weeks or longer for growth. This study assessed the hypothesis that simultaneous embolization of portal and hepatic veins (PVE/HVE) accelerates hypertrophy and improves resectability. METHODS: All centres of the international DRAGON trials study collaborative were asked to provide data on patients who had PVE/HVE or PVE on 2016-2019 (more than 5 PVE/HVE procedures was a requirement). Liver volumetry was performed using OsiriX MD software. Multivariable analysis was performed for the endpoints of resectability rate, FLR hypertrophy and major complications using receiver operating characteristic (ROC) statistics, regression, and Kaplan-Meier analysis. RESULTS: In total, 39 patients had undergone PVE/HVE and 160 had PVE alone. The PVE/HVE group had better hypertrophy than the PVE group (59 versus 48 per cent respectively; P = 0.020) and resectability (90 versus 68 per cent; P = 0.007). Major complications (26 versus 34 per cent; P = 0.550) and 90-day mortality (3 versus 16 per cent respectively, P = 0.065) were comparable. Multivariable analysis confirmed that these effects were independent of confounders. CONCLUSION: PVE/HVE achieved better FLR hypertrophy and resectability than PVE in this collaborative experience.

Natural nanomorphous Ni/NiO magnetic multilayers: structure and magnetism of the high-Ar pressure series.

Natural nanomorphous Ni/NiO multilayers have exhibited interesting magnetic properties, such as an unusual positive surface anisotropy and perpendicular magnetic anisotropy. Most attention has been paid to multilayers prepared by radio frequency magnetron sputtering under relatively low (3 x 10(-3) mbar) Ar pressure. Here we report on the correlation between structural and magnetic properties for a new series of multilayers, prepared under relatively high (3 x 10(-2) mbar) Ar pressure. The crystalline Ni individual layer thickness ranges between 5-8 nm. The amorphous NiO layer thickness is constant, about 1.1 nm thick. X-ray reflectivity showed that in some of the multilayers the high-order Bragg peaks become broader and diminish quickly. Cross-section transmission electron microscopy reveals that this occurs because the first bilayers are formed in accordance to the growth conditions, while the ones near the top are vanished. Despite the deterioration of the interface quality, all samples show tendency for perpendicular magnetic anisotropy even for large bilayer thickness of about 9 nm. Similar tendency is observed even by a 330 nm thick non-multilayered Ni film grown under the same conditions. This observation reveals the important role of strain and magnetoelastic anisotropy as a source of perpendicular magnetic anisotropy in the Ni/NiO multilayers.

Exploration of verbal and non-verbal semantic knowledge and autobiographical memories starting from popular songs in Alzheimer's disease.

BACKGROUND: In mild Alzheimer's disease (AD), a deficit in episodic memory, particularly autobiographical memory, is clearly established. Several recent studies have also shown impaired semantic memory from the onset of the disease. Musical memory capacities may be especially preserved and listening to music might encourage autobiographical recall. The aim of this study was to explore recall of popular songs in AD. METHODS: We tested 12 patients with mild AD and 12 control subjects. We created a tool made up of old French popular songs: POP 10. This tool is a questionnaire composed of several subtests: melodic free recall, chorus free recall, melodic recognition, chorus recognition, semantic knowledge, autobiographical recall about the song, and autobiographical recall about the interpreter. RESULTS: We used non-parametric tests, the Mann-Whitney test (M-W), the Friedman test, and the a posteriori Wilcoxon test. Results of AD patients were rather similar to those of control participants for melodic memory. Concerning chorus memory (except recognition), semantic knowledge, and autobiographical recall about the interpreter, results of AD patients were significantly weaker than those of control participants. The most important result concerned autobiographical recall about the song: we found no impairment-related differences between the two groups. CONCLUSION: Our findings demonstrate that popular songs can be excellent stimuli for reminiscence, such as the ability to produce an autobiographical memory related to a song. Thus, we confirm that musical semantic knowledge associated with a song may be relatively preserved in the early stages of AD. This leads to new possibilities for cognitive stimulation.

Magnetic properties of textured CoPd nanocrystalline thin films.

CoPd is an important nanomaterial for magnetic and magneto-optic storage of information. In this work, CoPd alloyed thin films are grown via radio frequency magnetron sputtering on silicon, glass and polyimide substrates in a vacuum chamber with base pressure of 5 x 10(-8) mbar. The films are nanocrystalline with grain size between 4 and 80 nm. The magnetic properties of thoroughly textured CoPd alloyed thin films are compared to random polycrystalline ones. Magnetization hysteresis loops recorded under fields up to 12 kOe via a home-made magneto-optic Kerr-effect magnetometer reveal strong tendency for perpendicular magnetic anisotropy for the textured film. This anisotropy leads to the formation of well-defined stripe or labyrinthine ferromagnetic domains with the local spins oriented perpendicular to the film plane. The domain patterns and the hysteresis loops are simulated with micromagnetic calculations. Finally, an induced magnetic moment of 0.44 microB/atom is measured for Pd via X-ray magnetic circular dichroism and it is separated into spin and orbital magnetic moment contributions.

A cost-effective growth of SiO(x) thin films by reactive sputtering: photoluminescence tuning.

We present a new cost-effective method to produce substoichiometric SiO2 thin films by means of a simple sputter-coater operated at a base pressure of 1 x 10(-3) mbar. During sputtering air is introduced through a fine valve so that the sputtering gas is a mixture of air/Ar. High-resolution electron microscopy shows the formation of amorphous SiO(x) thin films for the as-deposited samples. The index x approaches 1 when the ratio of the partial pressure of air/Ar tends to 0.1. On the other hand, pure silica is formed when the ratio of the partial pressure of air/Ar approaches 0.5. The films in the as-deposited state show intense green-yellow photoluminescence. This fades away with short annealing under air at 950 degrees C. If on the other hand, prolonged annealing is performed under Argon atmosphere at 1000 degrees C, red-infrared photoluminescence is recorded due to the formation of Si nanocrystals embedded in SiO2. This simple method could be suitable for the production of thin SiO(x) films with embedded nanocrystals for optoelectronic or photovoltaic applications.

[Semantic knowledge in MCI and Alzheimer's disease: the French version of the New Words Interview]. / Connaissance des nouveaux mots de la langue française dans les troubles cognitifs légers de type amnésique et la maladie d'Alzheimer.

INTRODUCTION: The first decline in cognitive performance in Alzheimer's disease can appear when assessing semantic memory and can be detected long before the typical symptoms of Alzheimer's disease (AD), appearing with Mild Cognitive Impairment (MCI). PATIENTS AND METHOD: We propose the French version of the New Words Interview (fNWI) using 22 words to investigate semantic knowledge. The fNWI uses 11 words, which entered the French dictionary between 1996 and 1997, and 11 other words, which entered between 2006 and 2007. Words were paired according to orthographic and semantic criteria. Each word was associated with three sub-tests: free evocation, discrimination of the best definition from three propositions, and recognition of the accurate word context (two sentences were proposed). Regarding evocation, we distinguished conceptual definition, life situation examples or examples by use. We tested 12 patients with AD, 12 patients with amnesic Mild Cognitive Impairment (aMCI) and 72 controls (12 were paired with patients for age and education level). RESULTS: MCI patients and AD patients exhibited lower performance than controls in the three sub-tests and for the words of both periods. From the early stage of MCI, the patients were more impaired in the fNWI than in the context recognition task, and they failed to provide conceptual definitions of new words. Therefore, MCI patients suffer from semantic impairments before obvious clinical signs of AD. CONCLUSION: In patients with AD, performance worsened on all subtests, and more strongly in the definition discrimination task, which suggests the impairment of stored semantic knowledge. They provided fewer conceptual definitions and failed to use the strategy observed in MCI patients, who compensated for conceptual difficulties by providing examples.

Laryngeal paragangliomas - controversies in diagnosis and management.

Paragangliomas of the larynx are rare neuroendocrine tumors with difficulties in diagnosis and management. A review of the literature was carried out, using Medline and other available databases. Electronic links and related books were also included. The most reliable diagnostic imaging procedures are MRI, CT scan, and octreotide scintigraphy. Complete surgical excision with the maximal possible preservation of the laryngeal function is the treatment of choice. Many different surgical techniques have been reported but open surgical procedures seem to provide better results with lower recurrence rates, although endoscopic approaches and laser surgery have also been used with variable results. The use of long-acting depot octreotide has been used for the relief of symptoms and stabilization of the disease, especially in inoperable lesions with positive initial octreotide scintigraphy imaging. Detailed preoperative assessment and treatment planning in individual basis are essential in the management of these tumors.

[Semantic dementia: reflexions of a French working group for diagnostic criteria and constitution of a patient cohort]. / Démence sémantique: réflexions d'un groupe de travail pour des critères de diagnostic en français et la constitution d'une cohorte de patients.

Semantic dementia (SD) is a syndrome of progressive loss of semantic knowledge for objects and people. International criteria propose that SD be included in the frontotemporal lobar degeneration syndromes, with progressive non-fluent aphasia and frontotemporal dementia (FTD). However, several related syndromes have been defined that clinically and conceptually share both similarities and differences with SD: fluent progressive aphasia, progressive prosopagnosia, temporal variant of FTD. In order to establish a French consensus for the diagnosis and modalities of evaluation and follow-up of SD, a working group, composed of neurologists, neuropsychologists and speech-therapists, was established by the Groupe de réflexion sur les évaluations cognitives (GRECO). New criteria were elaborated, based on clinical, neuropsychological, and imaging data. They define typical and atypical forms of SD. A diagnosis of typical SD relies on an isolated and progressive loss of semantic knowledge, attested by a deficit of word comprehension and a deficit of objects and/or people identification, with imaging showing temporal atrophy and/or hypometabolism. SD is atypical if the deficit of semantic knowledge is present only within a single modality (verbal versus visual), or if non-semantic deficits (mild and not present at onset) and/or neurological signs, are associated with the semantic loss.

Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies.

BACKGROUND: The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available. AIM: To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1. METHODS: Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 µmol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1-2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days. RESULTS: The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between-group difference in SCr concentration of -53.0 µmol/L (P < 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin-treated patients. CONCLUSIONS: Terlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS-1. Terlipressin treatment is associated with improved renal function. (ClinicalTrials.gov identifier: OT-0401, NCT00089570; REVERSE, NCT01143246).

Thermally induced magnetic relaxation in square artificial spin ice.

The properties of natural and artificial assemblies of interacting elements, ranging from Quarks to Galaxies, are at the heart of Physics. The collective response and dynamics of such assemblies are dictated by the intrinsic dynamical properties of the building blocks, the nature of their interactions and topological constraints. Here we report on the relaxation dynamics of the magnetization of artificial assemblies of mesoscopic spins. In our model nano-magnetic system - square artificial spin ice - we are able to control the geometrical arrangement and interaction strength between the magnetically interacting building blocks by means of nano-lithography. Using time resolved magnetometry we show that the relaxation process can be described using the Kohlrausch law and that the extracted temperature dependent relaxation times of the assemblies follow the Vogel-Fulcher law. The results provide insight into the relaxation dynamics of mesoscopic nano-magnetic model systems, with adjustable energy and time scales, and demonstrates that these can serve as an ideal playground for the studies of collective dynamics and relaxations.

Influenza A among hospital personnel and patients. Implications for recognition, prevention, and control.

An outbreak of influenza A/Philippines H3N2 at a 1156-bed Veterans Administration Hospital involved 118 hospital personnel and 49 patients. Prospective surveillance methods that had been established within the hospital were not useful in identifying the number of involved individuals. Community indicators of influenza, which were reviewed retrospectively, would not have identified circulating influenza in this population. Control of the outbreak was accomplished using a creative approach that immunized over a third of the physician and nursing staff. This immunization program was successfully used in subsequent years to increase personnel compliance with the Immunization Practices Advisory Committee recommendations to annually immunize hospital personnel.

Risk factors for severe hypoglycaemia in type 2 diabetic patients admitted to hospital in Piraeus, Greece.

A 3-year study assessed the prevalence and causes of severe treatment-related hypoglycaemia in type 2 diabetes mellitus patients admitted to hospital in Piraeus. Out of the 2858 patients admitted, 207 (7.2%) had severe hypoglycaemia: 72 were being managed with insulin, 132 oral hypoglycaemic drugs and 3 combined insulin/oral drugs. Only 28.5% of patients were attending a diabetes clinic. The cause of the hypoglycaemic attack could be determined for 86.1% of cases; 30.8% were due to a missed meal. Interviews showed that education and level of knowledge about diabetes mellitus, and particularly hypoglycaemia symptoms, was inadequate. Logistic regression analysis showed that knowledge about diabetes mellitus correlated with educational status and with follow-up in a diabetes clinic.

Factors affecting haemoglobin synthesis in the mouse.

The effect of various forms of haematopoietic stress on haemoglobin production was studied in mice. During acute anaemia, recovery from polycythaemia or irradiation, there was an increase in the number of reticulocytes, and this was associated with a marked increase in the total protein synthesis. The specific activity in reticulocytes increased up to 20-fold from the normal. The maximum specific activity usually preceded the maximum peak of reticulocytosis. The proportion of minor haemoglobin increased by up to 30%, and there was a significant correlation between the specific activity in reticulocytes and the proportion of minor haemoglobin synthesized. These results indicate that erythropoietic stress results in the release of a new population of reticulocytes that are very active in protein synthesis as measured by markedly increased specific activity, and that this coincides with an increase in the proportion of minor haemoglobin produced.