Considerations for medical nutrition therapy management of the critically ill patient with hematological malignancies: A narrative review.

Patients with hematological malignancies (HMs) are more frequently admitted now than in the past to the intensive care unit (ICU) due to more aggressive approaches in primary therapy of HMs and the need for critical care support. Pathophysiological alterations derived from HMs and the different hematological therapies, such as chemotherapy, negatively affect gastrointestinal (GI) function, metabolism, and nutrition status. Further, malnutrition strongly influences outcomes and tolerance of the different hematological therapies. In consequence, these critically ill patients frequently present with malnutrition and pathophysiological alterations that create challenges for the delivery of medical nutrition therapy (MNT) in the ICU. Frequent screening, gauging tolerance, and monitoring nutrition status are mandatory to provide individualized MNT and achieve nutrition objectives. The present review discusses how HM impact GI function and nutrition status, the importance of MNT in patients with HM, and specific considerations for guidance in providing adequate MNT to these patients when admitted to the ICU.

Photo-Cross-Linked Fullerene-Based Hole Transport Material for Moisture-Resistant Regular Fullerene Sandwich Perovskite Solar Cells.

Despite the high efficiencies currently achieved with perovskite solar cells (PSCs), the need to develop stable devices, particularly in humid conditions, still remains. This study presents the synthesis of a novel photo-cross-linkable fullerene-based hole transport material named FT12. For the first time, the photo-cross-linking process is applied to PSCs, resulting in the preparation of photo-cross-linked FT12 (PCL FT12). Regular PSCs based on C60-sandwich architectures were fabricated using FT12 and PCL FT12 as dopant-free hole transport layers (HTLs) and compared to the reference spiro-OMeTAD. The photovoltaic results demonstrate that both FT12 and PCL FT12 significantly outperform pristine spiro-OMeTAD regarding device performance and stability. The comparison between devices based on FT12 and PCL FT12 demonstrates that the photo-cross-linking process enhances device efficiency. This improvement is primarily attributed to enhanced charge extraction, partial oxidation of the HTL, increased hole mobility, and improved layer morphology. PCL FT12-based devices exhibit improved stability compared to FT12 devices, primarily due to the superior moisture resistance achieved through photo-cross-linking.

Biobased Composites of Poly(Lactic Acid) Melt Compounded with Bacterial and Vegetal Nanocelluloses Incorporated through Different Strategies.

In the current contribution, bacterial nanocellulose obtained from a by-product of Kombucha tea production and vegetal nanocellulose isolated from milled rice husks were employed as fillers of PLA-based composites prepared by intensive mixing followed by compression molding. Given the challenges associated with the incorporation of nanocelluloses-initially obtained as aqueous suspensions-into melt compounding processes, and also with achieving a proper dispersion of the hydrophilic nanofillers within PLA, three different nanofibrils incorporation strategies were studied: i.e., direct mixing of dried milled nanocelluloses and PLA; masterbatching by solvent casting of native nanocelluloses followed by melt compounding; and masterbatching by solvent casting of acetylated nanocelluloses followed by melt compounding. Composites with varying filler content (from 0.5 wt.% to 7 wt.%) were characterized in terms of morphology, optical properties, and mechanical performance. Results revealed the relative suitability of each strategy employed to promote nanocelluloses dispersion within the PLA matrix. PLA/nanocellulose masterbatches prepared by solvent casting proved to be particularly useful for feeding the nanocelluloses into the processing equipment in a dry state with limited hornification. Acetylation also contributed to a better dispersion of both nanocelluloses within the PLA matrix, although no clear positive impact on the mechanical properties of the films was observed. Finally, filler loading played an important role in the films' properties by increasing their stiffness while reducing their translucency.

N-terminal pro-B-type natriuretic peptide post-discharge monitoring in the management of patients with heart failure and preserved ejection fraction - a randomized trial: The NICE study.

AIMS: There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post-discharge management of patients with heart failure (HF) and preserved ejection fraction (HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N-terminal pro-B-type natriuretic peptide (NT-proBNP) into the post-discharge management of HFpEF patients. METHODS AND RESULTS: Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open-label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT-proBNP monitoring (n = 79) or no access to NT-proBNP (control group, n = 78) during pre-scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT-proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.47-2.81, p = 0.760). Regarding secondary endpoints, the NT-proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02-0.09), whereas non-HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance. Awareness of NT-proBNP levels were associated with higher doses of diuretics and renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers) in the NT-proBNP monitoring group. CONCLUSIONS: Post-discharge monitoring of NT-proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.

Enteral nutrition in septic shock: a call for a paradigm shift.

PURPOSE OF REVIEW: The purpose of this review is to identify contemporary evidence evaluating enteral nutrition in patients with septic shock, outline risk factors for enteral feeding intolerance (EFI), describe the conundrum of initiating enteral nutrition in patients with septic shock, appraise current EFI definitions, and identify bedside monitors for guiding enteral nutrition therapy. RECENT FINDINGS: The NUTRIREA-2 and NUTRIREA-3 trial results have better informed the dose of enteral nutrition in critically ill patients with circulatory shock. In both trials, patients with predominant septic shock randomized to receive early standard-dose nutrition had more gastrointestinal complications. Compared to other contemporary RCTs that included patients with circulatory shock, patients in the NUTRIREA-2 and NUTRIREA-3 trials had higher bowel ischemia rates, were sicker, and received full-dose enteral nutrition while receiving high baseline dose of vasopressor. These findings suggest severity of illness, vasopressor dose, and enteral nutrition dose impact outcomes. SUMMARY: The provision of early enteral nutrition preserves gut barrier functions; however, these benefits are counterbalanced by potential complications of introducing luminal nutrients into a hypo-perfused gut, including bowel ischemia. Findings from the NUTRIREA2 and NUTRIREA-3 trials substantiate a 'less is more' enteral nutrition dose strategy during the early acute phase of critical illness. In the absence of bedside tools to guide the initiation and advancement of enteral nutrition in patients with septic shock, the benefit of introducing enteral nutrition on preserving gut barrier function must be weighed against the risk of harm by considering dose of vasopressor, dose of enteral nutrition, and severity of illness.

Africanized honey bee colonies in Costa Rica: first evidence of its management, brood nest structure and factors associated with varroa mite infestation.

Management, brood nest structure and factors associated with varroa mite infestation were studied in 60 apiaries of Africanized honey bees in the northwest region of the Central Valley of Costa Rica. Apiaries were monitored two times. The first monitoring was taken forward during the rainy season between May and November 2019. The second monitoring during the dry season between February and March 2020. Information about the beekeepers, apiaries and management was collected through a survey. Amount of open and capped brood, honey and pollen were measured in the field. The infestation rate of varroa (IRV) was quantified using standard laboratory methods. A determination of multi-residue pesticides in bee bread was made through GC-MS/MS and LC-MS/MS techniques. According to the results, most of the beekeepers produce honey (96.7%), participate in training activities (82.2%), and change the bee queens annually (70%). The first monitoring was characterized by a lower amount of capped brood and honey reserves compared to the second one. IRV was significantly higher in the first monitoring (6.0 ± 0.4) in comparison with the second one (3.0 ± 0.3) (U Mann-Whitney p < 0.001). The maximum value for the first monitoring exceeds 40%, while this value was close to 25% in the second monitoring. Mite infestation exposed significant differences in relation to the variables associated to the beekeeper's management, i.e., change of bee queen (p = 0.002) or when beekeepers monitor varroa mites (p = 0.004). Additionally, the IRV had inverse correlations (p < 0.01) with the number of comb sides with capped brood (Spearman's rho coefficient = - 0.190), and honey reserves (Spearman's rho coefficient = - 0.168). Furthermore, 23 of 60 bee bread samples presented one to five pesticide residues, being the most frequent antifungal agrochemicals.

Multicentre randomised trial of screening with sFlt1/PlGF and planned delivery to prevent pre-eclampsia at term: protocol of the PE37 study.

INTRODUCTION: Pre-eclampsia affects ~5%-7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term pre-eclampsia accounts for 70% of all cases and a large proportion of maternal-fetal morbidity related to this condition. Unlike in preterm pre-eclampsia, the prediction and prevention of term pre-eclampsia remain unsolved. Previously proposed approaches are based on combined third-trimester screening and/or prophylactic drugs, but these policies are unlikely to be widely implementable in many world settings. Recent evidence shows that the soluble fms-like tyrosine kinase-1 (s-Flt-1) to placental growth factor (PlGF) ratio measured at 35-37 weeks' gestation predicts term pre-eclampsia with an 80% detection rate. Likewise, recent studies demonstrate that induction of labour beyond 37 weeks is safe and well accepted by women. We hypothesise that a single-step universal screening for term pre-eclampsia based on sFlt1/PlGF ratio at 35-37 weeks followed by planned delivery beyond 37 weeks reduces the prevalence of term pre-eclampsia without increasing the caesarean section rates or worsening the neonatal outcomes. METHODS AND ANALYSIS: We propose an open-label randomised clinical trial to evaluate the impact of a screening of term pre-eclampsia with the sFlt-1/PlGF ratio followed by planned delivery in asymptomatic nulliparous women at 35-37 weeks. Women will be assigned 1:1 to revealed (sFlt-1/PlGF known to clinicians) versus concealed (unknown) arms. A cut-off of >90th centile is used to define the high risk of subsequent pre-eclampsia and offer planned delivery from 37 weeks. The efficacy variables will be analysed and compared between groups primarily following an intention-to-treat approach, by ORs and their 95% CI. This value will be computed using a Generalised Linear Mixed Model for binary response (study group as fixed effect and the centre as intercept random effect). ETHICS AND DISSEMINATION: The study is conducted under the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 20 November 2020. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04766866.

Population pharmacokinetics and humanized dosage regimens matching the peak, area, trough, and range of amikacin plasma concentrations in immune-competent murine bloodstream and lung infection models.

Amikacin is an FDA-approved aminoglycoside antibiotic that is commonly used. However, validated dosage regimens that achieve clinically relevant exposure profiles in mice are lacking. We aimed to design and validate humanized dosage regimens for amikacin in immune-competent murine bloodstream and lung infection models of Acinetobacter baumannii. Plasma and lung epithelial lining fluid (ELF) concentrations after single subcutaneous doses of 1.37, 13.7, and 137 mg/kg of body weight were simultaneously modeled via population pharmacokinetics. Then, humanized amikacin dosage regimens in mice were designed and prospectively validated to match the peak, area, trough, and range of plasma concentration profiles in critically ill patients (clinical dose: 25-30 mg/kg of body weight). The pharmacokinetics of amikacin were linear, with a clearance of 9.93 mL/h in both infection models after a single dose. However, the volume of distribution differed between models, resulting in an elimination half-life of 48 min for the bloodstream and 36 min for the lung model. The drug exposure in ELF was 72.7% compared to that in plasma. After multiple q6h dosing, clearance decreased by ~80% from the first (7.35 mL/h) to the last two dosing intervals (~1.50 mL/h) in the bloodstream model. Likewise, clearance decreased by 41% from 7.44 to 4.39 mL/h in the lung model. The humanized dosage regimens were 117 mg/kg of body weight/day in mice [administered in four fractions 6 h apart (q6h): 61.9%, 18.6%, 11.3%, and 8.21% of total dose] for the bloodstream and 96.7 mg/kg of body weight/day (given q6h as 65.1%, 16.9%, 10.5%, and 7.41%) for the lung model. These validated humanized dosage regimens and population pharmacokinetic models support translational studies with clinically relevant amikacin exposure profiles.

The demographic history and adaptation of Canarian goat breeds to environmental conditions through the use of genome-wide SNP data.

BACKGROUND: The presence of goats in the Canary Islands dates back to the late 1st millennium BC, which coincides with the colonization by the Amazigh settlers. However, the exact geographic origin of Canarian goats is uncertain since the Amazigh peoples were distributed over a wide spatial range. Nowadays, three Canarian breeds (Palmera, Majorera and Tinerfeña) are officially recognized, along with two distinct South and North Tinerfeña ecotypes, with the South Tinerfeña and Majorera goats thriving in arid and dry semi-desertic environments and the Palmera and North Tinerfeña goats are adapted to humid and temperate areas that are influenced by trade winds. Genotypes for 224 Canarian goats were generated using the Illumina Goat single nucleotide polymorphism (SNP)50 BeadChip. By merging these data with the genotypes from 1007 individuals of African and Southern European ancestry, our aim was to ascertain the geographic origin of the Canarian goats and identify genes associated with adaptation to diverse environmental conditions. RESULTS: The diversity indices of the Canarian breeds align with most of those of the analyzed local breeds from Africa and Europe, except for the Palmera goats that showed lower levels of genetic variation. The Canarian breeds demonstrate a significant genetic differentiation compared to other populations, which indicates a history of prolonged geographic isolation. Moreover, the phylogenetic reconstruction indicated that the ancestry of the Canarian goats is fundamentally North African rather than West African. The ADMIXTURE and the TreeMix analyses showed no evidence of gene flow between Canarian goats and other continental breeds. The analysis of runs of homozygosity (ROH) identified 13 ROH islands while the window-based FST method detected 25 genomic regions under selection. Major signals of selection were found on Capra hircus (CHI) chromosomes 6, 7, and 10 using various comparisons and methods. CONCLUSIONS: This genome-wide analysis sheds new light on the evolutionary history of the four breeds that inhabit the Canary Islands. Our findings suggest a North African origin of the Canarian goats. In addition, within the genomic regions highlighted by the ROH and FST approaches, several genes related to body size and heat tolerance were identified.

Anti-SARS-CoV-2-specific antibodies in human breast milk following SARS-CoV-2 infection during pregnancy: a prospective cohort study.

BACKGROUND: While the presence of SARS-CoV-2 in human breast milk is contentious, anti-SARS-CoV-2 antibodies have been consistently detected in human breast milk. However, it is uncertain when and how long the antibodies are present. METHODS: This was a prospective cohort study including all consecutive pregnant women with confirmed SARS-CoV-2 infection during pregnancy, recruited at six maternity units in Spain and Hong Kong from March 2020 to March 2021. Colostrum (day of birth until day 4 postpartum) and mature milk (day 7 postpartum until 6 weeks postpartum) were prospectively collected, and paired maternal blood samples were also collected. Colostrum samples were tested with rRT-PCR-SARS-CoV-2, and skimmed acellular milk and maternal sera were tested against SARS-CoV-2 specific immunoglobulin M, A, and G reactive to receptor binding domain of SARS-CoV-2 spike protein 1 to determine the presence of immunoglobulins. Then, we examined how each immunoglobulin type in the colostrum was related to the time of infection by logistic regression analysis, the concordance between these immunoglobulins in the colostrum, maternal serum, and mature milk by Cohen's kappa statistic, and the relationship between immunoglobulin levels in mature milk and colostrum with McNemar. RESULTS: One hundred eighty-seven pregnant women with confirmed SARS-CoV-2 infection during pregnancy or childbirth were recruited and donated the milk and blood samples. No SARS-CoV-2 was found in the human breast milk. Immunoglobulin A, G, and M were present in 129/162 (79·6%), 5/163 (3·1%), and 15/76 (19·7%) colostrum samples and in 17/62 (27·42%), 2/62 (3·23%) and 2/62 (3·23%) mature milk samples, respectively. Immunoglobulin A was the predominant immunoglobulin found in breast milk, and its levels were significantly higher in the colostrum than in the mature milk (p-value < 0.001). We did not find that the presence of immunoglobulins in the colostrum was associated with their presence in maternal, the severity of the disease, or the time when the infection had occurred. CONCLUSIONS: Since anti-SARS-CoV-2 antibodies are found in the colostrum irrespective of the time of infection during pregnancy, but the virus itself is not detected in human breast milk, our study found no indications to withhold breastfeeding, taking contact precautions when there is active disease.

Triple vasodilator therapy in pulmonary arterial hypertension associated with congenital heart disease.

OBJECTIVE: This study assessed the long-term effects of triple therapy with prostanoids on patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD), as there is limited information on the safety and efficacy of this treatment approach. METHODS: A retrospective cohort study was conducted on patients with PAH-CHD who were actively followed up at our centre. All patients were already receiving dual combination therapy at maximum doses. Clinical characteristics, including functional class (FC), 6-minute walking test distance (6MWTD) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, were documented before initiating triple therapy and annually for a 2-year follow-up period. RESULTS: A total of 60 patients were included in the study, with a median age of 41 years and 68% being women. Of these, 32 had Eisenmenger syndrome, 9 had coincidental shunts, 18 had postoperative PAH and 1 had a significant left-to-right shunt. After 1 year of triple combination initiation, a significant improvement in 6MWTD was observed (406 vs 450; p=0.0027), which was maintained at the 2-year follow-up. FC improved in 79% of patients at 1 year and remained stable in 76% at 2 years. NT-proBNP levels decreased significantly by 2 years, with an average reduction of 199 ng/L. Side effects were experienced by 33.3% of patients but were mostly mild and manageable. Subgroup analysis showed greater benefits in patients without Eisenmenger syndrome and those with pre-tricuspid defects. CONCLUSIONS: Triple therapy with prostanoids is safe and effective for patients with PAH-CHD, improving FC, 6MWTD and NT-proBNP levels over 2 years. The treatment is particularly beneficial for patients with pre-tricuspid defects and non-Eisenmenger PAH-CHD.

Single and longitudinal genome-wide association studies for dairy traits available in goats with three recorded lactations.

Milk yield and composition phenotypes are systematically recorded across several lactations in goats, but the majority of genome-wide association studies (GWAS) performed so far have rather ignored the longitudinal nature of such data. Here, we have used two different GWAS approaches to analyse data from three lactations recorded in Murciano-Granadina goats. In Analysis 1, independent GWAS have been carried out for each trait and lactation, while a single longitudinal GWAS, jointly considering all data, has been performed in Analysis 2. In both analyses, genome-wide significant QTL for lactose percentage on chromosome 2 (129.77-131.01 Mb) and for milk protein percentage on the chromosome 6 (74.8-94.6 Mb) casein gene cluster region were detected. In Analysis 1, several QTL were not replicated in all three lactations, possibly due to the existence of lactation-specific genetic determinants. In Analysis 2, we identified several genome-wide significant QTL related to milk yield and protein content that were not uncovered in Analysis 1. The increased number of QTL identified in Analysis 2 suggests that the longitudinal GWAS is particularly well suited for the genetic analysis of dairy traits. Moreover, our data confirm that variability within or close to the casein complex is the main genetic determinant of milk protein percentage in Murciano-Granadina goats.

Adenoma Hepatocelular. A propósito de un caso

El Adenoma Hepatocelular (AH) es un tumor hepático benigno, su diagnóstico ha avanzado gracias a los avances en los métodos moleculares, facilitaron dividirlos en subtipos, con diferentes pronósticos e indicaciones terapéuticas. Se presenta el caso clínico de una paciente, de 40 años con hallazgo ecográfico de tumor hepático, la Tomografía de Abdomen y Pelvis voluminosa lesión sólida heterogénea, en la Resonancia Magnética compatible con Adenoma esteatósico (asociado a mutación HNF1 alfa). Se decide tratamiento quirúrgico, con resección de los segmentos 6 y 7. La Anatomía patológica concluye: Compatible con el subtipo inflamatorio. Los Adenoma hepáticos (AH) son tumores raros, solitarios de estirpe epitelial, benignos. Se presentan en mujeres de edad fértil y asociado al consumo de anticonceptivos orales y estrógenos. Estos tumores predominan en hígado derecho, con proliferación de células parecidas a los hepatocitos normales, pero desorganizados y sin arquitectura lobular normal, sin ductos biliares ni tejido conectivo de sostén. Los AH así como el resto de los tumores hepáticos benignos, han aumentado su incidencia de la mano con el avance de la imagenología abdominal. La importancia de la diferenciación con el resto de los tumores hepáticos benignos surge del potencial maligno de éstos. Podemos clasificar a los pacientes según el perfil molecular asociado a marcadores inmunohistoquímicos. Los estudios de imagen son fundamentales para la diferenciación tumoral en diagnóstico y planear la terapéutica. El tratamiento será individualizado, determinada por la clínica, la variedad de subtipos, y la evolución. Debido a la complejidad de la enfermedad, el tratamiento de la HA es uno de los mejores ejemplos de abordaje individualizado en unidades hepatobiliares.

Hepatocellular adenoma (HA) is a benign liver tumor, its diagnosis has advanced thanks to advances in molecular methods, which facilitated its division into subtypes, with different prognoses and therapeutic indications. We present the clinical case of a 40-year-old patient with an ultrasound finding of a liver tumor, a voluminous heterogeneous solid lesion on a CT scan of the abdomen and pelvis, compatible with a steatotic adenoma on MRI (associated with HNF1 alpha mutation). Surgical treatment was decided, with resection of segments 6 and 7. The pathology concluded in short: Compatible with the inflammatory subtype. Hepatic adenomas (HA) are rare, solitary, benign epithelial tumors. They occur in women of childbearing age and associated with the consumption of oral contraceptives and estrogens. These tumors predominate in the right liver, with proliferation of cells similar to normal hepatocytes, but disorganized and without normal lobular architecture, without bile ducts or supporting connective tissue. HA, as well as the rest of the benign liver tumors, have increased their incidence in the hand with the advancement of abdominal imaging. The importance of differentiation with the rest of the benign liver tumors arises from the malignant potential of these. We can classify patients according to the molecular profile associated with immunohistochemical markers. Imaging studies are fundamental for tumor differentiation in diagnosis and therapeutic planning. The treatment will be individualized, determined by the clinic, the variety of subtypes, and the evolution. Due to the complexity of the disease, the treatment of AH is one of the best examples of an individualized approach in hepatobiliary units.

O adenoma hepatocelular (AH) éum tumor benigno do fígado, seu diagnóstico avançougraçasaosavanços dos métodos moleculares, que facilitaramsuadivisão em subtipos, com diferentes prognósticos e indicaçõesterapêuticas. Apresentamos o caso clínico de umadoente de 40 anoscomachadoultrassonográfico de tumor hepático, volumosalesão sólida heterogénea à TC de abdómen e pelve, compatívelcom adenoma esteatótico à RM (associado a mutação HNF1 alfa ). Optou-se por tratamentocirúrgico, comressecção dos segmentos 6 e 7. A patologiaconcluiu-se resumidamente: Compatívelcom o subtipo inflamatório. Os adenomas hepáticos (AH) são tumores epiteliais raros, solitários e benignos. Ocorrem em mulheres em idadereprodutiva e associadasao consumo de anticoncepcionaisorais e estrogênios. Esses tumores predominam no fígadodireito, comproliferação de células semelhantesaoshepatócitosnormais, porém desorganizados e semarquitetura lobular normal, sem ductos biliares outecido conjuntivo de sustentação. O HA, assim como os demais tumores hepáticos benignos, têm aumentado suaincidêncianamãocom o avanço da imagem abdominal. A importância da diferenciaçãocom os demais tumores hepáticos benignos decorre do potencial maligno destes. Podemos classificar os pacientes de acordocom o perfil molecular associado a marcadores imuno-histoquímicos. Os estudos de imagemsãofundamentais para a diferenciação tumoral no diagnóstico e planejamentoterapêutico. O tratamento será individualizado, determinado pela clínica, variedade de subtipos e evolução. Pela complexidade da doença, o tratamento da HA é um dos melhoresexemplos de abordagem individualizada nas unidades hepatobiliares.

Neoplasia quística mucinosa hepática, reporte de un caso y análisis de la patología / Hepatic mucinous cystic neoplasm, case report and pathology analysis / Neoplasia cística mucinosa hepática, relatório de um caso e análise da patologia

Desde los primeros reportes en la bibliografía, la nomenclatura de las lesiones quísticas hepatobiliares se ha ido modificando, habiéndose descripto dos tipos de lesiones: las serosas y las mucinosas. En 2010 la Organización Mundial de la Salud estableció una nueva clasificación donde los términos cistoadenomas y cistoadenocarcinomas hepatobiliares son reemplazados por entidades más específicas como la neoplasia mucinosa quística y los tumores quísticos intraductales (neoplasia papilar intraductal, neoplasma tubulopapilar intraductal y neoplasma oncocitico papilar). En cuanto a la neoplasia mucinosa quística, la presencia de estroma ovárico le confiere características distintivas en lo patológico y biológico, siendo esto un requisito en la clasificación de la OMS. Esta característica lo diferencia de los hamartomas biliares, los quistes congénitos y la enfermedad de Caroli. Dichas neoplasias son infrecuentes, con una incidencia menor al 5% de las lesiones quísticas hepáticas y ocurren casi exclusivamente en mujeres, frecuentemente perimenopáusicas. Su potencial de malignización ha sido descrito, siendo éste la indicación de tratamiento quirúrgico resectivo. Presentamos el caso clínico de una paciente portadora de una neoplasia quística mucinosa hepática, catalogada como cistoadenoma hepático según la antigua clasificación.

Since the early reports in the literature, the nomenclature of hepatobiliary cystic lesions has been modified, with two types of lesions being described: serous and mucinous. In 2010, the World Health Organization established a new classification in which the terms hepatobiliary cystadenomas and cystadenocarcinomas were replaced by more specific entities such as mucinous cystic neoplasms and intraductal cystic tumors (intraductal papillary neoplasm, intraductal tubulopapillary neoplasm, and intraductal oncocytic papillary neoplasm). Regarding mucinous cystic neoplasms, the presence of ovarian stroma confers distinctive pathological and biological characteristics, which is a requirement in the WHO classification. This characteristic differentiates it from biliary hamartomas, congenital cysts, and Caroli's disease. Such neoplasms are rare, with an incidence of less than 5% of hepatic cystic lesions, and occur almost exclusively in women, often perimenopausal. Their potential for malignancy has been described, and this is the indication for surgical resection treatment. We present a clinical case of a patient with a mucinous cystic hepatic neoplasm, classified as a hepatic cystadenoma according to the old classification.

Desde os primeiros relatos na literatura, a nomenclatura das lesões císticas hepatobiliares tem sido modificada, sendo descritos dois tipos de lesões,asserosas e as mucinosas. Em 2010, a Organização Mundial da Saúdeestabeleceuuma nova classificação, naqual os termos cistoadenomas e cistoadenocarcinomas hepatobiliares foramsubstituídos por entidades mais específicas, como a neoplasia mucinosa cística e os tumores císticos intraductais (neoplasia papilar intraductal, neoplasma tubulopapilar intraductal e neoplasma oncocítico papilar). Em relação à neoplasia mucinosa cística, a presença de estroma ovarianoconfere características distintas do ponto de vista patológico e biológico, sendoesseum requisito naclassificação da OMS. Essa característica a diferencia dos hamartomas biliares, cistoscongênitos e doença de Caroli. Essas neoplasias são raras, comumaincidência menor que 5% das lesões císticas hepáticas, e ocorremquase exclusivamente em mulheres, frequentementeperimenopáusicas. Seu potencial de malignizaçãotem sido descrito, sendoesta a indicação para tratamentocirúrgicoressectivo. Apresentamos o caso clínico de uma paciente portadora de uma neoplasia cística mucinosa hepática, classificada como cistoadenoma hepático de acordocom a antigaclassificação.

Formic Acid Decomposition Using Palladium-Zinc Preformed Colloidal Nanoparticles Supported on Carbon Nanofibre in Batch and Continuous Flow Reactors: Experimental and Computational Fluid Dynamics Modelling Studies.

The need to replace conventional fuels with renewable sources is a great challenge for the science community. H2 is a promising alternative due to its high energy density and availability. H2 generation from formic acid (FA) decomposition occurred in a batch and a packed-bed flow reactor, in mild conditions, using a 2% Pd6Zn4/HHT (high heated treated) catalyst synthesised via the sol-immobilisation method. Experimental and theoretical studies took place, and the results showed that in the batch system, the conversion was enhanced with increasing reaction temperature, while in the continuous flow system, the conversion was found to decrease due to the deactivation of the catalyst resulting from the generation of the poisoning CO. Computational fluid dynamics (CFD) studies were developed to predict the conversion profiles, which demonstrated great validation with the experimental results. The model can accurately predict the decomposition of FA as well as the deactivation that occurs in the continuous flow system. Of significance was the performance of the packed-bed flow reactor, which showed improved FA conversion in comparison to the batch reactor, potentially leading to the utilisation of continuous flow systems for future fuel cell applications for on-site H2 production.

Evolution of economic burden of heart failure by ejection fraction in newly diagnosed patients in Spain.

OBJECTIVE: To describe healthcare resource utilization (HCRU) and costs, in patients with newly diagnosed heart failure (HF) according to ejection fraction (EF) in Spain. METHODS: Retrospective cohort study that analyzed anonymized, integrated and computerised medical records in Spain. Patients with ≥ 1 new HF diagnosis between January 2013 and September 2019 were included and followed-up during a 4-year period. Rates per 100 person-years of HCRU and costs were estimated. RESULTS: Nineteen thousand nine hundred sixty-one patients were included, of whom 43.5%, 26.3%, 5.1% and 25.1% had HF with reduced, preserved, mildly reduced and unknown EF, respectively. From year 1 to 4, HF rates of outpatient visits decreased from 1149.5 (95% CI 1140.8-1159.3) to 765.5 (95% CI 745.9-784.5) and hospitalizations from 61.7 (95% CI 60.9-62.7) to 15.7(14.7-16.7) per 100 person-years. The majority of HF-related healthcare resource costs per patient were due to hospitalizations (year 1-4: 63.3-38.2%), followed by indirect costs (year 1-4: 12.2-29.0%), pharmacy (year 1-4: 11.9-19.9%), and outpatient care (year 1-4: 12.6-12.9%). Mean (SD) per patient HF-related costs decreased from 2509.6 (3518.5) to 1234.6 (1534.1) Euros (50% cost reduction). At baseline, 70.1% were taking beta-blockers, 56.3% renin-angiotensin system inhibitors, 11.8% mineralocorticoid receptor antagonists and 8.9% SGLT2 inhibitors. At 12 months, these numbers were 72.3%, 65.4%, 18.9% and 9.8%, respectively. CONCLUSIONS: Although the economic burden of HF decreased over time since diagnosis, it is still substantial. This reduction could be partially related to a survival bias (sick patients died early), but also to a better HF management. Despite that, there is still much room for improvement.

De Novo Donor-Specific Antibodies after Heart Transplantation: A Comprehensive Guide for Clinicians.

Antibodies directed against donor-specific human leukocyte antigens (HLAs) can be detected de novo after heart transplantation and play a key role in long-term survival. De novo donor-specific antibodies (dnDSAs) have been associated with cardiac allograft vasculopathy, antibody-mediated rejection, and mortality. Advances in detection methods and international guideline recommendations have encouraged the adoption of screening protocols among heart transplant units. However, there is still a lack of consensus about the correct course of action after dnDSA detection. Treatment is usually started when antibody-mediated rejection is present; however, some dnDSAs appear years before graft failure is detected, and at this point, damage may be irreversible. In particular, class II, anti-HLA-DQ, complement binding, and persistent dnDSAs have been associated with worse outcomes. Growing evidence points towards a more aggressive management of dnDSA. For that purpose, better diagnostic tools are needed in order to identify subclinical graft injury. Cardiac magnetic resonance, strain techniques, or coronary physiology parameters could provide valuable information to identify patients at risk. Treatment of dnDSA usually involves plasmapheresis, intravenous immunoglobulin, immunoadsorption, and ritxumab, but the benefit of these therapies is still controversial. Future efforts should focus on establishing effective treatment protocols in order to improve long-term survival of heart transplant recipients.

Single-Element Dual-Interferometer for Precision Inertial Sensing: Sub-Picometer Structural Stability and Performance as a Reference for Laser Frequency Stabilization.

Future GRACE-like geodesy missions could benefit from adopting accelerometer technology akin to that of the LISA Pathfinder, which employed laser interferometric readout at the sub-picometer level in addition to the conventional capacitive sensing, which is at best at the level of 100 pm. Improving accelerometer performance holds great potential to enhance the scientific output of forthcoming missions, carrying invaluable implications for research in climate, water resource management, and disaster risk reduction. To reach sub-picometer displacement sensing precision in the millihertz range, laser interferometers rely on suppression of laser-frequency noise by several orders of magnitude. Many optical frequency stabilization methods are available with varying levels of complexity, size, and performance. In this paper, we describe the performance of a Mach-Zehnder interferometer based on a compact monolithic optic. The setup consists of a commercial fiber injector, a custom-designed pentaprism used to split and recombine the laser beam, and two photoreceivers placed at the complementary output ports of the interferometer. The structural stability of the prism is transferred to the laser frequency via amplification, integration, and feedback of the balanced-detection signal, achieving a fractional frequency instability better than 6 parts in 1013, corresponding to an interferometer pathlength stability better than 1pm/Hz. The prism was designed to host a second interferometer to interrogate the position of a test mass. This optical scheme has been dubbed "single-element dual-interferometer" or SEDI.

Parenteral Nutrition: Current Use, Complications, and Nutrition Delivery in Critically Ill Patients.

BACKGROUND: Parenteral nutrition (PN) is needed to avoid the development of malnutrition when enteral nutrition (EN) is not possible. Our main aim was to assess the current use, complications, and nutrition delivery associated with PN administration in adult critically ill patients, especially when used early and as the initial route. We also assessed the differences between patients who received only PN and those in whom EN was initiated after PN (PN-EN). METHODS: A multicenter (n = 37) prospective observational study was performed. Patient clinical characteristics, outcomes, and nutrition-related variables were recorded. Statistical differences between subgroups were analyzed accordingly. RESULTS: From the entire population (n = 629), 186 (29.6%) patients received PN as initial nutrition therapy. Of these, 74 patients (11.7%) also received EN during their ICU stay (i.e., PN-EN subgroup). PN was administered early (<48 h) in the majority of patients (75.3%; n = 140) and the mean caloric (19.94 ± 6.72 Kcal/kg/day) and protein (1.01 ± 0.41 g/kg/day) delivery was similar to other contemporary studies. PN showed similar nutritional delivery when compared with the enteral route. No significant complications were associated with the use of PN. Thirty-two patients (43.3%) presented with EN-related complications in the PN-EN subgroup but received a higher mean protein delivery (0.95 ± 0.43 vs 1.17 ± 0.36 g/kg/day; p = 0.03) compared with PN alone. Once adjusted for confounding factors, patients who received PN alone had a lower mean protein intake (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.18-0.47; p = 0.001), shorter ICU stay (HR: 0.96; 95% CI: 0.91-0.99; p = 0.008), and fewer days on mechanical ventilation (HR: 0.85; 95% CI: 0.81-0.89; p = 0.001) compared with the PN-EN subgroup. CONCLUSION: The parenteral route may be safe, even when administered early, and may provide adequate nutrition delivery. Additional EN, when possible, may optimize protein requirements, especially in more severe patients who received initial PN and are expected to have longer ICU stays. NCT Registry: 03634943.

Converting carbon black into an efficient and multi-site ORR electrocatalyst: the importance of bottom-up construction parameters.

To boost efficient energy transitions, alternatives to expensive and unsustainable noble metal-based electrocatalysts for the oxygen reduction reaction (ORR) are needed. Having this in mind, carbon black - Black Pearls 2000 (BP) was enriched in active nitrogen-containing centers, including single-atom Fe-N sites surrounded by Fe nanoclusters, through a synthesis methodology employing only broadly available precursors. The methodical approach taken to optimize the synthesis conditions highlighted the importance of (1) a proper choice of the Fe precursor; (2) melamine as an N source to limit the formation of magnetite crystals and modulate the charge density nearby the active sites, and glucose to chelate/isolate Fe atoms and thus allow the Fe-N coordination to be established, with a limiting formation of Fe0 clusters; and (3) a careful dosing of the Fe load. The ORR on the optimized electrocatalyst (Fe0.06-N@BP) proceeds mostly through a four-electron pathway, having an onset potential (0.912 V vs. RHE) and limiting current density (4.757 mA cm-2) above those measured on Pt/C (0.882 V and 4.657 mA cm-2, respectively). Moreover, the current density yielded by Fe0.06-N@BP after 24 h at 0.4 V vs. RHE was still above that of Pt/C at t = 0 (4.44 mA cm-2), making it a promising alternative to noble metal-containing electrocatalysts in fuel cells.