RESUMEN
BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options. RNS60 is an immunomodulatory and neuroprotective investigational product that has shown efficacy in animal models of ALS and other neurodegenerative diseases. Its administration has been safe and well tolerated in ALS subjects in previous early phase trials. METHODS: This was a phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial. Participants diagnosed with definite, probable or probable laboratory-supported ALS were assigned to receive RNS60 or placebo administered for 24 weeks intravenously (375 ml) once a week and via nebulization (4 ml/day) on non-infusion days, followed by an additional 24 weeks off-treatment. The primary objective was to measure the effects of RNS60 treatment on selected biomarkers of inflammation and neurodegeneration in peripheral blood. Secondary objectives were to measure the effect of RNS60 on functional impairment (ALS Functional Rating Scale-Revised), a measure of self-sufficiency, respiratory function (forced vital capacity, FVC), quality of life (ALS Assessment Questionnaire-40, ALSAQ-40) and survival. Tolerability and safety were assessed. RESULTS: Seventy-four participants were assigned to RNS60 and 73 to placebo. Assessed biomarkers did not differ between arms. The mean rate of decline in FVC and the eating and drinking domain of ALSAQ-40 was slower in the RNS60 arm (FVC, difference 0.41 per week, standard error 0.16, p = 0.0101; ALSAQ-40, difference -0.19 per week, standard error 0.10, p = 0.0319). Adverse events were similar in the two arms. In a post hoc analysis, neurofilament light chain increased over time in bulbar onset placebo participants whilst remaining stable in those treated with RNS60. CONCLUSIONS: The positive effects of RNS60 on selected measures of respiratory and bulbar function warrant further investigation.
Asunto(s)
Esclerosis Amiotrófica Lateral , Enfermedades Neurodegenerativas , Humanos , Esclerosis Amiotrófica Lateral/diagnóstico , Calidad de Vida , Método Doble Ciego , Biomarcadores , Resultado del TratamientoRESUMEN
The appearance of emerging variants of SARS-CoV-2 carrying mutations into the spike protein has recently raised concern with respect to tracking their transmission and mitigating the impact in the evolving pandemic across countries. AY.4.2, a recently detected Delta variant sublineage, is considered a new variant under investigation (VUI) as it carries specific genetic signatures present in the spike protein, called Y145H and A222V. Here, using genomic epidemiology, we provide the first preliminary insight regarding the circulation of this emerging VUI in Italy.
Asunto(s)
COVID-19/epidemiología , Genoma Viral/genética , SARS-CoV-2/genética , Adolescente , Adulto , Anciano , COVID-19/virología , Niño , Femenino , Genómica , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Mutación , Filogenia , ARN Viral/genética , SARS-CoV-2/aislamiento & purificación , Adulto JovenRESUMEN
OBJECTIVE: We investigated the genetic diversity, molecular epidemiology and evolutionary dynamics of Staphylococcus aureus (SA) isolated from SLE patients by means of phylogenetic analysis. METHODS: Consecutive SLE patients (ACR 1997 criteria) were enrolled: clinical/laboratory data were collected and nasal swab for SA identification was performed. On the basis of the translation elongation factor (tuf) gene, a phylogenetic analysis was performed to investigate relationships and to assess significant clades. Selective pressure analysis was used to investigate the evolution of the SA tuf gene. The gene sequences from non-SLE individuals, downloaded from the GenBank database, were compared through phylogenetic analysis with the tuf gene from SLE patients. RESULTS: We enrolled 118 patients [M/F 10/108; median (interquartile range (IQR)) age 45.5 (13.2) years; median (IQR) disease duration 120 (144) months]. Twenty-four patients (20.3%) were SA carriers (SA+), three of them MRSA. SA+ SLE showed significantly higher SLEDAI-2k values [SA+: median (IQR) 2 (3.75); SA-: 0 (2); P = 0.04]. The phylogenetic analysis, restricted to 21 non-MRSA SA+, revealed a statistically supported larger clade (A, n = 17) and a smaller one (B, n = 4). Patients located in clade A showed a significantly higher prevalence of joint involvement (88.2%) in comparison with clade B (50.0%, P < 0.0001) and SA- (62.7%, P < 0.0001). Haematological manifestations were significantly more frequent in clade A (64.7%) compared with B (50.0%, P = 0.004). CONCLUSION: We suggest a possible role of SA nasal carriage status in SLE disease activity. Moreover, our findings support the hypothesis that bacterial genetic variants may be associated with specific disease features.
Asunto(s)
Genes Bacterianos/genética , Artropatías , Lupus Eritematoso Sistémico , Cavidad Nasal/microbiología , Infecciones Estafilocócicas , Staphylococcus aureus/genética , Correlación de Datos , Femenino , Variación Genética , Humanos , Inmunidad , Italia , Artropatías/diagnóstico , Artropatías/etiología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/microbiología , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Filogenia , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/inmunología , Evaluación de Síntomas/métodos , Evaluación de Síntomas/estadística & datos numéricosRESUMEN
Madariaga Virus (MADV) is an emergent Alphavirus of the eastern equine encephalitis virus (EEEV) strain complex causing epizootic epidemics. In this study the genetic diversity and the transmission dynamics of Madariaga virus has been investigated by Bayesian phylogenetics and phylodynamic analysis. A database of 32 sequences of MADV group structural polyprotein were downloaded from GenBank, aligned manually edited by Bioedit Software. ModelTest v. 3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data. Neighbor-joining tree was generated using MEGA7. The phylogenetic signal of the dataset was tested by the likelihood mapping analysis. The Bayesian phylogenetic tree was built using BEAST. Selective pressure analysis revealed one positive selection site. The phylogenetic trees showed two main clusters. In particular, Lineage II showed an epizootic infection in monkeys and Lineage III, including 2 main clusters (IIIa and IIIB), revealing an epizootic infection in humans in Haiti and an epizootic infection in humans in Venezuela during the 2016, respectively. The Bayesian maximum clade credibility tree and the time of the most common recent ancestor estimates, showed that the root of the tree dated back to the year 346 with the probable origin in Brazil. Gene flow analysis revealed viral exchanges between different neighbor countries of South America. In conclusion, Bayesian phylogenetic and phylodynamic represent useful tools to follow the transmission dynamic of emergent pathogens to prevent new epidemics spreading worldwide.
Asunto(s)
Virus de la Encefalitis Equina del Este/genética , Virus de la Encefalitis Equina del Este/patogenicidad , Encefalomielitis Equina/epidemiología , Encefalomielitis Equina/transmisión , Encefalomielitis Equina/virología , Filogenia , Infecciones por Alphavirus , Animales , Secuencia de Bases , Teorema de Bayes , Brasil , Virus de la Encefalitis Equina del Este/clasificación , Epidemias , Evolución Molecular , Flujo Génico , Variación Genética , Haití , Haplorrinos , Humanos , ARN Viral/genética , Alineación de Secuencia , América del Sur , VenezuelaRESUMEN
Procalcitonin and Mid-regional pro Adrenomedullin have been proposed for sepsis diagnosis, antibiotic therapy guidance and prognosis. A retrospective analysis of PCT and MR-proADM on 571 consecutive patients with sepsis diagnosis was performed. Median values were compared using the non-parametric Mann-Whitney's test. Receiver operating characteristic analysis was performed to define cutoff points for sepsis diagnosis. Pretest odds, posttest odds, and posttest probability have been calculated. Data were analyzed using Med-Calc 11.6.1.0 software. PCT resulted excellent in gram-negative, but less performant in gram-positive and fungal etiologies. MR-proADM values resulted homogenously distributed within the different microbial classes and increased significantly in septic shock. PCT highest PPV value was found to distinguish gram-negative from fungal sepsis and septic shock (>3. 57â¯ng/mL, PPV 0.96 andâ¯>â¯8.77â¯ng/mL, PPV 0.96, respectively). Good diagnostic accuracy was evidenced to discriminate gram-negative from gram-positive septic shock (>3.88â¯ng/mL PPV 0.89). Lower diagnostic accuracy was evidenced to discriminate gram-negative and gram-positive sepsis (>0.80â¯ng/mL, PPV 0.78) and gram-positive from fungal septic shock (>1.74â¯ng/mL PPV 0.75). The lowest PCT PPV (0.28) was found in gram-positive and fungal sepsis distinction. MR-proADM discriminating cut-offs were homogeneously distributed in Gram-negative and Gram-positive sepsis and were higher in septic shock, but not influenced by pathogen etiologies. MR-proADM cut-off valuesâ¯>â¯3.39â¯nmol/L in sepsis and >4.33â¯nmol/L in septic shock were associated with significant higher risk of 90-days mortality. In conclusion, PCT and MR-proADM combination represents an advantage for sepsis diagnosis and for 90-days mortality risk stratification.
Asunto(s)
Adrenomedulina/farmacología , Polipéptido alfa Relacionado con Calcitonina/farmacología , Precursores de Proteínas/farmacología , Sepsis/diagnóstico , Sepsis/tratamiento farmacológico , Choque Séptico/diagnóstico , Choque Séptico/tratamiento farmacológico , Adrenomedulina/uso terapéutico , Adulto , Anciano , Antibacterianos/farmacología , Bacterias/clasificación , Bacterias/patogenicidad , Combinación de Medicamentos , Femenino , Hongos/clasificación , Hongos/patogenicidad , Humanos , Italia , Masculino , Persona de Mediana Edad , Polipéptido alfa Relacionado con Calcitonina/uso terapéutico , Pronóstico , Precursores de Proteínas/uso terapéutico , Curva ROC , Estudios Retrospectivos , Sepsis/microbiología , Sepsis/mortalidad , Choque Séptico/microbiología , Choque Séptico/mortalidadRESUMEN
OBJECTIVES: Chronic neuropathies are a common cause of neurological disability worldwide. However, few reports have evaluated, in real life, the prevalence of the several conditions which can cause it. PATIENTS AND METHODS: The authors reviewed informatic database for outpatient office to confirm identification of chronic neuropathy in a 3-year interval period. RESULTS: Among the 100 selected patients with chronic neuropathies, almost one fifth (19%) remained idiopathic. The most common etiologies were diabetes (17%), dysimmune neuropathies (38%), and vitamin B12 deficiency (9%). In the "dysimmune neuropathies" group, we distinguished various etiologies, including dysimmune neuropathies associated or not with systemic autoimmune diseases (7 and 3%, respectively), chronic inflammatory polyneuropathy (CIDP) (8%), multifocal motor neuropathy (MMN) (3%), paraproteinemic (8%), celiac disease-related (6%), and paraneoplastic (3%) neuropathies. CONCLUSIONS: In this report from a single neurological center, treatable causes of chronic neuropathies, such as dysimmune neuropathies, including CIDP, and celiac disease-associated neuropathy, were common. These findings suggest the utility of routine screening with blood testing for dysimmune neuropathy and celiac disease for all patients presenting with idiopathic chronic polyneuropathy in whom primary diagnostic testings had failed to identify an etiology for the disease. SIGNIFICANCE: Our results indicate that patients with peripheral neuropathy could receive a benefit from being evaluated routinely in a specialized neurological center, as many of the conditions that were discovered represented potentially treatable causes of neuropathy.
Asunto(s)
Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedad Crónica , Complicaciones de la Diabetes/epidemiología , Femenino , Humanos , Enfermedades del Sistema Inmune/complicaciones , Enfermedades del Sistema Inmune/epidemiología , Masculino , Prevalencia , Estudios Retrospectivos , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/epidemiologíaRESUMEN
Pseudomonas aeruginosa causes a wide variety of nosocomial infections. In the study, phylogenetic, selective pressure analysis and homology modelling were applied to oprD efflux pump gene with the aim to characterize multi-drug resistant strains circulating in the nosocomial setting, their transmission dynamics and ongoing evolution. One hundred ninety-three consecutive inpatients with Pseudomonas aeruginosa infection were enrolled at the University Campus Bio-Medico of Rome, between January 2015 and December 2016. oprD gene was sequenced in 20 nosocomial multi-drug resistant P. aeruginosa strains. Phylogeographic, selective pressure, residue conservation analysis and homology modelling were performed. Clinical epidemiological data were extracted from patient medical records. Multi-drug resistant strains accounted for the 36% of total strains and were responsible of 20 cases of nosocomial infections. P. aeruginosa infections occurred prevalently in the West area, especially at the location IIIW and in the Geriatric ward. The time of the most recent common ancestor indicated that strains could have been introduced in the hospital since the end of the year 2009 with the most probable location in general surgery ward. By selective pressure analysis, 29 positions under diversifying selection have been identified and mapped onto the OprD model. Most of the observed residue substitutions are predicted to be destabilizing and some of them occurred in the Loops 2 and 3 that are involved in solute selection and carbapenem susceptibility. The molecular and evolutionary analysis of Multi-drug resistant strains circulating in the nosocomial setting may provide useful insights into the epidemiology and the mechanisms leading to resistance, contributing to infection control improvement.
Asunto(s)
Infección Hospitalaria/epidemiología , Farmacorresistencia Bacteriana Múltiple , Epidemiología Molecular , Filogenia , Porinas/genética , Pseudomonas aeruginosa/patogenicidad , Secuencia de Bases , Carbapenémicos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Hospitales , Humanos , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Porinas/química , Porinas/clasificación , Infecciones por Pseudomonas , Pseudomonas aeruginosa/efectos de los fármacos , Ciudad de Roma/epidemiología , Alineación de SecuenciaRESUMEN
The efficacy of standard rehabilitative therapy for improving upper limb functions after stroke is limited; thus, alternative strategies are needed. Vagus nerve stimulation (VNS) paired with rehabilitation is a promising approach, but the invasiveness of this technique limits its clinical application. Recently, a noninvasive method to stimulate vagus nerve has been developed. The aim of the present study was to explore whether noninvasive VNS combined with robotic rehabilitation can enhance upper limb functionality in chronic stroke. Safety and efficacy of this combination have been assessed within a proof-of-principle, double-blind, semirandomized, sham-controlled trial. Fourteen patients with either ischemic or haemorrhagic chronic stroke were randomized to robot-assisted therapy associated with real or sham VNS, delivered for 10 working days. Efficacy was evaluated by change in upper extremity Fugl-Meyer score. After intervention, there were no adverse events and Fugl-Meyer scores were significantly better in the real group compared to the sham group. Our pilot study confirms that VNS is feasible in stroke patients and can produce a slight clinical improvement in association to robotic rehabilitation. Compared to traditional stimulation, noninvasive VNS seems to be safer and more tolerable. Further studies are needed to confirm the efficacy of this innovative approach.
Asunto(s)
Rehabilitación de Accidente Cerebrovascular/métodos , Estimulación Eléctrica Transcutánea del Nervio/métodos , Extremidad Superior/fisiopatología , Estimulación del Nervio Vago/métodos , Adulto , Anciano , Presión Sanguínea , Método Doble Ciego , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Robótica , Resultado del TratamientoRESUMEN
Hepatitis B virus (HBV) is a DNA virus belonging to Hepadnaviridae family. Chronic infection with HBV is one major risk factor of hepatic disease. In Madagascar, former studies classified the country as part of high endemic area, as HBV prevalence can reach 23% in general population. However, this prevalence differs largely between urban and rural areas and is estimated to be, respectively, 5% and 26%. The aims of the present study were to describe the genetic diversity of HBV strains from different regions of Madagascar, and to describe the viral gene flow throughout the country by using phylogenetic analysis. This is the first large-scale molecular and phylogenetic study analyzing HBV sequences from 28 different Malagasy areas, never sampled in the past. In this study, the most prevalent genotype/sub-genotypes was E. Migration analysis showed a gene flow from zone 3 (rural) to zone 2 (suburban), and a greater gene flow from the middle part of Madagascar to the north than to the south. It is important to study the HBV infections in Madagascar and to monitor the potential spread of this viral strain inside this country. J. Med. Virol. 88:2138-2144, 2016. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Evolución Molecular , Flujo Génico , Variación Genética , Virus de la Hepatitis B/genética , Hepatitis B/epidemiología , Hepatitis B/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , ADN Viral/genética , Femenino , Genotipo , Humanos , Madagascar , Masculino , Persona de Mediana Edad , Filogenia , Reacción en Cadena de la Polimerasa , Prevalencia , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
There is great interest about the individual differences that influence the ability of dealing with risky decisions. In this light, an intriguing question is whether decision-making during risk is related to other cognitive abilities, especially executive functions. To investigate, in healthy subjects, the existence of a possible correlation between risk-taking and cognitive abilities, the balloon analogue risk task (BART) has been exploited to assess risk-taking propensity and the random number generation (RNG), to investigate cognitive functions. The risk-taking propensity is significantly correlated with the Cycling factor, a feature of RNG performance specifically related to the ability of updating and monitoring information. In particular, an excessive activity of monitoring (expressed by lower values of Cycling factor) is related to a more risk-averse behavior. An overlapping between the circuits involved in both RNG and BART, centered on the dorsolateral prefrontal cortex, could be the possible neurophysiological substrate for this correlation. This study suggests a relevant contribution of executive functions in risk-taking behavior. This could have relevant implications in neuroeconomics and neuropsychiatry of addiction and pathological gambling.
Asunto(s)
Toma de Decisiones/fisiología , Pruebas Neuropsicológicas , Asunción de Riesgos , Adulto , Femenino , Humanos , Masculino , Estadística como AsuntoRESUMEN
Niemann-Pick disease type C (NP-C) is an inherited sphingolipidosis characterized by progressive neurological deterioration and early mortality. The symptomatology and disease progression of NP-C are markedly affected by the age at onset of neurological manifestations, and categorization into early-infantile, late-infantile, juvenile, adolescent/adult neurological onset forms can aid evaluation of disease course and responses to therapy. Here, we review current information on the detection, diagnosis, monitoring and treatment of NP-C, with a focus on the adolescent/adult-onset form. A recent analysis indicated that the combined incidence of NP-C related to NPC1 gene mutations (NPC1) and NP-C related to NPC2 gene mutations (NPC2) is approximately 1 case in every 89 000 live births. In particular, late-onset phenotypes might well provide a greater contribution to the overall incidence than has previously been reported. Some neuropathological features in NP-C are held in common with other advanced age-onset diseases such as Alzheimer's disease. Visceral symptoms such as splenomegaly are frequently asymptomatic in patients with adolescent/adult-onset NP-C, and are only occasionally detected during routine ultrasound assessments. In contrast, most patients with adolescent/adult-onset exhibit some degree of slowly progressive, non-disease-specific movement disorders (e.g. cerebellar ataxia), and/or more pathognomonic neurological signs such as vertical supranuclear gaze palsy. An increasing number of adolescent/adult-onset cases have been reported following initial recognition of cognitive impairment and/or psychiatric signs. The recent development and implementation of new clinical screening tools (e.g. the NP-C suspicion index) and biomarkers (e.g. plasma oxysterols) should help identify patients who warrant further investigation and possible treatment.
Asunto(s)
Enfermedad de Niemann-Pick Tipo C/diagnóstico , Adolescente , Adulto , Humanos , Enfermedad de Niemann-Pick Tipo C/fisiopatología , Enfermedad de Niemann-Pick Tipo C/terapiaRESUMEN
There is great interest about the therapeutic potentialities of transcutaneous vagus nerve stimulation (tVNS) applied to neuropsychiatric disorders. However, the mechanisms of action of tVNS and its impact on cortical excitability are unclear. To this regard, transcranial magnetic stimulation (TMS) can be useful because it is able of evaluating non-invasively excitatory and inhibitory circuitry of the human cortex. Aim of the present study is to investigate the effects of tVNS on cerebral cortex excitability in healthy volunteers by means of TMS. Ten healthy subjects participated in this randomized placebo-controlled double-blind study. Real tVNS was administered at left external acoustic meatus, while sham stimulation was performed at left ear lobe, both of them for 60 min. We evaluated motor thresholds, motor evoked potential amplitude, recruitment curves, and short-interval intracortical inhibition (SICI) in right and left motor cortex. Such parameters were evaluated before and 60 min after the exposure to tVNS, for both the real and the sham stimulation. Cardiovascular parameters were monitored during the stimulation. A generalized linear model for repeated measures was implemented to assess the effect of time and stimulation type on cardiovascular and neurophysiological variables. SICI, a double-pulse TMS paradigm informative of GABA-A activity, was significantly increased in right motor cortex after real tVNS. Other neurophysiological parameters, as well as cardiovascular variables, remained unchanged. Our findings confirm that tVNS is a safe and effective way to stimulate vagus nerve and provide innovative data about the possible mechanisms of action that supports the potential therapeutic application of this technique.
Asunto(s)
Corteza Motora/fisiología , Estimulación del Nervio Vago/métodos , Adulto , Presión Sanguínea/fisiología , Método Doble Ciego , Oído , Potenciales Evocados Motores/fisiología , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Modelos Lineales , Masculino , Movimiento/fisiología , Inhibición Neural/fisiología , Factores de Tiempo , Estimulación Magnética Transcraneal/métodos , Estimulación del Nervio Vago/efectos adversosRESUMEN
A comparative evaluation of the turnaround time (TAT) of positive blood culture before and after matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) introduction in the laboratory routine was performed. A total of 643 positive blood cultures, of which 310 before and 333 after MALDI-TOF technique introduction, were collected. In the post MALDI-TOF period, blood culture median TAT decreased from 73.53 hours to 71.73 for Gram-positive, from 64.09 hours to 63.59 for Gram-negative and from 115.7 hours to 47.62 for anaerobes. MALDI-TOF significantly decreased the TAT of anaerobes, for which antimicrobial susceptibility test is not routinely performed. Furthermore, the major advantage of MALDI-TOF introduction was the decrease of the time for pathogen identification (TID) independently from the species with an improvement of 93% for Gram-positive, 86% for Gram-negative and 95% for anaerobes. In addition, high species-level identification rates and cost savings than conventional methods were achieved after MALDI-TOF introduction.
Asunto(s)
Bacteriemia/sangre , Bacterias/aislamiento & purificación , Sangre/microbiología , Bacteriemia/diagnóstico , Bacteriemia/microbiología , Bacterias/química , Bacterias/clasificación , Humanos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/instrumentación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Factores de TiempoRESUMEN
Carbapenem-resistant Klebsiella pneumoniae isolates are an important cause of nosocomial infections. This study evaluated a rapid cost-saving method based on MALDI-TOF technology, was and compared it with phenotypic, genotypic and epidemiological data for characterization of KPC-Kp strains consecutively isolated during a supposed outbreak. Twenty-five consecutive KPC Klebsiella pneumoniae isolates were identified and clustered by the MALDI Biotyper (Bruker, Daltonics). To display and rank the variance within a data set, principal component analysis (PCA) was performed. ClinProTools models were generated to investigate the highest sum of recognition capability and cross-validation. A Class dendrogram of isolates was constructed using ClinproTool. MLST was performed sequencing gapA, infB, mdh, pgi, rpoB, phoE and tonB genes. blakpc and cps genes were typed. Phylogenetic analysis and genetic distance of the KPC gene were performed using the MEGA6 software. PCA analysis defined two clusters, I and II, which were identified in a dendrogram by both temporal split and different antimicrobial susceptibility profiles. These clusters were composed mostly of strains of the same sequence type (ST512), the most prevalent ST in Italy, and the same cps (type 2). In cluster II, blakpc genotype resulted more variable than in cluster I. Phylogenetic analysis confirmed the genetic diversity in both clusters supported by the epidemiological data. Our study confirms that MALDI-TOF can be a rapid and cost-saving method for epidemiological clustering of KPC K. pneumoniae isolates and its association with blakpc genotyping represents a reliable method to recognize possible clonal strains in nosocomial settings.
Asunto(s)
Carbapenémicos/farmacología , Infección Hospitalaria/microbiología , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/química , Klebsiella pneumoniae/genética , Filogenia , Espectrometría de Masas en Tándem/métodos , beta-Lactamasas/genética , Proteínas Bacterianas/genética , Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Farmacorresistencia Bacteriana , Genotipo , Humanos , Italia/epidemiología , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/clasificación , Klebsiella pneumoniae/efectos de los fármacos , Tipificación de Secuencias Multilocus , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
BACKGROUND: Prevalence of bioprosthetic valve degeneration (BVD) is rising as the use of bioprosthetic aortic valves increases. Detecting early signs of BVD remains a challenge, with conventional imaging methods often failing to identify early deterioration stages. 18F-fuoride positron emission tomography (PET-CT) is an emerging technique that offers promising prospects to detect subclinical BVD. This study aimed to compare early PET parameters of fluoride uptake with echocardiographic hemodynamic parameters and compare outcomes according to anticoagulation in patients who received bioprosthetic valves. METHODS: This is a sub-study of the ANTIPRO clinical trial, which involved patients undergoing surgical aortic valve replacement (SAVR) with a porcine bioprosthesis and randomized them into anticoagulated and non-anticoagulated groups. Hemodynamic changes were assessed by transthoracic echocardiography (TTE), while 18F-fluoride PET-CT quantified fluoride uptake and divided the patients in two groups: high-uptake and low-uptake. Mean and maximum gradients by TTE at three years were compared between the two uptake groups. Fluoride uptake was also compared between the anticoagulated and control groups. RESULTS: We found no significant differences in transprosthetic gradients between high-uptake(21.4 ± 8.6 mmHg) and low-uptake(17.3 ± 11.2 mmHg.p = 0.244) PET-defined groups in this specific timeframe. Notably, anticoagulated patients exhibited significantly risk of higher fluoride uptake(OR = 4.34;95%CI:1.04-18.21.p = 0.045). CONCLUSIONS: No association was found between fluoride uptake and hemodynamic evaluation. Anticoagulation was associated with higher fluoride uptake. These findings highlight the emerging role of PET-CT in studying bioprosthetic aortic valves and emphasize the need for extended follow-up to evaluate the impact of anticoagulation on valve degeneration.
RESUMEN
BACKGROUND: Most evidence for anticoagulation in aortic bioprosthesis is centered on embolic events, bleeding and re-intervention risk. The effect of anticoagulation on hemodynamics has not been previously assessed. Our hypothesis was that patients with anticoagulation (AC) early after aortic valve replacement (AVR) with porcine bioprosthesis have better hemodynamics at 3 years of follow-up. METHODS: This is a follow-up evaluation of the ANTIPRO trial. All patients undergoing AVR with porcine bioprosthesis were consecutively recruited. The AC group received warfarin+aspirin and the non-AC(control) only aspirin. The primary outcome was mean gradient after 3 years of AVR and change in New York Heart Association (NYHA) class. Secondary outcomes were major and minor bleeding and embolic events. RESULTS: Of 140 participants in the study, 71 were assigned to the AC group and 69 to the control group. Mean age of the overall population was 72.4(SD: 7.1) years. Global euroSCORE was 7.65(SD: 5.73). At 3 years the mean gradient was similar between both groups (19.4(SD: 9.6 mmHg) and 18.6(SD: 8.2 mmHg) in the control and AC group respectively, p = 0.7). No differences in functional class at 3 years were found among groups. No differences were found among groups in the secondary outcomes. CONCLUSIONS: The addition of 3 months of oral anticoagulation to anti-aggregation treatment did not affect bioprosthetic hemodynamics nor functional class at years after AVR.
RESUMEN
OBJECTIVE: Multiple sclerosis (MS) is a complex disorder in which environmental and genetic factors interact modifying disease risk and course. This multicentre, case-control study involving 18 Italian MS Centres investigated MS course by ethnicity and native-country economic status in foreign-born patients living in Italy. METHODS: We identified 457 MS patients who migrated to Italy and 893 age- and sex-matched native-born Italian patients. In our population, 1225 (93.2%) subjects were White Europeans and White Northern Americans (WENA) and 89 (6.8%) patients were from other ethnical groups (OEG); 1109 (82.1%) patients were born in a high-income (HI) Country and 241 (17.9%) in a low-middle-income (LMI) Country. Medical records and patients interviews were used to collect demographic and disease data. RESULTS: We included 1350 individuals (973 women and 377 men); mean (SD) age was 45.0 (11.7) years. At onset, 25.45% OEG patients vs 12.47% WENA (p = 0.039) had > 3 STIR spine lesions. At recruitment, the same group featured mean (SD) EDSS score of 2.85 (2.23) vs 2.64 (2.28) (p = 0.044) reached in 8.9 (9.0) vs 12.0 (9.0) years (p = 0.018) and underwent 1.10 (4.44) vs. 0.99 (0.40) annual MRI examinations (p = 0.035). At disease onset, patients from LMI countries had higher EDSS score than HI patients (2.40 (1.43) vs 1.99 (1.17); p = 0.032). DISCUSSION: Our results suggested that both ethnicity and socio-economic status of native country shape MS presentation and course and should be considered for an appropriate management of patients. To the best of our knowledge, this is the first study reporting on the impact of ethnicity in MS at an individual level and beyond an ecological population-perspective.
Asunto(s)
Esclerosis Múltiple , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Etnicidad , Renta , Italia/epidemiología , Italia/etnología , Esclerosis Múltiple/etnología , Población Blanca , Pueblos de América del Norte , América del Norte/etnología , Europa (Continente)/etnologíaRESUMEN
A Real-time polymerase chain reaction (PCR) with melting analysis was devised to target bacterial and fungal genes together with the most prevalent antimicrobial resistance genes in 250 positive blood culture broths. This method allowed the blood culture cultivated pathogens to be classified into clinically relevant groups such as Enterobacteriaceae, oxidase-positive bacilli, oxidase-positive coccobacilli, S. aureus and yeast. Enterococci and streptococci could be distinguished from CoNS only by the Gram stain. Gram-positive bacilli were discriminated from Gram-positive cocci by Gram stain. Furthermore, the most important antimicrobial resistant genes such as mecA, vanA, bla TEM , bla SHV and bla CTX-M could be identified. All results were obtained with a turnaround time of three hours from the moment of blood culture positivity compared to 24-72 hours for phenotypic methods. In conclusion, the proposed approach can allow the clinician to implement proper early management of sepsis patients.
Asunto(s)
Farmacorresistencia Bacteriana Múltiple/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Sepsis/microbiología , Humanos , Italia , Pruebas de Sensibilidad Microbiana , Sepsis/diagnóstico , Factores de TiempoRESUMEN
BACKGROUND AND PURPOSE: Using transcranial magnetic stimulation, we investigated short-interval intracortical inhibition and short-latency afferent inhibition in acute ischemic stroke. METHODS: We evaluated short-interval intracortical inhibition and short-latency afferent inhibition in the affected hemisphere and unaffected hemisphere in 16 patients and correlated electrophysiological parameters with outcome at 6 months. RESULTS: Affected hemisphere short-latency afferent inhibition was significantly reduced in patients, and short-latency afferent inhibition level correlated with functional outcome. CONCLUSIONS: Reduced afferent inhibition in acute stroke correlates with long-term recovery.