Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure.

BACKGROUND AND AIMS: Oxaliplatin (OX) has been described as a potential etiologic agent for porto-sinusoidal vascular disorder (PSVD). Our aim was to describe the natural history of PSVD due to OX in colon cancer (CRC) and identify risk factors for its development. METHODS: We made a multicenter retrospective case-control (ratio 1:3) study with patients diagnosed of PSVD-OX. Baseline data, end of treatment, years of follow-up and diagnosis of PSVD were collected and compared to controls (without PSVD). Besides, 16 different SNPs were selected from bibliography and analyzed by genotyping in the case group to identify potential genetic risk factors. RESULTS: 41 cases were identified, with a median time to PSVD diagnosis after the end of OX of 34 months. Spleen diameter was the strongest predictor of PSVD during treatment (OR 43.94 (14.48-133.336); p < 0.0001). Additionally, thrombocytopenia (<150 × 10^9) at one year was a significant disease risk marker (OR 9.35; 95% CI: 3.71-23.58; p = 0.001). We could not establish any significant association between the selected SNPs and PSVD diagnosis. CONCLUSION: The increase of spleen diameter is the strongest predictor of PSVD in patients treated with OX for CRC. These patients could be candidates for a specific follow-up of portal hypertension-related complications.

Adolescent polycystic ovary syndrome without obesity: HOTAIR rs1443512 genotype relates to fat mass and to the redistribution of fat mass on low-dose pioglitazone.

INTRODUCTION: Adolescent polycystic ovary syndrome (PCOS) is characterized by androgen excess and oligo-amenorrhea, and often results from ectopic lipid storage due to a mismatch between early adipogenesis and later lipogenesis. Endogenous HOX transcript antisense RNA (HOTAIR) and exogenous pioglitazone are enhancers of subcutaneous adipogenesis, particularly in the gluteofemoral region. The A allele of HOTAIR rs1443512 is an equivalent of a natural knock-down and is, thus, a candidate to influence the distribution of fat mass, and also the redistribution of fat mass by pioglitazone in adolescent PCOS-without-obesity. SUBJECTS AND METHODS: We performed two post hoc analyses by HOTAIR rs1443512 genotype. In the first, we analyzed the pooled pre-treatment data (auxology; endocrinology; body composition by dual X-ray absorptiometry; abdominal fat distribution by magnetic resonance imaging) of 65 adolescent girls with PCOS-without-obesity in three reported studies (ISRCTN45546616; ISRCTN29234515; ISRCTN11062950). In the second, we analyzed the results of 24 adolescent girls with PCOS-without-obesity, who received pioglitazone (7.5 mg/d for 1 year) as part of a randomized combination treatment (with spironolactone and metformin) in two reported studies (ISRCTN29234515; ISRCTN11062950). All data had been obtained in a blinded-to-genotype way. RESULTS: The pre-treatment data disclosed that the girls-with-A-allele of HOTAIR rs1443512 had developed PCOS with a lower BMI (22.3 ± 2.3 kg/m2; N = 17) than the other girls (24.1 ± 2.7 kg/m2; N = 48), this difference being essentially attributable to a lower fat mass (mean difference 4.6 kg; P < 0.01). On low-dose pioglitazone, girls-with-A-allele (N = 12) raised their fat mass while the other girls (N = 12) did not (total fat mass + 2.2 ± 1.8 kg vs - 0.9 ± 2.2 kg; P < 0.001), particularly in the gynoid area (gluteofemoral fat + 0.6 ± 0.4 kg vs - 0.1 ± 0.5 kg; hip circumference + 2.3 ± 1.9 cm vs - 1.7 ± 3.1 cm; both P < 0.001). CONCLUSION: The present findings suggest that the HOTAIR rs1443512 genotype influences not only the distribution of fat mass in adolescent girls with PCOS-without-obesity but also the redistribution of fat mass during prolonged treatment with low-dose pioglitazone. TRIAL REGISTRATION: ISRCTN45546616 ( https://doi.org/10.1186/ISRCTN45546616 ). ISRCTN29234515 ( https://doi.org/10.1186/ISRCTN29234515 ). ISRCTN11062950 ( https://doi.org/10.1186/ISRCTN11062950 ).

Decreased expression of surfactant Protein-C and CD74 in alveolar epithelial cells during influenza virus A(H1N1)pdm09 and H3N2 infection.

The primary replication site of Influenza A virus (IAV) is type II alveolar epithelial cells (AECII), which are central to normal lung function and present important immune functions. Surfactant components are synthesized primarily by AECII, which play a crucial role in host defense against infection. The aim of this study was to analyze if the impact of influenza infection is differential between A(H1N1)pdm09 and A/Victoria/3/75 (H3N2) on costimulatory molecules and ProSP-C expression in AECII from BALB/c mice infected and A549 cell line infected with both strains. Pandemic A(H1N1)pdm09 and A/Victoria/3/75 (H3N2) were used to infect BALB/c mice and the A549 cell line. We evaluated the surface expression of co-stimulatory molecules (CD45/CD31/CD74/ProSP-C) in AECII and A549 cell lines. Our results showed a significant decrease in ProSP-C+ CD31- CD45- and CD74+ CD31- CD45- expression in AECII and A549 cell line with the virus strain A(H1N1)pdm09 versus A/Victoria/3/75 (H3N2) and controls (non-infection conditions). Our findings indicate that changes in the expression of ProSP-C in AECII and A549 cell lines in infection conditions could result in dysfunction leading to decreased lung compliance, increased work of breathing and increased susceptibility to injury.

Tic disorders and premonitory urges: validation of the Spanish-language version of the Premonitory Urge for Tics Scale in children and adolescents.

INTRODUCTION: Most people with persistent tics report an unpleasant sensation (premonitory urge) before the tic. In recent years, interest in these sensory phenomena has increased due to their important role in behavioural therapy. However, instruments for assessing these sensations remain scarce. Among the available instruments, the Premonitory Urge for Tics Scale (PUTS) is the most widely used. METHODS: We examined the psychometric properties and factor structure of the Spanish-language version of the PUTS in a sample of 72 children and adolescents with Tourette syndrome or persistent tic disorders. We analysed data from the total sample and by age group (children up to 10 years old and children/adolescents over 10). RESULTS: The PUTS presented good internal consistency and moderate correlations between items on the scale (except for item 1). Divergent validity was good, test-retest reliability was adequate, and a bifactorial structure was identified (one dimension related to mental phenomena reported in obsessive-compulsive disorder, and another related to the quality and frequency of premonitory urges). These results were replicated in both age groups, with lower divergent validity and test-retest reliability in the younger group. CONCLUSIONS: The Spanish-language version of the PUTS is a valid, reliable tool for assessing premonitory urges in both children and adolescents, especially after the age of 10.

Indications related to antidepressant prescribing in the Nivel-PCD database and the SIDIAP database.

BACKGROUND: Antidepressant drug consumption has increased, mainly in the elderly. This trend could be explained by the use for indications other than depression. We aimed to describe the indications related to antidepressant drug new users in two primary care settings. METHODS: A longitudinal study of new antidepressant users aged ≥65 was conducted, with data from the Nivel-PCD (The Netherlands) and SIDIAP (Catalonia) databases (2010-2015). As a proxy for indication, diagnoses registered around the 3 months of antidepressant prescribing were collected. Indications were classified in seven categories and an additional one of non-selected indications. The percentage and incidence calculated over the total population registered was described. RESULTS: A total of 16,537 and 199,168 new antidepressant users were identified in the Nivel-PCD and SIDIAP databases, respectively (women aged 65-69 were the most prevalent). Depression was the most frequent indication (24.0% and 31.3%), followed by anxiety (12.5% and 19.5%) and sleep disorders (10.2% and 26.4%). Tricyclic antidepressants were the most commonly prescribed in Nivel-PCD (48.7%), mainly associated with neuropathic pain, and selective serotonin reuptake inhibitor antidepressants in SIDIAP (63.1%), associated with depression. The non-selected indications category showed an upward trend in the Nivel-PCD database while in the SIDIAP database it decreased. LIMITATIONS: It is not mandatory for physicians to register a diagnosis with each prescription. CONCLUSIONS: Depression was the most common prescribing indication in The Netherlands and Spain, followed by anxiety and sleep disorders. The most commonly prescribed antidepressant differed between the countries and is likely explained by differences in local guidelines.

COVID-19 pandemic: Impact on the rate of viral conjunctivitis.

OBJECTIVE: The COVID-19 pandemic led Spain to order a state of alert with the cessation of non-essential activities on 14 March 2020, and to implement public health interventions (such as home confinement) and other health recommendations to prevent the spread of the SARS-CoV-2 virus (hand washing and the obligation to wear face-masks). These factors could have influenced the rate of viral conjunctivitis. METHOD: In this retrospective, noninterventional, descriptive study, the incidence of viral conjunctivitis in an emergency department of a national hospital is compared over two distinct time periods: pre-COVID (13 March-30 September 2019, one year before the start of the pandemic) and COVID (13 March-30 September 2020). RESULTS: In the first period there were 436 cases of conjunctivitis, of which 168 (38.5%) were confirmed cases of viral conjunctivitis 168 (38.5%), while in the second period there were 121 recorded cases, of which the most frequent were allergic and traumatic (23 cases; 19% each group), bacterial (15 cases; 12.3%) and viral (15 cases; 12.3%). The diagnosis of viral conjunctivitis is the one that suffered the most significant relative reduction (48.5%), while other types of conjunctivitis hardly changed their relative frequency between these two periods of time. CONCLUSIONS: Viral conjunctivitis is the most frequent infectious disease of the eye and has a transmission rate similar to that of coronavirus, so the measures implemented could positively affect its incidence.

Can we correct first metatarsal rotation and sesamoid position with the 3D Lapidus procedure?

OBJECTIVE: We examine the technique and radiographic outcomes obtained with triplanar first tarsometatarsal arthrodesis (3D Lapidus) for the surgical correction of hallux valgus (HV). This procedure, apart from correcting angular deformity 1st-2nd intermetatarsal angle, HV angle, etc., is specifically intended to act on first ray pronation and place the sesamoids in their normal position, to alleviate the metatarsalgia often occurring in HV before and after surgery, possibly caused by their abnormal position. This study aims to examine the radiographic outcomes of the 3D Lapidus procedure. MATERIALS AND METHODS: Retrospective study of 37 feet operated on from April 2019 to December 2019, with a minimum 1-year follow-up (mean 420 days), using the 3D Lapidus procedure. Radiographic outcomes were evaluated. RESULTS: The intermetatarsal angle decreased from a mean value of 16.42° to 5.62° (p < 0.0001). The HV angle decreased from a mean value of 32.12° to 8.05° (p < 0.0001). The preoperative first metatarsocuneiform angle, with a mean value of 21.86°, was null after arthrodesis (p < 0.0001). The tibial sesamoid position, according to the Hardy and Clapham classification, decreased from a mean value of 4.84 to 1.27 after surgery, within normality (p < 0.0001). DISCUSSION: Correction of the deformity in a single plane is generally insufficient. It is necessary to act on the three planes of space to correct the deformity, obtain good outcomes, and avoid recurrence. CONCLUSIONS: Radiographic outcomes of triplanar correction with the 3D Lapidus procedure are excellent, achieving statistically significant differences in all parameters studied.

[COVID-19 pandemic: Impact on the rate of viral conjunctivitis]. / Pandemia COVID-19: impacto sobre la tasa de conjuntivitis virales.

OBJECTIVE: The COVID-19 pandemic led Spain to order a state of alert with the cessation of non-essential activities on 14 March 2020, and to implement public health interventions (such as home confinement) and other health recommendations to prevent the spread of the SARS-CoV-2 virus (hand washing and the obligation to wear face-masks). These factors could have influenced the rate of viral conjunctivitis. METHOD: In this retrospective, noninterventional, descriptive study, the incidence of viral conjunctivitis in an emergency department of a national hospital is compared over two distinct time periods: pre-COVID (13 March-30 September 2019, one year before the start of the pandemic) and COVID (13 March-30 September 2020). RESULTS: In the first period there were 436 cases of conjunctivitis, of which 168 (38.5%) were confirmed cases of viral conjunctivitis 168 (38.5%), while in the second period there were 121 recorded cases, of which the most frequent were allergic and traumatic (23 cases; 19% each group), bacterial (15 cases; 12.3%) and viral (15 cases; 12.3%). The diagnosis of viral conjunctivitis is the one that suffered the most significant relative reduction (48.5%), while other types of conjunctivitis hardly changed their relative frequency between these two periods of time. CONCLUSIONS: Viral conjunctivitis is the most frequent infectious disease of the eye and has a transmission rate similar to that of coronavirus, so the measures implemented could positively affect its incidence.

Adherence to Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation: A Cross-National Comparison in Six European Countries (2008-2015).

Aims: To describe and compare the adherence to different direct oral anticoagulants (DOACs) in eight European databases representing six countries. Methods: Longitudinal drug utilization study of new users (≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of non-valvular atrial fibrillation (2008-2015). Adherence was examined by estimating persistence, switching, and discontinuation rates at 12 months. Primary non-adherence was estimated in BIFAP and SIDIAP databases. Results: The highest persistence rate was seen for apixaban in the CPRD database (81%) and the lowest for dabigatran in the Mondriaan database (22%). The switching rate for all DOACs ranged from 2.4 to 13.1% (Mondriaan and EGB databases, respectively). Dabigatran had the highest switching rate from 5.0 to 20.0% (Mondriaan and EGB databases, respectively). The discontinuation rate for all DOACs ranged from 16.0 to 63.9% (CPRD and Bavarian CD databases, respectively). Dabigatran had the highest rate of discontinuers, except in the Bavarian CD and AOK NORDWEST databases, ranging from 23.2 to 64.6% (CPRD and Mondriaan databases, respectively). Combined primary non-adherence for examined DOACs was 11.1% in BIFAP and 14.0% in SIDIAP. There were differences in population coverage and in the type of drug data source among the databases. Conclusion: Despite the differences in the characteristics of the databases and in demographic and baseline characteristics of the included population that could explain some of the observed discrepancies, we can observe a similar pattern throughout the databases. Apixaban was the DOAC with the highest persistence. Dabigatran had the highest proportion of discontinuers and switchers at 12 months in most databases (EMA/2015/27/PH).

Tic disorders and premonitory urges: validation of the Spanish-language version of the Premonitory Urge for Tics Scale in children and adolescents. / Trastornos de tics e impulso premonitorio: validación de la versión española de la «Escala para el Impulso Premonitorio al Tic¼ en niños y adolescentes.

INTRODUCTION: Most people with persistent tics report an unpleasant sensation (premonitory urge) before the tic. In recent years, interest in these sensory phenomena has increased due to their important role in behavioural therapy. However, instruments for assessing these sensations remain scarce. Among the available instruments, the Premonitory Urge for Tics Scale (PUTS) is the most widely used. METHODS: We examined the psychometric properties and factor structure of the Spanish-language version of the PUTS in a sample of 72 children and adolescents with Tourette syndrome or persistent tic disorders. We analysed data from the total sample and by age group (children up to 10 years old and children/adolescents over 10). RESULTS: The PUTS presented good internal consistency and moderate correlations between items on the scale (except for item one). Divergent validity was good, test-retest reliability was adequate, and a bifactorial structure was identified (one dimension related to mental phenomena reported in obsessive-compulsive disorder, and another related to the quality and frequency of premonitory urges). These results were replicated in both age groups, with lower divergent validity and test-retest reliability in the younger group. CONCLUSIONS: The Spanish-language version of the PUTS is a valid, reliable tool for assessing premonitory urges in both children and adolescents, especially after the age of 10.

Embarazo en enfermedad inflamatoria intestinal: no solo 9 meses de cuidado

The prevalence of inflammatory bowel disease (IBD) increased in the last decades. Thus, the number of pregnant women with the condition is also increasing. Given that active disease itself is the main risk factor for complications during pregnancy, it is necessary to achieve a complete remission before planning a pregnancy. Also, pregnant women with IBD must be monitored noninvasively and be treated proactively, including escalated therapies, if needed, to prevent potential flares during pregnancy. Patients can undergo vaginal delivery in most forms of IBD. However, cesarean delivery is still preferable in women with a history of ileal pouch-anal anastomoses (IPAA) or active perianal disease.

[Inflammatory bowel disease during pregnancy]. / Embarazo en enfermedad inflamatoria intestinal: no solo 9 meses de cuidado.

The prevalence of inflammatory bowel disease (IBD) increased in the last decades. Thus, the number of pregnant women with the condition is also increasing. Given that active disease itself is the main risk factor for complications during pregnancy, it is necessary to achieve a complete remission before planning a pregnancy. Also, pregnant women with IBD must be monitored noninvasively and be treated proactively, including escalated therapies, if needed, to prevent potential flares during pregnancy. Patients can undergo vaginal delivery in most forms of IBD. However, cesarean delivery is still preferable in women with a history of ileal pouch-anal anastomoses (IPAA) or active perianal disease.

Study of antidepressant use in 5 European settings. Could economic, sociodemographic and cultural determinants be related to their use?

BACKGROUND: We aimed at describing the trends in antidepressants use (AD) by age and sex, during 2007-2011, in 5 European settings (Sweden, Norway, Denmark, Catalonia and Veneto), and to assess whether the differences found across settings could be related to economic, social and cultural determinants. METHODS: We collected data of AD use expressed in defined daily doses (DDD). Data were retrieved from population-based databases. We calculated DDD/1000 inhabitants/day. We analysed which economic, social, and cultural covariates determined between-settings differences in AD consumption. RESULTS: The use of AD showed an increasing trend during the study period, being Selective Serotonin Reuptake Inhibitors the most consumed, followed "others AD". Women and the elderly showed the highest AD consumption. Between-settings variability in AD consumption showed a positive correlation with pharmaceutical expenditure and a negative one with general practitioner's rate. After adjusting by pharmaceutical expenditure and general practitioners rate Masculinity, Long-Term Orientation and Individualism cultural dimensions were associated with AD use by using the Hofstede´s cultural dimensions model. LIMITATIONS: This study has been conducted in administrative databases, with no information on AD use by indication; differences among AD use could be related to their prescription for other disorders. Analyses were based on a small dataset and none of the results reached statistical significance. CONCLUSIONS: AD use increased through 2007-2011. Pharmaceutical expenditure and General Practitioners rate, Masculinity, Long-Term Orientation and Individualism explained the differences in AD use between countries. People's attitude should be considered when designing national campaigns to improve antidepressant use.

The sequence of prenatal growth restraint and postnatal catch-up growth: normal heart but thicker intima-media and more pre-peritoneal fat in late infancy.

BACKGROUND: The sequence of prenatal growth restraint and postnatal catch-up growth leads to a thicker intima-media and more pre-peritoneal fat by age 3-6 years. OBJECTIVES: To study whether carotid intima-media thickness (cIMT) and pre-peritoneal fat differ already between catch-up small-for-gestational-age (SGA) infants and appropriate-for-gestational-age (AGA) controls in late infancy (ages 1 and 2 years) and whether such differences - if any - are accompanied by differences in cardiac morphology and function. METHODS: Longitudinal assessments included body height and weight; fasting glucose, insulin, Insulin-like growth factor (IGF-I), high-molecular-weight adiponectin; body composition (by absorptiometry); cIMT, aortic IMT, pre-peritoneal fat partitioning (by ultrasound); cardiac morphometry and function (by echocardiography) in AGA and SGA infants at birth, at age 1 year (N = 87), and again at age 2 years (N = 68). RESULTS: Catch-up SGA infants had already a thicker cIMT than AGA controls at ages 1 and 2 years, and more pre-peritoneal fat by age 2 years (all p values between <0.01 and <0.0001); all cardiac and endocrine-metabolic results were similar in AGA and SGA infants at ages 1 and 2 years. CONCLUSIONS: From late infancy onwards, catch-up SGA infants have a thicker cIMT and more pre-peritoneal fat than AGA controls, but their cardiac morphology and function remain reassuringly similar.

Liver volume and hepatic adiposity in childhood: relations to body growth and visceral fat.

BACKGROUND AND OBJECTIVE: The sequence of prenatal growth restraint and postnatal catch-up growth may lead to hepato-visceral adiposity, insulin resistance and low-grade inflammation before the onset of puberty. In prepubertal children born appropriate for gestational age (AGA) or small for gestational age (SGA), we assessed potential relationships between the aforementioned sequence and liver volume. SUBJECTS/METHODS: The study population consisted of 86 children (41 AGA and 45 SGA with catch-up growth; age (mean±s.e.m.), 8.5±0.1 years), recruited into two prospective longitudinal studies. Anthropometry, endocrine-metabolic variables and inflammatory and hepatic markers were assessed, along with liver volume, hepatic adiposity and abdominal fat partitioning (by magnetic resonance imaging). RESULTS: AGA and SGA children differed in hepato-visceral adiposity, but had similar liver volumes. Boys had larger livers than girls, and higher sex hormone binding globulin and inflammation markers. Liver volume correlated with height Z-score, body mass index Z-score, HOMA-IR (homeostasis model assessment-insulin resistance) and with subcutaneous and visceral fat, but not with birth weight Z-score or with hepatic adiposity. Height, visceral fat, gender and HOMA-IR were major determinants of liver volume, together explaining 61% of its variance. CONCLUSIONS: The trajectory from prenatal restraint, via postnatal catch-up, to hepato-visceral adiposity and insulin resistance does not appear to be detectably influenced by prepubertal alterations of liver volume. Further follow-up will disclose the potential role of liver volume in the pubertal segment of this trajectory, and whether the augmented fat content and visceral adiposity in SGA subjects is followed by the development of metabolic syndrome and hepatic dysfunction in adulthood.

Antibodies Directed toward Neuraminidase N1 Control Disease in a Mouse Model of Influenza.

There is increasing evidence to suggest that antibodies directed toward influenza A virus (IAV) neuraminidase (NA) are an important correlate of protection against influenza in humans. Moreover, the potential of NA-specific antibodies to provide broader protection than conventional hemagglutinin (HA) antibodies has been recognized. Here, we describe the isolation of two monoclonal antibodies, N1-7D3 and N1-C4, directed toward the N1 NA. N1-7D3 binds to a conserved linear epitope in the membrane-distal, carboxy-terminal part of the NA and reacted with the NA of seasonal H1N1 isolates ranging from 1977 to 2007 and the 2009 H1N1pdm virus, as well as A/Vietnam/1194/04 (H5N1). However, N1-7D3 lacked NA inhibition (NI) activity and the ability to protect BALB/c mice against a lethal challenge with a range of H1N1 viruses. Conversely, N1-C4 bound to a conformational epitope that is conserved between two influenza virus subtypes, 2009 H1N1pdm and H5N1 IAV, and displayed potent in vitro antiviral activity mediating both NI and plaque size reduction. Moreover, N1-C4 could provide heterosubtypic protection in BALB/c mice against a lethal challenge with 2009 H1N1pdm or H5N1 virus. Glutamic acid residue 311 in the NA was found to be critical for the NA binding and antiviral activity of monoclonal antibody N1-C4. Our data provide further evidence for cross-protective epitopes within the N1 subtype and highlight the potential of NA as an important target for vaccine and therapeutic approaches.IMPORTANCE Influenza remains a worldwide burden on public health. As such, the development of novel vaccines and therapeutics against influenza virus is crucial. Human challenge studies have recently highlighted the importance of antibodies directed toward the viral neuraminidase (NA) as an important correlate of reduced influenza-associated disease severity. Furthermore, there is evidence that anti-NA antibodies can provide broader protection than antibodies toward the viral hemagglutinin. Here, we describe the isolation and detailed characterization of two N1 NA-specific monoclonal antibodies. One of these monoclonal antibodies broadly binds N1-type NAs, and the second displays NA inhibition and in vitro and in vivo antiviral activity against 2009 H1N1pdm and H5N1 influenza viruses. These two new anti-NA antibodies contribute to our understanding of the antigenic properties and protective potential of the influenza virus NA antigen.

GLP-1 and IGF-I levels are elevated in late infancy in low birth weight infants, independently of GLP-1 receptor polymorphisms and neonatal nutrition.

Low birth weight followed by rapid postnatal weight gain is associated with increased risks for obesity and diabetes in adulthood. Modulation of glucagon-like-peptide 1 (GLP-1) secretion by (epi)genetic mechanisms or nutrition may, in part, influence this risk. Formula-fed infants born small-for-gestational-age (SGA) have higher circulating GLP-1 at age 4 months than breastfed SGA or appropriate-for-gestational-age (AGA) infants. Here we assessed GLP-1 concentrations in healthy AGA (n=149) and SGA (n=107) subjects at age 12 months and their association with endocrine-metabolic and body composition parameters and GLP-1 receptor (GLP-1R) rs6923761 and rs3765467 polymorphisms. At birth, cord GLP-1 concentrations were comparable in AGA and SGA infants. At age 12 months, insulin-like growth factor I (IGF-I) and GLP-1 levels were higher than at birth; SGA infants displayed higher IGF-I and GLP-1 concentrations than AGA infants (both P<0.001) that were unrelated to neonatal nutrition or GLP-1R genotype and that were paralleled by a significant increase in weight Z-score (P<0.001 vs AGA). In conclusion, SGA infants have augmented IGF-I and prefeeding GLP-1 concentrations in late infancy. Increased GLP-1 levels may impair hypothalamic and/or peripheral GLP-1R signaling, exert long-term negative effects on the hypothalamic nuclei regulating energy homeostasis and increase the risks for obesity and diabetes.

Perirenal fat is related to carotid intima-media thickness in children.

BACKGROUND/OBJECTIVES: It is well known that increased abdominal fat is associated with cardiovascular (CV) risk. Perirenal fat has been recently associated with CV risk in adults. However, studies with children are lacking. We investigated the relationship of perirenal fat and other abdominal fat depots (including preperitoneal, intra-abdominal and subcutaneous fat) with carotid intima-media thickness (cIMT-a surrogate marker of CV risk) in prepubertal children, so as to identify novel markers that can be easily assessed and used in the early prevention of cardiovascular disease. SUBJECTS/METHODS: Subjects were 702 asymptomatic prepubertal Caucasian children (418 lean, 142 overweight and 142 obese) who were recruited in a primary care setting. Ultrasound measurements (perirenal, preperitoneal, intra-abdominal and subcutaneous fat and cIMT), clinical (body mass index (BMI) and systolic blood pressure) and metabolic parameters (insulin resistance (HOMA-IR), high molecular weight (HMW) adiponectin and serum lipids) were assessed. RESULTS: Perirenal fat was associated with diverse metabolic and CV risk factors in all the studied subjects. However, in overweight and obese children, perirenal fat was mostly associated with cIMT (P<0.001) and was the only fat depot that showed independent associations with cIMT in multivariate analyses (overweight chidren: ß=0.250, P=0.003, r2=12.8%; obese children: ß=0.254, P=0.002, r2=15.5%) after adjusting for BMI, gender, age and metabolic parameters. Perirenal fat was also the only fat depot that showed independent associations with HMW-adiponectin in obese children (ß=-0.263, P=0.006, r2=22.8%). CONCLUSIONS: Perirenal fat is the main abdominal fat depot associated with cIMT, especially in overweight and obese children, and may thus represent a helpful parameter for assessing CV risk in the pediatric population.

Terapia combinada en enfermedad inflamatoria intestinal: ¿una asociación necesaria? / Combination therapy in inflammatory bowel disease: a necessary association?

The management of inflammatory bowel disease (IBD) is constantly changing due to the arrival of new therapeutic agents. Combined therapy (biological associated with immunosuppressive therapy) has proven to be effective, reducing immunogenicity (antibody formation), optimizing the pharmacokinetics of biological therapy with anti-TNF. This therapeutic strategy has associated risks (neoplasia and intercurrent infections) that are not only explained by the use of drugs but also by the increase of cases in older ages. It is essential for the medical team to be familiar with the optimization and personalization of the therapy to achieve clear therapeutic objectives with the lowest possible risks.

El manejo de la enfermedad inflamatoria intestinal (EII) está en constante cambio, debido a la llegada de nuevos agentes terapéuticos. La terapia combinada (terapia biológica asociada a inmunosupresores) ha demostrado ser efectiva al disminuir la inmunogenicidad (formación de anticuerpos) permitiendo la optimización farmacocinética. Esta estrategia terapéutica tiene riesgos asociados (neoplasias e infecciones intercurrentes) que no sólo se explican por el uso de fármacos sino también por el aumento de casos en edades más avanzadas. Es fundamental que el equipo tratante este familiarizado con la optimización y personalización de la terapia para así lograr objetivos terapéuticos claros con los menores riesgos posibles.