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Context Inflammatory biomarkers have prognostic value in cancer patients, but the feasibility of their use with terminal cancer patients and the related cutoff points are poorly explored. Objectives To describe the percentiles values of inflammatory biomarkers; to identify their cutoff points in relation to death; and to determine the prognostic value of C-reactive protein (CRP), leukocytes, neutrophils, neutrophil/lymphocyte ratio (NLR), CRP/albumin ratio (CAR), and modified Glasgow Prognostic Score for death within 90 days, in terminal cancer patients receiving palliative care. Methods Prospective cohort study that included patients who received palliative care at the Palliative Care Unit of the National Cancer Institute (Brazil) between October 2019 and March 2020. Receiver operating characteristic curves were used to identify the optimal cutoff points of the inflammatory biomarkers for the prediction of death in 90 days. Kaplan-Meier curves and Cox regression were used to verify the prognostic value of these cutoff points and concordance statistic (C-statistic) was used to test their predictive accuracy. Results A total 205 patients (mean age: 62.5 years; female: 59%) were included in the study. The optimal cutoff points were CRP ≥6.7mg/L, CAR ≥2.0, leukocytes ≥9300/μL, neutrophils ≥7426/μL and NLR ≥6.0. All biomarkers showed prognostic value and good predictive accuracy when their cutoff points were used, especially CAR, which presented excellent discrimination power (C-statistic: 0.80). Conclusion The inflammatory biomarkers analyzed are independent predictive factors for death within 90 days in terminal cancer patients. CAR appears to be the most useful parameter for predicting survival in these patients.

OBJECTIVE To assess the frequency and factors associated of the provision of nutrition support (NS) in the last 30 days of life in patients with advanced cancer in the palliative or non-palliative setting. METHODS Retrospective cohort study in palliative and non-palliative care units at a specialized cancer center for oncology in Brazil. The use of oral nutrition supplements (ONS) and enteral (EN) and parenteral (PN) nutrition in the 30 days before death were assessed. RESULTS The 239 patients included were predominantly older (>60 years; 63.2%) and female (61.1%). The use of ONS was lower in palliative than non-palliative care during the last 30 (52% vs. 6%), 7 (42% vs. 4%), and 3 (23% vs. 2%) days before death (all P < .001). The use of EN and PN was lower in palliative care, decreasing with the approach of death. The independent factors associated with ONS in non-palliative care were (odds ratio): breast tumor (3.03), hypoalbuminemia (1.10), and nutrition risk (16.98); in palliative care, only the Karnofsky Performance Status (KPS) ≥40% (1.24) was associated to the use of ONS. The use of EN and PN was associated with head-neck (HN) tumor in both settings (5.41) in non-palliative and (8.74) in palliative. Others independent factors were: hypoalbuminemia (3.12) in non-palliative care and KPS (1.31) in palliative care. CONCLUSIONS The use of NS near the end of life was high in the non-palliative and less frequent in palliative care setting. The factors associated with NS differed according to the clinical oncology setting, with one of the factors in palliative care being a better prognosis.

Introduction and objective The management of renal tumors ≤4 cm in elderly population or patients with comorbidities is a challenge, for which ablative therapies are an interesting alternative. The objective is to evaluate in our center the role of percutaneous radiofrequency in the treatment of small renal masses, the associated complications and the results obtained. Material and methods Retrospective evaluation of the radiofrequency treatments carried out between April 2010 and April 2020 in our center. Demographic data, associated comorbidities, tumor characteristics, complications and oncological and functional outcomes were reviewed. Results Fifty-seven tumors were treated in 53 patients. Mean follow-up of 48.2 months. The percentage of complete ablations obtained was of 89.5%. There were 19.3% of complications. According to Clavien-Dindo and SIR classification systems, 3.5% and 5.3% were major complications. A statistically significant association was found between the initial result of ablation and age (p = 0.047), RENAL-m (p = 0.044), the presence of cystic component (p = 0.049) and tumor size (p = 0.01). The cut-off point for size was established at 25 mm (p = 0.012). In multivariate analysis, only size remained as a predictor of initial ablation result (p = 0.01 OR = 1.183 CI 95% = 1.041–1.345). Cancer-specific survival and 5-year recurrence-free survival were 98.1% and 89.5%, respectively. A mean decrease of MDRD-4 of 6.59 mL/min (p = 0.005) was observed in the first 6 months after RFA. Conclusions Given the excellent oncological and functional results demonstrated, ultrasound-guided percutaneous radiofrequency ablation is an effective and safe treatment for small renal masses in selected patients.

We evaluated the administration of ARI-0001 cells (chimeric antigen receptor T cells targeting CD19) in adult and pediatric patients with relapsed/refractory CD19+ malignancies. Patients received cyclophosphamide and fludarabine followed by ARI-0001 cells at a dose of 0.4–5 × 106 ARI-0001 cells/kg, initially as a single dose and later split into 3 fractions (10%, 30%, and 60%) with full administration depending on the absence of cytokine release syndrome (CRS). 58 patients were included, of which 47 received therapy: 38 with acute lymphoblastic leukemia (ALL), 8 with non-Hodgkin’s lymphoma, and 1 with chronic lymphocytic leukemia. In patients with ALL, grade ≥3 CRS was observed in 13.2% (26.7% before versus 4.3% after the amendment), grade ≥3 neurotoxicity was observed in 2.6%, and the procedure-related mortality was 7.9% at day +100, with no procedure-related deaths after the amendment. The measurable residual disease-negative complete response rate was 71.1% at day +100. Progression-free survival was 47% (95% IC 27%–67%) at 1 year: 51.3% before versus 39.5% after the amendment. Overall survival was 68.6% (95% IC 49.2%–88%) at 1 year. In conclusion, the administration of ARI-0001 cells provided safety and efficacy results that are comparable with other academic or commercially available products. This trial was registered as ClinicalTrials.gov: NCT03144583 .

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8–0.9 per week increase; p Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

WOS:000613461600006 PubMed ID: 32926494 Objectives To evaluate the maternal and perinatal outcomes of pregnancies affected by SARS-CoV-2 infection. Methods This was a multinational retrospective cohort study including women with a singleton pregnancy and laboratory-confirmed SARS-CoV-2 infection, conducted in 72 centers in 22 different countries in Europe, the USA, South America, Asia and Australia, between 1 February 2020 and 30 April 2020. Confirmed SARS-CoV-2 infection was defined as a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of nasopharyngeal swab specimens. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit (ICU), use of mechanical ventilation and death. Results In total, 388 women with a singleton pregnancy tested positive for SARS-CoV-2 on RT-PCR of a nasopharyngeal swab and were included in the study. Composite adverse maternal outcome was observed in 47/388 (12.1%) women; 43 (11.1%) women were admitted to the ICU, 36 (9.3%) required mechanical ventilation and three (0.8%) died. Of the 388 women included in the study, 122 (31.4%) were still pregnant at the time of data analysis. Among the other 266 women, six (19.4% of the 31 women with first-trimester infection) had miscarriage, three (1.1%) had termination of pregnancy, six (2.3%) had stillbirth and 251 (94.4%) delivered a liveborn infant. The rate of preterm birth before 37 weeks' gestation was 26.3% (70/266). Of the 251 liveborn infants, 69/251(27.5%) were admitted to the neonatal ICU, and there were five (2.0%) neonatal deaths. The overall rate of perinatal death was 4.1% (11/266). Only one (1/251, 0.4%) infant, born to a mother who tested positive during the third trimester, was found to be positive for SARS-CoV-2 on RT-PCR. Conclusions SARS-CoV-2 infection in pregnant women is associated with a 0.8% rate of maternal mortality, but an 11.1% rate of admission to the ICU. The risk of vertical transmission seems to be negligible. (C) 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Hypospadias is a congenital malformation of the male lower urinary tract, consisting of a ventral urethral opening proximal to the glans penis. This condition is corrected surgically in the paediatric age, with a great variety of techniques available. Traditionally, a tubularized genital skin was used for one- or two-stage repairs. Nowadays, the tendency is to use preputial or oral mucosa grafts, dorsally located, to avoid diverticula formation and prevent hair growth in the neourethra. We present a case of a patient born with proximal hypospadias with penoscrotal transposition, surgically corrected in his childhood, using dorsal penile skin island flap. The patient is referred to urology consultation in his adulthood for a weak urinary stream, recurrent infections, and a large amount of hair exiting through the urethral meatus.

BACKGROUND: It has still to be ascertained whether severe acute respiratory syndrome coronavirus 2 infection in pregnancy is associated with worse maternal and fetal outcomes compared to low risk gestations. OBJECTIVE: This study aimed to evaluate maternal and perinatal outcomes in high- and low-risk pregnancies complicated by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: This was a multinational retrospective cohort study involving women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection from 76 centers from 25 countries in Europe, the United States, South America, Asia, and Australia from April 4, 2020, to October 28, 2020. The primary outcome was a composite measure of maternal mortality and morbidity, including admission to the intensive care unit, use of mechanical ventilation, or death. The secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal and perinatal death, and admission to the neonatal intensive care unit. All outcomes were assessed in high- and low-risk pregnancies. Pregnancies were considered high risk in case of either preexisting chronic medical conditions in pregnancy or obstetrical disorders occurring in pregnancy. The Fisher exact test and logistic regression analysis were used to analyze the data. RESULTS: A total of 887 singleton pregnancies who tested positive for severe acute respiratory syndrome coronavirus 2 infection using reverse transcription-polymerase chain reaction of nasal and pharyngeal swab specimens were included in the study. The risk of composite adverse maternal outcomes was higher in high-risk pregnancies than in low-risk pregnancies (odds ratio, 1.52; 95% confidence interval, 1.03-2.24; P=.035). In addition, women carrying high-risk pregnancies were at higher risk of hospital admission (odds ratio, 1.48; 95% confidence interval, 1.07-2.04; P=.002), presence of severe respiratory symptoms (odds ratio, 2.13; 95% confidence interval, 0.41-3.21; P=.001), admission to the intensive care unit (odds ratio, 2.63; 95% confidence interval, 1.42-4.88), and invasive mechanical ventilation (odds ratio, 2.65; 95% confidence interval, 1.19-5.94; P=.002). When exploring perinatal outcomes, high-risk pregnancies were at high risk of adverse perinatal outcomes (odds ratio, 1.78; 95% confidence interval, 0.15-2.72; P=.009). However, such association was mainly because of the higher incidence of miscarriage in high-risk pregnancies compared with that in low-risk pregnancies (5.3% vs 1.6%, P=.008); furthermore, there was no difference in other explored outcomes between the 2 study groups. At logistic regression analysis, maternal age (odds ratio, 1.12; 95% confidence interval, 1.02-1.22; P=.023) and high-risk pregnancy (odds ratio, 4.21; 95% confidence interval, 3.90-5.11; P

Wheat flour enrichment is a public health strategy recommended to prevent micronutrient deficiencies, including iron deficiency. The objective of this study was to determine iron content in enriched wheat flour and flour products and their contribution to nutritional recommendations for children.Observational, analytical, cross-sectional study based on the total diet study method. Enriched wheat flour (as per Law no. 25630) and the most frequently consumed flour products were analyzed. Products were selected using a questionnaire on the frequency of food intake and a 24-hour recall interview with the parents of children aged 6 months to 7 years. Food iron levels were determined based on atomic absorption spectrometry and their contribution to the estimated average requirement was assessed.Enriched flour and flour products showed the expected iron amount, except for French bread and breadcrumbs. The contribution of studied products to iron requirements was 7 % in children aged 6 months to 1 year, 81 % in those aged 1-3 years, and 45 % in those older than 4 years.Except for French bread and breadcrumbs, studied flour and flour products showed the expected enrichment level. The consumption of this type of food does not provide significant amounts of iron to infants, but it does to children older than 1 year.Introducción. El enriquecimiento de la harina de trigo es una de las estrategias de salud pública recomendadas para prevenir las deficiencias de micronutrientes, entre ellos el hierro. El objetivo de este trabajo fue determinar el contenido de hierro en harina de trigo enriquecida y sus derivados, y la contribución de estos a las recomendaciones nutricionales en niños. Población y métodos. Estudio observacional, analítico, de corte transversal, basado en la metodología de estudio de dieta total. Se analizaron la harina de trigo enriquecida (según la ley 25630) y sus derivados más consumidos. Para seleccionar los alimentos, se realizó un cuestionario de frecuencia de consumo y recordatorio de 24 horas a los padres de niños con edades entre 6 meses y 7 años. Se determinó la concentración de hierro en los alimentos mediante absorción atómica y se evaluó su contribución al requerimiento promedio estimado. Resultados. La harina enriquecida y sus derivados tuvieron la cantidad de hierro esperada, excepto el pan francés y el pan rallado. La contribución a los requerimientos de hierro de los alimentos evaluados fue el 7 % en niños de 6 meses a 1 año, el 81 % en el grupo de 1 a 3 años y el 45 % en los mayores de 4 años. Conclusiones. Excepto el pan francés y el pan rallado, las harinas y sus derivados analizados presentaron el nivel de enriquecimiento esperado. El consumo de estos alimentos no aporta cantidades significativas de hierro en los lactantes, pero sí en los niños mayores de 1 año.

Introduction The majority of women admitted with threatened preterm labour (PTL) do not delivery prematurely. While those with microbial invasion of the amniotic cavity (MIAC) represent the highest risk group, this is a condition that is not routinely ruled out since it requires amniocentesis. Identification of low-risk or high-risk cases might allow individualisation of care, that is, reducing overtreatment with corticosteroids and shorten hospital stay in low-risk women, while allowing early antibiotic therapy in those with MIAC. Benefits versus risks of amniocentesis-based predictor models of spontaneous delivery within 7 days and/or MIAC have not been evaluated. Methods and analysis This will be a Spanish randomised, multicentre clinical trial in singleton pregnancies (23.0-34.6 weeks) with PTL, conducted in 13 tertiary centres. The intervention arm will consist in the use of amniocentesis-based predictor models: if low risk, hospital discharge within 24 hours of results with no further medication will be recommended. If high risk, antibiotics will be added to standard management. The control group will be managed according to standard institutional protocols, without performing amniocentesis for this indication. The primary outcome will be total antenatal doses of corticosteroids, and secondary outcomes will be days of maternal stay and the occurrence of clinical chorioamnionitis. A cost analysis will be undertaken. To observe a reduction from 90% to 70% in corticosteroid doses, a reduction in 1 day of hospital stay (SD of 2) and a reduction from 24% to 12% of clinical chorioamnionitis, a total of 340 eligible patients randomised 1 to 1 to each study arm is required (power of 80%, with type I error alpha=0.05 and two-sided test, considering a dropout rate of 20%). Randomisation will be stratified by gestational age and centre. Ethics and dissemination Prior to receiving approval from the Ethics Committee (HCB/2020/1356) and the Spanish Agency of Medicines and Medical Devices (AEMPS) (identification number: 2020-005-202-26), the trial was registered in the European Union Drug Regulating Authorities Clinical Trials database (2020-005202-26). AEMPS approved the trial as a low-intervention trial. All participants will be required to provide written informed consent. Findings will be disseminated through workshops, peer-reviewed publications and national/international conferences. Protocol version V.4 10 May 2021., This research has received a grant from the Instituto Carlos III (PI21/00972)

ObjectivesWe aimed (1) to assess the nutritional status (NS) using different methods, according to the primary tumour site and (2) to evaluate the performance of these methods in patients with incurable cancer from a reference centre in Brazil.MethodsCross-sectional analysis of data from patients admitted to the palliative care unit of a reference cancer centre in Brazil, between July 2016 and March 2020. The primary tumour site was the independent variable and the NS using different methods were the dependent variables. Logistic regressions were performed.ResultsA total of 2,144 patients were included in the study. The most common primary tumour site was the upper gastrointestinal (GI) tract (18.0%), followed by gynaecological (17.6%) and head and neck (HN) (13.5%). Our results showed that patients with tumours of the upper GI tract followed by HN presented significantly higher risk of worse NS. In contrast, breast tumours, bone and connective tissues and melanoma presented inverse association. The gynaecological cancer was variably associated with nutritional impairment, according to the assessment method.ConclusionsPatients with incurable cancer present high prevalence of NS impairment, depending on the tumour site, shown to be elevated in patients with tumour in the upper GI tract.

The aim of the present study was to evaluate the association between sarcopenia, diagnosed by different muscle mass measurement techniques, with nutritional status and overall survival in patients with advanced cancer under palliative care.To investigate the association of sarcopenia, according to distinct muscle mass measurement methods, with nutritional status and overall survival (OS).This observational and prospective study, including 334 patients, defined sarcopenia as reduced muscle mass and strength. Muscle mass was evaluated adopting 3 different methods, mid-upper arm muscle area (MUAMA), calf circumference (CC) and appendicular skeletal muscle mass (ASMI) described by Baumgartner (1998) and adjusted for height. Strength was defined using a handgrip dynamometer and OS was established based on a 90 days follow-up after inclusion date. Kaplan-Meier curves were conducted for survival analyzes and the association between sarcopenia and OS was evaluated by Cox regression model RESULTS: Prevalence of sarcopenia varied from 27-65% according to the method used to evaluate muscle mass. Malnutrition assessed by different parameters was significantly higher in patients with sarcopenia. Patients considered sarcopenic by MUAMA (43 versus 67 days, p0.001), CC (44 versus 77 days, p0.001) and ASMI (48 versus 75 days, p0.001) had significantly lower OS compared to non-sarcopenic patients. Sarcopenia evaluated by MUAMA (HR, 1.57; 95% CI, 1.12-2.18) and CC (HR, 2.00; 95% CI, 1.45-2.76) showed a higher risk of mortality.Sarcopenia diagnosed by MUAMA and CC could predict mortality and CC proved to be the best prognostic method for estimating OS in patients with advanced cancer in palliative care.

Significance Colorectal cancer (CRC) is a heterogeneous disease, with significant variation in genotype and phenotype within each individual tumor. This intratumor heterogeneity emerges during tumor development due to clonal evolution and in part can explain therapy resistance in CRC. However, a detailed understanding of the spatiotemporal development of tumors underlying cancer evolution and intratumor heterogeneity remains absent. Here, we use lineage-tracing experiments of human CRC cells transplanted into immunocompromised mice, in combination with computational modeling, to study the growth mode of CRC. We found that the clonal position is crucial for clonal outgrowth. This demonstrates that, in addition to the genetic composition, the environment and the geometry of tumor growth play a significant role in shaping tumor evolution., Cancer evolution is predominantly studied by focusing on differences in the genetic characteristics of malignant cells within tumors. However, the spatiotemporal dynamics of clonal outgrowth that underlie evolutionary trajectories remain largely unresolved. Here, we sought to unravel the clonal dynamics of colorectal cancer (CRC) expansion in space and time by using a color-based clonal tracing method. This method involves lentiviral red-green-blue (RGB) marking of cell populations, which enabled us to track individual cells and their clonal outgrowth during tumor initiation and growth in a xenograft model. We found that clonal expansion largely depends on the location of a clone, as small clones reside in the center and large clones mostly drive tumor growth at the border. These dynamics are recapitulated in a computational model, which confirms that the clone position within a tumor rather than cell-intrinsic features, is crucial for clonal outgrowth. We also found that no significant clonal loss occurs during tumor growth and clonal dispersal is limited in most models. Our results imply that, in addition to molecular features of clones such as (epi-)genetic differences between cells, clone location and the geometry of tumor growth are crucial for clonal expansion. Our findings suggest that either microenvironmental signals on the tumor border or differences in physical properties within the tumor, are major contributors to explain heterogeneous clonal expansion. Thus, this study provides further insights into the dynamics of solid tumor growth and progression, as well as the origins of tumor cell heterogeneity in a relevant model system.

Comprehensive geriatric assessment (CGA) has shown to benefit older patients undergoing urological and orthopedic surgery. However, this approach has been scarcely assessed in patients elected for colorectal surgery.Retrospective cohort of patients aged ≥70 years admitted for elective colorectal cancer surgery to a single hospital between 2008 and 2012. Upon admission, patients were assigned to a usual care (UC) plan or a CGA-based care (GS) plan conducted by a multidisciplinary team, according to standard clinical criteria.Analyzed outcomes included the incidence of delirium and other geriatric syndromes during hospital stay, mortality, readmissions, andnumber of perioperative complications.The cohort included 310 patients, 203 assigned to the GS group and 107 to the UC group. Patients in the GS group had significantly lower Barthel and Lawton scores, higher prevalence of dementia and heart failure, and higher comorbidity burden. Fifty-four (17.5%) patientsexperienced delirium (23 [11.3%] and 31 [29.2%] in the GS and UC groups, respectively; p .001), and 49 (15.8%) patient experienced other geriatric syndromes (21 [10.3%] and 28 [26.2%] in the GS and UC groups, respectively; p .001). Serious complications were more frequent in the GS group: 154 (75.9%) vs 60 (56.1%) in the UC group; p .001. No significant differences were observed between groups regarding readmissions, and in-hospital and post-discharge (1 year follow-up) mortality.Despite the poorer clinical condition of patients in the GS group, the CGA-based intervention resulted in a lower incidence of delirium and other geriatric syndromes compared with the UC group.

Urethral haemangiomas are rare benign vascular tumours. They usually cause painless urethral bleeding and haematospermia. Urethroscopy is the preferred diagnostic tool, while complementary radiologic studies could describe the extension of the tumour. Treatment should be tailored to each case, considering size, location, and number of lesions. We present a case of a male patient diagnosed with urethral haemangiomas following painless spontaneous urethral bleeding associated with voiding symptoms.

Background Antibiotic stewardship in the pretravel care of older adults is important to effectively treat infections while minimizing harm from side effects and unnecessary antibiotic use. The objective of this study was to compare the characteristics, risk behaviors, infectious diseases, and antibiotic use between older (≥60 years) and younger (18–59 years) travelers. Methods TravMil is a prospective, observational cohort of United States (US) Department of Defense beneficiaries traveling outside the continental US for ≤6.5 months. For this analysis, we included adults enrolled pretravel between January 2010 and August 2018 and excluded active duty personnel on deployment. Pre and post-travel surveys captured trip characteristics, exposures, illnesses, and antibiotic use. Results A total of 1742 travelers were analyzed: 747 (42.9%) were aged ≥60 years and 995 (57.1%) were aged 18–59 years. Older travelers were less likely to engage in high-risk dietary behaviors and experience travelers’ diarrhea than younger travelers (18.2% vs 22.9%; P, Older travelers (≥60 years) are less likely to engage in high-risk dietary behaviors and experience travelers’ diarrhea than younger travelers (18–59 years). Antibiotics are often used inappropriately for mild or self-limited diarrhea and influenza-like illnesses during travel.

BackgroundLafora disease (LD) is a fatal childhood-onset dementia characterized by the extensive accumulation of glycogen aggregates—the so-called Lafora Bodies (LBs)—in several organs. The accumulation of LBs in the brain underlies the neurological phenotype of the disease. LBs are composed of abnormal glycogen and various associated proteins, including p62, an autophagy adaptor that participates in the aggregation and clearance of misfolded proteins.MethodsTo study the role of p62 in the formation of LBs and its participation in the pathology of LD, we generated a mouse model of the disease (malinKO) lacking p62.ResultsDeletion of p62 prevented LB accumulation in skeletal muscle and cardiac tissue. In the brain, the absence of p62 altered LB morphology and increased susceptibility to epilepsy.ConclusionsThese results demonstrate that p62 participates in the formation of LBs and suggest that the sequestration of abnormal glycogen into LBs is a protective mechanism through which to reduce the deleterious consequences of its accumulation in the brain.

Infant neurodevelopment is a complex process which may be affected by different events during pregnancy, such as hypertensive disorders of pregnancy (HDP). We conducted a prospective cohort study to compare the prevalence of neurodevelopmental disorders in infants born to mothers with and without HDP at six months of age. Participants attended the Health Observatory of Instituto de Desarrollo e Investigaciones Pediátricas “Prof. Dr. Fernando E. Viteri” during 2018 and 2019. Infant neurodevelopment was assessed with the Bayley Scales of Infant and Toddler Development—Third Edition (Bayley-III). Data were analyzed using Chi-square, Student’s t-test and Mann–Whitney test. Of the 132 participating infants, 68 and 64 were born to mothers with and without HDP, respectively. At six months, the prevalence of risk of neurodevelopmental delay was significantly higher in infants born to mothers with than without HDP (27.9% vs. 9.4%; p = 0.008) (odds ratio, 3.71; 95% confidence interval, 1.30; 12.28). In conclusion, infants born to mothers with HDP had three times increased risk of neurodevelopmental delay at six months of age.

Background To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the cause of COVID-19 disease) exposure in pregnancy, compared to non-exposure, is associated with infection-related obstetric morbidity. Methods We conducted a multicentre prospective study in pregnancy based on a universal antenatal screening program for SARS-CoV-2 infection. Throughout Spain 45 hospitals tested all women at admission on delivery ward using polymerase-chain-reaction (PCR) for COVID-19 since late March 2020. The cohort of positive mothers and the concurrent sample of negative mothers was followed up until 6-weeks post-partum. Multivariable logistic regression analysis, adjusting for known confounding variables, determined the adjusted odds ratio (aOR) with 95% confidence intervals (95% CI) of the association of SARS-CoV-2 infection and obstetric outcomes. Main outcome measures: Preterm delivery (primary), premature rupture of membranes and neonatal intensive care unit admissions. Results Among 1009 screened pregnancies, 246 were SARS-CoV-2 positive. Compared to negative mothers (763 cases), SARS-CoV-2 infection increased the odds of preterm birth (34 vs 51, 13.8% vs 6.7%, aOR 2.12, 95% CI 1.32–3.36, p = 0.002); iatrogenic preterm delivery was more frequent in infected women (4.9% vs 1.3%, p = 0.001), while the occurrence of spontaneous preterm deliveries was statistically similar (6.1% vs 4.7%). An increased risk of premature rupture of membranes at term (39 vs 75, 15.8% vs 9.8%, aOR 1.70, 95% CI 1.11–2.57, p = 0.013) and neonatal intensive care unit admissions (23 vs 18, 9.3% vs 2.4%, aOR 4.62, 95% CI 2.43–8.94, p Conclusion This prospective multicentre study demonstrated that pregnant women infected with SARS-CoV-2 have more infection-related obstetric morbidity. This hypothesis merits evaluation of a causal association in further research.

Introduction During the COVID-19 pandemic, the national transplant activity has been reduced due to the overload of the health system and concern for patient safety in this situation. The aim of our work is to expose the activity of kidney transplantation in Cantabria during the state of alarm, as well as to assess the safety of the transplantation program. Material and methods Retrospective study of kidney transplants performed in our Center from the beginning of the state of alarm until the beginning of the lockdown easing in Cantabria. Descriptive analysis of the demographic data of recipients and their donors, intraoperative data and postoperative outcomes. Comparative analysis with the data of the same period in 2017–2019, by means of the X2 for categorical variables, Student’s T and Mann-Whitney U tests in case of quantitative variables of normal and non-normal distribution, respectively. Results Fifteen kidney transplants were performed in the period described. Delayed renal function (DRF) was seen in 7.5% of patients, and 26.6% showed data of acute rejection; no patient presented COVID-19 disease. Comparative analysis showed a remarkable increase in the number of transplants in comparison with previous periods (15 vs 5.6), at the expense of donors from outside Cantabria (93.3%). We found no statistically significant differences in terms of cold ischemia time (p 0.77), DRF (p 0.73), need for dialysis (p 0.54), or appearance of post-surgical complications (p 0.61). Conclusions The evolution of the pandemic in our region, and the adoption of strict protective measures has allowed the early and safe resumption of the renal transplantation program, increasing the number of transplants performed compared to previous years and maintaining comparable early post-operative results.

Background. Vertical transmission of the Coronavirus Disease 2019 (COVID-19) is still controversial. Additionally, the consequences of the infection during pregnancy in the offspring also are unknown. Case. A transitory fetal skin edema and polyhydramnios have been demonstrated by ultrasound in a pregnant patient with COVID-19 after a negative RT-PCR for SARS-CoV-2. The fetal findings presented a spontaneous resolution in utero, and abnormal findings were not found in the newborn. Conclusion. Women who have undergone SARS-CoV-2 infection during pregnancy should receive a subsequent appropriate follow-up in order to clarify the fetal consequences of the novel coronavirus, if any.

Lafora disease (LD) is a fatal adolescence-onset neurodegenerative condition. The hallmark of LD is the accumulation of aberrant glycogen aggregates called Lafora bodies (LBs) in the brain and other tissues. Impeding glycogen synthesis from early embryonic stages by genetic suppression of glycogen synthase (MGS) in an animal model of LD prevents LB formation and ultimately the pathological manifestations of LD thereby indicating that LBs are responsible for the pathophysiology of the disease. However, it is not clear whether eliminating glycogen synthesis in an adult animal after LBs have already formed would halt or reverse the progression of LD.Herein we generated a mouse model of LD with inducible MGS suppression. We evaluated the effect of MGS suppression at different time points on LB accumulation as well as on the appearance of neuroinflammation, a pathologic trait of LD models.In the skeletal muscle, MGS suppression in adult LD mice blocked the formation of new LBs and reduced the number of glycogen aggregates. In the brain, early but not late MGS suppression halted the accumulation of LBs. However, the neuroinflammatory response was still present, as shown by the levels of reactive astrocytes, microglia and inflammatory cytokines.Our results confirm that MGS as a promising therapeutic target for LD and highlight the importance of an early diagnosis for effective treatment of the disease.

The COVID-19 pandemic has raised questions about the possible cross immunity resulting from common vaccination programs and SARS-CoV-2 infection. Therefore, the Spanish Obstetric Emergency group performed a multicenter prospective study on the vaccination status of Influenza and Tdap (diphtheria, tetanus and pertussis vaccine boost administered in adulthood) in consecutive cases of SARS-CoV-2 infection in a pregnancy cohort, in order to assess its possible association with the clinical presentation and severity of symptoms of SARS-CoV-2 infection, as well as to determine the factors that may affect vaccination adherence. A total of 1150 SARS-CoV-2 positive pregnant women from 78 Spanish hospitals were analyzed: 183 had not received either vaccine, 23 had been vaccinated for Influenza only, 529 for Tdap only and 415 received both vaccines. No association was observed between the vaccination status and the clinical presentation of SARS-CoV-2 infection and/or the severity of symptoms. However, a lower adherence to the administration of both vaccines was observed in the Latin-American subgroup. Based on the results above, we reinforce the importance of maternal vaccination programs in the actual pandemic. Health education campaigns should be specially targeted to groups less likely to participate in these programs, as well as for a future SARS-CoV-2 vaccination campaign., This research was supported by public funds obtained in competitive calls: Grant COV20/ 00021 from the Instituto de Salud Carlos III-Spanish Ministry of Health, and co-financed with Fondo Europeo de Desarrollo Regional (FEDER) funds

Objectives Previous attempts to classify cancer cachexia (CC) have demonstrated limitations regarding stages and diagnostic criteria. This study aims to develop and validate a new staging system for CC in patients with incurable cancer. Methods This is an analysis of a database from a prospective cohort study of 1325 patients with advanced cancer referred for palliative care between 2016 and 2020. The cohort was randomly divided into two groups: Development (882 patients) and validation (443 patients) sets. A hierarchical cluster analysis was performed to distinguish different stages of CC in the development set. Next, the optimal cutoff points and ideal combinations of the most important factors associated with the CC groups (clusters) were ascertained. Finally, the relationship between the CC stages determined using the new system and body composition, quality of life, and overall survival was verified with the validation set. Results The new system classified CC into three stages: Precachexia (10.8%), cachexia (57.8%), and refractory cachexia (31.4%), based on a combination of percentage weight loss in the past 6 mo ( 26.4 kg/m2), and mid-upper-arm muscle area (≥38.0/≥35.5 or Conclusions This study presents a useful, valid system for CC staging in the clinical setting, and is also capable of predicting outcomes, including quality of life and overall survival.

In acute myeloid leukemia (AML) with inv(3)(q21;q26) or t(3;3)(q21;q26), a translocated GATA2 enhancer drives oncogenic expression of EVI1. We generated an EVI1-GFP AML model and applied an unbiased CRISPR/Cas9 enhancer scan to uncover sequence motifs essential for EVI1 transcription. Using this approach, we pinpointed a single regulatory element in the translocated GATA2 enhancer that is critically required for aberrant EVI1 expression. This element contained a DNA-binding motif for the transcription factor MYB, which specifically occupied this site at the translocated allele and was dispensable for GATA2 expression. MYB knockout as well as peptidomimetic blockade of CBP/p300-dependent MYB functions resulted in downregulation of EVI1 but not of GATA2. Targeting MYB or mutating its DNA-binding motif within the GATA2 enhancer resulted in myeloid differentiation and cell death, suggesting that interference with MYB-driven EVI1 transcription provides a potential entry point for therapy of inv(3)/t(3;3) AMLs. Significance: We show a novel paradigm in which chromosomal aberrations reveal critical regulatory elements that are nonfunctional at their endogenous locus. This knowledge provides a rationale to develop new compounds to selectively interfere with oncogenic enhancer activity. This article is highlighted in the In This Issue feature, p. 2659

Handgrip strength (HGS) is a potential predictor of outcomes in cancer setting. However, reference values for this population are lacking. The study aimed to describe reference values and cutoff point for HGS in adults with incurable cancer in Brazil and to verify the association of reference values with prognostic. Secondary analysis of a prospective cohort, conducted with 1,868 patients at the National Cancer Institute in Brazil were analyzed. HGS (kg) data were obtained with a Jamar® hydraulic dynamometer. Description of percentile values of HGS was stratified by sex and age groups. Receiver operating characteristic curve was performed to determine the optimal HGS cutoff point by sex and age according to performance status. Kaplan–Meier curves was used to analyze the probability of survival and Cox’s proportional model used to identify whether HGS predict 180-d mortality. HGS value was significantly higher in male than in female and decreased with increasing age. Sex-specific HGS cutoff values ranged from 32.5 to 24.5 kg in males and 20.5 to 18.5 kg in females (with younger adults stronger than the older ones). When compared to HGS ≥50th, patients with HGS ≤10th percentile had significantly lower survival, as well as patients classified below the HGS cutoff point. In addition, patients with lower HGS percentiles showed increased risk of mortality regardless of sex and age. Reference values can inform the clinical assessment of HGS, which is recognized as an important part of the identification of patients with incurable cancer with reduced physical function and short survival.

Simple Summary The chemotherapy agent pemetrexed is currently considered in combination with other therapies for the treatment of advanced nonsquamous non-small-cell lung cancer (NSCLC) in patients negative for gene mutations/rearrangements. The aim of this review was to highlight data from clinical studies with pemetrexed in patients with advanced nonsquamous NSCLC positive for gene mutations/rearrangements. The results of the review suggest that pemetrexed could be a treatment option in patients with advanced nonsquamous NSCLC positive for certain gene mutations/rearrangements. Abstract Pemetrexed is currently mainly considered for the treatment of advanced nonsquamous non-small-cell lung cancer (NSCLC) negative for gene mutations/rearrangements (wild-type disease (WTD)). This narrative review aimed to highlight the role of pemetrexed in the treatment of onco-driven nonsquamous advanced NSCLC by reviewing published clinical studies. For epidermal growth factor receptor (EGFR) mutations, patient survival following first-line pemetrexed–platinum was longer than for WTD. Later-line pemetrexed-based treatment after tyrosine kinase inhibitor (TKI) failure provided greater benefits than non-pemetrexed regimens. First- and later-line pemetrexed-based therapy also provided survival benefits in patients with anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 (ROS1) rearrangements. In patients with rearranged during transfection (RET) proto-oncogene rearrangements, survival with pemetrexed was similar to that in ALK- and ROS1-positive patients and longer than that in patients with Kirsten rat sarcoma (KRAS) virus proto-oncogene mutations or WTD, although the available studies were limited. For Erb-b2 receptor tyrosine kinase 2 (ERRB2) mutations, first-line pemetrexed showed outcomes similar to those for EGFR and KRAS alterations. Data on pemetrexed in patients with KRAS mutations or MNNG HOS-transforming (MET) expression were limited. Pemetrexed could be an option for first- and second-line treatment for TKI failure in nonsquamous advanced NSCLC with select targetable driver mutations.

The hallmark of Lafora disease, a fatal neurodegenerative disorder, is the accumulation of intracellular glycogen aggregates called Lafora bodies. Until recently, it was widely believed that brain Lafora bodies were present exclusively in neurons and thus that Lafora disease pathology derived from their accumulation in this cell population. However, recent evidence indicates that Lafora bodies are also present in astrocytes. To define the role of astrocytic Lafora bodies in Lafora disease pathology, we deleted glycogen synthase specifically from astrocytes in a mouse model of the disease (malinKO). Strikingly, blocking glycogen synthesis in astrocytes—thus impeding Lafora bodies accumulation in this cell type—prevented the increase in neurodegeneration markers, autophagy impairment, and metabolic changes characteristic of the malinKO model. Conversely, mice that over-accumulate glycogen in astrocytes showed an increase in these markers. These results unveil the deleterious consequences of the deregulation of glycogen metabolism in astrocytes and change the perspective that Lafora disease is caused solely by alterations in neurons.

This study aimed to evaluate the prognostic value of nutritional and inflammatory status in patients with advanced cancer receiving palliative care.The systemic inflammatory response was assessed using the modified Glasgow Prognostic Score (mGPS), and nutritional status was evaluated according to the Patient-Generated Subjective Global Assessment (PG-SGA) in 172 patients evaluated on their first visit in the Palliative Care Unit at the National Cancer Institute in Brazil. The receiver operating characteristic (ROC) curve was used to define the best cutoff point for the death-related PG-SGA score in 90 d. Kaplan-Meier curves were conducted for survival analyses, and logistic regression analyses were performed using the Cox proportional hazards model.According to the PG-SGA, 83.6% of the patients (n = 143) were malnourished (B + C) and 34.8% (n = 53) had mGPS ≥1. The best cutoff of the PG-SGA score for death was ≥19 points (area under the curve, 0.69; P = 0.041). Patients with scores ≥19, mGPS ≥1, albumin3.5 g/dL, and C-reactive protein ≥10 mg/L had a significantly lower overall survival. According to the multivariate analysis, albumin3.5 g/dL (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.16-3.58), mGPS ≥1 (HR, 1.46; 95% CI, 1.09-2.22), and PG-SGA score ≥19 (HR, 1.66; 95% CI, 1.08-2.55) were independent prognostic factors for overall survival.The severity of the systemic inflammation and the poor nutritional status predict survival and were considered independent prognostic factors. Thus they can be useful tools for nutritional evaluation in palliative care.

A majority of patients with advanced or metastatic non-small cell lung cancer (NSCLC) will experience disease progression after first-line therapy. Patients who have advanced NSCLC that is especially aggressive, which is defined as disease that rapidly progresses on first-line treatment or disease that is refractory to first-line treatment, have a critical unmet medical need. These patients have a poor prognosis in the second-line setting. Several studies have recently shown that treatment with an antiangiogenic therapy may benefit these patients. This review summarizes the approved antiangiogenic therapies for the treatment of patients with advanced NSCLC in the second-line setting, specifically focusing on the outcomes from subgroups of patients with rapidly progressing or refractory disease. Several antiangiogenic agents, as monotherapy or in combination with other treatments, have been or are currently being studied in patients with advanced NSCLC. Antiangiogenics that are approved for use in patients with advanced NSCLC are limited to bevacizumab in combination with chemotherapy (nonsquamous NSCLC), ramucirumab in combination with docetaxel (all histologies), and nintedanib in combination with docetaxel (adenocarcinoma histology). This review focuses on the efficacy, safety, and quality of life outcomes in the subpopulation of patients with rapidly progressing or refractory NSCLC treated with approved antiangiogenic therapies in the second-line setting. We also discuss the impact of newly approved immunotherapy agents on the outcomes of patients with aggressive or refractory disease. Studies in progress and planned future research will determine if combination treatment with antiangiogenics and immunotherapies will benefit patients with aggressive, advanced NSCLC.

Phase angle (PA) is a ratio between the reactance and resistance obtained by bioelectric impedance analysis and has been interpreted as a cell membrane integrity indicator and a predictor of total body cell mass. A low PA may suggest deterioration of the cell membrane, which in advanced cancer patients may result in a reduced overall survival (OS). This systematic review sought to investigate the current evidence regarding whether there is an association between PA and OS in patients with advanced cancer (ie, metastatic disease). The search was conducted on electronic databases in August 2017. A total of 34 articles were identified in the initial literature search. Nine studies reporting on 1496 patients were deemed eligible according to our inclusion criteria. PA data were analyzed as continuous variables or according to different cutoffs, under a frequency of 50 Khz. Low PA was associated with worse nutrition status evaluated by body mass index, serum albumin level, transferrin, and fat-free mass. The median OS of the included papers varied from 25.5-330 days, and all studies analyzed showed a significant association between PA and OS, in that patients with low PA had worse OS. Future studies are necessary to justify the use of PA in therapeutic decisions for this population and to evaluate whether nutrition status can influence the association between PA and survival.

Early detection of heterozygous familial hypercholesterolemia (HFH) is needed to prevent premature cardiovascular events. Our aim isto describe the course of an HFH screening detection day in the Northern Cadiz Health Area in Spain and to analyze the data recorded.Descriptive study of an FH cascade screening program. Index cases (ICs) and their 1st and 2nd grade relatives were appointed during a weekend by the FH Foundation. Venous blood samples were taken from the subjects for genetic, blood, and chemistry tests; specialized medical consultation and physical examination were performed.The study sample consisted of 132 subjects: 21 ICs and 111 relatives (16 under 18years old), with a mean age of 11.4years (SD4.57). Mean age of subjects over 18years was 45.2years. A gene mutation was found in 90 relatives. Mean age at diagnosis was 25years (SD17.7) for relatives and for 36.4years (SD17.2; P=.01) for ICs. Smoking rate was higher in relatives than in ICs (26.3% vs 4.8%; P=.02) and corneal arcus was more common in ICs as compared to relatives (47.6% vs 12.6%; P.001). Prior myocardial infarction was recorded in 14.3% of ICs and 4.2% of relatives respectively (P=.07). Maximum lipid lowering treatment was being administered to 43.1%.The screening detection approach identified the estimated 4% population with HFH in the area, and allows for diagnosing HFH 11.4years earlier.

Background and objectives: Adalimumab (ADA), a monoclonal humanised anti-TNF antibody, is usually prescribed as a second-line treatment in paediatric Crohn's disease (CD) patients who have become unresponsive or developed intolerance to infliximab (IFX). In the case series reported, more than 70% of patients had initially been treated with IFX. Data on short- and long-term efficacy of ADA in anti-TNF naïve patients is limited. The aim of this study is to describe our experience with ADA as a first-line anti-TNF in paediatric CD patients. Material and methods: This is a multicentre retrospective study including anti-TNF naïve paediatric CD patients treated with ADA as first-line anti-TNF. Results: Sixty-two patients (34 males), with a mean age of 13.0 ± 2.4 years and a disease duration of 7.3 (IQR 2.7–21) months were included. Median wPCDAI was 35 (IQR 24.3–47.5). Fifty-eight out of 62 (93.5%) were on combo therapy at baseline. Clinical remission at week 12 was achieved in 50 out of 62 (80.6%) and in 57 out of 60 (95.0%) at week 52. Eight patients (13%) reported adverse events. Mean height, growth rate and BMI z-scores improved significantly between baseline and week 52, especially in patients with growth failure. Conclusions: ADA treatment leads to lasting clinical remission in anti-TNF naïve paediatric patients with CD. ADA significantly improved growth rate in children with CD who had growth delay at baseline. Some patients remain in remission for prolonged time periods under monotherapy; however, some patients would require dose escalation. Resumen: Introducción y objetivos: Adalimumab (ADA), anticuerpo anti-TNF-α monoclonal recombinante de origen humano, generalmente se emplea como tratamiento de segunda línea en niños con enfermedad de Crohn (EC) que no han respondido o han perdido respuesta a infliximab (IFX). En las series publicadas más del 70% de los pacientes habían sido tratados inicialmente con IFX. Los datos sobre la eficacia a corto y a largo plazo de ADA en pacientes naïve a anti-TNF son muy limitados. El objetivo del presente estudio es describir nuestra experiencia con ADA como tratamiento anti-TNF de primera línea en niños con EC. Material y método: Estudio multicéntrico, retrospectivo que incluye pacientes con EC tratados con ADA como anti-TNF de primera línea. Resultados: Se incluyeron 62 pacientes (34 varones) con una edad media de 13,0 ± 2,4 años, un tiempo de evolución de la enfermedad de 7,3 meses (RIQ 2,7-21) y un wPCDAI de 35 puntos (RIQ 24,3-47,5). En el momento de comenzar ADA, 58 pacientes (93,5%) estaban recibiendo tratamiento inmunomodulador. A las 12 semanas de tratamiento el 80,6% (50/62) habían alcanzado la remisión clínica, así como el 95% (57/60) a las 52 semanas. Ocho pacientes (13%) presentaron efectos adversos. Se constató un incremento significativo de los z-scores de talla, velocidad de crecimiento e índice de masa corporal (IMC) a las 52 semanas de tratamiento, en especial en aquellos con retraso de crecimiento. Conclusiones: El tratamiento con ADA favorece una remisión clínica prolongada en pacientes naïve a anti-TNF. El tratamiento con ADA mejora la velocidad de crecimiento en niños con EC y retraso de crecimiento al inicio del tratamiento.

Background The purpose of this study was to evaluate the prognostic significance of the Patient-Generated Subjective Global Assessment (PG-SGA) in patients receiving palliative care for advanced cancer. Methods The PG-SGA was used to assess nutrition status of 120 patients admitted to the Palliative Care Unit at the National Cancer Institute in Brazil. Results According to the PG-SGA, 94.2% (n = 113) of the patients were evaluated as malnourished. The PG-SGA evaluated that xerostomia was the only symptom associated with a short survival (odds ratio [OR], 2.54; 95% confidence interval [CI], 1.2-5.38; P = .014). Survival was found to be significantly higher in well-nourished (PG-SGA A) than malnourished (PG-SGA B [ P = .021] or C [ P = .013]) patients. Total PG-SGA score (hazard ratio [HR], 1.06; 95% CI, 1.001-1.09; P = .045) and Karnofsky Performance Status of 20%-30% (HR, 15.4; 95% CI, 1.63-92.9; P = .001) and 40%-50% (HR, 10.0; 95% CI, 1.22-64.9; P = .031) were found to be independent prognostic survival factors. Conclusion The scored PG-SGA is an independent prognostic factor of survival and thus can be a useful tool for nutrition evaluation in palliative care.

iNeuroinflammation is one of the hallmarks of Alzheimer's disease. One of the enzymes involved in neuroinflammation, even in early stages of the disease, is COX-2, an inducible cyclooxygenase responsible for the generation of eicosanoids and for the generation of free radicals. Individuals with Down syndrome develop Alzheimer's disease early in life. Previous studies pointed to the possible overexpression of COX-2 and correlated it to brain regions affected by the disease. We analysed the COX-2 expression levels in individuals with Down syndrome and in young, adult and old mice of the Ts65Dn mouse model for Down syndrome. We have observed an overexpression of COX-2 in both, Down syndrome individuals and mice. Importantly, mice already presented an overexpression of COX-2 at postnatal day 30, before neurodegeneration begins; which suggests that neuroinflammation may underlie the posterior neurodegeneration observed in individuals with Down syndrome and in Ts65Dn mice and could be a factor for the premature appearance of Alzheimer's disease./i.

Introduction: Malnutrition on admission is closely related to a longer hospital stay and a higher morbidity. The prevalence of hospital malnutrition has been reported as almost as high as 50%, with 6% being the lowest. DHOSPE study investigates nutrition status in Spanish hospitals and its outcome during the hospital stay. Patients and methods: A longitudinal, multicentre, descriptive, cross-sectional study, with a short follow-up period was conducted in 32 hospitals during 2011. A total of 991 patients were included, with ages from 0 to 17 years. Each patient was measured at admission (weight, length, weight for length -W/L-, length for age -L/A-), and at 7 and 14 days. The STAMP nutritional screening tool was completed on admission. Anthropometric measurements were reported as z-score, and nutrition status classified according to W/L and L/A for acute and chronic malnutrition, respectively. Results: The prevalence of malnutrition was 7.1% for moderate, and 0.7% for severe acute malnutrition. For chronic malnutrition, 2.7% was moderate, and 1.4% severe. There were significant differences according to the underlying condition but not according to age. Results of STAMP show that around 75% of patients had a moderate to high risk of malnutrition. Nutritional status changed during admission for weight, as well as W/L and L/A. A worse nutritional status at admission and a higher STAMP score were positively correlated with the need for nutrition support. Conclusions: The prevalence of undernutrition was slightly lower (

Microglia are brain-resident immune cells and regulate mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by a supernumerary chromosome 21, containing also genes related to the immune system. In the hippocampus of the Dp(16) mouse model of DS and DS individuals, we found activated microglia, as assessed by their morphology; activation markers; and, for DS mice, electrophysiological profile. Accordingly, we found increased pro-inflammatory cytokine levels and altered interferon signaling in Dp(16) hippocampi. DS mice also showed decreased spine density and activity of hippocampal neurons and hippocampus-dependent cognitive behavioral deficits. Depletion of defective microglia or treatment with a commonly used anti-inflammatory drug rescued the neuronal spine and activity impairments and cognitive deficits in juvenile Dp(16) mice. Our results suggest an involvement of microglia in Dp(16)-mouse cognitive deficits and identify a new potential therapeutic approach for cognitive disabilities in DS individuals.

Although genome-wide association studies have identified a number of common variants associated with multiple sclerosis (MS) susceptibility, little is known about the relevance of rare variants. Here, we aimed to explore the role of rare variants in 14 MS risk genes (FCRL1, RGS1, TIMMDC1, HHEX, CXCR5, LTBR, TSFM, GALC, TRAF3, STAT3, TNFSF14, IFI30, CD40, and CYP24A1) by targeted resequencing in an Iberian population of 524 MS cases and 546 healthy controls. Four rare variants-enriched regions within CYP24A1, FCRL1, RGS1, and TRAF3 were identified as significantly associated with MS. Functional studies revealed significantly decreased regulator of G protein signaling 1 (RGS1) gene expression levels in peripheral blood mononuclear cells from MS patients with RGS1 rare variants compared to noncarriers, whereas no significant differences in gene expression were observed for CYP24A1, FCRL1, and TRAF3 between rare variants carriers and noncarriers. Immunophenotyping showed significant decrease in RGS1 expression in peripheral blood B lymphocytes from MS patients with RGS1 rare variants relative to noncarriers. Lastly, peripheral blood mononuclear cell from MS patients carrying RGS1 rare variants showed significantly lower induction of RGS1 gene expression by interferon-β compared to MS patients lacking RGS1 variants. The presence of rare variants in RGS1 reinforce the ideas of high genetic heterogeneity and a role of rare variants in MS pathogenesis., This work was supported by grants from the Fondo de Investigación Sanitaria (FIS; grant number PI12/02229; Ministry of Science and Innovation, Spain), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarollo Regional (FEDER; grant number BFU2016‐77961‐P), Direcció General de Recerca ‐ Generalitat de Catalunya (2017‐SGR‐00702), Unidad de Excelencia María de Maeztu (MINECO; MDM‐2014‐0370), and Vall d'Hebrón Institut de Recerca (predoctoral grants program 2014).

Purpose To evaluate and compare the effect of misalignment and tilt on the optical performance of different aspheric intraocular lens (IOL) designs. Methods Three aspheric IOLs with a different quantity of spherical aberration (SA) have been designed and the effect of IOL misalignment and tilt on the imaging quality of an eye model has been numerically assessed using a commercial optical design software. The prototypes have been manufactured by lathe turning and tested in vitro using the same optical bench (PMTF, Lambda-X) that complies with International Organization for Standardization standard 11979-2 requirements. Image quality was evaluated from the modulation transfer functions (MTFs), through-focus modulation transfer functions (TF-MTFs), root mean square (RMS) values of defocus, astigmatism and coma, and images of the United States Air Force (USAF) target were taken. A comparison with the optical performance of spherical IOLs has also been performed. Results Intraocular lens misalignment and tilt increased wavefront aberrations; the effect of misalignment on root mean square (RMS) astigmatism and coma was positively correlated with the spherical aberration of the IOL. Aberration-free IOLs showed the highest MTF for all misalignment values and for IOLs with negative SA correction the MTF decays below 0.43 when they are decentered 0.50 mm. Conclusions Aspherical IOLs are more sensitive than spherical IOLs to misalignment or tilt, depending on their SA correction. The optical degradation caused by IOL misalignment had a greater effect on IOL designs with a higher amount of negative spherical aberration. In contrast, the effect of tilt on the optical performance was less sensitive to the IOL design.

Background Alterations in the structure and physiology of interneurons in the prefrontal cortex (PFC) are important factors in the etiopathology of different psychiatric disorders. Among the interneuronal subpopulations, parvalbumin (PV) expressing cells appear to be specially affected. Interestingly, during development and adulthood the connectivity of these interneurons is regulated by the presence of perineuronal nets (PNNs), specialized regions of the extracellular matrix, which are frequently surrounding PV expressing neurons. Previous reports have found anomalies in the density of PNNs in the PFC of schizophrenic patients. However, although some studies have described alterations in PNNs in some extracortical regions of bipolar disorder patients, there are no studies focusing on the prefrontocortical PNNs of bipolar or major depression patients. For this reason, we have analyzed the density of PNNs in post-mortem sections of the dorsolateral PFC (DLPFC) from the Stanley Neuropathology Consortium, which includes controls, schizophrenia, bipolar and major depression patients. Results We have not observed differences in the distribution of PV+ cells or PNNs, or in the percentage of PV+ interneurons surrounded by PNNs. The density of PV+ interneurons was similar in all the experimental groups, but there was a significantly lower density of PNNs in the DLPFC of bipolar disorder patients and a tendency towards a decrease in schizophrenic patients. No differences were found when evaluating the density of PV+ cells surrounded by PNNs. Interestingly, when assessing the influence of demographic data, we found an inverse correlation between the density of PNNs and the presence of psychosis. Conclusions The present results point to prefrontocortical PNNs and their role in the regulation of neuronal plasticity as putative players in the etiopathology of bipolar disorder and schizophrenia. Our findings also suggest a link between these specialized regions of the extracellular matrix and the presence of psychosis.

Nutritional impairment is common in cancer patients and adversely affects quality of life (QoL). The aim of this study was to investigate the association between nutritional status and QoL in incurable cancer patients in palliative care. A prospective cohort with incurable cancer patients referred to the specialized Palliative Care Unit of the National Cancer Institute in Brazil was conducted. The nutritional risk (NR) was assessed using the Patient-Generated Subjective Global Assessment short form (PG-SGA SF), and cancer cachexia (CC) was defined according to the international consensus. QoL was evaluated using the Quality of Life Questionnaire Core 15 Palliative (QLQ-C15-PAL). Multivariate linear regressions analyses were performed to assess the relationship between the nutritional status and QoL scores. A total of 1039 consecutive patients were included. A high prevalence of NR (85.4%) and CC (78.7%) were observed. The patients with worse nutritional status presented significantly poorer physical, emotional, symptoms domains scales, and overall QoL. CC were significantly associated with QoL scores for dyspnea (p = 0.013), insomnia (p = 0.046), and appetite loss (p = 0.015), while NR were associated with all the QoL domains scales covered in QLQ-C15-PAL. Our findings support that impaired nutritional status was associated with poor QoL in incurable cancer patients. NR assessed by PG-SGA SF better reflects physical, emotional, symptom burden, and overall QoL scores. Thus, this tool may contribute in identifying patients at risk of deterioration QoL.

Current data suggest that low skeletal muscle mass provides prognostic information in patients with cancer and may even be considered a biomarker in research and clinical evaluations. The aim of this systematic review was to explore whether low muscle mass is associated with overall survival (OS) in patients with incurable cancer. A systematic search was conducted for published literature using PubMed/MEDLINE, Scopus, LILACS, and the Cochrane Library, with no restrictions on language or publication date, to examine whether low muscle mass is associated with OS in patients with incurable cancer. Eligible studies included low muscle mass evaluated using gold standard techniques (dual energy x-ray absorptiometry or computed tomography). The studies quality assessment was performed using the Newcastle-Ottawa Scale. Thirteen studies were included. The studies reported on 1959 patients between 54.3 (median) and 72.9 (mean) y of age; pancreatic cancer was the most common type of tumor. According to the survival curves and most of the multivariate analyses, there was no statistically significant association between loss of muscle mass and reduced OS. Four studies reported that overweight or obese patients with muscle mass depletion had significantly shorter OS. These results indicate that there is insufficient evidence to associate low muscle mass with OS in patients with incurable cancer. Further studies deploying other muscle measurement methods suggest that use of low muscle mass cutoff alone is still necessary in the pursuit of OS prediction in this population.

Oxidative stress (OS) has been previously linked to the aging process, as have some diseases and geriatric syndromes as frailty and sarcopenia. The aim of the present study was to perform a systematic review on oxidative stress activity and extreme longevity in humans.We conducted a systematic literature review following the PRISMA guidelines. Observational studies assessing OS-biomarkers and/or antioxidants in long-lived individuals (97 years old or over) comparing them to those of one or more age groups, (at least one of which from comprising elderly subjects) were considered for inclusion. A narrative synthesis was planned. Quality of selected studies was assessed using the Newcastle-Ottawa quality assessment scale (NOS).After screening and eligibility phases, 12 articles were finally selected, with 646 long-lived participants and 1052 controls, 447 adults (20-60 years old) and 605 elderly individuals (over 60 years old). The average score on NOS scale of studies was 4,8 out of 9. Centenarians showed significantly less (p0,05) oxidative damage to lipids in different samples, lower levels of oxidized proteins in plasma and lower superoxide anion levels in neutrophils than elderly groups. Centenarian presented significantly lower superoxide dismutase and higher glutathione reductase activities, higher levels of vitamins A and E, lower of coenzyme Q10, and lower susceptibility to lipid peroxidation than elderly controls.Based on studies of medium-low quality, available evidence suggests that long-lived individuals display less oxidative damage, particularly lower plasma lipid peroxidation biomarkers, than controls. More studies with better experimental designs are needed.

Introdução: O ângulo de fase (AF) pode estar relacionado ao estado nutricional em indivíduos com câncer. Objetivo: Investigar a correlação entre o AF e o estado nutricional em pacientes com câncer avançado. Método: Estudo transversal com indivíduos de ambos os sexos, idade >20 anos, em seu primeiro atendimento na unidade de cuidados paliativos do Instituto Nacional de CâncerJosé Alencar Gomes da Silva (INCA). O AF foi avaliado por meio da impedância bioelétrica, sendo considerados como baixos os valores

Obesity-associated hypoandrogenemia is increasing in parallel to the obesity epidemic. The prevalence of hypoandrogenemia in nondiabetic young men with obesity is not known. This study aimed to evaluate the prevalence of hypoandrogenemia and associated risk factors in this population.This cross-sectional study included 266 nondiabetic men 50 years of age with obesity who were referred from primary care. Total testosterone (high-performance liquid chromatography mass spectrometry), sex hormone-binding globulin, free testosterone (FT), luteinizing hormone (LH), high-sensitivity C-reactive protein, and homeostatic model assessment of insulin resistance were determined. Body composition and erectile function were also assessed. Hypoandrogenemia was defined as FT level 70 pg/mL.Subnormal FT concentrations were found in 25.6% of participants. Hypoandrogenemia prevalence was different along the BMI continuum, being 75% in individuals with BMI ≥ 50 kg/mIn a primary care-based cohort of nondiabetic young men with obesity, hypoandrogenemia was a very prevalent finding and was directly associated with adiposity. Obesity, age, and reduced LH levels were independent risk factors associated with hypoandrogenemia. Further prospective studies are needed to evaluate the long-term consequences of hypoandrogenemia in this population.

Summary Background & aims It is a challenge in clinical practice to identify and classify cancer cachexia. Currently, it has been extensively discussed if the presence of alterations in inflammatory biomarkers implies the presence of cachexia. This study aimed to evaluate the clinical relevance of cachexia classification through modified Glasgow Prognostic Score (mGPS) in advanced cancer patients in palliative care. Methods Observational prospective cohort study conducted at a Palliative Care Unit in Brazil. Cachexia classification was performed according to mGPS (based on albumin and C-reactive protein) in four different stages: no cachexia (NCa), undernourished (Un), pre cachexia (PCa), and refractory cachexia (RCa). Logistic regression models were used to test the association between cachexia stages and clinical, nutritional and functional domains. Kaplan–Meier curve and Cox multivariate model were used to analyze overall survival (OS). Results A total of 1166 patients were included in the study. According to the cachexia framework 37.5% were NCa, 32.3% Un, 3.9% PCa and 26.4% RCa. Significant differences were observed among cachexia stages for most of the outcome measures. This classification was able to predict mortality in 90 days [Un (HR, 1.55; 95% CI, 1.25; 1.93); PCa (HR, 2.00; 95% CI, 1.34; 2.98); RCa (HR, 2.45; 95% CI, 1.34; 2.98)]. Conclusion Cachexia stages were associated with significant differences in poor clinical outcomes and were also capable of predicting OS. This framework based on simple and objective criteria can be used as part of the routine to characterize the presence and stages of cachexia in advanced cancer patients.

Research among former Physical Education (PE) school students has demonstrated how fat phobia in PE classes is oppressive and makes it extremely difficult for most students to develop positive subjectivities. This study explores how a group of pre-service Health and Physical Education (HPE) specialist teachers from an Australian university construct fatness discourses. Taking a Foucauldian perspective, focusing particularly on the concepts of surveillance and normalisation, this paper explores the dominant discourses that pre-service HPE specialist teachers construct about fatness. Semi-structured, in-depth interviews (three interviews per participant) were conducted with 14 students (11 females and three males) aged between 18 and 26 at the time of the first interview. The results of a content analysis of the interview data suggest that students generally tend to classify certain bodies as ‘decent’ and ‘normal’, implying the existence of ‘indecent’ and ‘abnormal’ bodies. Participants also expressed a paternalistic approach and moral judgments towards people they considered to be fat. The results suggest that HPE specialist teachers have certain constructions of fatness that could be explored in their undergraduate degrees so as to minimise any possible ramifications for their teaching.

Obesity is associated with decreased circulating testosterone levels, the main male sex hormone. However, there are a number of different male sex hormones whose dynamics remain poorly understood regarding this pathology. In this regard, 17 hydroxyprogesterone (17-OH progesterone), as an important precursor of testosterone synthetized in testes and adrenal glands, could play an essential role in testosterone deficiency in male obesity. Moreover, similarly to testosterone, 17-OH progesterone could be closely associated with visceral fat distribution and metabolic dysfunction. Thus, the aim of this study was to assess serum 17-OH progesterone levels in non-diabetic obese young men and to evaluate their relationship with clinical, analytical, and anthropometric parameters. We conducted a cross-sectional study including 266 non-diabetic men with obesity (BMI &ge, 30 kg/m2) aged 18&ndash, 49 years, 17-OH progesterone and total testosterone (TT) were determined by high-performance liquid chromatography mass spectrometry. 17-OH progesterone levels were significantly lower in tertile 3 of body fat percentage in comparison with tertile 1 (0.74 ng/mL vs. 0.94 ng/mL, p &lt, 0.01, Bonferroni correction) and in comparison with tertile 2 (0.74 ng/mL vs. 0.89 ng/mL, p = 0.02, Bonferroni correction). 17-OH progesterone levels correlated negatively with weight, BMI, waist circumference, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and visceral fat, and positively with TT, free testosterone (FT), luteinizing hormone, and fat-free mass percentage. Multivariate linear-regression analysis showed that body fat percentage and HOMA-IR were inversely associated with 17-OH progesterone levels, while FT and ACTH were positively linked to circulating 17-OH progesterone levels. In conclusion, in a population of non-diabetic obese young men, 17-OH progesterone levels were inversely associated with adiposity. Body fat percentage and insulin resistance were negatively related to 17-OH progesterone levels, whereas FT and ACTH levels were positively associated with 17-OH progesterone levels.