Dose escalation of adalimumab as a strategy to overcome anti-drug antibodies:A case report of infantile-onset inflammatory bowel disease

BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics.Secondary loss of response is frequently caused by the production of anti-drug antibodies,a well-known problem in IBD patients on biologic treatment.We present a case of IO-IBD treated with therapeutic drug monitoring(TDM)-guided high-dose anti-tumor necrosis factor therapy,in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies.CASE SUMMARY A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life,as well as relapsing perianal abscess and growth failure.Hypoalbuminemia,anemia,and elevated inflammatory markers were also present.Endoscopic assessment revealed skip lesions with deep colic ulcerations,inflammatory anal sub-stenosis,and deep fissures with persistent abscess.A diagnosis of IO-IBD Crohn-like was made.The patient was initially treated with oral steroids and fistulotomy.After the perianal abscess healed,adalimumab(ADA)was administered with concomitant gradual tapering of steroids.Clinical and biochemical steroid-free remission was achieved with good trough levels.After 3 mo,antibodies to ADA(ATA)were found with undetectable trough levels;therefore,we optimized the therapy schedule,first administering 10 mg weekly and subsequently up to 20 mg weekly(2.8 mg/kg/dose).After 2 mo of high-dose treatment,ATA disappeared,with concomitant high trough levels and stable clinical and biochemical remission of the disease.CONCLUSION TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production.This strategy could be a good alternative to combination therapy,especially in very young patients.

Minimally invasive surgery for paediatric inflammatory bowel disease: Personal experience and literature review

The incidence of paediatric inflammatory bowel disease(PIBD) has dramatically increased in the last 20 years. Although first reported in mid 1970s',diagnostic laparoscopy has started to be routinely adopted in paediatric surgical practice since late 1990s'. Minimally invasive surgery was first limited to diagnostic purposes. After 2002 it was also applied to the radical treatment of PIBD,either Crohn's disease(CD) or Ulcerative colitis. During the last decade minimally invasive approaches to PIBD have gained popularity and have recently became the "gold standard" for the treatment of such invalidating and troublesome chronic diseases. The authors describe and track the historical evolution of minimally invasive surgery for PIBD and address all available opportunities,including most recent advancements such as robotic surgery,single port approaches and minimally invasive treatment of perianal fistulising CD. A systematic review of all series of PIBD treated with minimally invasive approaches published so far is provided in order to determine the incidence and type of patients' complications reported up to present days. The authors also describe their experience with minimally invasive surgery for PIBD and will report the results of 104 laparoscopic procedures performed in a series of 61 patients between January 2006 and December 2014.

Cerebellum and neurodegenerative diseases:Beyond conventional magnetic resonance imaging

The cerebellum plays a key role in movement control and in cognition and cerebellar involvement is described in several neurodegenerative diseases.While conventional magnetic resonance imaging(MRI) is widely used for brain and cerebellar morphologic evaluation,advanced MRI techniques allow the investigation of cerebellar microstructural and functional characteristics.Volumetry,voxel-based morphometry,diffusion MRI based fiber tractography,resting state and task related functional MRI,perfusion,and proton MR spectroscopy are among the most common techniques applied to the study of cerebellum.In the present review,after providing a brief description of each technique's advantages and limitations,we focus on their application to the study of cerebellar injury in major neurodegenerative diseases,such as multiple sclerosis,Parkinson's and Alzheimer's disease and hereditary ataxia.A brief introduction to the pathological substrate of cerebellar involvement is provided for each disease,followed by the review of MRI studies exploring structural and functional cerebellar abnormalities and by a discussion of the clinical relevance of MRI measures of cerebellar damage in terms of both clinical status and cognitive performance.

Associations among depression, suicidal behavior, and quality of life in patients with human immunodeficiency virus

AIM: To investigate the potential associations among major depression, quality of life, and suicidal behavior in human immunodeficiency virus(HIV) patients. METHODS: A detailed MEDLINE search was carried out to identify all articles and book chapters in English published from January 1995 to January 2015. RESULTS: Based on the main findings, the prevalence of major depressive disorder(MDD) ranged from 14.0% to 27.2%. Furthermore, the prevalence of suicidal ideation varied from 13.6% to 31.0% whereas, attempted suicides were reported to range from 3.9% to 32.7%. Interestingly, various associated risk factors for both depression and suicide were identified in HIV patients. Finally, consistent associations were reported among MDD, suicidal ideation, and poor quality of life in individuals living with HIV. CONCLUSION: Although additional studies are needed to elucidate this complex association, our results suggest the importance of early detection of both MDD and suicidality in patients living with HIV.

Oral mucositis induced by risperidone:rare side effect of a frequently prescribed medication

Risperidone is a safe second-generation antipsychotic which is rarely associated with the emergence of a few adverse effects,such as oral lesions and stomatitis.We report the case of a 77-year-old woman affected by a neurocognitive disorder with psychotic features and treated with risperidone 2 mg/day.After 1 week,she showed a burning mouth syndrome with oral lesions and risperidone was discontinued.Antipsychotic-induced oral ulcerations may be caused by the reduction of saliva protection with minor adverse effects related to oral movement disorders or impairment of the bacterial flora of saliva.

Nanotechnology meets atopic dermatitis: Current solutions, challenges and future prospects. Insights and implications from a systematic review of the literature

Atopic dermatitis is a chronic,relapsing,non-contiguous,exudative eczema/dermatitis,which represents a complex,multi-factorial disorder,due to an impairment of the stratum corneum barrier.Currently available drugs have a low skin bioavailability and may give rise to severe adverse events.Nanotechnologies,including nanoparticles,liposomes,nano-gels,nano-mixtures,nano-emulsions and other nano-carriers,offer unprecedented solutions to these issues,enabling:i)the management of different clinical forms of atopic dermatitis,especially the recalcitrant ones,i)a better bio-availability and trans-dermal drug targeted delivery at the inflammation site,ii)dose control,iii)significant improvements both in clinical symptoms and immune responses,iv)with less adverse events being reported and a better safety profile.However,some nano-sized structures could amplify and even worsen symptoms in particularly susceptible individuals.Furthermore,most studies included in the present systematic review have been conducted in-vitro or in-vivo,with few randomized controlled clinical trials(RCTs).Future investigations should adopt this design in order to enable scholars achieving robust findings and evidence.Therefore,given the above-mentioned shortcomings,further research in the field is urgently warranted.

Inflammation in the anterior visual pathway in multiple sclerosis:what do the animal models teach us?

A provocative and overly reductive mantra is that"the back of the eye is the front of the brain".Retinal imaging techniques that take advantage of this"window"to the central nervous system can provide valuable information regarding injury to the nervous system with relative ease and with a limited burden to patients.The retina develops embryonically as part of the neuroectoderm,is made up principally of neurons and their supporting cells,and is synaptically tied to the central nervous system(CNS).This has led to significant interest in using retinal health as a biomarker for brain health-given the relatively limited accessibility of brain tissue in chronic neurodegenerative diseases that progress over decades.The retina is not truly part of the CNS,and as with much of brain imaging-the grounds for asserting the pathological specificity of retinal imaging is limited.Biophotonics-based methods such as optical coherence tomography indirectly provide an opportunity to evaluate retinal neurodegeneration,while autopsy studies,histology and immunohistochemistry predominate as the methods that collect direct pathological data.Our understanding of pathological retinal lesions characteristic of demyelinating diseases,specifically diseases showing anterior visual pathway involvement,has grown significantly in recent years.However,much of the underlying pathobiology of injury remain unexplored.This review aims to highlight the major pathological features of the retina in multiple sclerosis,and its most used animal models(experimental autoimmune encephalomyelitis and cuprizone),with a particular focus on n the role of inflammation.