Disappearing colorectal liver metastases in the era of state-of-the-art triple-modality diagnostic imaging.

INTRODUCTION: Systemic therapy can result in disappearance of colorectal liver metastases in up to 40% of patients. This might be an overestimation caused by suboptimal imaging modalities. The aim of this study was to investigate the use of imaging modalities and the incidence, management and outcome of patients with disappearing liver metastases (DLMs). METHODS: This was a retrospective study of consecutive patients treated for colorectal liver metastases at a high volume hepatobiliary centre between January 2013 and January 2015 after receiving induction or neoadjuvant systemic therapy. Main outcomes were use of imaging modalities, incidence, management and longterm outcome of patients with DLMs. RESULTS: Of 158 patients included, 32 (20%) had 110 DLMs. Most patients (88%) had initial diagnostic imaging with contrast enhanced-CT, primovist-MR and FDG-PET and 94% of patients with DLMs were restaged using primovist-MR. Patients with DLMs had significantly smaller metastases and the median initial size of DLMs was 10 mm (range 5-61). In the per lesion analysis, recurrence after "watch & wait" for DLMs occurred in 36%, while in 19 of 20 resected DLMs no viable tumour cells were found. Median overall (51 vs. 28 months, p < 0.05) and progression free survival (10 vs. 3 months, p = 0.003) were significantly longer for patients with DLMs. CONCLUSION: Even state-of-the-art imaging and restaging cannot solve problems associated with DLMs. Regrowth of these lesions occurs in approximately a third of the lesions. Patients with DLMs have better survival.

The Contribution of Transpiration to Precipitation Over African Watersheds.

The redistribution of biological (transpiration) and non-biological (interception loss, soil evaporation) fluxes of terrestrial evaporation via atmospheric circulation and precipitation is an important Earth system process. In vegetated ecosystems, transpiration dominates terrestrial evaporation and is thought to be crucial for regional moisture recycling and ecosystem functioning. However, the spatial and temporal variability in the dependency of precipitation on transpiration remains understudied, particularly in sparsely sampled regions like Africa. Here, we investigate how biological and non-biological sources of evaporation in Africa contribute to rainfall over the major watersheds in the continent. Our study is based on simulated atmospheric moisture trajectories derived from the Lagrangian model FLEXPART, driven by 1° resolution reanalysis data over 1981-2016. Using daily satellite-based fractions of transpiration over terrestrial evaporation, we isolate the contribution of vegetation to monthly rainfall. Furthermore, we highlight two watersheds (Congo and Senegal) for which we explore intra- and interannual variability of different precipitation sources, and where we find contrasting patterns of vegetation-sourced precipitation within and between years. Overall, our results show that almost 50% of the annual rainfall in Africa originates from transpiration, although the variability between watersheds is large (5%-68%). We conclude that, considering the current and projected patterns of land use change in Africa, a better understanding of the implications for continental-scale water availability is needed.

Genotypic spectrum underlying tetrahydrobiopterin metabolism defects: Experience in a single Mexican reference center.

Background: Pterin profiles or molecular analyses of hyperphenylalaninemia (HPA) caused by phenylalanine hydroxylase (PAH) deficiency or tetrahydrobiopterin deficiency (BH4D) are not always available in low- or middle-income countries, including Mexico, limiting information regarding the phenotypic and genotypic characteristics of patients exhibiting BH4D. Objective: To report the genotypes underlying BH4D and the clinical presentation in unrelated Mexican HPA pediatric patients with normal PAH genotypes who attended a single metabolic reference center in Mexico. Methods: Automated Sanger sequencing of the PTS, QDPR, and PCBD1 genes of 14 HPA patients was performed. Predicted effects on protein structure caused by missense variants were assessed by in silico protein modeling. Results and discussion: A high prevalence of BH4D was noted in our HPA cohort (9.8%, N = 14/142). Clinically relevant biallelic genotypes were identified in the PTS (N = 7/14 patients), QDPR (N = 6/14 patients), and PCBD1 (N = 1/14 patients) genes. Four novel QDPR variants [c.714dup or p.(Leu239Thrfs*44), c.106-1G>T or p.(?), c.214G>T or p.(Gly72*), and c.187_189dup or p.(Gln63dup)] were identified. In silico protein modeling of six missense variants of PTS [p.(Thr67Met), p.(Glu81Ala), and p.(Tyr113Cys)], QDPR [p.(Cys161Phe) and p.(Pro172Leu)], and PCBD1 [p.(Glu97Lys)] supports their pathogenicity. Progressive neurological symptoms (mainly intellectual and motor impairment and even death in three patients) were noted in all patients with biallelic QDPR genotypes and in 5/7 patients bearing biallelic PTS genotypes. The single homozygous PCBD1 p.(Glu97Lys) patient remains asymptomatic. Conclusion: A higher proportion of BH4D (9.8 vs. 1%-2% worldwide), attributable to a heterogeneous mutational spectrum and wide clinical presentation, was noted in our Mexican HPA cohort, with the PTS-related HPA disorder being the most frequent. Sequencing-based assays could be a reliable approach for diagnosing BH4D in our population.

Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

African Swine Fever Virus (ASFV) Indirect ELISA Test Based on the Use of the Soluble Cytoplasmic Semi- purified Antigen (ASFV CP-Ag).

The present chapter describes a simple and economic indirect enzyme immunoassay (ELISA ) for African swine fever virus (ASFV) antibody detection based on the use of the soluble cytoplasmic fraction of ASFV-infected monkey stable cells (MS). The soluble antigen proteins of ASFV-infected cells are separated by sucrose precipitation centrifugation, and the supernatant above the sucrose layer is used as an ELISA antigen. The test serum sample reacts with the cytoplasmic soluble fraction, and antibodies are detected using a protein A-peroxidase conjugate. This crude antigen is currently recommended as a test reagent in screening and diagnostic tests by the World Organization for Animal Health (OIE).

Indirect Immunoperoxidase Test (IPT) for Detection of Antibodies Against African Swine Fever Virus (ASFV) on African Green Monkey Cell Lines (Vero, MS).

The immunoperoxidase technique (IPT) is an immunocytochemistry technique on fixed infected cells to determine the antibody-antigen complex formation through the action of the peroxidase enzyme. In this procedure, African green monkey established cell lines, such as Vero or MS, are infected with African swine fever virus (ASFV)-adapted isolates to these cell cultures. The infected cells are fixed and then used as antigens to determine the presence of the specific antibodies against ASFV in samples of swine origin. IPT has many advantages for the serological diagnosis of ASF. Firstly, IPT has a higher sensitivity than ELISA or immunoblot assay (IB) for the detection of antibodies against ASFV. Secondly, it has greater versatility to analyze any type of clinical sample of porcine origin and to conduct research studies on the epidemiological situation, through the presence of antibody titers in exudates from organs and tissues. Thirdly, the preparation of IPT plates with cells infected with ASFV is simple, although laborious, that can be stored for a long time and allow the analysis of a large number of samples.

Effects of Drought on Mortality in Macro Urban Areas of Brazil Between 2000 and 2019.

A significant fraction of Brazil's population has been exposed to drought in recent years, a situation that is expected to worsen in frequency and intensity due to climate change. This constitutes a current key environmental health concern, especially in densely urban areas such as several big cities and suburbs. For the first time, a comprehensive assessment of the short-term drought effects on weekly non-external, circulatory, and respiratory mortality was conducted in 13 major Brazilian macro-urban areas across 2000-2019. We applied quasi-Poisson regression models adjusted by temperature to explore the association between drought (defined by the Standardized Precipitation-Evapotranspiration Index) and the different mortality causes by location, sex, and age groups. We next conducted multivariate meta-analytical models separated by cause and population groups to pool individual estimates. Impact measures were expressed as the attributable fractions among the exposed population, from the relative risks (RRs). Overall, a positive association between drought exposure and mortality was evidenced in the total population, with RRs varying from 1.003 [95% CI: 0.999-1.007] to 1.010 [0.996-1.025] for non-external mortality related to moderate and extreme drought conditions, from 1.002 [0.997-1.007] to 1.008 [0.991-1.026] for circulatory mortality, and from 1.004 [0.995-1.013] to 1.013 [0.983-1.044] for respiratory mortality. Females, children, and the elderly population were the most affected groups, for whom a robust positive association was found. The study also revealed high heterogeneity between locations. We suggest that policies and action plans should pay special attention to vulnerable populations to promote efficient measures to reduce vulnerability and risks associated with droughts.

Side effects of the BNT162b2 vaccine in the personnel of the Military Central Hospital.

OBJECTIVE: The pandemic disease by SARS-CoV-2 infection does not have an effective treatment. To prevent the disease, scientists developed vaccines that the clinicians use as an emergency licensed vaccine. The objective of this study was to determine the side effects in personnel vaccinated at the Military Central Hospital of Mexico with the BNT162b2 vaccine. PATIENTS AND METHODS: This study included the subjects who had received both doses of the BNT162b2 vaccine between December 2020 and February 2021. We asked about the side effects after the first and the second vaccine doses. One group had no history of COVID-19, and the second had a history of COVID-19. ANTI-SARS-CoV-2 antibodies were measured by the immunodetection technique in the second group only. RESULTS: We included 946 participants, 62% were women, and 80% were without comorbidities; 680 were included in the first group, and only 266 were in the second group. After the first dose, 77% of the first group and 86% of the second group presented some side effects. After the second dose, 84% of the first group and 89% of the second group showed some side effects. The main side effect was mild pain. All participants (126) were IgG positive, and only 26.9% were IgM positive at 17.5 days (12.8 days, 20.3 days) after the second dose. CONCLUSIONS: There is a positive correlation between side effects after the first dose in patients with a history of previous SARS-CoV-2 infection compared to those who did not. Nevertheless, this correlation is not present after the second dose. The low percentage of IgM could be related to the time interval between vaccination and sample measure.

Rendimiento del ASAS Health Index en pacientes con Espondiloartritis de la vida real / Performance of ASAS Health Index in real life spondyloarthritis patients

Introducción: El cuestionario "Assessment of Spondyloarthritis International Society Health Index" (ASAS-HI) fue desarrollado para medir de manera global la funcionalidad y el estado de salud en pacientes con espondiloartritis (EspA). Se han propuesto puntos de corte para determinar diferentes estados de salud que fueron poco evaluados en pacientes de la vida real. Objetivos: Describir el estado de salud medido por ASAS-HI en pacientes argentinos con EspA axial (EspAax) y periférica (EspAp) en la práctica diaria y evaluar los factores asociados al pobre estado de salud. Materiales y métodos: Estudio de corte transversal, analítico y multicéntrico. Se incluyeron consecutivamente pacientes con EspAax y EspAp según criterios ASAS, de 15 centros argentinos. Análisis estadístico: Se realizó estadística descriptiva, análisis bivariado y multivariado (regresión logística múltiple) para evaluar los factores asociados al pobre estado de salud (ASAS-HI ≥12). Para analizar la validez de constructo de la herramienta se realizó correlación de Spearman entre el ASAS-HI y otros parámetros de evaluación de la enfermedad. Resultados: Se incluyeron 274 pacientes con EspA, con una edad media de 49 (±14) años y una duración mediana de la enfermedad de 62 meses (p25-75: 24-135), 155 (56,6%) de los pacientes eran de sexo masculino, 129 pacientes (47%) con EspAax y 145 (52,9%) EspAp. Según el ASAS-HI 119 pacientes (43,4%) presentaban buen estado de salud, 117 (42,7%) tenían estado de salud moderado y 38 (13.9%) pobre estado de salud. En los pacientes con EspAp el valor de ASAS-HI mediano fue de 7 (p25-75: 3-10). El ASAS-HI correlacionó positivamente con: DAS28: rho: 0.5 (p<0.001) y HAQ: rho: 0.54 (p<0.001). La variable asociada de manera independiente con pobre estado de salud fue el DAS28 (OR: 1.9, IC95% 1.1-3.4, p: 0.029). En los pacientes con EspAax el valor de ASAS-HI mediano fue de 6 (p25-75: 2.75-10). El ASAS-HI mostró correlación con: BASDAI: rho: 0.7 (p<0.001), ASDAS-ERS: rho: 0.7 (p<0,001), ASQoL: rho: 0.8 (p<0.001), BASFI rho: 0.75 (p<0.001). La variable que se asoció de manera independiente a pobre estado de salud fue el ASDAS-ERS (OR 6.6, IC95% 2-22, p 0.002). Conclusión: Un pobre estado de salud se asoció independientemente a mayor actividad de la enfermedad en pacientes con EspAax y EspAp. El ASAS-HI correlacionó con otros parámetros de la enfermedad, lo que refuerza la validez de constructo de esta nueva herramienta.

Introduction: The "Assessment of Spondyloarthritis International Society Health Index" (ASAS-HI) questionnaire was developed to globally measure function and health status in patients with spondyloarthritis (SpA). Cut-off points have been proposed to determine different health states that were poorly evaluated in real-life patients. Objectives: To describe the health status measured by ASAS-HI in Argentine patients with axial SpA (AxSpA) and peripheral SpA (SpAp) in daily practice and to evaluate the factors associated with poor health. Materials and methods: Cross-sectional, analytical and multicenter study. Patients with SpAax and SpAp were consecutively included according to ASAS criteria, from 15 Argentine centers. Statistical analysis: Descriptive statistics, bivariate and multivariate analysis (multiple logistic regression) were performed to evaluate the factors associated with poor health status (ASAS-HI ≥12). To analyze the construct validity of the tool, Spearman correlation was performed between the ASAS-HI and other disease evaluation parameters. Results: 274 patients with SpA were included, with a mean age of 49 (± 14) years and a median duration of the disease of 62 months (p25-75: 24-135), 155 (56.6%) were male, 129 patients (47%) with AxSpA and 145 (52.9%) SpAp. According to the ASAS-HI, 119 patients (43.4%) had good health, 117 (42.7%) had moderate health and 38 (13.9%) had poor health. In patients with SpAp, the mean ASAS-HI value was 7 (p25-75: 3-10). The ASAS-HI positively correlated with: DAS28: rho: 0.5 (p <0.001) and HAQ: rho: 0.54 (p <0.001). The variable independently associated with poor health status was DAS28 (OR: 1.9, 95% CI 1.1-3.4, p: 0.029). In patients with AxSpA, the mean ASAS-HI value was 6 (p25-75: 2.75-10). The ASAS-HI showed correlation with: BASDAI: rho: 0.7 (p <0.001), ASDAS-ERS: rho: 0.7 (p <0.001), ASQoL: rho: 0.8 (p <0.001), BASFI rho: 0.75 (p <0.001). The variable that was independently associated with poor health was the ASDAS-ERS (OR 6.6, 95% CI 2-22, p 0.002). Conclusion: Poor health status was independently associated with higher disease activity in patients with AxSpA and SpAp. The ASAS-HI correlated with other parameters of the disease, which reinforces the construct validity of this new tool.

Protein retention, growth performance and carcass traits of individually housed immunocastrated male- and female- and surgically castrated male Iberian pigs fed diets of increasing amino acid concentration.

Immunocastration (IC, vaccination against gonadotropin releasing hormone (GnRH)) is one alternative to surgical castration (SC) for preventing sexual development and boar taint in male pigs. A temporal increase in performance has been described for IC pigs before the second vaccination against GnRH. The objective of this work was to assess the effects of IC on Iberian male and female pigs (fed diets of increasing CP content) on performance, nitrogen retention (NR) and digestibility, and carcass traits. Fifty-four pure Iberian pigs individually housed were allocated to a 3 × 3 factorial arrangement with three sex groups (IC males, IC females and SC males), three diets (153, 137 and 119 g CP/kg DM; 14 MJ metabolisable energy/kg DM) and six pigs per treatment combination. Pigs were vaccinated at 18 weeks of age (40 kg BW) and seven weeks later (70-80 kg BW) and fed at 0.9 × ad libitum on BW basis. Two digestibility and nitrogen balance assays were performed before and after the second vaccination, respectively. Pigs were slaughtered at 105 kg BW. Before the second vaccination, Iberian IC males showed higher growth rate (g/day), feed efficiency, NR (g/day) and efficiency of NR than the other groups (P < 0.001). The NR and efficiency of NR was 40% greater in IC v. SC males (P < 0.001). After the second vaccination, no differences in performance between sex groups were detected (P > 0.05). Growth rate and feed efficiency were higher in IC males than in the other groups for the whole experimental period (from the first vaccination to slaughter; P < 0.001). After the second vaccination, differences among sex groups in NR and the efficiency of NR disappeared (P > 0.05). NR efficiency was 0.177 on average. No significant effects of dietary CP were detected on performance. The NR was greater in pigs fed the 153 CP diet (17 to 37%; P > 0.05). Lean components of carcass (sirloin, loin and butt lean) were greater in IC males than in the other groups (0.001 < P < 0.05). There were no significant sex group×dietary CP interactions. Iberian IC males grew at higher rate, deposited more protein, and more efficiently, than Iberian SC males before the second vaccination against GnRH. Iberian IC females showed similar growth performance to SC males and intermediate protein deposition efficiency between IC and SC males. Despite the higher growth performance, protein deposition rate, and efficiency of protein deposition of IC males v. SC males, no significant differences in amino acid requirements were detected between them.

Impact of the COVID-19 pandemic on hospitalizations for acute coronary syndromes: a multinational study.

BACKGROUND: COVID-19 has challenged the health system organization requiring a fast reorganization of diagnostic/therapeutic pathways for patients affected by time-dependent diseases such as acute coronary syndromes (ACS). AIM: To describe ACS hospitalizations, management, and complication rate before and after the COVID-19 pandemic was declared. DESIGN: Ecological retrospective study. Methods: We analyzed aggregated epidemiological data of all patients > 18 years old admitted for ACS in twenty-nine hub cardiac centers from 17 Countries across 4 continents, from December 1st, 2019 to April 15th, 2020. Data from December 2018 to April 2019 were used as historical period. RESULTS: A significant overall trend for reduction in the weekly number of ACS hospitalizations was observed (20.2%; 95% confidence interval CI [1.6, 35.4] P = 0.04). The incidence rate reached a 54% reduction during the second week of April (incidence rate ratio: 0.46, 95% CI [0.36, 0.58]) and was also significant when compared to the same months in 2019 (March and April, respectively IRR: 0.56, 95%CI [0.48, 0.67]; IRR: 0.43, 95%CI [0.32, 0.58] p < 0.001). A significant increase in door-to-balloon, door-to-needle, and total ischemic time (p <0.04 for all) in STEMI patents were reported during pandemic period. Finally, the proportion of patients with mechanical complications was higher (1.98% vs. 0.98%; P = 0.006) whereas GRACE risk score was not different. CONCLUSIONS: Our results confirm that COVID-19 pandemic was associated with a significant decrease in ACS hospitalizations rate, an increase in total ischemic time and a higher rate of mechanical complications on a international scale.

Drought effects on specific-cause mortality in Lisbon from 1983 to 2016: Risks assessment by gender and age groups.

Portugal (Southwestern Europe) experiences a high incidence of dry hazards such as drought, a phenomenon that entails a notable burden of morbidity and mortality worldwide. For the first time in the Lisbon district, a time-series study was conducted to evaluate the impact of drought measured by the Standardised Precipitation Index (SPI) and Standardised Precipitation-Evapotranspiration Index (SPEI) on the daily natural, circulatory, and respiratory mortality from 1983 to 2016. An assessment by gender and adult age population groups (45-64, 65-74, ≥75 years old) was included. To estimate the relative risks and attributable risks, generalised linear models with a Poisson link were used. Additionally, the influence of heatwaves and atmospheric pollution for the period from 2007 to 2016 (available period for pollution data) was considered. The main findings indicate statistically significant associations between drought conditions and all analysed causes of mortality. Moreover, SPEI shows an improved capability to reflect the different risks. People in the 45-64 year-old group did not indicate any significant influence in any of the cases, whereas the oldest groups had the highest risk. The drought effects on mortality among the population varied across the different study periods, and in general, the men population was affected more than the women population (except for the SPEI and circulatory mortality during the long study period). The short-term influence of droughts on mortality could be explained primarily by the effect of heatwaves and pollution; however, when both gender and age were considered in the Poisson models, the effect of drought also remained statistically significant when all climatic phenomena were included for specific groups of the total population and men. This type of study facilitates a better understanding of the population at risk and allows the development of more effective measures to mitigate the drought effects on the population.

Point-of-care lung ultrasound predicts in-hospital mortality in acute heart failure.

BACKGROUND: B-lines have been associated with adverse clinical outcomes in patients with heart failure (HF) when found at hospital discharge or during outpatient visits. Whether lung ultrasound (LUS) assessed B-lines may predict in-hospital mortality in patients with acute HF is still undetermined. AIM: To evaluate the association between B-lines on admission and in-hospital mortality among patients admitted with acute HF. METHODS: Hand-held LUS was used to examine patients with acute HF. LUS was performed in eight chest zones with a pocket ultrasound device and analyzed offline. The association between B-lines and in-hospital mortality was assessed using Cox regression models. RESULTS: We included 62 patients with median age 56 years, 69.4% men, and median left ventricle ejection fraction 25%. The sum of B-lines ranged from 0 to 53 (median 6.5). An optimal receiver operating characteristic-determined cut-off of ≥19 B-lines demonstrated a sensitivity of 57% and a specificity of 86% (area under the curve 0.788) for in-hospital mortality. The incremental prognostic value of LUS when compared with lung crackles or peripheral edema by integrated discrimination improvement was 12.96% (95% CI: 7.0-18.8, P = 0.02). Patients with ≥19 B-lines had a 4-fold higher risk of in-hospital mortality (HR 4.38; 95% CI: 1.37-13.95, P < 0.01). CONCLUSION: In patients admitted with acute HF, point-of-care LUS measurements of pulmonary congestion (B-lines) are associated with in-hospital mortality.

Short-term effects of drought on daily mortality in Spain from 2000 to 2009.

Spain is a country of southern Europe that is prone to drought, and it is likely that this type of hydrological extreme will become substantially more frequent and intense in the 21st century, which could lead to greater health risks if adequate adaptive measures are not taken. For the first time, we calculated the relative risks (RRs) of daily natural (ICD10: A00-R99), circulatory (ICD10: I00-I99), and respiratory (ICD: J00-J99) mortality associated with drought events in each province of Spain from 2000 to 2009. For this purpose, we compared the performance of the Standardized Precipitation Index (SPI) and Standardized Precipitation- Evapotranspiration Index (SPEI) obtained at 1 month of accumulation (denoted as SPI-1/SPEI-1) to estimate the short-term risks of droughts on daily mortality using generalised linear models. Attributable risks were calculated from the RR data. The main findings of this study revealed statistically significant associations between the different causes of daily mortality and drought events for the different provinces of Spain, and clear spatial heterogeneity was observed across the country. Western Spain (northwest to southwest) was the region most affected, in contrast to northern and eastern Spain, and daily respiratory mortality was the group most strongly linked to the incidence of drought conditions. Moreover, for a considerable number of provinces, the effect of SPI-1 and SPEI-1 largely reflected the impact of atmospheric pollution and/or heatwaves; however, for other regions, the effect of drought conditions on daily mortality remained when these different climatic events were controlled in Poisson models. When the performances of the SPEI and SPI were compared to identify and estimate the risks of drought on daily mortality, the results were very similar, although there were slight differences in the specific causes of daily mortality.

Effects of lysine deficiency on carcass composition and activity and gene expression of lipogenic enzymes in muscles and backfat adipose tissue of fatty and lean piglets.

The purpose of this study was to investigate potential mechanisms involved in fat deposition promoted by dietary lysine deficiency, particularly intramuscular fat (IMF), and differential responses between fatty and lean pigs. Carcass traits and lipogenic enzyme activities and gene expression levels in muscles and adipose tissue were investigated in Iberian (fatty) and Landrace × Large White (LDW) pigs under identical feeding level (based on body weight (BW)) and management conditions. Twenty-eight barrows of 10 kg initial BW, 14 per breed, were fed two isoproteic (200 g CP /kg DM) and isocaloric (14.7 MJ metabolizable energy/kg DM) diets with identical composition except for the lysine content (1.09% for diet adequate in lysine and 0.52% for diet deficient in lysine). At a BW of 25 kg, pigs were slaughtered. Compared with pigs fed the lysine-adequate diet, in both genotypes lysine-deficient diet led to lower carcass protein concentration, lower relative proportions of leaner components (loin, ham and shoulder; P < 0.01), and higher carcass fatty components and carcass lipid concentration (P < 0.001). Irrespective of diet, the activity and gene expression of lipogenic enzymes (fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PDH)) were greater in Iberian than in LDW pigs, particularly in adipose tissue where transcriptional regulators involved in the control of adipogenesis and lipogenesis were also upregulated in Iberian animals. In backfat tissue, there was a small decrease induced by or no effects of lysine-deficient diet on the activity and gene expression of lipogenic enzymes, nor in gene expression levels of upstream regulators of lipogenesis and adipogenesis. In longissimus muscle, the activity of FAS, G6PDH and ME increased with lysine deficiency in both genotypes (P < 0.01) and an upregulation of gene expression of lipogenic enzymes was specifically observed in Iberian pigs (P < 0.05 to P < 0.001). In biceps femoris muscle of lysine-deficient pigs, the activity of FAS and ME enzymes increased, ME1 gene was upregulated (added to FASN gene in the case of Iberian pigs; P < 0.01 to P < 0.001) and PPARA gene was downregulated (P < 0.05). The results show that in both fatty and lean pigs, the effect of lysine deficiency on lipid metabolism was tissue-specific, with an activation of lipogenesis in longissimus and biceps femoris muscle but no apparent stimulation in backfat adipose tissue. Suitable feeding protocols including lysine-deficient diets should be designed for each pig type in order to increase intramuscular lipids without penalizing the growth of lean carcass components.

Increased multimodality treatment options has improved survival for Hepatocellular carcinoma but poor survival for biliary tract cancers remains unchanged.

BACKGROUND: Primary hepatobiliary cancer incidence in the UK is rising and survival rates are low. Surgery is the main curative option for these cancers, but multimodality therapies are expanding. The aim of our original study was to determine trends in survival, over an 8-year period, of patients treated for primary hepatobiliary cancers at our tertiary referral Centre. METHOD: Patients treated for the most common types of primary hepatobiliary cancers, namely Hepatocellular carcinoma (HCC), Cholangiocarcinoma and Gallbladder cancer between January 2009 and December 2016 were retrospectively analysed from a prospective database linked to UK Hospital Episode Statistics data. RESULTS: A total of 1536 patients with primary hepatobiliary cancers were assessed and treatment plans formulated at our supra-regional specialist Hepatobiliary MDT. The primary hepatobiliary cancers treated were HCC (n = 836), Cholangiocarcinoma (n = 516), and Gallbladder cancer (n = 184). Survival for all the 3 cancers was significantly better with curative treatment. Overall median survival times were 350, 180, and 150 days respectively for HCC, Cholangiocarcinoma and Gallbladder cancer. Excluding best supportive care patients, the respective survival figures were 900, 600, and 400 days. Survival for HCC patients improved over time and was significantly increased in the final 3 years of the study (p ≤ 0.011 for all). Cholangiocarcinoma and Gallbladder cancer survivals were poor and did not change significantly over time. CONCLUSION: HCC outcome has improved in association with expanded multimodal therapies. Survivals for cholangiocarcinoma and gallbladder cancer remain poor in parallel with limited expansion of multimodal therapies highlighting an unmet therapeutic need for biliary tract cancers.