Efficacy of Adalimumab as first-line “top-down” therapy in pediatric Crohn's Disease: 12 months of follow-up

Objectives and Study: Anti-tumour necrosis factor (TNF) agents are highly efficient in inducing and maintaining remission in pediatric Crohn's disease (CD). The question is who is the right patient and when is the right moment to introduce anti-TNF medication. Recent ECCO-ESPGHAN guidelines indicate a clear place of anti-TNF biologics in patients with positive predictors of poor outcome. The aim of our study was to evaluate the efficacy of adalimumab (ADA) as first-line therapy by comparing two НiffОrОnt stratОgiОsŚ χDχ “top Нown” in immunomoНulator anН anti-TNF naïve CD patients versus a “stОp up” stratОgy in patiОnts rОМОiving immunosupprОssivО agОnts (thiopurinО anН/or infliximabΨ before ADA. Method: Patients followed for CD at Necker hospital that started their ADA therapy between 2005 and 2017 were retrospectively reviewed. The beginning of the study (M0) was the date of first ADA injection. Enrolled patients were divided into 2 groups according to the treatment strategy. Group A was composed of patients naïve of immunosuppressors and anti TNF agents who started early ADA aftОr inНuМtion of rОmission, rОsulting in a “top Нown” stratОgy whilО group ψ was МomposОН by patiОnts who startОН χDχ aftОr a morО МlassiМal stratОgy (iО “stОp up” stratОgy using immunosuppressive agents then infliximab). For each patient were collected data at M0, M3, M6, M9 and M12 regarding the disease activity score (wPCDAI), auxological parameters, biological parameters (CRP, ESR, Albumin, ADA trough levels and antibodies anti-ADA). Results: 83 patients (43 boys) were enrolled in the study, 43,3% (n=36) in group A and 56,6% (n=47) in group B. Mean age at the start of ADA was 13.6 ± 2.6 years. At inclusion the 2 groups were comparable with a mean wPCDAi of 40.75 ± 14,8 in group A versus 45.6 ± 15,5 in group B. At 6 months, the 2 groups were in clinical remission with a median wPCDAI of 0 (0-12.5 IQR) in group A (n = 30) versus 0 (0-7.5 IQR) in group B (n=38) (p: 0.509). CRP level decreased from 15.5 (4.7-35.8 IQR) to 1.1 (0.5-5.6 IQR) in group A vs 17.1 (6.5-37.7 IQR) to 4,8 (0.7-6.1 IQR) in group B (p: 0.945 e p: 0.086). For the subgroup of patients who reached the 1 year follow up, there were no significant differences regarding the mean wPCDAI, CRP, ESR and serum allbumin between the 2 groups. Conclusion: ThО prОsОnt stuНy НОmonstratОs that thО “top Нown” stratОgy using Оarly χDχ monotherapy in disease course is as effective as a step-up strategy. Moreover, ADA monotherapy is as effective as combotherapy in maintaining clinical and biological remission at 1 year of follow-up in paediatric CD patients. Those results are very important to identify the best strategy in pediatric CD patients, where safety concerns are major

True Precocious Puberty Following Treatment of a Leydig Cell Tumor. Two Case Reports and Literature Review

Leydig cell testicular tumors are a rare cause of precocious pseudopuberty in boys. Surgery is the main therapy and shows good overall prognosis. The physical signs of precocious puberty are expected to disappear shortly after surgical removal of the mass. We report two children, 7.5 and 7.7 year-old boys, who underwent testis-sparing surgery for a Leydig cell testicular tumor causing precocious pseudopuberty. During followup, after an immediate clinical and laboratory regression, both boys presented signs of precocious puberty and ultimately developed central precocious puberty. They were successfully treated with gonadotropin-releasing hormone (GnRH) analogs. Only six other cases have been described regarding the development of central precocious puberty after successful treatment of a Leydig cell tumor causing precocious pseudopuberty. Gonadotropin-dependent precocious puberty should be considered in children treated for a Leydig cell tumor presenting persistent or recurrent physical signs of puberty activation. In such cases, therapy with GnRH analogs appears to be the most effective medical treatment

Robotic Assessment of Wrist Proprioception During Kinaesthetic Perturbations: A Neuroergonomic Approach

Position sense refers to an aspect of proprioception crucial for motor control and learning. The onset of neurological diseases can damage such sensory afference, with consequent motor disorders dramatically reducing the associated recovery process. In regular clinical practice, assessment of proprioceptive deficits is run by means of clinical scales which do not provide quantitative measurements. However, existing robotic solutions usually do not involve multi-joint movements but are mostly applied to a single proximal or distal joint. The present work provides a testing paradigm for assessing proprioception during coordinated multi-joint distal movements and in presence of kinaesthetic perturbations: we evaluated healthy subjects' ability to match proprioceptive targets along two of the three wrist's degrees of freedom, flexion/extension and abduction/adduction. By introducing rotations along the pronation/supination axis not involved in the matching task, we tested two experimental conditions, which differed in terms of the temporal imposition of the external perturbation: in the first one, the disturbance was provided after the presentation of the proprioceptive target, while in the second one, the rotation of the pronation/ supination axis was imposed during the proprioceptive target presentation. We investigated if (i) the amplitude of the perturbation along the pronation/supination would lead to proprioceptive miscalibration; (ii) the encoding of proprioceptive target, would be influenced by the presentation sequence between the target itself and the rotational disturbance. Eighteen participants were tested by means of a haptic neuroergonomic wrist device: our findings provided evidence that the order of disturbance presentation does not alter proprioceptive acuity. Yet, a further effect has been noticed: proprioception is highly anisotropic and dependent on perturbation amplitude. Unexpectedly, the configuration of the forearm highly influences sensory feedbacks, and significantly alters subjects' performance in matching the proprioceptive targets, defining portions of the wrist workspace where kinaesthetic and proprioceptive acuity are more sensitive. This finding may suggest solutions and applications in multiple fields: from general haptics where, knowing how wrist configuration influences proprioception, might suggest new neuroergonomic solutions in device design, to clinical evaluation after neurological damage, where accurately assessing proprioceptive deficits can dramatically complement regular therapy for a better prediction of the recovery path

Role of non-acid gastro-esophageal reflux in children with respiratory symptoms

Objectives: Respiratory symptoms are a possible atypical clinical picture of gastro-esophageal reflux disease (GERD). However, a significant number of patients with GERD-related respiratory symptoms do not report improvement despite aggressive acid-suppressive therapy. Some of these refractory casesmay be due to the recently appreciated entity of non-acid or weakly acidic reflux. The aim of our study is to assess the pH-impedance features of GER inducing airway symptoms, compared with GER inducing typical gastro-intestinal (GI) symptoms. Methods: We prospectively enrolled infants and children with GERD-related respiratory symptoms from January 2015 to December 2015. Age-and sex-matched patients with GERD-related GI symptoms were enrolled as comparison group. The overall number, the acidity pattern, and the height of reflux episodes were compared between the two groups. Results: Forty patients (M/F: 20/20; mean age: 58.3 months) were enrolled in the study group and 40 in the comparison group. The mean acid exposure index was 7.9% within the study group and 15.9% within the comparison group (p:0.026). Children with respiratory symptoms versus children with GI symptoms had a mean of 40.8 acid reflux episodes versus 62.4 (p:0.001), a mean of 2.2 weakly acid reflux episodes versus 20.1 (p:0.002), and a mean of 22.1 weakly alkaline reflux episodes versus 10.2 (P < 0.001). Separate analysis of both infants and children was performed. Conclusions: The main finding of this prospective, controlled study is that children >1 year with GERD-related respiratory symptoms showed a significantly higher number of weakly alkaline refluxes than children with GERD-related GI symptoms. This supports the hypothesis that respiratory symptoms are less related to acidity than GI symptoms

Diagnostic Tests in Pediatric Constipation

Constipation is one of the most common gastrointestinal symptoms in children. With a median reported prevalence of 12%, it accounts for about 25% of all pediatric gastroenterology consultations. The majority of children experiences functional constipation and do not usually require any diagnostic testing. For those children not responding to conventional medical treatment or in the presence of a more significant clinical picture, however, an accurate instrumental assessment is usually recommended to evaluate either the underlying pathophysiologic mechanisms or a possible organic etiology. The present review analyzes the possible diagnostic investigations for severely constipated children, focusing on their actual indications and their utility in clinical practice. During the last decade, there has been a remarkable increase in our knowledge of normal and abnormal colonic and anorectal motility in children, and a number of different techniques to measure transit and motility have been developed and are discussed in this narrative review

Evaluating Viscoelastic Properties of the Wrist Joint During External Perturbations: Influence of Velocity, Grip, and Handedness

In this study, we designed a robot-based method to compute a mechanical impedance model that could extract the viscoelastic properties of the wrist joint. Thirteen subjects participated in the experiment, testing both dominant and nondominant hands. Specifically, the robotic device delivered position-controlled disturbances in the flexion-extension degree of freedom of the wrist. The external perturbations were characterized by small amplitudes and fast velocities, causing rotation at the wrist joint. The viscoelastic characteristics of the mechanical impedance of the joint were evaluated from the wrist kinematics and corresponding torques. Since the protocol used position inputs to determine changes in mean wrist torque, a detailed analysis of wrist joint dynamics could be made. The scientific question was whether and how these mechanical features changed with various grip demands and perturbation velocities. Nine experimental conditions were tested for each hand, given by the combination of three velocity perturbations (fast, medium, and slow) and three hand grip conditions [self-selected grip, medium and high grip force, as percentage of the maximum voluntary contraction (MVC)]. Throughout the experiments, electromyographic signals of the extensor carpi radialis (ECR) and the flexor carpi radialis (FCR) were recorded. The novelty of this work included a custom-made soft grip sensor, wrapped around the robotic handle, to accurately quantify the grip force exerted by the subjects during experimentation. Damping parameters were in the range of measurements from prior studies and consistent among the different experimental conditions. Stiffness was independent of both direction and velocity of perturbations and increased with increasing grip demand. Both damping and stiffness were not different between the dominant and nondominant hands. These results are crucial to improving our knowledge of the mechanical characteristics of the wrist, and how grip demands influence these properties. This study is the foundation for future work on how mechanical characteristics of the wrist are affected in pathological conditions

Growth Hormone (GH) Therapy During the Transition Period: Should We Think About Early Retesting in Patients with Idiopathic and Isolated GH Deficiency?

To investigate growth hormone (GH) secretion at the transition age, retesting of all subjects who have undergone GH replacement therapy is recommended when linear growth and pubertal development are complete to distinguish between transitional and persistent GH deficiency (GHD). Early retesting of children with idiopathic and isolated GHD (i.e., before the achievement of final height and/or the adult pubertal stage) can avoid possible over-treatment. Here, we report data from our population with idiopathic and isolated GHD to encourage changes in the management and timing of retesting. We recruited 31 patients (19 males) with idiopathic GHD who received recombinant GH (rGH) for at least 2 years. All of the patients were retested at the transition age at least 3 months after rGH discontinuation. Permanent GHD was defined as a GH peak of <19 ng/mL after administration of growth hormone⁻releasing hormone (GHRH) + arginine as a provocative test. Permanent GHD was confirmed in only five of 31 patients (16.13%). None of these patients presented low serum insulin-like growth factor (IGF)-1 levels (<-2 standard deviation score (SDS)). Only one male patient with an IGF-1 serum level lower than -2 SDS showed a normal GH stimulation response, with a GH peak of 44.99 ng/mL. Few patients with idiopathic and isolated GHD demonstrated persistence of the deficit when retested at the transition age, suggesting that the timing of retesting should be anticipated to avoid overtreatment