Current perspectives on pediatric inflammatory bowel disease focusing on transitional care management. What should we consider?

The prevalence of inflammatory bowel disease (IBD) continues to rise around the globe. Although the percentage of pediatric IBD patients seems to be increasing, rates are surprisingly heterogeneous among different populations. Although the pathogenesis of IBD is believed to be multifactorial, a genetic predisposition may be especially relevant in pediatric-onset IBD. Phenotypic characteristics can also be significantly different when comparing pediatric and adult-onset IBD. Patients that develop the disease at a younger age usually present with more extensive and more aggressive disease and develop complications faster when compared to those that develop it during adulthood. Children with IBD are found to have frequent mood disorders and have a higher risk of developing socio-economic hardship, failing to meet development milestones. Therefore, IBD management should always involve a multidisciplinary team that is not limited to medical providers. Most institutions do not have an established transition protocol and lack the resources and training for transition care. Although there is no consensus on an optimal timing to transition the patient's care to an adult team, it is usually accepted they should be eligible for adult care when most of the key transition points have been met. Management strategies should be tailored to each patient's developmental level and environment. A successful transition can improve the long-term outcomes such as sustained remission, medication adherence, mental health and social and academic performance, while decreasing healthcare utilization. Every institution that manages pediatric IBD patients should have a well-established transition protocol in order to make sure to maintain continuity of care.

Hamstring muscle architecture and myotonometer measurements in elite professional football players with a prior strained hamstring.

The purpose of this study was to compare the fascicle length, angle pennation and mechanical properties of the biceps femoris long head (BFlh) in dominant and non-dominant limbs in previously injured and uninjured professional football players. Fifteen professional football players were recruited to participate in this study. Seven players had suffered a BFlh injury during the previous season. Myotonometry mechanical properties were measured in the proximal, common tendon and distal BFlh using MyotonPRO, and angle pennation and fascicle length were also measured. We observed significantly higher distal BFlh frequency, stiffness, decrement, relaxation and creep than in the common tendon and proximal BFlh. The previously injured players showed significantly higher frequency and stiffness, and lower relaxation and creep in the dominant BFlh than did uninjured players. There were no significant differences between the fascicle length and angle pennation in previously injured and uninjured BFlh. Myotonometric measurement provides a quick and inexpensive way to check the properties of the BFlh in professional football players. Professional football players with previous BFlh injury showed higher intrinsic tension and a poorer capacity to deform than did players with no injury to the BFlh.

Fecal microbiota transplant, its usefulness beyond Clostridioides difficile in gastrointestinal diseases.

Fecal microbiota transplant (FMT) is currently recommended for recurrent Clostridioidesdifficile infection. However, it is interesting to acknowledge the potential therapeutic role in other diseases associated with dysbiosis. This review will focus on the current and potential indications of FMT in gastrointestinal diseases, evaluating the available evidence and also exposing the necessary requirements to carry it out.

Treat-to-target approach in the management of inflammatory Bowel disease.

With the advent of biologic and small molecule therapies, there has been a substantial change in the treatment of inflammatory bowel disease. These advances have had a great impact in preventing disease progression, intestinal damage and, therefore, have contributed to a better quality of life. Discordance between symptom control and mucosal healing has been demonstrated. This has led to the search for new disease control targets. The treat to target strategy, based on expert recommendations and now a randomized controlled trial, has determined that clinical and endoscopic remission should be the goal of therapy. Biomarkers (fecal calprotectin) can be a surrogate target. Although histological healing has shown benefits, there is inadequate evidence and inadequate therapy for that to be a fixed goal at this time. This review will focus on therapeutic goals, according to the evidence currently available, and evaluate strategies to achieve them.

Pregnancy in Inflammatory Bowel Disease: Experience of a Chilean cohort. / Embarazo en enfermedad inflamatoria intestinal: experiencia en una cohorte chilena.

BACKGROUND: In inflammatory bowel disease (IBD) a high percentage of women are diagnosed during their reproductive age. IBD in remission is the ideal scenario when planning a pregnancy. AIMS: To describe the clinical characteristics of pregnancy/newborn and assess disease activity at the time of conception and throughout the pregnancy in patients with IBD treated at a tertiary centre in Chile. METHODS: We retrospectively reviewed women diagnosed with IBD who were pregnant or delivered between 2017 and 2020. Demographic, clinical, obstetric and delivery data were obtained from the IBD registry, approved by the local IRB. Descriptive statistics and association tests were performed (χ2, p ≤ 0.05). RESULTS: Sixty women with IBD were included. At the beginning of pregnancy, 21 (35%) had active disease and 39 (65%) were in remission. Of those with active disease, 16 (66%) remained active and 6 had spontaneous abortions. In those who were in remission, 26 (69%) remained in this condition. Nine patients (15%) discontinued treatment, and 6 of these had inflammatory activity during pregnancy. Preconception counselling was performed in 23 of the 60 patients, being higher in the group that remained in remission during pregnancy (65% vs. 35%, p = 0.02). Patients who had a flare during pregnancy had more probability of preterm birth (<37 weeks) and newborn with lower weight compared with the group that always remained in remission (89% vs. 74%, p = 0.161) and (2.885 vs 3.370 g; p = 0.0014). CONCLUSION: Remission presents better outcomes in pregnancy and preconception counselling would allow a better IBD control during pregnancy.

Infliximab in inflammatory bowel disease. Is premedication necessary? / Infliximab en enfermedad inflamatoria intestinal. ¿Es necesario premedicar?

BACKGROUND: The use of infliximab (IFX) in inflammatory bowel disease (IBD) has been associated with a 1-6% risk of infusion reactions. The usefulness of premedication with corticosteroids, paracetamol and /or antihistamines is controversial. AIM: The aim of this study is to assess, in IBD patients on IFX, whether there are differences in secondary reactions to the infusion between those who use premedication or not. METHODS: A retrospective cohort study was performed identifying patients with a diagnosis of IBD who received IFX at our institution between January 2009 and July 2019. Acute reactions were defined as those that occurred in the first 24 hours postinfusion and late reactions for more than 24 hours. Infusion reactions were classified as mild, moderate and severe. Descriptive and association statistics were used (χ2; p < 0.05). RESULTS: Sixty-four patients were included with 1,263 infusions in total, 52% men. Median infusions per patient was 22 (2-66). All induction infusions were administered with premedication, and in maintenance in 57% of them. Premedication was given with hydrocortisone, chlorphenamine and paracetamol. Most of reactions were acute, mild or moderate in severity and no patient needed to discontinue IFX. In the maintenance group, there were 9/718 (1.2%) infusion reactions with premedication and 4/358 (1.1%) without it (p = 0.606). In the induction group, there were 8/187 (4.3%) infusion reactions, significantly higher when compared with both maintenance groups. CONCLUSIONS: In this group, premedication use during maintenance was not effective at reducing the rate of infusion reactions. These results suggest that premedication would not be necessary.

Solvent-Assisted Hot Melt Extrusion of a Thermally Labile, High Melting Point Compound.

Molecular dispersions are a highly effective method of increasing bioavailability for a poorly soluble active pharmaceutical ingredient (API) and can be prepared on a large scale by hot melt extrusion (HME). Processing thermally labile active pharmaceutical ingredients (APIs) via HME is generally more difficult, with operating temperatures limited to below that of the API melting point. API melting is considered essential to facilitate the formation of a fully homogeneous amorphous system. Processing below the melting point renders the system much more susceptible to residual crystalline content; hence, HME is not suitable for APIs which degrade upon melting. In the following work, meloxicam (MEL) was used as a model API, possessing properties of high melting temperature and thermal lability. In this proof of concept work, a modified HME method, termed solvent-assisted HME, was used to overcome this issue and prepare an amorphous solid dispersion using HME, wherein a solvent was incorporated in the formulation blend during extrusion and removed post-processing. Formulations containing 10%wt meloxicam (MEL) and 90%wt polyvinylpyrrolidone vinyl acetate (PVPVA) copolymer were extruded using a twin-screw extruder at temperatures below the melting point of MEL. Dimethylformamide (DMF) solvent was added directly into the extruder barrel through a liquid addition port, resulting in extrudate products having a higher conversion of API to the amorphous form. The incorporation of solvent allowed a significant reduction in processing temperatures due to its increased mobility, while also driving the conversion of the API to its amorphous form. The solvent was successfully reduced through a secondary drying step using a vacuum oven. This advancement has demonstrated the potential for thermally labile APIs to be processed via HME expanding the applications of this technology.

[Cervicocranial arterial dissection. Experience in 57 patients]. / Caracterización clínica e imagenológica de una serie de pacientes con disección de arterias cervicales e intracraneales.

BACKGROUND: Cervicocranial arterial dissection (CIAD) is an important cause of stroke. AIM: To describe the clinical and imaging characteristics of patients with CIAD. MATERIAL AND METHODS: An anonymous registry was made including all patients admitted to a private hospital with a diagnosis of CIAD. Patients were subdivided as having an anterior or posterior circulation dissection (ACD or PCD, respectively). RESULTS: Fifty-seven patients aged 40 ± 8 years (60% women) were included in the study, 39 with PCD and 18 with ACD. Cervical pain was the most common symptom. CIAD was diagnosed with no clinical or imaging signs of stroke in 49% of patients. Fifty one percent of patients had focal neurological deficits and 72% had a NIH stroke score below five. No significant differences between patients with ACD or PCD were found. Fifty patients received antiplatelet therapy (simple or dual), seven patients were anticoagulated and 13 were subjected to stenting due to progression of stenosis with hemodynamic involvement or bilateral dissection with scarce collaterals. The lesion was located in V3 segment in 27 patients and cervical segment of the internal carotid in 16 cases. A favorable Modified Rankin Scale (0-2) was achieved in 85.9%, with a trend towards achieving better functional prognosis in PCD. CONCLUSIONS: Due to the greater availability of non-invasive imaging methods, 50% of these patients with CIAD did not have a stroke. Thus, an earlier and more timely management is feasible.

Is possible an eccentric overload in a rotary inertia device? Comparison of force profile in a cylinder-shaped and a cone-shaped axis devices.

The aims of this study were to compare the force profile of using a horizontal cylinder-shaped axis or a vertical cone-shaped axis to provide resistance in rotary inertia devices, and to report the evolution of kinetic and kinematic variables in experienced athletes during a half-squat exercise. Twenty-two healthy active men participated in the assessment of time, peak velocity, peak force, time to reach the peak force, average force, impulse, and range of movement, during a half-squat incremental test performed on conical inertial device (CP) and on cylinder inertial device (YY). The analysis showed that YY during CON-ECC phased generates substantial higher peak_force, mean_force, impulse, time, and a lower peak_velocity, than CP. We never obtained eccentric overload for peak_force or mean_force. CP offers less resistance to accelerate-decelerate the movement with respect to YY, we need checking whether eccentric overload it is being produced, and the impulse was the only kinetic variable that was able to discriminate between the inertias and devices.

[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.

Field Methods to Estimate Fat-free Mass in International Soccer Players.

Based on the high financial and logistical costs associated with the assessment of body composition with dual-energy X-ray absorptiometry (DXA), this study determined which field method has the best correlation with DXA data, and developed an equation to estimate fat-free mass (FFM) using the field anthropometric data in international soccer players. A total of 17 international soccer players participated in this study. DXA values provided a criterion measure of FFM. Correlation coefficients, biases, limits of agreement, and differences were used as validity measures, and regression analyses were used to develop the prediction equation. All field methods used to obtain FFM data showed positive correlations (r from 0.90-0.96) with DXA. Only the equation developed by Deurenberg et al. [6] showed no differences from DXA with a low bias. The main strength of this study was providing a valid and accurate equation to estimate FFM specifically in international soccer players.

Eccentric-concentric Ratio: A Key Factor for Defining Strength Training in Soccer.

The aims of this study were to analyse the effect of chronic strength training over concentric power (CON), eccentric power (ECC), ECC/CON ratio, and 20 m linear sprint performance in elite young soccer players. Twenty young elite Spanish soccer players were assigned to an experimental group (CPG) which performed a front-step exercise using a conical pulley, 2-3 sets of 6 repetitions each leg, during 9 weeks (CPG, n=10) in addition to its usual strength training, or to a control group (CG, n=10). The improvements in the ECC mean power (36%, ES=1.61), and ECC / CON ratio (17%, ES=1.77) were substantially greater in the CPG than in the CG while the CON mean power (16%, ES=0.83) was substantially greater in the CG than in the CPG. The sprinting time for 10 m (2.8%, ES=0.78) and the 10 m flying time between 10-20 m (1.72%, ES=0.41) were substantially enhanced in CPG and CG respectively. To be efficient when defining a functional strength training and performance increments using an inertial device, the mean power output need to be measured during the CON and ECC phases and an analysis of the ECC / CON ratio should be included.

Primary sclerosing cholangitis and inflammatory bowel disease: Intestine-liver interrelation. / Colangitis esclerosante primaria y enfermedad inflamatoria intestinal: interrelación intestino-hígado.

The association between inflammatory bowel disease (IBD) and primary sclerosing cholangitis should be considered a distinct clinical entity. This association involves genetic abnormalities, epidemiological factors (more common in men, with no a geographical pattern) and, commonly, subclinical inflammation, predominance of the right colon (endoscopic and histological), backwash ileitis and rectal sparing. Furthermore, there is an increased risk of colorectal cancer and cholangiocarcinoma. The aim of this review is to show how IBD influences the progression of this entity, transplantation requirements and recurrence. We also discuss the current evidence on the use of biological therapy in this group of patients.

Metabolic consequences of snoring in adolescents and younger adults: a population study in Chile.

STUDY OBJECTIVES: To investigate the potential association between snoring and other symptoms indicative of sleep-disordered breathing and metabolic syndrome (MetS) in Hispanic adolescents and younger adults using a large population-based survey. METHODS: Sleep-related information, anthropometric measurements and fasting blood samples markers of MetS were obtained from subjects aged 15-40 years collected through the 2nd Chilean Health Survey. Regression models were constructed to evaluate the associations of snoring with MetS, hypertension and serum cholesterol levels. The modulating effect of sleep duration was accounted for in the models. RESULTS: A total of 2147 subjects (42% males, mean age 27.9±7.6 years) were included. Snoring and short sleep duration were present in 43.5 and 25% of the entire population, respectively. MetS was detected in 19.5% of the subjects. In the adjusted regression model, the odds of MetS among snoring subjects were 2.13 times higher (95% confidence interval (CI): 1.52-2.99; P<0.01), and 1.53-fold higher odds of elevated cholesterol also emerged (95% CI: 1.12-2.10; P<0.01). However, the odds of hypertension were not increased by the presence of snoring after adjusting for confounders. In addition, snoring was associated with an increase of 7.26 and 6.56 mg dl-1 for total and low-density lipoprotein cholesterol, respectively, even after adjusting for age, sex and body mass index. Short sleep duration was associated with a small albeit significant risk increase for high systolic blood pressure. CONCLUSIONS: In this large population-based sample of young Hispanic adults and adolescents, snoring, but not sleep duration, emerged as an independent risk factor for dyslipidemia and MetS, but not for hypertension.

Recent Y chromosome divergence despite ancient origin of dioecy in poplars (Populus).

All species of the genus Populus (poplar, aspen) are dioecious, suggesting an ancient origin of this trait. Despite some empirical counter examples, theory suggests that nonrecombining sex-linked regions should quickly spread, eventually becoming heteromorphic chromosomes. In contrast, we show using whole-genome scans that the sex-associated region in Populus trichocarpa is small and much younger than the age of the genus. This indicates that sex determination is highly labile in poplar, consistent with recent evidence of 'turnover' of sex-determination regions in animals. We performed whole-genome resequencing of 52 P. trichocarpa (black cottonwood) and 34 Populus balsamifera (balsam poplar) individuals of known sex. Genomewide association studies in these unstructured populations identified 650 SNPs significantly associated with sex. We estimate the size of the sex-linked region to be ~100 kbp. All SNPs significantly associated with sex were in strong linkage disequilibrium despite the fact that they were mapped to six different chromosomes (plus 3 unmapped scaffolds) in version 2.2 of the reference genome. We show that this is likely due to genome misassembly. The segregation pattern of sex-associated SNPs revealed this to be an XY sex-determining system. Estimated divergence times of X and Y haplotype sequences (6-7 Ma) are much more recent than the divergence of P. trichocarpa (poplar) and Populus tremuloides (aspen). Consistent with this, in P. tremuloides, we found no XY haplotype divergence within the P. trichocarpa sex-determining region. These two species therefore have a different genomic architecture of sex, suggestive of at least one turnover event in the recent past.

Septic shock in children in an urban area in Western Germany--outcome, risk factors for mortality and infection epidemiology.

BACKGROUND: Only sparse data exist about children with septic shock in Europe. The present study aimed to evaluate demographics, treatment, outcome and risk factors for mortality in Western Germany. PATIENTS: Children with septic shock aged 2 months to 17 years. METHODS: In a multi-center retrospective study of 20 children's hospitals data were obtained and analyzed by chart review. Risk factors for mortality were identified and assessed by multivariate regression analysis. RESULTS: Overall mortality in 83 cases with septic shock was 25% (21 patients). Significant risk factors were high PRISM III score, low pH, low arterial systolic blood pressure, presence of disseminated intravascular coagulation and extent of multi-organ failure, but not lactate (p=0.05) and base excess (p=0.065). Mortality in hospitals which treated 10 or more patients (category 1) was 17% and increased to 22% in hospitals which treated 3-6 patients (category 2). In hospitals with only 1 or 2 patients (category 3) mortality rate was 61% (p<0.01 when compared to category 1 or 2). A stepwise increase was also seen in the severely sick patients according to PRISM III (>19): category 1: 23%, category 2: 40%, category 3: 62.5% (p<0.05 for comparison of category 1 and 3). Multivariate analysis of significant risk factors revealed low number of treated patients as the only individual risk factor for mortality. CONCLUSION: Mortality from pediatric septic shock in an urban area in Western Germany is high. Disease severity and treatment in a department with few cases were associated with increased mortality.

[Dental caries and early childhood development: a pilot study]. / Caries dental y desarrollo infantil temprano. Estudio piloto.

OBJECTIVE: To investigate the association between dental caries and early childhood development in 3-year-olds from Talca, Chile. METHOD: A pilot study with a convenience sample of 3-year-olds from Talca (n = 39) who attend public healthcare centers. Child development was measured by the Psychomotor Development Index (PDI), a screening tool used nationally among pre-school children to assess language development, fine motor skills and coordination areas. Dental caries prevalence was evaluated by decayed, missing, filled teeth (DFMT) and decayed, missing, filled tooth surfaces (DFMS) ceo-d and ceo-s indexes. The children were divided into two groups according to the PDIscore: those with a score of 40 or more were considered developmentally normal (n = 32), and those with a score below 40 were considered as having impaired development (n = 7). RESULTS: The severity of caries (DMFT) was negatively correlated with PDI (r = -0.82), and children with the lowest TEPSI score had the highest DFMT values. The average DMFT in children with normal development was 1.31, and 3.57 for those with impaired development. CONCLUSION: This pilot study indicates that the severity of dental caries is correlated with early childhood development.

Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population.

The prevalence of genetic polymorphisms identified as predictors of therapeutic-induced hepatitis C virus (HCV) clearance differs among ethnic groups. However, there is a paucity of information about their prevalence in South American populations, whose genetic background is highly admixed. Hence, single-nucleotide polymorphisms rs12979860, rs1127354 and rs7270101 were characterized in 1350 healthy individuals, and ethnicity was assessed in 259 randomly selected samples. The frequency of rs12979860CC, associated to HCV treatment response, and rs1127354nonCC, related to protection against hemolytic anemia, were significantly higher among individuals with maternal and paternal Non-native American haplogroups (64.5% and 24.2%), intermediate among admixed samples (44.1% and 20.4%) and the lowest for individuals with Native American ancestry (30.4% and 6.5%). This is the first systematic study focused on analyzing HCV predictors of antiviral response and ethnicity in South American populations. The characterization of these variants is critical to evaluate the risk-benefit of antiviral treatment according to the patient ancestry in admixed populations.

Relationship between childhood obesity cut-offs and metabolic and vascular comorbidities: comparative analysis of three growth standards.

BACKGROUND: To compare the association between metabolic and vascular comorbidities and the body mass (BMI)-for-age cut-off criteria from three growth standards [Centers for Disease Control and Prevention (CDC), 2000; World Health Organization (WHO), 2007; Spanish Reference Criteria (Carrascosa Lezcano et al., 2008)] that are used to define being overweight and obese in childhood. METHODS: A prospective study was conducted in 137 children (aged 8-16 years). Based on BMI-for-age Z-scores according to WHO cut-offs, 59 participants were obese, 35 were overweight and 43 were normal-weight. All participating children were subsequently reclassified applying the CDC and Spanish Reference Criteria. Blood pressure (BP), biochemical variables and vascular parameters (stiffness and intima-media thickness) were analysed. RESULTS: According to WHO and CDC references, 48% and 43% of the children, respectively, were categorised as obese, whereas 16% were considered as obese using the Spanish Reference Criteria. Applying WHO criteria, obese children showed significantly higher levels of insulin, homeostasis model assessment index and most vascular parameters, as well as lower high-density lipoprotein (HDL)-cholesterol than overweight children. Moreover, overweight children showed higher BP, insulin and uric acid, and lower HDL-cholesterol than normal weight children. The CDC criteria yielded similar results, although with fewer differences between obese and overweight children. Applying Spanish criteria, the differences between obese and overweight children disappeared. CONCLUSIONS: WHO and CDC BMI-for-age references and cut-offs are useful for defining obesity and being overweight in children because they clearly identify metabolic and vascular comorbidities. The Spanish Reference Criteria underdiagnose obesity because overweight children show comorbidities typical of the obese.