Bone metabolism in children with normal weight and overweight/obesity in a northeastern region of Spain.

Objectives: Bone mass progressively increases to peak during childhood and adolescence, which determines future bone health. Bone formation-resorption processes are assessed using bone markers. However, studies on the impact of obesity on bone turnover markers at this age are limited, and results are inconsistent. The objective of this study was to examine the potential impact of overweight/obesity on bone metabolism. Methods: A study was performed to compare parameters of bone metabolism in 45 girls and boys with normal weight (controls) and in a group of 612 girls and boys with overweight/obesity (cases) from the Exergames study (University of Zaragoza). Ages ranged from 8 to 12 years. Results: Higher values of phosphorus and IGFBP-3 were observed in children with overweight/obesity, as compared to children with normal weight, (p=0.042) and (p=0.042), respectively. BAP, osteocalcin, magnesium, vitamin D and IGF-I concentrations were lower in the group with overweight/obesity, whereas calcium concentrations were higher in this group, although differences were not statistically significant. A negative correlation was found (r=-0.193) (p=0.049) between BAP and BMI. Conclusions: Although differences did not reach statistical significance, BAP and osteocalcin concentrations were lower in children with overweight/obesity. This added to the negative correlation found between BAP and MIC may demonstrate that overweight/obesity may negatively affect bone health already at a young age.

Predictors of Immunotherapy Efficacy in Metastatic Non-Small Cell Lung Cancer: Lung Immune Prognostic Index and Immune-Related Toxicity.

Background: Immune checkpoint inhibitors (ICIs) have been proposed as the standard first-line and subsequent treatment for metastatic non-small cell lung cancer (NSCLC). This study analyzed whether patients with good lung immune prognostic index (LIPI) have a better response to ICIs and the relationship between immune-related adverse events (irAEs) and response in clinical practice. Methods: This was an observational, retrospective, single-center study. Patients with stage IV NSCLC between 2016 and 2021 were included in the study. Toxicity was assessed according to The Common Terminology Criteria for Adverse Events. Response assessment was performed according to RECIST 2.0 and immuno-related criteria. Descriptive and survival analyses were conducted. Degree of toxicity and response to treatment (based on treatment and histology) were assessed. LIPI and response were assessed. LIPI included dNLR (absolute neutrophil count/(white blood cell count - absolute neutrophil count)) ≥ 3 and lactate dehydrogenase (LDH) greater than the upper limit of normal. Patients were stratified into good (G), intermediate (I), and poor (P) prognostic groups. Results: A total of 168 patients were included (130 men and 38 women, mean age 64.3 years). ICI use in the first- or second-line treatment was 65% and 35%, respectively. Fifteen (9%) patients showed complete response (CR), 50 (30%) showed partial response (PR), 39 (22%) had stable disease (SD), 45 (28%) had progressive disease (PD), and 19 (11%) were not evaluated (NE). Patients with good prognostic LIPI (dNLR < 3 and normal LDH levels) showed a better response. Progression-free survival (PFS) was 19 months in G, 6 months in I, and 2 months in P. Overall survival (OS) was 27 months in G, 8 months in I, and 3 months in P. One hundred fourteen patients died (56% G, 76% I, 93% P). Patients with adenocarcinoma were 116 (77 with irAEs G1-4 (13 CR, 31 PR, 21 SD, eight PD, and four NE)), and without were 39 (three PR, six SD, 21 PD, and nine NE). Fifty-two patients had squamous carcinoma (27 with irAEs G1-4 (two CR, 12 PR, nine SD, and four PD)), and 25 did not (four PR, three SD, 12 PD, and six NE)). IrAEs appearance was observed in longer PFS (19 vs. 2 months) and OS (27 vs. 4 months; P < 0.0001). Conclusions: LIPI was a positive predictor of response to ICI. The presence of irAEs is associated with a better immune response. In contrast, the absence of toxicity predicted a worse prognosis.

Screening and risk of hepatocellular carcinoma in patients with advanced fibrosis after hepatitis C virus eradication.

INTRODUCTION: The risk of hepatocellular carcinoma (HCC) after eradication of the hepatitis C virus (HCV) is highly variable in patients with advanced fibrosis (F3). Long-term surveillance for HCC after sustained virological response (SVR) is controversial in these patients. Our objective is to describe the post-SVR follow-up in clinical practice in patients with F3 and determine the predictive factors for the development of HCC. PATIENTS AND METHODS: a multicenter, observational, and retrospective study, which included HCV-monoinfected patients with F3 fibrosis determined by transient elastography who achieved SVR between 2015 and 2022 and with follow-up until May 2023. Clinical-demographic, laboratory, elastography, and ultrasound variables were recorded before and after treatment. A descriptive and inferential analysis, Cox regression analysis, and survival analysis were carried out with the R statistical software. RESULTS: 219 patients were included (65.3% men, median age 57 years). 175 (79.9%) received ultrasound screening after SVR for 62 [6-90] months. The prescribing service was the only independent variable related to performing ultrasound surveillance (p=0.004). Eight patients developed HCC. In multivariate analysis adjusted for sex, age, presence of diabetes, and alcohol consumption, a post-SVR FIB-4 ≥ 3.25 was associated with a 12-fold increase in HCC risk. The cumulative probability of HCC was higher in the group of patients with FIB-4 ≥ 3.25 after SVR (p<0.001). CONCLUSION: post-SVR follow-up of patients with F3 fibrosis is variable in clinical practice. Using the FIB-4 after SVR allows us to identify those patients with a higher risk of HCC who benefit from biannual ultrasound screening.

Percutaneous left atrial appendage closure in patients with gastrointestinal bleeding associated with oral anticoagulants.

INTRODUCTION: Percutaneous left atrial appendage closure (LAAC) has shown non-inferiority compared to oral anticoagulation (OAC) in preventing atrial fibrillation (AF)-related stroke. The objective of this study was to assess whether LAAC reduces the incidence of gastrointestinal bleeding (GIB) and/or chronic anaemia associated with OAC, as well as the consumption of healthcare resources. MATERIALS AND METHODS: Prospective, single-center study from 2016 to 2022, LAAC was performed. Clinical, analytical and healthcare resource consumption data were collected (endoscopies, blood transfusions, hospital admissions) prior and 6 months after LAAC. RESULTS: 43 patients were included, with an average age of 77.6 years. LAAC indication was upper, low and obscure GIB in 7 (16%), 8 (19%) and 28 patients (65%) respectively. GIB source was intestinal angiodysplasias in 27 patients (63%), occult origin in 12 (28%), and others (antral vascular ectasia, portal hypertension gastropathy, etc.) in 4 patients (9%). The mean number of packed red blood cells per patient before LAAC was (mean ± SD) 7.29 ± 5 vs 0.42 ± 1.3 (p < 0.001); endoscopic procedures were 4.34 ± 2.85 vs 0.27 ± 0.76 (p < 0.001); and hospitalizations 2.67 ± 2.14 vs 0.03 ± 0.17 (p < 0.001), with a hospital stay of 21.5 ± 17.3 vs 0.09 ± 0.5 days (p < 0.001) at 6 months post-intervention. Haemoglobin value increased from 8.1 ± 1.2g/dl to 12.4 ± 2.2g/dl (p < 0.001) at 6 months. No thromboembolic events were registered during a median follow-up of 16.6 months (range 6-65). CONCLUSIONS: LAAC could be a safe and effective alternative to OAC in patients with non-valvular AF presenting significant, recurrent or potentially unresolvable GIB. This intervention also leads to important savings in the consumption of healthcare resources.

Maresin 1 Exerts a Tissue-Specific Regulation of Adipo-Hepato-Myokines in Diet-Induced Obese Mice and Modulates Adipokine Expression in Cultured Human Adipocytes in Basal and Inflammatory Conditions.

This study analyses the effects of Maresin 1 (MaR1), a docosahexaenoic acid (DHA)-derived specialized proresolving lipid mediator with anti-inflammatory and insulin-sensitizing actions, on the expression of adipokines, including adiponectin, leptin, dipeptidyl peptidase 4 (DPP-4), cardiotrophin-1 (CT-1), and irisin (FNDC5), both in vitro and in in vivo models of obesity. The in vivo effects of MaR1 (50 µg/kg, 10 days, oral gavage) were evaluated in epididymal adipose tissue (eWAT), liver and muscle of diet-induced obese (DIO) mice. Moreover, two models of human differentiated primary adipocytes were incubated with MaR1 (1 and 10 nM, 24 h) or with a combination of tumor necrosis factor-α (TNF-α, 100 ng/mL) and MaR1 (1-200 nM, 24 h) and the expression and secretion of adipokines were measured in both models. MaR1-treated DIO mice exhibited an increased expression of adiponectin and Ct-1 in eWAT, increased expression of Fndc5 and Ct-1 in muscle and a decreased expression of hepatic Dpp-4. In human differentiated adipocytes, MaR1 increased the expression of ADIPONECTIN, LEPTIN, DPP4, CT-1 and FNDC5. Moreover, MaR1 counteracted the downregulation of ADIPONECTIN and the upregulation of DPP-4 and LEPTIN observed in adipocytes treated with TNF-α. Differential effects for TNF-α and MaR1 on the expression of CT-1 and FNDC5 were observed between both models of human adipocytes. In conclusion, MaR1 reverses the expression of specific adipomyokines and hepatokines altered in obese mice in a tissue-dependent manner. Moreover, MaR1 regulates the basal expression of adipokines in human adipocytes and counteracts the alterations of adipokines expression induced by TNF-α in vitro. These actions could contribute to the metabolic benefits of this lipid mediator.

Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry.

BACKGROUND AND AIMS: Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. METHODS: Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. RESULTS: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. CONCLUSIONS: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.

Role of Branched-Chain Amino Acids and Their Derivative ß-Hydroxy-ß-Methylbutyrate in Liver Cirrhosis.

Branched-chain amino acids (BCAA) supplementation is used to promote protein synthesis in different clinical conditions in which proteolysis is increased. In addition, lower plasma BCAA levels have been related to an increased risk of hepatic encephalopathy in liver cirrhosis. In this article we will review the role of supplementation with BCAAs and BCAA derivative ß-hydroxy-ß-methylbutyrate (HMB) in liver cirrhosis, focusing on nutritional and clinical effects. Evidence shows that BCAA supplementation slightly increases muscle mass and body mass index, with an upward trend in muscular strength and no change in fat mass. Moreover, BCAA supplementation improves symptoms of hepatic encephalopathy, and is indicated as second-line therapy. The evidence is more limited for BCAA derivatives. HMB supplementation appears to increase muscle mass in chronic diseases associated with cachexia, although this effect has not yet been clearly demonstrated in liver cirrhosis studies. To date, HMB supplementation has no clinical indication in liver cirrhosis.

Cardiorespiratory fitness decreases the odds for subclinical carotid plaques in apolipoprotein e4 homozygotes.

Some studies suggest that being an apolipoprotein e4 (APOE e4) carrier increases the risk of atherosclerosis, and others suggest that cardiorespiratory fitness (CRF) could play a key role in atherosclerotic prevention. Our aim was to analyze the association of APOE e4 with carotid atherosclerosis and the association of CRF with atherosclerosis in APOE e4 carriers. A cross-sectional analysis based on a subsample of 90 participants in the Aragon Workers' Health Study was carried out. Ultrasonography was used to assess the presence of plaques in carotid territory; the submaximal Chester Step Test was used to assess CRF; and behavioral, demographic, anthropometric, and clinical data were obtained by trained personnel during annual medical examinations. APOE e4e4 participants were categorized into Low-CRF (VO2max < 35 mL/kg/min) and High-CRF (VO2max ≥ 35 mL/kg/min) groups. After adjusting for several confounders, compared with APOE e3e3, those participants genotyped as APOE e3e4 and APOE e4e4 showed an OR = 1.60 (95% CI 0.45, 5.71) and OR = 4.29 (95% CI 1.16, 15.91), respectively, for carotid atherosclerosis. Compared to Low-CRF APOE e4e4 carriers, the odds of carotid plaque detection were 0.09 (95% CI 0.008, 0.98) times lower among High-CRF APOE e4e4 carriers. The APOE e4e4 genotype was associated with increased carotid atherosclerosis. However, CRF is a modifiable factor that may be targeted by APOE e4e4 to decrease the elevation of atherosclerotic risk due to this genetic condition.

Impacto de la bacteriemia por Staphylococcus aureus en pacientes con COVID-19 / Impact of Staphylococcus aureus bacteremia in COVID-19 patients

Introducción. La enfermedad causada por SARS-CoV-2 (COVID-19) ha supuesto un desafío para los profesionales sanitarios desde su aparición. Staphylococcus aureus es uno de los principales patógenos causantes de infecciones bacterianas en pandemias virales. Sin embargo, se debe estudiar bien la co-infección por S. aureus causante de bacteriemia en pacientes con COVID-19. Métodos. Se analizaron los casos de bacteriemia por S. aureus (BSA) atendidos en el Hospital Miguel Servet (Zaragoza) desde marzo de 2020 hasta febrero de 2021. Se compararon las características clínicas, los factores de riesgo y mortalidad de los pacientes con BSA asociada a COVID-19 respecto los pacientes no-COVID-19. Resultados. Se identificaron 95 pacientes con BSA. El 27,3% fueron COVID-19 positivos. La BSA representó el 9,9% de las bacteriemias, siendo el segundo microorganismo en frecuencia tras E. coli. La bacteriemia nosocomial fue más frecuente en el grupo de pacientes con COVID-19. La fuente de BSA fue desconocida en el 46,2% de los pacientes con COVID-19. La fuente de BSA más frecuente en estos pacientes fue la respiratoria (26,9% vs 0%; P<0,001) seguida de la cutánea (15,5% vs 15,9%; P=1). El desarrollo de sepsis fue más frecuente en los pacientes con COVID-19 (61,5% vs 7,8%; P=0,336) y de ellos, los que recibieron dosis de dexametasona >6 mg/día (62,5% vs 37,5%; P< 0,05). Conclusiones. Nuestros datos sugieren que la BSA influye negativamente en la evolución de los pacientes con COVID-19. Sin embargo, se requieren más estudios y preferiblemente prospectivos para obtener datos sólidos sobre el impacto de la BSA en los pacientes con coronavirus. (AU)

Introduction. The disease caused by SARS-CoV-2 (COVID-19) has been a challenge for healthcare professionals since its appearance. Staphylococcus aureus has been described as one of the main pathogens causing bacterial infections in viral pandemics. However, co- infection with S. aureus causing bacteremia in patients with COVID-19 has yet to be well studied. Methods. We performed a e study of S. aureus bacteremia (SAB) at Hospital Miguel Servet (Zaragoza) from March 2020 to February 2021. The clinical characteristics, mortality and risk factors of adults hospitalized patients with BSA associated COVID-19 compared to patients without COVID-19. Results. A total of 95 patients with SAB were identified. 27.3% were positive for SARS-CoV-2. SAB represented 9.9% of bacteremia, being the second agent in frequency after E. coli. Nosocomial bacteremia was more frequent in the group of COVID-19 patients. The most frequent source of BSA in these patients was the respiratory source (26.9% vs 0%; P<0.001) followed by the skin (15.5% vs 15.9%; P=1). The development of sepsis was more frequent in COVID-19 patients (61,5% vs 7,8%; P=0,336) and among them, who received dexamethasone at doses > 6 mg/day (62.5% vs. 37.5%, P<0.05). Conclusions. Our data suggest that BSA has a negative impact on the evolution of patients with COVID-19. However, further and preferably prospective studies are required to obtain solid data on the impact of BSA on coronavirus patients. (AU)

Diagnosis of Malnutrition According to GLIM Criteria Predicts Complications and 6-Month Survival in Cancer Outpatients.

Background and Aims: Malnutrition is a condition that has a great impact on oncology patients. Poor nutritional status is often associated with increased morbidity and mortality, increased toxicity, and reduced tolerance to chemotherapy, among other complications. The recently developed GLIM criteria for malnutrition aim to homogenize its diagnosis, considering the baseline disease status. We aimed to evaluate the performance of these new criteria for the prediction of complications and mortality in patients with cancer. Methods: This work is a prospective, single-center study. All outpatients under active treatment for head and neck, upper gastrointestinal, and colorectal tumors between February and October 2020 were recruited. These patients were followed up for 6 months, assessing the occurrence of complications and survival based on GLIM diagnoses of malnutrition. Results: We enrolled 165 outpatients, 46.66% of whom were malnourished. During the 6-month follow-ups, patients with malnutrition (46.7%, according to GLIM criteria) had a ~3-fold increased risk of hospital admission (p < 0.001) and occurrence of severe infection (considered as those requiring hospitalization, intravenous antibiotics, and/or drainage by interventional procedures) (p = 0.002). Similarly, malnourished patients had a 3.5-fold increased risk of poor pain control and a 4.4-fold increased need for higher doses of opioids (both p < 0.001). They also had a 2.6-fold increased risk of toxicity (p = 0.044) and a 2.5-fold increased likelihood of needing a dose decrease or discontinuation of cancer treatment (p = 0.011). The 6-month survival of malnourished patients was significantly lower (p = 0.023) than in non-malnourished patients. Conclusions: Diagnoses of malnutrition according to the GLIM criteria in oncology patients undergoing active treatment predict increased complications and worse survival at 6-month follow-ups, making them a useful tool for assessing the nutritional status of oncology patients.

Rheological Properties and Stability of Thickeners for Clinical Use.

The adaptation of liquids for patients with dysphagia requires precision and individualization in the viscosities used. We describe the variations of viscosity in water at different concentrations and evolution over time of the three compositions of commercial thickeners that are on the market (starch, starch with gums, and gum). By increasing the concentration in water, the viscosity of gum-based thickeners increases linearly, but it did not reach pudding texture, whereas the viscosity of the starch-based thickeners (alone or mixed with gums) rapidly reaches very thick textures. We modeled the viscosity at different concentrations of the four thickeners using regression analysis (R2 > 0.9). We analyzed viscosity changes after 6 h of preparation. The viscosity of gum-based thickeners increased by a maximum of 6.5% after 6 h of preparation, while starch-based thickeners increased by up to 43%. These findings are important for correct handling and prescription. Gum-based thickeners have a predictable linear behavior with the formula we present, reaching nectar and honey-like textures with less quantity of thickener, and are stable over time. In contrast, starch thickeners have an exponential behavior which is difficult to handle, they reach pudding-like viscosity, and are not stable over time.

Institutionalized elderly are able to detect small viscosity variations in thickened water with gum-based thickeners: should texture classifications be reviewed?

BACKGROUND: The prevalence of dysphagia is very high in institutionalized elderly. Knowledge of the rheological and sensory characteristics of the various thickeners in elderly is limited, although it has been seen that there are differences between the rheological behaviors of gum-based thickeners with different composition. Moreover, we have not found sensory studies of viscosity in institutionalized elderly. Our hypothesis was that viscosity ranges established by the scientific societies, such as the National Dysphagia Diet Task Force (NDD), seem to be very wide and individuals might be able to detect small differences within the same texture range. The objectives of our study were 1) comparing the rheological characteristics of two commercial gum-based thickeners with different composition, dissolved in water under standard conditions, and 2) perform a sensory analysis (with both adults and institutionalized elderly) to detect different viscosities within the same texture (nectar and honey). METHODS: Two commercial thickeners based on gums (NC and RC) were studied analyzing their viscosity in water with different concentrations (shear rate: 50 s- 1; temperature: 22-25 °C). A sensory analysis involving 26 elderly and 29 adult controls was carried out to evaluate whether differences within nectar and honey textures among gum-based thickeners could be distinguished. RESULTS: As the shear rate increases, viscosity decreases (non-Newtonian and pseudoplastic behavior). At the same concentration, each thickener produces a different viscosity (p < 0.05). Institutionalized elderly detected viscosity differences in nectar range of 49.9 (2.5) mPa·s (p < 0.05) and 102.2 (4.7) mPa·s (p < 0.0001). They also detected viscosity differences in honey texture range of 134.6 (9.7) mPa·s (p < 0.05) y 199.3 (9.2) mPa·s (p < 0.0001). Their caregivers also detected viscosity differences in both viscosity ranges (p < 0.0001) and with greater intensity than the elderly in honey texture (p: 0.016). CONCLUSIONS: Our results suggest that the accepted viscosity ranges by NDD for the different textures might be too wide because institutionalized elderly and their caregivers are able to discern small differences in viscosity in nectar and honey textures. Gum-based thickeners with different composition showed differences in viscosity capacity, so they are not interchangeable.

Regulation of p27 and Cdk2 Expression in Different Adipose Tissue Depots in Aging and Obesity.

Aging usually comes associated with increased visceral fat accumulation, reaching even an obesity state, and favoring its associated comorbidities. One of the processes involved in aging is cellular senescence, which is highly dependent on the activity of the regulators of the cell cycle. The aim of this study was to analyze the changes in the expression of p27 and cdk2 in different adipose tissue depots during aging, as well as their regulation by obesity in mice. Changes in the expression of p27 and CDK2 in visceral and subcutaneous white adipose tissue (WAT) biopsies were also analyzed in a human cohort of obesity and type 2 diabetes. p27, but not cdk2, exhibits a lower expression in subcutaneous than in visceral WAT in mice and humans. p27 is drastically downregulated by aging in subcutaneous WAT (scWAT), but not in gonadal WAT, of female mice. Obesity upregulates p27 and cdk2 expression in scWAT, but not in other fat depots of aged mice. In humans, a significant upregulation of p27 was observed in visceral WAT of subjects with obesity. Taken together, these results show a differential adipose depot-dependent regulation of p27 and cdk2 in aging and obesity, suggesting that p27 and cdk2 could contribute to the adipose-tissue depot's metabolic differences. Further studies are necessary to fully corroborate this hypothesis.

Muscle Thickness and Echogenicity Measured by Ultrasound Could Detect Local Sarcopenia and Malnutrition in Older Patients Hospitalized for Hip Fracture.

BACKGROUND: The aim of this work was to assess whether the muscle thickness and echogenicity were associated with dysphagia, malnutrition, sarcopenia, and functional capacity in acute hospital admission for a hip fracture. METHODS: Observational study that assessed nutritional status by Global Leadership Initiative on Malnutrition, risk of dysphagia and sarcopenia by European Working Group on Sarcopenia in Older People and Barthel functional index. We measured muscle thickness and echogenicity of masseter, bicipital, and quadriceps rectus femoris (RF) and vastus intermedius (VI) by ultrasound. RESULTS: One hundred and one patients were included in the study (29.7% sarcopenia and 43.8% malnutrition). Logistic regression models adjusted for age, sex, and body mass index showed an inverse association of the masseter thickness with both sarcopenia (OR: 0.56) and malnutrition (OR: 0.38) and quadriceps with sarcopenia (OR: 0.74). In addition, patients at high risk of dysphagia had lower masseter thickness (p: 0.0001) while patients able to self-feeding had thicker biceps (p: 0.002) and individuals with mobility on level surfaces higher thickness of biceps (p: 0.008) and quadriceps (p: 0.04). CONCLUSION: Thickness of the masseter was associated with risk of dysphagia, biceps with the ability to self-feed, and that of the quadriceps RF-VI with mobility.

Can Physical Activity Reduce the Risk of Cognitive Decline in Apolipoprotein e4 Carriers? A Systematic Review.

Physical activity (PA) reduces the risk of cognitive decline (CD) in the general population. However, little is known about whether the presence of the apolipoprotein E epsilon 4 allele (APOE e4) could modify this beneficial effect. The aim of this systematic review was to analyze and synthetize the scientific evidence related to PA levels and CD risk in cognitively healthy APOE e4 carriers. Four electronic databases were analyzed. Only original articles with longitudinal study design were selected to analyze the relationship between PA and CD in APOE e4 carriers. Five studies were included in the systematic review. All studies except one stated that PA is a protective factor against CD in APOE e4 carriers. Moreover, partial support was found for the hypothesis that a greater amount and intensity of PA are more beneficial in CD prevention. The results support the idea that PA is a protective factor against CD in APOE e4 carriers. Nevertheless, it would be necessary to carry out further studies that would allow these findings to be contrasted.

Mini Nutritional Assessment - Short Form Is a Useful Malnutrition Screening Tool in Patients with Liver Cirrhosis, Using the Global Leadership Initiative for Malnutrition Criteria as the Gold Standard.

BACKGROUND: The use of nutrition-screening tools in cirrhotic patients is not systematized. Recently, specific tools have been proposed for patients with cirrhosis, but their diagnostic capabilities have been scarcely studied. METHODS: This was a prospective study that includes outpatients with liver cirrhosis undergoing follow-up in the hepatology consultations of a tertiary-care university hospital. A trained gastroenterologist applied the screening tools: Liver Disease Universal Screening Tool (LDUST), Royal Free Hospital-Nutrition Prioritizing Tool (RFH-NPT), and Mini Nutritional Assessment-Short Form (MNA-SF). Subsequently, the diagnosis of malnutrition was made according to Global Leadership Initiative for Malnutrition (GLIM) criteria by an endocrinologist, who was blind to the results of the screening tools. RESULTS: Sixty-three patients (38.1% women, mean age 63.1 ± 9.9 years) with cirrhosis (60.3% Child-Pugh A, 34.9% Child-Pugh B, and 4.8% Child-Pugh C) were evaluated. The prevalence of malnutrition was 38.1% (15.9% moderate, 22.2% severe). Advanced stages of cirrhosis were associated with a higher prevalence of malnutrition (P = .021). MNA-SF was the most accurate screening tool, being superior to RFH-NPT and LDUST. It presented better sensitivity than RFH-NPT (88% [0.68-0.97] vs 67% [0.45-0.84], P = .031) and better specificity than both LDUST (97% [0.87-0.99] vs 62% [0.45-0.77], P < .001) and RFH-NPT (97% [0.87-0.99] vs 82% [0.67-0.93], P = .016). CONCLUSIONS: According to the GLIM criteria, malnutrition affected 38.1% of patients with cirrhosis, being severe in 22% of the patients. MNA-SF is the most accurate screening test, superior even to tools specifically designed for cirrhotic patients (LDUST).

Efectos adversos inmunomediados gastrointestinales y hepáticos inducidos por los inhibidores del punto de control inmunitario: estudio descriptivo observacional / Gastrointestinal and liver immune-related adverse effects induced by immune checkpoint inhibitors: A descriptive observational study

Introducción: Los inhibidores del punto de control inmunitario (immune checkpoint inhibitors [ICI]) son fármacos eficaces en el tratamiento de diversas neoplasias. Sin embargo, se han relacionado con eventos adversos inmunomediados (EAI) gastrointestinales y hepáticos que pueden desencadenar su interrupción temporal o definitiva. Objetivo: Evaluar, en condiciones de práctica real, la eficacia y la toxicidad gastrointestinal y hepática de los ICI en tratamientos oncológicos. Material y métodos: Estudio retrospectivo con inclusión de pacientes con diagnóstico de neoplasia avanzada que habían recibido al menos una dosis de ICI entre mayo de 2015 y septiembre de 2018. Resultados: Se incluyeron 132 pacientes con neoplasia de pulmón no microcítico (65,15%, n=86), melanoma (22,7%, n=30), carcinoma renal (9,09%, n=12) y otros tumores (3%, n=4). Los fármacos empleados fueron nivolumab (n=82), pembrolizumab (n=28), atezolizumab (n=13), durvalumab (n=2), ipilimumab (n=1) y la combinación anti-CTLA-4/PD-1 (n=6). El 38,6% (n=51) desarrollaron EAI, de tipo gastrointestinal en el 12,9% (n=17). De ellos, el 47% (n=8) requirieron esteroides, y un paciente precisó cirugía por perforación intestinal. En el 3,03% (n=4) se objetivaron EAI hepáticos gradoI: el 50% (n=2) requirieron corticoterapia y en un paciente fue preciso interrumpir el tratamiento. Entre los pacientes con tratamiento combinado, el 66,6% (n=4) presentaron EAI gastrointestinales. La incidencia de EAI no se relacionó con la edad, ni con el sexo, ni con la respuesta al fármaco empleado. Conclusiones: Los EAI gastrointestinales figuran entre los más frecuentemente observados en pacientes en tratamiento con ICI. El manejo multidisciplinar y un mayor conocimiento de dichos eventos podrían ayudarnos a reducir su morbilidad, así como las interrupciones del tratamiento.(AU)

Introduction: Immune checkpoint inhibitors (ICIs) are effective agents against several malignancies. However, they are associated with gastrointestinal and liver immune-related adverse events (GI-IrAEs and LI-IrAEs), which can lead to their temporary or permanent discontinuation. Aim: The aim of this study was to evaluate the efficacy and gastrointestinal and liver toxicity of ICIs in oncological treatments in actual clinical practice. Material and methods: Patients with advanced cancer who received at least 1ICI dose between May 2015 and September 2018 were retrospectively assessed. Results: 132 patients with non-small cell lung cancer (65.15%, n=86); melanoma (22.7%, n=30); renal carcinoma (9.09%, n=12); and other tumours (3%, n=4) were included. The treatments administered were nivolumab (n=82), pembrolizumab (n=28), atezolizumab (n=13), durvalumab (n=2), ipilimumab (n=1) and the antiCTLA-4/PD-1 combination (n=6). In total, 51 patients (38.6%) developed IrAEs, 17 (12.9%) of which experienced GI-IrAEs. Of these, 8 (47%) needed steroids and 1patient required surgery due to intestinal perforation. Grade I Li-IrAEs were observed in 4 patients (3.03%): 2 (50%) required corticosteroids and 1 patient had to discontinue treatment. Four patients (66.6%) who received combination therapy experienced GI-IrAEs. IrAE incidence were not associated with age, gender or drug response. Conclusions: GI-IrAEs are one of the most common adverse events in patients receiving ICIs. A multidisciplinary approach and a greater understanding of these events could help to reduce morbidity and therapy discontinuation.(AU)

Gastrointestinal and liver immune-related adverse effects induced by immune checkpoint inhibitors: A descriptive observational study. / Efectos adversos inmunomediados gastrointestinales y hepáticos inducidos por los inhibidores del punto de control inmunitario: estudio descriptivo observacional.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are effective agents against several malignancies. However, they are associated with gastrointestinal and liver immune-related adverse events (GI-IrAEs and LI-IrAEs), which can lead to their temporary or permanent discontinuation. AIM: The aim of this study was to evaluate the efficacy and gastrointestinal and liver toxicity of ICIs in oncological treatments in actual clinical practice. MATERIAL AND METHODS: Patients with advanced cancer who received at least 1ICI dose between May 2015 and September 2018 were retrospectively assessed. RESULTS: 132 patients with non-small cell lung cancer (65.15%, n=86); melanoma (22.7%, n=30); renal carcinoma (9.09%, n=12); and other tumours (3%, n=4) were included. The treatments administered were nivolumab (n=82), pembrolizumab (n=28), atezolizumab (n=13), durvalumab (n=2), ipilimumab (n=1) and the antiCTLA-4/PD-1 combination (n=6). In total, 51 patients (38.6%) developed IrAEs, 17 (12.9%) of which experienced GI-IrAEs. Of these, 8 (47%) needed steroids and 1patient required surgery due to intestinal perforation. Grade I Li-IrAEs were observed in 4 patients (3.03%): 2 (50%) required corticosteroids and 1 patient had to discontinue treatment. Four patients (66.6%) who received combination therapy experienced GI-IrAEs. IrAE incidence were not associated with age, gender or drug response. CONCLUSIONS: GI-IrAEs are one of the most common adverse events in patients receiving ICIs. A multidisciplinary approach and a greater understanding of these events could help to reduce morbidity and therapy discontinuation.