Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU): Trial Satisfaction and Attitudes towards Future Clinical Trials.

BACKGROUND: Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU). METHODS: We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants' clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials. RESULTS: Survey responses were received over a sixteen-month window during 2020-2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial's demographic distribution. Participants' decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome. CONCLUSION: Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4-7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.

Survey of selected viral agents (herpesvirus, adenovirus and hepatitis E virus) in liver and lung samples of cetaceans, Brazil.

Hepatic and pulmonary lesions are common in cetaceans, despite their poorly understood viral etiology. Herpesviruses (HV), adenoviruses (AdV) and hepatitis E virus (HEV) are emerging agents in cetaceans, associated with liver and/or pulmonary damage in mammals. We isolated and molecularly tested DNA for HV and AdV (n = 218 individuals; 187 liver and 108 lung samples) and RNA for HEV (n = 147 animals; 147 liver samples) from six cetacean families. All animals stranded or were bycaught in Brazil between 2001 and 2021. Positive-animals were analyzed by histopathology. Statistical analyses assessed if the prevalence of viral infection could be associated with the variables: species, family, habitat, region, sex, and age group. All samples were negative for AdV and HEV. Overall, 8.7% (19/218) of the cetaceans were HV-positive (4.8% [9/187] liver and 11.1% [12/108] lung), without HV-associated lesions. HV-prevalence was statistically significant higher in Pontoporiidae (19.2%, 10/52) when compared to Delphinidae (4.1%, 5/121), and in southeastern (17.1%, 13/76)-the most industrialized Brazilian region-when compared to the northeastern region (2.4%, 3/126). This study broadens the herpesvirus host range in cetaceans, including its description in pygmy sperm whales (Kogia breviceps) and humpback whales (Megaptera novaeangliae). Further studies must elucidate herpesvirus drivers in cetaceans.

High-resolution gridded population datasets for Latin America and the Caribbean using official statistics.

"Leaving no one behind" is the fundamental objective of the 2030 Agenda for Sustainable Development. Latin America and the Caribbean is marked by social inequalities, whilst its total population is projected to increase to almost 760 million by 2050. In this context, contemporary and spatially detailed datasets that accurately capture the distribution of residential population are critical to appropriately inform and support environmental, health, and developmental applications at subnational levels. Existing datasets are under-utilised by governments due to the non-alignment with their own statistics. Therefore, official statistics at the finest level of administrative units available have been implemented to construct an open-access repository of high-resolution gridded population datasets for 40 countries in Latin American and the Caribbean. These datasets are detailed here, alongside the 'top-down' approach and methods to generate and validate them. Population distribution datasets for each country were created at a resolution of 3 arc-seconds (approximately 100 m at the equator), and are all available from the WorldPop Data Repository.

[Cognitive impairment in the elderly patient with symptomatic severe aortic stenosis. Therapeutic decisions and impact on one-year mortality]. / Deterioro cognitivo en el paciente mayor con estenosis aórtica grave sintomática. Toma de decisiones terapéuticas e impacto sobre la mortalidad al año.

INTRODUCTION: Interventional treatment of severe aortic stenosis includes valve replacement by surgery or transcatheter - transcatheter aortic valve implantation (TAVI). In order to make an adequate selection and to rule out patients with little/no therapeutic benefit, it is recommended to assess comorbidities, frailty and cognitive impairment. AIMS: a) To determine the prevalence of cognitive impairment in older patients with severe aortic stenosis; b) to analyse its influence on decision-making (surgery, TAVI or conservative treatment); and c) to analyse its impact on mortality at one year. MATERIAL AND METHODS: Prospective, longitudinal epidemiological study of patients aged 75 years and older with severe aortic stenosis treated by the Heart-Team. VARIABLES: sociodemographic, clinical, cardiological, functional and mental variables; cognitive impairment assessed by applying the Mini-Mental State Examination (MMSE). RESULTS: We included 300 patients in the study (83.99 ± 4.02 years old; 61.2%, women). Prevalence of cognitive impairment of 15.3%, which was associated with albumin level - odds ratio (OR): 0.082; p = 0.011 - and Barthel (OR: 0.962; p = 0.02) and Lawton (OR: 0.787; p = 0.025) index scores. Surgery was chosen in 24.7% of cases; TAVI in 63.3%; and conservative treatment in 12%. This decision was associated with the score on the Barthel (OR: 0.93; p = 0.012) and Lawton indices (OR: 0.678; p = 0.014), the Short Physical Performance Battery (OR: 0.75; p = 0.037) and the MMSE (OR: 0.691; p < 0.001). Mortality at one year was 14%, and higher in patients with MMSE scores <24 (23.5% vs. 12.8%; p = 0.094). CONCLUSIONS: Cognitive impairment is a very common geriatric syndrome in older patients with severe aortic stenosis that is associated with functional disability in activities of daily living. Cognitive impairment has a high impact on decision-making and appears to be a variable associated with increased mortality.

TITLE: Deterioro cognitivo en el paciente mayor con estenosis aórtica grave sintomática. Toma de decisiones terapéuticas e impacto sobre la mortalidad al año.Introducción. El tratamiento intervencionista de la estenosis aórtica grave incluye el recambio valvular mediante cirugía o vía transcatéter ­implante transcatéter de la válvula aórtica (TAVI)­. Para realizar una adecuada selección y descartar pacientes con escaso/nulo beneficio terapéutico, se recomienda evaluar las comorbilidades, la fragilidad y el deterioro cognitivo. Objetivos. a) Determinar la prevalencia de deterioro cognitivo en pacientes mayores con estenosis aórtica grave; b) analizar su influencia en la toma de decisiones (cirugía, TAVI o tratamiento conservador), y c) analizar su impacto sobre la mortalidad al año. Material y métodos. Estudio epidemiológico longitudinal y prospectivo sobre pacientes de 75 años o más con estenosis aórtica grave atendidos por el Heart-Team. Variables: sociodemográficas, clínicas, cardiológicas, funcionales y mentales; deterioro cognitivo evaluado aplicando el Minimental State Examination (MMSE). Resultados. Incluimos a 300 pacientes en el estudio (83,99 ± 4,02 años; 61,2%, mujeres). Prevalencia de deterioro cognitivo del 15,3%, que se asoció con el nivel de albúmina ­odds ratio (OR): 0,082; p = 0,011­ y las puntuaciones en los índices de Barthel (OR: 0,962; p = 0,02) y Lawton (OR: 0,787; p = 0,025). En el 24,7% de los casos se decidió cirugía; en el 63,3%, TAVI; y en el 12%, tratamiento conservador. Esta decisión se asoció con la puntuación en los índices de Barthel (OR: 0,93; p = 0,012) y Lawton (OR: 0,678; p = 0,014), la Short Physical Performance Battery (OR: 0,75; p = 0,037) y el MMSE (OR: 0,691; p menor de 0,001). La mortalidad al año fue del 14%, superior en los pacientes con puntuaciones en el MMSE menor de 24 (23,5% frente a 12,8%; p = 0,094). Conclusiones. El deterioro cognitivo es un síndrome geriátrico muy frecuente en pacientes mayores con estenosis aórtica grave que se asocia con incapacidad funcional en las actividades de la vida diaria. El deterioro cognitivo tiene un elevado impacto en la toma de decisiones y parece presentarse como una variable asociada a mayor mortalidad.

Deterioro cognitivo en el paciente mayor con estenosis aórtica grave sintomática. Toma de decisiones terapéuticas e impacto sobre la mortalidad al año / Cognitive impairment in the elderly patient with symptomatic severe aortic stenosis. Therapeutic decisions and impact on one-year mortality

Introducción: El tratamiento intervencionista de la estenosis aórtica grave incluye el recambio valvular mediante cirugía o vía transcatéter –implante transcatéter de la válvula aórtica (TAVI)–. Para realizar una adecuada selección y descartar pacientes con escaso/nulo beneficio terapéutico, se recomienda evaluar las comorbilidades, la fragilidad y el deterioro cognitivo. Objetivos: a) Determinar la prevalencia de deterioro cognitivo en pacientes mayores con estenosis aórtica grave; b) analizar su influencia en la toma de decisiones (cirugía, TAVI o tratamiento conservador), y c) analizar su impacto sobre la mortalidad al año. Material y métodos. Estudio epidemiológico longitudinal y prospectivo sobre pacientes de 75 años o más con estenosis aórtica grave atendidos por el Heart-Team. Variables: sociodemográficas, clínicas, cardiológicas, funcionales y mentales; deterioro cognitivo evaluado aplicando el Minimental State Examination (MMSE). Resultados: Incluimos a 300 pacientes en el estudio (83,99 ± 4,02 años; 61,2%, mujeres). Prevalencia de deterioro cognitivo del 15,3%, que se asoció con el nivel de albúmina –odds ratio (OR): 0,082; p = 0,011– y las puntuaciones en los índices de Barthel (OR: 0,962; p = 0,02) y Lawton (OR: 0,787; p = 0,025). En el 24,7% de los casos se decidió cirugía; en el 63,3%, TAVI; y en el 12%, tratamiento conservador. Esta decisión se asoció con la puntuación en los índices de Barthel (OR: 0,93; p = 0,012) y Lawton (OR: 0,678; p = 0,014), la Short Physical Performance Battery (OR: 0,75; p = 0,037) y el MMSE (OR: 0,691; p < 0,001). La mortalidad al año fue del 14%, superior en los pacientes con puntuaciones en el MMSE <24 (23,5% frente a 12,8%; p = 0,094). Conclusiones: El deterioro cognitivo es un síndrome geriátrico muy frecuente en pacientes mayores con estenosis aórtica grave que se asocia con incapacidad funcional en las actividades de la vida diaria...(AU)

Introduction: Interventional treatment of severe aortic stenosis includes valve replacement by surgery or transcatheter – transcatheter aortic valve implantation (TAVI). In order to make an adequate selection and to rule out patients with little/no therapeutic benefit, it is recommended to assess comorbidities, frailty and cognitive impairment. Aims: a) To determine the prevalence of cognitive impairment in older patients with severe aortic stenosis; b) to analyse its influence on decision-making (surgery, TAVI or conservative treatment); and c) to analyse its impact on mortality at one year. Material and methods: Prospective, longitudinal epidemiological study of patients aged 75 years and older with severe aortic stenosis treated by the Heart-Team. Variables: sociodemographic, clinical, cardiological, functional and mental variables; cognitive impairment assessed by applying the Mini-Mental State Examination (MMSE). Results: We included 300 patients in the study (83.99 ± 4.02 years old; 61.2%, women). Prevalence of cognitive impairment of 15.3%, which was associated with albumin level – odds ratio (OR): 0.082; p = 0.011 – and Barthel (OR: 0.962; p = 0.02) and Lawton (OR: 0.787; p = 0.025) index scores. Surgery was chosen in 24.7% of cases; TAVI in 63.3%; and conservative treatment in 12%. This decision was associated with the score on the Barthel (OR: 0.93; p = 0.012) and Lawton indices (OR: 0.678; p = 0.014), the Short Physical Performance Battery (OR: 0.75; p = 0.037) and the MMSE (OR: 0.691; p < 0.001). Mortality at one year was 14%, and higher in patients with MMSE scores <24 (23.5% vs. 12.8%; p = 0.094). Conclusions: Cognitive impairment is a very common geriatric syndrome in older patients with severe aortic stenosis that is associated with functional disability in activities of daily living. Cognitive impairment has a high impact on decision-making and appears to be a variable associated with increased mortality.(AU)

Barcelona scale for buccophonatory apraxia: Quantitative assessment tool.

INTRODUCTION: Currently there is no tool to quantify buccophonatory apraxia to stratify, compare and monitor patients longitudinally in an objective manner. Our aim in this study is to create a quantitative scale for buccophonatory apraxia and evaluate it in patients with the non-fluent/grammatical variant of primary progressive aphasia (nfvPPA) and other neurodegenerative diseases that occur with speech and/or language problems. METHODS: The scale was designed based on useful elements in the assessment of buccophonatory apraxia and the total was quantified in seconds. The scale was administered to 64 participants with diagnoses of: nfvPPA, semantic variant of primary progressive aphasia (svPPA), logopenic variant of primary progressive aphasia (lvPPA), Huntington's disease, Parkinson's disease, as well as a group of healthy controls. RESULTS: Patients showed a significantly higher score compared to controls. The nfvPPA group had the highest mean score on the scale (429 seconds ± 278). The scale was useful to differentiate vnfPPA from svPPA and Parkinson's disease (area under curve [AUC] of 0.956 and 0.989, respectively), but less to differentiate it from Huntington's disease (AUC = 0.67) and lvPPA. There was a statistically significant relationship between total score and disease severity in nfvPPA (P < .029). CONCLUSIONS: The Barcelona scale for buccophonatory apraxia could be useful to quantitatively evaluate buccophonatory apraxia in different neurodegenerative diseases, and compare patients, especially in nfvPPA.

La técnica de superposición de cúspides en TAVI con dispositivo autoexpandible optimiza la profundidad del implante y reduce la necesidad de marcapasos permanente / Cusp-overlapping TAVI technique with a self-expanding device optimizes implantation depth and reduces permanent pacemaker requirement

Introducción y objetivos: Una profundidad más alta del implante percutáneo de una válvula aórtica autoexpandible minimiza el daño en el sistema de conducción y puede reducir las tasas de marcapasos permanente a 30 días. El objetivo es determinar la seguridad y la eficacia de modificar la técnica de implante clásica para el reemplazo percutáneo de la válvula aórtica a una técnica de proyección de superposición de cúspides (PSC) para lograr una profundidad más alta del implante y reducir la necesidad de marcapasos permanente. Métodos: Desde marzo de 2017 se incluyó a 226 pacientes consecutivos: 113 tratados con técnica de implante PSC frente a 113 casos consecutivos previos con implante clásico. La profundidad del implante se evaluó mediante 3 métodos en todos los pacientes (cúspide no coronaria a válvula cardiaca percutánea (VCP); media de cúspide no coronaria y cúspide coronaria izquierda a VCP y el borde más profundo de cúspide coronaria izquierda y cúspide no coronaria a VCP). Resultados: El grupo de PSC presentó una profundidad del implante menor que el del grupo de implante clásico (4,8±2,2 frente a 5,7±3,1 mm; p=0,011; 5,8±3,1 frente a 6,5±2,4 mm; p=0,095; 7,1±2,8 frente a 7,4±3,2 mm; p=0,392). A los 30 días de seguimiento, 40 pacientes (17,7%) requirieron el implante de marcapasos permanente, menos en el grupo de PSC (el 12,4 frente al 23%; p=0,036). La técnica de implante PSC protegió contra el evento principal (OR=0,45; IC95%, 0,21-0,97; p=0,043), con parecidos éxito del procedimiento y complicaciones. Conclusiones: La técnica de implante PSC es una simple modificación en el protocolo que proporciona una profundidad del implante más alta de la prótesis valvular autoexpandible con menores alteraciones de la conducción y tasas de marcapasos permanente (AU)

Introduction and objectives: This study aimed to determine the safety and efficacy of modifying the classic implantation technique for aortic transcatheter heart valve (THV) implantation to a cusp-overlap-projection (COP) technique to achieve a higher implantation depth and to reduce the burden of new permanent pacemaker implantation (PPMI) at 30 days. Aortic self-expanding THV carries an elevated risk for PPMI. A higher implantation depth minimizes the damage in the conduction system and may reduce PPMI rates. Methods: From March 2017, 226 patients were consecutively included: 113 patients were treated using the COP implantation technique compared with the previous 113 consecutive patients treated using the classic technique. In all patients, implantation depth was assessed by 3 methods (noncoronary cusp to the THV, mean of the noncoronary cusp and the left coronary cusp to the THV, and the deepest edge from the left coronary cusp and the noncoronary cusp to the THV). Results: The COP group had a lower implantation depth than the group treated with the classic technique (4.8 mm± 2.2 vs 5.7 mm± 3.1; P=.011; 5.8 mm± 3.1 vs 6.5 mm± 2.4; P=.095; 7.1 mm± 2.8 vs 7.4 mm±3.2; P=.392). Forty patients (17.7%) required a new PPMI after the 30-day follow-up but this requirement was significantly lower in the COP group (12.4% vs 23%, P=.036). The COP implantation technique consistently protected against the main event (OR, 0.45; 95%CI, 0.21-0.97; P=.043), with similar procedural success rates and complications. Conclusions: The COP implantation technique is a simple modification of the implantation protocol and provides a higher implantation depth of self-expanding-THV with lower conduction disturbances and PPMI rates (AU)

Infectivity and pathobiology of H7N1 and H5N8 high pathogenicity avian influenza viruses for pigeons (Columba livia var. domestica).

Avian influenza (AI) is one of the most important viral diseases in poultry, wildlife and humans. Available data indicate that pigeons play a minimum role in the epidemiology of AI. However, a degree of variation exists in the susceptibility of pigeons to highly pathogenic AI viruses (HPAIVs), especially since the emergence of the goose/Guangdong H5 lineage. Here, the pathogenesis of H5N8 HPAIV in comparison with a H7N1 HPAIV and the role of pigeons in the epidemiology of these viruses were evaluated. Local and urban pigeons (Columba livia var. domestica) were intranasally inoculated with 105 ELD50 of A/goose/Spain/IA17CR02699/2017 (H5N8) or A/Chicken/Italy/5093/1999 (H7N1) and monitored during 14 days. Several pigeons inoculated with H5N8 or H7N1 seroconverted. However, clinical signs, mortality, microscopic lesions and viral antigen were only detected in a local pigeon inoculated with H5N8 HPAIV. This pigeon presented prostration and neurological signs that correlated with the presence of large areas of necrosis and widespread AIV antigen in the central nervous system, indicating that the fatal outcome was associated with neurological dysfunction. Viral RNA in swabs was detected in some pigeons inoculated with H7N1 and H5N8, but it was inconsistent, short-term and at low titres. The present study demonstrates that the majority of pigeons were resistant to H5N8 and H7N1 HPAIVs, despite several pigeons developing asymptomatic infections. The limited viral shedding indicates a minimum role of pigeons as amplifiers of HPAIVs, regardless of the viral lineage, and suggests that this species may represent a low risk for environmental contamination. RESEARCH HIGHLIGHTS H7N1 and H5N8 HPAIVs can produce subclinical infections in pigeons. The mortality caused by H5N8 HPAIV in one pigeon was associated with neurological dysfunction. Pigeons represent a low risk for environmental contamination by HPAIVs.

Experimental infection of domestic geese (Anser anser var. domesticus) with H5N8 Gs/GD and H7N1 highly pathogenic avian influenza viruses.

Prior to the emergence of the Asian-origin H5 Goose/Guangdong/1/96 (Gs/GD) lineage, highly pathogenic avian influenza viruses (HPAIV) had rarely caused high mortalities in domestic geese. In 2016/2017 European epidemics, H5N8 Gs/GD clade 2.3.4.4 Group B produced an unprecedented number of outbreaks in waterfowl holdings. In this study, the pathogenesis of H5N8 HPAIV in comparison with H7N1 HPAIV, and the role of domestic geese in the epidemiology of these viruses, were evaluated. Local and commercial geese (Anser anser var. domesticus) were intranasally inoculated with 105 ELD50 of A/goose/Spain/IA17CR02699/2017 (H5N8) or A/Chicken/Italy/5093/1999 (H7N1) and monitored daily during 15 days. H5N8 was highly virulent to domestic geese, reaching 100% mortality by 10 days post-infection. Systemic microscopic necrotizing lesions associated with widespread AIV-antigen were detected by IHC techniques, the central nervous system being the most severely affected. High viral loads, measured by qRT-PCR, were present in all samples collected: oral and cloacal swabs, plasma tissues, and moderate levels in pool water. Domestic geese were also susceptible to H7N1 infection, as demonstrated by seroconversion and detection of viral RNA in tissues and plasma in some geese, but all lacked clinical signs. Viral shedding was confirmed in only some geese and was restricted to the oral route, but levels were high and still detected at the end of the study. Overall, H7N1 presents a lower lethality and shedding than H5N8 in geese; however, the viral shedding indicates that these species could play a role in the epidemiology of Gs/GD and other lineages of HPAIVs. RESEARCH HIGHLIGHTS H5N8 Gs/GD clade 2.3.4.4 Group B is highly virulent to domestic geese. The severity of H5N8 is associated with multisystemic replication. H7N1 can infect domestic geese but is avirulent to this species. Domestic geese could play a role in the epidemiology of Gs/GD HPAIVs.

Multicentre evaluation of case volume in minimally invasive hepatectomy.

BACKGROUND: Surgical outcomes may be associated with hospital volume and the influence of volume on minimally invasive liver surgery (MILS) is not known. METHODS: Patients entered into the prospective registry of the Italian Group of MILS from 2014 to 2018 were considered. Only centres with an accrual period of at least 12 months and stable MILS activity during the enrolment period were included. Case volume was defined by the mean number of minimally invasive liver resections performed per month (MILS/month). RESULTS: A total of 2225 MILS operations were undertaken by 46 centres; nine centres performed more than two MILS/month (1376 patients) and 37 centres carried out two or fewer MILS/month (849 patients). The proportion of resections of anterolateral segments decreased with case volume, whereas that of major hepatectomies increased. Left lateral sectionectomies and resections of anterolateral segments had similar outcome in the two groups. Resections of posterosuperior segments and major hepatectomies had higher overall and severe morbidity rates in centres performing two or fewer MILS/month than in those undertaking a larger number (posterosuperior segments resections: overall morbidity 30·4 versus 18·7 per cent respectively, and severe morbidity 9·9 versus 4·0 per cent; left hepatectomy: 46 versus 22 per cent, and 19 versus 5 per cent; right hepatectomy: 42 versus 34 per cent, and 25 versus 15 per cent). CONCLUSION: A volume-outcome association existed for minimally invasive hepatectomy. Complex and major resections may be best managed in high-volume centres.

ANTECEDENTES: Los resultados quirúrgicos pueden estar relacionados con el volumen de casos del hospital, pero no se conoce la influencia en la cirugía mínimamente invasiva del hígado (minimally­invasive liver surgery, MILS). MÉTODOS: Se incluyeron los pacientes registrados en el registro prospectivo del grupo italiano de MILS desde 2014 a 2018. Solo se consideraron centros con extensión de ≥ 12 meses y actividad estable de MILS durante el periodo de reclutamiento. El volumen de casos se definió como el número de MILS efectuado por mes. RESULTADOS: Se llevaron a cabo un total de 2.225 MILS en 46 centros, 9 de ellos con > 2 MILS/mes (n = 1.376 pacientes) y 37 centros con ≤ 2 MILS/mes (n = 849). La proporción de resecciones de segmentos anterolaterales disminuyó con el volumen de casos, mientras que la proporción de hepatectomías mayores aumentó. Los resultados para ambos grupos fueron similares en las seccionectomías lateral izquierda y en las resecciones del segmento anterolateral. Las resecciones del segmento posterosuperior y las hepatectomías mayores presentaron tasas más altas de morbilidad global y morbilidad grave en centros que realizaban ≤ 2 MILS/mes que en los que realizaban > 2 MILS/mes (resecciones del segmento posterosuperior, morbilidad global 30,4 versus 18,7%, morbilidad grave 9,9 versus 4,0%; hepatectomía izquierda, 46,2 versus 22,0%, 19,2 versus 5,5%; hepatectomía derecha, 41,7 versus 33,8%, 25,0 versus 14.9%). CONCLUSIÓN: Se observó una asociación volumen­resultado para la resección hepática mínimamente invasiva. Las resecciones complejas y mayores se pueden manejar mejor en centros de gran volumen.

Risk-adjusted benchmarks in laparoscopic liver surgery in a national cohort.

BACKGROUND: This study aimed to assess the best achievable outcomes in laparoscopic liver resection (LLR) after risk adjustment based on surgical technical difficulty using a national registry. METHODS: LLRs registered in the Italian Group of Minimally Invasive Liver Surgery registry from November 2014 to March 2018 were considered. Benchmarks were calculated according to the Achievable Benchmark of Care (ABC™). LLRs at each centre were divided into three clusters (groups I, II and III) based on the Kawaguchi classification. ABCs for overall and major morbidity were calculated in each cluster. Multivariable analysis was used to identify independent risk factors for overall and major morbidity. Significant variables were used in further risk adjustment. RESULTS: A total of 1752 of 2263 patients fulfilled the inclusion criteria: 1096 (62·6 per cent) in group I, 435 (24·8 per cent) in group II and 221 (12·6 per cent) in group III. The ABCs for overall morbidity (7·8, 14·2 and 26·4 per cent for grades I, II and II respectively) and major morbidity (1·4, 2·2 and 5·7 per cent) increased with the difficulty of LLR. Multivariable analysis showed an increased risk of overall morbidity associated with multiple LLRs (odds ratio (OR) 1·35), simultaneous intestinal resection (OR 3·76) and cirrhosis (OR 1·83), and an increased risk of major morbidity with intestinal resection (OR 4·61). ABCs for overall and major morbidity were 14·4 and 3·2 per cent respectively for multiple LLRs, 30 and 11·1 per cent for intestinal resection, and 14·9 and 4·8 per cent for cirrhosis. CONCLUSION: Overall morbidity benchmarks for LLR ranged from 7·8 to 26·4 per cent, and those for major morbidity from 1·4 to 5·7 per cent, depending on complexity. Benchmark values should be adjusted according to multiple LLRs or simultaneous intestinal resection and cirrhosis.

ANTECEDENTES: Este estudio tuvo como objetivo evaluar los mejores resultados que se pueden conseguir en la resección hepática laparoscópica (laparoscopic liver resection, LLR) después del ajuste por riesgos basado en la dificultad de la técnica quirúrgica utilizando un registro nacional. MÉTODOS: Se consideraron las LLRs incluidas en el Registro del Grupo Italiano de Cirugía Hepática Mínimamente Invasiva desde 11/2014 a 03/2018. Los resultados de referencia (benchmarks) se calcularon de acuerdo con el Achievable Benchmark of Care (ABC™). Las LLRs de cada uno de los centros se dividieron en 3 grupos (Grupo I, II y III) en base a la clasificación de Kawaguchi. Se calculó el ABC de la morbilidad global y de la morbilidad mayor para cada grupo. Se realizó un análisis multivariable para identificar los factores independientes de riesgos para la morbilidad global y morbilidad mayor. Se utilizaron variables significativas para realizar ajustes de riesgo adicionales. RESULTADOS: Un total de 1.752 pacientes de los 2.263 cumplían los criterios de inclusión, de los cuales 1.096 (62,6%) se incluyeron en el Grupo I, 435 (24,8%) en el Grupo II y 221 (12,6%) en el Grupo III. El ABC de la morbilidad global (7,8%, 14,2%, 26,4%) y de la morbilidad mayor (1,4%, 2,2%, 5,7%) aumentó del Grupo I al Grupo III. El análisis multivariable mostró un incremento del riesgo para la morbilidad global asociada con múltiples LLRs (razón de oportunidades, odds ratio, OR 1,349), resección intestinal simultánea (OR 3,760) y cirrosis (OR 1,825), y para la morbilidad mayor con la resección intestinal (OR 4,606). Los ABC de la morbilidad global y morbilidad mayor fueron 14,4% y 3,2% para las LLR múltiples, 30% y 11% para la resección intestinal, y 14,9% y 4,8% para la cirrosis, respectivamente. CONCLUSIÓN: Los resultados de referencia (benchmark) para la morbilidad global y morbilidad mayor en la LLR variaron entre un 8% y un 26% y entre un 1,4% y un 5,7%, dependiendo de la complejidad. Los valores de referencia deberían ajustarse de acuerdo con la práctica de LLRs múltiples o resección intestinal simultánea y cirrosis.

Clinical applicability of diagnostic biomarkers in early-onset cognitive impairment.

BACKGROUND AND PURPOSE: Several diagnostic biomarkers are currently available for clinical use in early-onset cognitive impairment. The decision on which biomarker is used in each patient depends on several factors such as its predictive value or tolerability. METHODS: There were a total of 40 subjects with early-onset cognitive complaints (<65 years of age): 26 with Alzheimer's disease (AD), five with frontotemporal dementia and nine with diagnostic suspicion of non-neurodegenerative disorder. Clinical and neuropsychological evaluation, lumbar puncture for cerebrospinal fluid (CSF) AD core biochemical marker determination, medial temporal atrophy evaluation on magnetic resonance imaging, amyloid-positron emission tomography (PET) and 18 F-fluorodeoxyglucose-PET were performed. Neurologists provided pre- and post-biomarker diagnosis, together with diagnostic confidence and clinical/therapeutic management. Patients scored the tolerability of each procedure. RESULTS: Cerebrospinal fluid biomarkers and amyloid-PET increased diagnostic confidence in AD (77.4%-86.2% after CSF, 92.4% after amyloid-PET, P < 0.01) and non-neurodegenerative conditions (53.6%-75% after CSF, 95% after amyloid-PET, P < 0.05). Biomarker results led to diagnostic (32.5%) and treatment (32.5%) changes. All tests were well tolerated. CONCLUSIONS: Biomarker procedures are well tolerated and have an important diagnostic/therapeutic impact on early-onset cognitive impairment.

Pronóstico de la enfermedad tromboembólica venosa en cirugía ortopédica o pacientes traumatológicos y uso de tromboprofilaxis / Prognosis of venous thromboembolism in orthopaedic surgery or trauma patients and use of thromboprophylaxis

Antecedentes: Hay escasa evidencia sobre el pronóstico de la tromboembolia venosa en pacientes sometidos a cirugía ortopédica y en pacientes que sufren un trauma no quirúrgico. Métodos: Utilizamos la base de datos RIETE (Registro Informatizado de pacientes con Enfermedad TromboEmbólica) para comparar el pronóstico del tromboembolismo venoso y el uso de tromboprofilaxis en pacientes sometidos a diferentes procedimientos ortopédicos y en pacientes con traumatismo que no requiere cirugía. Resultados: Desde marzo de 2001 a marzo de 2015, se inscribieron un total de 61.789 pacientes en RIETE. De estos, 943 (1.52%) desarrollaron tromboembolismo venoso después de artroplastia electiva, 445 (0.72%) después de fractura de cadera, 1.045 (1.69%) después de cirugía ortopédica no mayor y 2,136 (3.46%) después de trauma no quirúrgico. En general, 2.283 pacientes (50%) presentaron inicialmente embolia pulmonar. En los primeros 90 días de tratamiento, 30 pacientes (0.66%, IC 95% 0.45-0.93) murieron por embolia pulmonar. La tasa de embolia pulmonar fatal fue significativamente mayor después de cirugía de fractura de cadera (n = 9 [2.02%]) que después de la artroplastia electiva (n = 5 [0.53%]), cirugía ortopédica no mayor (n = 5 [0.48%]) o traumatismo no quirúrgico (n = 11 [0,48%]). La tromboprofilaxis se utilizó con mayor frecuencia para la fractura de cadera (93%) o la artroplastia electiva (94%) que para la cirugía ortopédica no mayor (71%) o traumatismo no quirúrgico (32%). La hemorragia mayor fue significativamente mayor después de la cirugía de fractura de cadera (4%) que después de artroplastia electiva (1,6%), cirugía ortopédica no mayor (1,5%) o traumatismo no quirúrgico (1,4%). Conclusiones: La tromboprofilaxis se utilizó con menos frecuencia en los procedimientos de menor riesgo a pesar del número absoluto de embolia pulmonar fatal después de cirugía ortopédica no mayor o traumatismo no quirúrgico, excedieron los observados después de procedimientos de alto riesgo

Background: There is scarce evidence about the prognosis of venous thromboembolism in patients undergoing orthopedic surgery and in patients suffering non-surgical trauma. Methods: We used the RIETE database (Registro Informatizado de pacientes con Enfermedad Trombo Embólica) to compare the prognosis of venous thromboembolism and the use of thromboprophylaxis in patients undergoing different orthopedic procedures and in trauma patients not requiring surgery. Results: From March 2001 to March 2015, a total of 61,789 patients were enrolled in RIETE database. Of these, 943 (1.52%) developed venous thromboembolism after elective arthroplasty, 445 (0.72%) after hip fracture, 1,045 (1.69%) after non-major orthopedic surgery and 2,136 (3.46%) after non-surgical trauma. Overall, 2,283 patients (50%) initially presented with pulmonary embolism. Within the first 90 days of therapy, 30 patients (0.66%; 95% CI 0.45-0.93) died from pulmonary embolism. The rate of fatal pulmonary embolism was significantly higher after hip fracture surgery (n = 9 [2.02%]) than after elective arthroplasty (n = 5 [0.53%]), non-major orthopedic surgery (n = 5 [0.48%]) or non surgical trauma (n = 11 [0.48%]). Thromboprophylaxis was more commonly used for hip fracture (93%) or elective arthroplasty (94%) than for non-major orthopedic surgery (71%) or non-surgical trauma (32%). Major bleeding was significantly higher after hip fracture surgery (4%) than that observed after elective arthroplasty (1.6%), non-major orthopedic surgery (1.5%) or non-surgical trauma (1.4%). Conclusions: Thromboprophylaxis was less frequently used in lower risk procedures despite the absolute number of fatal pulmonary embolism after non-major orthopedic surgery or non-surgical trauma, exceeded that observed after high risk procedures

Prognosis of venous thromboembolism in orthopaedic surgery or trauma patients and use of thromboprophylaxis. / Pronóstico de la enfermedad tromboembólica venosa en cirugía ortopédica o pacientes traumatológicos y uso de tromboprofilaxis.

BACKGROUND: There is scarce evidence about the prognosis of venous thromboembolism in patients undergoing orthopedic surgery and in patients suffering non-surgical trauma. METHODS: We used the RIETE database (Registro Informatizado de pacientes con Enfermedad Trombo Embólica) to compare the prognosis of venous thromboembolism and the use of thromboprophylaxis in patients undergoing different orthopedic procedures and in trauma patients not requiring surgery. RESULTS: From March 2001 to March 2015, a total of 61,789 patients were enrolled in RIETE database. Of these, 943 (1.52%) developed venous thromboembolism after elective arthroplasty, 445 (0.72%) after hip fracture, 1,045 (1.69%) after non-major orthopedic surgery and 2,136 (3.46%) after non-surgical trauma. Overall, 2,283 patients (50%) initially presented with pulmonary embolism. Within the first 90 days of therapy, 30 patients (0.66%; 95% CI 0.45-0.93) died from pulmonary embolism. The rate of fatal pulmonary embolism was significantly higher after hip fracture surgery (n = 9 [2.02%]) than after elective arthroplasty (n = 5 [0.53%]), non-major orthopedic surgery (n = 5 [0.48%]) or non surgical trauma (n = 11 [0.48%]). Thromboprophylaxis was more commonly used for hip fracture (93%) or elective arthroplasty (94%) than for non-major orthopedic surgery (71%) or non-surgical trauma (32%). Major bleeding was significantly higher after hip fracture surgery (4%) than that observed after elective arthroplasty (1.6%), non-major orthopedic surgery (1.5%) or non-surgical trauma (1.4%). CONCLUSIONS: Thromboprophylaxis was less frequently used in lower risk procedures despite the absolute number of fatal pulmonary embolism after non-major orthopedic surgery or non-surgical trauma, exceeded that observed after high risk procedures.

A synergic approach of X-ray powder diffraction and Raman spectroscopy for crystal structure determination of 2,3-thienoimide capped oligothiophenes.

This work presents a Raman based approach for the rapid identification of the molecular conformation in a series of new 2,3-thienoimide capped quaterthiophenes, whose crystal structures were determined by synchrotron radiation X-ray powder diffraction. These systems display two conformational polymorphs, known as forms A and B, as a result of the anti-anti-anti and syn-anti-syn arrangements of the quaterthiophene cores. In a micro-Raman and computational study, the spectroscopic differences between the conformers were detected and proved to be suitable markers for polymorph identification. Thus, the synergic employment of diffraction and Raman spectroscopy techniques yields a full and reliable characterization of 2,3-thienoimide capped quaterthiophene compounds in their solid state.

Transmission and immunopathology of the avian influenza virus A/Anhui/1/2013 (H7N9) human isolate in three commonly commercialized avian species.

H7N9 virus infection is a global concern, given that it can cause severe infection and mortality in humans. However, the understanding of H7N9 epidemiology, animal reservoir species and zoonotic risk remains limited. This work evaluates the pathogenicity, transmissibility and local innate immune response of three avian species harbouring different respiratory distribution of α2,6 and α2,3 SA receptors. Muscovy ducks, European quails and SPF chickens were intranasally inoculated with 105 embryo infectious dose (EID)50 of the human H7N9 (A/Anhui/1/2013) influenza isolate. None of the avian species showed clinical signs or macroscopic lesions, and only mild microscopic lesions were observed in the upper respiratory tract of quail and chickens. Quail presented more severe histopathologic lesions and avian influenza virus (AIV) positivity by immunohistochemistry (IHC), which correlated with higher IL-6 responses. In contrast, Muscovy ducks were resistant to disease and presented higher IFNα and TLR7 response. In all species, viral shedding was higher in the respiratory than in the digestive tract. Higher viral shedding was observed in quail, followed by chicken and ducks, which presented similar viral titres. Efficient transmission was observed in all contact quail and half of the Muscovy ducks, while no transmission was observed between chicken. All avian species showed viral shedding in drinking water throughout infection.

A retrospective analysis of adverse effects of an in vivo fluoroquinolone antibiotic enrofloxacin treatment on oocyte quality in the common marmoset.

Here we report a retrospective analysis of negative effects of routine enrofloxacin treatment of recurrent diarrhea on the ovary and the developing oocytes of the common marmoset, a small New World primate. The most deleterious effect on oocytes was observed about two months post treatment suggesting that the enrofloxacin effect is on early growing follicles. Manifestations of toxicity included decreased numbers of growing follicles and recovered culturable oocytes, as well as signs of early atresia of granulosa cells. In addition, increased amounts of holed stroma after treatment strongly suggested increased death of the early growing follicles. Of the oocytes judged to be of adequate quality for culture, maturation rates were not affected but fertilization of in vitro matured MII oocytes and subsequent cleavage rates were severely reduced in the enrofloxacin treated animals. Further, the arrested oocytes, which failed to mature or fertilize, showed obvious meiotic spindle abnormalities.